Enhancement of protective immune responses to Venezuelan equine encephalitis (VEE) virus with microencapsulated vaccine.
Venezuelan equine encephalomyelitis (VEE) virus is a mosquito-borne arbovirus of major human health significance in the New World. Currently two forms of VEE virus are used for immunization of humans and horses, i.e. a live attenuated and a formalin-inactivated vaccine. Clinical evidence suggests that these vaccines are not fully efficacious and may produce certain undesirable side-effects. In the present study, microspheres composed of biocompatible and biodegradable poly (DL-lactide-co-glycolide) (DL-PLG) were evaluated for their effectiveness as a delivery system of whole, inactivated VEE virus vaccine for the induction of protective immune responses. Mice receiving 50 micrograms VEE virus in microspheres composed of an equimolar ratio of DL-lactide and glycolide (50:50 DL-PLG) exhibited a primary circulating IgG antibody response which was approximately 32-times higher than the response induced with the same dose of unencapsulated (free) virus. A similar difference in responses was seen with antigen doses ranging from 3.1 to 50 micrograms. A rapid increase in antibody activity was seen after the secondary immunization (day 50). Formalin fixation of inactivated VEE virus was important for immunogenicity since the circulating anti-VEE virus antibody response induced with microencapsulated nonformalin-fixed virus vaccine was lower than that induced with microencapsulated formalin-fixed virus vaccine. Furthermore, at low antigen concentrations, DL-PLG microsphere vaccines prepared with the solvent methylene chloride induced higher antibody responses than those prepared using ethyl acetate as the solvent. Microencapsulated vaccine also induced higher VEE virus neutralization titers than did free virus vaccine. Finally, the microencapsulated virus was more effective than the free virus in inducing immune responses protective against systemic challenge with virulent VEE virus. These results demonstrate that DL-PLG microspheres containing formalin-fixed, inactivated VEE virus were effective in augmenting circulating IgG antibody levels and neutralization titers to the VEE virus following systemic immunization and in affording enhanced protection against systemic challenge with virulent VEE virus. The effects of antigen form and the microsphere processing solvent on the immunogenicity of the vaccine are discussed.


The Mediterranean diet and risk of type 2 diabetes in Iranian population.
Type 2 diabetes (T2D) is fast increasing in recent decades. Limited prospective studies are available on Mediterranean diet protective effect against T2D development. We assessed longitudinal association of the Mediterranean diet with T2D risk in Iranian men and women. Diet was measured using a 168-item food frequency questionnaire in 2139 adults (free of T2D), aged 20-70 years. All individuals, based on the traditional Mediterranean diet score (MDS), received scores between 0 and 8 points. Multivariate hazard ratio (HR) and 95% confidence interval (CI) were reported for the association of T2D and the MDS, with adjustment of diabetes risk score (DRS) and dietary energy intakes. During follow-up, a total of 143 events occurred. Individuals who had higher intakes of fish/sea foods, legumes, nuts, and monounsaturated fatty acids (MUFAs) to saturated fatty acids (SFAs) ratio had a decreased risk of T2D. After adjustment for confounders, an inverse association was found between adherence to the MDS and T2D (HR = 0.48; 95% CI 0.27-0.83). Our findings demonstrated an inverse association between the Mediterranean diet score and incidence of T2D.


Islet autoantibodies in Latvian subjects with non-insulin-dependent diabetes mellitus: slow-onset type 1 diabetes or polyendocrine autoimmunity?
In Latvia diabetes mellitus is diagnosed using the WHO's clinical criteria; assays for the detection of autoantibodies are not available, and hence slowly progressive autoimmune diabetes is likely to be missed. Autoantibodies against glutamic acid decarboxylase (GAD65) and protein tyrosine phosphatase (IA-2) among patients with clinically diagnosed NIDDM identify group of patients with slow-onset type 1 diabetes or LADA. The aim of this study was to estimate the risk of polyendocrine autoimmunity among clinically diagnosed NIDDM patients from Latvia. One hundred NIDDM patients and 100 healthy controls were tested for GAD65 and IA-2 autoantibodies as well as 21-hydroxylase (21-OH) and tissue transglutaminase (TTG) antibodies by RIA assay. Age at onset was >or= 30 years, and duration of disease less than 5 years. Of 100 patients, 85 were on oral hypoglycemic agents and 15 were on insulin. Body mass index (BMI) under 19 was recorded in 1% (1 of 100 cases), while overweight (BMI > 25.5 in females and 27 in males) was documented in 45% (45 of 100 cases). GAD65 antibodies were found in 30 of 100 (30%) and IA-2 antibodies in 40 of 100 (40%) patients. Either GAD65 or IA-2 antibodies were found in 55 of 100 (55%). None of the patients carried antibodies against 21-OH and only 1 of 100 (1%) carried antibodies against TTG. From the results obtained in our study we conclude that in Latvian adult NIDDM subjects, islet autoantibodies identify groups of slow-onset type 1 diabetes but not polyendocrine autoimmunity.


[Effects of urokinase plasminogen activator on cultured human retinal epithelial cells].
to study the effects of urokinase plasminogen activator (UPA) on the human retinal pigment epithelium (hRPE) cell culture. The toxicity of 50 U/ml UPA was studied with the trypan blue exclusion test. Cell migration was assessed by the wound healing and modified Boyden chamber assays. Additionally, cell morphology, trypsin resistance, and Ki67 expression were investigated. Trypan exclusion test did not reveal any cytotoxicity of 50 U/ml UPA against hRPE cells. The agent appeared able to induce cellular cluster formation and increase the number of spindle-shaped cells (6.4±2.4 cells/field and 67.3±3.2 cells/field in the controls and in the presence of 50 U/ml UPA, respectively, p<0.001). Cell migration in the Boyden chamber also showed a statistically significant increase (1.75-fold, p=0.012). Monolayer wounds were found to heal at an accelerated rate (p<0.05). This effect was dose-dependent, just like the increase in Ki67-positive cells (from 2.5 to 50 U/ml). Moreover, there was a reduction in trypsin resistance of the hRPE cells (the number of resistant cells in the control and 50 U/ml UPA cultures was 5.2±1.7 cells/field and 0.46±0.32 cells/field, respectively, p<0.001). UPA, at concentrations of 50 U/ml or less, demonstrates no cytotoxicity against the hRPE cells. The effects of UPA on hRPE include stimulation of epithelial-mesenchymal transition, migration, proliferation, and intercellular interaction. At that, changes in migratory and proliferative activity are dose-dependent.


Mesial temporal subdural electrode as a substitute for depth electrode.
As a substitute for depth electrodes, mesial temporal subdural electrodes were devised. This electrode has a slender trapezoid shape and is easily introduced to the inner uppermost portion of the parahippocampal gyrus. Our results have shown that mesial temporal electrodes can detect not only interictal spikes but also subclinical and clinical seizure discharges from the mesiolimbic structures, and they have excellent capability for lateralization of the mesial temporal epileptic focus. If mesial temporal subdural strips are used in combination with lateral temporal subdural grids, comprehensive understanding of the focus distribution throughout the temporal lobes will be possible without using depth electrodes.


Paleobiology of a Precambrian Shale: Geology, organic geochemistry, and paleontology are applied to the problem of detection of ancient life.
Investigations have been made of crude oil, pristane, phytane, steranetype and optically active alkanes, porphyrins, microfossils, and the stable isotopes of carbon and of sulfur found in the Nonesuch shale of Precambrian age from Northern Michigan. These sediments are approximately 1 billion years old. Geologic evidence indicates that they were deposited in a nearshore deltaic environment. Porphyrins are found in the siltstones but not in the crude oils of the Nonesuch formation-evidence that these chemical fossils are adsorbed or absorbed and immobile. This immobility makes it highly unlikely that these porphyrins could have moved from younger formations into the Nonesuch sediments, and the widely disseminated particulate organic matters and fossils in this Precambrian shale are certainly indigenous.


Analysis of factors influencing clonogenic growth in vitro of cells from ovarian carcinoma patients.
Clonogenic growth (defined as the formation of greater than or equal to 5 colonies per 5 x 10(5) viable nucleated cells per plate) of ovarian cancer specimens assessed in our clonogenic assay system was significantly associated with the proportion of tumor cells in the suspensions plated (N = 87; P = 0.0006), although there was no quantitative relationship with the corresponding plating efficiencies. An inverse correlation was observed between monocytes/macrophages/mesothelial cells (M) proportion and clonogenic growth (P = 0.013). These associations were most evident when only effusions were considered. Univariate analyses identified tumor cell content, M proportion and, to a lesser degree, granulocyte content as the only factors out of 12 examined to be correlated with colony formation. Multivariate analysis using a logistic regression model identified the proportion of tumor cells as the only significant factor predicting clonogenic growth in vitro (P = 0.0006). The overall accuracy of prediction for growth or non-growth was 63.2%.


A comparison of a prototype electromyograph vs. a mechanomyograph and an acceleromyograph for assessment of neuromuscular blockade.
The extent of neuromuscular blockade during anaesthesia is frequently measured using a train-of-four stimulus. Various monitors have been used to quantify the train-of-four, including mechanomyography, acceleromyography and electromyography. Mechanomyography is often considered to be the laboratory gold standard of measurement, but is not commercially available and has rarely been used in clinical practice. Acceleromyography is currently the most commonly used monitor in the clinical setting, whereas electromyography is not widely available. We compared a prototype electromyograph with a newly constructed mechanomyograph and a commercially available acceleromyograph monitor in 43 anesthetised patients. The mean difference (bias; 95% limits of agreement) in train-of-four ratios was 4.7 (-25.2 to 34.6) for mechanomyography vs. electromyography; 14.9 (-13.0 to 42.8) for acceleromyography vs. electromyography; and 9.8 (-31.8 to 51.3) for acceleromyography vs. mechanomyography. The mean difference (95% limits of agreement) in train-of-four ratios between opposite arms when using electromyography was -0.7 (-20.7 to 19.3). There were significantly more acceleromyography train-of-four values > 1.0 (23%) compared with electromyography or mechanomography (2-4%; p < 0.0001). Electromyography most closely resembled mechanomyographic assessment of neuromuscular blockade, whereas acceleromyography frequently produced train-of-four ratio values > 1.0, complicating the interpretation of acceleromyography results in the clinical setting.


Accurate prediction of duodenal-ulcer healing rate by discriminant analysis.
Previous studies have shown that approximately 50% and 70% of duodenal ulcers heal after 2 and 4 wk, respectively, of cimetidine, and at least one-third heal after 4 wk of placebo. In order to identify these groups of ulcers before treatment, a two-phase study was performed, including an initial double-blind trial of cimetidine vs. placebo in 120 patients, and a subsequent open study with identical protocol of cimetidine vs. no cimetidine in another 60 patients. Forty clinical, personal, physiologic, and endoscopic characteristics were prospectively obtained in each patient, and were analyzed by stepwise discriminant analysis at the end of phase 1. This identified the discriminants against healing after 2 wk of cimetidine as late onset disease, body weight, and ulcer diameter; those after 4 wk of cimetidine as analgesic consumption, neurosis, low fasting serum gastrin, low pentagastrin D50 and ulcer diameter; and those after 4 wk of placebo as back pain, bleeding, and alcohol consumption. Based on the discriminant scores derived, the sensitivity, specificity, and efficiency of prediction for complete healing as determined endoscopically were 74.4%, 90%, and 82.3% for 2-wk cimetidine, 100%, 87.5%, and 97.5% for 4-wk cimetidine, and 85.7%, 83.3%, and 84.2% for 4-wk placebo treatment. In phase 2, correct predictions were made in 36 of 40, 39 of 40, and 17 of 20 patients treated, respectively, for 2 and 4 wk with cimetidine, and 4 wk without cimetidine. Accurate prediction of duodenal-ulcer healing rate with and without cimetidine is thus possible by discriminant analysis. As many medical and surgical modalities of treatment are now available, this approach should have the potential of selecting the appropriate form of treatment for a given patient.


Revisiting the specificity of the MHC class II transactivator CIITA in vivo.
CIITA is a master regulatory factor for the expression of MHC class II (MHC-II) and accessory genes involved in Ag presentation. It has recently been suggested that CIITA also regulates numerous other genes having diverse functions within and outside the immune system. To determine whether these genes are indeed relevant targets of CIITA in vivo, we studied their expression in CIITA-transgenic and CIITA-deficient mice. In contrast to the decisive control of MHC-II and related genes by CIITA, nine putative non-MHC target genes (Eif3s2, Kpna6, Tap1, Yars, Col1a2, Ctse, Ptprr, Tnfsf6 and Plxna1) were found to be CIITA independent in all cell types examined. Two other target genes, encoding IL-4 and IFN-gamma, were indeed found to be up- and down-regulated, respectively, in CIITA-transgenic CD4(+) T cells. However, there was no correlation between MHC-II expression and this Th2 bias at the level of individual transgenic T cells, indicating an indirect control by CIITA. These results show that MHC-II-restricted Ag presentation, and its indirect influences on T cells, remains the only pathway under direct control by CIITA in vivo. They also imply that precisely regulated MHC-II expression is essential for maintaining a proper Th1-Th2 balance.


Immune responses and protective efficacy in ponies immunised with an equine influenza ISCOM vaccine containing an 'American lineage' H3N8 virus.
Protective responses generated by vaccination with an immuno-stimulating complex (ISCOM)-based vaccine for equine influenza (EQUIP F), containing a new 'American lineage' H3N8 virus, were studied. Seven ponies in the vaccine group received two intramuscular injections of EQUIP F given 6 weeks apart. Aerosol challenge with an A/eq/Newmarket/1/93 reference strain 4 weeks after booster vaccination resulted in clinical signs of infection and viral shedding in 7 influenza-naive control animals whereas the vaccinated ponies were significantly protected from both clinical signs and virus excretion. Influenza virus-specific IgG responses in serum following immunisation with the ISCOM vaccine were predominantly of the IgGa and IgGb sub-isotypes, a pattern similar to that generated by equine influenza virus infection. However, in contrast to the response following infection, virus-specific antibody responses in nasal washes following immunisation were characterised by the presence of IgG but not IgA.These results demonstrated that an ISCOM-based vaccine containing A/eq/Kentucky/98 provides strong protective immunity against challenge with an 'American lineage' H3N8 reference virus.


Deep learning of endoscopic features for the assessment of neoadjuvant therapy response in locally advanced rectal cancer.
For locally advanced rectal cancer (LARC), accurate response evaluation is necessary to select complete responders after neoadjuvant therapy (NAT) for a watch-and-wait (W&W) strategy. Algorithms based on deep learning have shown great value in medical image analyses. Here we used deep learning algorithms of endoscopic images for the assessment of NAT response in LARC. 214 LARC patients were retrospectively included in the study. After NAT, these patients underwent total mesorectal excision (TME) surgery. Among them, 51 (23.8%) of the patients achieved a pathological complete response (pCR). 160 patients from Shanghai Changzheng Hospital were regarded as primary dataset, and the other 54 patients from Zhejiang Cancer Hospital were regarded as validation dataset. ResNet-18 and DenseNet-121 were applied to train the models based on endoscopic images after NAT. Deep learning models were valid in the validation dataset and compared to manual method. The performances were comparable in AUC between deep learning models and manual method. For mean metrics, sensitivity (0.750 vs. 0.417) and AUC (0.716 vs. 0.601) in ResNet-18 deep learning model were higher than those in the manual method. The deep learning models were able to identify the endoscopic features associated with NAT response by the heatmaps. A diagnostic flow diagram which integrated the deep learning model to assist the clinicians in making decisions for W&W strategy was constructed. We created deep learning models using endoscopic features for assessment of NAT in LARC. The deep learning models achieved modest accuracies and performed comparably to manual method.


Appraisal of a new rapid enzyme strip.
The accuracy and reliability of new blood glucose measurement strips, BM Test-Glycemie 20-800, were assessed in 99 consecutive patients attending the diabetic clinic and seven subjects at home. The BM Test-Glycemie 20-800 strip technique was compared with the automated hexokinase method and the Reflotest-Glucose test strip technique employing the Boehringer Reflomat. The mean of the blood glucose values was 12.6 +/- 0.6 mmol/L for the hexokinase method and 12.9 +/- 0.6 mmol/L for the 20-800 strip technique, with a mean difference between the hexokinase and the 20-800 strip methods of 1.9 +/- 0.2 mmol/L. In the range 4 mmol/L to 12 mmol/L, the 20-800 strips were found to be extremely accurate, but for blood glucose levels less than 3.5 mmol/L and greater than 12 mmol/L, they were less reliable. Importantly, the strips were often misleading in indicating hypoglycaemia. It is concluded that the BM Test-Glycemie 20-800 strips have a practical and valuable role when used by suitably instructed staff members, or by patients in the management of diabetes, and represent a major advance over urine testing on previously available direct reading enzyme strip methods.


Critical tissue residue approach linking accumulated metals in aquatic insects to population and community-level effects.
Whole body Zn concentrations in individuals (n = 825) from three aquatic insect taxa (mayflies Rhithrogena spp. and Drunella spp. and the caddisfly Arctopsyche grandis) were used to predict effects on populations and communities (n = 149 samples). Both mayflies accumulated significantly more Zn than the caddisfly. The presence/absence of Drunella spp. most reliably distinguished sites with low and high Zn concentrations; however, population densities of mayflies were more sensitive to increases in accumulated Zn. Critical tissue residues (634 μg/g Zn for Drunella spp. and 267 μg/g Zn for Rhithrogena spp.) caused a 20% reduction in maximum (90th quantile) mayfly densities. These critical tissue residues were associated with exposure to 7.0 and 3.9 μg/L dissolved Zn for Drunella spp. and Rhithrogena spp., respectively. A threshold in a measure of taxonomic completeness (observed/expected) was observed at 5.4 μg/L dissolved Zn. Dissolved Zn concentrations associated with critical tissue residues in mayflies were also associated with adverse effects in the aquatic community as a whole. These effects on populations and communities occurred at Zn concentrations below the U.S. EPA hardness-adjusted continuous chronic criterion.


Zebrafish model of the blood-brain barrier: morphological and permeability studies.
The blood-brain barrier (BBB) is a monolayer of endothelial cells that is regulated by the proximity of a unique basement membrane and a tightly controlled molecular interaction between specialized subsets of cells including pericytes, astrocytes, and neurons. Working together, these cells form a neurovascular unit (NVU) that is dedicated to the local regulation of vascular function in the brain and BBB integrity. Accordingly, the intrinsic complexity of the cell-matrix-cell interactions of the NVU has made analyzing gene function in cell culture, tissue explants, and even animal models difficult and the inability to study gene function in the BBB in vivo has been a critical hurdle to advancing BBB research.Zebrafish has emerged as a premier vertebrate organism to model and analyze complex cellular interactions in vivo and genetic mechanisms of embryonic development. To this end, we provide a technical overview of the procedures that can be used in Zebrafish to analyze BBB integrity with a focus on the cerebrovasculature of adult fish where the BBB is now defined. The techniques that are used to measure the functional integrity, the cell biology, and the ultrastructure of the BBB include permeability assays, fluorescent imaging of reporter genes, and electron microscopy, respectively. Each can be applied to the functional analysis of mutant fish in ways that characterize the molecular sequelae to pathological insults that compromise BBB integrity. Due to the highly conserved nature of both the genetics and cell biology of zebrafish when compared with higher vertebrates, drug discovery techniques can be used in zebrafish models to complement drug development studies in other model systems.


Insight into the molecular mechanism of the sulfur oxidation process by reverse sulfite reductase (rSiR) from sulfur oxidizer Allochromatium vinosum.
Sulfur metabolism is one of the oldest known biochemical processes. Chemotrophic or phototrophic proteobacteria, through the dissimilatory pathway, use sulfate, sulfide, sulfite, thiosulfate or elementary sulfur by either reductive or oxidative mechanisms. During anoxygenic photosynthesis, anaerobic sulfur oxidizer Allochromatium vinosum forms sulfur globules that are further oxidized by dsr operon. One of the key redox enzymes in reductive or oxidative sulfur metabolic pathways is the DsrAB protein complex. However, there are practically no reports to elucidate the molecular mechanism of the sulfur oxidation process by the DsrAB protein complex from sulfur oxidizer Allochromatium vinosum. In the present context, we tried to analyze the structural details of the DsrAB protein complex from sulfur oxidizer Allochromatium vinosum by molecular dynamics simulations. The molecular dynamics simulation results revealed the various types of molecular interactions between DsrA and DsrB proteins during the formation of DsrAB protein complex. We, for the first time, predicted the mode of binding interactions between the co-factor and DsrAB protein complex from Allochromatium vinosum. We also compared the binding interfaces of DsrAB from sulfur oxidizer Allochromatium vinosum and sulfate reducer Desulfovibrio vulgaris. This study is the first to provide a comparative aspect of binding modes of sulfur oxidizer Allochromatium vinosum and sulfate reducer Desulfovibrio vulgaris.


Observational study of patient-ventilator asynchrony and relationship to sedation level.
Clinicians frequently administer sedation to facilitate mechanical ventilation. The purpose of this study was to examine the relationship between sedation level and patient-ventilator asynchrony. Airway pressure and airflow were recorded for 15 minutes. Patient-ventilator asynchrony was assessed by determining the number of breaths demonstrating ineffective triggering, double triggering, short cycling, and prolonged cycling. Ineffective triggering index (ITI) was calculated by dividing the number of ineffectively triggered breaths by the total number of breaths (triggered and ineffectively triggered). Sedation level was assessed by the following 3 methods: Richmond Agitation-Sedation Scale (RASS), awake (yes or no), and delirium (Confusion Assessment Method for the intensive care unit [CAM-ICU]). Twenty medical ICU patients underwent 35 observations. Ineffective triggering was seen in 17 of 20 patients and was the most frequent asynchrony (88% of all asynchronous breaths), being observed in 9% +/- 12% of breaths. Deeper levels of sedation were associated with increasing ITI (awake, yes 2% vs no 11%; P < .05; CAM-ICU, coma [15%] vs delirium [5%] vs no delirium [2%]; P < .05; RASS, 0, 0% vs -5, 15%; P < .05). Diagnosis of chronic obstructive pulmonary disease, sedative type or dose, mechanical ventilation mode, and trigger method had no effect on ITI. Asynchrony is common, and deeper sedation level is a predictor of ineffective triggering.


Increasing predominance of G8P[8] species A rotaviruses in children admitted to hospital with acute gastroenteritis in Thailand, 2010-2013.
Rotavirus A is a well-known etiological cause of acute gastroenteritis in infants and young children worldwide. In this study, we investigated the prevalence and distribution of RVA genotypes circulating in children with acute gastroenteritis in Thailand from 2010 to 2013. A total of 1,032 fecal specimens were collected from children with an age range from neonatal to 15 years of age and tested for RVA by RT-PCR. Of these, 184 (17.8%) were positive for RVA. The highest detection rate of RVA was found in children aged between 12 and 24 months. The G1P[8] genotype was identified as the most dominant genotype (57.6%), followed by G2P[4] (12.5%), G8P[8] (10.4%), G9P[8] (7.1%), G3P[8] (4.9%), G1P[4] (2.2%), G2P[8] (1.7%), and mixed-infections of G1 and G3 in combination with P[8] (0.5%). In addition, the uncommon human rotavirus strains G4P[6] (1.1%), G9P[19] (0.5%), G12P[4] (0.5%), and G12P[6] (0.5%) were also detected in this study. Interestingly, the unusual G8P[8] strains were detected at a relatively high frequency, and phylogenetic analysis revealed that these G8 strains were genetically closely related to bovine and bovine-like human G8 rotavirus strains reported previously from Thailand, Japan, Vietnam, India and Taiwan. These G8P[8] strains displayed the DS-1-like genotype constellation of G8-P[8]-I2-R2-C2-M2-A2-N2-T2-E2-H2 (in the order VP7-VP4-VP6-VP1-VP2-VP3-NSP1-NSP2-NSP3-NSP4-NSP5/6, respectively). Overall, the data indicated a high degree of diversity of RVA genotypes, with the emergence of several uncommon RVA strains in children with acute gastroenteritis in Thailand.


Graded activity with and without daily-monitored-walking in patients with type 2 diabetes with low back pain: secondary analysis of a randomized-clinical trial.
Graded activity is gradually emerging as a preferred choice in improving psychosocial outcomes including pain self-efficacy, fear-avoidance beliefs, and back-pain beliefs in the general population with low back pain (LBP). Such evidence is, however, lacking among patients with concomitant LBP and type-2 diabetes mellitus (T2DM). This secondary analysis of a randomized control trial aimed to compare the efficacy between graded activity augmented with additional daily-monitored-walking and graded activity alone on disability, pain self-efficacy (PSE), fear-avoidance beliefs (FAB), back-pain beliefs (BPB) and glycaemic control (HbA1c) in patients with concomitant LBP and T2DM. Fifty-eight patients with concomitant LBP and T2DM were randomised into two groups, graded activity with daily-monitored-walking group (GAMWG = 29) or (graded activity group (GAG = 29) in this 12-week single-blind trial. Both groups received graded activity (home/work-place visits, back school and sub-maximal exercises) while the GAMWG received additional daily-monitored-walking. Disability and selected psychosocial outcomes were assessed at weeks 0, 4, 8 and 12 using Roland-Morris disability, fear-avoidance behaviour, pain self-efficacy and back belief questionnaires. Glycaemic control was assessed at weeks 0 and 12 using a point-of-care system (In2it, Biorad Latvia). Data were analysed using mean, median, Friedman's ANOVA, Mann-Whitney test and t-tests. Participants' mean age was 48.3 ± 9.4 years (95%CI: 45.6, 50.9) while 35.3% were males. The GAMWG participants (n = 25) had better outcomes (P < 0.05) than GAG participants (n = 26) on PSE (1.0, 3.0; r = - 0.1) and FAB (0.01, - 2.0; r = - 0.1) at week 4, LBP-related disability (0.01, - 2.0; r = - 0.2) at week 8 and glycaemic control at week 12 (- 0.59 ± 0.51%,-0.46 ± 0.22%). No other between-group comparisons were statistically significant. Graded activity with daily-monitored-walking provided earlier improvements on disability, pain self-efficacy, fear-avoidance beliefs, and glycaemic control, but not back pain beliefs, in patients with concomitant LBP and T2DM. PACTR201702001728564 ; 26 July, 2016 (retrospectively registered).


The Golem of Psychology and the Ecosystemic Epistemology.
The old controversy about the epistemic status of psychological sciences is useless and sterile. Psychology is ether a hard science nor a soft science. It is an ecological life science, whose object is the whole system of co-developmental relations constituted by the presence of the organism in a given environment. After criticizing the positions of the traditional epistemic debate between hard and soft views of psychology, I propose a way to fundament the core concepts in the method of complementary negation, based on cogenetic logic. Then, I defend the need to develop a third way: an ecological epistemology of psychology.


Explaining Brazil as a rising state, 2003‒2014: the role of policy diffusion as an international regulatory instrument.
In this paper, we examine Brazil's international activism and ascent to the status of rising state during the presidencies of Luiz Inácio Lula da Silva (2003-2010) and his chosen successor, Dilma Rousseff (2011-2014). We focus on the dissemination of social policies under an innovative model of development that reflected the political and economic context of a developing country. We argue that this activism was framed in terms of Brazil's socio-economic and cultural peculiarities, whereby these were treated not as obstacles but as positive contributions to developing states' attempts to reform global governance structures. We argue that this reflects an alternative form of foreign policy politicisation in which the social dilemmas, particularities and contradictions of the Brazilian experience are incorporated in the foreign policy agenda to leverage its international stature as a rising state. We explain how Brazil's international cooperation through transferring its public policies and development models (policies for fighting hunger and poverty, agrarian development and income generation) to its Southern partners has been discursively articulated as representing Brazil's normative potential to contribute to political and institutional solutions, and rebuild norms and standards that affect the distribution of international power and wealth.


High prevalence of elevated lead levels in pediatric dialysis patients.
After parents raised concerns about potential lead (Pb) contamination of calcium carbonate for treatment of hyperphosphatemia in chronic kidney disease (CKD), we measured blood Pb using high-resolution sector field inductively coupled mass spectrometry in a quality-assurance investigation of ten pediatric dialysis patients (nine on hemodialysis) and six patients before dialysis. We assessed the kidney function as cystatin C estimated glomerular filtration rate (eGFR), blood Pb levels, calcium carbonate dose, and standard laboratory parameters, as well as Pb levels in the dialysis feed water. Mean blood Pb concentration in the 16 pediatric CKD patients was 21.1 ± 15.8 µg/l with a maximum of 58 µg/l, which was significantly higher than that of 467 apparently healthy controls (median 6.35 µg/l, interquartile range 4.47, 8.71) and comparable to that of ten adult peritoneal dialysis (PD) patients. Lead levels correlated with red blood cell distribution width, eGFR, and calcium carbonate dose. Pb in dialysate feed water was always <0.00018 mg/l, which is below the accepted limit for water for dialysis of 0.005 mg/l. We found a high prevalence of elevated Pb levels in pediatric CKD patients that correlated with the calcium carbonate dose and GFR. Lead levels should be monitored in these patients.


Feasibility and application of 3-dimensional ultrasound for measurement of gastric volumes in healthy adults and adolescents.
Abnormal gastric accommodation to a meal results in dyspepsia. Current methods to measure gastric volume (GV) are invasive or involve ionizing radiation. The aims of this study were to compare fasting and postprandial (PP) GVs measured by (99m)Tc-single photon emission computed tomography (SPECT) and 3-dimensional ultrasound (3D-US) in adults, to assess the performance characteristics of 3D-US measurement of GV during fasting and postprandially, and to develop normative data of GVs in 24 healthy adolescents. Eleven adults underwent SPECT and 3D-US simultaneously to measure GV, and a second 3D-US alone within 1 week of the first study. Twenty-four adolescents underwent 1 3D-US measurement. Each study included fasting, a 300-mL Ensure meal, and 0 to 30-minute PP GV measurements. 3D-US identifies GV accommodation to 300mL Ensure. Delta (0-30 minutes average PP fasting) GV was 444mL (median, interquartile range [IQR]=422, 534) for 3D-US and 543mL (median, IQR=486, 564) for SPECT (P=0.15). There were larger interindividual coefficients of variation for GV by 3D-US (60.3% fasting and 21.3% average PP) compared with 19% fasting and 9.2% PP for SPECT. Intraindividual coefficients of variation for the 2 3D-US measurements in adults were 84% fasting and 44% average PP. The estimated GVs for the adolescent group (median [25th-75th IQR]) were 33 (18-53)mL fasting, 330 (284-357)mL 30 minutes PP, and 281 (240-324)mL for delta GV. 3D-US is a promising method to measure GV accommodation to a meal. Large coefficients of variation reflect the learning stage in development of this promising technique.


An enzyme-linked immunosorbent assay (ELISA) that discriminates between the venoms of Brazilian Bothrops species and Crotalus durissus.
Enzyme-linked immunosorbent assays (ELISAs) were developed to detect specific antigens from Bothrops sp. and Crotalus durissus snake venoms in Brazil. Cross-reactive immunoglobulins from hyperimmune horse anti-Bothrops and anti-Crotalus sera were removed by immunoaffinity chromatography. Specific IgGs for Bothrops sp. and C. durissus venom antigens were prepared and used to set up a sandwich-type ELISA. The specificity of the assay was demonstrated by its capacity to identify correctly the circulating antigens in mice experimentally inoculated with both venoms. Measurable absorbance signals were obtained with 5 ng of venom per assay. The ELISA was also used to identify circulating antigens in the sera of humans bitten by Bothrops sp. and C. durissus. These ELISAs could be valuable for clinicians and epidemiologists if they prove to have both the high sensitivity and specificity required for such tests.


Genome-wide identification and expression analysis of the response regulator gene family in alfalfa (Medicago sativa L.) reveals their multifarious roles in stress response.
As important components of the two-component regulatory system, response regulatory proteins (RRPs) play a crucial role in histidine phosphorylation-mediated signal transduction in response to environmental fluctuations. Accumulating evidence has revealed that RRPs play important roles in plant growth and stress response. However, the specific functions of RR genes (RRs) in cultivated alfalfa remain ambiguous. Therefore, in this study, we identified and characterized the RR family genes in the alfalfa genome using bioinformatics methods. Our analysis revealed 37 RRs in the alfalfa genome of Zhongmu No.1 that were unevenly distributed on the chromosomes. Cis-elements analysis revealed the involvement of RRs in responses to light, stress, and various plant hormones. Expression analysis of RRs in different tissues revealed their distinct tissue expression patterns. These findings provide preliminary insights into the roles of RRs in plant responses to abiotic stress, which can be used to improve the stress tolerance of autotetraploid-cultivated alfalfa plants via genetic engineering.


Effects of variation in cloudiness and stratospheric aerosol scattering upon tropospheric UV flux, photolysis rates, and the ozone urban plume.
Using a radiative transfer model, the sensitivity of tropospheric UV flux and photolysis rates for NO(2) and HNO(2) to variations in cloudiness and stratospheric aerosol scattering are evaluated. A lumped parameter ozone plume model combining photochemistry and diffusion is then utilized to investigate variations in downwind ozone concentrations caused by variations in cloudiness.


Do Peers Increase Older Adults' Participation in Strength Training? Pilot Randomized Trial.
Fewer than 20% of older adults participate in strength training (ST). Barriers to ST participation include not knowing where to go or not having someone to go with. To address these barriers, the authors provided older adults with a peer (older person already participating in ST) to support their engagement. The aim of this pilot randomized controlled trial was to determine whether older adults who were provided with a peer when participating in ST were more likely to be participating in ST 4 weeks postintervention, compared with those receiving ST alone. Fifty-one ST participants were recruited; 40 completed the intervention and postintervention data collection (78.4%). Providing peer support with ST did not significantly increase ST participation (p = .775). However, both groups made significant improvements over time in lower-limb strength and mobility. Participants in either group who continued the ST program (55%) had made additional significant improvements in lower-limb strength and mobility.


Synthesis of novel hierarchical micro/nanostructures AlOOH/AlFe and their application for As(V) removal.
Hierarchical micro/nanostructured composites, which contain iron and/or its (hydr)oxides, demonstrate high rate and capacity of arsenic adsorption. The main objective of this paper is the use of novel low toxicity AlOOH/AlFe hierarchical micro/nanostructures for arsenic removal. AlOOH/AlFe composite was obtained by simple water oxidation in mild conditions using AlFe bimetallic nanopowder as a precursor. AlFe bimetallic nanopowder was produced by electrical explosive of two twisted wires in argon atmosphere. The productivity of the electrical explosion assembly was 50 g/h, with the consumption of the electrical energy was 75 kW·h/kg. AlFe bimetallic nanoparticles were chemically active and interacted with water at 60 °C. This nanocomposite AlOOH/AlFe is low cost and adsorbs more than 200 mg/g As(V) from its aqueous solution. AlOOH/AlFe composite has flower-like morphology and specific surface area 247.1 m2/g. The phase composition of nanostructures is present AlOOH boehmite and AlFe intermetallic compound. AlOOH/AlFe composite was not previously used for this. The flower-shape AlOOH morphology not only facilitated deliverability, but increased the As(V) sorption capacity by up to 200 mg/g. The adsorption kinetics has been found to be described by a pseudo-second-order equation of Lagergren and Weber-Morris models while the experimental adsorption isotherm is closest to the Freundlich model. This indicates the energy heterogeneity of the adsorbent surface and multilayer adsorption. The use of non-toxic nanostructures opens up new options to treat water affected by arsenic pollution.


Action of thyroxine on the survival and neurite maintenance of cerebellar granule neurons in culture.
Developmental hypothyroidism causes severe impairments in the cerebellum. To understand the role of thyroid hormones (THs) in cerebellar development, we examined the effect of three different THs, thyroxine (T4), 3,5,3'-triidothyronine (T3), and 3,3',5'-triiodothyronine (reverse T3; rT3), on the survival and morphology of cerebellar granule neurons (CGNs) in culture and found novel actions specific to T4. Rat CGNs obtained at postnatal day 6 were first cultured for 2 days in serum-containing medium with 25 mM K(+) (K25), then switched to serum-free medium with physiological 5 mM K(+) (K5) or with K25 and cultured for an additional 2 or 4 days. CGNs underwent apoptosis in K5 but survived in K25. Addition of T4 at concentrations of 100-200 nM but not T3 or rT3 rescued CGNs from cell death in K5 in a dose-dependent manner. Furthermore, 200 nM T4 was also effective in maintaining the neurites of CGNs in K5. In K5, T4 suppressed tau phosphorylation at two developmentally regulated sites as well as phosphorylation of c-jun N-terminal kinase (JNK) necessary for its activation and localization to axons. These results suggest that, during cerebellar development, T4 exerts its activity in cell survival and neurite maintenance in a manner distinct from the other two thyroid hormones through regulating the activity and localization of JNK.


Anesthesia for pediatric magnetic resonance imaging: a review of practices and current pathways.
Magnetic resonance imaging (MRI) is an ever-expanding investigation modality in children. This review aims to present current strategies to perform MRI in pediatrics efficiently and safely. The latest evidence on approaches, safety and costs of MRI with no sedation or with sedation provided by anesthesiologists and non-anesthesiologists are outlined and discussed. MRI under sedation provided by either anesthesiologists or non-anesthesiologists has a low incidence of minor adverse events and rarely severe complications. Propofol infusion with or without dexmedetomidine appears the ideal anesthetic, as it allows spontaneous breathing and fast turnover. Intranasal dexmedetomidine is safe and the most effective medication when a nonintravenous route is employed.New scanning techniques and patient's preparation methods can increase the chances to successfully perform MRI with no sedation by shortening sequences, reducing artifacts, and improving child's cooperation. MRI under sedation can be considered safe. Proper patient selection, clear decision-making and medico-legal pathways are particularly necessary for nurse-only sedated scans. Nonsedated MRIs are feasible and cost-effective but require optimal scanning techniques and patient's preparation to be successful. Further research should be focused on identifying the most effective modalities to perform MRI without sedation and clarify protocols for the nurse-only sedations.Anesthesia service will likely remain pivotal for complex and critically ill patients and to provide assistance in case of adverse events.


Broadening the Dental Hygiene Students' Perspectives on the Oral Health Professionals: A Text Mining Analysis.
Professional identity formation, an important component of education, is influenced by participation, social relationships, and culture in communities of practice. As a preliminary investigation of dental hygienists' professional identity formation, this study examined changes in the dental hygiene students' perceptions of oral health professionals over the three years of their undergraduate program. At a Japanese dental hygiene school, 40 students participated in surveys with open-ended questions about professional groups several times during their studies. The text data were analyzed through content analysis with text mining software. The themes that characterized their dental hygienist profession perceptions in their programs each year were identified as: "Supporters at the dental clinic"; "Engagement with interprofessional care" and "Improved problem-solving skills for clinical issues regarding the oral region"; and "Active contribution to general health" and "Recognition of the roles considering relationships" (in the first, second, and third years, respectively). The students acquired professional knowledge and recognized the significance and roles of oral health professionals in practice. They gained more learning experiences in their education, including clinical placements and interprofessional education. This study provides insight into curriculum development for professional identity formation in dental hygiene students.


Untoward sequelae of prolonged intubation.
Laryngeal sequelae following prolonged endotracheal intubation are being observed with increasing frequency as this technique of airway management is being employed for extended periods of time. Many etiologic factors have been implicated in the development of these problems with the exact reasons being as yet unknown. After reviewing the records of 372 consecutive patients intubated over an 18-month period, we have observed an increased frequency of these complications in the diabetic female patient and suggest that early tracheostomy should be considered in these individuals when the use of prolonged intubation is anticipated. The possible pathophysiology of this problem in the diabetic, as well as the non-diabetic intubated patient, and its possible prevention will be discussed.


Association of short-term exposure to ambient PM1 with total and cause-specific cardiovascular disease mortality.
The acute effects of exposure to ambient particulate matter with an aerodynamic diameter ≤1 μm (PM1) on cardiovascular disease (CVD) mortality remain unclear. To investigate whether short-term exposure to ambient PM1 was associated with mortality from total and/or cause-specific CVDs, and estimate the excess mortality. A time-stratified case-crossover study was conducted among 1,081,507 CVD deaths in Jiangsu province, China from 2015 to 2020. We assessed daily residential ambient PM1 exposures using a validated grid dataset for each subject. Conditional logistic regression models and distributed lag linear or nonlinear models were employed to quantify the association of PM1 exposure with mortality during the same day of CVD death and 1 day prior. Each 10 μg/m3 increase of PM1 exposure was significantly associated with a 1.46 % (95 % confidence interval: 1.28 %, 1.65 %), 1.95 % (1.28 %, 2.63 %), 1.16 % (0.86 %, 1.47 %), 1.41 % (1.13 %, 1.69 %), and 1.83 % (1.37 %, 2.30 %) increased odds of mortality from total CVDs, hypertensive diseases (HDs), ischemic heart diseases (IHDs), stroke, and sequelae of stroke, respectively (all p <0.05). No significant association was identified with mortality from pulmonary heart disease or chronic rheumatic heart diseases. The excess fraction of total CVD mortality attributable to PM1 exposure was 5.71 %, while the cause-specific excess fractions ranged from 4.98 % for IHDs to 7.46 % for HDs. Significantly higher excess fractions were observed for total and certain cause-specific CVD mortality in adults 80 years or older. We found that short-term exposure to ambient PM1 was significantly associated with an increased odds of mortality from total and specific CVDs and may lead to considerable excess mortality especially among older adults. Our findings highlight a potential approach to prevent premature CVD deaths by reducing PM1 exposures and provide essential quantitative data for the development of future air quality standards for ambient PM1.


ncRNAs-mediated high expression of SEMA3F correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is notorious for its poor prognosis. Increasing evidence has demonstrated that semaphorin 3F (SEMA3F) plays key roles in initiation and progression of several types of human cancer. However, the specific role and mechanism of SEMA3F in HCC remains not fully determined. In this study, we first performed pan-cancer analysis for SEMA3F's expression and prognosis using The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) data and found that SEMA3F might be a potential oncogene in HCC. Subsequently, noncoding RNAs (ncRNAs) contributing to SEMA3F overexpression were identified by a combination of a series of in silico analyses, including expression analysis, correlation analysis, and survival analysis. Finally, the TMPO-AS1/SNHG16-let-7c-5p axis was identified as the most potential upstream ncRNA-related pathway of SEMA3F in HCC. Moreover, SEMA3F level was significantly positively associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. Collectively, our findings elucidated that ncRNAs-mediated upregulation of SEMA3F correlated with poor prognosis and tumor immune infiltration in HCC.


Cytogenetic and molecular genetic methods for diagnosis and treatment response in chronic granulocytic leukemia.
Today, laboratory geneticists help clinical hematologists diagnose chronic granulocytic leukemia (CGL) and monitor the response of patients undergoing treatment. The most common genetic tests for CGL include quantitative cytogenetic studies, fluorescence in situ hybridization with probes for BCR and ABL, Southern blot analysis, and reverse transcriptase polymerase chain reaction. No single genetic testing procedure fulfills all the needs of clinicians who care for patients who have CGL. Thus, it has become important to use combinations of testing methods that are both accurate and cost-effective for any given clinical situation in the diagnosis and treatment of patients with CGL.


Beta3-adrenoceptors mediate relaxation of guinea pig taenia caecum by BRL37344A and BRL35135A.
Beta-adrenoceptor-mediated relaxation of guinea pig taenia caecum was investigated by studying the effects of the beta3-adrenoceptor agonists, BRL37344A [(R*,R*)-(+/-)-4-[2'-[2-hydroxy-2-(3-chlorophenyl) ethylamino] propyl] phenoxyacetic acid sodium salt sesquihydrate] and BRL35135A [(R*,R*)-(+/-)-methyl-4-[2-[2-hydroxy-2-(3-chlorophenyl) ethylamine] propyl] phenoxyacetate hydrobromide]. BRL37344A and BRL35135A caused dose-dependent relaxation of the guinea pig taenia caecum. The concentration-response curves for BRL37344A and BRL35135A were unaffected by propranolol, ICI118551 [erythro-1-(7-methylindan-4-yloxy)-3-(isopropylamine)-but an-2-ol], atenolol, butoxamine, prazosin, yohimbine and phentolamine. Bupranolol produced shifts of the concentration-response curves for BRL37344A and BRL35135A. Schild regression analyses carried out for bupranolol against BRL37344A and BRL35135A gave pA2 values of 5.79 and 5.84, respectively. These results suggest that the relaxant response to BRL37344A and BRL35135A of the guinea pig taenia caecum is mediated by beta3-adrenoceptors.


Percutaneous absorption of 17 beta-estradiol in ovariectomized rhesus monkeys: skin and serum pharmacokinetics.
The skin and serum kinetics of percutaneous estradiol (E2) gel (Oestrogel; Besins-Iscovesco Laboratories, Paris, France) absorption in 11 ovariectomized rhesus monkeys (3 pretreated with diethylstilbestrol [DES]) was studied. The gel (1.5 mg E2) mixed with 7.5 x 10(5) cpm tritiated E2 (3H-E2) was applied to abdominal skin. Serial skin biopsies were taken from the application area and at 1 and 3 cm beyond, as well as from perineum and dorsal skin; and radioactivity measured to estimate tissue levels of E2 derived from percutaneous delivery. Simultaneous femoral serum samples were taken for RIA of E2. Skin 3H-E2 reached a peak at approximately 60 minutes, which was sustained for about 10 hours. Lateral diffusion of the radiolabeled E2 was limited to about 1 cm. Serum E2 levels reached a peak at 60 minutes and remained elevated for 20 hours after a single application. A strong correlation existed between skin and serum E2 levels: r = 0.828. DES did not modify the E2 skin absorption kinetics, but in 2 of 3 monkeys DES reduced the E2 serum levels, suggesting an effect after skin absorption. We conclude that percutaneously delivered E2 manifests a sustained entry into serum. The steady state of continuous release of E2 into circulation derives from a postabsorption skin reservoir of estrogen product.


Differentiation of human thyroid follicle cells from normal subjects and Basedow's disease in three-dimensional collagen gel culture.
Thyroid follicles, an essential functional unit of the thyroid, exist in the extracellular matrix of the tissue in vivo. Therefore, in any monolayer culture system, the follicles cannot be reconstructed. Our previous study adopting three-dimensional collagen gel culture showed that isolated porcine follicle cells reconstructed thyroid follicles specific for the thyroid gland in vivo. To elucidate whether this culture system is also applicable to human follicle cells, and furthermore to provide a culture system for investigations of the pathogenesis of human thyroid diseases, we tried to culture isolated human follicle cells of normal thyroid tissue and of Basedow's disease in three-dimensional collagen gel. In this culture system, they apparently reconstructed thyroid follicles. The component cells of the reconstructed follicles exhibited structural polarity specific for human thyroid follicle cells and produced thyroid hormones. In addition, the cells responded to a TSH-stimulation in terms of morphological and functional differentiation, and they presented HLA-DR antigen with an interferon-gamma-stimulation. This report is a first instance of reconstruction of human thyroid follicles and HLA-DR antigen induction in three-dimensional follicle structures in vitro. This culture system provides a more physiological environment in vitro for biological and pathogenetic investigations of human thyroid follicle cells than the monolayer culture system. Further experiments using this method will probably provide new clues to the pathogenetic mechanisms of human thyroid diseases.


Barriers and facilitators of the adoption and use of assistive technology for adults with an intellectual disability who live in supported accommodation: a mixed methods systematic review protocol.
The objective of this review is to identify the barriers and facilitators of assistive technology adoption and use in adults with intellectual disabilities living in supported accommodation. This will inform the development of an assistive technology adoption framework for these settings. Assistive technology has the potential to increase the independence and well-being of people with intellectual disabilities; however, it is often not adopted. Generic models of technology adoption exist, and a recent systematic review has explored factors influencing access to assistive technology by people with intellectual disabilities. However, no review has presented a framework of adoption or use of technology specifically for people with intellectual disabilities living in supported accommodation. This review will include qualitative, quantitative, and mixed method studies as well as gray literature published from 1989 to 2023 on the barriers and facilitators of technology adoption and use by adults with intellectual disabilities living in supported accommodation. Systematic reviews and theses will be excluded. The review will be conducted in accordance with the JBI methodology for mixed methods systematic reviews and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases to be searched will include PubMed, Scopus, Web of Science Core Collection, CINAHL, IEEE Xplore, and SocINDEX. Two independent reviewers will screen titles and abstracts for relevance and quality. Data will be extracted by 1 reviewer and validated by a second, independently. Data analysis will use a convergent integrated approach, with quantitative data "qualitized" using thematic analysis to allow comparison. All data will be mapped onto an existing framework of technological adoption via framework synthesis. PROSPERO CRD42022353732.


Fast start-up of anammox process: Effects of extracellular polymeric substances addition on performance, granule properties, and bacterial community structure.
The slow startup is the major obstacle to the application of anaerobic ammonium oxidation (anammox) process in mainstream wastewater treatment. Extracellular polymeric substances (EPS) are one potential resource for stable anammox reactor operation. Response surface analysis was used to optimize the specific anammox activity (SAA) with the addition of EPS; SAA was maximum at a temperature of 35 °C and the EPS concentration of 4 mg/L. By comparing the nitrogen removal of anammox reactors with no EPS (R0), immobilized EPS (EPS-alginate beads) (R1), and liquid EPS (R2), we found that EPS-alginate beads significantly speed up the startup of anammox process and enable the start time to be shortened from 31 to 19 days. As a result of the higher MLVSS content, higher zeta potential, and lower SVI30, anammox granules of R1 exhibited a stronger capacity to aggregate. Moreover, EPS extracted from R1 had higher flocculation efficiencies than EPS derived from R0 and R2. Phylogenetic analysis of 16S rRNA genes revealed that the main anammox species in R1 is Kuenenia taxon. To clarify the relative significance of stochastic vs deterministic processes in the anammox community, neutral model and network analysis are employed. In R1, community assembly became more deterministic and stable than in other cultures. Our results show that EPS might inhibit heterotrophic denitrification and thereby promote anammox activity. This study suggested a quick start-up strategy for the anammox process based on resource recovery, which is helpful for environmentally sustainable and energy-efficient wastewater treatment.


Assessing cumulative acute toxicity of chemoradiotherapy in head and neck cancer with or without induction chemotherapy.
To compare cumulative acute toxicity in head and neck cancer patients treated with concurrent chemoradiotherapy alone (CCRT) versus induction chemotherapy (IC) followed by CCRT (I/CCRT). 77 patients underwent definitive CCRT (30 I/CCRT and 47 CCRT). Toxicity was graded using the Common Terminology Criteria for Adverse Events version 4.0. Using the TAME adverse event reporting system, short-term toxicity (T) scores were generated for IC (TIC), CCRT (TCCRT), total treatment duration (TRx), post-treatment period (TPT) and an overall score (Toverall) from treatment start to post treatment period. Acute toxicity other than dysphagia, odynophagia, or dermatitis was reported in 90.0% and 66.0% of I/CCRT and CCRT patients, respectively (P=0.02). Compared to CCRT group, I/CCRT patients reported greater mean TRx (TRx: 2.11 vs. 2.87, P=0.01) and Toverall (Toverall: 2.60 vs. 3.70, P=0.003). I/CCRT patients reported more cumulative acute toxicity during treatment compared to CCRT patients using the TAME reporting system.


Evaluation of the surface ECG in detecting isthmus conduction block after ablation of typical atrial flutter.
To investigate the value of changes in P wave morphology and duration detected by surface electrocardiogram (ECG) during proximal coronary sinus (PCS) and low lateral right atrial (LLRA) stimulation as a marker for complete bidirectional isthmus conduction block in the procedure of typical atrial flutter ablation. Morphology, duration, and ratio of a positive terminal P wave were estimated in 52 typical atrial flutter patients before and after radiofrequency catheter ablation (RFCA). Atrial flutter ablation resulted in a complete bidirectional isthmus block in all 52 patients. The terminal portion of the P wave towards a positive morphology was detected in 90.7% (47/52) patients both during PCS and LLRA stimulation. These changes were predominantly observed in the inferior leads. Positive morphological changes of the terminal P wave portion and the measured P wave ratio (40% +/- 12%) in the inferior leads indicating bidirectional isthmus conduction block with a sensitivity of 87.5% and a specificity of 91.7% were observed. An increment of 20 ms or more in P wave duration during the PCS stimulation and 10 ms or more during the LLRA stimulation indicating the conduction block with a sensitivity of 90% and a specificity of 100%. The variation of P wave morphology and duration in inferior leads of the surface ECG is a helpful technique to assess the complete bidirectional isthmus conduction block in the procedure of typical atrial flutter ablation.


Photon management in two-dimensional disordered media.
Elaborating reliable and versatile strategies for efficient light coupling between free space and thin films is of crucial importance for new technologies in energy efficiency. Nanostructured materials have opened unprecedented opportunities for light management, notably in thin-film solar cells. Efficient coherent light trapping has been accomplished through the careful design of plasmonic nanoparticles and gratings, resonant dielectric particles and photonic crystals. Alternative approaches have used randomly textured surfaces as strong light diffusers to benefit from their broadband and wide-angle properties. Here, we propose a new strategy for photon management in thin films that combines both advantages of an efficient trapping due to coherent optical effects and broadband/wide-angle properties due to disorder. Our approach consists of the excitation of electromagnetic modes formed by multiple light scattering and wave interference in two-dimensional random media. We show, by numerical calculations, that the spectral and angular responses of thin films containing disordered photonic patterns are intimately related to the in-plane light transport process and can be tuned through structural correlations. Our findings, which are applicable to all waves, are particularly suited for improving the absorption efficiency of thin-film solar cells and can provide a new approach for high-extraction-efficiency light-emitting diodes.


Processing cord blood from premature infants into autologous red-blood-cell products for transfusion.
The use of umbilical cord blood (UCB) for transfusion purposes has gained interest the past years. UCB transfusion could serve premature infants, who often need transfusions early in life. We investigated the suitability of different storage media. UCB was collected after 25 0/7--35 6/7 gestational weeks and centrifuged to concentrate red cells subsequently stored in saline-adenine-glucose-mannitol (SAGM), or in additive solution-3 (AS-3), or stored as whole blood in citrate-phosphate-dextrose-adenine-1. Quality parameters were measured at 7 day intervals during 35 days and compared to the standard RBC product. White-blood-cell- and platelet counts were higher in the UCB products. In the fractionated units, haemolysis remained below 1·0% in 64% after 14 days, and in 30% after 21 days. Storage in SAGM or AS-3 showed similar quality. Whole blood UCB showed better pH and haemolysis rates after 21 days. UCB can be processed into autologous products for premature infants. Shelf-life is limited to 14-21 days and compares unfavourably to stored whole blood. Considering the early transfusion needs in these infants, a short shelf-life would not be a practical objection.


Reversible photodynamic chloride-selective sensor based on photochromic spiropyran.
We report here for the first time on a reversible photodynamic bulk optode sensor based on the photoswitching of a spiropyran derivative (Sp). The photoswitching of Sp induces a large basicity increase in the polymeric phase, which triggers the extraction of Cl(-) and H(+). Cl(-) is stabilized by a lipophilic chloride-selective ionophore inside the membrane, while H(+) binds with the open form of Sp and induces a spectral change, hence providing the sensor signal. The system was studied with spectroscopic and electrochemical methods.


Preoperative high respiratory quotient correlates with lower weight loss after bariatric surgery.
The respiratory coefficient (RQ), as determined by indirect calorimetry (IC), classifies diet as being carbohydrate rich (RQ = 0.7-0.8), fat rich (RQ = 0.9-1.0), or overfeeding (RQ > 1). We hypothesized that preoperative RQ may be associated with weight-loss outcomes after bariatric surgery. From 2016 to 2018, 137 obese patients were enrolled in a Bariatric Registry and underwent dietary and behavioral counseling, followed by preoperative IC. Resting energy expenditure (REE) and RQ of all patients was measured. Patients were classified as over-feeders (OF; 42, 31%) with RQ > 1 or non-over-feeders (NOF; 95, 69%) with RQ < 1. At baseline, there was no difference between groups in gender [female: 105 (76.6%), male: 32 (23.4%)], body mass index (BMI; OF: 46.8 ± 7.8 vs. NOF: 44.8 ± 7.4 kg/m2, p = 0.40), or baseline REE (OF: 1897 ± 622 vs. NOF: 1874 ± 579, p = 0.74), although OF were younger [mean age (OF: 47.1 ± 13.0 years vs. NOF: 43.1 ± 13.4; p = 0.009). At 6-month follow-up 94 patients [53.28%; OF: 35 (83%) vs. NOF: 59 (62%), p = 0.016] were seen and 48 [35.03%; OF: 23 (55%) vs. NOF: 25 (59%), p = 0.001] at 12-month follow-up. On preoperative psychological assessment, OF had a significantly higher rate of childhood neglect (OF: 28 (47.46%) vs. NOF: 40 (28.99%); p = 0.01). At 1 year postoperatively, the OF had a significantly higher BMI (OF: 34.3 ± 6.5 vs. NOF: 29.3 ± 5.1 kg/m2, p = 0.009). Differences in weight were not significant at 6-month (OF: 36.0 ± 6.5 vs. NOF: 33.5 ± 5.9 kg/m2, p = 0.07). There was no difference between type of operation and RQ group (RYGB; OF: 55 (75%) vs. NOF: 18 (25%) and SG; OF: 40 (62%) vs. NOF: 24 (38%), p = 0.14), nor in BMI loss after operation. Evidence of overfeeding in the preoperative period prior to bariatric surgery is associated with higher resultant BMI at 1 year. Calculation of the RQ with IC has prognostic significance in bariatric surgery, and calculation of REE based on assumed normal RQ potentiates error. It is unclear if overfeeding is purely behavioral or secondary to potentially reversible metabolic etiology.


HBsAg detection by passive hemagglutination (Hepanosticon--Organon). Advantages and disadvantages in comparison with other methods.
Investigated comparatively with immunodiffusion, electroimmunodiffusion, complement fixation and Latex agglutination, passive hemagglutination with the Hepanosticon--Organon reagent proved to be an easy, rapid, highly reproducible method for HBsAg detection.


Dense GAN and multi-layer attention based lesion segmentation method for COVID-19 CT images.
As the COVID-19 virus spreads around the world, testing and screening of patients have become a headache for governments. With the accumulation of clinical diagnostic data, the imaging big data features of COVID-19 are gradually clear, and CT imaging diagnosis results become more important. To obtain clear lesion information from the CT images of patients' lungs is helpful for doctors to adopt effective medical methods, and at the same time, is helpful to screen the patients with real infection. Deep learning image segmentation is widely used in the field of medical image segmentation. However, there are some challenges in using deep learning to segment the lung lesions of COVID-19 patients. Since image segmentation requires the labeling of lesion information on a pixel by pixel basis, most professional radiologists need to screen and diagnose patients on the front line, and they do not have enough energy to label a large amount of image data. In this paper, an improved Dense GAN to expand data set is developed, and a multi-layer attention mechanism method, combined with U-Net's COVID-19 pulmonary CT image segmentation, is proposed. The experimental results showed that the segmentation method proposed in this paper improved the segmentation accuracy of COVID-19 pulmonary medical CT image by comparing with other image segmentation methods.


Hydroxyl orientation in muscovite as indicated by electrostatic energy calculations.
The electrostatic energy of the 2M(1) muscovite structure, KAl(2)(Si(3)Al)- O(10)(OH)(2), has been calculated as a function of the orientation of the hydroxyl group (O-H distance = 0.97 angstrom). The minimum in the electrostatic energy occurs when the OH bond makes an angle of 18 degrees with the cleavage plane and an angle of 31 degrees with the b-axis (in the a-b plane), which is 2.5 degrees away from the orientation of the transition moment as determined from infrared measurements on single crystals. If the K+ ion is excluded from the calculation, the O-H bond makes an angle of 53 degrees with the cleavage plane. This indicates the strong influence that the interlayer cation exerts on the hydroxyl hydrogen in mica structures.


Early spondyloarthropathy: scintigraphic, biological, and clinical findings in MRI-positive patients.
There are no specific diagnostic tests or a gold standard method for measuring disease activity and outcome in spondyloarthropathies (SpA). Many different methods have been developed to assess the signs and symptoms in SpA. The aim of this study was to evaluate the value of scintigraphy, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and Bath Ankilosing Spondylitis Disease Activity Index (BASDAI) in the evaluation of disease activity in early axial SpA diagnosed with magnetic resonance imaging (MRI). Thirty early MRI-positive axial SpA patients (23 males, 7 females) with a median age of 35 (18-55) years and a median duration of inflammatory low back pain of 24 (8-60) months were included in the study. In the patients with sacroiliitis, the sensitivity, specificity, and positive and negative predictive values of disease activity parameters were determined regarding MRI as the gold standard method. The sensitivities of quantitative scintigraphy, visual scintigraphy, ESR, CRP, and BASDAI were 32, 82, 35, 71, and 60%, respectively. The specificities of quantitative scintigraphy, ESR, CRP, and BASDAI were 100, 100, 50, and 100%, respectively. The positive predictive values of quantitative scintigraphy, visual scintigraphy, ESR, CRP, and BASDAI were 100, 92, 100, 95, and 100%, respectively. The negative predictive values of quantitative scintigraphy, ESR, CRP, and BASDAI were 9, 10, 11, and 15%, respectively. Regarding MRI as the gold standard in the evaluation of disease activity, combined visual and quantitative bone scintigraphy can be valuable in patients with MRI-incompatible implants. Additionally, use of cheaper, simple, and readily reproducible tests such as CRP and BASDAI together could be valuable and practical in detecting disease activity in long-term follow-up of these patients.


Impact of coronary calcium on arterial age and coronary heart disease risk estimation using the MESA arterial age calculator.
We evaluated the impact of arterial age calculation on reclassification of global coronary heart disease risk using the Framingham risk score. We applied CHD risk factor data from the Prospective Army Coronary Calcium Project to the MESA arterial age calculator (available at http://www.mesa-nhlbi.org). Subjects (N=1998) were studied with measured CHD risk factors and electron beam computed tomography for the identification of coronary artery calcium. Framingham risk scores (FRS), using the 10-year CHD risk model with and without arterial age, were calculated using the MESA arterial age calculator. The mean FRS of the cohort (42.9 + or - 2.7 years, male gender 82%) was 4.5 + or - 3.6%. Coronary calcium was present in 394 subjects (19.7%). Application of the arterial age calculator increased mean age from 42.9 + or - 2.7 to 43.6 + or - 10.4 years (P<.001), and the mean FRS increased from 4.5 + or - 3.6 to 7.3 + or - 8.1% (P<.001). Reclassification was seen primarily among male subjects, in whom the mean age (chronological vs. arterial age) increased from 42.9 + or - 2.7 to 44.2 + or - 11.0 (P<.001) and the prevalence of high CHD risk increased from 0.6% (10 of 1639) to 10% (165 of 1639; P<.001). Among healthy individuals ages 40-50, application of the MESA arterial age calculator reclassifies 1 in 10 men from low to intermediate risk and 1 in 15 men from low to high risk.


[Rhythmic circulatory dysregulation in stiff man syndrome].
A woman with severe stiff-man syndrome showed periodic cardiovascular dysregulation. The blood pressure changed spontaneously every 5-10 min. This rhythm was also maintained after relaxation. However, the vegetative and motoric disturbances disappeared after intrathecal application of baclofen. It is speculated that spinal GABAergic mechanisms are responsible for the tonic regulation of the cardiovascular system.


In silico analysis of the possible crosstalk between O-linked β-GlcNAcylation and phosphorylation sites of Disabled 1 adaptor protein in vertebrates.
Disabled 1 (Dab1) is an adaptor protein with essential functions regulated by reelin signaling and affects many biological processes in the nervous system, including cell motility, adhesion, cortical development, maturation, and synaptic plasticity. Posttranslational modifications directly guide the fates of cytoplasmic proteins to complete their functions correctly. Reciprocal crosstalk between O-GlcNAcylation and phosphorylation is a dynamic modification in cytoplasmic proteins. It modulates the functions of the proteins by regulating their interactions with other molecules in response to the continuously changeable cell microenvironment. Although Dab1 contains conserved recognition sites for phosphorylation in their N-terminal protein interaction domain, the O-β-GlcNAcylation and phosphorylation sites of human Dab1 sequence, their reciprocal crosstalk, and potential kinases catalyzing the phosphorylation remain unknown. In this study, we determined potential thirty-seven O-β-GlcNAcylation and sixty-seven phosphorylation sites. Conserved twenty-one residues of these glycosylated sites were also phosphorylated with various kinases, including ATM, CKI, DNAPK, GSK3, PKC, PKG, RSK, cdc2, cdk5, and p38MAPK. In addition, we analyzed these conserved sites at our constructed two- and three-dimensional structures of human Dab1 protein. Dab1 protein models were frequently composed of coil structures as well as α-helix and β-strands. Many of these conserved crosstalk sites between O-β-GlcNAcylation and phosphorylation were localized at the coil region of the protein model. These findings may guide biochemical, genetic, and glyco-biology based on further experiments about the Dab1 signaling process. Understanding these modifications might change the point of view of the Dab1 signaling process and treatment for pathological conditions in neurodegenerative diseases such as Alzheimer's disease.


Stable Confinement of Black Phosphorus Quantum Dots on Black Tin Oxide Nanotubes: A Robust, Double-Active Electrocatalyst toward Efficient Nitrogen Fixation.
A conceptually new, metal-free electrocatalyst, black phosphorus (BP) is presented, which is further downsized to quantum dots (QDs) for larger surface areas, and thus, more active sites than the bulk form. However, BP QDs are prone to agglomeration, which inevitably results in the loss of active sites. Besides, their poor conductivity is not favorable for charge transport during electrolysis. To solve these problems, an electrochemically active, electrically conductive matrix, black tin oxide (SnO2-x ) nanotubes, is employed for the first time. Through facile self-assembly, BP QDs are stably confined on the SnO2-x nanotubes due to Sn-P coordination, resulting in a robust, double-active electrocatalyst. Benefiting from their synergistic superiority, the BP@SnO2-x nanotubes deliver impressively high ammonia yield and Faradaic efficiency, which represent a successful attempt toward advanced hybrid electrocatalysts for ambient nitrogen fixation.


Major histocompatibility complex-linked immune-responsiveness is acquired by lymphocytes of low-responder mice differentiating in thymus of high-responder mice.
Female murine T cells can respond to the Y antigen of male cells by generating cytotoxic T-killer lymphocytes. Responsiveness is linked to several H-2 genes. Two types of low responders can be distinguished: the B10.A(5R) (H-2i5) strain, a low responder because it lacks Y-specific precursor T cells able to differentiate into cytotoxic T-killer cells; and the CBA/J (H-2k) strain, a low responder because it lacks Y-specific T-helper cells able to support differentiation of T-killer cell precursors. B10.A(5R) stem cells differentiating in an x-irradiated (CBA/J X C57BL/6) (H-2k X H-2b)F1 host respond to Y antigen by generating T-killer cells whereas CBA/J stem cells do not. The results are consistent with the hypothesis that diversity of T-cell receptors is generated by somatic mutation of germ-line genes encoding specificity for self-H-2. A detailed account of this hypothesis is presented.


The Beclin 1-VPS34 complex--at the crossroads of autophagy and beyond.
An increasing body of research on autophagy provides overwhelming evidence for its connection to diverse biological functions and human diseases. Beclin 1, the first mammalian autophagy protein to be described, appears to act as a nexus point between autophagy, endosomal, and perhaps also cell death pathways. Beclin 1 performs these roles as part of a core complex that contains vacuolar sorting protein 34 (VPS34), a class III phosphatidylinositol-3 kinase. The precise mechanism of Beclin 1-mediated regulation of these cellular functions is unclear, but substantial progress has recently been made in identifying new players and their functions in Beclin 1-VSP34 complexes. Here we review emerging studies that are beginning to unveil the physiological functions of Beclin 1-VPS34 in the central control of autophagic activity and other trafficking events through the formation of distinct Beclin 1-VPS34 protein complexes.


Smoking history and physical performance in midlife: results from the British 1946 birth cohort.
The adverse effects of smoking on individual medical conditions are well known; however, the cumulative effect of smoking on physical performance is not well characterized, particularly in midlife. In the British 1946 Birth Cohort Study, cigarette pack-years were examined with standing balance, chair rising, grip strength, and an overall composite index. Pack-years were calculated from data collected at ages 20, 25, 31, 36, 43, and 53 years, whereas physical performance, cognitive function, anthropometry, and spirometry were assessed at age 53 years in 2,394 men and women. Regression and cubic splines were used to assess the relationship between pack-years and physical performance. Greater pack-years smoked were associated with lower overall physical performance and lower performance in standing balance and chair rising; however, there was no association with grip strength. For every 10 pack-years smoked, the overall physical performance index decreased by 0.11 SD (95% confidence interval: 0.07-0.15, p < .001), standing balance time decreased by 0.09 SD (0.05-0.13), and the reciprocal of chair rise time decreased by 0.11 SD (0.07-0.16). Adjustment for education, social class, lung function, cognitive function, and medical conditions attenuated the effect, but pack-years remained significantly associated with standing balance and chair rising time. Lifetime cigarette pack-years are strongly related to physical performance in the fifth decade of life, suggesting that smokers will enter older adulthood with decreased physiological reserve. As smoking prevalence remains high in many developed countries and is rapidly growing in developing countries, these findings underscore the need for effective smoking cessation and prevention programs.


3D geometric morphometric analysis of the distal radius insertion sites of the palmar radiocarpal ligaments indicates a relationship between wrist anatomy and unique locomotor behavior in hylobatids.
The objective of this study is to explore the anatomical differences in the insertion sites of the palmar radiocarpal ligaments between hylobatids and other hominoids that may be related to their different locomotor behaviors. The morphology of the insertion sites of the palmar radiocarpal ligaments was analyzed with three-dimensional geometric morphometrics (3D GM) in the distal radial epiphysis of 44 hylobatids, 25 Pan, 31 Gorilla and 15 Pongo. Relative to other hominoids, hylobatid insertion sites of the palmar radiocarpal ligaments were relatively larger and the insertion site of the short radiolunate ligament had a palmar orientation. Larger palmar radiocarpal ligaments in hylobatids can help stabilize the wrist during the radial and ulnar displacement that occurs in ricochetal brachiation, the characteristic locomotor behavior of hylobatids, and compensate for the large traction loads on the wrist during extended-elbow vertical climbing.


Cross-Validated Bagged Learning.
Many applications aim to learn a high dimensional parameter of a data generating distribution based on a sample of independent and identically distributed observations. For example, the goal might be to estimate the conditional mean of an outcome given a list of input variables. In this prediction context, bootstrap aggregating (bagging) has been introduced as a method to reduce the variance of a given estimator at little cost to bias. Bagging involves applying an estimator to multiple bootstrap samples, and averaging the result across bootstrap samples. In order to address the curse of dimensionality, a common practice has been to apply bagging to estimators which themselves use cross-validation, thereby using cross-validation within a bootstrap sample to select fine-tuning parameters trading off bias and variance of the bootstrap sample-specific candidate estimators. In this article we point out that in order to achieve the correct bias variance trade-off for the parameter of interest, one should apply the cross-validation selector externally to candidate bagged estimators indexed by these fine-tuning parameters. We use three simulations to compare the new cross-validated bagging method with bagging of cross-validated estimators and bagging of non-cross-validated estimators.


PDZ domain-containing 1 (PDZK1) protein regulates phospholipase C-β3 (PLC-β3)-specific activation of somatostatin by forming a ternary complex with PLC-β3 and somatostatin receptors.
Phospholipase C-β (PLC-β) is a key molecule in G protein-coupled receptor (GPCR)-mediated signaling. Many studies have shown that the four PLC-β subtypes have different physiological functions despite their similar structures. Because the PLC-β subtypes possess different PDZ-binding motifs, they have the potential to interact with different PDZ proteins. In this study, we identified PDZ domain-containing 1 (PDZK1) as a PDZ protein that specifically interacts with PLC-β3. To elucidate the functional roles of PDZK1, we next screened for potential interacting proteins of PDZK1 and identified the somatostatin receptors (SSTRs) as another protein that interacts with PDZK1. Through these interactions, PDZK1 assembles as a ternary complex with PLC-β3 and SSTRs. Interestingly, the expression of PDZK1 and PLC-β3, but not PLC-β1, markedly potentiated SST-induced PLC activation. However, disruption of the ternary complex inhibited SST-induced PLC activation, which suggests that PDZK1-mediated complex formation is required for the specific activation of PLC-β3 by SST. Consistent with this observation, the knockdown of PDZK1 or PLC-β3, but not that of PLC-β1, significantly inhibited SST-induced intracellular Ca(2+) mobilization, which further attenuated subsequent ERK1/2 phosphorylation. Taken together, our results strongly suggest that the formation of a complex between SSTRs, PDZK1, and PLC-β3 is essential for the specific activation of PLC-β3 and the subsequent physiologic responses by SST.


Maternal and child's vitamin D supplement use and vitamin D level in relation to childhood lung function: the KOALA Birth Cohort Study.
Vitamin D is associated with lung function in adults, but its relation with childhood lung function is still unclear. To investigate whether prenatal and postnatal vitamin D supplementation and plasma level is associated with childhood lung function. In the KOALA Birth Cohort Study, children's lung function (n=436) was measured at age 6-7 years by means of spirometry and presented as forced expiratory volume in 1 s (FEV1) z scores and forced vital capacity z scores. The mother and child's 25-hydroxyvitamin D plasma level was determined around 36 weeks of pregnancy and at age 2 years. Vitamin D supplement intake during pregnancy was defined based on the amount of vitamin D in supplements, and trimester and duration of use. Data on child's vitamin D supplement use were collected through questionnaires at ages 1, 2 and 6-7 years. 25-Hydroxyvitamin D level and vitamin D supplement use in childhood were not associated with lung function. Maternal use of vitamin D at ≤10 μg/day (adjusted beta (AdjB -0.37; 95% CI -0.69 to -0.05)), vitamin D containing multivitamin use in the second and/or third trimester (AdjB -0.26; 95% CI -0.49 to -0.03), and use for two trimesters (AdjB -0.25; 95% CI -0.49 to -0.02) were associated with a significantly lower FEV1 z score compared with no supplements. Maternal use of vitamin D at ≥10 μg/day and use in the first or all trimesters was not associated with significantly lower lung function levels. The authors found no association between 25-hydroxyvitamin D levels, vitamin D supplementation in childhood or recommended vitamin D dosage of ≥10 μg/day during pregnancy and lung function in children aged 6-7 years.


Further studies of diabetes-prone BHE/Cdb rats: increased sensitivity to calcium ion suppression of oxidative phosphorylation.
The responsiveness of hepatic mitochondria isolated from hyperthyroid and control Sprague-Dawley (SD) and diabetes-prone BHE/Cdb rats was studied. Hyperthyroidism was induced through the addition of thyroxine (T(4)) to the diet (2 mg/kg of diet). Oxidative phosphorylation (OXPHOS) with the addition of adenosine diphosphate (ADP) or an 8:1 mixture of adenosine monophosphate (AMP):ADP was studied. Dose response curves of state 3 and state 4 respiration, respiratory control (RC) ratio, and ADP:O ratio to calcium levels (0-7.5 microm) were generated. Mitochondria from BHE/Cdb rats were more sensitive to the addition of calcium than mitochondria from SD rats, as judged by losses in OXPHOS. T(4) treatment potentiated this strain difference and we conclude that the diabetes phenotype in the BHE/Cdb rat is probably related not only to the previously described mutation in the F(O)ATPase but also to a defect in the efflux of the calcium ion that, in turn, affected the regulation of OXPHOS.


Erratum: Lycorine hydrochloride inhibits melanoma cell proliferation, migration and invasion via down-regulating p21Cip1/WAF1.
[This corrects the article on p. 1391 in vol. 11, PMID: 33948364.].


Pullulan film incorporated with nanocapsules improves pomegranate seed oil anti-inflammatory and antioxidant effects in the treatment of atopic dermatitis in mice.
This study aimed to prepare pullulan films containing pomegranate seeds oil (PSO) based nanocapsules, and evaluate the formulation efficacy in the treatment of atopic dermatitis (AD)-like lesions induced by 2,4-dinitrochlorobenzene (DNCB). The Eudragit RS 100® nanocapsules (PSONC) were prepared by the interfacial precipitation of preformed polymer, whereas the films were produced by the solvent casting method. Pomegranate seed oil nanoemulsions (PSONE) were prepared by the spontaneous emulsification method for comparative reasons. Both nanosystems presented adequate mean diameter (248 ± 16 nm for PSONE and 181 ± 6 nm for PSONC), polydispersity index (below 0.2), zeta potential (-25.63 ± 1.1 mV for PSONE and + 43.13 ± 0.7 mV for PSONC) and pH in the acid range (6.77 ± 0.27 and 5.31 ± 0.17, PSONE and PSONC). By a pre-formulation study, sorbitol (6.5%) and PEG 400 (1.5%) were considered the most suitable plasticizers for developing pullulan films (6%) intending topical application. In general, pullulan films were classified as flexible and hydrophilic, with high occlusive properties, 57.6 ± 0.8%, 64.6 ± 0.8% for vehicle, PSONCF (pullulan film containing PSONC), respectively. All formulations (films and nanocarriers) presented no irritant potential in the chorioallantoic membrane test. In the in vivo model, the treatments with free PSO and PSONCF attenuated the skin injury as well as the mechanical hypernociceptive behavioral induced by DNCB exposure to mice. Importantly, the biochemical analyses provided evidence that only the treatment with PSONCF modulated the inflammatory and the oxidative stress parameters evaluated in this study. In conclusion, these data lead us to believe that PSONC incorporation into a pullulan film matrix improved the biological properties of the PSO in this AD-model.


Elevated prevalence of multidrug-resistant gram-negative organisms in HIV positive men.
Routes of transmission of multidrug-resistant gram-negative organisms (MDRGN) are not completely understood. Since sexual transmission of MDRGN might represent a potential mode that has not been noticed so far, this study evaluated transmission of MDRGN in HIV positive men. Between November 2014 and March 2016, we retrospectively investigated the MDRGN prevalence in rectal swabs of n = 109 males tested positive for HIV (HP). These findings were compared to the MDRGN prevalence in n = 109 rectal swabs in age-matched males tested negative for HIV (HN) within the same period. According to the infection control protocol of University Hospital Frankfurt, Germany (UHF), patients admitted to intensive/intermediate care units have to be screened for MDRGN on day of admittance. Patients without HIV testing or MDRGN screening were excluded. MDRGN prevalence in rectal swabs was significantly higher (p = 0.002) in male HP (23.9%; 95% confidence interval 16.2-32.9%) than in age-matched male HN (8.3%; 3.8-15.1%). In total, 35 MDRGN species were detected. The most frequent MDRGN species was Escherichia coli with resistance due to ESBL expression and additional resistance to fluoroquinolones with n = 25/35 (71.4%; 53.7-85.4%). Thereof, n = 19/26 (73.1%; 52.2-88.4%) were detected in HP and n = 6/9 (66.7%; 29.9-92.5%) in HN, respectively. Prevalence of MDRGN is significantly higher in male HIV positive than in male HIV negative individuals. This might indicate sexual transmission of MDRGN within the male HIV positive population. As treatment options in case of MRGN infections are limited, prevention of MDRGN transmission is strongly emphasized.


Coordinate based meta-analysis of networks in neuroimaging studies.
Meta-analysis of summary results from published neuroimaging studies independently testing a common hypothesis is performed using coordinate based meta-analysis (CBMA), which tests for consistent activation (in the case of functional MRI studies) of the same anatomical regions. Using just the reported coordinates it is also possible to meta-analyse coactivated regions to reveal a network-like structure of coordinate clusters (network nodes) distributed at the coactivated locations and a measure of the coactivation strength (network edges), which is determined by the presence/absence of reported activation. Here a new coordinate-based method to estimate a network of coactivations is detailed, which utilises the Z score accompanying each reported. Coordinate based meta-analysis of networks (CBMAN) assumes that if the activation pattern reported by independent studies is truly consistent, then the relative magnitude of these Z scores might also be consistent. It is hypothesised that this is detectable as Z score covariance between coactivated regions provided the within study variances are small. Advantages of using the Z scores instead of coordinates to measure coactivation strength are that censoring by the significance thresholds can be considered, and that using a continuous measure rather than a dichotomous one can increase statistical power. CBMAN uses maximum likelihood estimation to fit multivariate normal distributions to the standardised Z scores, and the covariances are considered as edges of a network of coactivated clusters (nodes). Here it is validated by numerical simulation and demonstrated on real data used previously to demonstrate CBMA. Software to perform CBMAN is freely available.


Impact of contact precautions on falls, pressure ulcers and transmission of MRSA and VRE in hospitalized patients.
Hospitals use contact precautions to prevent the spread of meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). There is concern that contact precautions may have adverse effects on the safety of isolated patients. In November 2010, the infection control policy at an academic medical centre was modified, and contact precautions were discontinued for patients colonized or infected with MRSA or VRE (MRSA/VRE patients). To assess the rates of falls and pressure ulcers among MRSA/VRE patients and other adult medical-surgical patients, as well as changes in MRSA and VRE transmission before and after the policy change. A single-centre retrospective hospital-wide cohort study was performed from 1st November 2009 to 31st October 2011. Rates of falls and pressure ulcers were significantly higher among MRSA/VRE patients compared with other adult medical-surgical patients before the policy change (falls: 4.57 vs 2.04 per 1000 patient-days, P < 0.0001; pressure ulcers: 4.87 vs 1.22 per 1000 patient-days, P < 0.0001) and after the policy change (falls: 4.82 vs 2.10 per 1000 patient-days, P < 0.0001; pressure ulcers: 4.17 vs 1.19 per 1000 patient-days, P < 0.0001). No significant differences in the rates of falls and pressure ulcers among MRSA/VRE patients were found after the policy change compared with before the policy change. There was no overall change in MRSA or VRE hospital-acquired transmission. MRSA/VRE patients had higher rates of falls and pressure ulcers compared with other adult medical-surgical patients. Rates were not affected by removal of contact precautions, suggesting that other factors contribute to these complications. Further research is required among this population to prevent complications.


Acetyl-11-keto-β-boswellic acid regulates the repair of rat sciatic nerve injury by promoting the proliferation of Schwann cells.
This study aimed to study the effects of acetyl-11-keto-β-boswellic acid (AKBA) on the regeneration of injured peripheral nerves and the ability of the extracellular signal-regulated kinase (ERK) signaling pathway to regulate the proliferation of Schwann cells and the formation of myelin. A sciatic nerve crush injury model rats were randomly divided into the model control, low-, medium-, and high-dose AKBA groups. The repair of myelin damage was observed through Luxol Fast Blue staining and the expression of neurofilament-200 (NF200) protein was detected through immunohistochemical tests. The relative expression levels of ERK, Phosphorylated-ERK (p-ERK), c-Jun N-terminal Kinase (JNK), and Phosphorylated-JNK (p-JNK) proteins were detected in vitro in Schwann cells treated with AKBA. The effect of AKBA on P0 and P75 protein expression in Schwann cells was detected through siRNA-mediated ERK gene knockout. AKBA promotes the repair of rat sciatic nerve injury by elevating the phosphorylation of the ERK signaling pathway and by regulating the proliferation and myelination of Schwann cells. This test can provide data support for AKBA to repair sciatic nerve injury, provide a theoretical basis for further revealing AKBA repair mechanism, and provide reference for clinical development of sciatic nerve injury drugs.


Conservative management of distal bicipital tendinopathy with lateral antebrachial nerve entrapment: A case report.
Kettlebell snatches are an efficient and effective exercise. If the kettlebell being utilized is too heavy or too many repetitions are executed, this can lead to an overuse injury such as a tendinopathy. Multiple orthopedic tests exist to evaluate for a distal biceps tendon rupture. At present, there are no publications utilizing shockwave and active rehabilitation to treat distal bicipital tendinopathy with Lateral Antebrachial Cutaneous Nerve (LABCN) entrapment. Currently, no published manuscripts are reporting distal bicipital tendinopathy with LABCN nerve entrapment being treated successfully with shockwave and active rehabilitation over the course of 5 weeks. The objective of this case report is to examine the conservative management of a 37-year-old male with a diagnosis of distal bicipital tendinopathy and LABCN entrapment. The patient presents with discomfort originated weeks prior after an intense block of kettlebell training. The patient was diagnosed with brachioradialis tendinopathy due to the specifics of his injury. Following the initial evaluation, the patient was unable to supinate the forearm past 45° actively, yet he can passively achieve 90°, although this is done with minor discomfort. The patient's rehab began with the execution of wrist, elbow, and shoulder controlled articular rotation (CARS). The concept of CARs is to train the joint and soft tissues to respond to full range activity. A progressive approach utilizing isometric to eccentric exercise with extracorporeal shockwave was used. The authors studied forty-eight patients with chronic distal biceps tendinopathy. After five shockwave therapy treatments over three months, there was a significant decrease in symptomology without complications (Furia et al., 2017). This case report demonstrates that active rehabilitation and shockwave therapy effectively resolved the patient's symptoms with no adverse reactions. Additionally, the case report can be a suggested management protocol for successful conservative management for patients with suspected distal bicipital tendinopathy with LABCN entrapment going forward.