Evaluating the effects of vitamin D Level on airway obstruction in two asthma endotypes in humans and in two mouse models with different intake of vitamin D during early-life.
Asthma is primarily divided into two categories: type 2 (T2-high) and non-type 2 (T2-low). A relationship between asthma severity and vitamin D deficiency has been identified, but its impact on each asthma endotype remains unknown. We clinically examined the influence of vitamin D on patients with T2-high (n = 60) or T2-low asthma (n = 36) compared with controls (n = 40). Serum 25(OH)D levels, inflammatory cytokines and spirometry were measured. Mouse models were then used to further analyze the effects of vitamin D on both asthmatic endotypes. BALB/c mice were fed with vitamin D-deficient (LVD), -sufficient (NVD), or -supplemented diets (HVD) throughout lactation and offspring followed the same diet after weaning. Offspring were sensitized/challenged with ovalbumin (OVA) to establish "T2-high" asthma or OVA combined with ozone exposure (OVA + ozone) to induce "T2-low" asthma. Spirometry and serum, bronchoalveolar lavage fluid (BALF), and lung tissues were analyzed. Serum 25(OH)D levels were decreased in asthmatic patients compared with controls. Patients with vitamin D deficiency (Lo) had varying degrees of elevation of the pro-inflammatory cytokines IL-5, IL-6, and IL-17A, decreased expression of the anti-inflammatory cytokine IL-10, and altered forced expiratory volume in the first second as a percentage of predicted value (FEV1%pred) in both asthmatic endotypes. Vitamin D status had a stronger correlation with FEV1%pred in T2-low asthma than T2-high asthma, and 25(OH)D level was only positively linked to maximal mid-expiratory flow as a percentage of predicted value (MMEF%pred) in the T2-low group. Inflammation, hyperresponsiveness, and airway resistance (RL) was increased in both asthma models compared with controls while vitamin D deficiency further increased airway inflammation and airway obstruction. These findings were particularly prominent in T2-low asthma. The potential function and mechanisms of vitamin D and both asthma endotypes should be studied individually, and further analysis of the potential signaling pathways involved with vitamin D on T2-low asthma is warranted.


PTEN regulates TLR5-induced intestinal inflammation by controlling Mal/TIRAP recruitment.
Defective IL-10 allele is a risk factor for intestinal inflammation. Indeed, IL-10(-/-) mice are predisposed to spontaneous colitis in the presence of intestinal microbiota, indicating that microbial factors contribute to developing intestinal inflammation. By recognizing flagellin, TLR5 plays a quintessential role in microbial recognition in intestinal epithelial cells. Here, we treated flagellin (1.0 μg/mouse/d) in mouse colon and found that it elicited colonic inflammation in IL-10(-/-) mice, characterized with tissue hypertrophy, inflamed epithelium, and enhanced cytokine production in the colon (MPO, KC, IL-6; ≥2-fold; P < 0.05). These inflammatory effects were dramatically inhibited in TLR5(-/-);IL-10(-/-) mice. Intestinal epithelium specific PTEN deletion significantly attenuated flagellin-promoted colonic inflammation in IL-10(-/-) mice. As a molecular mechanism that PTEN deletion inhibited TLR5-elicited responses, we hypothesized that PTEN regulated TLR5-induced responses by controlling the involvement of Mal in TLR5 engagement. Mal interacted with TLR5 on flagellin, and Mal deficiency inhibited flagellin-induced responses in intestinal epithelial cells. Similarly, Mal(-/-);IL-10(-/-) mice showed reduced flagellin-promoted responses. Furthermore, PTEN deletion disrupted Mal-TLR5 interaction, resulting in diminished TLR5-induced responses. PTEN deletion impeded Mal localization at the plasma membrane and suppressed Mal-TLR5 interaction. These results suggest that, by controlling Mal recruitment, PTEN regulates TLR5-induced inflammatory responses.


Complete removal of endocrine disrupting compound and toxic dye by visible light active porous g-C3N4/H-ZSM-5 nanocomposite.
Photocatalytic degradation of toxic pollutants is an efficient technique to completely remove the toxic pollutants from water bodies. In the present investigation, photocatalytic degradation of pollutants was studied over porous g-C3N4/H-ZSM-5 nanocomposite under visible light irradiation. The composite g-C3N4/H-ZSM-5 was synthesized by mixing an aqueous solution of H-ZSM-5 zeolite (increases surface area and provides active sites for degradation) with melamine (precursor of g-C3N4) for 10-12 h followed by calcinations at 550 °C. The photocatalyst was characterized by XRD, BET, HRTEM, FESEM, EDS and elemental mapping analysis. These techniques confirmed that, g-C3N4/H-ZSM-5 composite have layered and porous structure with uniform distribution of g-C3N4 on H-ZSM-5 surface. The BET N2 adsorption-desorption analysis verified that the catalyst has high surface area (∼175 m2/g) having mesopores and micropores. The prepared catalyst was then used for the photodegradation of a model dye, Methylene Blue (MB) and an endocrine disrupting compound, Fipronil (FIP). Effects of various parameters such as pH, catalyst dose and scavengers were also studied. The % photocatalytic degradation of MB and FIP were around ∼92% and ∼84% with a high rate constants of 0.00997 and 0.00875 min-1, respectively. From the scavenger study, OH (hydroxyl radical) and radical was found to be the major reactive species for MB and FIP degradation. From these studies it is revealed that, the catalyst is visible active, easy to prepare and an efficient photocatalyst for toxic pollutant degradation.


[Theoretical basis for and the results of using bone marrow-devoid spongy allografts in the surgery of tuberculous spondylitis in adults].
Experimental studies over 189 animals have proved that spongy allografts, devoid of the bone marrow, possess high plastic properties, get very soon replaced with a newly formed bone tissue and reconstruct. Experimental and clinical findings advocate, the rationality of their use of antero-lateral spondylodesis in tuberculous spondylitis.


VIIa/tissue factor interaction results in a tissue factor cytoplasmic domain-independent activation of protein synthesis, p70, and p90 S6 kinase phosphorylation.
FVIIa binding to tissue factor (TF) and subsequent signal transduction have now been implicated in a variety of pathophysiological processes, including cytokine production during sepsis, tumor angiogenesis and neoangiogenesis, and leukocyte diapedesis. The molecular details, however, by which FVIIa/TF affects gene expression and cellular physiology, remain obscure. Here we show that FVIIa induces a transient phosphorylation of p70/p85(S6K) and p90(RSK) in BHK cells stably transfected with either full-length TF or with a cytoplasmic domain-truncated TF but not in wild type BHK cells. Phosphorylation of these kinases was also observed in HaCaT cells, expressing endogenous TF. Phosphorylation of p70/p85(S6K) coincided with protein kinase B and GSK-3beta phosphorylation. Activation of p70/p85(S6K) was sensitive to inhibitors of phosphatidylinositol 3-kinase and to rapamycin, whereas phosphorylation of p90(RSK) was sensitive to PD98059. FVIIa stimulation of p70/p85(S6K) and p90(RSK) correlated with phosphorylation of the eukaryotic initiation factor eIF-4E, up-regulation of protein levels of eEF1alpha and eEF2, and enhanced [(35)S]methionine incorporation. These effects were not influenced by inhibitors of thrombin or FXa generation and were strictly dependent on the presence of the extracellular domain of TF, but they did not require the intracellular portion of TF. We propose that a TF cytoplasmic domain-independent stimulation of protein synthesis via activation of S6 kinase contributes to FVIIa effects in pathophysiology.


Complex retinal detachment treated with silicone oil or sulfur hexafluoride gas: a randomized clinical trial.
To determine if either silicone oil or sulfur hexafluoride gas (SF6) is superior to the other in the treatment of complex retinal detachment after previously failed vitreous surgery. In this randomized clinical trial, 18 patients received treatment with silicone oil and 16 patients received SF6. The primary outcome was defined as successful anatomic attachment of the retina. Secondary outcomes included the time to retinal detachment, visual acuity, anatomic macular attachment, and any complications of surgery. The odds of successful reattachment with silicone oil were 50% greater than they were with SF6, but this difference was not statistically significant. There were no differences between the two groups in any of the secondary outcomes. This study did not have enough statistical power to detect a small but clinically important difference between the two treatment groups. Physicians must use their clinical judgment to select a vitreal substitute for complex retinal detachment when clinical trials are inconclusive. Data pooling is one method of overcoming the limitation of clinical trials with small sample sizes.


A rapid and simplified technique for the assay of chicken hemolytic complement.
The technique described is a modification of a qualitative hemolytic radial diffusion technique. The test involves the use of sensitized sheep erythrocytes that have been incorporated into agarose. Tube dilutions were made of chicken serum and samples of each dilution were placed into wells cut in the agarose. The test is quantitative for hemolytic complement in that the highest dilution showing visible hemolysis of sensitized erythrocytes in agarose is determined to be the endpoint for that serum sample. The test as compared with the standard tube assay was determined to be less sensitive by approximately one dilution. The advantages of speed, simplicity, and cost more than offset the decrease in sensitivity of the test.


Neuropsychological basic deficits in preschoolers at risk for ADHD: a meta-analysis.
Widely accepted neuropsychological theories on attention deficit hyperactivity disorder (ADHD) assume that the complex symptoms of the disease arise from developmentally preceding neuropsychological basic deficits. These deficits in executive functions and delay aversion are presumed to emerge in the preschool period. The corresponding normative developmental processes include phases of relative stability and rapid change. These non-linear developmental processes might have implications for concurrent and predictive associations between basic deficits and ADHD symptoms. To derive a description of the nature and strength of these associations, a meta-analysis was conducted. It is assumed that weighted mean effect sizes differ between basic deficits and depend on age. The meta-analysis included 25 articles (n=3005 children) in which associations between assessments of basic deficits (i.e. response inhibition, interference control, delay aversion, working memory, flexibility, and vigilance/arousal) in the preschool period and concurrent or subsequent ADHD symptoms or diagnosis of ADHD had been analyzed. For response inhibition and delay aversion, mean effect sizes were of medium to large magnitude while the mean effect size for working memory was small. Meta-regression analyses revealed that effect sizes of delay aversion tasks significantly decreased with increasing age while effect sizes of interference control tasks and Continuous Performance Tests (CPTs) significantly increased. Depending on the normative maturational course of each skill, time windows might exist that allow for a more or less valid assessment of a specific deficit. In future research these time windows might help to describe early developing forms of ADHD and to identify children at risk.


Is 640 nm high-fluence visible red light a valuable adjunct for treating pemphigus vegetans? A single case report.
Pemphigus vegetans is an autoimmune bullous disorder characterized by vegetating lesions commonly over the flexures. This disorder is characterized by vegetating lesions more commonly over flexures. Cerebriform tongue, a morphology with typical pattern of sulci and gyri over dorsum of the tongue, is a well-known sign seen in pemphigus vegetans. To emphasize the exceptional but successful use of corticosteroid and 640 nm high-fluence visible red light in pemphigus vegetans. The patient was successfully treated with low dose systemic corticosteroid (methylprednisolone 20 mg daily) and high-fluence 640 nm LED red light on pustules and exudates (LIFOTRONICR, 120 mw/cm2 power density and 210 J/cm2 energy density). The cerebriform plaques improved quickly after the treatment of corticosteroid and 640 nm high-fluence visible red light. We propose to consider low dosage of methylprednisolone and 640 nm high fluence visible red light as first-line monotherapy in pemphigus vegetans, especially in elderly patients with comorbidities and contraindications to standard therapy, as it avoids the toxicities of systemic corticosteroids and immunosuppressants.


iDNA-ABT: advanced deep learning model for detecting DNA methylation with adaptive features and transductive information maximization.
DNA methylation plays an important role in epigenetic modification, the occurrence, and the development of diseases. Therefore, identification of DNA methylation sites is critical for better understanding and revealing their functional mechanisms. To date, several machine learning and deep learning methods have been developed for the prediction of different DNA methylation types. However, they still highly rely on manual features, which can largely limit the high-latent information extraction. Moreover, most of them are designed for one specific DNA methylation type, and therefore cannot predict multiple methylation sites in multiple species simultaneously. In this study, we propose iDNA-ABT, an advanced deep learning model that utilizes adaptive embedding based on Bidirectional Encoder Representations from Transformers (BERT) together with transductive information maximization (TIM). Benchmark results show that our proposed iDNA-ABT can automatically and adaptively learn the distinguishing features of biological sequences from multiple species, and thus perform significantly better than the state-of-the-art methods in predicting three different DNA methylation types. In addition, TIM loss is proven to be effective in dichotomous tasks via the comparison experiment. Furthermore, we verify that our features have strong adaptability and robustness to different species through comparison of adaptive embedding and six handcrafted feature encodings. Importantly, our model shows great generalization ability in different species, demonstrating that our model can adaptively capture the cross-species differences and improve the predictive performance. For the convenient use of our method, we further established an online webserver as the implementation of the proposed iDNA-ABT. Our proposed iDNA-ABT and data are freely accessible via http://server.wei-group.net/iDNA_ABT and our source codes are available for downloading in the GitHub repository (https://github.com/YUYING07/iDNA_ABT). Supplementary data are available at Bioinformatics online.


Influence of dibutyryl cyclic AMP on thymidine uptake by herpes simplex virus infected cells and the intracellular level of cyclic AMP.
Dibutyryl cyclic AMP inhibits the increase of dThd and BrdUrd transport normally observed after infection with Herpesvirus hominis, type I and II. Incorporation is also reduced. Inhibition of uptake is non-competitive as analysed by the Lineweaver-Burk plot. Addition of this drug to infected cells also reduces the activity of the thymidine kinase (EC 184.108.40.206). Transport of dUrd, dCyd and dAdo is not reduced. 4--8 h after infection with thymidine kinase (+) herpes strains the level of cAMP increases. On infection with a thymidine kinase (-) virus, only a small elevation of cAMP can be shown. It was also found that early addition of actinomycin D or of cycloheximide prevents the increase of the cAMP level. This increase seems to depend on the activity of the herpes genome, because ultraviolet irradiation of infective particles destroys this ability.


New reference value and the background exposure for the PAH metabolites 1-hydroxypyrene and 1- and 2-naphthol in urine of the general population in Germany: basis for validation of human biomonitoring data in environmental medicine.
Reference values for environmental pollutants in the German population are established continuously by the Human Biomonitoring Commission of the German Federal Environment Agency. The reference value for 1-hydroxypyrene in urine was derived from the representative adult population data collection of the 1998 German Environmental Survey (GerES III) and the representative data collection for children of the German Environmental Survey on Children, 2003/06 (GerES IV). For the non-smoking general population (aged 3-69 years) the commission derived a reference value of 0.5 microg/l (corresponding to 0.3 microg/g creatinine) for 1-hydroxypyrene in urine. For 1- and 2-naphthol levels in urine the amount of data is small and not representative of the German population. Therefore, the commission recommends the following upper margins of background exposures for adult non-smokers: 1-naphthol less than 30 microg/l, 2-naphthol less than 20 microg/l.


Asymmetric dimethylarginine and all-cause mortality: a systematic review and meta-analysis.
Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), impairs the beneficial effect of NO. The predictive value of ADMA for all-cause mortality remains controversial, though it is important in the development of cardiovascular disease (CVD) and progression to dialysis in renal disease. This systematic review and meta-analysis was conducted to investigate the association between circulating ADMA and all-cause mortality. Studies with data pertinent to the association between circulating ADMA and all-cause mortality were reviewed and OR, HR or RR with 95% CI derived from multivariate Cox's proportional-hazards analysis were extracted. A total of 34 studies reporting 39137 participants were included in final analysis. The results demonstrated that circulating ADMA was independently associated with all-cause mortality (RR = 1.27, 95% CI: 1.20-1.34). The association was still statistically significant in patients with pre-existing renal disease (RR = 1.30, 95% CI: 1.19-1.43) and pre-existing CVD (RR = 1.26, 95% CI: 1.16-1.37). In those without pre-existing renal or CVD, ADMA also predicted all-cause mortality (RR = 1.31, 95% CI: 1.13-1.53). The present study suggests a positive association of circulating ADMA with all-cause mortality. Further studies are needed to investigate the effects of interventions on ADMA, and the value of ADMA as a biomarker.


Molecular biology of translation in yeast.
The combination of genetic, molecular and biochemical approaches have made the yeast Saccharomyces cerevisiae a convenient organism to study translation. The sequence similarity of translation factors from yeast and other organisms suggests a high degree of conservation in the translational machineries. This view is also strengthened by a functional analogy of some proteins implicated in translation. Beautiful genetic experiments have confirmed existing models and added new insights in the mechanism of translation. This review summarizes recent experiments using yeast as a model system for the analysis of this complex process.


Eosinophil accumulation in pulmonary airways of guinea-pigs induced by exposure to an aerosol of platelet-activating factor: effect of anti-asthma drugs.
1. Exposure of guinea-pigs to aerosols of platelet activating factor (PAF) (0.01 to 100 micrograms ml-1) induced a dose-dependent increased incidence of eosinophils in bronchoalveolar lavage fluid (BAL) at 48 h. Total leucocyte numbers and the percentages of lymphocytes and neutrophils were unchanged in BAL fluid. 2. Increased numbers of eosinophils were detected in BAL 1 h after exposure to PAF but eosinophilia was not maximal until 48 h. One week after exposure to PAF, the percentage of eosinophils in BAL was within the normal range. 3. Depletion of circulating platelets or neutrophils by intravenous injection of specific antisera did not modify accumulation of eosinophils in the airway lumen following inhalation of PAF (10 micrograms ml-1). 4. PAF-induced pulmonary airway eosinophil accumulation was inhibited by treatment with SDZ 64-412, a selective PAF-antagonist, whether the compound was administered before, or 30 min after, inhalation of PAF. 5. Pulmonary airway eosinophil accumulation due to inhaled PAF (10 micrograms ml-1) was inhibited by prior treatment with aminophylline, cromoglycate, ketotifen, dexamethasone and AH 21-132. 6. Pulmonary airway eosinophil accumulation due to inhaled PAF (10 micrograms ml-1) was not inhibited by prior treatment with indomethacin, salbutamol or mepyramine.


Effect of hydroxychloroquine on glucose control in patients with and without diabetes: a systematic review and meta-analysis of randomized controlled clinical trials.
The aim of this meta-analysis of randomized controlled trials was to evaluate the effect of hydroxychloroquine on glucose control. Randomized controlled trials examining the impact of hydroxychloroquine on glycemic markers were searched in PubMed, Web of Science, Scopus, and Google Scholar databases. Meta-analysis was performed using a random-effects model and sensitivity analysis through the leave-one-out method. Meta-analysis revealed a significant reduction of fasting glucose (WMD: - 8.05 mg/dl; 95% CI: - 11.17, - 4.93; I2 = 75%; p ˂0.0001), 2-h postprandial glucose (WMD: - 15.52 mg/dl; 95% CI: - 20.61, - 10.42; I2 = 53%; p ˂0.00001), and glycated hemoglobin (HbA1c) values (WMD: - 0.19%, 95% CI: - 0.37, - 0.02; I2 = 94%; p = 0.03) after hydroxychloroquine treatment. Otherwise, meta-analysis showed no significant effect of hydroxychloroquine on insulin levels (WMD: 16.52 μUI/ml; 95% CI: - 16.35, 49.40; I2 = 90%; p = 0.32) and HOMA-β (WMD: - 14.62; 95% CI: - 45.84, 16.59; I2 = 0%; p = 0.36). The present meta-analysis revealed that treatment with hydroxychloroquine improves glucose control through the reduction of fasting glucose, 2-h postprandial glucose, and HbA1c values. Given that the effect of hydroxychloroquine on beta-cell function is based only on two clinical trials, it is not possible to draw definitive conclusions.


Hemorrhagic shock induces a proinflammatory milieu in the gut lumen.
Intestinal injury is a consequence of hemorrhagic shock and resuscitation. The intestinal mucosa has been shown to respond to ischemia/reperfusion injury with production of inflammatory mediators. Previous work in our laboratory indicates that intestinal epithelial cells secrete proinflammatory cytokines in the direction of both the lamina propria and intestinal lumen. The ability of the intestinal mucosa to transmit inflammatory signals into the gut lumen after hemorrhagic shock is unknown. We hypothesized that hemorrhagic shock results in secretion of proinflammatory cytokines into the gut lumen. Male C57/Bl6 mice underwent femoral artery cannulation and hemorrhage to a systolic blood pressure of 20 mmHg for 1 h, then resuscitation with lactated Ringer's (LR) solution. Sham animals were cannulated only. Mice were decannulated and sacrificed at intervals. Stool and succus were removed from intestinal segments, weighed, and placed into buffer solution. Specimens were analyzed via enzyme-linked immunosorbent assay (ELISA). Compared with sham-injured mice, hemorrhagic shock resulted in increased intestinal luminal cytokines. At 3 h after injury, elevated levels of IL-6 were found in the cecal stool. At 6 h after injury, TNFα, IL-6, and MIP-2 were significantly elevated in the cecal stool, and IL-6 and MIP-2 were significantly elevated in the distal colonic stool. Hemorrhagic shock results in secretion of proinflammatory cytokines into the intestinal lumen. These findings suggest that the intestinal mucosa may transmit and receive signals in a paracrine fashion via the gut lumen.


Self-selected fluid volume and flavor strength does not alter fluid intake, body mass loss, or physiological strain during moderate-intensity exercise in the heat.
The purpose of this study was to determine the effects of ad libitum flavor and fluid intake on changes in body mass (BM) and physiological strain during moderate intensity exercise in the heat. Ten subjects (24±3yrs, 7M/3F) performed 60 min of treadmill walking at 1.3 m/s and 7% grade in an environmental chamber set to 33 °C and 10% relative humidity while carrying a 22.7 kg pack on two different occasions. Subjects consumed either plain water or water plus flavor (Infuze), ad libitum, at each visit. Pre and post exercise, fluid consumption (change in fluid reservoir weight) and BM (nude) were measured. During exercise, heart rate (HR), systolic blood pressure (SBP), rate of perceived exertion (RPE), oxygen consumption (VO2), respiratory exchange ratio (RER), core temperature (TC), and physiological strain index (PSI) were recorded every 15 min during exercise. No significant differences were observed for fluid consumption between fluid conditions (512 ± 97.2 mL water vs. 414.3 ± 62.5 mL Infuze). Despite a significant decrease from baseline, there were no significant differences in overall change of BM (Δ -1.18 vs. -0.64 Kg) or percent body weight loss for water and Infuze conditions, respectively (1.58 ± 0.6 and 0.79 ± 0.2%). Furthermore, there were no significant differences in HR (144 ± 6 vs. 143 ± 8 bpm), SBP (157 ± 5 vs. 155 ± 5 mmHg), RPE, VO2 (27.4 ± 0.9 vs. 28.1 ± 1.2 ml/Kg/min), RER, TC (38.1 ± 0.1 vs. 37.0 ± 0.1 °C), and peak PSI (5.4 ± 0.4 vs. 5.7 ± 0.8) between conditions. Offering individuals the choice to actively manipulate flavor strength did not significantly influence ad libitum fluid consumption, fluid loss, or physiological strain during 60 min of moderate intensity exercise in the heat.


Taurine activates delayed rectifier Kv channels via a metabotropic pathway in retinal neurons.
Taurine is one of the most abundant amino acids in the retina, throughout the CNS, and in heart and muscle cells. In keeping with its broad tissue distribution, taurine serves as a modulator of numerous basic processes, such as enzyme activity, cell development, myocardial function and cytoprotection. Despite this multitude of functional roles, the precise mechanism underlying taurine's actions has not yet been identified. In this study we report findings that indicate a novel role for taurine in the regulation of voltage-gated delayed rectifier potassium (K(V)) channels in retinal neurons by means of a metabotropic receptor pathway. The metabotropic taurine response was insensitive to the Cl(-) channel blockers, picrotoxin and strychnine, but it was inhibited by a specific serotonin 5-HT(2A) receptor antagonist, MDL11939. Moreover, we found that taurine enhanced K(V) channels via intracellular protein kinase C-mediated pathways. When 5-HT(2A) receptors were expressed in human embryonic kidney cells, taurine and AL34662, a non-specific 5-HT(2) receptor activator, produced a similar regulation of K(IR) channels. In sum, this study provides new evidence that taurine activates a serotonin system, apparently via 5-HT(2A) receptors and related intracellular pathways.


Virtual muscularity: a content analysis of male video game characters.
The 150 top-selling video games were content analyzed to study representations of male bodies. Human males in the games were captured via screenshot and body parts measured. These measurements were then compared to anthropometric data drawn from a representative sample of 1120 North American men. Characters at high levels of photorealism were larger than the average American male, but these characters did not mirror the V-shaped ideal found in mainstream media. Characters at low levels of photorealism were also larger than the average American male, but these characters were so much larger that they appeared cartoonish. Idealized male characters were more likely to be found in games for children than in games for adults. Implications for cultivation theory are discussed.


Effects of different types of exercise on skeletal muscle atrophy, antioxidant capacity and growth factors expression following myocardial infarction.
Myocardial infarction (MI) is accompanied with skeletal muscle abnormalities. The aims are to explore an optimal exercise mode to improve cardiac function and prevent skeletal muscle atrophy, and detect the possible mechanisms of exercise-induced inhibition of muscle atrophy. Rats were subjected to four weeks of different types of exercise after MI surgery (resistance training, RT; moderated-intensity continuous aerobic exercise, MCE and high-intensity intermittent aerobic exercise, HIA). Cardiac function, histological changes of heart and skeletal muscle, oxidative stress, antioxidant capacity and the expression of muscle atrophy-related factors were detected in skeletal muscle. The three types of exercise improved heart function, reduced cardiac fibrosis and increased muscle weight and cross-section area (CSA) of muscle fibers in different degrees. The survival rates of MI rats intervened by RT and MCE were higher than HIA. Exercise down-regulated the mRNA levels of murf1 and atrogin-1, decreased reactive oxygen species level, increased antioxidant capacity, regulated the expression of insulin-like growth factor 1 (IGF1), mechano growth factor (MGF), Neuregulin1 (NRG1) and Myostatin (MSTN), and activated Akt and Erk1/2 signalings in soleus muscle. Furthermore, CSA of muscle fibers and the expression of IGF1, MGF, NRG1 in skeletal muscle had correlations with cardiac function. RT and MCE are the first two choices for the early exercise rehabilitation following MI. All types of exercise can effectively inhibit skeletal muscle atrophy through increasing the antioxidant capacity, reducing oxidative stress and protein degradation, and regulating the growth factors expression in skeletal muscle.


Acquisition and Use of 'Priors' in Autism: Typical in Deciding Where to Look, Atypical in Deciding What Is There.
Individuals with Autism Spectrum Disorder (ASD) are thought to under-rely on prior knowledge in perceptual decision-making. This study examined whether this applies to decisions of attention allocation, of relevance for 'predictive-coding' accounts of ASD. In a visual search task, a salient but task-irrelevant distractor appeared with higher probability in one display half. Individuals with ASD learned to avoid 'attentional capture' by distractors in the probable region as effectively as control participants-indicating typical priors for deploying attention. However, capture by a 'surprising' distractor at an unlikely location led to greatly slowed identification of a subsequent target at that location-indicating that individuals with ASD attempt to control surprise (unexpected attentional capture) by over-regulating parameters in post-selective decision-making.


Precise synthesis of poly(macromonomer)s containing sugars by repetitive ring-opening metathesis polymerisation.
Various poly(macromonomer)s containing sugars have been prepared by ROMP of norbornene macromonomers substituted with ROMP block copolymers containing acetal-protected sugars as the side chain, which upon removal of the protecting group affords a novel amphiphilic architecture.


Laser interstitial thermal therapy for newly diagnosed glioblastoma.
Gliomas are the most frequent primary brain tumor in adults. Patients with glioblastoma (GBM) tumors deemed inoperable with open surgical techniques and treated only with chemo/radiation have a median overall survival of less than 9 months. Laser interstitial thermal therapy (LITT) has emerged as a cytoreductive alternative to surgery for these patients. The present study describes the outcomes of twenty patients with newly diagnosed, IDH wild-type glioblastoma treated with LITT. We retrospectively reviewed patients with newly diagnosed, unresectable GBM who underwent LITT at our institution. Progression-free survival (PFS) was the primary endpoint measured in our study, defined as time from LITT to disease progression. Results Twenty patients were identified with newly diagnosed, inoperable GBM lesions who underwent LITT. The overall median PFS was 4 months (95% CI = 2 - N/A, upper limit not reached). The median progression-free survival (PFS) for patients with less than 1 cm 3 residual tumor (gross total ablation, GTA) was 7 months (95% CI = 6 - N/A, upper limit not reached), compared to 2 months (95% CI = 1 - upper limit not reached) for patients with a lower GTA (p = .0019). The median overall survival was 11 months (95% CI = 6 - upper limit not reached). Preoperative Karnofsky performance score (KPS) less than or equal to 80 and deep-seated tumor location were significantly associated with decreased PFS (HR, .18, p = .03; HR, .08, p = .03, respectively). At the end of 1 month, only 4 patients (20%) experienced persistent motor deficits. LITT is a safe and effective treatment for patients with unresectable, untreated GBM with rates of survival and local recurrence comparable to patients with surgically accessible lesions treated with conventional resection. Careful patient selection is needed to determine if GTA is attainable.


Chimerism and tolerance: from freemartin cattle and neonatal mice to humans.
Bone marrow transplantation (BMT) results in hematopoietic chimeras that demonstrate donor specific tolerance to tissue and cellular grafts. The clinical application of chimerism to induce tolerance is limited by the morbidity associated with human BMT: failure of engraftment, graft-versus-host disease (GVHD), and toxic host conditioning. BMT in an immunologically mature host has until recently been believed to require complete ablation of the host's immune system to allow donor engraftment. Lethal conditioning is associated with significant morbidity and mortality. Stable multilineage mixed allogeneic chimerism has more recently been achieved in mice using partial myeloablation prior to BMT. Chimeras prepared in this fashion exhibit donor specific tolerance in vitro and in vivo similar to lethally-conditioned recipients. A second factor that has limited the widespread application of BMT to nonmalignant disease, including attempts to induce tolerance, is GVHD. Although T-cell depletion of donor marrow reduces the incidence of GVHD, engraftment is often jeopardized. Although highly purified stem cells (SC) engraft at relatively low doses in syngeneic recipients, they do not durably engraft in MHC-disparate recipients. It has recently become clear that a second cell (facilitating cell) that enhances bone marrow engraftment and minimizes the occurrence of GVHD is required for SC to engraft in MHC-disparate recipients. Methods to optimize engraftment yet minimize GVHD may provide an approach to apply BMT clinically. With decreased morbidity through incomplete recipient conditioning and the ability to engineer a bone marrow graft to contain only the desired cells to optimize engraftment, BMT may provide a reasonable strategy to treat nonmalignant diseases including enzyme deficiencies, hemoglobinopathies, autoimmune diseases, and species-specific viral infections such as HIV. BMT-induced donor specific tolerance may benefit recipients of solid organ transplants by eliminating the need for nonspecific immunosuppression and by preventing chronic rejection. This review will focus on approaches to enable BMT yet minimize recipient morbidity and mortality.


Examining health disparities and characteristics in general practice utilization: based on outpatient data from 2014 - 2018 in Shanghai.
Since 2000, China has been developing primary care institutions to serve as the gateway to the healthcare system. However, the investment of resources in primary care institutions is not based on the actual medical demands of the public. This study analysed primary care utilization to provide targeted guidance for the improvement of primary healthcare delivery in China. We extracted outpatient visit data from all community healthcare centres in Shanghai from 2014 to 2018. Diseases were then classified according to ICD-10 codes. The disease spectrum (frequency, proportion, rank) was stratified by sex, age, and region. Most primary care outpatients were female (58.20%), 60-79 years old (57.91%), and in suburban regions (62.18%). Chronic diseases accounted for the majority (91.41%). Hypertension, chronic ischaemic heart disease, diabetes, and acute upper respiratory tract infections were the top four disorders for primary care visits regardless of sex. In the group aged 0-18 years, symptoms, signs and abnormal clinical and laboratory findings not elsewhere classified accounted for 37.96% of the top 20 reasons. Acute upper respiratory tract infections were the most common diseases in the groups aged 0-18 (11.20%) and 19-39 (11.14%) years. However, hypertension was the most common disease in the group aged > 39 years old (> 20%). There were more outpatients with respiratory and digestive diseases in suburban areas than in urban areas. In addition, problems associated with medical equipment and other healthcare deficiencies were relatively more common in suburban areas (suburban: 4.13%, rank 5; urban: 2.29%, rank 10). To meet the patients' needs and to develop the primary care system, the Shanghai government should focus on diseases with regionally high proportions. Disease diagnosis and treatment should be improved in the younger and suburban populations.


Time trends of HIV-I antibody prevalence in homosexual men.
1840 homosexual and bisexual men were tested for human immunodeficiency virus type I (HIV) infection at the Landesinstitut für Tropenmedizin, Berlin between April 1983 and December 1987. A total of 25.1% were seropositive for HIV, but the percentage was seemingly declining. During the study period we observed also a steady decrease in the prevalence of lymphadenopathy syndrome (LAS), antibodies to hepatitis B and syphilis, and high-risk sexual behaviour in the study population. By adjusting for these changes of population characteristics we assessed the odds of HIV infection which had more than doubled between 1983 and 1986 (prevalence odds ratio 2.43, 95% confidence interval 1.58 to 3.76). In 1987 the HIV prevalence odds showed a drop which, however, was not significant (p = 0.34) when compared with the odds in 1986. Methodological aspects of time trend estimation based on data of voluntary HIV testing are discussed.


Potential conflicts in midwifery practice regarding conscientious objection to abortions in Scotland.
This study was developed as a result of a court case involving conflicts between midwives' professional practice and their faith when caring for women undergoing abortions in Scotland. What are practising Roman Catholics' perspectives of potential conflicts between midwives' professional practice in Scotland with regard to involvement in abortions and their faith? How relevant is the 'conscience clause' to midwifery practice today? and What are participants' understandings of Canon 1398 in relation to midwifery practice? The theoretical underpinning of this study was Gadamer's hermeneutic out of which the method developed by Fleming et al. involving a five-stage approach was utilised. The research was conducted in the south of Scotland. A purposive sampling method was used. Eight participants who were practising Roman Catholics familiar with the subject of conscientious objection who were either midwives, lawyers (civil, canon or both) or priests contributed. The major ethical issues related to respect for autonomy, maintaining confidentiality and obtaining voluntary informed consent. Parish priests agreed to act as gatekeepers to prospective participants. All legal requirements were addressed regarding data collection and storage. Approval was given by the ethics committee of the university with which one of the researchers were associated. Three key themes provide an understanding of the situation in which midwives find themselves when considering the care for a woman admitted for an abortion: competing legal systems, competing views of conscience and limits of participation. Clear guidelines for practice should be developed by a multi-professional and consumer group based on an update of the abortion law to reflect the change from a surgical to medical procedure. Clarification of Canon 1398 in relation to what is and is not participation in the procurement of abortion would be of benefit to midwives with a conscientious objection.


Development of a cold storage solution for pancreas preservation.
Canine pancreas tissue slices were incubated at 5 degrees C for 24 hr in solutions containing different saccharides (raffinose, sucrose, mannitol, or glucose). At the end of incubation tissue water (TW expressed as kg H2O/kg dry wt) was determined as a measure of tissue edema. Tissue edema was greatest in slices stored in Eurocollins (EC) solution (TW = 4.96 +/- 0.14) which contains glucose for osmotic pressure. The degree of edema was decreased by saccharides in proportion to their molecular mass: mannitol (MW = 180, TW = 3.84 +/- 0.08), sucrose (MW = 348, TW = 3.54 +/- 0.08), and raffinose (MW = 594, TW = 3.30 +/- 0.07). Tissue edema was also greatest in slices incubated in solutions containing the smallest molecular mass anions: Cl- (TW = 4.02 +/- 0.16), gluconate (TW = 3.69 +/- 0.10), and lactobionate (TW = 3.28 +/- 0.13). Cold storage of the intact pancreas in EC solution for 24 hr did not induce as much edema as in slices (TW = 2.88 +/- 0.10). However, on isolated reperfusion at normothermia (37 degrees C) the pancreas became edematous (TW = 3.33 +/- 0.12). Storage of the pancreas in a lactobionate-raffinose solution did not induce edema after 90 min of normothermic reperfusion. The suppression of tissue edema in the pancreas may be essential to obtaining long-term preservation (24-72 hr) of this organ which is currently limited to about 6-8 hr in EC solution. The newly developed lactobionate-raffinose solution appears to control tissue edema in both tissue slices and the intact-flushed out organ.


Studies on the surgical induction of endometriosis in the rat.
As a model to examine the pathophysiologic attributes of endometriosis, attempts were made to surgically induce the disease in the rat by autotransplanting endometrial or uterine tissue to the peritoneum. Rats (n = 46) were randomly assigned to one of four surgical techniques: (1) four uterine squares sutured to the peritoneal cavity; (2) uterine luminal lavages instilled into the peritoneal cavity; (3) endometrial scrapings flushed into the peritoneal cavity; and (4) sham-operated controls. Rats were examined at various days after surgery for the presence of endometrial implants. The autotransplantation of uterine squares to the peritoneal cavity was the only treatment that yielded healthy endometriotic implants. These implants grew into ellipsoidal cystic structures that were composed of both endometrial glands and stroma and were found to contain prostaglandin F (202 ng/mg) at concentrations similar to those measured in uterine tissue (205 ng/mg). To examine the effect of surgically induced endometriosis upon fecundity, rats (n = 40) were autotransplanted with uterine squares or were sham operated and mated. The presence of ectopic endometrial tissue reduced the number of pups at term by 48% and the number of day 14 embryos by 28% (P less than 0.05). Peritoneal adhesions were greater in rats with induced endometriosis than in sham-operated controls (P less than 0.05); however, in rats with induced endometriosis, no differences were noted in the severity of adhesions between pregnant and nonpregnant rats. Endometriotic implants underwent complete regression in the day 14 pregnant rat but had doubled in size in the nonpregnant rat. At term, the endometriotic implants were larger than in the day 14 pregnant rat (P less than 0.05) and similar to their original size. The successful growth and development of surgically transplanted endometrial tissue in the rat offers a research model that can be used to study those aspects of endometriosis that cannot be adequately investigated in women.


Chronic electrical stimulation of the auditory nerve at high stimulus rates: a physiological and histopathological study.
A major factor associated with recent improvements in the clinical performance of cochlear implant patients has been the development of speech-processing strategies based on high stimulation rates. While these processing strategies show clear clinical advantage, we know little of their long-term safety implications. The present study was designed to evaluate the physiological and histopathological effects of long-term intracochlear electrical stimulation using these high rates. Thirteen normal-hearing adult cats were bilaterally implanted with scala tympani electrode arrays and unilaterally stimulated for periods of up to 2100 h using either two pairs of bipolar or three monopolar stimulating electrodes. Stimuli consisted of short duration (25-50 microseconds/phase) charge-balanced biphasic current pulses presented at 1000 pulses per second (pps) per channel for monopolar stimulation, and 2000 pps/channel for bipolar stimulation. The electrodes were shorted between current pulses to minimize any residual direct current, and the pulse trains were presented using a 50% duty cycle (500 ms on; 500 ms off) in order to simulate speech. Both acoustic (ABR) and electrical (EABR) auditory brainstem responses were recorded periodically during the chronic stimulation program. All cochleas showed an increase in the click-evoked ABR threshold following implant surgery; however, recovery to near-normal levels occurred in approximately half of the stimulated cochleas 1 month post-operatively. The use of frequency-specific stimuli indicated that the most extensive hearing loss generally occurred in the high-frequency basal region of the cochlea (12 and 24 kHz) adjacent to the stimulating electrode. However, thresholds at lower frequencies (2, 4 and 8 kHz), appeared at near-normal levels despite long-term electrode implantation and electrical stimulation. Our longitudinal EABR results showed a statistically significant increase in threshold in nearly 40% of the chronically stimulated electrodes evaluated; however, the gradient of the EABR input/output (I/O) function (evoked potential response amplitude versus stimulus current) generally remained quite stable throughout the chronic stimulation period. Histopathological examination of the cochleas showed no statistically significant difference in ganglion cell densities between cochleas using monopolar and bipolar electrode configurations (P = 0.67), and no evidence of cochlear damage caused by high-rate electrical stimulation when compared with control cochleas. Indeed, there was no statistically significant relationship between spiral ganglion cell density and electrical stimulation (P = 0.459), or between the extent of loss of inner (IHC, P = 0.86) or outer (OHC, P = 0.30) hair cells and electrical stimulation. Spiral ganglion cell loss was, however, influenced by the degree of inflammation (P = 0.016) and electrode insertion trauma. These histopathological findings were consistent with the physiological data. Finally, electrode impedance, measured at completion of the chronic stimulation program, showed close correlation with the degree of tissue response adjacent to the electrode array. These results indicated that chronic intracochlear electrical stimulation, using carefully controlled charge-balanced biphasic current pulses at stimulus rates of up to 2000 pps/channel, does not appear to adversely affect residual auditory nerve elements or the cochlea in general. This study provides an important basis for the safe application of improved speech-processing strategies based on high-rate electrical stimulation.


Association of Neurodevelopmental Outcomes With Environmental Exposure to Cyclohexanone During Neonatal Congenital Cardiac Operations: A Secondary Analysis of a Randomized Clinical Trial.
Cyclohexanone is an industrial solvent used as a coupling agent in medical plastics. Perioperative exposure to cyclohexanone could play a role in lower scores on measures of neurodevelopmental outcomes after neonatal cardiac operations. To examine the presence and association of serum cyclohexanone level with neonatal cardiac operations and neurodevelopmental outcomes. This ad hoc secondary analysis used data from the Corticosteroid Therapy in Neonates Undergoing Cardiopulmonary Bypass randomized clinical trial. The cohort included neonates younger than 31 days and with at least 37 weeks postgestational age at surgical treatment who were enrolled at a single center between June 1, 2012, and October 31, 2016, and who had completed a neurodevelopmental assessment at age 12 months. Data were analyzed from July 8 to August 20, 2019. Serum cyclohexanone and its metabolites were measured preoperatively (prior to skin incision), postoperatively (immediately after the surgical procedure was completed), and 12 hours postoperatively. Cyclohexanone and the molar sum of its metabolites were examined at each point and as a geometric mean of all 3 points. Neurodevelopment was assessed at age 12 months with the Bayley Scales of Infant and Toddler Development III, assessing cognitive, language, and motor function composite scores standardized to a population mean (SD) of 100 (15). Linear regression models were used to determine covariate-adjusted differences in 12-month cognitive, language, and motor composite scores per interquartile range increase in cyclohexanone level or summed metabolite molar concentrations. Among 85 included neonates, mean (SD) age at surgical treatment was 9.7 (5.3) days, 49 (58%) were boys, and 54 (64%) underwent corrective repair. Mean (SD) Bayley Scales of Infant and Toddler Development III composite scores were 108.2 (12.2) for cognitive function, 104.7 (11.0) for language function, and 94.7 (15.7) for motor function. Median (interquartile range) cyclohexanone levels increased approximately 3-fold from immediately prior to surgical treatment to immediately after surgical treatment (572 [389-974] vs 1744 [1469-2291] μg/L; P = .001). In adjusted analyses, higher geometric mean cyclohexanone levels were associated with significantly lower composite scores for cognitive (-4.23; 95% CI, -7.39 to -1.06; P = .01) and language (-3.65; 95% CI, -6.41 to -0.88; P = .01) function. The difference in composite scores for motor function among infants with higher geometric mean cyclohexanone levels was not statistically significant(-3.93, 95% CI: -8.19 to 0.33, P = .07). The findings of this secondary analysis of a randomized clinical trial suggest that infants who underwent neonatal cardiac surgical treatment with cardiopulmonary bypass had substantial cyclohexanone levels, which were associated with adverse neurodevelopmental function at age 12 months. ClinicalTrials.gov identifier: NCT01579513.


Amino acid patterns in human gastric juice in health and gastric disease.
The amino acids in human gastric juice were measured in the hospital control (n = 9), gastric ulcer (n = 10), duodenal ulcer (n = 12), gastroduodenal ulcer (n = 9), and gastric cancer patients (n = 16) by high performance liquid chromatography, and the total of 15 kinds of amino acids was correlated with value determined by Ninhydrin method. The patients with gastric cancer had elevated levels of all amino acids, especially alanine, leucine, valine and threonine. In all but the gastric cancer disease groups, the aromatic amino acids, phenylalanine and tyrosine as well as leucine were at high levels in 15 amino acids. The different patterns of amino acids in these four groups tended to correlate with the variabilities of protein loss from the gastric wall.


Secondary cytoreductive surgery for low-grade appendiceal mucinous neoplasms.
In patients with low-grade appendiceal mucinous neoplasms (LAMN), a secondary cytoreductive surgery (SCRS) is often performed if recurrent disease is detected. In patients with a complete cytoreductive surgery (CRS), the clinical- and treatment-related variables associated with the index CRS and the SCRS were statistically assessed for their impact on overall survival after SCRS. Eighty-eight patients of 450 patients (19.6%) had SCRS. The mean survival was 15.3 years for patients requiring SCRS as compared to 24.5 years for the group as a whole. Variables associated with improved survival as a result of the index CRS by multivariant modeling were absence of total gastrectomy (p = 0.0038), moderate peritoneal cancer index of 15-30 (p = 0.0020) and time interval of greater than 36 months from CRS to SCRS (p = 0.0013). Multivariant modeling associated with SCRS were complete CRS (p = 0.0104) and disease progression limited to the abdominal wall (p = 0.0106). Early postoperative intraperitoneal chemotherapy (EPIC) 5-fluorouracil used with CRS improved the outcome with SCRS (p = 0.0095). A requirement for SCRS in 88 patients decreased median survival to 15.3 years as compared to 24.5 years in all 450 LAMN patients (p < 0.0001). Prognostic indicators from both the index CRS and the SCRS had an impact on the outcome of SCRS.


Impact of the Dementia Care in Hospitals Program on acute hospital staff satisfaction.
To evaluate the impact of the Dementia Care in Hospitals Program (DCHP) on clinical and non-clinical staff job satisfaction, level of confidence and comfort in caring for patients with cognitive impairment (CI). Staff perceptions of how organisational support and hospital environment met the needs of patients with CI were also assessed. The DCHP was implemented across four acute hospital sites across Australia. Clinical and non-clinical staff received training on CI screening and communication strategies for patients with CI. A staff satisfaction survey was administered pre- and post-implementation of the DCHP. One thousand seven hundred forty-eight staff received DCHP education and 1375 staff participated in the survey. Self-reported confidence and level of comfort in caring for patients with CI significantly improved following implementation. Staff also reported increased job satisfaction and organisational support at all hospital sites. The DCHP implementation within an acute hospital setting was found to show an improvement in staff confidence, comfort, and job satisfaction when caring for patients with CI. This study has significant implications for the improvement of care for patients with CI as well as staff retention and job satisfaction. Further research is required to determine whether these improvements are sustained in the longer term.


Reliability and normative values for the foot mobility magnitude: a composite measure of vertical and medial-lateral mobility of the midfoot.
A study was conducted to determine the reliability and minimal detectable change for a new composite measure of the vertical and medial-lateral mobility of the midfoot called the foot mobility magnitude. Three hundred and forty-five healthy participants volunteered to take part in the study. The change in dorsal arch height between weight bearing and non-weight bearing as well as the change in midfoot width between weight bearing and non-weight bearing were measured at 50% of total foot length and used to calculate the foot mobility magnitude. The reliability and minimal detectable change for the measurements were then determined based on the assessment of the measurements by three raters with different levels of clinical experience. The change in dorsal arch height between weight bearing and non-weight bearing, midfoot width between weight bearing and non-weight bearing, and the foot mobility magnitude were shown to have high levels of intra-rater and inter-rater reliability. Normative data are provided for the left and right feet of both the female (n = 211) and male (n = 134) subjects. While the measurements of navicular drop and drift have been used as a clinical method to assess both the vertical and medial-lateral mobility of the midfoot, poor to fair levels of inter-rater reliability have been reported. The results of the current study suggest that the foot mobility magnitude provides the clinician and researcher with a highly reliable measure of vertical and medial-lateral midfoot mobility.


Matching geometry and stimulation parameters of electrodes for deep brain stimulation experiments--numerical considerations.
Deep brain stimulation, the electric stimulation of basal ganglia nuclei, is a treatment for movement disorders such as Parkinson's disease. The underlying mechanisms are studied in animals, e.g. rodents. Designs and materials of commercially available microelectrodes, as well as experimentally applied driving signals vary tremendously. We used finite integration modeling to compare the electric field and current density distributions induced by various electrodes. Current density or field strength "hot spots", which are located particularly at sites of high curvature and material interfaces coincided with corrosion and erosion at poles and insulation, respectively, as shown by scanning electron microscopy of stainless steel electrodes. Cell constants, i.e. geometry factors relating the electrode impedance to the specific medium conductivity, were calculated to determine the electrode voltage for a given stimulation current. Nevertheless, for electrodes of the same cell constant but of different geometry, current and field distributions may be very dissimilar. We found geometry-dependent limiting values of the stimulation current, above which electric tissue damage may occur. These values limit the reach of the stimulation signal for a given electrode geometry. Also, electrode geometries determine the shape of the stimulated tissue volume. This study provides tools for choosing the most appropriate geometry for targeting different-sized brain areas.


[Experimental study on the Sanxiansinli capsule against fatigue and viability of mice].
To investigate the effect of the Sanxianxinli capsule against fatigue and viability of mice. The mouse shinning, burden swimming, heat-resistant, cold resistant and tolerating anoxia were detected by experiment. The results showed that the Sanxansinli capsule have function of improveing the stamina, cold resistant, heat-resistant and tolerating anoxia,and prolonging were the survival time in cold, high temperature and anoxia. The Sanxianxinli capsule have function against fatigue and can also improve the resistibility of body.


The Cinderella of positive psychology: spiritual well-being as an emerging dimension of flourishing in pastoral work.
The invaluable, yet challenging role of pastors in the community signifies the need to understand and care for their well-being. Well-being, conceptualized in the multidimensional construct of flourishing, does not explicitly include spiritual well-being, yet, it is the foundation of pastors' well-being. In this article we aim to describe pastors' spiritual well-being and in so doing, highlight its fundamental importance in pastors' flourishing in the ministry. Positioned in the interpretive pragmatic paradigm, data were gathered and analysed from three focus groups with 18 pastors in the Dutch Reformed Church and the Uniting Reformed Church of South Africa. Interactive qualitative analysis was applied, and results were conceptually refined through narrative synthesis. Four themes were constructed to describe pastors' spiritual well-being namely: i) an altruistic calling; ii) discipleship iii) seasons of the ministry; and iv) ethics. The findings highlight the importance and essence of the spiritual aspects predominant to pastors' well-being. Attending to spiritual well-being will enhance their resilience and constructive coping and is integral to their way of flourishing at work. This proposes an extension of the flourishing framework to include spiritual well-being as an explicitly conceptualized sub-dimension for application to the study's Christian pastoral context.


Hardware acceleration for real time simulation of physiological systems.
Testing of medical equipment such as pacemaker is a critical task, because any malfunction may cause patient death or serious and long-lasting health consequences. Thus, device behavior under normal functioning conditions as well as under faulty conditions should be tested as thoroughly as possible under the project's budget. This paper presents a real-time digital simulator (DRTS) for possible use in testing of medical devices. The simulator runs a model of a physiological system (an organ or a group of organs) in real time and uses A/D and D/A cards to interface the simulation results to real medical equipment. With this simulator, the tests can be made as thorough as needed without much increase in cost.


Intravitreal ranibizumab in the treatment of butterfly-shaped pattern dystrophy associated with choroidal neovascularization: a case report.
To present and document the effectiveness of intravitreal ranibizumab in the treatment of patients with choroidal neovascularization due to butterfly-shaped pattern dystrophy (PD) of the macula. Three intravitreal ranibizumab injections of 0.5 mg/0.05 ml in monthly intervals were given to a patient with a previously diagnosed butterfly-shaped PD who subsequently developed subfoveal choroidal neovascularization on the right eye. The patient had previously received a combination of verteporfin/photodynamic therapy for a juxtafoveal choroidal neovascular membrane on the left eye. At the end of the treatment course, there was significant improvement of the patient's vision and the appearance of the macula on optic coherence tomography and fluorescein angiography. Best-corrected visual acuity improved from 6/12 to 6/6 and retinal thickness at the macula decreased from 323 to 247 μm. No subretinal fluid remained. The patient is clinically stable over a 12-month follow-up period. Intravitreal ranibizumab seems to be an effective and safe option for the treatment of subfoveal choroidal neovascularization in patients with butterfly-shaped PD.


Altered Fc glycosylation of anti-HLA alloantibodies in hemato-oncological patients receiving platelet transfusions.
The formation of alloantibodies directed against class I human leukocyte antigens (HLA) continues to be a clinically challenging complication after platelet transfusions, which can lead to platelet refractoriness (PR) and occurs in approximately 5%-15% of patients with chronic platelet support. Interestingly, anti-HLA IgG levels in alloimmunized patients do not seem to predict PR, suggesting functional or qualitative differences among anti-HLA IgG. The binding of these alloantibodies to donor platelets can result in rapid clearance after transfusion, presumably via FcγR-mediated phagocytosis and/or complement activation, which both are affected by the IgG-Fc glycosylation. To characterize the Fc glycosylation profile of anti-HLA class I antibodies formed after platelet transfusion and to investigate its effect on clinical outcome. We screened and captured anti-HLA class I antibodies (anti-HLA A2, anti-HLA A24, and anti-HLA B7) developed after platelet transfusions in hemato-oncology patients, who were included in the PREPAReS Trial. Using liquid chromatography-mass spectrometry, we analyzed the glycosylation profiles of total and anti-HLA IgG1 developed over time. Subsequently, the glycosylation data was linked to the patients' clinical information and posttransfusion increments. The glycosylation profile of anti-HLA antibodies was highly variable between patients. In general, Fc galactosylation and sialylation levels were elevated compared to total plasma IgG, which correlated negatively with the platelet count increment. Furthermore, high levels of afucosylation were observed for two patients. These differences in composition of anti-HLA Fc-glycosylation profiles could potentially explain the variation in clinical severity between patients.


Inhibition of nuclear translocation of nuclear factor-kappaB despite lack of functional IkappaBalpha protein overcomes multiple defects in apoptosis signaling in human B-cell malignancies.
Defective apoptosis signaling is a typical feature of classic Hodgkin's lymphoma, multiple myeloma, and activated B-cell-like diffuse large B-cell lymphoma. In these malignancies, the transcription factor nuclear factor-kappaB (NF-kappaB) is a critical mediator of apoptosis resistance and oncogenic growth, making it an attractive therapeutic target. Here, we sought to determine how to overcome apoptosis resistance experimentally in these malignancies by targeting NF-kappaB. We investigated the effect of different inhibitors of NF-kappaB on classic Hodgkin's lymphoma, multiple myeloma, and activated B-cell-like diffuse large B-cell lymphoma cell lines harboring different molecular defects in apoptosis signaling both quantitatively and qualitatively. The cyclopentenone prostaglandin, 15-deoxy-Delta12,14-prostaglandin J(2), a known inhibitor of NF-kappaB, induced caspase-dependent apoptosis; it restored mitochondrial apoptotic signaling by down-regulation of X-linked inhibitor of apoptosis protein and heat shock protein 27 and led to breakdown of the mitochondrial membrane potential and, finally, cleavage of caspase-3 irrespective of IkappaBalpha mutational status. Surprisingly, 15-deoxy-Delta12,14-prostaglandin J(2) and the IkappaB kinase inhibitor curcumin both reduced nuclear levels of p65 in cell lines lacking IkappaBalpha, suggesting that inhibition of nuclear translocation of NF-kappaB can occur in the absence of IkappaBalpha. Finally, a synthetic peptide that specifically abrogates the assembly of the IkappaB kinase complex killed IkappaBalpha-defective cells by induction of apoptosis, paralleled by reduction of nuclear NF-kappaB. These results show that molecular defects in apoptotic signaling, such as IkappaBalpha mutations, can be circumvented by targeting NF-kappaB through inhibition of the IkappaB kinase complex followed by induction of apoptosis in classic Hodgkin's lymphoma, multiple myeloma, and activated B-cell-like diffuse large B-cell lymphoma. Thus, targeting IkappaB kinases may represent an attractive therapeutic approach against these malignancies regardless of the mutational status of IkappaBalpha.


Supporting tools in psychiatric treatment decision-making: sertraline outcome investigation with artificial neural network method.
Controlled trials in clinical psychopharmacology may fail to provide reliable information about the benefit of treatment for the patient when considered in a real-life setting rather than as a part of a well-defined sampling procedure. Previously, we applied the mathematical model of an artificial neural network (ANN) to a pool of clinical information gathered through case descriptions provided by senior psychiatrists in clinical charts of patients receiving their first exposure to sertraline. In the present study, we applied the same mathematical model to a larger sample. The performance of the ANN model in forecasting successful and unsuccessful treatment showed an overall accuracy of classification of 97.12%. This result supports our previous finding about the potential application of this method as a reliable predictor of a given psychiatric patient's outcome during a specific psychopharmacological therapy.


Characterization of Orungo virus, an orbivirus from Uganda and Nigeria.
Orungo virus was studied in cell culture and mice by light and electron microscopy. The virus developed in the cytoplasm of infected cells in mouse brain and cell culture in association with a specific viral granular matrix and accompanying filaments. Virus particle size was 63 nm with a core diameter of 34 nm. Most particles were released from infected cells by lysis, but some budded through membranes and assumed a "pseudoenvelope". In its morphology and mode of morphogenesis, Orungo virus was indistinguishable from other described orbiviruses.


An experimental study of covert extinction on smoking cessation.
Twenty-one subjects participated on a volunteer nonpaid basis in a smoking cessation treatment experiment. The subjects were randomly assigned to three groups: one receiving training in covert extinction, one in relaxation, and a waiting list group serving as a control group. Behavioral (number of cigarettes smoked), physiological (pulse rate during treatment sessions) and cognitive (craving for cigarettes) assessments were made during and between sessions. Analysis of variance showed the time variable to be significant for number of cigarettes. Tukey's HSD tests showed a significant decrease in smoking after treatment for all three groups, and also for the two treatment groups until the follow-up occasion, although smoking had returned to a higher level (though not the initial one) after one month. There were also significant differences between the control group and both treatment groups with regards to pulse rate changes in treatment sessions. There was no significant change in craving, although a tendency pointed in the same direction for pulse rates. A tentative conclusion is that covert extinction is not a specific effective treatment method surpassing other nonspecific treatment procedures.


Exposure to neonicotinoids and serum testosterone in men, women, and children.
Neonicotinoids are the most used pesticides in the world and, despite being harmful to honeybees, they are considered safe for mammals. However, they have been associated with decreasing testosterone levels in several experimental animal models. In the present study, we aimed to determine the association of urinary neonicotinoids with serum testosterone in humans. We analyzed data on 2014 male and female participants to the National Health and Nutrition Examination Survey conducted between 2015 and 2016 aged 6 or older. In linear regression adjusted for age and potential confounders, serum total testosterone was 37.78% lower with 10-fold increase in urinary total neonicotinoids (95% CI: -58.82, -6.00), 20.81% lower with 10-fold increase in urinary 5-hydroxy-imidacloprid (95% CI: -34.94, -3.62) and 25.01% lower with 10-fold increase in urinary n-desmethyl-acetamiprid (95% CI: -39.80, -6.58) among males. Serum free androgen index (FAI) was also decreased with higher urinary n-desmethyl-acetamiprid. In females, serum total testosterone was 32.91% lower with 10-fold increase in urinary total neonicotinoids (95% CI: -54.93, -0.13), 21.32% lower with 10-fold increase in urinary 5-hydroxy-imidacloprid (95% CI: -29.31, -12.42) and 15.42% lower with urinary detection of 5-hydroxy-imidacloprid (95% CI: -22.80, -7.34). FAI was likewise reduced with higher urinary levels of 5-hydroxy-imidacloprid and N-desmethyl-acetamiprid. In conclusion, this study using a sample representative of the US population is the first to report that exposure to neonicotinoids is associated with decreased serum testosterone levels in humans. However, future prospective studies are warranted to confirm these findings.


Past exposure to fruit and vegetable variety moderates the link between fungiform papillae density and current variety of FV consumed by children.
Higher fungiform papillae density (FPD) has been associated with lower taste sensitivity thresholds and greater perceived taste intensity along with consumption of fewer fruit and vegetables (FV). Children exposed to greater variety of FV tend to habitually consume more FV, however, it is unknown whether exposure effects are attenuated by individual differences in FPD or whether these effects vary according to sensory properties of FV. This study examined the links between children's FPD, current variety of FV consumed, and past experiences with variety of fruit and vegetables. FPD counts were obtained from 61 children between 5 and 9years old, in schools from affluent areas of Birmingham (UK). Parents completed food frequency questionnaires indicating the variety of FV consumed by children in the last 7days. Parents also indicated the number of different FV types the children had tasted in their lifetime. FV were subdivided to reflect differences in their sensory properties. The results showed that children with higher FPD who in their lifetime had tasted a greater variety of FV ate a larger variety of FV compared to children with higher FPD, but with lower past exposure. When examining effects within specific subcategories of fruits and vegetables, this pattern held for non-astringent fruit and showed a trend for non-bitter vegetables. Children with lower FPD consumed similar variety of FV irrespective of past experiences with variety of FV. The results suggest that when strong or irritant sensory food properties are not a barrier to intake, higher FPD in the presence of supportive home food environment may be beneficial for FV intake. Individual phenotypic differences may affect responsiveness to environmental factors in children's intake of FV.


Thermal shrinkage reveals the feasibility of pulse-delay photocuring technique.
To resolve the feasibility of the pulse-delay photocuring technique as a clinical strategy for reducing the detrimental polymerization stress induced in dental composites during the photocuring process. Model dental composites with high and low-filler contents were cured with the pulse-delay photocuring technique using different combinations of photocuring variables (irradiance, exposure time, and delay time). Irradiance used ranged from 0.1W/cm2 to 4W/cm2. The exposure time of the first pulse varied from 0.2s to 27.2s and the delay times ranged from 10s to 120s. The radiant exposure was varied from 4J/cm2 to 20J/cm2. A cantilever-beam based instrument (NIST Standards Reference Instrument 6005) was used to implement the photocuring technique for the measurement of the polymerization properties (the degree of monomer conversion, polymerization stress induced due to shrinkage, and temperature change due to the reaction exotherm and curing light absorbance) simultaneously in real-time. These properties were compared with those obtained using the conventional photocuring technique (i.e., using a constant irradiance for a fixed exposure time, a uniform exposure). There exists a minimum radiant exposure, such that a reduction in the polymerization stress can be achieved without sacrificing the degree of monomer conversion by using the pulse-delay over the conventional photocuring technique. More specifically, stress reductions of up to 19% and 32% was observed with the pulse-delay when compared with the conventional photocuring technique at an irradiance of 0.5W/cm2 and 4W/cm2, respectively. The reduction occurred when the exposure time of the first pulse was greater than, but closer to, the gelation time (i.e., lower than the vitrification time) of the composite, regardless of the delay time used. Lower thermal shrinkage (contraction) during the post-curing time, rather than the stress relaxation during the delay time or lower degree of monomer conversion as claimed in the literature, is the cause of the reduction in the polymerization stress. The study clarifies a long-standing confusion and controversy on the applicability of the pulse-delay photocuring technique for reducing the polymerization stress and promotes its potential clinical success for dental restorative composites.


Characterisation of silica-based heparin affinity sorbents from equilibrium binding studies on plasma fractions containing thrombin.
The binding properties of rigid heparin sorbents, synthesised by end-point-attachment of heparin onto aminopropylderivatised silica through reductive amination, were characterised through batch-adsorption studies employing human plasma fractions containing thrombin. Thrombin was quantified using a chromogenic assay that had been specially modified for these studies. These investigations yielded information regarding the maximum adsorption capacities/stoichiometries and binding affinities for thrombin present in complex protein mixtures. Of the two types of heparin-silica evaluated, heparin-Fractosil 1000, with a pore size of 1000 A, displayed a capacity of 2.4 mol of thrombin/mol of heparin (mol T-mol H). This stoichiometry was significantly higher than the value of 1.8 mol T-mol H obtained for the commercial soft gel heparin-Sepharose CL-6B. Furthermore, the heparin-Fractosil 1000 sorbents were superior in capacity and binding site accessibility to heparin-LiChroprep Si60 sorbents, where the smaller pore size of 60 A largely restricts the ligand-protein interactions to the outer surface of the sorbent particles. Nevertheless, heparin-LiChroprep Si60 sorbents were useful, in that they simulated a non-porous particle system, in which intra-pore diffusion effects are eliminated. The batch adsorption results with these sorbents indicated that the adsorption involved both high and low binding affinity characteristics. This bimodal binding mechanism was also evident with the commercial heparin-Sepharose sorbent. Binding stoichiometries and affinities in the high concentration range were similar to values reported for a largely non-specific electrostatic thrombin-heparin interaction. Dissociation constants in the nanomolar range were observed in the low concentrations range. This stronger binding affinity is more similar to highly specific bio-affinity interactions. Thus, the results indicated that heparin-thrombin interactions with these systems involve both a weak electrostatic and a strong biospecific interaction component.


Digestion of cattle manure under mesophilic and thermophilic conditions: characterization of organic matter applying thermal analysis and 1H NMR.
Digestion of cattle manure collected from a livestock farm together with bedding material (straw) has been studied under mesophilic and thermophilic conditions in batch reactors. The digestion was carried out for a prolonged period with the aim of evaluating the changes undergone by the organic matter. The mesophilic digestion carried out revealed a greater capacity to produce gas and transform organic matter, while a higher conversion rate, but a lower gas yield, was obtained under thermophilic conditions. Degradation of the organic matter was evaluated by means of thermal analysis and (1)H NMR. Stabilisation through anaerobic digestion (either mesophilic or thermophilic) resulted in an increase in the quality of the organic matter, as characterised by an enrichment in thermostable compounds, and an accumulation of long chain aliphatic materials. The experiments performed demonstrated the transformation of organic matter into complex materials under anaerobic conditions with an accumulation of aliphatic components under both types of conditions tested. Degradation through mesophilic digestion, in comparison to the thermophilic process, resulted in a greater destruction of straw particles.


Urologic complications of hip arthroplasty.
Significant intrapelvic injuries from routine hip surgery are rare but may result in long-term urologic morbidity. Two illustrative cases are presented with attention given to the close anatomic proximity of the intrapelvic structures to the hip joint and their potential for injury after hip surgery. A review of similar cases with their management is presented.


A novel guanine nucleotide exchange factor MyoGEF is required for cytokinesis.
The cleavage furrow is created by an actomyosin contractile ring that is regulated by small GTPase proteins such as Rac1 and RhoA. Guanine nucleotide exchange factors (GEFs) are positive regulators of the small GTPase proteins and have been implicated as important factors in regulating cytokinesis. However, it is still unclear how GEFs regulate the contractile ring during cytokinesis in mammalian cells. Here we report that a novel GEF, which is termed MyoGEF (myosin-interacting GEF), interacts with non-muscle myosin II and exhibits activity toward RhoA. MyoGEF and non-muscle myosin II colocalize to the cleavage furrow in early anaphase cells. Disruption of MyoGEF expression in U2OS cells by RNA interference (RNAi) results in the formation of multinucleated cells. These results suggest that MyoGEF, RhoA, and non-muscle myosin II act as a functional unit at the cleavage furrow to advance furrow ingression during cytokinesis.


Chemical genomics: a challenge for de novo drug design.
De novo design provides an in silico toolkit for the design of novel small molecular structures to a set of specified structural constraints. With the avalanche of bioinformatics data, de novo design is ideally suited for exploring molecules that could be useful for chemical genomics. The design process involves manipulation of the input, modification of structural constraints, and further processing of the de novo generated molecules using various modular toolkits. The development of a theoretical framework for each of these stages will provide novel practical solutions to the problem of creating compounds with maximal chemical diversity. This short review describes the fundamental problems encountered in the application of novel chemical design technologies to chemical genomics by means of a formal representation. This notation helps to outline and clarify ideas and hypotheses that can then be explored using mathematical algorithms. It is only by developing this rigorous foundation that in silico design can progress in a rational way.


Urinary hematin calculi.
We report 2 cases of nephrolithiasis owing to hematin stones. One patient had no apparent explanation for this finding, while the other was receiving warfarin anticoagulation for a prosthetic aortic valve. The chemical nature, etiology and clinical features of hematin calculi are discussed.


Congenital rubella.
The original concept of the rubella syndrome as a triad of abnormalities affecting the eye, heart, and hearing organs has changed dramatically in the past 30 years. This paper describes the various clinical manifestations of congenital rubella now recognized and the varied consequences of rubella virus infection upon the fetus. The pathogenesis of intrauterine rubella is discussed in relation to the immunologic response of the fetus and to possible mechanisms of cell and tissue damage. The need for preventive measures is discussed in relation to the total number of children damaged annually and the importance of multiple defects leading to severe handicaps. Active immunization procedures to prevent congenital rubella defects are reviewed, with comments on the differences between vaccination policies in the United Kingdom and in the United States. The importance of surveillance of congenital rubella defects is emphasized; details of the National Rubella Surveillance Scheme in the United Kingdom are discussed.


Humoral immune response against a 70-kilodalton heat shock protein of Entamoeba histolytica in a group of patients with invasive amoebiasis.
In order to investigate the humoral immune response against Entamoeba histolytica a lambda ZapII cDNA library was constructed from trophozoites of the pathogenic E. histolytica strain SFL-3. The library was screened with serum IgG from a patient with invasive amoebiasis. Forty-nine immunopositive lambda clones were isolated and partial sequences from the inserts were obtained. By comparison of the sequences with the merged database MIPSX from the Martinsried Institute for Protein Sequences we were able to identify homologous proteins for 36 of the clones. Twenty-six of the clones encoded intracellular proteins, among these, the major part (16 clones) were highly homologous to the eukaryotic 70-kDa heat shock proteins (Hsps). The open reading frame of one complete clone encodes a protein of 656 amino acid residues of 71.5 kDa which has 69.8% sequence identity with the human Hsp70 protein. In a larger screening experiment only 3 out of 12 patients detected with their IgG the phage which expressed the 70-kDa heat shock protein(s).


Association of the gut microbiome and metabolome with wheeze frequency in childhood asthma.
While the microbiome has an established role in asthma development, less is known about its contribution to morbidity in children with asthma. In this ancillary study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we analyzed the gut microbiome and metabolome of wheeze frequency in children with asthma. Bacterial 16S ribosomal RNA microbiome and untargeted metabolomic profiling were performed on fecal samples collected from 3-year-old children with parent-reported physician-diagnosed asthma. We analyzed wheeze frequency by calculating the proportion of quarterly questionnaires administered between ages 3 and 5 years in which parents reported the child had wheezed (wheeze proportion). Taxa and metabolites associated with wheeze were analyzed by identifying log fold changes with respect to wheeze frequency and correlation/linear regression analyses, respectively. Microbe-metabolite and microbe-microbe correlation networks were compared between subjects with high and low wheeze proportion. Specific taxa, including the genus Veillonella and histidine pathway metabolites, were enriched in subjects with high wheeze proportion. Among wheeze-associated taxa, Veillonella and Oscillospiraceae UCG-005, which was inversely associated with wheeze, were correlated with the greatest number of fecal metabolites. Microbial networks were similar between subjects with low versus high wheeze frequency. Gut microbiome features are associated with wheeze frequency in children with asthma, suggesting an impact of the gut microbiome on morbidity in childhood asthma.


Dietary nitrate intake and vegetable consumption, ambient particulate matter, and risk of hypertension in the Nurses' Health study.
Studies have suggested that dietary nitrate could lower blood pressure levels whereas ambient particulate matter (PM) may increase risk of hypertension. However, it is unknown if these exposures may modify each other. We collected information on dietary nitrate intake and vegetables consumption and estimated long-term exposures to ambient PM for women in the Nurses' Health Study. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of hypertension were calculated using Cox proportional hazards models with adjustment for potential demographic, lifestyle and dietary confounders. Interactions were assessed with multiplicative interaction terms and stratified models. Increases in dietary nitrate intake (per 150 mg/d) and green leafy vegetables consumption (per serving/day) were both significantly associated with decreases in hypertension risk (both multivariable-adjusted HRs were 0.97, 95% CI: 0.94, 0.99). Long-term exposure to ambient PM with an aerodynamic diameter ≤ 2.5 µm (PM2.5) was associated with an increased risk of hypertension, with a multivariable-adjusted HR of hypertension of 1.06 (95% CI: 1.02, 1.11) per 10 µg/m3 increase in PM2.5. Ambient PM2.5 significantly modified the associations of dietary nitrate intake (Pinteraction = 0.02) and green leafy vegetables consumption (Pinteraction = 0.004). The associations with dietary factors were gradually weakened with increasing PM2.5: the fully-adjusted HRs for risk of hypertension were 0.94 (95% CI: 0.89, 0.99) and 0.94 (95% CI: 0.90, 0.99) for per 150 mg/d increase in nitrate intake and per serving/d increase in green leafy vegetables consumption, respectively, in the lowest PM2.5 quartile, and 1.00 (95% CI: 0.94, 1.06) and 1.02 (95% CI: 0.97, 1.08), respectively, in the highest PM2.5 quartile. Our research highlights a potentially protective effect of dietary nitrate intake in the prevention of hypertension and suggests that these benefits are attenuated by increasing exposure to ambient PM2.5.


Effects of early protein-calorie malnutrition on the immune response.
Intrauterine and early postnatal malnutrition caused a marked and protracted weight reduction of the body, spleen, and thymus. The mean body weight of the offspring of the malnourished mothers at weaning was 25 +/- 10 g whereas that of the controls was 75 +/- 20 g. At weaning the mean spleen weight of the malnourished offspring was 0.19 +/- 0.05 g and that of their controls was 0.4 +/- 0.13 g. During refeeding the spleen weight but not the thymus weight of the malnourished offspring caught up with that of the controls after about 70 days. After refeeding for as long as 4 months the thymus weight of the malnourished was still significantly (P less than 0.01) less than that of the corresponding weight-matched controls. Primary and secondary plaque-forming cells (PFC) in both the spleen and thymus of the weanling malnourished offspring were barely detectable whereas spleen of their controls had mean approximate values of 50 x 10(3) primary PFC and 70 x 10(3) secondary PFC. The corresponding values in the control thymus were 20 x 10(2) primary PFC and 8 x 10(2) secondary PFC. After refeeding for 4 months of the weanling malnourished offspring their primary and secondary PFC in the spleen increased to about one-half the level of that in their controls whereas the PFC in the thymus were still barely detectable. On the other hand, mean primary and secondary rosette-forming cells (RFC) in the spleen of the weanling malnourished offspring were less than 1 x 10(3) in comparison to the 80-90 x 10(3) in the controls (P less than 0.001). In the thymus too, mean primary and secondary RFC were also less than 1 x 10(3), whereas the corresponding figure in the controls was 30-50 x 10(3) RFC. After refeeding for 4 months the mean values of both the primary and secondary RFC in the spleen and thymus continued to remain less than 1 x 10(3). Although cell morphology in the spleen of the malnourished offspring had returned to normal appearance after 4 months of refeeding, that of the corresponding thymus had not done so completely. For instance, thymic corticomedullary function had reappeared by this time but thymocytes were still less in number than in the controls. By the 8th postnatal day serum IgG2b allotype became detectable in the control offspring, but it was not until day 20 that this IgG allotype could be detected in the malnourished offspring. IgG2a allotype could be detected in the sera of both the malnourished and control offspring.


Evidence that insulin can directly inhibit hepatic glucose production.
In order to evaluate the role of portal insulin in the modulation of hepatic glucose production (HGP), measurements of plasma glucose and insulin concentrations and both HGP and peripheral glucose disappearance rates were made following an infusion of a dose of tolbutamide (0.74 mg x m(-2) x min[-1]) in healthy volunteers that does not result in an increase in peripheral vein insulin concentrations or metabolic clearance rate of glucose. The results showed that the infusion of such a dose of tolbutamide was associated with a significant and rapid decline in both HGP (from 9.0 +/- 0.5 to 7.7 +/- 0.5 micromol x kg(-1) x min(-1) or delta = -13.8 +/- 4.5%; p < 0.001 compared to saline) and plasma glucose concentration (from 5.1 +/- 0.2 to 4.4 +/- 0.1 mmol/l or delta = -13.0 +/- 2.1%; p < 0.01 compared to saline). Since neither HGP nor fasting glucose fell when tolbutamide-stimulated insulin secretion was inhibited by the concurrent administration of somatostatin, it indicated that tolbutamide by itself, does not directly inhibit HGP. Finally, HGP fell by 26.3 +/- 6.0% at 10 min after a dose of tolbutamide that elevated both peripheral and portal insulin concentrations, at a time when HGP had barely increased (delta = +6.9 +/- 5.3%). The difference in the magnitude of the two responses was statistically significant (p < 0.03), providing further support for the view that insulin can directly inhibit HGP, independent of any change in flow of substrates from periphery to liver.


Correction: Panel of three novel serum markers predicts liver stiffness and fibrosis stages in patients with chronic liver disease.
[This corrects the article DOI: 10.1371/journal.pone.0173506.].


3-Month physical activity checklist: development and validation with Taiwanese adults with mental illness.
Physical activity has been shown to be an effective intervention to improve psychological and emotional functions for individuals with mental illness. Many scales have been used to measure physical activity in general populations, but most existing scales may not be easily applied to individuals with mental illness. The aim of this study was to test the reliability and validity of the 3-Month Physical Activity Checklist developed to measure physical activity performance in Taiwanese adults with mental illness. A survey questionnaire design was used to gather cross-sectional data for the scale. DATA COLLECTION AND PARTICIPANTS: Data were collected from a convenience sample of patients recruited in 2007-2010 from two mental health clinics in central Taiwan. The study was conducted in three phases: test-retest reliability and scale restructuring (n=28), test-retest reliability and criterion-validity testing of the restructured scale (n=60), and cross-sample testing (n=273). In third phase, participants were diagnosed with anxiety disorders (n=153), schizophrenia (n=98), and bipolar disorders (n=22). Data were collected by self-report 3-Month Physical Activity Checklist and an administered Chinese version of the 7-Day Physical Activity Recall. Data were analyzed by intraclass correlation coefficients and chi-square test. The restructured scale had 2-week test-retest reliability coefficients for light, moderate, and vigorous activity of 0.71, 0.78, and 0.86, respectively. Moderate to high agreement was found between the two scales for light (r=0.47), moderate (r=0.64), and vigorous activities (r=0.73). Recommended physical activity levels were achieved by 28.6% of participants (n=78) and differed significantly by type of mental disorder (χ(2)=21.98, p<0.000). The 3-Month Physical Activity Checklist has acceptable reliability and criterion validity to measure physical activity performance of Taiwanese adults with mental illness. The scale can be used by mental health professionals to identify levels and types of physical activity, which may be used to evaluate treatment effects or nursing care outcomes for patients with mental illness.


Active Tuberculosis After Solid Organ Transplantation in Individuals With Negative Pretransplant QuantiFERON-TB Gold Testing: A Case Series.
Active tuberculosis (TB) in solid organ transplant (SOT) recipients most commonly occurs due to reactivation of latent infection and is associated with poor clinical outcomes, including allograft loss and death. National transplant societies, including the American Society of Transplantation, recommend screening for latent TB prior to transplant, with treatment in the peritransplant setting to reduce the subsequent risk of TB reactivation. Though screening is traditionally conducted using laboratory-based assays, such as the QuantiFERON-TB Gold, false negatives may occur in SOT candidates due to anergy from end-stage organ dysfunction, highlighting the need for a multimodal diagnostic approach. In this case series, we describe the clinical characteristics and outcomes of 3 SOT recipients at the University of Pennsylvania with negative pretransplant QuantiFERON-TB Gold testing who subsequently developed active TB in the posttransplant setting, contributing to a growing body of knowledge regarding this challenging population. Each patient experienced a complicated clinical course that arose in part from the lack of diagnosis of TB prior to transplant. Because all had epidemiologic risk factors for TB, the findings of our study highlight the need for more individualized approaches to pretransplant TB screening.


Link between the early calcium deposition in placenta and nanobacterial-like infection.
The placenta is a vitally important organ in the regulation of embryonic development. That is why extensive calcium deposition [also named as pathological placental calcification (PPC)] could have serious negative consequences for the adequate growth of embryos. The nature and mechanism of PPC development has not been defined as yet. In the present investigation, we have tested the hypothesis that the molecular basis of PPC development consists of nanobacteria-induced calcification in infected female placenta. Electron microscopy findings support this hypothesis. The initial stage of micro-calcification may originate from the external surface of individual nanobacteria-like particles found mainly in placental extracellular matrix, where initial calcium deposition occurs as a needle surface deposition or as an amorphous-like surface precipitate. Further calcific propagation in placenta takes place in the newly formed macro-cavities, which are characterized by low electron density, possibly reflecting its liquid content around calcium deposition. The micro-cavities contain free nanobacterial-like particles, which may relate to atypical Gram-negative bacteria but not to apoptotic bodies by morphological characters and DNA/RNA distribution. We hypothesize that the increased placental calcification might be caused, at least in part, by nanobacterial infection.


First International Meeting on "Stem Cell Applications in the Craniofacial Region".
During the 1st International Meeting on "Stem Cell Applications in the Craniofacial Region" promoted in Naples (Italy), invited researchers presented theirwork and the most innovative methods regarding stem cells (SCs) and their application to the craniofacial region of the human body. In addition, some researchers showed their case-reports on craniofacial reconstruction using either osteo-distraction or reconstruction surgical methods. The aim of this biannual meeting is to stimulate discussion, improve knowledge and promote scientific collaboration among basic and clinical scientists in the main topics of SC use in therapy. A summary of this meeting is given.