Hydrothermal Fabrication of WO₃ Hierarchical Architectures: Structure, Growth and Response.
Recently hierarchical architectures, consisting of two-dimensional (2D) nanostructures, are of great interest for potential applications in energy and environmental. Here, novel rose-like WO₃ hierarchical architectures were successfully synthesized via a facile hydrothermal method. The as-prepared WO₃ hierarchical architectures were in fact assembled by numerous nanosheets with an average thickness of ~30 nm. We found that the oxalic acid played a significant role in governing morphologies of WO₃ during hydrothermal process. Based on comparative studies, a possible formation mechanism was also proposed in detail. Furthermore, gas-sensing measurement showed that the well-defined 3D WO₃ hierarchical architectures exhibited the excellent gas sensing properties towards CO.


Association between pulmonary mycobacterium avium complex infection and lung cancer.
Patients with lung cancer are sometimes found to have respiratory cultures growing Mycobacterium avium complex (MAC). This study describes the clinical, pathologic, and radiographic -characteristics of individuals who harbor concomitant lung cancer and MAC. Retrospective analysis of patients with positive respiratory cultures for MAC (370 men, 475 women) and with newly diagnosed lung cancer (792 men, 840 women) from 1995 to 2010. Of the patients with respiratory cultures growing MAC, 8.6% of men and 6.3% of women had lung cancer. Twenty-five percent of patients with lung cancer and 3% with nonbronchiectatic benign lung disease grew MAC from their respiratory cultures. Significantly fewer women with both MAC and lung cancer were smokers than the control group of women with lung cancer and negative MAC cultures (68% versus 89%, p < 0.01). Squamous cell carcinoma occurred in 40% of women in the MAC/lung cancer group versus 28% of women in the lung cancer control group. Peripherally located squamous cell carcinomas were found in 71% of the MAC/lung cancer group versus 40% of the lung cancer control group (p = 0.01) The percentage of smokers among women with both MAC and lung cancer was lower than among the lung cancer control group who did not grow MAC. The presence of MAC in respiratory cultures of lung cancer patients was particularly associated with squamous cell carcinomas located in the periphery of the lung. Because MAC typically affects distal airways, this possible association between MAC infection and lung cancer warrants further study.


Development of a cellular model to study alternative splicing of type II collagen gene.
To study regulation of alternative splicing of type II collagen (COL2) pre-mRNA, we constructed a mouse COL2 "minigene" containing genomic sequences spanning exon 1 to exon 4 of COL2 downstream of a cytomegalovirus (CMV) promoter. This minigene was introduced into ATDC5 cells, which undergo chondrocytic differentiation when treated with insulin. Alternative splicing of the COL2 minigene was evaluated by comparing the expression of the two mRNAs transcribed from the minigene to the expression of alternatively spliced transcripts from the endogenous COL2 gene. This analysis suggested that regulation of alternative splicing of pre-mRNAs from the minigene and the endogenous COL2 gene are accomplished by similar mechanisms. We conclude that the cloned genomic fragment contains key sequences necessary for alternative splicing of COL2 pre-mRNA. This system provides a useful model to begin the process of identifying cis- and trans-acting factors that carry out alternative splicing of COL2 pre-mRNA during chondrocyte differentiation.


[Natural history of localized prostate cancer. Preliminary data on progression and mortality].
To address the effect of therapy options and other factors on the natural history of localized prostate cancer (PCa). Men with diagnosed clinically localized PCa who underwent radical prostatectomy (RP), radiotherapy (RT) or watchful waiting (WW). Rates of biochemical progression (BQP) and clinical progression (CLP) were calculated. The effects of therapy, initial PSA, presence of palpable tumor and Gleason score were assessed with Kaplan-Meier analysis and log-rank test. Similar methods were used to study overall and disease-specific survival. A total of 228 patients were studied (135 underwent RP, 46 RT, and 47 WW). Median followup time was 2.5 years. Forty patients presented with BQP. The probability of being free from BQP after 2 and 5 years was 76.8% and 57.9% respectively for the whole population, 70.9% and 57.6% for RP patients, 100% and 100% for RT, and 87.1% and 47.2% for WW (p = 0.031). Nineteen patients presented with CLP, with no significant differences with regard to therapy option. A poorly differentiated Gleason score favoured the probability of presenting with CLP (p = 0.022) and shift to metastatic disease (p < 0.001). No cancer-specific mortality was recorded in the studied population. Short and medium-term prognosis is excellent for localized prostate cancer in terms of survival. Nevertheless, some patients show a higher risk of progressing to metastatic disease (poorly differentiated Gleason score).


Relationships between central tear film thickness and tear menisci of the upper and lower eyelids.
To investigate the relationship between central tear film thickness (TFT) and tear menisci of the upper and lower eyelids using real-time optical coherence tomography (OCT). Both eyes of healthy subjects were imaged with a real-time OCT to obtain height, curvature, and area of upper and lower tear menisci simultaneously. Central TFT was indirectly measured by calculating the difference between baseline measurements of the central corneal thickness plus tear film and the true corneal thickness obtained after instillation of artificial tears. Results from two normal blinks were obtained from one eye at each visit and repeated the next day. The average central TFT was 3.4 +/- 2.6 microm. The upper tear meniscus curvature, height, and area were 239 +/- 112 microm, 268 +/- 68 microm, and 22,732 +/- 11,974 microm2 respectively. There were no significant differences in curvatures, heights, or areas between upper and lower tear menisci, nor were there any differences in measured variables between the two blinks at each visit or between the two repeated visits in the right and left eye groups (P > 0.05). The upper and lower tear menisci in each eye group on each day correlated strongly with curvature, height, and area (all P < or = 0.03). However, no tear meniscus variable was a significant predictor of TFT (all P > 0.44). OCT is a promising tool in the measurements of TFT and dimensional variables of tear menisci. Upper and lower tear menisci have nearly identical dimensions.


An x-ray penumbral imager for measurements of electron-temperature profiles in inertial confinement fusion implosions at OMEGA.
Hot-spot shape and electron temperature (Te) are key performance metrics used to assess the efficiency of converting shell kinetic energy into hot-spot thermal energy in inertial confinement fusion implosions. X-ray penumbral imaging offers a means to diagnose hot-spot shape and Te, where the latter can be used as a surrogate measure of the ion temperature (Ti) in sufficiently equilibrated hot spots. We have implemented a new x-ray penumbral imager on OMEGA. We demonstrate minimal line-of-sight variations in the inferred Te for a set of implosions. Furthermore, we demonstrate spatially resolved Te measurements with an average uncertainty of 10% with 6 μm spatial resolution.


Arginine regulation of gramicidin S biosynthesis.
Several amino acids are known to affect the gramicidin S producer Bacillus brevis ATCC 9999 with respect ot growth, soluble gramicidin S synthetase formation, antibiotic production, or a combination of these. Our studies confirmed that arginine has paradoxical effects on the B. brevis fermentation; it markedly increased growth and antibiotic production, yet decreased the soluble heavy gramicidin S synthetase activity. We found that arginine did not repress heavy gramicidin S synthetase. The amino acid stimulated growth and increased specific antibiotic production presumably by supplying a limiting precursor (ornithine) for gramicidin S synthesis. Although the amino acid decreased the specific activity of the soluble heavy gramicidin S synthetase, it markedly increased the particulate enzyme activity which persisted hours after the soluble heavy gramicidin S synthetase disappeared. One percent arginine was the optimum level for growth and gramicidin S production. After growth in 1% arginine, heavy synthetase activity in the particulate fraction more than doubled. We propose that arginine leads to the soluble enzyme becoming membrane bound and more stable in vivo. Although we found arginine capable of inhibiting the action of soluble heavy gramicidin S synthetase, this was not the mechanism involved in the lowering of soluble heavy gramicidin S synthetase specific activity.


Multi-compartmental diffusion characterization of the human cervical spinal cord in vivo using the spherical mean technique.
The purpose of this work was to evaluate the feasibility and reproducibility of the spherical mean technique (SMT), a multi-compartmental diffusion model, in the spinal cord of healthy controls, and to assess its ability to improve spinal cord characterization in multiple sclerosis (MS) patients at 3 T. SMT was applied in the cervical spinal cord of eight controls and six relapsing-remitting MS patients. SMT provides an elegant framework to model the apparent axonal volume fraction vax , intrinsic diffusivity Dax , and extra-axonal transverse diffusivity Dex_perp (which is estimated as a function of vax and Dax ) without confounds related to complex fiber orientation distribution that reside in diffusion MRI modeling. SMT's reproducibility was assessed with two different scans within a month, and SMT-derived indices in healthy and MS cohorts were compared. The influence of acquisition scheme on SMT was also evaluated. SMT's vax , Dax , and Dex_perp measurements all showed high reproducibility. A decrease in vax was observed at the site of lesions and normal appearing white matter (p < 0.05), and trends towards a decreased Dax and increased Dex_perp were seen. Importantly, a twofold reduction in acquisition yielded similarly high accuracy with SMT. SMT provides a fast, reproducible, and accurate method to improve characterization of the cervical spinal cord, and may have clinical potential for MS patients.


Management of genital infection caused by human papillomavirus.
Recent studies of genital wart therapy have evaluated laser surgery, interferon, and 5-fluorouracil. On the basis of considerations of efficacy, cost, adverse effects, and recurrence rates, cryotherapy with liquid nitrogen remains the recommended therapy for most sexually transmitted warts. None of the treatment methods eradicates the papillomavirus, and genital wart recurrences are seen with each method. The influence of treatment of genital warts on the natural course and sequelae of genital papillomavirus infection is unknown.


Evaluation of the indications for performing magnetic resonance imaging of the female pelvis at a referral center for cancer, according to the American College of Radiology criteria.
To evaluate the indications for performing magnetic resonance imaging of the female pelvis at a referral center for cancer. This was a retrospective, single-center study, conducted by reviewing medical records and imaging reports. We included 1060 female patients who underwent magnetic resonance imaging of the pelvis at a cancer center between January 2013 and June 2014. The indications for performing the examination were classified according to the American College of Radiology (ACR) criteria. The mean age of the patients was 52.6 ± 14.8 years, and 49.8% were perimenopausal or postmenopausal. The majority (63.9%) had a history of cancer, which was gynecologic in 29.5% and nongynecologic in 34.4%. Of the patients evaluated, 44.0% had clinical complaints, the most common being pelvic pain (in 11.5%) and bleeding (in 9.8%), and 34.7% of patients had previously had abnormal findings on ultrasound. Most (76.7%) of the patients met the criteria for undergoing magnetic resonance imaging, according to the ACR guidelines. The main indications were evaluation of tumor recurrence after surgical resection (in 25.9%); detection and staging of gynecologic neoplasms (in 23.3%); and evaluation of pelvic pain or of a mass (in 17.1%). In the majority of the cases evaluated, magnetic resonance imaging was clearly indicated according to the ACR criteria. The main indication was local recurrence after surgical treatment of pelvic malignancies, which is consistent with the routine protocols at cancer centers.


Haplotype-resolved de novo assembly of the Vero cell line genome.
The Vero cell line is the most used continuous cell line for viral vaccine manufacturing with more than 40 years of accumulated experience in the vaccine industry. Additionally, the Vero cell line has shown a high affinity for infection by MERS-CoV, SARS-CoV, and recently SARS-CoV-2, emerging as an important discovery and screening tool to support the global research and development efforts in this COVID-19 pandemic. However, the lack of a reference genome for the Vero cell line has limited our understanding of host-virus interactions underlying such affinity of the Vero cell towards key emerging pathogens, and more importantly our ability to redesign high-yield vaccine production processes using Vero genome editing. In this paper, we present an annotated highly contiguous 2.9 Gb assembly of the Vero cell genome. In addition, several viral genome insertions, including Adeno-associated virus serotypes 3, 4, 7, and 8, have been identified, giving valuable insights into quality control considerations for cell-based vaccine production systems. Variant calling revealed that, in addition to interferon, chemokines, and caspases-related genes lost their functions. Surprisingly, the ACE2 gene, which was previously identified as the host cell entry receptor for SARS-CoV and SARS-CoV-2, also lost function in the Vero genome due to structural variations.


A diagnostic subgroup comparison of health care utilization patterns in individuals with eating disorders diagnosed in childhood and/or adolescence.
This study examined a 2-year period after diagnosis of an eating disorder to compare health care utilization in diagnostic subgroups including: anorexia nervosa (AN), bulimia nervosa (BN), binge-eating disorder (BED), avoidant/restrictive food intake disorder (ARFID), and other specified eating disorders (Other). We conducted a retrospective study of children diagnosed with AN (n = 674), BN (n = 230), BED (n = 59), ARFID (n = 171), and Other (n = 315). We used a general population cohort for comparison, matched 5:1 to the diagnostic subgroups on sex and birth date. We then conducted a separate analysis using the ARFID subgroup as a reference group compared to the other subgroups. Outcomes were determined using data linkage with health administrative databases and included hospitalizations, emergency department, general practitioner, psychiatry, and pediatrician visits. Odds ratios (dichotomous outcomes) and rate ratios (continuous outcome) were calculated. Mental health care utilization was higher for all subgroups compared to the general population. When the subgroups were compared to the ARFID subgroup, those with ARFID appeared to have similar health care utilization to the other subgroups, except when compared to those with AN. The AN subgroup had higher odds of a mental health related hospitalization (OR 1.62, 95% CI 1.04-2.5) higher rates of mental health related pediatrician visits (RR 1.76, 95% CI 1.26-2.46) and psychiatry visits (RR 1.69, 95% CI 1.07-2.68). Those with ARFID have similar utilization as other subtypes of eating disorders, except when compared to those with AN who have higher health care utilization. Our study found that the health service needs of young people with all types of eating disorders are substantially higher than the general population, and it appears that Avoidant/Restrictive Food Intake Disorder (ARFID) has similar health care utilization to other eating disorders.


Immediate as well as delayed post learning sleep but not wakefulness enhances declarative memory consolidation in children.
While there is mounting evidence for the importance of sleep for declarative memory consolidation in adults, so far this issue has not been investigated in children despite considerable differences in sleep duration and sleep architecture between children and adults. Here, 27 children (aged between 9 and 12yr) were examined on two conditions: on the Sleep-Wake condition, subjects learned word pairs in the evening and delayed recall was tested first in the next morning after sleep and then again in the following evening after daytime wakefulness. On the Wake-Sleep condition, learning took place in the morning and delayed recall was tested in the evening of the same day and again in the next morning after sleep. In both conditions retention of declarative memory was significantly increased only after an interval of sleep that either followed immediately after learning (as in the Sleep-Wake condition) or that followed after daytime wakefulness (as in the Wake-Sleep condition), respectively. The results support the hypothesis that sleep plays an active role in declarative memory consolidation even if delayed and further show for the first time the importance of sleep for declarative memory consolidation during childhood.


Effect of decreased O2 supply to tissue on the lactate: pyruvate ratio in blood.
Experiments were performed with trained conscious dogs with permanently implanted intravascular catheters. With the dogs in a basal resting state, the concentrations of lactate (L) and pyruvate (P) in arterial blood fluctuated widely from day to day, whereas their concentration ratio (L/P) remained relatively constant. By contrast, decrease in tissue O(2) supply induced by severe chronic anemia increased the arterial blood L/P, specifically, with only random accompanying changes in the lactate or pyruvate concentrations themselves. When systemic O(2) consumption was increased acutely by muscular exercise, cardiac output increased, and the changes in blood L/P were small and not consistent between different dogs. But when O(2) supply to the tissues was simultaneously limited by anemia, L/P increased during exercise, and the magnitude of the increase was proportional to the severity of the anemia. These results suggest that changes in blood L/P during exercise are related specifically to tissue O(2) supply.


Transplant genetics and genomics.
Ever since the discovery of the major histocompatibility complex, scientific and clinical understanding in the field of transplantation has been advanced through genetic and genomic studies. Candidate-gene approaches and recent genome-wide association studies (GWAS) have enabled a deeper understanding of the complex interplay of the donor-recipient interactions that lead to transplant tolerance or rejection. Genetic analysis in transplantation, when linked to demographic and clinical outcomes, has the potential to drive personalized medicine by enabling individualized risk stratification and immunosuppression through the identification of variants associated with immune-mediated complications, post-transplant disease or alterations in drug-metabolizing genes.


Regulation of inflammation by airway smooth muscle.
Inflammatory mediators play a critical role in the pathogenesis of chronic airway diseases and facilitate the recruitment, activation, and trafficking of inflammatory cells in the airways. Compelling evidence now shows that airway smooth muscle expresses adhesion molecules and secretes inflammatory mediators. Airway myocytes also express a repertoire of immunomodulatory proteins such as Toll-like receptors, chemokines, and cytokines. The underlying mechanisms by which these molecules modulate airway inflammation and the physiological consequences of these molecules are now being elucidated, suggesting that airway smooth muscle plays an important role in orchestrating and perpetuating airway inflammation, remodeling, and fibrosis in chronic airway diseases.


Synthesis and photocatalytic properties of highly crystalline and ordered mesoporous TiO2 thin films.
Highly crystalline and ordered mesoporous TiO2 thin films have been synthesized by stabilization of the mesostructure with confined carbon; the films exhibit 2.5% photoconversion efficiency for the water photolysis at zero-bias and Xe lamp illumination of 40 mW cm(-2).


Development and Validation of a Prediction Score for Low-Cardiac-Output Syndrome After Adult Cardiac Surgery.
The authors aimed to develop a simple prediction score to help identify patients at high risk of low-cardiac-output syndrome after adult cardiac surgery. A single-center, retrospective, observational study. At a tertiary hospital. Adult patients who underwent on-pump cardiac surgery between April 2016 and March 2021. None. Among the 2,806 patients retained for final analyses, 355 (12.7%) developed low-cardiac-output syndrome. Using a stepwise backward variable selection procedure applied to a multivariate logistic regression, a prediction model, including 8 risk factors, could be identified-preoperative left ventricular ejection fraction, glomerular filtration rate <60 mL/min according to the Cockcroft formula or preoperative dialysis, combined surgery, nonelective surgery, mitral valve surgery for mitral valve regurgitation, history of extracardiac arteriopathy, preoperative hemoglobin <13 g/dL, and New York Heart Association functional class III or IV. A clinical prediction score was derived from the regression coefficients. The model had a good discriminative ability, with an area under the receiver operating characteristics curve of 0.8 (95% CI: 077-0.84). Using a threshold value of 5, the score had a 68% sensitivity, 79% specificity, a positive-predictive value of 33%, and a negative-predictive value of 94%. These results were validated on a validation sample using the bootstrap resampling technique. The authors developed a clinical score to facilitate the prediction of low- cardiac-output syndrome after adult cardiac surgery. This could help tailor patient management by contributing to the early identification of those at high risk of postoperative low cardiac output.


A longitudinal study characterising a large adult primary ciliary dyskinesia population.
Primary ciliary dyskinesia (PCD) in adults has not been well described. In this retrospective observational study we aimed to characterise a large adult population and identify features associated with disease progression.We retrospectively analysed 151 adult patients at a single tertiary centre at baseline and longitudinally for a median of 7 years.We found significant variation in age at diagnosis (median 23.5 years; range <1-72 years). Older age at diagnosis was associated with impaired baseline forced expiratory volume in 1 s (FEV1) (r= -0.30, p=0.01) and increased Pseudomonas aeruginosa colonisation (difference in medians 17 years (95% CI 4.5-20 years); p=0.002). Lung function decline was estimated at FEV1 decline of 0.49% predicted per year. Lung function decline was associated with ciliary ultrastructure, with microtubular defect patients having the greatest decline (p=0.04). High-resolution computed tomography (HRCT) scores of severity of bronchial wall dilatation (p<0.001) and extent of bronchiectasis (p=0.03) additionally showed evidence of modifying FEV1 decline with age.Our study reveals that a large proportion of adult PCD patients are diagnosed late, with impaired FEV1 and increased P. aeruginosa colonisation. Increased disease burden on HRCT and ciliary ultrastructure may predict progressive lung function decline. This study characterises a large adult PCD population, identifies features associated with disease progression and highlights the need for prospective trials to determine whether early diagnosis of high-risk subgroups alongside optimal management can modify disease progression.


Evaluation of IL-6 and IL-17A gene polymorphisms in Iraqi patients infected with COVID-19 and type 2 diabetes mellitus.
In patients with COVID-19, diabetes mellitus type 2 (T2DM) increases the risk of hospitalization and death. Patients who have IL-6 and IL-17A single nucleotide polymorphisms (SNPs) are more likely to have severe COVID-19. This study aims to determine whether SNPs of the IL-6 gene at rs1800795 (G > C) and the IL-17A gene at rs2275913 (G > A) are associated with COVID-19 and T2DM in the Iraqi population. Twenty-four people were divided into 4 groups as follows: six patients with severe COVID-19 and T2DM were placed in Group 1 as "G1", six patients with COVID-19 but no T2DM were placed in Group 2 as "G2", and six patients with T2DM were placed in Group 3 as "G3". There were also six healthy controls included in each group. Polymerase chain reaction (PCR) was used to amplify the target genes after genomic DNA from the blood samples was extracted. Sanger sequencing was used to find the SNPs in both the forward and reverse directions for each sample. In the case of IL-6 SNP at rs1800795, the GG genotype was more common in "G3", the CC genotype was less common in all patient groups than in controls, and the GC allele was more common in "G2" than in the control group. In comparison to the controls, the three patient groups showed lower frequencies of the C allele and higher frequencies of the G allele. Regarding IL-17A gene polymorphism, the AA and GA genotypes were more prevalent in "G2" and "G3", respectively. The GG genotype and G allele frequency dropped in all patient groups compared to the control group, whereas the A allele frequency increased in all patient groups. The IL-6 gene at rs1800795 (G/C) and the IL-17A gene at rs2275913 (G/A) loci were associated with COVID-19 and T2DM in Iraqi population.


An Empirical Study of Economic Cycle, Air Quality, and National Health Since Reform and Opening Up.
Since the reform and opening up of China, the economy has continued to grow, and diverse needs have generated different types and periods of economic activities. This has caused people to have an unhealthy diet, lack of exercise, irregular work and rest, lack of sleep, mental stress, high psychological pressure, long-term bad moods, and other health problems. The proportion of the sub-healthy population continues to increase and health problems are becoming increasingly prominent. Based on this, we examine the internal mechanism of the economic cycle on national health since the reform and opening up of China. For a long time, China has actively responded to the UN's call for environmental protection and proposed that "clear waters and lush mountains are invaluable assets." Therefore, this study combines air quality in the process of environmental governance in China to investigate national health. Data from 22 provinces, five autonomous regions, and four municipalities from 2004 to 2017 are selected as research samples to examine the relationship between economic cycles, air quality, and national health for empirical testing. Studies have shown that the economic cycle is significantly correlated with national health. The better the macroeconomy, the better the health of the human body; that is, the lower the unemployment rate, the lower the mortality rate. After introducing air quality, it was found to have a significant regulating effect on the relationship between the economic cycle and national health. Our conclusions reveal that economic development is closely related to national health. China should attach great significance to the environment and air quality in the process of economic development to achieve sustainable development and create a green economy.


Perineal Groove: An Anorectal Malformation Network, Consortium Study.
To review the Anorectal Malformation Network experience with perineal groove (PG) focusing on its clinical characteristics and management. Data on patients with PG managed at 10 participating Anorectal Malformation Network centers in 1999-2019 were collected retrospectively by questionnaire. The cohort included 66 patients (65 females) of median age 1.4 months at diagnosis. The leading referral diagnosis was anal fissure (n = 20 [30.3%]): 23 patients (34.8%) had anorectal malformations. Expectant management was practiced in 47 patients (71.2%). Eight (17%) were eventually operated for local complications. The median time to surgery was 14 months (range, 3.0-48.6 months), and the median age at surgery was 18.3 months (range, 4.8-58.0 months). In the 35 patients available for follow-up of the remaining 39 managed expectantly, 23 (65.7%) showed complete or near-complete self-epithelization by a mean age 15.3 months (range, 1-72 months) and 4 (11.4%) showed partial self-epithelization by a mean age 21 months (range, 3-48 months). Eight patients showed no resolution (5 were followed for ≤3 months). Nineteen patients (28.7%) were primarily treated with surgery. In total, 27 patients were operated. Dehiscence occurred in 3 of 27 operated patients (11.1%). PG seems to be an underestimated anomaly, frequently associated with anorectal malformations. Most cases heal spontaneously; therefore, expectant management is recommended. When associated with anorectal malformations requiring reconstruction, PG should be excised in conjunction with the anorectoplasty.


Plasma morphine concentrations and clinical effects after thoracic extradural morphine or diamorphine.
Twenty-seven patients undergoing thoracotomy received either morphine sulphate 2 mg or diamorphine hydrochloride 2 mg by thoracic extradural injection for postoperative analgesia. Arterial plasma morphine concentrations were measured by specific radioimmunoassay, and the analgesic, respiratory and biochemical effects noted. The plasma morphine concentrations were significantly greater after extradural diamorphine than after extradural morphine in the first 30 min after injection. The maximum increase in plasma morphine concentration was significantly (P less than 0.02) greater after extradural diamorphine, and mean peak values occurred at 5 and 10 min for diamorphine and morphine, respectively. There were significant decreases in respiratory rate and plasma cortisol concentration with maximum effects between 90 and 180 min after the extradural injection. The analgesia produced by these doses was inadequate. The role of lipophilicity is discussed.


The efficacy of a modified Dix-Hallpike test with a pillow under shoulders.
Dix-Hallpike (DH) test is sometimes done in a modified or reduced manner in a clinical setting. However, there has been no study that evaluated the reliability of this modified test. The purposes of this study were to determine whether the efficacy of a modified DH test, named the 'pillow under shoulders' test, was equivalent to the standard DH test and to assess the difference in patient discomfort between the two methods. Randomized controlled study at three academic referral hospitals, conducted in compliance with the CONSORT statement. Patients suspected for BPPV based on symptoms were randomly assigned to Group A or Group B. Patients in Group A received a standard DH test initially, followed by a modified DH test with a pillow under shoulders. Patients in Group B also received the two tests, but in the reverse order. The diagnostic results of both tests and patients' subjective scoring for uneasiness (discomfort, pain, anxiety) were statistically analyzed. McNemar's test and Kappa statistics showed a statistically equivalent diagnostic value between standard and modified DH tests (Cohen's kappa = 0.823 and McNemar P = 0.18). The modified DH test had high sensitivity (95.5%) and fairly good specificity (87.9%). There was no statistical significance in the patients' subjective scoring for uneasiness between the two methods, although most patients reported less inconvenience after the modified DH test compared to the standard DH test. The modified version of the standard DH test, the 'pillow under shoulders' method, may be a reliable, comfortable option to diagnose vertical canal BPPV. We suggest that this method can be used when head hanging is not feasible or sufficient for the standard DH test.


Characteristics of 21 Types of Tea Waste for Adsorbance of Ionic Dyes from Aqueous Solutions.
In this study, 21 tea types (six black, four green, three Oolong, two herb, and five medicinal) were used to remove ionic dye from wastewater, as they could be potential adsorbents for several ionic dyes without purification or activated treatment. The majority of the 21 teas could adsorb cationic (MB) and anionic (ORII) dyes, with greater suitability for cationic dyes, as well as BB54 and BR46. Black dye (KBla), a mixture of several dyes, was adsorbed to a high degree. The tea waste treatment resulted in chromaticity reduction of the dye solution and turbidity changes. Dye adsorption was greater at higher temperatures than lower ones, although the effect of temperature was not strong. The adsorptions fit the pseudo-second-order-model; therefore, they involved chemical adsorption. The tea waste had great potential for the adsorption of several types of dyes without purification or activated treatment, although the mechanisms are yet to be determined. Therefore, the physical properties and structural components of each tea type should be analyzed by comparing common or different features of tea types. Taken together, many types of tea that are consumed worldwide can be used for efficient adsorption of ionic dyes by application of the tea waste.


Effect of flavin compounds on glutathione reductase activity: in vivo and in vitro studies.
Increases or decreases of red cell glutathione reductase (GR) have been described in connection with many clinical abnormalities. We find that GR activity as measured in hemolysates represents only a portion of the available GR activity. The addition of small amounts of flavin adenine dinucleotide (FAD), but not of flavin mononucleotide or riboflavin, activates the GR of hemolysates. 1 muM FAD results in a maximal activation within 10 min; gradually increasing activation occurs at much lower, for example, 20 mmuM FAD concentrations. Once FAD has activated GR, dilution or dialysis does not reverse activation of the enzyme. Activation of GR by FAD can be inhibited by adenosine triphosphate (ATP), and to a lesser extent by adenosine diphosphate (ADP) and adenosine monophosphate (AMP), if these adenine nucleotides are added before the addition of FAD, but only to a slight extent if FAD is added before the adenine nucleotides. The addition of FAD to GR does not alter its electrophoretic mobility but produces intensification of the bands. The administration of 5 mg of riboflavin daily produces marked stimulation of red cell GR activity within only 2 days. After cessation of riboflavin administration, the GR activity again begins to fall. The degree of stimulation of GR activity by riboflavin is inversely correlated with the level of dietary riboflavin intake. The base line GR activity of normal individuals is directly correlated with the level of dietary riboflavin intake. The previously unexplained variations of glutathione reductase in health and disease must be reevaluated in light of the state of riboflavin nutrition and metabolism of the subject.


Proenzyme from of cathepsin L produced by thymic epithelial cells promotes proliferation of immature thymocytes in the presence of IL-1, IL-7, and anti-CD3 antibody.
A thymic epithelial cell line (TEC1-4) established from newborn mouse thymus produced a cofactor to promote proliferation of double-negative (CD4-8-) thymocytes in the presence of IL-1, IL-7, and anti-CD3 antibody. Based upon the sequence of 8 amino acid residues near the N terminal portion, the factor was identified as the mouse proenzyme form of cathepsin L which is almost identical to the rat proenzyme form of cathepsin L (95% in homology). Production of the proenzyme form of cathepsin L was confirmed in the TEC1-4 and mouse embryonic thymus by Western blotting analysis and Northern blotting analysis. Furthermore, immunohistologically, the presence of cathepsin L was observed in the epithelial cells of the subcapsular layer and around the small vessels in the thymic cortex. It has been concluded that a subpopulation of thymic cortical epithelial cells produces the proenzyme form of cathepsin L which can act as a cofactor to promote proliferation of DN immature thymocytes.


Lysophosphatidic acid is the unique platelet-activating substance in human malignant ascites.
Pathological blood platelet activation promotes thrombosis in cancer patients, but the specific substances involved are still under investigation. Tumor exudates have been described to contain lysophosphatidic acid (LPA), a known platelet-activating substance, and the concentration of mediators present in malignant ascites are constantly equilibrated with the concentration in plasma. We hypothesized that the ascites of cancer patients might activate platelets, and that this may be caused by LPA. Indeed, ascites samples from 15 different patients with cancer induced shape change and an increase of cytosolic Ca2+ of isolated platelets; both responses were cross-desensitized by lysophosphatidic acid (LPA), but not by other platelet stimuli. Moreover shape change, Ca2+ mobilization and aggregation induced by ascites could be completely blocked by pretreatment of platelets with specific LPA-receptor antagonists. Phospholipids were extracted from ascites, separated by thin layer chromatography, and individual fractions were tested for activity on platelets. The platelet activating substance co-migrated with LPA, whereas other fractions were inactive. Notably, ascites induced through LPA-receptor activation platelet aggregation in whole blood. Our results suggest that LPA plays an essential role in the pathological platelet activation in cancer patients. We propose that LPA receptor antagonists could be effective in blocking cancer-associated platelet activation and thus preventing thrombosis.


Nicotinic receptor modulation of dopamine transporter function in rat striatum and medial prefrontal cortex.
Nicotine activates nicotinic acetylcholine receptors (nAChRs) on dopamine (DA) terminals to evoke DA release, which subsequently is taken back up into the terminal via the DA transporter (DAT). nAChRs may modulate DAT function thereby contributing to the regulation of synaptic DA concentrations. The present study determined the dose-response for nicotine (0.1-0.8 mg/kg, s.c.) to modulate DA clearance in striatum and medial prefrontal cortex (mPFC) using in vivo voltammetry in urethane anesthetized rats and determined if this effect was mediated by nAChRs. Exogenous DA (200 microM) was pressure-ejected at 5-min intervals until reproducible baseline signals were obtained. Subsequently, nicotine or saline was administered, and DA pressure ejection continued at 5-min intervals for 60 min. In both striatum and mPFC, signal amplitude decreased by approximately 20% across the 60-min session in saline-injected rats. A monophasic dose-response curve was found in striatum, with a maximal 50% decrease in signal amplitude after 0.8 mg/kg. In contrast, a U-shaped dose-response curve was found in mPFC, with a maximal 50% decrease in signal amplitude after 0.4 mg/kg. Onset of nicotine response occurred 10 to 15 min after injection in both brain regions; however, the amount of time before maximal response was 45 and 30 min in striatum and mPFC, respectively. Mecamylamine (1.5 mg/kg) completely inhibited the nicotine-induced (0.8 and 0.4 mg/kg) decrease in signal amplitude in striatum and mPFC, respectively, indicating mediation by nAChRs. Thus, nicotine enhances DA clearance in striatum and mPFC in a mecamylamine-sensitive manner, indicating that nAChRs modulate DAT function in these brain regions.


LncRNAs in DNA damage response and repair in cancer cells.
In order to maintain integrity of the genome, eukaryotic cells develop a complex DNA damage/repair response network, which can induce cell cycle arrest, apoptosis, or DNA repair. Chemo- and radiation therapies, which act primarily through the induction of DNA damage, are the most commonly used therapies for cancer. Impairment in the DNA damage response and repair system that protect cells from persistent DNA damage can affect the therapeutic efficacy of cancer. To date, accumulating evidence has suggested that long non-coding RNAs (lncRNAs) are involved in the regulation of the DNA damage/repair network. LncRNAs have been demonstrated to be master regulators of the genome at the transcriptional and post-transcriptional levels and play a key role in many physiological and pathological processes of cells. In this review, we will discuss the function of lncRNAs in regulating the cellular response to DNA damage.


[Digital dynamic telethermography: an aid in the study of vascular reactivity to cold].
Vascular reactivity to cold has been studied on 22 patients by means of digital dynamic thermography. Using an interface the thermographic images are digitized in real time and stocked in the computer. After the cooling (two minutes in water at 10 degrees C) the warming-up is followed by sequential thermographic images. Profiles of thermic evolution are represented for 12 regions of interest (at the level of each finger and two for the back of the hands). Four types of thermic profiles are observed: Type 0: all fingers and back of hands have the same basal temperature. After cooling the warming-up is immediate, synchronic for all fingers and goes on more or less rapidly. Type I: at the basal state all fingers have identical temperature. After cooling, the warming-up starts after a latency period of several minutes, which is identical for all fingers. After it the warming-up is fast and synchronic with a thermic "overshot" phenomenon at the end of the examination. Only the thumbs are warmed-up without a latency period. Type II: a latency period similar that of type I is observed but the following warming-up takes place with variable speeds for each considered finger. Type III: at the basal state the fingers are colder than the back of the hand. Spontaneously, some fingers are warmed only by the influence of the hand vertical position. After cooling, the warming-up takes place with variable speeds and after variable latency periods which are a characteristic of each finger.(ABSTRACT TRUNCATED AT 250 WORDS)


Symposium on surgical techniques in small animal practice. Surgery of the esophagus.
There are many anastomotic techniques available that have been used successfully but no one technique guarantees 100 per cent success. Therefore the surgeon should be capable of altering his planned approach according to the circumstances. No matter what anastomotic technique is selected, for a consistently successful outcome it is imperative that the whole animal be considered in all aspects of care and rude handling of tissues be avoided during the surgical procedure. The simple interrupted approximating suture technique is recommend as one which meets the general goals of intestinal anastomosis in dogs and cats.


Diagnosis of chronic myelogenous leukemia in a dog using morphologic, cytochemical, and flow cytometric techniques.
Chronic myelogenous leukemia was diagnosed in a 3.5-year-old neutered male Golden Retriever. The diagnosis was based on persistent leukocytosis (>73.0X10(3)/microliter), composed of a proportionate left shift to progranulocytes with no evidence of underlying inflammation, infection, or neoplasia. Marked dysplasia was evident in neutrophils and platelets in peripheral blood. Bone marrow and splenic aspirates were dominated by mature and immature neutrophils with < 2% myeloblasts. Cytochemical and flow cytometric assays confirmed that cells in the peripheral blood and spleen were of committed neutrophil lineage. The dog responded initially to treatment with hydroxyurea, but developed acute undifferentiated leukemia approximately 83 days after initial presentation.


Metabolism of arachidonic acid by pancreatic acini: relation to amylase secretion.
Isolated guinea pig pancreatic acini were incubated with exogenous [14C]arachidonic acid (10 microM) at 37 degrees C for 3 min. The lipids were extracted and separated by thin-layer chromatography. Radiolabeled metabolites were identified by comigration with standards: 0.024% of the recovered radioactivity comigrated with prostaglandin E2 (PGE2), 0.016% comigrated with PGF2 alpha, 4.9% was incorporated into triglycerides, 1.8% was incorporated into phospholipids, and 93.2% remained as arachidonic acid. The synthesis of PGE2 and PGF2 alpha was inhibited by indomethacin (ID50, 30 nM). Simultaneous addition of carbachol or caerulein with the [14C]arachidonic acid did not alter the metabolism of the arachidonate. Further studies were done on the role of arachidonate metabolites in the secretion of amylase. Exogenously added PGE2 and PGF2 alpha (0.3-100 nM) did not induce amylase secretion from isolated acini. Incubation of isolated acini with indomethacin (0.1-28 microM) did not inhibit the release of amylase induced by carbachol or caerulein. From these data, we conclude that isolated guinea pig pancreatic acini are capable of converting a small percentage of exogenous arachidonate to PGE2 and PGF2 alpha. However, there is no evidence for a role of these compounds in stimulus-secretion coupling.


Longterm Prognosis of 121 Patients with Eosinophilic Granulomatosis with Polyangiitis in Japan.
We investigated the risk factors for relapse or prognosis of eosinophilic granulomatosis with polyangiitis (EGPA) in Japanese patients presenting to our hospital. From June 1999 through March 2015, we retrospectively recruited 121 patients with EGPA according to the American College of Rheumatology criteria. Frequent relapse was defined as disease occurrence at least once every 2 years after a period of initial remission. The study endpoint was the last examination performed. We used multiple logistic regression to analyze risk factors for relapse or survival in EGPA. Gastrointestinal (GI) involvement with both abnormalities on endoscopy and biopsy (p < 0.01) and symptoms; myocardial involvement with both abnormalities on 1 or more cardiac investigations and symptoms (p < 0.01); and treatment at initial or maintenance with immunosuppressants (p < 0.01) or administration of intravenous immunoglobulin (IVIG; p < 0.01) were associated significantly more often with frequent relapse than with infrequent. Overall 5-, 10-, and 20-year survival rates were 91.1%, 83.7%, and 68.6%, respectively. Survival in EGPA was associated with age of onset < 65 years. Age at onset of EGPA was the only significant predictor of survival (p < 0.01). Myocardial or GI tract involvement did not affect mortality risk. Patients with myocardial or GI tract involvement had frequent relapses, but these conditions were not reflected in increased mortality. Treatment with immunosuppressants or IVIG in addition to corticosteroids might have improved the prognosis in Japanese patients with EGPA.


Not all games are created equal: Adolescents who play and spend money on simulated gambling games show greater risk for gaming disorder.
Research reports positive associations between gaming disorder (GD) in adolescents and loot box purchasing but has not examined this relationship for other types of simulated gambling. This study examined whether greater engagement and expenditure in three types of simulated gambling were associated with meeting the criteria for GD in adolescents. A sample of Australians aged 12-17 years (N = 826) was recruited through an online panel aggregator. It included 646 gamers (57.7% male) with 89 being classified as having past-year GD, as defined and measured by the Internet Gaming Disorder Scale. Independent variables comprised past-month engagement in three simulated gambling activities (games with 'mini' gambling components, social casino games, and loot boxes), loot box purchasing, other microtransactions, impulsiveness, and demographics. Logistic regressions first examined whether engagement in each of the three simulated gambling activities was individually associated with GD, then with all three in the same model, and then controlling for demographic variables and impulsivity. Logistic regressions also examined whether microtransactions and purchasing loot boxes were individually associated with GD, then with both in the same model, and then controlling for demographic variables and impulsivity. Adolescents who had engaged in each simulated gambling activity in the past month were more likely to report meeting the criteria for GD. These relationships remained significant when controlling for common demographics and impulsiveness. Past-month engagement in social casino games increased the odds of GD 2.5 times (95% CI: 1.54; 4.02), 2.4 times for games with 'mini' gambling components (95% CI: 1.42; 3.90) and 2.0 times for engaging in loot boxes (95% CI: 1.22; 3.21), but only social casino games remained significant when controlling for engagement in all three activities. The likelihood of meeting the criteria for GD increased 3.8 times with expenditure on microtransactions (95% CI: 2.32; 6.27) and 4.6 times for buying loot boxes, and each remained significant when both were included in the model. Compared to digital games without simulated gambling elements, simulated gambling appears to attract adolescents who report GD. Implications of the results are discussed in detail.


Rapid classification of virgin and recycled EPS containers by Fourier transform infrared spectroscopy and chemometrics.
A rapid and sensitive method for classification of virgin and recycled expanded polystyrene (EPS) food containers was developed using Fourier transform infrared spectroscopy (FTIR) and chemometrics. This method includes preparing a transparent film by dissolution, examining by FTIR and developing classification models. The degradation of EPS containers occurring during the recycling process was reflected by the carbonyl region of the infrared spectrum which was used as variables for multivariate data analysis. PCA was used to reduce the data dimension and view the sample similarities. Soft independent modelling of class analogy (SIMCA), partial least squares-discrimination analysis (PLS-DA) and linear discrimination analysis (LDA) were applied to construct three classification models. The best discrimination results were obtained by an LDA model, with all samples correctly classified. PLS-DA and SIMCA could not classify the recycled EPS samples with low levels of adulteration. When applying this method to commercially available EPS containers, about 45% of samples were shown to contain recycled polystyrene resins. It is concluded that the carbonyl region of the infrared spectra coupled with chemometrics could be a powerful tool for the classification of virgin and recycled EPS food containers.


An Integrated Surgical Management for Giant Dermatofibrosarcoma Protuberans of Anterior Abdominal Wall.
Giant dermatofibrosarcoma protuberans (DFSP) is a very rare dermal sarcoma whose diagnosis and management are important because of the high local recurrence but low metastatic potential. Complete surgical excision of giant DFSP in a single stage is difficult but has a high cure rate. A 47-year-old man presented with a gradually increasing large (18 x 15 x 7 cm) DFSP in the epigastrium. A 3 cm circumferential wide local excision (WLE) with microscopic tumor-free margin confirmed by frozen section was performed. Immediate single staged tension-free primary closure of resultant defect was done on the principle of abdominal wall reconstruction (AWR) in ventral hernia repair. This technique of anterior component separation and bridge meshplasty is functional, avoids multiple surgeries, is cost-effective, and can be done in a resource-limited setting in developing countries. A multidisciplinary and integrated surgical approach to treat giant DFSP over epigastrium, by three-dimensional WLE and immediate AWR with anterior component separation technique (CST) and bridging meshplasty, can be of immense help in managing such rare cases in developing countries.


Hemodynamics of orthostatic intolerance: implications for gender differences.
Women have a greater incidence of orthostatic intolerance than men. We hypothesized that this difference is related to hemodynamic effects on regulation of cardiac filling rather than to reduced responsiveness of vascular resistance during orthostatic stress. We constructed Frank-Starling curves from pulmonary capillary wedge pressure (PCWP), stroke volume (SV), and stroke index (SI) during lower body negative pressure (LBNP) and saline infusion in 10 healthy young women and 13 men. Orthostatic tolerance was determined by progressive LBNP to presyncope. LBNP tolerance was significantly lower in women than in men (626.8 +/- 55.0 vs. 927.7 +/- 53.0 mmHg x min, P < 0.01). Women had steeper maximal slopes of Starling curves than men whether expressed as SV (12.5 +/- 2.0 vs. 7.1 +/- 1.5 ml/mmHg, P < 0.05) or normalized as SI (6.31 +/- 0.8 vs. 4.29 +/- 0.6 ml.m-2.mmHg-1, P < 0.05). During progressive LBNP, PCWP dropped quickly at low levels, and reached a plateau at high levels of LBNP near presyncope in all subjects. SV was 35% and SI was 29% lower in women at presyncope (both P < 0.05). Coincident with the smaller SV, women had higher heart rates but similar mean arterial pressures compared with men at presyncope. Vascular resistance and plasma norepinephrine concentration were similar between genders. We conclude that lower orthostatic tolerance in women is associated with decreased cardiac filling rather than reduced responsiveness of vascular resistance during orthostatic challenges. Thus cardiac mechanics and Frank-Starling relationship may be important mechanisms underlying the gender difference in orthostatic tolerance.


Acute lung injury/acute respiratory distress syndrome (ALI/ARDS): the mechanism, present strategies and future perspectives of therapies.
Acute lung injury/acute respiratory distress syndrome (ALI/ARDS), which manifests as non-cardiogenic pulmonary edema, respiratory distress and hypoxemia, could be resulted from various processes that directly or indirectly injure the lung. Extensive investigations in experimental models and humans with ALI/ARDS have revealed many molecular mechanisms that offer therapeutic opportunities for cell or gene therapy. Herein the present strategies and future perspectives of the treatment for ALI/ARDS, include the ventilatory, pharmacological, as well as cell therapies.


Ultrasound Imaging for Traumatic Brain Injury.
Traumatic brain injury (TBI) is challenging to assess even with recent advancements in computed tomography and magnetic resonance imaging. Ultrasound (US) imaging has previously been less utilized in TBI compared to conventional imaging because of limited resolution in the intracranial space. However, there have been substantial improvements in contrast-enhanced US and development of novel techniques such as intravascular US. Also, continued research provides further insight into cerebrovascular parameters from transcranial Doppler imaging. These advancements in US imaging provides the community of TBI imaging researchers and clinicians new opportunities in clinically monitoring and understanding the pathologic mechanisms of TBI.


Aberrant Feeding and Growth in Neonates With Prenatal Opioid Exposure: Evidence of Neuromodulation and Behavioral Changes.
Opioid use disorder (OUD) among pregnant women over the last decade has led to more than a fivefold increase in the number of neonates born with withdrawal signs known as Neonatal Abstinence Syndrome (NAS) or Neonatal Opioid Withdrawal Syndrome (NOWS). The impact of prenatal opioid exposure on these neonates remains a public health and research priority due to both its short and long-term effects on offspring. Among the adverse long-term effects associated with OUD is a metabolic syndrome with accompanying cardiovascular comorbidities. The susceptibility to metabolic diseases may begin as early as conception. Neonates born in a setting of prenatal opioid exposure are known to have aberrant early growth, e.g., lower birth weight and smaller head size, and dysregulated feeding behavior that ranges from feeding difficulty to hyperphagia which may predispose these neonates to metabolic syndrome in adulthood. However, studies on this topic are lacking. In this article, we describe the reported association between OUD and metabolic syndrome in adults, animal data linking opioid receptors with the development of diet-induced obesity, the inflammatory modulation of opioids and finally, neonatal salivary transcriptomic data from our laboratory that highlighted the sex-specific impact of opioids on the hypothalamic and reward receptors that regulate feeding behavior in opioid-exposed neonates. There is a great need for future research linking opioids with epigenetic and gene expression changes, as well as neuromodulatory effects in the developing brain, that may underlie the dysregulated feeding, growth, and long-term metabolic and cardiovascular risks for these neonates.


Hybrid reconstruction of the upper limb in a patient with chronic limb ischemia.
Hybrid vascular interventions performed in patients with chronic limb ischemia are considered minimally invasive techniques for treating complex multilevel arterial occlusive disease. We report the case of a 42-year-old woman with a critical upper limb ischemia, who underwent angioplasty and secondary stenting of the distal-third of the axillary artery followed by a brachial-brachial bypass using an autologous graft. The patient had an uneventful recovery. To our knowledge, this is the first case reported in the literature of hybrid vascular reconstruction in the upper limb due to atherosclerosis. Hybrid revascularization procedure in the upper limb is technically feasible, safe for the patient, and should become a part of the armamentarium of the modern vascular surgeon.


Oxide thin films based on ordered arrays of 1D nanostructure. A possible approach toward bridging material gap in catalysis.
TiO(2) thin films based on ordered arrays of 1D nanostructures (nanorods, nanotubes) are proposed as suitable model materials in studies for bridging material and complexity gap in catalysis. The samples were prepared by anodic oxidation of Ti foils. By changing the preparation conditions (pH, procedure of application of the potential), different types of 1D nanostructure and different characteristics of the ordered array of these 1D nanostructures could be obtained. This allows studying the effect of nanodimension and 3D nanoarchitecture on the characteristics and reactivity of these catalysts. It is also shown that TiO(2) thin films characterized by a well-ordered array of titania nanorod behave as photonic materials, thus showing unique properties of light harvesting efficiency.


Haploid Genome Analysis Reveals a Tandem Cluster of Four HSP20 Genes Involved in the High-Temperature Adaptation of Coriolopsis trogii.
Coriolopsis trogii is a typical thermotolerant basidiomycete fungus, but its thermotolerance mechanisms are currently unknown. In this study, two monokaryons of C. trogii strain Ct001 were assembled: Ct001_29 had a genome assembly size of 38.85 Mb and encoded 13,113 genes, while Ct001_31 was 40.19 Mb in length and encoded 13,309 genes. Comparative intra- and interstrain genomic analysis revealed the rich genetic diversity of C. trogii, which included more than 315,194 single-nucleotide polymorphisms (SNPs), 30,387 insertion/deletions (indels), and 1,460 structural variations. Gene family analysis showed that the expanded families of C. trogii were functionally enriched in lignocellulose degradation activities. Furthermore, a total of 14 allelic pairs of heat shock protein 20 (HSP20) genes were identified in the C. trogii genome. The expression profile obtained from RNA sequencing (RNA-Seq) showed that four tandem-duplicated allelic pairs, HSP20.5 to HSP20.8, had more than 5-fold higher expression at 35°C than at 25°C. In particular, HSP20.5 and HSP20.8 were the most highly expressed HSP20 genes. Allelic expression bias was found for HSP20.5 and HSP20.8; the expression of Ct29HSP20.8 was at least 1.34-fold higher than that of Ct31HSP20.8, and that of Ct31HSP20.5 was at least 1.5-fold higher than that of Ct29HSP20.5. The unique structural and expression profiles of the HSP20 genes revealed by these haplotype-resolved genomes provide insight into the molecular mechanisms of high-temperature adaptation in C. trogii. IMPORTANCE Heat stress is one of the most frequently encountered environmental stresses for most mushroom-forming fungi. Currently available fungal genomes are mostly haploid because high heterozygosity hinders diploid genome assembly. Here, two haplotype genomes of C. trogii, a thermotolerant basidiomycete, were assembled separately. A conserved tandem cluster of four HSP20 genes showing allele-specific expression was found to be closely related to high-temperature adaptation in C. trogii. The obtained haploid genomes and their comparison offer a more thorough understanding of the genetic background of C. trogii. In addition, the responses of HSP20 genes at 35°C, which may contribute to the growth and survival of C. trogii at high temperatures, could inform the selection and breeding of elite strains in the future.


Lactic dehydrogenase isoenzymes in normal and pathological spinal fluids.
Spinal fluid lactate dehydrogenase (L.D.H.) isoenzyme patterns have been investigated in normal subjects, in those with non-destructive nervous disease, and in those with destructive lesions in the nervous system.The spinal fluid from organic disease in general showed a significantly increased level of L.D.H.(2) and L.D.H.(3) so that the combined values of L.D.H.(2) and L.D.H.(3) might perhaps be of value in determining the presence of destructive nervous lesions.


Injectable Click-Crosslinked Hyaluronic Acid Depot To Prolong Therapeutic Activity in Articular Joints Affected by Rheumatoid Arthritis.
The aim of this study was to design a click-crosslinked hyaluronic acid (HA) (Cx-HA) depot via a click crosslinking reaction between tetrazine-modified HA and trans-cyclooctene-modified HA for direct intra-articular injection into joints affected by rheumatoid arthritis (RA). The Cx-HA depot had significantly more hydrogel-like features and a longer in vivo residence time than the HA depot. Methotrexate (MTX)-loaded Cx-HA (MTX-Cx-HA)-easily prepared as an injectable formulation-quickly formed an MTX-Cx-HA depot that persisted at the injection site for an extended period. In vivo MTX biodistribution in MTX-Cx-HA depots showed that a high concentration of MTX persisted at the intra-articular injection site for an extended period, with little distribution of MTX to normal tissues. In contrast, direct intra-articular injection of MTX alone or MTX-HA resulted in rapid clearance from the injection site. After intra-articular injection of MTX-Cx-HA into rats with RA, we noted the most significant RA reversal, measured by an articular index score, increased cartilage thickness, extensive generation of chondrocytes and glycosaminoglycan deposits, extensive new bone formation in the RA region, and suppression of tumor necrosis factor-α or interleukin-6 expression. Therefore, MTX-Cx-HA injected intra-articularly persists at the joint site in therapeutic MTX concentrations for an extended period, thus increasing the duration of RA treatment, resulting in an improved relief of RA.


Effect of streptozotocin diabetes on the hypothalamic-pituitary-thyroid axis in the rat.
Studies of the hypothalamic-pituitary-thyroid axis have been performed in streptozotocin (STZ)-diabetic Wistar rats and their controls. Plasma PBI concentration, plasma and pituitary TSH, contents, and hypothalamic TRH content were measured by RIA in basal and stimulated conditions. Compared to controls, rats made diabetic by 6.0 or 7.5 mg STZ/100 g BW showed decreased plasma PBI and TSH and diminished pituitary TSH content, with greater alterations in rats receiving the highest STZ dose. Both diabetic groups showed an almost 50% reduction of hypothalamic TRH content in comparison with the mean control value. After thyroidectomy, pituitary TSH secretion increased in diabetic, ad libitum fed, and semistarved animals, but it was lower in the diabetic group in which the reduction in plasma PBI was similar or greater. To evaluate pituitary sensitivity to the inhibitory action of L-T4 on TSH secretion in diabetes, thyroidectomized control (Thx-C), thyroidectomized diabetic (Thx-D), and thyroidectomized semistarved (Thx-S) rats were injected twice daily for 7 days with either saline or a fractional L-T4 dose of 0.25, 0.50, or 1.00 microgram/100 microgram/100 g BW. In Thx-D rats, a daily dose of 1.00 microgram L-T4 was sufficient to normalize pituitary TSH secretion, while a dose of 2.00 microgram was required to induce a similar effect in the Thx-C and Thx-S animals. Pituitary TSH content was increased in the Thx-C group with increasing T4 doses. No modification in this parameter was seen in the Thx-D and Thx-S animals. The fact that diabetes caused a reduction in the hypothalamic TRH content indicates that the primary cause of pituitary-thyroid alterations in STZ-diabetic rats lies in the hypothalamus, although the metabolic imbalance induced by diabetes and, in less degree, by undernutrition could also be partly responsible for some of the described modifications.


The outcome of reoperative pulmonary endarterectomy surgery.
Pulmonary endarterectomy (PEA) is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension (PH). Despite excellent outcomes following PEA, a small proportion of patients have residual proximal disease or present with recurrent chronic thromboembolic PH and may benefit from further surgery. The aim of this study was to analyse outcomes following reoperative PEA at a high-volume national tertiary referral centre for the management of chronic thromboembolic PH. This retrospective analysis was performed using our prospectively maintained PH database to identify all patients who underwent reoperative PEA surgery between the commencement of the programme in 1997 and January 2017, and the patients' data were collected for analysis. Twelve patients underwent reoperative PEA during the period of study. The mean interval between primary procedure and reoperative procedure was 6.3 years. Significant improvements were observed in pulmonary haemodynamics following reoperative PEA. Mean pulmonary arterial pressure decreased from 46.8 to 29.8 mmHg (P < 0.0001) and pulmonary vascular resistance decreased from 662 to 362 dyne·s·cm-5 (P = 0.0007). A significant functional improvement in the 6-min walking test distance was also observed, increasing from 327 to 460 m at 6 months postoperatively (P = 0.0018). Median length of hospital stay was 12 days. In-hospital mortality was 8.3% with 1-year survival of 83.3%. Reoperative PEA is technically possible and relatively safe, achieving good functional and physiological outcomes. Patients must be carefully selected by a multidisciplinary team, and surgery should be performed in experienced centres.


eHealth in Geriatric Rehabilitation: An International Survey of the Experiences and Needs of Healthcare Professionals.
While eHealth can help improve outcomes for older patients receiving geriatric rehabilitation, the implementation and integration of eHealth is often complex and time-consuming. To use eHealth effectively in geriatric rehabilitation, it is essential to understand the experiences and needs of healthcare professionals. In this international multicentre cross-sectional study, we used a web-based survey to explore the use, benefits, feasibility and usability of eHealth in geriatric rehabilitation settings, together with the needs of working healthcare professionals. Descriptive statistics were used to summarize quantitative findings. The survey was completed by 513 healthcare professionals from 16 countries. Over half had experience with eHealth, although very few (52 of 263 = 20%) integrated eHealth into daily practice. Important barriers to the use or implementation of eHealth included insufficient resources, lack of an organization-wide implementation strategy and lack of knowledge. Professionals felt that eHealth is more complex for patients than for themselves, and also expressed a need for reliable information concerning available eHealth interventions and their applications. While eHealth has clear benefits, important barriers hinder successful implementation and integration into healthcare. Tailored implementation strategies and reliable information on effective eHealth applications are needed to overcome these barriers.


Stepwise requirement of c-kit tyrosine kinase in mouse ovarian follicle development.
Ovarian follicle development is controlled by the cycling variation of gonadotrophins derived from the central nervous system. Intragonadal signals are also required, especially in the autonomous development of small follicles. Receptor tyrosine kinase c-kit and its ligand SLF (Steel factor) are expressed on the surface of specific populations of follicle-forming cells in a contiguous manner and are thought to have important roles in follicular development. We blocked the interaction of c-kit and its ligand by administering the function-blocking antibody ACK2 to developing mice at various times after birth and monitored ovarian follicle development. A blockade of c-kit function disturbed the onset of primordial follicle development, primary follicle growth, follicular fluid formation of preantral follicles, and penultimate-stage ovarian follicle maturation before ovulation. Ovarian follicle growth was dependent on c-kit during the first 5 days after birth when the functional FSH receptor is not yet expressed in mouse ovary. In contrast, primordial follicle formation and survival, small preantral or antral follicle development, ovulation, and luteinization of the ovulated follicle were not affected by this antibody. These findings indicate the stepwise requirement of c-kit and its ligand interaction system in the developing ovarian follicle and that c-kit with its ligand supports the autonomous development of ovarian follicle independent of gonadotrophins.


[Chlamydia trachomatis infection in sexually active teenagers].
The prevalence of Chlamydia trachomatis infections among Polish teenagers remains unknown. Sexually active teenagers are exposed at sexually transmitted infections, including Chlamydia trachomatis (CT). Most infections are asymptomatic and, therefore, untreated. Early detection and treatment of cervical chlamydial infections may prevent pelvic inflammatory diseases and prevent later infertility. to determine the prevalance and risk factors of Chlamydia trachomatis infections among sexually active female teenager. 243 sexually active girls, 16-19 year-olds, attending the outpatient clinic were enrolled in this study between 2005-2007. The participants filled in a questionnaire containing such information as age, purpose of visit, level of education, age at the first intercourse, number of sexual partners, number of current partners (in the past 3 months), contraceptive methods, use of condoms, past history of STD and obstetric history at the first visit. Pelvic examination was performed to check the following: vaginal discharge, presence of abnormalites of the cervix (ectopy, erythema, tenderness of uterine and adnexal) and to take a Pap smear and a cervical swab for Chlamydia trachomatis. Cervical swabs for Chlamydia trachomatis were tested by polymerase chain reaction (PCR). The prevalence of CT genital infection in the studied group was 2,9%. Adolescent females infected by CT less frequently admitted to the use of condom and more often did not use any contraception at all, in comparison with the girls without CT genital infections (29% and 57% vs. 37% and 19%). There were statistically significant differences in the results of the abnormal Pap smears (ASCUS, LGSIL) between the two groups.


Triclabendazole: new skills to unravel an old(ish) enigma.
Triclabendazole was introduced in the early 1980s for the treatment of Fasciola hepatica infections in livestock. Due to its high activity against immature flukes, it has become established as the principal anti-fluke drug on the market. More recently, triclabendazole has been used to treat human cases of fascioliasis and is now the drug of choice for this infection, too. Resistance to triclabendazole was first reported in 1995 in a field population in Australia and, since that time, resistant populations have been identified in several countries in Europe. Parallel to the spread of resistance has been a sharp increase in the prevalence of fascioliasis, which has been attributed largely to climate changes. Consequently, farmers are faced with an alarming scenario, as none of the other fasciolicides on the market possess such high activity against the damaging immature stages of fluke. The main aim of this review is to assess current understanding of the mechanism of action of triclabendazole against the fluke and the mechanism by which the fluke has become resistant to it. The use of triclabendazole against animal and human infections is summarized and suggestions are given on ways to deal with resistance. Gaps in the knowledge of various aspects of its use are highlighted and this may serve to open up future research areas.


Observations in immunotherapy of lymphoma and melanoma patients.
Maintenance of remission solely by repeated BCG vaccinations in seven patients with non-Hodgkin's lymphoma who had achieved a complete clinical remission with initial standard therapy has provided sufficient encouragement to begin a randomized clinical trial. In vitro lymphocyte responses to mitogens and PPD used as parameters of cell-mediated immunity have not proved to be of value in predicting early or late recurrence in six pre-trial and trial patients. Eight out of twenty-one patients with malignant melanoma have shown a satisfactory clinical response (10-34 months) to immunotherapy. Those who respond must show immunological reactivity to the stimulating agent, however the best clinical responses were not associated with the highest degrees of in vivo and in vitro sensitization. The skin reactivity and the in vitro lymphocyte response to PPD as well as a 2-3-fold increase in the appearance of colony-forming units in the peripheral blood following the intratumour injection of BCG or PPD are helpful in prognosis and management of these patients. All patients with malignant melanoma who presented with a PHA response less than 40% of normal made a poor response to immunotherapy. Autopsies performed on seven patients dying with extensive melanocarcinomatous disease failed to show any serious adverse toxic reactions or infections from oral and intratumour injections of BCG.


A Rare Case of Monogenic Obesity due to a Novel Variant in the ADCY3 Gene: Challenges in Follow-up and Treatment.
Adenylate cyclase 3 (ADCY3) gene alterations have been found to be associated with obesity. However, few patients with homozygous mutations have been reported so far, and the follow-up procedure and treatment options have not been clarified. A 10-month-old female presented with increased appetite and weight gain. She was born from a consanguineous marriage. Weight, height, head circumference measurements and standard deviation scores (SDS) were 19 kg (+6.98 SDS), 82 cm (+3.53 SDS), and 49 cm (+3.07 SDS), respectively. Laboratory tests revealed a fasting glucose level of 103 mg/dL (5.7 mmol/L), insulin level of 25.39 µIU/mL, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) value of 6.43. Whole-exome sequencing revealed a novel, homozygous c.1102G>A(p.Asp368Asn) variant in ADCY3. Her parents and healthy sister were heterozygous for the variant. At the age of 2.5 years, neurodevelopmental delay was observed. At the age of 3.5 years, the patient's weight, height, and body mass index values were 49.5 kg (+8.16 SDS), 111 cm (+2.59 SDS), and 40.18 kg/m2 (+6.48 SDS), respectively. Signs of Blount's disease and acanthosis nigricans were distinctive, and she had hyperphagia. She was undergoing speech therapy. Homozygous ADCY3 variants may present with early onset, severe obesity, insulin resistance, and neurodevelopmental delay in children. Severe complications may occur even at young ages. More data regarding the follow-up process and treatment of these patients are needed.


Scrambling free combinatorial labeling of alanine-β, isoleucine-δ1, leucine-proS and valine-proS methyl groups for the detection of long range NOEs.
Specific isotopic labeling of methyl groups in proteins has greatly extended the applicability of solution NMR spectroscopy. Simultaneous labeling of the methyl groups of several different amino acid types can offer a larger number of useful probes that can be used for structural characterisations of challenging proteins. Herein, we propose an improved AILV methyl-labeling protocol in which L and V are stereo-specifically labeled. We show that 2-ketobutyrate cannot be combined with Ala and 2-acetolactate (for the stereo-specific labeling of L and V) as this results in co-incorporation incompatibility and isotopic scrambling. Thus, we developed a robust and cost-effective enzymatic synthesis of the isoleucine precursor, 2-hydroxy-2-(1'-[(2)H2], 2'-[(13)C])ethyl-3-keto-4-[(2)H3]butanoic acid, as well as an incorporation protocol that eliminates metabolic leakage. We show that application of this labeling scheme to a large 82 kDa protein permits the detection of long-range (1)H-(1)H NOE cross-peaks between methyl probes separated by up to 10 Å.


Toxicity profiling of flame retardants in zebrafish embryos using a battery of assays for developmental toxicity, neurotoxicity, cardiotoxicity and hepatotoxicity toward human relevance.
Following the voluntary phase-out of brominated flame retardants (BFRs) due to their environmental persistence and toxicity, the organophosphorus flame retardants (OPFRs) are emerging replacements. However, there is limited information on the potential human health effects of the OPFRs. Zebrafish embryos are a viable vertebrate model organism with many advantages for high throughput testing toward human hazard assessment. We utilized zebrafish embryos to assess developmental toxicity, neurotoxicity, cardiotoxicity and hepatotoxicity, of eight replacement OPFRs: (triphenyl phosphate [TPHP], isopropylated phenyl phosphate [IPP], 2-ethylhexyl diphenyl phosphate [EHDP], tert-butylated phenyl diphenyl phosphate [BPDP], trimethyl phenyl phosphate [TMPP], isodecyl diphenyl phosphate [IDDP], tris(1,3-dichloroisopropyl) phosphate [TDCIPP], and tris(2-chloroethyl) phosphate [TCEP]) and two BFRs (3,3',5,5'- tetrabromobisphenol A [TBBPA] and 2,2'4,4'-brominated diphenyl ether [BDE-47]). To determine potential effects on teratogenicity, embryos were exposed to flame retardants (FRs) at 4 h post fertilization (hpf) to 4 days post fertilization (dpf) and morphological alterations and corresponding survival were evaluated at 2 and 4 dpf. Internal concentrations were measured in larvae used in this assay by liquid chromatography-mass spectrometry. Locomotor activity was assessed in larvae treated for 48 h (from 3 dpf to 5 dpf), followed by hepatotoxicity evaluation. Finally, alterations in heart rate and rhythmicity were assessed to determine cardiotoxicity in 48 hpf embryos exposed to compounds for 3 h. Results suggest that several OPFRs (BPDP, EHDP; IPP, TMPP; TPHP and TDCIPP) produced adverse effects in multiple target organs at concentrations comparable to the two BFRs. As these OPFRs have the capacity to disrupt an integrated vertebrate model, they potentially have the capacity to affect mammalian biology. Then, we compared the lowest effective levels (LEL) in zebrafish with estimated or measured human plasma concentrations using biomonitoring data (human plasma, breast milk, handwipe samples and house dust) and a high throughput toxicokinetic (HTTK) model. Results indicate that for some compounds, the nominal LELs were within the range of human exposures, while internal LELs in zebrafish are above internal exposures in humans. These findings demonstrate the value of the zebrafish model as a relevant screening tool and support the need for further hazard characterization of the OPFRs.


Induction of Apoptosis by Berberine in Hepatocellular Carcinoma HepG2 Cells via Downregulation of NF-κB.
Hepatocellular carcinoma (HCC) is highly resistant to traditional chemotherapeutic approaches, which causes difficulty in the development of effective drugs for the treatment of HCC. Berberine, a major ingredient of Rhizoma coptidis, is a natural alkaloid used in traditional Chinese medicine. Berberine exhibits potent antitumor activity against HCC due to its high efficiency and low toxicity. In the present study, we found that berberine sensitized HepG cells to NF-κB-mediated apoptosis. Berberine exhibited a significant antiproliferation effect on the HepG2 cells and promoted apoptosis. Both qRT-PCR and immunofluorescence staining revealed that berberine reduced the NF-κB p65 levels in HepG2 cells. Moreover, p65 overexpression rescued berberine-induced cell proliferation and prevented HepG2 cells from undergoing apoptosis. These results suggest that berberine inhibits the growth of HepG2 cells by promoting apoptosis through the NF-κB p65 pathway.


Contribution of excision repair cross-complementing group 1 genotypes to triple negative breast cancer risk.
Compared with other subgroups of breast cancer, triple negative breast cancer (TNBC) is considered to be the one with the greatest invasiveness and metastatic mobility, and the highest recurrence rate. Considering the lack of predictive markers for TNBC, we aimed to examine the contribution of excision repair cross complementing-group 1 (ERCC1) genotypes to TNBC. The rs11615 and rs3212986 of ERCC1 were investigated and evaluated for their associations with susceptibility to breast cancer, especially TNBC, in Taiwan. In this study, 1,232 breast cancer patients (104 were TNBC) and 1,232 healthy controls were recruited and their genotypes at ERCC1 rs11615 and rs3212986 were revealed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Our results indicated that genotypes of ERCC1 rs11615 (Ptrend = 2.2*10E-9), but not rs3212986 (Ptrend = 0.6181), were associated with breast cancer risk. In the allelic frequency distribution analysis, breast cancer patients carried the T allele of ERCC1 rs11615 a higher rate than the control subjects, further supporting the idea that ERCC1 rs11615 TT genotype is positively associated with breast cancer susceptibility. More importantly, the frequency of the ERCC1 rs11615 TT genotype was even higher among TNBC patients than among other subtypes of breast cancer patients (P = 0.0001, odds ratio = 1.73, 95% confidence interval = 1.15-2.63). The genotypes of ERCC1 rs11615 were not associated with Ki67 status. Our findings firstly show that the T allele of ERCC1 rs11615 can serve as a predictive biomarker for breast cancer and TNBC. We believe that ERCC1 could serve as a target for personalized treatment of breast cancer, especially for TNBC.


Evaluation of compatibility and stability of filtered 99mTc-sulfur colloid when combined with fluorescent indocyanine green dye.
It is a common practice to administer dyes and radiopharmaceuticals separately for the localization of sentinel nodes in patients with biliary tract malignancies. The objective of this study was to evaluate the chemical properties and particle size of filtered (99m)Tc-sulfur colloid before and after it is combined with indocyanine green for injection. This study also evaluated the compatibility and stability of the two when combined, for the possibility of a single injection. (99m)Tc-sulfur colloid was prepared according to the package insert, and the final preparation was passed through a sterile 0.2-μm filter. Green dye was also prepared as per the package insert. In a sterile syringe, 0.25 mL of 14.8-MBq (400-μCi) filtered (99m)Tc-sulfur colloid was mixed with 0.25 mL of 1.25-mg green dye in a 1:1 proportion for a total volume of 0.50 mL. The radiochemical purity and pH of filtered (99m)Tc-sulfur colloid were obtained immediately and at 1 and 2 h after preparation. Particle size was analyzed using an electron microscope immediately and at 2 h. The average radiochemical purity was 97.6% ± 2.0% (n = 51). The average pH was 5.56 ± 0.26 (n = 51). Evaluation of the particle size of filtered (99m)Tc-sulfur colloid with the green dye was determined by electron microscopy to be an average of 53 ± 30 nm (n = 365) at 0 h and 60 ± 35 nm (n = 303) at 2 h. This was compared with filtered (99m)Tc-sulfur colloid without the green dye, which averaged 71 ± 41 nm (n = 41). Measurements of unfiltered (99m)Tc-sulfur colloid were recorded at 253 ± 192 nm (n = 21) for additional comparisons. The chemical properties and particle size of filtered (99m)Tc-sulfur colloid were not affected by the addition of the green dye; thus, combination of filtered (99m)Tc-sulfur colloid and green dye in the same syringe for administration is suitable.


DBSI: DNA-binding site identifier.
In this study, we present the DNA-Binding Site Identifier (DBSI), a new structure-based method for predicting protein interaction sites for DNA binding. DBSI was trained and validated on a data set of 263 proteins (TRAIN-263), tested on an independent set of protein-DNA complexes (TEST-206) and data sets of 29 unbound (APO-29) and 30 bound (HOLO-30) protein structures distinct from the training data. We computed 480 candidate features for identifying protein residues that bind DNA, including new features that capture the electrostatic microenvironment within shells near the protein surface. Our iterative feature selection process identified features important in other models, as well as features unique to the DBSI model, such as a banded electrostatic feature with spatial separation comparable with the canonical width of the DNA minor groove. Validations and comparisons with established methods using a range of performance metrics clearly demonstrate the predictive advantage of DBSI, and its comparable performance on unbound (APO-29) and bound (HOLO-30) conformations demonstrates robustness to binding-induced protein conformational changes. Finally, we offer our feature data table to others for integration into their own models or for testing improved feature selection and model training strategies based on DBSI.


[Injuries from violence in young children--signs, management and diagnostics].
Inflicted injuries in infants and toddlers may easily be missed unless clinicians who care for children are alert to sometimes subtle clues in the history and physical exam. Any injury which is unexplained or incompatible with the developmental capabilities of the child or inconsistent with the given history should prompt a medical evaluation for suspected physical abuse. The most common cause of serious head injuries in infants younger than 12 months is child abuse. Shaking and blunt head trauma can result in injuries such as subdural hemorrhage, diffuse retinal hemorrhage, and brain and spine injury. Early detection of child physical abuse requires a systematic and careful diagnostic approach. The physician must be able to recognize suspicious injuries, as well as possess an understanding of the mimics that may be confused with inflicted injuries. Health care professionals are mandated by Swedish law to promptly report suspected abuse to child protective services.


Postnatal development of myogenic contractile activity and excitatory innervation of rat urinary bladder.
Bladder strips from newborn compared with adult rats exhibited marked differences in both myogenic properties and postganglionic excitatory innervation. In the first 2-wk of life myogenic contractile activity progressively changed from a quiescent state (at birth) to the asynchronous contractile activity typical of bladder strips from adult animals. After birth activation of muscarinic cholinoceptors changed the myogenic contractile activity in a manner similar to that observed at later stages of development. Neurogenic contractions of bladders from newborn animals were atropine sensitive in the whole range of frequencies studied. During the first 2 wk the atropine-resistant component of these contractions increased progressively to reach an adult-like condition, i.e., atropine-resistant contractions account for over 90% and approximately 60% of contractions elicited at 0.1 and 1-20 Hz, respectively.


Esterification reactions of lipase in reverse micelles.
The activities of lipase from Candida cylindracea and Rhizopus delemar have been investigated in water/AOT/iso-octane reverse micellar media through the use of two esterification reactions: fatty acid-alcohol esterification and glyceride synthesis. Such media promotes the occurrence of these two lipase-catalyzed reactions due to its low water content. The effect of various parameters on the activity of lipase from C. cylindracea in reverse micelles was determined and compared to results where alternate media were employed. It was observed that the structure of the media, as dictated by the type and concentration of the substrates and products and by the water/AOT ratio, w(0), had a strong impact on enzyme activity. Strong deactivation of both typase types occurred in reverse micelles, especially in the absence of substrates and for w(0) values greater than 3.0. Glyceride synthesis was realized with lipase from R. delemar, but not with that from C. cylindracea; the temperature and concentration of substrates and water strongly dictated the reaction rate and the percent conversion.


Efficient H2O2 electrogeneration at graphite felt modified via electrode polarity reversal: Utilization for organic pollutants degradation.
Electrochemical synthesis of H2O2 offers a great potential for water treatment. However, a significant challenge is the development of efficient cathode materials for the process. Herein, we implement a practical electrochemical cathode modification to support efficient H2O2 electrogeneration via the reduction of dissolved anodic O2. Graphite felt (GF) is in situ anodically modified by electrode polarity reversal technique in an acid-free, low-conductivity electrolyte. The modified GF exhibits a significantly higher activity towards O2 reduction. Up to 183.3% higher H2O2 yield is obtained by the anodized GF due to the increased concentrations of oxygen-containing groups and the hydrophilicity of the surface, which facilitates electron and mass transfer between GF and the electrolyte. Another significant finding is the ability to produce H2O2 at a high yield under neutral pH and low current intensity by the modified GF (35% of the charge need to produce the same amount by unmodified GF). Long-term stability testing of the modified GF showed a decay in the electrode's activity for H2O2 production after 30 consecutive applications. However, the electrode regained its optimal activity for H2O2 production after a secondary modification by electrode polarity reversal. Finally, in situ electrochemically modified GF is more effective for removal of reactive blue 19 (RB19, 20 mg/L) and ibuprofen (IBP, 10 mg/L) by the electro-Fenton process. The modified GF removed 62.7% of RB19 compared to only 28.1% by the unmodified GF in batch reactors after 50 min. Similarly, 75.3% IBP is removed by the modified GF compared to 57.6% by the unmodified GF in a flow-through reactor after 100 min.


[Clinical application of mesenchymal stem cells for hematological diseases].
Mesenchymal stem cells (MSCs) perform multiple functions, such as immunomodulation and tissue repair, and they are also capable of differentiation into bone, cartilage, and fat cells. Furthermore, an MSC culture method has been established, and clinical safety is guaranteed; therefore, MSCs can be clinically applied for the treatment of many diseases. MSC treatment for hematological diseases is expected to be effective against refractory acute graft-versus-host disease (GVHD). It is presently used for treating chronic GVHD, preventing GVHD, promoting the engraftment of hematopoietic stem cells, and treating refractory aplastic anemia. However, owing to the cellular properties of MSCs, there are some concerns including increases in relapse, the deterioration of infectious diseases, and tumor formation or malignant transformation of MSCs. In the present review, I describe the present situation, problems, and prospects of the clinical application of MSCs for treating hematological diseases, including recent topics such as placental-derived decidual stromal cells and highly purified MSCs.


Histone deacetylase inhibitors, N-butyric acid and trichostatin A, induce caspase-8- but not caspase-9-dependent apoptosis in human malignant glioma cells.
Histone deacetylase (HDAC) inhibitors have both apoptotic and differentiating effects on various tumor cells. However, the mechanisms underlying the effect of HDAC inhibitors remain unclear. In this study, we investigated the function of anti-proliferative effects of HDAC inhibitors, N-butyric acid and trichostatin A, on human malignant glioma cell lines, U251-MG and D54. MTT assay showed a dose-dependent inhibition of cellular proliferation in both cell lines. Cell cycle analysis revealed increased sub-G1 population in both lines, and G1 arrest only in U251-MG cells. Induction of apoptosis was also supported by the occurrence of DNA fragmentation in tumor cells treated with HDAC inhibitors. Furthermore, caspase inhibition assay indicated that HDAC inhibitor-induced apoptosis was caspase-dependent. Neither mitochondrial membrane potential nor the expression of caspase-9 was changed by treatment with HDAC inhibitors, suggesting the possibility that HDAC inhibitor-induced apoptosis was not mediated by the mitochondrial cell death pathway. On the other hand, immunoblot assay confirmed increased expression of caspase-8 in both lines, and elevation of p21 but not p27 protein in U251-MG cells following HDAC inhibitor treatment. Taken together, the HDAC inhibitors, N-butyric acid and trichostatin A, induce caspase-8- but not caspase-9-dependent apoptosis with or without p21-mediated G1 arrest in human malignant glioma cells.


The values you endorse set the body you see: The protective effect of intrinsic life goals on men's body dissatisfaction.
The mass media portrayal of a muscular body type ideal has been increasingly tied to men's body image dissatisfaction. We examined the role of self-determination theory's intrinsic life goals within this body image ideal and its potential as a moderator of this dissatisfaction. We first tested the moderating effect of intrinsic life goals on the link between magazine consumption and body image dissatisfaction via an online questionnaire (Study 1; N = 826), then experimentally manipulated these goals and exposure to images of muscular male models (Study 2; N = 150). A robust protective effect of intrinsic goals on body image satisfaction was observed - the relationship between magazine consumption and body image dissatisfaction was only significant among individuals with a lower level of intrinsic life goal orientation. When participants' intrinsic goals were momentarily heightened, they reported significantly less body image dissatisfaction, compared to those not receiving a strengthening of these goals. The results are the first to find a protective effect of intrinsic life goals on men's body image, and have important implications for intervention.


Systemic tumor necrosis factor-related apoptosis-inducing ligand delivery shows antiatherosclerotic activity in apolipoprotein E-null diabetic mice.
Although in vitro studies have suggested that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) might be involved in vascular biology, its potential role in the pathogenesis and/or treatment of atherosclerosis has not been investigated. Both recombinant human TRAIL and an adeno-associated virus vector expressing human TRAIL were used to deliver TRAIL in apolipoprotein E (apoE)-null mice in which diabetes mellitus was induced by destruction of islet cells with streptozotocin. Diabetes in apoE-null mice was associated with a significant increase in atherosclerotic plaque area and complexity in the aorta as assessed by a marked increase in interstitial collagen, cellular proliferation, and macrophage infiltration and a focal loss of endothelial coverage. Repeated intraperitoneal injections of recombinant human TRAIL and a single intravenous injection of adeno-associated virus-human TRAIL significantly attenuated the development of atherosclerotic plaques in apoE-null animals. TRAIL also markedly affected the cellular composition of plaque lesions by inducing apoptosis of infiltrating macrophages and increasing the vascular smooth muscle cell content. Moreover, TRAIL promoted the in vitro migration of cultured human aortic vascular smooth muscle cells but not of monocytes or macrophages. Conversely, TRAIL selectively induced apoptosis of human cultured macrophages but not of vascular smooth muscle cells. Overall, data from the present study indicate that atherosclerosis in diabetic apoE-null mice is ameliorated by systemic TRAIL administration and that adeno-associated virus-mediated TRAIL gene delivery might represent an innovative method for the therapy of diabetic vascular diseases.


Scanning electron microscopy of Escherichia coli encapsulated in a spacerized graphene sandwich.
Electron microscopy of biological materials such as bacteria allows multifaceted analysis to understand their structure and function with high resolution, which is difficult to achieve with optical microscopy. However, the samples are damaged or broken by electron beam irradiation and by the vacuum environment. Here, we observed bacteria in a suspension encapsulated in a graphene sandwich that prevents electron beam damage without the need for fixation. Specifically, we demonstrated in situ scanning electron microscopy observation of Escherichia coli in a graphene sandwich containing a perforated membrane as a spacer, encapsulating non-immobilized E. coli between the graphene layers. However, E. coli activity, such as division, was not observed, although the irradiated cells grew slightly when resuspended under optimal culture conditions. Our findings suggest that the graphene sandwich methodology enables the observation of wet E. coli cells by electron microscopy but requires refinement to allow the live imaging of biological materials.