Long-term follow-up of infrared coagulator ablation of anal high-grade dysplasia in men who have sex with men.
We previously reported on infrared coagulator ablation of anal high-grade intraepithelial squamous lesions in HIV-positive and HIV-negative men who have sex with men (MSM) with a median follow-up of 1.5 years. We sought to determine high-grade intraepithelial squamous lesion recurrence rates after long-term follow-up for infrared coagulator ablation, and whether patients progressed to invasive cancer. : This study investigated a retrospective cohort. This study was set in an office-based practice. The patients evaluated were MSM who underwent at least 1 infrared coagulator anal high-grade intraepithelial squamous lesion ablation between 1999 and 2005 with at least 1-year additional follow-up. Infrared coagulator ablation had been performed. The primary outcomes measured were high-grade intraepithelial squamous lesion recurrence and progression to anal squamous-cell carcinoma. Ninety-six MSM were included (44 HIV-positive) with a median follow-up of 48 and 69 months in HIV-negative and HIV-positive MSM. Thiry-five percent of HIV-positive and 31% of HIV-negative subjects from the original cohort were lost to follow-up. In HIV-negative MSM, 32 (62%) had a recurrence in a mean of 14 months. Recurrence rates after the second and third treatments were 48% and 57%. In HIV-positive MSM, 40 (91%) had a recurrence in a mean of 17 months. Recurrence rates after the second, third, and fourth infrared coagulator ablations were 63%, 85%, and 47%. After the first ablation, HIV-positive MSM were 1.9 times more likely to have a recurrence than HIV-negative MSM (P = .009). One year after the first ablation, 61% of HIV-positive MSM had recurrent high-grade intraepithelial squamous lesions in comparison with 38% of HIV-negative MSM. One year after the second ablation, 49% of HIV-positive MSM had recurrent high-grade intraepithelial squamous lesions in comparison with 28% of HIV-negative MSM. In HIV-negative and HIV-positive MSM, the probability of curing an individual lesion after first ablation was 80% and 67%. Most recurrence was due to the development of metachronous lesions occurring in 82% and 52% of HIV-positive and HIV-negative subjects after their first infrared coagulator treatment. The mean number of recurrent lesions for both HIV-positive and HIV-negative MSM was never >2. No MSM developed squamous-cell carcinoma, and there were no serious adverse events. At last visit, 82% of HIV-positive MSM and 90% of HIV-negative MSM were high-grade intraepithelial squamous lesion free. This was a retrospective, observational study with significant loss to follow-up. Infrared coagulator ablation is an effective treatment for high-grade intraepithelial squamous lesions, and no patients progressed to cancer. HIV-positive patients are significantly more likely to have a recurrence, and recurrence occurred more rapidly in these patients. Continued follow-up is important.


Comparison of Thermal Safety Practice Guidelines for Diagnostic Ultrasound Exposures.
This article examines the historical evolution of various practice guidelines designed to minimize the possibility of thermal injury during a diagnostic ultrasound examination, including those published by the American Institute of Ultrasound in Medicine, British Medical Ultrasound Society and Health Canada. The guidelines for prenatal/neonatal examinations are in general agreement, but significant differences were found for postnatal exposures. We propose sets of thermal index versus exposure time for these examination categories below which there is reasonable assurance that an examination can be conducted without risk of producing an adverse thermal effect under any scanning conditions. If it is necessary to exceed these guidelines, the occurrence of an adverse thermal event is still unlikely in most situations because of mitigating factors such as transducer movement and perfusion, but the general principle of "as low as reasonably achievable" should be followed. Some limitations of the biological effects studies underpinning the guidelines also are discussed briefly.


Comparative outcomes of endoscopic and radiological gastrostomy tube placement: a systematic review and meta-analysis with GRADE analysis.
Percutaneous endoscopic gastrostomy (PEG) and percutaneous radiological gastrostomy (PRG) are invasive interventions used for enteral access. We performed a systematic review and meta-analysis with assessment of certainty of evidence to compare the risk of adverse outcomes and technical failure between PEG and PRG. We queried PubMed, EMBASE, and Cochrane from inception through January 2022 to identify studies comparing outcomes of PEG and PRG. The primary outcome was 30-day all-cause mortality; secondary outcomes included the risk of colon perforation, peritonitis, bleeding, technical failure, peristomal infections, and tube-related complications. We performed GRADE assessment to assess the certainty of evidence and leave-one-out analysis for sensitivity analysis. In the final analysis, 33 studies, including 26 high-quality studies, provided data on 275,117 patients undergoing PEG and 192,691 patients undergoing PRG. Data from high quality studies demonstrated that, compared to PRG, PEG had significantly lower odds of selected outcomes, including 30-day all-cause mortality (odds ratio [OR] 0.75, 95% confidence interval [CI] 0.60-0.95; P=0.02), colon perforation (OR 0.61, 95%CI 0.49-0.75; P<0.001), and peritonitis (OR 0.71, 95%CI 0.63-0.81; P<0.001). There was no significant difference between PEG and PRG in terms of technical failure, bleeding, peristomal infections or mechanical complications. The certainty of the evidence was rated moderate for colon perforation and low for all other outcomes. PEG is associated with a significantly lower risk of 30-day all-cause mortality, colon perforation, and peritonitis compared to PRG, while having a comparable technical failure rate. PEG should be considered as the first-line technique for enteral access.


Maintenance of accuracy during amino acid starvation.
The kinetics of the tRNA cycle is in itself capable of keeping the translational error level almost unaffected by amino acid starvation. There is no need to assume any yet unknown mechanism or property. Kinetic analysis shows that the concentration of aminoacyl-tRNA can stay high even for large reductions in aminoacylation, since the pool of uncharged tRNA normally is very small. An enhanced binding of uncharged tRNA to the ribosome could increase the effect and produce an extremely efficient error damping. A similar result is obtained when EF-Tu is partially inhibited by ppGpp.


Symmetric Euler orientation representations for orientational averaging.
A new kind of orientation representation called symmetric Euler orientation representation (SEOR) is presented. It is based on a combination of the conventional Euler orientation representations (Euler angles) and Hamilton's quaternions. The properties of the SEORs concerning orientational averaging are explored and compared to those of averaging schemes that are based on conventional Euler orientation representations. To that aim, the reflectance of a hypothetical polycrystalline material with orthorhombic crystal symmetry was calculated. The calculation was carried out according to the average refractive index theory (ARIT [T.G. Mayerhöfer, Appl. Spectrosc. 56 (2002) 1194]). It is shown that the use of averaging schemes based on conventional Euler orientation representations leads to a dependence of the result from the specific Euler orientation representation that was utilized and from the initial position of the crystal. The latter problem can be overcome partly by the introduction of a weighing factor, but only for two-axes-type Euler orientation representations. In case of a numerical evaluation of the average, a residual difference remains also if a two-axes type Euler orientation representation is used despite of the utilization of a weighing factor. In contrast, this problem does not occur if a symmetric Euler orientation representation is used as a matter of principle, while the result of the averaging for both types of orientation representations converges with increasing number of orientations considered in the numerical evaluation. Additionally, the use of a weighing factor and/or non-equally spaced steps in the numerical evaluation of the average is not necessary. The symmetrical Euler orientation representations are therefore ideally suited for the use in orientational averaging procedures.


Why Does Australia Appear to Have the Highest Rates of Food Allergy?
Australia has reported the highest rates of food allergy, using the gold standard, oral food challenge. This phenomenon, which appears linked to the "modern lifestyle" and has coincided with the explosion of the new diseases of affluence in the 21st century, dubbed "affluenza," has spurred a multitude of theories and academic investigations. This review focuses on potentially modifiable lifestyle factors for the prevention of food allergy and presents the first data to emerge in the Australian context that centers around the dual allergen exposure hypothesis, the vitamin D hypothesis, and the hygiene hypothesis.


Greenberger-Horne-Zeilinger states and few-body Hamiltonians.
The generation of Greenberger-Horne-Zeilinger (GHZ) states is a crucial problem in quantum information. We derive general conditions for obtaining GHZ states as eigenstates of a Hamiltonian. We find that a necessary condition for an n-qubit GHZ state to be a nondegenerate eigenstate of a Hamiltonian is the presence of m-qubit couplings with m≥[(n+1)/2]. Moreover, we introduce a Hamiltonian with a GHZ eigenstate and derive sufficient conditions for the removal of the degeneracy.


Efficacy of ICT-based interventions in improving psychological outcomes among older adults with MCI and dementia: A systematic review and meta-analysis.
The purpose of this systematic review and meta-analysis was to investigate empirical evidence about the effectiveness of Information and Communication Technology-based interventions (ICTs) on different psychological outcomes in adults aged over 60 years with Mild Cognitive Impairment (MCI) or dementia. We conducted a systematic search on Pubmed, Web of Science, Scopus, and PsycInfo with publication year between January 2010 up to April 2021. Any pre-post quantitative intervention study with at least one of the following domains examined: quality of life (QoL), psychological well-being, social interaction, engagement, mood, anxiety, stress, loneliness, self-efficacy, or self-esteem was included. The risk of bias and quality of evidence were assessed using tools based on the Cochrane Handbook for Systematic Review of Interventions criteria. Forty-eight studies with a total of 1488 participants met the selection criteria. Because of the high heterogeneity, we ran nine different random effects meta-analyses divided by outcome and type of cognitive decline which indicated that these treatments were ineffective overall, with some exceptions. Only anxiety (small effect size =-0.375 [-0.609; -0.140]) and behavioral symptoms (BS) (medium effect size =-0.585 [-1.019; -0.152]) in people with dementia (PwD) were found to change significantly. Moreover, effect sizes for QoL in dementia and for mood in people with MCI became significant when moderated by type of ICT, living situation, and experimental setting. In particular, Virtual Reality (VR) appeared to be more effective than other devices for both PwD and MCI, and nursing homes were found to be the best setting for administering these treatments. The trim and fill method found no evidence of publication bias in any of the 9 analyses. However, quality of evidence within (RoB 2, RoB 2 Crossover, ROBINS) and across (GRADE assessment) studies was low, thus these findings should be interpreted with caution. In general, ICT-based intervention can be considered a promising approach for improving anxiety and BS in PwD, and for improving QoL in PwD and mood in people with MCI, specifically when VR is used, when participants live in nursing homes, and when interventions are carried out in nursing homes.1.


Development and applications of a solid-phase radioimmunoassay for the PO protein of peripheral myelin.
This is the first report of a quantitative radioimmunoassay for PO. The assay uses antigen-coated plastic microwells, with antibody binding detected by 125I-labeled protein A. Either peripheral myelin proteins or purified PO may be used as the antigen. Optimal extraction of tissue samples for PO immunoassay requires careful attention to the sodium dodecyl sulfate-to-protein ratio. Sodium dodecyl sulfate interference with antibody binding can be minimized by adding an excess of nonionic detergent and carrier protein to the incubation buffer. This method allows the detection of 0.8 ng of PO (20 ng/ml). Results from this assay showed little or no immunoreactivity in extracts of brain, centra myelin, liver, purified myelin basic proteins, cultured, purified secondary Schwann cells, or membrane preparations from these cells. PO was clearly detectable in Schwann cell cultures from 3- to 4-day-old rats at 12-18 h after dissociation (4% of the level in adult sciatic nerve) and in extracts of one-day-old rat sciatic nerve (2% of the level in adult nerve). Myelin basic protein radioimmunoassays showed that the ratio of PO to myelin basic protein is essentially constant in extracts of sciatic nerve from ne-day-old, four-day-old, and young adult rats. Another result was that PO levels are reduced in the trembler mouse sciatic nerve.


Pepleomycin-induced pneumonitis resulting in death.
Two cases of fatal pneumonitis induced by pepleomycin, a new antitumour antibiotic analogous to bleomycin, are described. In the first case, the patient received radiation in combination with intra-arterial administration of pepleomycin to a total dose of 100 mg. for the treatment of an epidermoid carcinoma of the maxilla. The pulmonary changes were noted two weeks after cessation of the chemotherapy and the patient died of pulmonary insufficiency despite intensive therapy with antibiotics and a steroid. The other case with an epidermoid carcinoma of the cheek and oropharynx was treated by radiation and pepleomycin given to a total dose of 205 mg. Pepleomycin was replaced by predonin soon after bilateral shadows were noticed on a chest radiograph, but the patient died of pneumonitis 10 months later. Various factors which may affect the development of pulmonary toxicity by pepleomycin are discussed.


Chromatographic Determination of the Mycotoxin Patulin in 219 Chinese Tea Samples and Implications for Human Health.
Patulin (PAT) is a mycotoxin, with several acute, chronic, and cellular level toxic effects, produced by various fungi. A limit for PAT in food of has been set by authorities to guarantee food safety. Research on PAT in tea has been very limited although tea is the second largest beverage in the world. In this paper, HPLC-DAD and GC-MS methods for analysis of PAT in different tea products, such as non-fermented (green tea), partially fermented (oolong tea, white tea, yellow tea), completely fermented (black tea), and post-fermented (dark tea and Pu-erh tea) teas were developed. The methods showed good selectivity with regard to tea pigments and 5-hydroxymethylfurfural (5-HMF) and a recovery of 90-102% for PAT at a 10-100 ppb spiking level. Limit of detection (LOD) and limit of quantification (LOQ) in tea were 1.5 ng/g and 5.0 ng/g for HPLC-UV, and 0.25 ng/g and 0.83 ng/g for GC-MS. HPLC was simpler and more robust, while GC-MS showed higher sensitivity and selectivity. GC-MS was used to validate the HPLC-UV method and prove its accuracy. The PAT content of 219 Chinese tea samples was investigated. Most tea samples contained less than 10 ng/g, ten more than 10 ng/g and two more than 50 ng/g. The results imply that tea products in China are safe with regard to their PAT content. Even an extreme daily consumption of 25 g of the tea with the highest PAT content (124 ng/g), translates to an intake of only 3 μg/person/day, which is still an order of magnitude below the maximum allowed daily intake of 30 µg for an adult.


Modeling of drying and ameliorative effects of relative humidity (RH) against β-carotene degradation and color of carrot (Daucus carota var.) slices.
Drying and β-carotenes retention kinetics were predicted using models in relative humidity (RH) drying condition. This was achieved by drying carrot slices using RH-convective hot-air dryer at 60, 70 and 80 °C under RH (10% 20% and 30%) conditions at 2.0 m/s air velocity. Three mathematical models describing thin layer were compared to their goodness of fit in terms of coefficient of correlation (R2), root mean square error (RMSE) and reduced Chi square ( χ 2 ). The Wang and Singh model could satisfactorily describe RH-convective drying of carrot slices with R2, RMSE and χ 2 in the ranges of 0.996-0.999, 5.4 × 10-4-9.4 × 10-4 and 0.0150-0.03353 respectively. The results reveal that a range of 3.61-8.2% retention of β-carotene was observed for every 10% increase in RH in various drying air temperature. In summary, higher temperatures were mainly responsible for β-carotenes degradation however this can be mitigated when drying is conducted under higher RH.


The economic value of medical research: is it worth the investment?
To provide a brief commentary regarding the economic evaluation of medical research by summarizing a recent report from the Mary Woodard Lasker Charitable Trust. A review of the report Exceptional Returns: The Economic Value of America's Investment in Medical Research was conducted. In this report, nine economists translated the accomplishments of medical research into dollars by placing a monetary value on better health and longer life. This manuscript focuses on implications of this report to women's health research. After first isolating the impact of medical research from other gains unrelated to research and development, the increase in life expectancy due to advances in health during the 1970s and 1980s were worth $57 trillion to Americans. Gains associated with prevention and treatment of cardiovascular disease alone totaled $31 trillion. Our nation's contribution into medical research provides a very high "return on investment." The likely returns from research are so favorable that the payoff from any "portfolio" of research investments would be enormous.


Somatic mutation profiling and HER2 status in KRAS-positive Chinese colorectal cancer patients.
KRAS is an independent negative predictor for anti-epidermal growth factor receptor (anti-EGFR) treatment in colorectal cancers (CRCs). However, 30% to 50% of CRC patients are KRAS-positive and do not benefit from anti-EGFR therapy. In this study, we investigated the mutational features and clinical significance of KRAS-positive Chinese CRC patients. A total of 139 Chinese CRC patients who received clinical KRAS testing (Sanger sequencing) were examined by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Fifty KRAS-positive specimens were further detected by next-generation sequencing (NGS). The most prevalent mutation in KRAS was G12D (46%), followed by G12V (20%), and G13D (18%). In addition to KRAS, 72 unique alterations in another 12 genes were also detected. The most common mutated genes were TP53 (62%), APC (46%), and PIK3CA (22%). The proportion of HER2 amplifications in KRAS-positive CRC patients was 4.4%, which was lower than that in KRAS -negative CRC patients (14.3%). No relationship was found between HER2 amplification and KRAS status (p = 0.052). However, the odds ratio is very low (0.279). In addition, these gene mutations were not significantly associated with age, sex, tumor size, lymph node metastasis, mismatch repair-deficient, or tumor differentiation. However, TP53 mutations were more prevalent in colon cancer with KRAS mutations than in rectal cancer (75.0% vs 28.6%, respectively, p = 0.004). The negative predictive value of the IHC analysis for predicting HER2 amplification reached to 98.39%, while the positive predictive value reached only 50%. Overall, the mutation profiling of Chinese CRC patients with KRAS mutations is different from that of Western CRC patients. Our results will help us to understand the molecular features of Chinese CRC patients.


[Caesarean section: closure or non-closure of peritoneum? A randomized trial of postoperative morbidity].
To evaluate postoperative morbidity with non-closure of the visceral and parietal peritoneum during caesarean section. A prospective randomized study of 170 patients. Operative time, postoperative pain, postoperative morbidity (febrile morbidity, wound haematoma, wound infection, postoperative ileus) and length of hospital stay were compared between the two groups. Duration of operation was significantly shorter without peritoneal closure (38.89 vs 42.00 minutes; P<0.05). Wound haematoma were more frequent when peritoneum was closed (P<0.029). There were no significant difference between the two groups for postoperative ileus, length of hospital stay, postoperative pain and other complications. We report the first French study on this subject. In this study, non-closure of both visceral and parietal peritoneum is associated with shorter operation duration and seems to reduce immediate complications. A long-term evaluation of morbidity, regarding adhesions is necessary.


A little rein on addiction.
Rewarding and aversive experiences influence emotions, motivate specific behaviors, and modify future action in animals. Multiple conserved vertebrate neural circuits have been discovered that act in a species-specific manner to reinforce behaviors that are rewarding, while attenuating those with an adverse outcome. A growing body of research now suggests that malfunction of the same circuits is an underlying cause for many human disorders and mental ailments. The habenula (Latin for "little rein") complex, an epithalamic structure that regulates midbrain monoaminergic activity has emerged in recent years as one such region in the vertebrate brain that modulates behavior. Its dysfunction, on the other hand, is implicated in a spectrum of psychiatric disorders in humans such as schizophrenia, depression and addiction. Here, I review the progress in identification of potential mechanisms involving the habenula in addiction.


Investigation of biogenic volatile organic compounds emissions in the Qinghai-Tibetan Plateau.
Biogenic volatile organic compounds (BVOCs), which are produced and emitted by plants, have significant chemical reactivity in the atmosphere and impacting climate change. Qinghai Province, a vital component of the plateau, has abundant vegetation resources, primarily grasslands and forests, yet BVOCs emissions and their impact on air quality remain understudied. In this study, the emissions rates and compositions of BVOCs from seven dominant vegetation types in Qinghai Province were sampled and analyzed using a closed-loop stripping dynamic headspace sampling approach combined with GC-MS, and the total emissions of BVOCs in Qinghai province in 2021 were estimated by using G95 model. At the same time, the emission characteristics of various vegetation types were also analyzed. The results showed that the emissions rates and compositions of BVOCs differed significantly among vegetation types, with monoterpenes being the dominant emission composition in coniferous forests, which accounted for >70 % of the total BVOCs emissions, while isoprene being the main composition in alpine meadow, accounting for 84.96 %. The emissions of three typical vegetation types, Picea asperata, alpine meadow and alpine steppe, were monitored daily, revealing significant diurnal and clear unimodal patterns. The study also found that the annual average BVOCs emissions from vegetation sources in Qinghai Province were estimated to be 1550.63 Gg yr-1, with isoprene contributing the highest proportion of emissions, accounting for 56.94 %. Grassland was the largest BVOCs emission source in Qinghai Province, with an annual average emission of 1438.52 Gg yr-1. Additionally, BVOCs emissions in Qinghai Province showed strong seasonal and daily variation patterns, with the highest emissions occurring in summer, with the peak in July. These findings provide the characteristics of BVOCs emissions from vegetation sources in the Tibetan Plateau, which will contribute to a better understanding of their impact on atmospheric chemistry and climate change.


Automated crystallographic ligand building using the medial axis transform of an electron-density isosurface.
Automatic fitting methods that build molecules into electron-density maps usually fail below 3.5 A resolution. As a first step towards addressing this problem, an algorithm has been developed using an approximation of the medial axis to simplify an electron-density isosurface. This approximation captures the central axis of the isosurface with a graph which is then matched against a graph of the molecular model. One of the first applications of the medial axis to X-ray crystallography is presented here. When applied to ligand fitting, the method performs at least as well as methods based on selecting peaks in electron-density maps. Generalization of the method to recognition of common features across multiple contour levels could lead to powerful automatic fitting methods that perform well even at low resolution.


Dietary patterns derived using principal component analysis and associations with sociodemographic characteristics and overweight and obesity: A cross-sectional analysis of Iranian adults.
This study examined the cross-sectional association between household dietary patterns and sociodemographic characteristics and BMI in a nationally representative sample of Iranian adults. Data on 6,833 households (n = 17,824 adults) from the National Comprehensive Study on Household Food Consumption Pattern and Nutritional Status 2001-2003 were used. Principal component analysis (PCA) was used to extract dietary patterns from three household 24-h dietary recalls. Linear regression analyses were used to examine associations between dietary patterns and sociodemographic characteristics and BMI. Three dietary patterns were identified: the first was characterized by high citrus fruit intake, the second by high hydrogenated fats intake and the third by high non-leafy vegetables intake. The first and third patterns were associated with household heads with higher education and living in urban areas, while the second was associated with household heads with lower education and living in rural areas. All dietary patterns were positively associated with BMI. The strongest association was found with the first dietary pattern (β: 0.49, 95% CI: 0.43, 0.55). While all three dietary patterns were positively associated with BMI, the sociodemographic characteristics of Iranian adults who consumed them differed. These findings inform the design of population-level dietary interventions to address rising obesity rates in Iran.


High dietary salt intake increases urinary NGAL excretion and creatinine clearance in healthy young adults.
In rodents and older patients with elevated blood pressure (BP), high dietary sodium increases excretion of biomarkers of kidney injury, but it is unclear whether this effect occurs in healthy young adults. The purpose of this study was to determine whether short-term high dietary salt increases urinary excretion of the kidney injury biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) in healthy young adults. Twenty participants participated in a double-blind, placebo-controlled, randomized crossover study. For 10 days each, participants were asked to consume salt (3,900 mg sodium) or placebo capsules. We measured BP during each visit, obtained 24-h urine samples for measurements of electrolytes, NGAL, and KIM-1, and assessed creatinine clearance. Compared with placebo, salt loading increased daily urinary sodium excretion (placebo: 130.3 ± 62.4 mmol/24 h vs. salt: 287.2 ± 72.0 mmol/24 h, P < 0.01). There was no difference in mean arterial BP (placebo: 77 ± 7 mmHg vs. salt: 77 ± 6 mmHg, P = 0.83) between conditions. However, salt loading increased the urinary NGAL excretion rate (placebo: 59.8 ± 44.4 ng/min vs. salt: 80.8 ± 49.5 ng/min, P < 0.01) and increased creatinine clearance (placebo: 110.5 ± 32.9 mL/min vs. salt: 145.0 ± 24.9 mL/min, P < 0.01). Urinary KIM-1 excretion was not different between conditions. In conclusion, in healthy young adults 10 days of dietary salt loading increased creatinine clearance and increased urinary excretion of the kidney injury biomarker marker NGAL but not KIM-1.NEW & NOTEWORTHY In healthy young adults, 10 days of dietary salt loading increased creatinine clearance and increased urinary excretion of the kidney injury biomarker marker neutrophil gelatinase-associated lipocalin despite no change in resting blood pressure.


The three-dimensional structure of 3,3',4,4'-tetrachlorobiphenyl, a dioxin-like polychlorinated biphenyl (PCB).
The crystal structure of PCB 77 (3,3',4,4'-tetrachlorobiphenyl, C(12)H(6)Cl(4)), a dioxin-like PCB congener, is described. The dihedral angle of PCB 77 is 43.94(6) degrees, which is slightly larger than calculated or experimental dihedral angles of biphenyl derivatives in solution but smaller than experimental dihedral angles in the gas phase.


Amantadine reduces the duration of levodopa-induced dyskinesia: a randomized, double-blind, placebo-controlled study.
We evaluated the effects of amantadine on levodopa-induced dyskinesia (LID) in eighteen consecutive Parkinson's disease (PD) patients in a randomized, double-blind, placebo-controlled study. The primary outcomes were the Clinical Dyskinesia Rating Scale (CDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS) part IVa score changes. The secondary outcomes were the UPDRS II and III score changes. Amantadine did not change the CDRS score for hyperkinesia or dystonia, but decreased the duration of LID and its influence on daily activities (p=0.04) and the UPDRS II score (p=0.01) more than placebo. These findings show that amantadine reduces the duration of LID and improves motor disability in PD.


Bioavailability of anthocyanins and colonic polyphenol metabolites following consumption of aronia berry extract.
A single-dose pharmacokinetic trial was conducted in 6 adults to evaluate the bioavailability of anthocyanins and colonic polyphenol metabolites after consumption of 500mg aronia berry extract. UHPLC-MS methods were developed to quantitate aronia berry polyphenols and their metabolites in plasma and urine. While anthocyanins were bioavailable, microbial phenolic catabolites increased ∼10-fold more than anthocyanins in plasma and urine. Among the anthocyanins, cyanidin-3-O-galactoside was rapidly metabolized to peonidin-3-O-galactoside. Aronia polyphenols were absorbed and extensively metabolized with tmax of anthocyanins and other polyphenol catabolites from 1.0h to 6.33h in plasma and urine. Despite significant inter-individual variation in pharmacokinetic parameters, concentrations of polyphenol metabolites in plasma and urine at 24h were positively correlated with total AUC in plasma and urine (r=0.93, and r=0.98, respectively). This suggests that fasting blood and urine collections could be used to estimate polyphenol bioavailability and metabolism after aronia polyphenol consumption.


Inhibitory effect of rhynchophylline on platelet aggregation and thrombosis.
Rhynchophylline (Rhy) inhibited rabbit platelet aggregation induced by arachidonic acid (AA), collagen, and ADP. The values of IC50 were 0.72, 0.74, and 0.67 mmol.L-1, respectively. Rhy reduced the thromboxane B2 (TXB2) generation in PRP induced by collagen but failed to reduce that induced by AA. Rhy suppressed malondialdehyde (MDA) formation in platelet suspension stimulated by thrombin, inhibited the platelet factor 4 (PF4) release. It did not alter intraplatelet cAMP concentration. Rhy 10-20 mg.kg-1 iv showed a significant inhibition of venous thrombosis and cerebral thrombosis in rats.


Long Non-coding RNA Growth Arrest-specific Transcript 5 (GAS5) Inhibits Liver Fibrogenesis through a Mechanism of Competing Endogenous RNA.
Effective control of hepatic stellate cell (HSC) activation and proliferation is critical to the treatment of liver fibrosis. Long non-coding RNAs have been shown to play a pivotal role in the regulation of cellular processes. It has been reported that growth arrest-specific transcript 5 (GAS5) acts as a crucial mediator in the control of cell proliferation and growth. However, little is known about the role and underlying mechanism of GAS5 in liver fibrosis. In this study, our results indicated that GAS5 expression was reduced in mouse, rat, and human fibrotic liver samples and in activated HSCs. Overexpression of GAS5 suppressed the activation of primary HSCs in vitro and alleviated the accumulation of collagen in fibrotic liver tissues in vivo. We identified GAS5 as a target of microRNA-222 (miR-222) and showed that miR-222 could inhibit the expression of GAS5. Interestingly, GAS5 could also repress miR-222 expression. A pulldown assay further validated that GAS5 could directly bind to miR-222. As a competing endogenous RNAs, GAS5 had no effect on primary miR-222 expression. In addition, GAS5 was mainly localized in the cytoplasm. Quantitative RT-PCR further demonstrated that the copy numbers of GAS5 per cell are higher than those of miR-222. GAS5 increased the level of p27 protein by functioning as a competing endogenous RNA for miR-222, thereby inhibiting the activation and proliferation of HSCs. Taken together, a new regulatory circuitry in liver fibrosis has been identified in which RNAs cross-talk by competing for shared microRNAs. Our findings may provide a new therapeutic strategy for liver fibrosis.


Constitutively active MyD88/CD40 costimulation enhances expansion and efficacy of chimeric antigen receptor T cells targeting hematological malignancies.
Successful adoptive chimeric antigen receptor (CAR) T-cell therapies against hematological malignancies require CAR-T expansion and durable persistence following infusion. Balancing increased CAR-T potency with safety, including severe cytokine-release syndrome (sCRS) and neurotoxicity, warrants inclusion of safety mechanisms to control in vivo CAR-T activity. Here, we describe a novel CAR-T cell platform that utilizes expression of the toll-like receptor (TLR) adaptor molecule, MyD88, and tumor-necrosis factor family member, CD40 (MC), tethered to the CAR molecule through an intentionally inefficient 2A linker system, providing a constitutive signal that drives CAR-T survival, proliferation, and antitumor activity against CD19+ and CD123+ hematological cancers. Robust activity of MC-enhanced CAR-T cells was associated with cachexia in animal models that corresponded with high levels of human cytokine production. However, toxicity could be successfully resolved by using the inducible caspase-9 (iC9) safety switch to reduce serum cytokines, by administration of a neutralizing antibody against TNF-α, or by selecting "low" cytokine-producing CD8+ T cells, without loss of antitumor activity. Interestingly, high basal activity was essential for in vivo CAR-T expansion. This study shows that co-opting novel signaling elements (i.e., MyD88 and CD40) and development of a unique CAR-T architecture can drive T-cell proliferation in vivo to enhance CAR-T therapies.


Aloe vera waste biomass-based adsorbents for the removal of aquatic pollutants: A review.
Aloe vera has been cultivated for many centuries for its beneficial properties, finding application in a wide range of medical and health products. Nowadays, the research has also focused on an alternative use of Aloe vera which is related to environmental applications such as clean water technology/wastewater treatment process. In recent years, biosorption has been shown to be a cost-effective and efficient alternative method for removing various pollutants from wastewater and water. This work provides a comprehensive review on using Aloe vera waste biomass-based sorbents, as well as modified counterparts, for the removal of heavy metals, dyes and other pollutants from aqueous media. The discussed biosorbents have been grouped in five categories based on the treatment of the Aloe vera leaves. Adsorption mechanisms, in addition to the significant factors influencing sorption capability like physical and chemical properties of the adsorbent, initial concentration, initial pH and temperature of the solution, dosage and contact time, have been discussed in detail. Furthermore, the applied equilibrium and kinetic models have been also summarized. The history, taxonomy, botany, and applications of Aloe vera are also presented in brief.


Local facilitation of hippocampal metabotropic glutamate receptor-dependent long-term depression by corticosterone and dexamethasone.
Long-term potentiation and long-term depression (LTD) of synaptic efficacy, two major forms of synaptic plasticity, are believed to underlie learning processes and memory storage. We have recently shown that acute stress, through corticosterone release and stimulation of glucocorticoid receptors (GRs), facilitates the LTD elicited by the group 1 metabotropic glutamate receptor (mGluR) agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) in hippocampal CA1 neurons. However, it is unknown whether sustained corticosterone release, per se, is also able to facilitate DHPG-elicited LTD in control (i.e. unstressed) conditions, and if so, whether it acts on local (i.e. hippocampal) or distant GRs. Here, we show that a brief application of 100 nM corticosterone to rat hippocampal slices lowers the threshold for DHPG-elicited LTD, an effect mimicked by the local application of the GR agonist dexamethasone. These results show that high corticosterone release facilitates hippocampal CA1 mGluR-dependent LTD, and does so through local GRs.


Performance of a one-step quantitative duplex RT-PCR for detection of rotavirus A and noroviruses GII during two periods of high viral circulation.
Rotavirus A (RVA) and noroviruses (NoV) are the major viral agents of acute gastroenteritis (AGE) worldwide. In the present study, we aimed to evaluate the performance of a one-step duplex quantitative RT-PCR (dRT-qPCR) assay, established for detection and quantification of RVA and NoV genogroup II (GII) using a single DNA standard curve (SC), as well as to investigate the association between fecal viral load and optical density (OD) values, and viruses' genotyping. The results obtained by dRT-qPCR in 530 fecal samples from AGE cases were compared with methods employed for the diagnosis of those viruses as follows: enzyme immunoassay (EIA) and polyacrylamide gel electrophoresis (PAGE) for RVA; and qualitative PCR for NoV. By using dRT-qPCR, we detected RVA and NoV in 353 (66%), increasing the positivity rate by 22.5% for RVA and 11.5% NoV, comparing the number of positive samples. RVA and NoV GII were detected in a range of 5.17 × 10(3) to 6.56 × 10(9) and 3.76 × 10(3) to 9.13 × 10(10) genome copies per gram of feces, respectively. We observed a significant direct correlation between genome copies values and optical density, using dRT-qPCR and EIA assays, respectively (Spearman ρ=0.41; p<0.0001). Viruses characterization demonstrated a predominance of NoV GII.4 Sidney 2012 variant during October 2013 to February 2014, followed by the emergence of RVA genotype G12P[8] in 2014. The established assay using a single SC provides an early feedback concerning detection and quantification, with the advantage of detecting simultaneously RVA and NoV GII, reducing time and reagent costs.


Toxicological evaluations of Stigma maydis (corn silk) aqueous extract on hematological and lipid parameters in Wistar rats.
Despite the acclaimed phytotherapeutic attributes of Stigma maydis in folkloric medicine, there is paucity of information on its toxicity profile on hematological and lipid parameters. The toxicological effect of aqueous extract of corn silk at 100, 200 and 400 mg/kg body weight on hematological indices in Wistar rats were evaluated progressively at 24 h after 1, 7, 14, 21 and 28 days. Lipid parameters were also analyzed at the end of the experimental period. We observed that the extract did not exhibit any significant (p > 0.05) effect on red blood cells, hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and mean platelet volume at all the tested doses. The study however showed a significant increase in the serum levels of white blood cell, platelet, lymphocytes, high-density lipoprotein cholesterol; as well as feeding pattern in the animals, while the concentrations of total cholesterol, low-density lipoprotein cholesterol, and artherogenic index value were significantly lowered. These findings are suggestive of non-hematotoxic potential of the extract. Overall, the effect exhibited by corn silk extract in this study proved that, it is unlikely to be hematotoxic and could be a good candidature in the management of coronary heart diseases if consumed at the doses investigated.


Spatiotemporal dynamics of distributed synthetic genetic circuits.
We propose and study models of two distributed synthetic gene circuits, toggle-switch and oscillator, each split between two cell strains and coupled via quorum-sensing signals. The distributed toggle switch relies on mutual repression of the two strains, and oscillator is comprised of two strains, one of which acts as an activator for another that in turn acts as a repressor. Distributed toggle switch can exhibit mobile fronts, switching the system from the weaker to the stronger spatially homogeneous state. The circuit can also act as a biosensor, with the switching front dynamics determined by the properties of an external signal. Distributed oscillator system displays another biosensor functionality: oscillations emerge once a small amount of one cell strain appears amid the other, present in abundance. Distribution of synthetic gene circuits among multiple strains allows one to reduce crosstalk among different parts of the overall system and also decrease the energetic burden of the synthetic circuit per cell, which may allow for enhanced functionality and viability of engineered cells.


Framing the detection of incipient tuberculosis infection: A qualitative study of political prioritisation.
Incipient Tuberculosis (ITB) refers to Mycobacterium tuberculosis infection that is likely to progress to active disease in the absence of treatment, but without clinical signs, symptoms, radiographic or microbiological evidence of disease. Biomarker-based tests to diagnose incipient TB hold promise for better prediction and, through TB preventive therapy, prevention of disease. This study explored current and future framing and prioritisation of ITB. Twenty-two interviews across eight countries were conducted. A modified Shiffman & Smith Framework, containing four categories-Ideas, Issue Characteristics, Actor Power, and Political Contexts-was used to analyse the current landscape and potential for prioritisation of diagnosis and treatment of ITB. Latent TB policy implementation has been slow due to technical, logistical and financial challenges, and because it has been framed in a manner non-conducive to gaining political priority. Framing ITB testing as 'early detection' rather than 'prediction', and its management as 'treatment' rather than 'preventive therapy', may help raise its importance in policies, and its acceptance among actors. Consensus surrounding the framing of ITB will be crucial for the successful adoption of ITB diagnostics and treatment. When designing ITB tools and policies, it will be important to address challenges that pertain to latent TB policies.


The utility of ADAMTS13 in differentiating TTP from other acute thrombotic microangiopathies: results from the UK TTP Registry.
Thrombotic microangiopathies (TMAs) are frequently difficult to differentiate clinically, and measurement of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) remains vital in thrombotic thrombocytopenic purpura (TTP) diagnosis. We retrospectively reviewed cases referred for ADAMTS13 testing, using UK TTP Registry screening data. Of a total 810 cases, 350 were confirmed as TTP. The 460 non-TTP cases comprised secondary TMAs (24·57%) and haemolytic uraemic syndrome (HUS) (27·17% aHUS, 2·83% Shiga-like toxin-producing E. coli [STEC]-HUS); the remainder were TMAs with no clear association, not TMAs, or had no confirmed diagnosis. ADAMTS13 levels were significantly lower in TTP than STEC-HUS, aHUS and other TMAs. TTP patients had significantly lower platelet count (15 × 10(9) /l; range 0-96) than aHUS (57 × 10(9) /l; range 13-145, P < 0·0001) or STEC-HUS (35 × 10(9) /l; range 14-106, P < 0·0001); they also had lower creatinine levels (92 μmol/l; range 43-374) than aHUS (255 μmol/l; range 23-941, P < 0·0001) and STEC-HUS (324 μmol/l; range 117-639, P < 0·0001). However, 12/34 (35·3%) aHUS patients had a platelet count <30 × 10(9) /l and 26/150 (17·3%) of TTP patients had a platelet count >30 × 10(9) /l; 23/150 (15·3%) of TTP patients had a creatinine level >150 μmol/l. This study highlights the wide variety of TMA presentations, and confirms the utility of ADAMTS13 testing in TTP diagnosis.


Laparoscopic Strassman metroplasty in a postmenarcheal adolescent girl with Herlyn-Werner-Wunderlich müllerian anomaly variant, obstructed noncommunicating didelphic uterus without gartner duct pseudocyst.
Asymmetric obstructed uterus didelphys (Herlyn-Werner-Wunderlich syndrome), also known as obstructed hemivagina with ipsilateral renal agenesis syndrome, is a rare congenital müllerian duct anomaly. Herein we present a case report of incomplete Herlyn-Werner-Wunderlich syndrome, with absence of the hemivaginal septum, diagnosed in a 12-year-old girl. Treatment of the severe pain using an analgesic agent was ineffective. Therefore, laparoscopic metroplastic surgery via the modified Strassman procedure was performed. After surgery, the patient no longer reported dysmenorrhea.


Burden and Depression among Empirically-Derived Subgroups of Family Caregivers for Individuals With Dementia.
Dementia caregiving experiences are not universal and different factors may influence the risk for burden and depression. This study examined factors such as the relationship with the care recipient, severity of dementia, and relationship satisfaction to uncover different types of caregiver burden profiles using baseline assessment for a telephone-based intervention study for dementia caregivers. Participants (n = 233) completed a battery of psychological and caregiving related surveys. The sample was predominantly White and female. Latent class analysis suggested four class models in subsamples of spousal caregivers and adult children caregivers. The results suggested four distinct classes among samples of spousal and adult child caregivers. Differences in burden emerged across both spouses and adult children, and differences in depression also emerged in the spousal sample. Our findings demonstrate the diversity of the caregiving experience and suggest that future psychosocial interventions may benefit from being tailored to the needs of caregiver subgroups.


Acute-on-chronic liver failure: A 20-year retrospective review of a tertiary paediatric liver centre.
Acute-on-chronic liver failure (ACLF) is an acute deterioration of pre-existing chronic liver disease related to a precipitating event. We characterised paediatric ACLF at Birmingham Children's Hospital (BCH) utilising European Association of Liver Disease CLIF criteria, including prevalence, triggers and outcomes. All BCH patients from 2000 to 2020 with CLD who underwent initial liver transplant or died on the transplant waiting list or whilst too unwell to be listed were reviewed. From 2000 to 2020, 24 (4%) children with ACLF were identified. Death occurred in 18 (75%). Transplant occurred in 9 (36%), 3 of which died. ACLF triggers were sepsis organism negative 11 (46%), sepsis organism positive 8 (33%) and GI bleed 5 (17%). Bilirubin at the time of transplant/death in those with ACLF who lived compared with those who died was 529 umol/L (381) versus 665 (210) (p=0.38), creatinine 138 umol/L (147) versus 67 (46) (p=0.41), PT 33 sec (14) versus (32 (15) (p = 0.72), Grade 3, 4 hepatic encephalopathy 1 (17%) versus 10 (56%) (p = 0.17), vasopressor use 1 (17%) versus 17 (94%) (p = 0.001) and ventilation 3 (50%) versus 17 (94%) (p = 0.035). Acute-on-chronic liver failure whilst infrequent has high rates of mortality. The use of vasopressors and ventilation is more frequent in those who die from ACLF.


Inherited factors in thrombosis.
Patients with inherited defects or abnormalities that impair the naturally-occurring anticoagulant and fibrinolytic systems are at risk of developing venous and, more rarely, arterial thromboembolism. The prevalence of inherited thrombophilia in the general population is higher than that of inherited bleeding disorders (ca. 1 in 7500 vs 1 in 20,000). Low levels or dysfunctional forms of antithrombin III, protein C and protein S and abnormal fibrinogens are the most frequent and well-established inherited causes for thrombosis. Less frequent and/or less established causes are low heparin cofactor II and plasminogen and high levels of plasminogen activator inhibitor and histidine-rich glycoprotein. The pathophysiology, genetic and clinical aspects and laboratory diagnosis of inherited thrombotic disorders are reviewed and an approach to prophylaxis and therapy is outlined.


Sonocatalyzed decolorization of synthetic textile wastewater using sonochemically synthesized MgO nanostructures.
The present study focused on the synthesis of nanostructured MgO via sonochemical method and its application as sonocatalyst for the decolorization of Basic Red 46 (BR46) dye under ultrasonic irradiation. The sonocatalyst was characterized using X-ray diffraction (XRD) and field emission scanning electron microscopy (FE-SEM) equipped with energy dispersive X-ray microanalysis (EDX). In the following, the sonocatalytic removal of the dye under different operational conditions was evaluated kinetically on the basis of pseudo first-order kinetic model. The reaction rate of sonocatalyzed decolorization using MgO nanostructures (12.7 × 10(-3) min(-1)) was more efficient than that of ultrasound alone (2.0 × 10(-3) min(-1)). The increased sonocatalyst dosage showed better sonocatalytic activity but the application of excessive dosage should be avoided. The presence of periodate ions substantially increased the decolorization rate from 14.76 × 10(-3) to 33.4 × 10(-3) min(-1). Although the application of aeration favored the decolorization rate (17.8 × 10(-3) min(-1)), the addition of hydrogen peroxide resulted in a considerable decrease in the decolorization rate (9.5 × 10(-3) min(-1)) due to its scavenging effects at specific concentrations. Unlike alcoholic compounds, the addition of phenol had an insignificant scavenging effect on the sonocatalysis. A mineralization rate of 7.4 × 10(-3) min(-1) was obtained within 120 min. The intermediate byproducts were also detected using GC-MS analysis.


Innate Predator Odor Aversion Driven by Parallel Olfactory Subsystems that Converge in the Ventromedial Hypothalamus.
The existence of innate predator aversion evoked by predator-derived chemostimuli called kairomones offers a strong selective advantage for potential prey animals. However, it is unclear how chemically diverse kairomones can elicit similar avoidance behaviors. Using a combination of behavioral analyses and single-cell Ca(2+) imaging in wild-type and gene-targeted mice, we show that innate predator-evoked avoidance is driven by parallel, non-redundant processing of volatile and nonvolatile kairomones through the activation of multiple olfactory subsystems including the Grueneberg ganglion, the vomeronasal organ, and chemosensory neurons within the main olfactory epithelium. Perturbation of chemosensory responses in specific subsystems through disruption of genes encoding key sensory transduction proteins (Cnga3, Gnao1) or by surgical axotomy abolished avoidance behaviors and/or cellular Ca(2+) responses to different predator odors. Stimulation of these different subsystems resulted in the activation of widely distributed target regions in the olfactory bulb, as assessed by c-Fos expression. However, in each case, this c-Fos increase was observed within the same subnuclei of the medial amygdala and ventromedial hypothalamus, regions implicated in fear, anxiety, and defensive behaviors. Thus, the mammalian olfactory system has evolved multiple, parallel mechanisms for kairomone detection that converge in the brain to facilitate a common behavioral response. Our findings provide significant insights into the genetic substrates and circuit logic of predator-driven innate aversion and may serve as a valuable model for studying instinctive fear and human emotional and panic disorders.


Renal involvement of polyarteritis nodosa: CT and MR findings.
To evaluate the imaging findings in patients with renal involvement of Polyarteritis nodosa (PN) to diagnose as early as possible. Four patients diagnosed as having PN participated in the present study. Two patients underwent abdominal dynamic CT, one underwent only pre- and post-contrast CT, and the remaining patient underwent only noncontrast CT and MR imaging, including dynamic contrast study. The common findings of CT and MR imaging were diffuse enlargement, multiple small wedge-shaped less-enhanced areas on dynamic contrast study, and indistinctness of the margin between the cortex and medulla on equilibrium-phase CT. Renal arteriogram showed multiple microaneurysms on arterial phase image in all four cases, and PN was diagnosed. The common CT and MR findings of renal involvement of PN mimicked those of pyelonephritis, when microaneurysms were not demonstrated. The differentiation between PN and pyelonephritis on CT and MR imaging is difficult. Therefore, the radiologist should be familiar with the imaging findings of renal involvement of PN. When PN is suspected, angiography should be performed as early as possible to make a definite diagnosis.


[Clinical studies on the therapeutic effect of tinidazole ("Fasigyn") during treatment of urogenital trichomonas infections in women and men (with comparative laboratory studies on the effect of metronidazole and tinidazole)].
Tinidazole preparations are effective agents for the therapy of genitourinary trichomoniasis in women and men. The application of these drugs is very simple and, in particular, suitable as the application time is short and the occurrence of slight side effects shows a very low incidence. Unfortunately, these medicaments cannot be used during pregnancy and lactation. In addition, definite therapeutical recommendations are lacking and the published specific experiences in the therapy of obese persons with these drugs should be verified in future.


Increased stability and specificity through combined hybridization of peptide nucleic acid (PNA) and locked nucleic acid (LNA) to supercoiled plasmids for PNA-anchored "Bioplex" formation.
Low cellular uptake and poor nuclear transfer hamper the use of non-viral vectors in gene therapy. Addition of functional entities to plasmids using the Bioplex technology has the potential to improve the efficiency of transfer considerably. We have investigated the possibility of stabilizing sequence-specific binding of peptide nucleic acid (PNA) anchored functional peptides to plasmid DNA by hybridizing PNA and locked nucleic acid (LNA) oligomers as "openers" to partially overlapping sites on the opposite DNA strand. The PNA "opener" stabilized the binding of "linear" PNA anchors to mixed-base supercoiled DNA in saline. For higher stability under physiological conditions, bisPNA anchors were used. To reduce nonspecific interactions when hybridizing highly cationic constructs and to accommodate the need for increased amounts of bisPNA when the molecules are uncharged, or negatively charged, we used both PNA and LNA oligomers as "openers" to increase binding kinetics. To our knowledge, this is the first time that LNA has been used together with PNA to facilitate strand invasion. This procedure allows hybridization at reduced PNA-to-plasmid ratios, allowing greater than 80% hybridization even at ratios as low as 2:1. Using significantly lower amounts of PNA-peptides combined with shorter incubation times reduces unspecific binding and facilitates purification.


Sex differences in renal cell cancer presentation and survival: an analysis of the National Cancer Database, 1993-2004.
We analyzed patterns of disease presentation and outcome of renal cell carcinomas by gender using data from the National Cancer Database during a 10-year period. We hypothesized that women presented with lower stage disease and had increased survival than men due to increased imaging. The National Cancer Database is a nationwide oncology data set that currently captures approximately 75% of all newly diagnosed cancer cases from more than 1,400 facility based cancer registries in the United States annually since 1985. The National Cancer Database was queried for adults with renal cell carcinoma diagnosed between 1993 and 2004. Cases were examined according to gender in relation to mean age, American Joint Committee on Cancer stage, histology, grade, tumor size, mortality and race. We identified a total of 236,930 patients with renal cell carcinoma diagnosed between 1993 and 2004 from the National Cancer Database. A total of 89,243 (37.7%) were female and 147,687 (62.3%) were male. Mean age was greater in females (64.3) than in males (62.9) (p <0.001). Women had a higher percentage of stage I tumors (54.1% vs 48.5%, p <0.001). Progressive stage migration was documented in men and women. A trend toward increased survival was noted in women relative to men that did not reach statistical significance. Results from this study show a ratio of 1.65 of renal cell carcinoma for males compared to females. Women are more likely than men to have stage I tumors. Both men and women have demonstrated stage migration, although women more so than men.


JBrowse Connect: A server API to connect JBrowse instances and users.
We describe JBrowse Connect, an optional expansion to the JBrowse genome browser, targeted at developers. JBrowse Connect allows live messaging, notifications for new annotation tracks, heavy-duty analyses initiated by the user from within the browser, and other dynamic features. We present example applications of JBrowse Connect that allow users 1) to specify and execute BLAST searches by either running on the same host as the webserver, with a self-contained BLAST module leveraging NCBI Blast+ commands, or via a managed Galaxy instance that can optionally run on a different host, and 2) to run the primer design service Primer3. JBrowse Connect allows users to track job progress and view results in the context of the browser. The software is available under a choice of open source licenses including LGPL and the Artistic License.


Variables affecting eye tracking performance.
The effect of age and gender on eye tracking performance was studied in normal healthy subjects. Two measures of tracking performance, phase corrected cross-correlation coefficients and number of catch-up saccades were determined. The cross-correlation measures revealed a differential effect with the elderly men demonstrating significantly better tracking performance than elderly women. An aging effect was found in women and an aging trend in men using the catch-up saccade measure. Other variables influencing tracking performance, in addition to age and sex, were target speed and type of measure. Recognition of this differential effect largely explains the existing controversy as to whether age or sex variables influence tracking performance.


Variation over time of the factors influencing return to work and work capacities after a diagnosis of breast cancer: a study on the behalf of the Seintinelles research network.
To evaluate the dynamics of the determinants of returning to work (RTW) in a population of patients treated for breast cancer (BC) in a real-world setting. We conducted a retrospective study including 1278 BC patients working or looking for work at the time of diagnosis. We performed a focused principal component analysis to highlight the dimensions of a persistent decline in work capacity. Logistic regression analyses were performed to identify correlates of non-RTW 1 and 2 years after treatment. One-third (31%, n = 389) of patients continued working during treatment. At study inclusion, 1100 patients had returned to work (89%). Three-quarters (n = 508, 75%) of the women reported a decline in work capacity 1 year after RTW and 22% (n = 148) presented a persistent decline in work capacity 2 years after the diagnosis. The odds ratio for non-RTW at 1 year was significantly higher for patients treated with a combination of chemotherapy and trastuzumab (OR = 1.72, 95% CI [1.07-2.76]), manual workers (OR = 3.99, 95% CI [1.54-10.81]), patients with lower incomes (OR = 2.33, 95% CI [1.29-4.19]), and patients experiencing fatigue (OR = 1.81, 95% CI [1.34-2.48]). The odds ratio for non-RTW at 2 years was higher for various occupational categories (OR = 3.49, 95% CI [1.89-6.74] for clerks, OR = 4.58, 95% CI [1.48-12.82] for self-employed workers, OR = 8.98, 95% CI [2.69-27.89] for manual workers), patients with comorbidities (OR = 2.80, 95% CI [1.61-4.93]), and patients experiencing anxiety symptoms (OR = 2.54, 95% CI [1.18-5.76]), while the impact of the type of treatment was no longer significantly associated with RTW. The determinants of RTW change over time. Patients should be offered supportive interventions tailored to risk factors and time from diagnosis.


Nitric Oxide Scavenging and Hydrogen Sulfide Production Synergistically Treat Rheumatoid Arthritis.
To restore the disordered endogenous gas levels is an efficient alternative for the treatment of rheumatoid arthritis (RA). Both insufficient hydrogen sulfide (H2 S) and excessive nitric oxide (NO) contribute to synovial inflammation. Herein, a new block polymer PEG10 -b-PNAPA30 -b-PEG10 composed of an NO-responsive monomer and a cysteine-triggered H2 S donor, which can simultaneously scavenge NO and release therapeutic H2 S for RA treatment, is reported. In vitro experiments demonstrate that the polymer exhibits a synergistic effect on suppressing reactive oxygen species levels and pro-inflammatory cytokine production via NF-κB signaling pathway. It leads to the polarization of macrophages from M1 to M2 phenotype. Moreover, the released H2 S further restrains NO production by suppressing the expression of iNOS. In vivo experiments with an RA rat model show that the system markedly mitigates the synovial inflammation, osteoporosis, and clinical symptoms of RA rats, which is attributed to the combination therapy of H2 S release and NO depletion. This work provides new insight into the synergistic treatment of RA and endogenous gas-related diseases.


The 15-hydroxyprostaglandin dehydrogenase inhibitor SW033291 ameliorates abnormal hepatic glucose metabolism through PGE2-EP4 receptor-AKT signaling in a type 2 diabetes mellitus mouse model.
Type 2 diabetes mellitus (T2DM) is associated with high rates of morbidity and mortality worldwide. Prostaglandin E2 (PGE2) is a lipid signaling molecule that can ameliorate the symptoms of some metabolic diseases, including T2DM, and improve tissue repair and regeneration. Although SW033291 can increase PGE2 levels through its action as a small molecule inhibitor of the PGE2-degrading enzyme 15-hydroxyprostaglandin dehydrogenase, its effects on T2DM remain unclear. In the present study, we evaluated whether SW033291 treatment exerts a protective effect against T2DM and explored the underlying mechanisms. A T2DM mouse model was established using a high-fat diet combined with streptozotocin treatment. Palmitic acid-treated LO2 cells were used as an insulin-resistant cell model. SW033291 treatment reduced body weight and fasting blood glucose levels as well as serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels in vivo. In addition to ameliorating glucose and insulin tolerance, SW033291 treatment reversed the T2DM-induced decrease in glycogen synthesis and increase in gluconeogenesis in the liver. Furthermore, SW033291 administration increased hepatic glycogen synthase kinase 3 beta (GSK3β) phosphorylation levels to promote glycogen synthesis. SW033291 treatment also inhibited gluconeogenesis by upregulating AKT serine/threonine kinase (AKT) and forkhead box O1 (FOXO1) phosphorylation and reducing glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 expression in the livers of T2DM model mice. Additionally, SW033291 treatment improved abnormal hepatic glucose metabolism through the PGE2-EP4 receptor-AKT-GSK3β/FOXO1 signaling pathway in vitro. These results suggest a novel role of SW033291 in improving T2DM and support its potential as a novel therapeutic agent.


Flushing following interlaminar lumbar epidural steroid injection with dexamethasone.
Epidural steroid injections are commonly used in managing radicular pain. Most complications related to epidural injections are minor and self-limited. Flushing is considered as one such minor side effect. Flushing has been studied using various steroid preparations including methylprednisone, triamcinolone, and betamethasone but its frequency has never been studied using dexamethasone. This study evaluates the frequency of flushing associated with fluoroscopy-guided lumbar epidural steroid injections using dexamethasone. Retrospective cohort design study. Patients presenting with low back pain were evaluated and offered a fluoroscopically guided lumbar epidural steroid injection using dexamethasone via an interlaminar approach as part of a conservative care treatment plan. University-based Pain Management Center. All injections were performed consecutively over a 2-month period by one staff member using 16 mg (4 mg/mL) of dexamethasone. A staff physician specifically asked each participant about the presence of flushing following the procedure prior to discharge on the day of injection and again on follow-up within 48 hours after the injections. The answers were documented as "YES" or "NO." A total of 150 participants received fluoroscopically guided interlaminar epidural steroid injection. All participants received 16 mg (4 mg/mL) of dexamethasone with 2 mL of 0.2% ropiviciane. Overall incidence of flushing was 42 out of 150 cases (28%). Of the 42 participants who experienced flushing, 12 (28%) experienced the symptom prior to discharge following the procedure. Twenty-seven of the 42 (64%) were female (P < 0.05). All the participants who experienced flushing noted resolution by 48 hours. No other major side effects or complications were noted. Follow-up data were solely based on subjective reports by patients via telecommunication. Follow-up time was limited to only 48 hours, which overlooks the possibility that more participants might have noted flushing after the 48 hour limit. Flushing is commonly reported following epidural steroid injections. With an incidence of 28%, injections using dexamethasone 16 mg by interlaminar epidural route appear to be associated with more flushing reaction than previously reported with other steroid preparations. Additionally, female participants are more likely to experience flushing though the reactions seem to be self-limiting with resolution by 48 hours.


Development of a carcinogen-induced rat colon cancer with lymph-node metastases.
The progression from normal colonic mucosa to invasive adenocarcinoma of the colon with lymph-node metastases was documented in Sprague-Dawley rats receiving 30 mg of N-methyl-N-nitrosourea via intrarectal injections. Histologically, these tumors closely resemble human colonic cancer. This model is predictable and reproducible. It offers a genetically nonidentical rat model for the development of cancer biology and therapy models.


On not being able to read: doomscrolling and anxiety in pandemic times.
This article analyses 'doomscrolling', or the compulsive reading of anxiety-inducing online content during the COVID-19 pandemic, against the common idea that it is simply an addictive social practice that impedes mental flourishing. Instead, in order to open up its inclination towards care, I read doomscrolling through the anachronistic neologism that has come to define this specifically textual practice. Tracing the operations that doomscrolling and anxiety perform on lived time, the article uses the work of Eugène Minkowski, Sigmund Freud, Lauren Berlant, Walter Benjamin, and Lisa Baraitser to examine how these practices hope to take care of time when narratives of progressive history have worn thin. I include analyses of the anxious textuality of Don DeLillo's The Silence and Saidiya Hartman's reworking of W. E. B. Du Bois's 'The Comet' to demonstrate how doomscrolling emerges from a moment when trust is anxiously fractured, but how it works, nevertheless, to witness what gets to count when time is felt to be coming to an end.


Origin, evolution, and phylogeography of recent epidemic CHIKV strains.
Chikungunya virus (CHIKV) is an arthropod-borne virus of the Alphavirus genus, which is transmitted to humans by Aedes spp. mosquitoes and was firstly identified in Tanzania in the mid 1950s. In this article, the findings of a phylogenetic and phylogeographic analysis of the recent CHIKV pandemic are reported. We estimated time of origin of the ancestral virus, time and place of occurrence of A226V mutation, and the flow of viral strains from an area to the other. The Bayesian phylogenetic and phylogeographic analysis was performed on the whole dataset, which consisted of 195 E1 (envelope 1) CHIKV sequences, and on a subset (D2), including 146 of the 195 previous sequences. Using the relaxed clock model, we estimated a CHIKV E1 mean evolutionary rate (in the whole dataset) of 1.4 × 10(-3)substitution/site/year (95% highest posterior density interval HPD 6.4 × 10(-4)-2.5 × 10(-3)), and of 2.2 × 10(-3) (95% HPD 9.6 × 10(-4)-3.8 × 10(-3)) in the D2 subset, including only the strains involved in the recent Indian Ocean epidemic. The phylogeographical analysis suggested an African origin of CHIKV with a tMRCA of 146 years corresponding to 1863 (95% HPD 1741-1941). Moreover D2 subset most probably originated in Kenya, with a tMRCA corresponding to the year 2002 (95% HPD 2000-2004), then spread following two distinct routes: one throughout the Indian Ocean (Reunion, Comoros) and the other moving from India then scattered in the South East Asia and reached Italy. In conclusion, we reconstructed the geographic spread of CHIKV during the last epidemic wave, which showed an eastward path from Africa to Indian Ocean island to India, and from there to other South East Asian countries. Whether A226V variants followed the same migration path remains undefined, since local independent mutations, followed by fixation due to selective advantage conferred by better adaptation to local vectors of infection, cannot be excluded.


Tumor, tissue, and plasma pharmacokinetic studies and antitumor response studies of docetaxel in combination with 9-nitrocamptothecin in mice bearing SKOV-3 human ovarian xenografts.
We evaluated the antitumor activity of two different schedules of docetaxel and 9-nitrocamptothecin (9NC) in mice bearing human SKOV-3 ovarian carcinoma xenografts and evaluated the plasma, tissue, and tumor disposition of each agent alone and in combination. The following treatment groups were evaluated: (1) docetaxel 10 mg/kg IV on days 0 and 7; (2) 9NC 0.67 mg/kg PO qdx5dx2wk; (3) 9NC 0.67 mg/kg PO qdx5dx2wk in combination with docetaxel 10 mg/kg IV on days 0 and 7; and (4) 9NC 0.67 mg/kg PO qdx5dx2wk in combination with docetaxel 10 mg/kg IV on days 4 and 11; (5) vehicle controls for each agent; and (6) no treatment controls. All treatment regimens produced significant antitumor activity as compared with control groups (P < 0.05). Docetaxel administered on days 0 and 7 or on days 4 and 11 in combination with 9NC resulted in similar antitumor activity (P > 0.05). High docetaxel concentrations in tumor were maintained at late time points as compared with plasma and tissues with the retention of docetaxel at 24 h being 132-fold and 15-fold higher in tumor than in plasma and liver, respectively. After administration of 9NC alone, the ratio of the 9-aminocamptothecin (9AC) area under the concentration versus time curve (AUC) to 9NC AUC in plasma and tumor was 0.15 and 1.34, respectively. The combination of docetaxel and 9NC was effective against SKOV-3 xenografts. The lack of a difference in sequence-dependent antitumor activity may reflect the sensitivity of the SKOV-3 xenograft to 9NC. The factors associated with tumor-specific retention of docetaxel and the ratio of 9NC to 9AC in tumors is unknown.


Effects of floury-2 locus on zein accumulation and RNA metabolism during maize endosperm development.
Zein accumulation patterns during mutant and normal maize endosperm development were determined. Accompanying an increase in the number of floury-2 alleles present in the endosperm was a well-defined stepwise depression in zein accumulation. Analysis of the zein accumulated in endosperms containing zero, one, two, and three doses of the floury-2 allele by sodium dodecylsulfate--polyacrylamide gel electrophoresis revealed a proportionate reduction in the two major zein components, Z1 and Z2. In contrast, the relative proportions of the minor zein bands were altered. Membrane-bound polysomes isolated from kernels of floury-2 and normal maize were predominantly large size classes. The presence of increasing numbers of the floury-2 allele in the endosperm decreased recovery of membrane-bound polysomal material in a stepwise fashion. However, major alterations in polysome size-class distributions were not observed. The reduction in membrane-bound polysome material correlated linearly with reductions in in vitro zein synthesis and in vivo zein accumulation.


Characterisation of glycoforms of ascitic fluids in benign and malignant diseases.
To evaluate the differences in glycoforms of ascitic fluids which can be considered as useful in discrimination between benign and malignant patients. The investigations were carried out on 17 benign and 13 malignant patients. To obtain high molecular weight material, gel exclusion chromatography was applied. To evaluate the relative amounts of different glycoforms, ELISA tests with biotinylated lectins were used. The fucosylation pattern was found to be similar in malignant and benign group. Fucose linked by alpha 1-6 bond was the most abundant structure. Sialylation was found to be more typical for malignant patients. Alpha 2-6 bond was observed on higher level than alpha 2-3 linkage. T and Tn antigens were present on rather low level with a slight prevalence of T antigen in malignant group. The glycoforms recognized by DSA lectin were more numerous in benign patients. The evaluation of the level of some ascitic fluids glycoforms can be useful in differentiation between malignant and benign diseases.


Stimulation of the healing of experimental colon anastomoses by low-power lasers.
Anastomotic leakage following colorectal surgery remains a complication with high mortality and morbidity. Recent studies suggest that helium-neon (He-Ne) lasers at specific energy densities can be used to enhance wound healing in different tissues. In this experimental study we have tested the strength of end-to-end anastomosis of the rat colon irradiated by He-Ne laser by measuring bursting pressures and bursting wall tensions at 2, 4 and 7 days after operation. The study shows that He-Ne laser radiation induces a significant increase in colonic strength at the anastomosis. The laser does not cause the luminal narrowing observed in non-irradiated specimens.


Language and verbal fluency outcome after bilateral subthalamic Nucleus Deep Brain Stimulation in Parkinson's disease.
Language disorders in Parkinson's Disease (PD) following bilateral subthalamic Nucleus Deep Brain Stimulation (STN-DBS) are common. To assess STN-DBS impact on language and observe clinical and anatomical predictors of poor outcome. We prospectively included PD patients undergoing STN-DBS. We performed a neuropsychological evaluation focusing on language before (V0), 3 days after (V1), and 3 months after (V2) surgery. Patients performed all assessments in ON drug condition, V1 with the stimulation turned OFF to evaluate the lesion effect, and V2 with the stimulation turned ON to evaluate the stimulation effect. Electrodes and active contact locations were determined with MRI-Atlas fusion. The stimulation parameters and the total electrical energy delivered (TEED) were recorded for each patient. 18 PD patients consecutively operated were included. We identified a decline in phonemic verbal fluency (VFP) at V1 and V2 (p = 0.023 and 0.032 respectively), as well as in semantic verbal fluency (VFS) (p = 0.025 and 0.019, respectively). There was a significant slowdown in the verbs naming test (p = 0.048). No other language alteration was recorded. There was no correlation between demographic or clinical factors and verbal fluency (VF) evolution. Active contact location within substantia nigra was associated with VFP worsening (p = 0.047), while elevated TEED on the left-sided electrode was associated with VFS decline (p = 0.021). VF was significantly altered following STN-DBS. Location outside the dorsolateral sensorimotor STN, and high stimulation power appeared to promote this decline. Other language domains remained stable.


Inborn errors of copper metabolism.
Two copper-transporting ATPases are essential for mammalian copper homeostasis: ATP7A, which mediates copper uptake in the gastrointestinal tract and copper delivery to the brain, and ATP7B, which mediates copper excretion by the liver into bile. Mutations in ATP7A may cause three distinct X-linked conditions in infants, children, or adolescents: Menkes disease, occipital horn syndrome (OHS), and a newly identified allelic variant restricted to motor neurons called X-linked distal hereditary motor neuropathy. These three disorders show variable neurological findings and ages of onset. Menkes disease presents in the first several months of life with failure to thrive, developmental delay, and seizures. OHS features more subtle developmental delays, dysautonomia, and connective tissue abnormalities beginning in early childhood. ATP7A-related distal motor neuropathy presents even later, often not until adolescence or early adulthood, and involves a neurological phenotype that resembles Charcot-Marie-Tooth disease, type 2. These disorders may be treatable through copper replacement or ATP7A gene therapy. In contrast, mutations in ATP7B cause a single known phenotype, Wilson disease, an autosomal recessive trait that results from copper overload rather than deficiency. Dysarthria, dystonia, tremor, gait abnormalities, and psychiatric problems may be presenting symptoms, at ages from 10 to 40 years. Excellent treatment options exist for Wilson disease, based on copper chelation. In the past 2 years (2012-2013), three new autosomal recessive copper metabolism conditions have been recognized: 1) Huppke-Brendel syndrome caused by mutations in an acetyl CoA transporter needed for acetylation of one or more copper proteins, 2) CCS deficiency caused by mutations in the copper chaperone to SODI, and 3) MEDNIK syndrome, which revealed that mutations in the σ1A subunit of adaptor protein complex 1 (AP-1) have detrimental effects on trafficking of ATP7A and ATP7B.


A meta-regression of the impact of policy on the efficacy of individual placement and support.
Individual placement and support (IPS) has shown consistently better outcomes on competitive employment for patients with severe mental illness than traditional vocational rehabilitation. The evidence for efficacy originates from few countries, and generalization to different countries has been questioned. This has delayed implementation of IPS and led to requests for country-specific RCTs. This meta-analysis examines if evidence for IPS efficacy can be generalized between rather different countries. A systematic search was conducted according to PRISMA guidelines to identify RCTs. Overall efficacy was established by meta-analysis. The generalizability of IPS efficacy between countries was analysed by random-effects meta-regression, employing country- and date-specific contextual data obtained from the OECD and the World Bank. The systematic review identified 27 RCTs. Employment rates are more than doubled in IPS compared with standard vocational rehabilitation (RR 2.07 95% CI 1.82-2.35). The efficacy of IPS was marginally moderated by strong legal protection against dismissals. It was not moderated by regulation of temporary employment, generosity of disability benefits, type of integration policies, GDP, unemployment rate or employment rate for those with low education. The evidence for efficacy of IPS is very strong. The efficacy of IPS can be generalized between countries.


Reversible inactivation of the median raphe nucleus enhances consolidation and retrieval but not acquisition of passive avoidance learning in rats.
Involvement of median raphe nucleus (MRN) in acquisition, consolidation and retrieval of passive avoidance (PA) was investigated with functional suppression of this area by lidocaine. Rats carrying a chronically implanted cannula aimed at the MRN were trained on a step-through passive avoidance task and received intra-MRN injection of lidocaine or saline 5 min before training or 5, 90 and 360 min after acquisition trial or 5 min before the retrieval test. Lidocaine MRN inactivation had no effect on PA learning. Lidocaine injected 5 and 90 min after the acquisition trial significantly enhanced avoidance of the dark compartment in comparison with the control group injected with saline. But PA retention was not affected by lidocaine injected 360 min after acquisition or 5 min before training. Retention latency significantly increased, when lidocaine injected 5 min before retrieval test. Step-through latency of naive rats was not affected by MRN blockade. Furthermore, reversible inactivation of MRN did not have a significant effect on locomotor activity. Our results indicate that the MRN contributes to PA consolidation at least until 90 min after acquisition and involves in PA retrieval. It is concluded that functional ablation of the MRN may disrupt the inhibitory actions of MRN projections to sub-cortical circuits participating in PA memorization and retrieval.


Protein damage and repair controlling seed vigor and longevity.
The formation of abnormal isoaspartyl residues derived from aspartyl or asparaginyl residues is a major source of spontaneous protein misfolding in cells. The repair enzyme protein L: -isoaspartyl methyltransferase (PIMT) counteracts such damage by catalyzing the conversion of abnormal isoaspartyl residues to their normal aspartyl forms. Thus, this enzyme contributes to the survival of many organisms, including plants. Analysis of the accumulation of isoaspartyl-containing proteins and its modulation by the PIMT repair pathway, using germination tests, immunodetection, enzymatic assays, and HPLC analysis, gives new insights in understanding controlling mechanisms of seed longevity and vigor.


An investigation of the relationship between fear of negative evaluation and bulimic psychopathology.
The current study examined fear of negative evaluation (FNE), the core fear associated with social anxiety, in the context of the dual pathway model of the etiology of bulimia nervosa. Our primary aim was to improve the understanding of the development of bulimic psychopathology. We investigated the relationships between FNE, the risk factors of the dual pathway model and bulimic symptoms using path analysis in a sample of female undergraduates (N=210). The inclusion of FNE increased the predictive ability of the model to account for 49% of the variance in bulimic symptoms compared to previous findings in which the model accounted for 33% of the variance. Additionally, FNE was related to several risk factors of the dual pathway model including the pressure to be thin, thin-ideal internalization and negative affect, as well as contributing directly to bulimic symptoms. These findings suggest that FNE may increase the risk for developing established risk factors of the model, as well as bulimic symptoms, and that targeting FNE in prevention programs may be useful in circumventing this serious disorder.


Scan optimization of gadolinium contrast-enhanced three-dimensional MRA of peripheral arteries with multiple bolus injections and in vitro validation of stenosis quantification.
In this study, a T1-weighted three-dimensional (3D) spoiled gradient-echo scanning protocol was developed to image the complete arterial system of the pelvis and both legs along their entire length in patients with peripheral arterial disease. Three adjacent stations were to be acquired consecutively, with some overlap, to image the entire area of interest; per station one gadolinium (Gd) contrast bolus would be administered. In an in vitro phantom study, the scanning protocol was optimized. The optimal flip angle was found to be 50 degrees. Also, the optimal scan delay was chosen to be equal to the arrival time of the contrast bolus, thereby minimizing artifacts. Three contrast bolus injections showed sufficient enhancement of the vessels after image subtraction. Finally, stenosis quantification by manual caliper was performed by five observers in the magnetic resonance angiography (MRA) images and correlated with the percent diameter reduction determined by quantitative angiography from corresponding X-ray images. The MRA measurements were reproducible, and intra- and interobserver variabilities were statistically non-significant (p=0.54 and p=0.12, respectively). Stenosis quantification performed by four observers showed a good correlation with the X-ray-derived values (rp > 0.90, p < 0.02); the results from one observer were not significantly correlated. Five patients with proven peripheral disease were investigated with this new MRA scanning protocol, using standard hardware and software. The images were of good quality, which allowed adequate clinical evaluation; the original diagnoses obtained from X-ray examinations, were confirmed with MRA. In conclusion, peripheral arterial disease can be evaluated adequately with this magnetic resonance scanning protocol.


Acetyl Salicylic Acid Challenge in Children with Hypersensitivity Reactions to Nonsteroidal Anti-Inflammatory Drugs Differentiates Between Cross-Intolerant and Selective Responders.
Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in children are becoming a great concern. Most studies have focused on adults, with noted discrepancies observed in the classification of hypersensitivity reactions to NSAIDs in children when compared with adults. To phenotype a group of children with hypersensitivity reactions to NSAIDs, including paracetamol, and analyze the degree of agreement with the entities reported in adults and how they fit the proposed classifications. The study comprised 116 children aged 0.5 to 14 years, with a clinical history indicative of hypersensitivity reactions to NSAIDs. They all underwent a single-blind oral provocation test with acetyl salicylic acid, except in those cases when this was the suspected drug, in which case the challenge was done first with ibuprofen. If positive, cross-intolerance was established and if negative, an oral provocation test with the culprit drug was performed to establish a selective response or exclude allergy. Of the 26% diagnosed as hypersensitive to NSAIDs, 83% were cross-intolerant and 17% selective reactors. The highest significant differences between reactors and nonreactors were observed in the time to reaction after drug intake and the clinical entity (P < .0001), followed by drug involved and age (P < .01). From the total number of cases confirmed with NSAID hypersensitivity, 83% were cross-intolerant. In cross-intolerant reactions, both cutaneous and respiratory manifestations are common. Acetyl salicylic acid challenge as the first approach proved to be safe and useful to establish the diagnosis.


Induction of neuronal and myelin-related gene expression by IL-6-receptor/IL-6: a study on embryonic dorsal root ganglia cells and isolated Schwann cells.
The conditional knockdown of the Interleukin-6 (IL-6) family signal transducer (gp130) causes peripheral nerve demyelination and degeneration. In the present work, we investigated the effect of gp130 signaling on peripheral nerves and Schwann cells (SC). We stimulated gp130 signaling with IL6RIL6, a fusion molecule of IL-6 and IL-6R, in rat embryonic day 14 dorsal root ganglia (DRG) cell cultures. In neurons, IL6RIL6 strongly increased the axonal network. In SC, IL6RIL6 favored the appearance of elongated more mature cells versus stellar shaped cells. Gene expression profiling showed an increased expression of neuronal and glial-specific genes. mRNAs related to SC function, including myelin-specific genes, were increased by IL6RIL6 treatment of DRG cells, or of purified SCs isolated from rat sciatic nerve. In IL6RIL6-treated cells, immunostaining showed a strong nuclear signal for Krox-20, a transcription factor essential for differentiation of the SC lineage. On the contrary, we observed that IL6RIL6 inhibited the genes related to TGF-beta family as well as the production of smooth muscle actin.


Combined correction of an adult scimitar syndrome and coronary artery bypass grafting.
Combined scimitar syndrome and coronary artery disease is a rare combination of congenital and acquired cardiac disease in adults. Hence, no guidelines for surgical correction are available. We report on the case of a 60-year-old man with coronary artery disease and scimitar syndrome. The patient underwent arterial coronary revascularization and simultaneous correction of the scimitar syndrome utilizing a new surgical approach with a modified pericardium-baffle reconstruction of the anomalous right pulmonary vein.


Toll-like receptor 2-independent host innate immune response against an epidemic strain of Streptococcus suis that causes a toxic shock-like syndrome in humans.
Streptococcus suis is an emerging zoonotic agent causing meningitis and septicemia. Outbreaks in humans in China with atypical cases of streptococcal toxic shock-like syndrome have been described to be caused by a clonal epidemic S. suis strain characterized as sequence type (ST) 7 by multilocus sequence typing, different from the classical ST1 usually isolated in Europe. Previous in vitro studies showed that Toll-like receptor (TLR) 2 plays a major role in S. suis ST1 interactions with host cells. In the present study, the in vivo role of TLR2 in systemic infections caused by S. suis ST1 or ST7 strains using TLR2 deficient (TLR2(-/-)) mice was evaluated. TLR2-mediated recognition significantly contributes to the acute disease caused by the highly virulent S. suis ST1 strain, since the TLR2(-/-) mice remained unaffected when compared to wild type (WT) mice. The lack of mortality could not be associated with a lower bacterial burden; however, a significant decrease in the induction of pro-inflammatory mediators, as evaluated by microarray, real-time PCR and protein assays, was observed. On the other hand, TLR2(-/-) mice infected with the epidemic ST7 strain presented no significant differences regarding survival and expression of pro-inflammatory mediators when compared to the WT mice. Together, these results show a TLR2-independent host innate immune response to S. suis that depends on the strain.


3D Janus structure MXene/cellulose nanofibers/luffa aerogels with superb mechanical strength and high-efficiency desalination for solar-driven interfacial evaporation.
Interfacial solar steam generation (ISSG) is considered to be an attractive technique to address the water shortage. However, developing a sustainable thermal management, salt rejection, and excellent mechanical strength ISSG device for long-term stability desalination is still a challenge. Herein, a biomass ISSG device with superb mechanical properties was prepared by introducing a luffa sponge as the skeleton and constructing the MXene/cellulose nanofibers (CNFs) aerogels via freeze-drying. The Janus MXene-decorated CNFs/luffa (JMCL) aerogels integrated the multifunction of fast water transport, good thermal management, and efficient photothermal conversion in a single module, to achieve high-efficiency desalination. 3D Janus structure endowed the JMCL aerogel with opposite wettability, which is feasible to construct the localized photothermal generation and self-floating. The mechanical strength of JMCL aerogels is 437 times that of MXene/CNFs aerogels. The JMCL aerogels delivered a water evaporation rate of 1.40 kg m-2h-1 and an efficiency of 91.20% under 1 sun illumination. The excellent salt resistance during 24 h working and long-term solar vapor generation of up to 28 days were achieved. The multifunctional JMCL aerogels with 3D Janus structure offer new insights for developing good durability and eco-friendly biopolymer-based steam generators.


Mood phenotypes in rodent models with circadian disturbances.
Many physiological functions with approximately 24-h rhythmicity (circadian rhythms) are generated by an internal time-measuring system of the circadian clock. While sleep/wake cycles, feeding patterns, and body temperature are the most widely known physiological functions under the regulation of the circadian clock, physiological regulation by the circadian clock extends to higher brain functions. Accumulating evidence suggests strong associations between the circadian clock and mood disorders such as depression, but the underlying mechanisms of the functional relationship between them are obscure. This review overviews rodent models with disrupted circadian rhythms on depression-related responses. The animal models with circadian disturbances (by clock gene mutations and artifactual interventions) will help understand the causal link between the circadian clock and depression.


Determination of Cd, Co, Ni and Pb in biological samples by microcolumn packed with black stone (Pierre noire) online coupled with ICP-OES.
A simple and sensitive method using microcolumn (20-mm length x 2.0-mm i.d.) packed with black stone (Pierre noire) for the separation/preconcentration of Cd, Co, Ni and Pb in biological samples prior to their online determination by inductively coupled plasma optical emission spectrometry (ICP-OES) has been developed. Optimal experimental conditions including pH, eluent concentration and volume, sample volume and sample flow rate were investigated and established. The adsorption capacity of black stone for Cd, Co, Ni and Pb were found to be 23.4, 21.2, 18.1 and 22.2 mg g(-1), respectively. With a preconcentration time of 72 s and an elution time of 4s, an enrichment factor of 20 and a sampling frequency of 25 h(-1) were obtained. The detection limits corresponding to three times the standard deviations of the blank for Cd, Co, Ni and Pb were found to be 0.3, 0.4, 0.4 and 1.1 ng mL(-1). The precision for seven replicate determinations of Cd, Co, Ni and Pb gave relative standard deviations (RSDs) of 5.9, 4.8, 2.7 and 1.1%, respectively (n=7, C=10 ng mL(-1)). The method was validated with certified reference material GBW09103 human urine and the results obtained were in good agreement with the certified values. The method was also applied to the determination of the target analytes in biological samples with satisfactory results.


Evaluation of genotoxicity and effects on reproduction of nonylphenol in Oreochromis niloticus (Pisces: Cichlidae).
Nonylphenol ethoxylate (NPE) is widely used as a component of detergents, paints, pesticides, and many other products. In the aquatic environment NPE breakdown to 4-nonylphenol (NP), which is more stable and persistent. NP is estrogenic in fish, avian, and mammals and is described as an environmental pollutant with endocrine disruptor characteristics. The genotoxicity of NP was evaluated through micronuclei assay and single cell gel electrophoresis (Comet assay) in peripheral erythrocytes of Oreochromis niloticus exposed in vivo. The study on reproductive development was also carried out in male and female gonads of O. niloticus. Lethal concentration (LC 50%) of 0.032 ml l(-1) was previously determined. We ran assays with O. niloticus exposed to concentrations of 1.0, 10.0, and 16.0 microl l(-1) of NP diluted in water. Our results showed that NP was not genotoxic. However, 3-day exposure to NP in concentrations of 1.0, 10.0, and 16.0 microl l(-1) of water increased the frequency of reproductive stages in males and females. The histology of the reproductive tract of the treated fish was significantly altered in females treated with 16.0 microl l(-1) of water when compared to controls. Analogous estrogenic effects were observed, such as accelerated maturation of oocytes and spermatogenesis. These results showed that the O. niloticus reproductive system is sensitive to NP estrogenicity.


Relationships between the changes in compound muscle action potentials and selective injuries to the spinal cord and spinal nerve roots.
Compound muscle action potentials (CMAPs) evoked by transcranial electrical stimulation have been widely introduced to monitor motor function during spinal surgery. They may reflect segmental injuries as well as injuries to motor-related tracts in the spinal cord. However, we have experience with some patients who developed postoperative segmental motor weakness without any potential changes during surgery. To evaluate the efficacy of this method, we used a cat model to observe the relationships between potential changes and selective injuries to the white and gray matters of the spinal cord and spinal nerve roots. Ten CMAPs were obtained before and after injury to the spinal cord and spinal nerve roots in 20 cats. Changes in the amplitude, latency, and duration of CMAPs were analyzed. CMAPs decreased in amplitude significantly after the insult to the motor-related tracts in the spinal cord in all cats, while the potentials did not always change when the insult was restricted to a limited area in the anterior horn of the spinal cord or to the single spinal nerve root. CMAPs may not exactly reflect segmental injury, and careful attention should be paid to the interpretation of CMAPs.