The influence of lymphangiography on the development of hypothyroidism in patients irradiated for Hodgkin's disease.
There is no consensus in the literature regarding the role of lymphangiography in promoting hypothyroidism in individuals with Hodgkin's disease irradiated with a mantle field. We sought to analyze the onset and rate of developing clinical or chemical hypothyroidism as well as possible factors related to its development in patients who received irradiation to the thyroid gland during treatment of Hodgkin's disease. One hundred and forty-two patients with Hodgkin's disease were treated at the Fox Chase Cancer Center between June 1967 and October 1993. All patients were treated with curative intent with radiation therapy using a mantle field. After exclusion of patients without available thyroid function tests, < 200 days of follow-up, or no radiation to the thyroid, 104 patients were eligible for analysis. Follow-up ranged from 7-170 months (median: 43 months). Sixty-seven patients had a lymphangiogram. Seventy-three patients were treated with radiation alone and 31 with radiation plus chemotherapy. The actuarial 2-, and 5-year rates of biochemical hypothyroidism for all 104 patients were 18 and 37%, respectively. Forty patients developed hypothyroidism: 9 (23%) at < or = 1 year, 18 (45%) at < or = 2 years, and 33 (83%) at < or = 5 years. The actuarial 2-, and 5-year rates of biochemical hypothyroidism for patients who underwent a lymphangiogram were 23 and 42%, respectively, compared to 9 and 28%, respectively, for patients who received mantle irradiation without a lymphangiogram (p = 0.05). The effects of lymphangiogram, total thyroid dose, stage, chemotherapy, dose per fraction, energy, and age were evaluated for all patients by Cox proportional hazards regression analysis. The use of a lymphangiogram (p = 0.05) was the only variable that significantly influenced hypothyroidism. This paper demonstrates in a multivariate analysis accounting for other potentially important variables the significant effect of lymphangiography and subsequent radiation therapy on the development of hypothyroidism. This information must be balanced with the fact that lymphangiograms remain a useful aid in assessing lymph node involvement, staging patients, and planning treatment fields.


An experience sampling study on the links between daily teacher self-efficacy, need-supportive teaching and student intrinsic motivation.
Why are some teachers more successful at motivating students than others? We know from previous literature that teachers' self-efficacy relates to the extent in which they engage in need-supportive teaching in the classroom, which in turn relates to student intrinsic motivation. However, teachers' self-efficacy is hypothesized to be dependent on their previous mastery experiences, e.g., of engaging students in the classroom. This "feedback loop" where the teacher not only influences the student but also the other way around, in a process unfolding over time, can only be investigated empirically with an intensive longitudinal design. This is precisely what we did in the current study. Secondary school teachers (n = 4) and students (n = 90) participated in an experience sampling study throughout one school year, resulting in a unique dataset with 48-59 repeated measurement points per class. Visual exploration of the time series revealed that teacher self-efficacy can vary substantially from lesson to lesson, with characteristic patterns of stabilization and de-stabilization. We conducted Vector Autoregressive Analysis (VAR) for each of the four cases to test whether, and how, the variables relate to each other over time. We found an "overspill effect" for student motivation, meaning that students' motivation in today's lesson predicts their motivation in tomorrow's lesson. Furthermore, in two cases we found that today's student motivation predicts tomorrow's teacher self-efficacy, but not the other way around.


Improvement in albuminuria in patients with type 2 diabetes after laparoscopic adjustable gastric banding.
To determine the effects of laparoscopic adjustable gastric banding (LAGB) on albuminuria in patients with obesity, type 2 diabetes mellitus (T2DM) and established diabetic nephropathy. A retrospective analysis of clinical records from a tertiary diabetes service identified obese patients with T2DM who had micro- or macroalbuminuria prior to LAGB surgery. Clinical data from follow-up appointments including albuminuria were analysed. A total of 23 T2DM patients were included in the final study. Of 7 patients with macroalbuminuria at baseline, 2 reverted to normoalbuminuria, 2 reverted to microalbuminuria and 3 remained with macroalbuminuria on their final recording in the 36-month period of follow-up. Of 16 patients with microalbuminuria, 9 reverted to normoalbuminuria, while 6 remained with microalbuminuria. This study demonstrates significant improvements in albuminuria in patients with established diabetic nephropathy following LAGB. These results suggest the potential for LAGB to improve or reverse renal damage in patients with T2DM.


Eye movement dysfunction in first-degree relatives of patients with schizophrenia: a meta-analytic evaluation of candidate endophenotypes.
Several forms of eye movement dysfunction (EMD) are regarded as promising candidate endophenotypes of schizophrenia. Discrepancies in individual study results have led to inconsistent conclusions regarding particular aspects of EMD in relatives of schizophrenia patients. To quantitatively evaluate and compare the candidacy of smooth pursuit, saccade and fixation deficits in first-degree biological relatives, we conducted a set of meta-analytic investigations. Among 18 measures of EMD, memory-guided saccade accuracy and error rate, global smooth pursuit dysfunction, intrusive saccades during fixation, antisaccade error rate and smooth pursuit closed-loop gain emerged as best differentiating relatives from controls (standardized mean differences ranged from .46 to .66), with no significant differences among these measures. Anticipatory saccades, but no other smooth pursuit component measures were also increased in relatives. Visually-guided reflexive saccades were largely normal. Moderator analyses examining design characteristics revealed few variables affecting the magnitude of the meta-analytically observed effects. Moderate effect sizes of relatives v. controls in selective aspects of EMD supports their endophenotype potential. Future work should focus on facilitating endophenotype utility through attention to heterogeneity of EMD performance, relationships among forms of EMD, and application in molecular genetics studies.


Potential effects of decreased cervical cancer screening participation after HPV vaccination: an example from the U.S.
A concern with widespread implementation of HPV vaccination programs is that women may mistakenly decide that they do not need to be screened any longer, and thus be less likely to participate in cervical cancer screening, because they view themselves to be at low-risk of developing cervical cancer. We hypothesized that non-participation in screening among vaccinated young women in the 5 years following vaccination may result in missed CIN 2-3 cases that could progress to cancer. For instance, if 50% fewer women 26-30 years old, who were vaccinated, participate in screening in the United States over a 5 year time horizon, there would be approximately 4 women (per 1000) with missed CIN 2-3. On the other hand, non-participation will reduce the number of false-positive screening test results, as non-participation would avoid approximately 27 false-positive test results, with a decrease in follow-up procedures and costs. These results highlight the importance of educating women to ensure continued screening, as well as the need to consider new approaches to screening in the era of vaccination.


Isolation and Preparation of Bone Marrow-Derived Immune Cells for Metabolic Analysis.
The isolation of immune cells from the bone marrow is important for obtaining sufficient numbers for downstream analysis. Immune cells derived from the bone marrow may be subjected to metabolic assays for analysis or used to test the effect of infectious agents on immune cells. Here, we describe a process for the isolation of macrophages, dendritic cells, and neutrophils from mice. Using the methods described herein, specific immune cells with purity above 85-90% can be obtained from the bone marrow of mice.


Fully automated pixel-wise quantitative CMR-myocardial perfusion with CMR-coronary angiography to detect hemodynamically significant coronary artery disease.
We applied a fully automated pixel-wise post-processing framework to evaluate fully quantitative cardiovascular magnetic resonance myocardial perfusion imaging (CMR-MPI). In addition, we aimed to evaluate the additive value of coronary magnetic resonance angiography (CMRA) to the diagnostic performance of fully automated pixel-wise quantitative CMR-MPI for detecting hemodynamically significant coronary artery disease (CAD). A total of 109 patients with suspected CAD were prospectively enrolled and underwent stress and rest CMR-MPI, CMRA, invasive coronary angiography (ICA), and fractional flow reserve (FFR). CMRA was acquired between stress and rest CMR-MPI acquisition, without any additional contrast agent. Finally, CMR-MPI quantification was analyzed by a fully automated pixel-wise post-processing framework. Of the 109 patients, 42 patients had hemodynamically significant CAD (FFR ≤ 0.80 or luminal stenosis ≥ 90% on ICA) and 67 patients had hemodynamically non-significant CAD (FFR ˃ 0.80 or luminal stenosis < 30% on ICA) were enrolled. On the per-territory analysis, patients with hemodynamically significant CAD had higher myocardial blood flow (MBF) at rest, lower MBF under stress, and lower myocardial perfusion reserve (MPR) than patients with hemodynamically non-significant CAD (p < 0.001). The area under the receiver operating characteristic curve of MPR (0.93) was significantly larger than those of stress and rest MBF, visual assessment of CMR-MPI, and CMRA (p < 0.05), but similar to that of the integration of CMR-MPI with CMRA (0.90). Fully automated pixel-wise quantitative CMR-MPI can accurately detect hemodynamically significant CAD, but the integration of CMRA obtained between stress and rest CMR-MPI acquisition did not provide significantly additive value. • Full quantification of stress and rest cardiovascular magnetic resonance myocardial perfusion imaging can be postprocessed fully automatically, generating pixel-wise myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) maps. • Fully quantitative MPR provided higher diagnostic performance for detecting hemodynamically significant coronary artery disease, compared with stress and rest MBF, qualitative assessment, and coronary magnetic resonance angiography (CMRA). • The integration of CMRA and MPR did not significantly improve the diagnostic performance of MPR alone.


Single versus double hamstring tendon graft in anterior cruciate ligament reconstruction in the paediatric patient: a single-blind randomised controlled trial study protocol.
There is currently no clear indication in the literature regarding a single or double hamstring tendon (single bundle) autograft for anterior cruciate ligament (ACL) reconstruction in the paediatric patient. The primary aim of this single blind randomised controlled trial is to determine whether a single or double hamstring tendon graft ACLR leads to superior clinical outcomes postsurgery in paediatric patients with ACL injury. Single site, prospective, single blind, randomised controlled trial with two parallel treatment arms. 100 patients aged 10-18 years who present with an isolated ACL tear±meniscal injury, verified on MRI, will be randomly allocated to one of the two surgical groups. The primary outcomes will be side-to-side difference in anterior tibial translation and graft failure incidence 12 months postsurgery. Primary and secondary outcomes will also be assessed at 2-year and 5-year postsurgery. Results will be presented in peer-reviewed journals and at international conferences and disseminated to participants and healthcare professionals via newsletters and hospital presentations. This study is approved by the Children's Health Queensland Hospital and Health Service Human Research Ethics committee. ACTRN12620001170910p; Australian New Zealand Clinical Trials Registry.


Brain lactate during partial global ischemia and reperfusion: effect of pretreatment with dichloroacetate in a rat model.
Elevated cerebral lactate levels following cerebral ischemia have been associated with brain cell damage and death. We previously found that pre- or postischemia treatment with dichloroacetate (DCA), presumably by its activation of brain pyruvate dehydrogenase, effectively lowers cerebral lactate levels in rats subjected to 30 minutes of partial global ischemia (PGI) followed by 30 minutes of recirculation. The goal of the present study was to determine the effects of preischemia DCA treatment on cortical lactate levels during the ischemia period or during early recirculation. Rats (four in each group) received preischemia treatment with DCA and were then subjected to 0, 10, or 30 minutes of PGI or 30 minutes of PGI followed by 15 minutes of recirculation. Cortical lactate levels in pretreated animals were not significantly different from lactate levels of untreated rats at any time during PGI, but were significantly lower than levels in untreated rats at 15 minutes of recirculation (P less than .05, ANOVA). These results suggest that preischemia treatment with DCA does not limit the accumulation of cortical lactate during PGI but may promote its clearance during recirculation following PGI. If reperfusion events influence the degree of brain cell injury, DCA may enhance cell recovery by lower cortical lactate levels in the reperfusion period.


Comparison of segmented polyether urethane with polyethylene IUDs in rabbits.
A segmented polyether urethane IUD was compared with a polyethylene IUD in rabbits. The contraceptive efficacy of urethane IUDs was excellent. Moreover, the purulent slippery deposit present with the polyethylene IUDs and observed by Davis et al. (1) was absent. Our studies indicate that the polyether urethane IUDs have a high degree of antifertility activity in rabbits and these IUDs have reduced inflammatory response, based on leucocytic infiltration and tissue debris in the uterine lumen. It is suggested that polyether urethane IUDs not requiring copper or other medication can be designed for high contraceptive efficacy, intrauterine compatibility and with the necessary rigidity for proper uterine retention in humans.


Effect of microbial sanitizers for reducing biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa on stainless steel by cultivation with UHT milk.
Biofilm is a serious issue in the dairy factory due to it increases the opportunity for microbial contamination. Staphylococcus aureus and Pseudomonas aeruginosa are the bacteria capable to construct the biofilm on materials and equipments. Therefore, the bacterial growth and efficiency of sanitizing agents to solve the problems were evaluated. These bacteria grew well in UHT milk when they were cultivated at 37 °C, especially S. aureus. The exponential growth phase and biofilm on stainless steel were discovered by short contact time at 2 h. The mature stage of biofilm cycle was found at 4 h during bacteria growth and it was continuously constructed until 48 h. The 10, 24, and 48 h-old biofilm adhering on stainless steel were established with oxisan and chlorine used as microbial sanitizers. The 4% of sanitizing agents was the efficiency concentration to reduce biofilm on stainless steel up to 82% when these bacteria grew in UHT milk.


Determination of nanomolar dissolved sulfides in water by coupling the classical methylene blue method with surface-enhanced Raman scattering detection.
In this study, we proposed a novel method for the determination of nanomolar dissolved sulfides, including H2S, HS-, and S2- (defined as S(-II)) in water by coupling the classical methylene blue (MB) method with surface-enhanced Raman spectroscopy (SERS) detection. Overall, the following analytical procedures were employed: i) precipitation of S(-II) as zinc sulfide, ii) centrifugation to collect zinc sulfide, iii) derivatization of S(-II) to MB by the reaction with N, N-dimethyl-p-phenylenediamine in the presence of FeCl3 under acidic conditions, and iv) SERS detection. Parameters affecting the derivatization and SERS detection were optimized. Under the optimized conditions, a linear range of 12.3 nmol/L-200 nmol/L for S(-II) was obtained with a correlation coefficient (R2) of 0.99. Limits of detection and quantification of the developed method were estimated to be 3.7 nmol/L and 12.3 nmol/L, respectively. In addition, the proposed method demonstrated excellent tolerance to coexisting substances, such as NO2-, NO3-, SO32-, and other common ions. The proposed method demonstrates immense promise for the determination of nanomolar S(-II) in surface waters and wastewater.


Evidence for horizontal transfer of Wolbachia by a Drosophila mite.
Mites are common ectoparasites of Drosophila and have been implicated in bacterial and mobile element invasion of Drosophila stocks. The obligate endobacterium, Wolbachia, has widespread effects on gene expression in their arthropod hosts and alters host reproduction to enhance its survival and propagation, often with deleterious effects in Drosophila hosts. To determine whether Wolbachia could be transferred between Drosophila melanogaster laboratory stocks by the mite Tyrophagus putrescentiae, mites were introduced to Wolbachia-infected Drosophila vials. These vials were kept adjacent to mite-free and Wolbachia-uninfected Drosophila stock vials. The Wolbachia infection statuses of the infected and uninfected flies were checked from generation 1 to 5. Results indicate that Wolbachia DNA could be amplified from mites infesting Wolbachia-infected fly stocks and infection in the previously uninfected stocks arose within generation 1 or 2, concomitant with invasion of mites from the Wolbachia-infected stock. A possible mechanism for the transfer of Wolbachia from flies to mites and vice versa, can be inferred from time-lapse photography of fly and mite interactions. We demonstrated that mites ingest Drosophila corpses, including Wolbachia-infected corpses, and Drosophila larva ingest mites, providing possible sources of Wolbachia infection and transfer. This research demonstrated that T. putrescentiae white mites can facilitate Wolbachia transfer between Drosophila stocks and that this may occur by ingestion of infected corpses. Mite-vectored Wolbachia transfer allows for rapid establishment of Wolbachia infection within a new population. This mode of Wolbachia introduction may be relevant in nature as well as in the laboratory, and could have a variety of biological consequences.


Retinal microvascular dysfunction in hypercholesterolemia.
Hypercholesterolemia is one of the most important contributors to atherosclerosis. Whether hypercholesterolemia also affects the retinal microcirculation is unclear. The goal of our study was to assess the association of cholesterol levels with retinal microvascular function using dynamic and static retinal vessel analysis (RVA) in a primary prevention setting. This cross-sectional, observational study prospectively recruited 67 patients with hypercholesterolemia without known cardiovascular disease (mean age 64.4 ± 10.4 years; 45% female) and 78 healthy controls (mean age 61.8 ± 11.2 years; 45% female). The primary end point of the study was flicker-induced dilatation of retinal arterioles (FIDart) with secondary exploratory outcomes including venular FID (FIDven), arteriovenous ratio, flow-mediated dilatation and arterial stiffness as measured with augmentation index and pulse wave velocity. Multiple regression analysis was performed to study the association of cholesterol levels with retinal microvascular function. FIDart was significantly impaired in patients with hypercholesterolemia compared with healthy controls (mean FIDart 2.1 ± 1.8 vs 3.1 ± 1.8%, P = .001). This association remained when analysis was restricted to dyslipidemic patients without coexisting hypertension or lipid-lowering therapy. No significant differences remained for FIDven, flow-mediated dilatation, arteriovenous ratio, or arterial stiffness between the groups. Low-density lipoprotein, but not high-density lipoprotein, cholesterol was a significant negative predictor of FIDart in multiple regression analysis. Hypercholesterolemia is associated with significant retinal microvascular dysfunction as evidenced by a reduction in flicker-induced dilatation of retinal arterioles. Dynamic RVA may be a promising method for the study of retinal microvascular dysfunction in populations at elevated cardiovascular risk.


Large-scale genome reorganization in Saccharomyces cerevisiae through combinatorial loss of mini-chromosomes.
A highly efficient technique, termed PCR-mediated chromosome splitting (PCS), was used to create cells containing a variety of genomic constitutions in a haploid strain of Saccharomyces cerevisiae. Using PCS, we constructed two haploid strains, ZN92 and SH6484, that carry multiple mini-chromosomes. In strain ZN92, chromosomes IV and XI were split into 16 derivative chromosomes, seven of which had no known essential genes. Strain SH6484 was constructed to have 14 mini-chromosomes carrying only non-essential genes by splitting chromosomes I, II, III, VIII, XI, XIII, XIV, XV, and XVI. Both strains were cultured under defined nutrient conditions and analyzed for combinatorial loss of mini-chromosomes. During culture, cells with various combinations of mini-chromosomes arose, indicating that genomic reorganization could be achieved by splitting chromosomes to generate mini-chromosomes followed by their combinatorial loss. We found that although non-essential mini-chromosomes were lost in various combinations in ZN92, one mini-chromosome (18kb) that harbored 12 genes was not lost. This finding suggests that the loss of some combination of these 12 non-essential genes might result in synthetic lethality. We also found examples of genome-wide amplifications induced by mini-chromosome loss. In SH6484, the mitochondrial genome, as well as the copy number of genomic regions not contained in the mini-chromosomes, was specifically amplified. We conclude that PCS allows for genomic reorganization, in terms of both combinations of mini-chromosomes and gene dosage, and we suggest that PCS could be useful for the efficient production of desired compounds by generating yeast strains with optimized genomic constitutions.


A novel germline mutation in exon 5 of the multiple endocrine neoplasia type 1 gene.
The autosomal dominant multiple endocrine neoplasia type 1 (MEN1) syndrome is characterized by neoplasia of parathyroids, anterior pituitary, and gastrointestinal and pancreatic neuroendocrine tissues. Recently the gene responsible for the MEN1 syndrome has been identified on chromosome region 11q13. Most of the described mutations are nucleotide substitutions and small deletions affecting exons 2 and 3, causing protein truncation. Only one mutation in exon 5 has been found, and this corresponds to a MEN1 sporadic case. Small insertions are also rare. We studied a MENI family composed of five members, two of whom were clinically affected. We found a new germline 1 basepair insertional mutation affecting the exon 5 of the MEN1 gene in the two members affected in this MEN1 family.


Disease prevention and wellness in the twenty-first century.
Primary care physicians should continue their efforts in disease prevention and also should expand their scope of service to support patients' interests in wellness and health optimization. Taking on this role will require additional time and continuing education, but by knowledgeably helping patients to maximize their health, physicians will provide a needed service, contribute to the health of their patients, and reap the rewards of a stronger doctor-patient bond.


Multiple external electrical cardioversions for refractory neonatal atrial flutter.
This report describes a case of atrial flutter in a fetal/neonatal patient who did not respond to adenosine, a propafenone bolus, and three electrical external cardioversions. A fourth direct current cardioversion after propafenone premedication resolved the atrial flutter. The arrhythmia did not recur with propafenone therapy during a 12-month follow-up period.


Cyclosporine and alpha-interferon do not attenuate morphine withdrawal in rats but do impair thermoregulation.
Immunomodulating drugs as diverse as alpha-interferon and cyclosporine have been reported to attenuate physical signs of morphine withdrawal in rats. On the basis of these results, the immune system has been claimed to be involved in opiate addiction. To assess whether this is the case, the effects of alpha-interferon and cyclosporine were studied on objective signs of morphine withdrawal in morphine-dependent rats. Rats made dependent upon morphine by implantation of a 75-mg morphine pellet were challenged three days later by naloxone (1 mg/kg). Pretreatment with alpha-interferon (150 U/g) or cyclosporine (15 mg/kg) did not attenuate the reduction in body weight or the behavioral suppression induced by naloxone in morphine-dependent rats trained to press a lever for food reinforcement on a fixed-ratio 10 schedule. Alpha-interferon pretreatment blocked the capacity of naloxone to decrease body temperature in these rats and actually induced an hyperthermic response. In contrast, cyclosporine tended to enhance the drop in body temperature induced by naloxone. This last effect was more striking when the rats were placed in a cold room at 3.5 degrees C. Cyclosporine by itself induced a drop in body temperature in normal rats exposed to 3.5 degrees C. These results indicate that alpha-interferon and cyclosporine impair thermoregulation but do not directly interfere with morphine withdrawal signs.


Identification of an autophagy-related gene signature that can improve prognosis of hepatocellular carcinoma patients.
Autophagy is a programmed cell degradation mechanism that has been associated with several physiological and pathophysiological processes, including malignancy. Improper induction of autophagy has been proposed to play a pivotal role in the progression of hepatocellular carcinoma (HCC). Univariate Cox regression analysis of overall survival (OS) was performed to identify risk-associated autophagy-related genes (ARGs) in HCC data set from The Cancer Genome Atlas (TCGA). Multivariate cox regression was then performed to develop a risk prediction model for the prognosis of 370 HCC patients. The multi-target receiver operating characteristic (ROC) curve was used to determine the model's accuracy. Besides, the relationship between drug sensitivity and ARGs expression was also examined. A total of 62 differentially expressed ARGs were identified in HCC patients. Univariate and multivariate regression identified five risk-associated ARGs (HDAC1, RHEB, ATIC, SPNS1 and SQSTM1) that were correlated with OS in HCC patients. Of importance, the risk-associated ARGs were independent risk factors in the multivariate risk model including clinical parameters such as malignant stage (HR = 1.433, 95% CI = 1.293-1.589, P < 0.001). In addition, the area under curve for the prognostic risk model was 0.747, which indicates the high accuracy of the model in prediction of HCC outcomes. Interestingly, the risk-associated ARGs were also correlated with drug sensitivity in HCC cell lines. We developed a novel prognostic risk model by integrating the molecular signature and clinical parameters of HCC, which can effectively predict the outcomes of HCC patients.


Establishment and characterisation of murine cells constitutively expressing the fusion, nucleoprotein and matrix proteins of measles virus.
To advance our understanding of the immunobiology of measles virus (MV) infections, we have investigated the possibility of establishing cell lines constitutively expressing the individual MV antigens. In contrast to previously published studies, we show that it is possible to establish cell lines expressing high levels of fusion (F), nucleoprotein (NP) and matrix (M) MV proteins. Once cloned, the cell lines were stable with high levels of expression for more than six months. The size and cell distribution of the NP and F proteins were similar to those observed in MV- or vaccinia-MV recombinant-infected cells. In contrast, the distribution of the M protein, although being similar to that of MV-infected cells, differed from that of Vaccinia-M recombinant virus-infected cells. Preliminary results suggest that these cell lines will be useful tools for studying the contribution of individual MV antigens to the cell-mediated immune response to this virus.


Effect of ether lipids on mouse granulocyte-macrophage progenitor cells.
In this study we determined the potential bone marrow toxicity of the ether lipid derivatives 1-0-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine (OcMe-G-3-PC), 1-0-hexadecyl-propanediol-2-phosphocholine (He-Pr-2-PC), and hexadecylphosphocholine (He-PC). OcMe-G-3-PC inhibited the proliferation of mouse granulocyte-macrophage progenitor cells (GM-CFCs) at a dose of 1 micrograms/ml, whereas He-Pr-2-PC and He-PC started to inhibit the growth of hemopoietic precursors at 5 micrograms/ml. In contrast to this finding, NMRI mice given 10 mg/kg i.v. daily for 4 weeks and 20 or 30 mg/kg for 5 days showed no bone marrow toxicity. We conclude that the dose-dependent toxic effects observed in vitro are within the physiological tolerance in vivo.


Impaired cytoplasmic domain interactions cause co-assembly defect and loss of function in the p.Glu293Lys KNCJ2 variant isolated from an Andersen-Tawil syndrome patient.
Subunit interactions at the cytoplasmic domain interface (CD-I) have recently been shown to control gating in inward rectifier potassium channels. Here we report the novel KCNJ2 variant p.Glu293Lys that has been found in a patient with Andersen-Tawil syndrome type 1 (ATS1), causing amino acid substitution at the CD-I of the inward rectifier potassium channel subunit Kir2.1. Neither has the role of Glu293 in gating control been investigated nor has a pathogenic variant been described at this position. This study aimed to assess the involvement of Glu293 in CD-I subunit interactions and to establish the pathogenic role of the p.Glu293Lys variant in ATS1. The p.Glu293Lys variant produced no current in homomeric form and showed dominant-negative effect over wild-type (WT) subunits. Immunocytochemical labelling showed the p.Glu293Lys subunits to distribute in the subsarcolemmal space. Salt bridge prediction indicated the presence of an intersubunit salt bridge network at the CD-I of Kir2.1, with the involvement of Glu293. Subunit interactions were studied by the NanoLuc® Binary Technology (NanoBiT) split reporter assay. Reporter constructs carrying NanoBiT tags on the intracellular termini produced no bioluminescent signal above background with the p.Glu293Lys variant in homomeric configuration and significantly reduced signals in cells co-expressing WT and p.Glu293Lys subunits simultaneously. Extracellularly presented reporter tags, however, generated comparable bioluminescent signals with heteromeric WT and p.Glu293Lys subunits and with homomeric WT channels. Loss of function and dominant-negative effect confirm the causative role of p.Glu293Lys in ATS1. Co-assembly of Kir2.1 subunits is impaired in homomeric channels consisting of p.Glu293Lys subunits and is partially rescued in heteromeric complexes of WT and p.Glu293Lys Kir2.1 variants. These data point to an important role of Glu293 in mediating subunit assembly, as well as in gating of Kir2.1 channels.


(1) H and (13) C NMR data on natural and synthetic capsaicinoids.
Capsaicinoids are the compounds responsible for the pungency of chili peppers. These substances have attracted the attention of many research groups in recent decades because of their antinociceptive, analgesic, anti-inflammatory, and anti-obesity properties, among others. There are nearly 160 capsaicinoids reported in the literature. Approximately 25 of them are natural products, while the rest are synthetic or semi-synthetic products. A large amount of NMR data for the capsaicinoids is dispersed throughout literature. Therefore, there is a need to organize all this NMR data in a systematic and orderly way. This review summarizes the (1) H and (13) C NMR data on 159 natural and synthetic capsaicinoids, with a brief discussion of some typical and relevant aspects of these NMR data. Copyright © 2015 John Wiley & Sons, Ltd.


The Effects of Almond Consumption on Inflammatory Biomarkers in Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Conflicting findings have been reported regarding the effects of almond consumption on inflammatory markers. This study aimed to summarize the current literature to determine whether almonds can affect inflammatory markers. A systematic search was carried out in PubMed, Scopus, and ISI Web of Science up to March 2021. Randomized clinical trials that compared almond with no almond consumption were included. The outcomes of interest were changes in circulating C-reactive protein (CRP), IL-6, TNF-α, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) concentrations. The random-effects model was used to find the mean differences. In total, 18 trials with 847 participants were eligible for the current analysis. Participants' ages ranged from 26.3 to 69.6 y. Combining 16 studies, almond consumption significantly reduced serum concentrations of CRP [weighted mean difference (WMD): -0.25 mg/L; 95% CI: -0.43, -0.06 mg/L; I2 = 0.0%; P-heterogeneity = 0.633]. However, the beneficial effect of almond intake only occurred at doses <60 g/d. Pooling 11 effect sizes, almond interventions significantly decreased circulating IL-6 concentrations (WMD: -0.11 pg/mL; 95% CI: -0.21, -0.01 pg/mL; I2 = 19.9%; P-heterogeneity = 0.254). In subgroup analyses, effects on CRP and IL-6 were nonsignificant in unhealthy participants or those with obesity. In addition, almond consumption had no significant effect on TNF-α (WMD: -0.05 pg/mL; 95% CI: -0.11, 0.01 pg/mL; I2 = 0.0%; P-heterogeneity = 0.893; n = 6), ICAM-1 (WMD: 6.39 ng/mL; 95% CI: -9.44, 22.22 ng/mL; I2 = 66.6%; P-heterogeneity = 0.006; n = 7), or VCAM-1 (WMD: -8.31 ng/mL; 95% CI: -35.32, 18.71 ng/mL; I2 = 58.8%; P-heterogeneity = 0.033; n = 6). In conclusion, almond consumption beneficially affects CRP and IL-6 concentrations in adults. However, it has no beneficial effect on TNF-α, ICAM-1, or VCAM-1. More trials are needed to determine the effects of almonds on inflammation.


[Contiguous cutaneous inflammation].
Contiguous cutaneous inflammation is a circumscribed inflammatory reaction of the skin overlying a pathological process affecting an adjacent deep-seated anatomical structure. Contiguous cutaneous inflammation can sometimes reveal serious internal diseases. Through a case report and a literature review, we characterize the concept of contiguous cutaneous inflammation. A 77-year-old woman with a past medical history of rhinorrhoea and chronic headache was admitted for a verrucous and erythematous lesion on her right cheek, evolving for two months with incomplete remission after numerous antibiotics. Histopathological examination was inconclusive. Facial CT revealed pansinusitis. Diagnosis of contiguous cutaneous inflammation to sinusitis was retained. Complete healing of cutaneous lesions was observed after surgical treatment of the sinusitis. Contiguous cutaneous inflammation is characterized by localization over the causal disease, parallel evolution with the latter and the absence of clinicopathological specificity. The underlying pathological process is variable and may be tumoral or infectious, or simply the presence of an internal device. Migration of inflammatory cells and/or diffusion of mediators in a localized skin area could be involved in pathogenesis.


Nervous system responses of rats to subchronic inhalation of N-hexane and N-hexane + methyl-ethyl-ketone mixtures.
The effects of long-term continuous and intermittent inhalation exposure to selected concentrations of n-hexane and mixtures of n-hexane and methyl-ethyl-ketone (MEK) on the nervous system of rats were investigated. Animals exposed continuously (24 h/d, 7 d/week) to 500 ppm n-hexane displayed complete hindlimb paralysis after 9 weeks. Histological examination showed hexacarbon-specific axonal lesions in peripheral nerves, particularly tibial branches to calf muscles, and in the gracile tract at cervical levels of the spinal cord. Similar clinical and pathological signs of neuropathy appeared one week earlier in animals treated with a mixture of 500 ppm n-hexane/MEK (4:1 or 3:2) and 5 weeks earlier with 700 n-hexane/MEK mixture (5:2) or 700 ppm of n-hexane alone. Rats exposed to the latter concentrations intermittently, 8 hours daily for 40 weeks, did not develop clinical or morphological signs of a hexacarbon neuropathy.


Editorial Commentary: Obesity Is Associated With Lower Hip Function Pre- and Postoperatively and Increased Time to Patient Acceptable Symptom State After Hip Arthroscopy.
In 2015, worldwide, there were more than 1.9 billion adults classified as having overweight (body mass index [BMI] >25), with 600 million of these individuals meeting the definition of obesity (BMI >30). Hip arthroscopy in patients with obesity can lead to improve outcomes, albeit with lower absolute levels of patient-reported outcome scores and with increased risk of complications and conversion rates to total hip arthroplasty when compared with their counterparts without obesity. Importantly, a significantly longer time to patient acceptable symptoms state achievement is seen for patients with class I obese than patients with normal BMI. Unfortunately, the hip is quite susceptible to the effects of obesity, with greater acetabular depth/deformity, reduced femoral head cartilage, greater forces experienced with ambulation, and a predisposition to femoroacetabular impingement syndrome. Thus, almost 42% of patients operated on in North America for femoroacetabular impingement syndrome are classified as having overweight or obesity. This does not need to deter from the consideration of arthroscopic hip surgery in the population with obesity; rather, it supports a discussion between surgeon and patient on expectations and timeline for improvement.


The effect of the pyrrolizidine alkaloids, monocrotaline and trichodesmine, on tissue pyrrole binding and glutathione metabolism in the rat.
One day after in vivo administration of equitoxic doses of the hepatotoxic and pneumotoxic pyrrolizidine alkaloid, monocrotaline (65 mg/kg, i. p.) or the related hepatotoxic and neurotoxic alkaloid trichodesmine (15 mg/kg, i. p.) hepatic GSH levels are increased by more than 50%. These doses of alkaloids represent 60% of the LD50 values. Accompanying these changes in GSH levels is an increase in the overall rate of GSH synthesis in supernatants of alkaloid-exposed livers. The ability of the rat to metabolize the two alkaloids was shown by the appearance of tissuebound pyrrolic metabolites of pyrrolizidines in various organs. The levels of these metabolites appear to correlate with organ toxicity. For the hepatic and pneumotoxic alkaloid, monocrotaline, higher levels are found in liver (17 nmoles/g tissue) and lung (10 nmoles/g) than for trichodesmine (7 nmoles/g and 8 nmoles/g, respectively). For the neurotoxic alkaloid, trichodesmine, higher levels are found in brain (3.8 nmoles/g tissue) than for monocrotaline (1.7 nmoles/g tissue).


FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial.
Vascular leakage is a major feature of acute respiratory distress syndrome (ARDS). We aimed to evaluate the efficacy of FX06, a drug under development that stabilizes interendothelial cell junctions, at reducing vascular leakage during SARS-CoV-2-induced ARDS. This multicenter, double-blinded, randomized trial included adults with COVID-19-associated ARDS who had received invasive mechanical ventilation for < 5 days and were randomized to receive either intravenous FX06 (400 mg/d, for 5 days) or its vehicle as placebo. The primary endpoint was the lowering-from day 1 to day 7-of the transpulmonary thermodilution-derived extravascular lung-water index (EVLWi). Twenty-five patients were randomized to receive FX06 and 24 the placebo. Although EVLWi was elevated at baseline (median [IQR] 15.6 mL/kg [13.5; 18.5]), its declines from day 1 to day 7 were comparable for FX06 recipients and controls (respectively, - 1.9 [- 3.3; - 0.5] vs. - 0.8 [- 5.5; - 1.1] mL/kg; estimated effect - 0.8 [- 3.1; + 2.4], p = 0.51). Cardiac indexes, pulmonary vascular permeability indexes, and fluid balances were also comparable, as were PaO2/FiO2 ratios and durations of mechanical ventilation. Adverse event rates were similar for the 2 groups, although more FX06 recipients developed ventilator-associated pneumonia (16/25 (64%) vs. 6/24 (24%), p = 0.009). In this unique-dosing-regimen study, FX06 did not lower SARS-CoV-2-induced pulmonary vascular leakage. Future investigations will need to evaluate its efficacy at earlier times during the disease or using other regimens. Trial registration NCT04618042. Registered 5 November 2020.


Phrenic nerve pacing for the treatment of central hypoventilation syndrome - state of the art and case report.
The application of phrenic nerve pacing is an effective method of respiratory support in adults with certain forms of acquired failure of automatic ventilation. The experience with one infant suffering from congenital central hypoventilation (Ondine's syndrome) is summarized in this report. Stimulation electrodes were implanted on the thoracic portion of each phrenic nerve. After a cumbersome period of intensive medical care and conditioning of the phrenic nerve-diaphragm-system, the patient could be weaned off the respirator. Severe upper airway obstruction, however, required tracheostomy. Bilateral simultaneous pacing has been effective now for more than 2 years providing the desired normal ventilation during sleep. The state of the art of phrenic nerve pacing is described.


Betaproteobacteria dominance and diversity shifts in the bacterial community of a PAH-contaminated soil exposed to phenanthrene.
In this study, the PAH-degrading bacteria of a constructed wetland collecting road runoff has been studied through DNA stable isotope probing. Microcosms were spiked with (13)C-phenanthrene at 34 or 337 ppm, and bacterial diversity was monitored over a 14-day period. At 337 ppm, PAH degraders became dominated after 5 days by Betaproteobacteria, including novel Acidovorax, Rhodoferax and Hydrogenophaga members, and unknown bacteria related to Rhodocyclaceae. The prevalence of Betaproteobacteria was further demonstrated by phylum-specific quantitative PCR, and was correlated with a burst of phenanthrene mineralization. Striking shifts in the population of degraders were observed after most of the phenanthrene had been removed. Soil exposed to 34 ppm phenanthrene showed a similar population of degraders, albeit only after 14 days. Results demonstrate that specific Betaproteobacteria are involved in the main response to soil PAH contamination, and illustrate the potential of SIP approaches to investigate PAH biodegradation in soil.


NIPBL rearrangements in Cornelia de Lange syndrome: evidence for replicative mechanism and genotype-phenotype correlation.
Cornelia de Lange syndrome (CdLS) is a multisystem congenital anomaly disorder characterized by mental retardation, limb abnormalities, distinctive facial features, and hirsutism. Mutations in three genes involved in sister chromatid cohesion, NIPBL, SMC1A, and SMC3, account for ~55% of CdLS cases. The molecular etiology of a significant fraction of CdLS cases remains unknown. We hypothesized that large genomic rearrangements of cohesin complex subunit genes may play a role in the molecular etiology of this disorder. Custom high-resolution oligonucleotide array comparative genomic hybridization analyses interrogating candidate cohesin genes and breakpoint junction sequencing of identified genomic variants were performed. Of the 162 patients with CdLS, for whom mutations in known CdLS genes were previously negative by sequencing, deletions containing NIPBL exons were observed in 7 subjects (~5%). Breakpoint sequences in five patients implicated microhomology-mediated replicative mechanisms-such as serial replication slippage and fork stalling and template switching/microhomology-mediated break-induced replication-as a potential predominant contributor to these copy number variations. Most deletions are predicted to result in haploinsufficiency due to heterozygous loss-of-function mutations; such mutations may result in a more severe CdLS phenotype. Our findings suggest a potential clinical utility to testing for copy number variations involving NIPBL when clinically diagnosed CdLS cases are mutation-negative by DNA-sequencing studies.


Identification of a new Bradyrhizobium japonicum gene (frxA) encoding a ferredoxinlike protein.
An open reading frame of 74 codons was identified downstream of the nifB gene of Bradyrhizobium japonicum 110. The predicted amino acid sequence shared 63% similarity with the Rhodopseudomonas palustris ferredoxin I sequence. We propose to name the gene frxA. The frxA gene was found to be cotranscribed with the nifB gene. An insertion mutation within frxA hardly affected nitrogen fixation activity.


Targeting and clustering citron to synapses.
Citron-N (citron) binds activated Rho and concentrates at excitatory postsynaptic densities on the smooth dendritic shafts of hippocampal GABAergic neurons. Since little is known about how cytoplasmic proteins become targeted and retained at synapses, we asked how citron attains this discrete distribution. We first sought to determine whether the synaptic localization machinery is unique to GABAergic interneurons, but in neurons cultured from either cerebral cortex or hippocampus, low levels of citron are found in a small population of glutamatergic neurons concentrated at the tips of dendritic spines in addition to shaft synapses. These data suggest that the targeting domains in citron can be utilized appropriately by any neuron, and consistent with this idea, tagged, exogenous, full-length citron becomes concentrated at postsynaptic sites in all hippocampal neurons in which it is introduced. Citron contains multiple sites for protein-protein interaction, including coiled-coil, pleckstrin homology, cysteine-rich zinc binding and CMG domains, as well as a proline-rich region and a PDZ binding tail that is known to interact with PSD-95/SAP90. Using citron deletion mutants, we find that the coiled-coil (CC) domain, located in the N-terminal half of the protein, mediates somatodendritic targeting, self-oligomerization and puncta formation independent of the Rho binding domain, while regions in the C-terminal half of citron are responsible for precise alignment of postsynaptic citron clusters at sites apposing presynaptic boutons. Rho binding and activation regulate membrane targeting and the number of synapses containing citron. Thus, citron's clustering at postsynaptic membranes is mediated by multiple domains, and its synaptic distribution is modified in response to Rho activation.


Ionic Current Rectification Triggered Photoelectrochemical Chiral Sensing Platform for Recognition of Amino Acid Enantiomers on Self-Standing Nanochannel Arrays.
Chirality is an intrinsic and essential property of nature, and the enantiomeric discrimination of chiral molecules can provide important information leading to a better understanding of chiral recognition in biological systems and furthering the development of useful molecular devices in biochemical and pharmaceutical studies. Therefore, the exploration of new detection techniques with high accuracy and reliability for high-throughput enantioselective detection is still highly desirable. Herein, a chiral enantiomers selective recognition platform based on self-standing titanium dioxide nanochannel arrays (TiO2 NCAs) is proposed to implement the ionic current rectification triggered photoelectrochemical (PEC) detection, which provides a novel sensing platform to discriminate chiral amino acid through synchronous output dual response signals of ionic current and photocurrent. The utilization of nanochannel arrays guaranteed the high-throughput detection, and the dual signal model avoided a "false positive" detection. In addition, based on the fabricated detection platform, various chiral substances can be facilely detected through integrating different chiral regulation units, which shed light on the construction of reliable chiral sensors for practical applications in a biological environment.


Multifunctional colorimetric cellulose acetate membrane incorporated with Perilla frutescens (L.) Britt. anthocyanins and chamomile essential oil.
A colorimetric cellulose acetate (CA) membrane incorporated with Perilla frutescens (L.) Britt. anthocyanins (PFA) and chamomile essential oil (CO) is developed via electrospinning technique for food freshness monitoring and shelf-life extending. The moieties of PFA and CO are well-dispersed in fiber matrix by hydrogen bonds and their incorporation increases the fiber size but with no obvious influence on the fiber morphology at incorporation levels. The presence of CO enhances membrane hydrophobicity. The target membrane of CA-PFA6-CO15 (PFA6%, CO15%) has a wide color change range of pH 2-12 which is high sensitive and reversible towards external pH-stimuli. The membrane has good antibacterial activity against E. coli and S. aureus besides antioxidant activity. The release of bioactive moieties is predominantly controlled by Fickian diffusion. The target membrane can simultaneously monitor pork freshness in real-time and double the shelf-life at 25 °C, indicating its potential application in active and intelligent food packaging.


Update of the European guidelines for basal cell carcinoma management.
European guidelines for the management of basal cell carcinoma (BCC) prepared by the former BCC subcommittee of the Guidelines Committee of the European Dermatology Forum (EDF) were published in 2006. To present updated guidelines that include consensual expert definitions on various BCC types, prognosis and risk factors for BCC as well as review recommendations for diagnosis and treatment reflecting current published evidence. These guidelines (S1 type) were prepared by the new BCC subgroup of the European Dermatology Forum (EDF)'s Guidelines Committee through extensive literature review (up to 2012) and expert experience; they were extensively discussed within the EDF subcommittee and approved by peer reviewers of the EDF. Results BCC is a common tumour with an incidence rising worldwide. Three major clinical types of BCC are recognized: nodular, superficial and morpheaform. Four histological subtypes are defined: superficial, nodular, infiltrative and morpheaform. On the basis of the risk of relapse, three prognosis groups have been identified: high, intermediate and low risk. According to these classifications and evidence-based evaluation of the therapeutic strategies available, a decision tree is proposed for the management of BCCs. The guidelines offer a useful tool that will help dermatologists to select the most appropriate treatment for individual patients.


Pharmaceutical gel analysis by NIR spectroscopy. Determination of the active principle and low concentration of preservatives.
Near infrared spectroscopy has proved highly suitable for the analysis of pharmaceutical formulations. However, its limited sensitivity can severely restrict its scope of application. In this work, we determine the active principle and two preservatives in a pharmaceutical preparation available as a hydrogel. The matrix of the pharmaceutical preparation exhibits strong absorption in the NIR spectral region; also, the two preservatives (parabens) are very similar in chemical and spectral terms, and present at low concentrations in the pharmaceutical. These complications make it rather difficult to accurately quantify the active principle and the preservatives, which can only be accomplished by using an effective design in order to prepare the samples to be included in the calibration set and select the optimum spectral range for measuring each analyte. The evaporation of solvents during the measurement process produces increasing errors related with sample's air exposition; the introductions of new samples with a wider range of the volatile components correct this effect. An ANOVA of the predictions obtained with the new models shows that correct the error due to evaporation. The proposed method was validated for the analytical control of the studied preparation.


A double lead stain method for enhancing contrast of ultrathin sections in electron microscopy: a modified multiple staining technique.
A modification of the conventional method for the staining of ultrathin sections resulted in an increase in contrast of ultrastructural detail in tissues. Tissues embedded in Spurr's low viscosity embedding medium were stained with freshly centrifuged Reynolds' lead citrate for 1-5 min, rinsed in double distilled water and dried prior to staining with a saturated solution of uranyl acetate for 40 min, and freshly centrifuged Reynolds' lead citrate for 20 min. Sections treated by this procedure showed enhanced staining of cellular organelles and cytoplasmic matrix. This procedure is recommended for tissues with poor staining qualities resulting from either prolonged fixation or from inadequacies in the buffer or embedding medium used.


Carbon fixation in eucalypts in the field : Analysis of diurnal variations in photosynthetic capacity.
The rate of CO2 assimilation at light saturation and an intercellular CO2 concentration of 350 μl l-1 (photosynthetic capacity), measured in leaves of Eucalyptus pauciflora, E. behriana, E. delegatensis and Acacia melanoxylon, declined over the course of cloudless days under naturally varying environmental conditions as well as under constant optimal conditions for high CO2 uptake. Since the capacity did not recover during the light period, it was different from the "midday depression" of gas exchange. The change appeared to be caused neither by the diurnal variation of total leaf water potential, by photoinhibition of redox-reaction centres in photosystems nor by changes in the intrinsic properties of Ribulose-bisphosphate carboxylase-oxygenase. The decline was more pronounced in winter than in summer. It was related to the duration of illumination or the cumulative carbon gain. It was reversible in the following dark phase, and it did not occur on changeable days with short peaks of high light.Despite the decline in photosynthetic capacity, the initial slope of the CO2 response of net photosynthesis, as obtained at low intercellular CO2 concentrations, remained constant during the day, but declined at night when photosynthetic capacity recovered. In all cases stomatal conductance varied in parallel with photosynthetic capacity. The relevance of changes in photosynthetic capacity for the intercellular CO2 concentration is discussed.


In utero aminoglycosides-induced nephrotoxicity in rat neonates.
Pregnant Wistar females were treated with gentamicin (G), netilmicin (N) or amikacin (A) during two periods of pregnancy covering organogenesis and the beginning of nephrogenesis. Deliveries occurred normally. We studied functional effects--influence of sex, litter size, diuresis, creatinine clearance, G-kidney concentration, and kidney morphological alterations--in rat neonates on day 1 of life. After G and N, the creatinine clearance of the neonates was decreased according to the dosage given to the mother. Whatever the aminoglycoside, kidneys presented proximal tubular alterations (close to those observed in adults) at protonic microscopy and, with electron microscopy, some modifications of distal tubules and of mature and immature glomeruli. It is concluded that the developing kidney can be altered after treating pregnant mothers with aminoglycosides. This model of in utero-induced nephrotoxicity is dose-dependent. Mature and/or immature structures could be affected. The toxicity of the investigated antibiotics could be asserted as G greater than or equal to N greater than A.


Practical internal and external cooling methods do not influence rapid recovery from simulated taekwondo performance.
The influence of post-exercise cooling on recovery has gained much attention in the empirical literature, however, data is limited in regards to optimizing recovery from taekwondo performance when combat is repeated in quick succession within the same day. The aim of this study was therefore to compare the effects of external and internal cooling after simulated taekwondo combat upon intestinal temperature (Tint), psychomotor skills (reaction time, response time, movement time), and neuromuscular function (peak torque, average power, time to reach peak torque). Using a randomized counterbalanced crossover design, 10 well-trained male taekwondo athletes completed four recovery methods on separate occasions: passive recovery (CON), a 5-minute thermoneutral water immersion (35°C) (TWI), a 5-min cold water immersion (15°C) (CWI), and ice slurry ingestion (-1°C) (ICE; consumed every 5 min for 30 min). Heart rate (HR), blood lactate (Blac) concentrations, and Tint were determined at rest, immediately after combat, and at selected intervals during a 90-min recovery period. Neuromuscular functional (measured with isokinetic dynamometer) and psychomotor indices were assessed at baseline and after the recovery period. ICE led to a significantly lower Tint at 30 min (P<0.01) and 45 min (P<0.01) after simulated combat; 15-30 min after cessation of ingesting ice slurry, compared with the CON and TWI conditions, respectively. However, there were no differences in Tint across time points between the other conditions (P>0.05). Psychomotor skills and neuromuscular function indices returned to baseline values after the 90 min recovery period (P>0.05) with no differences observed between conditions (P>0.05). The present findings suggest that internal (ICE) and external (CWI) recovery methods appear to have little impact on physiological and functional indices over the time course required to influence repeated taekwondo combat performance.


Chitosan/cyclodextrin surface-adsorbed naringenin-loaded nanocapsules enhance bacterial quorum quenching and anti-biofilm activities.
Pathogenic bacteria use quorum sensing (QS), a cell-to-cell communication process that relies on small signaling molecules, to regulate the genetic expression that leads to several essential virulence factors such as bioluminescence, biofilm formation, bacterial motility, among other. Naringenin (NAR), a bitter and colorless flavanone ubiquitous in herbs and fruits, has been shown to inhibit QS activity in P. aeruginosa by decreasing the production of pyocyanin and elastase. In this study, to evaluate the anti-QS activity of naringenin against an E. coli Top 10 biosensor, we developed a novel core-corona nanocapsule formulation comprising surface co-adsorbed β-cyclodextrin (Captisol®) and chitosan loaded with NAR. The results showed that both the nanocapsule (NC) and nanoemulsion (NE) formulations, NAR payload associated with high efficiency , namely ~ 92.88 and ~ 67.98%, respectively. These formulations remained stable for 24 h and showed a biphasic controlled release profile in bacterial M9 medium. Captisol® was effectively immobilized on the NC's surface, resulting in a surface charge inversion from positive (~ + 42 mV) to negative (~ -32 mV) ζ-potential. The biosensor assay revealed that NC outperformed NE in quenching the QS response and the incorporation of naringenin at the NC's multifunctional surface enhanced this bioactivity. Cytotoxicity assays showed that when NAR was associated in NC (188 µM) it was not cytotoxic to Caco2 cells, by contrast with its free form, thus highlighting the cytoprotective effect of the developed formulation. Biofilm formation was inhibited up to ~ 60% in NAR-loaded NC (188 μM), indicating the synergistic effect of positively charged chitosan with the bioactivity of NAR while harnessing the NC's high surface area-to-volume ratio.


Goal-focused Emotion-Regulation Therapy for young adult survivors of testicular cancer: Feasibility of a behavioral intervention.
Young adult cancer testicular survivors experience impairing, distressing, and modifiable physical, behavioral, and psychosocial adverse outcomes that persist long after the completion of primary medical treatment. These include psychological distress and poor psychosocial adjustment, impaired navigation of life goals, persistent treatment side effects, and fear associated with elevated risk of secondary malignancies and chronic illness. This paper describes the feasibility and acceptability of a novel intervention, Goal-focused Emotion-Regulation Therapy (GET) aimed at improving distress symptoms, emotion regulation, and goal navigation skills in young adult testicular cancer patients. Participants (N = 6) were recruited from a large comprehensive cancer center and received the GET intervention that included six individual sessions across eight weeks. Following all sessions, participants underwent a qualitative interview. Results supported the feasibility in recruitment and retention and overall positive satisfaction, working alliance, and helpfulness of the intervention. Clinically meaningful change was observed in both depression and anxiety. With slight adaptation, results support the feasibility of a future clinical trial.


Steroid-induced bilateral avascular necrosis of the lateral femoral condyles. A case report.
Osteonecrosis of both lateral femoral condyles was observed in a 42-year-old black woman under treatment with oral prednisone. She was treated by arthrotomy and debridement on the right side and conservative management on the left side. Lateral compartment osteonecrosis is most frequently associated with steroid therapy, but bilateral involvement is infrequent.


Retraction notice to "Why are we vaccinating children against COVID-19?" [Toxicol. Rep. 8 (2021) 1665-1684].
[This retracts the article DOI: 10.1016/j.toxrep.2021.08.010.].


Reduced influenza antiviral treatment among children and adults hospitalized with laboratory-confirmed influenza infection in the year after the 2009 pandemic.
Influenza antiviral treatment is recommended for all persons hospitalized with influenza virus infection. During the 2010-2011 influenza season, antiviral treatment of children and adults hospitalized with laboratory-confirmed influenza declined significantly compared with treatment during the 2009 pandemic (children, 56% vs 77%; adults, 77% vs 82%; both P < .01).


Clonally Expanded Decidual Effector Regulatory T Cells Increase in Late Gestation of Normal Pregnancy, but Not in Preeclampsia, in Humans.
Background: Regulatory T (Treg) cells are necessary for the maintenance of allogenic pregnancy. However, the repertoire of effector Treg cells at the feto-maternal interface in human pregnancy remains unknown. Our objective was to study T cell receptor (TCR) repertoires of Treg cells during pregnancy compared to normal and complicated pregnancies. Methods:Paired samples of peripheral blood and decidua in induced abortion and miscarriage cases were obtained from consenting patients. CD4+CD25+CD127low/-CD45RA- effector Treg cells were single-cell sorted from mononuclear cells. cDNAs of complementarity determining region 3 (CDR3) in TCRβ were amplified from the single cells by RT-PCR and the sequences were analyzed. The TCRβ repertoires were determined by amino acid and nucleotide sequences. Treg cells were classified into clonally expanded and non-expanded populations by CDR3 sequences. Results: We enrolled nine induced abortion cases in the 1st trimester, 12 cases delivered without complications in the 3rd trimester, 11 miscarriages with abnormal chromosomal karyotyped embryo, seven miscarriages with normal chromosomal karyotyped embryo, and seven cases of preeclampsia [median gestational week (interquartile range): 7 (7-9), 39 (38-40), 9 (8-10), 8 (8-10), and 34 (32-37), respectively]. The frequency of clonally expanded populations of effector Treg cells increased in decidua of 3rd trimester cases compared to 1st trimester cases [4.5% (1.4-10.8%) vs. 20.9% (15.4-28.1%), p < 0.001]. Clonally expanded Treg cells were rarely seen in peripheral blood. The ratio of clonally expanded populations of decidual effector Treg cells in miscarriages with abnormal and normal embryos was not significantly different compared with that in 1st trimester normal pregnancy. Interestingly, clonally expanded populations of effector Treg cells decreased in preeclampsia compared with that in 3rd trimester normal pregnancy [9.3% (4.4-14.5%) vs. 20.9% (15.4-28.1%), p = 0.003]. When repertoires in previous pregnancy and subsequent pregnancy were compared, some portions of the repertoire were shared. Conclusion: TCR repertoires of decidual effector Treg cells are skewed in the 3rd trimester of normal pregnancy. Failure of clonal expansion of populations of decidual effector Treg cells might be related to the development of preeclampsia.


PAHs composition of surface marine sediments: a comparison to potential local sources in Todos Santos Bay, B.C., Mexico.
The analysis of the 16 polyaromatic hydrocarbons (PAHs) listed as priority pollutants by EPA, was carried out on surface sediments at 32 stations at Todos Santos Bay, Baja California, Mexico. The purpose was to investigate concentration levels, distribution patterns and relate them to three suspected local sources. The PAHs composition of car exhaust, grass and shrubs combustion, and asphalt and tire dust, were all compared to the relative abundance of PAHs signature found on marine sediments of the bay. We used GC-MS analysis in selected ion monitoring (SIM) mode. The total concentration found was low (from 7.6 to 813 ng/g of dry sediment. The average concentration was 96 ng/g). PAHs concentration was somewhat correlated (r = 0.612; P < 0.05) with organic matter content. Surface distributions suggest depositional patterns conforming to the reported water circulation in the bay. The maximum concentration was found near Todos Santos Canyon. The largest concentrations found were those of fluoranthene (120.6 ng/g), Indene(1,2,3-c,d)pyrene (115.6 ng/g) and pyrene (109.9 ng/g). Percentagewise, the main components were PAHs with three and four rings. Several indexes were used to investigate origins including simple PAH ratios and ternary plots. These indexes and plots suggest the main origin as a combination of urban air and wood and brush fires with little influence of oil.


Natural history of HLA expression during tumour development.
HLA expression is frequently altered in tumours compared to the tissue from which they originate. Given the central role of MHC products in the restriction of T-cell recognition, regulation of tumour HLA expression might be a strategy for the evasion of immune surveillance by the malignant cells. Federico Garrido, Peter Stern and colleagues present data from a variety of tumour types, suggesting that HLA class I alterations may occur at a particular step between the development of an in situ lesion and an invasive carcinoma.


Post-ischemic therapy with CGS-19755 (alone or in combination with hypothermia) in gerbils.
Hypothermia or a glutamate receptor antagonist may offer protection when used before or within seconds of an ischemic insult. In this experiment, we tested the efficacy of hypothermia (34 degrees C) versus CGS-19755 (a potent competitive N-methyl-D-aspartate (NMDA) receptor blocker) and their combination which was administered 0.5 h after a 5-min forebrain ischemic insult in gerbils. Morphological assessments were done in Group A at the end of 7 days while Group B was evaluated at 29 days. Each group had four sets of animals: saline treated controls; hypothermia treated; CGS-19755 treated; and a combination of CGS-19755 + hypothermia treated animals. Group A showed significant 'protection', i.e. minimal neuronal damage in the animals treated with hypothermia alone. Protection was evident in the cerebral cortex (P < 0.001), hippocampus CA1 (P < 0.01), and in the striatum (P < 0.05). There was no evidence of neuronal protection in the animals that had received either CGS-19755 alone or a combination of hypothermia and CGS-19755. In Group B (29 day assessment) the neuroprotective effects were not evident in any of the animals when compared to the controls. Behavioral testing with Morris water-maze testing showed no significant differences between the control and any of the treated animals. Our data suggests that 'post-ischemic' therapy with hypothermia may delay the effects of ischemia but does not offer significant long-term neuronal protection. Protection seen at 7 days is not evident at 29 days.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of dietary Yucca schidigera extract supplementation on productive performance, egg quality, and gut health in laying hens with Clostridium perfringens and coccidia challenge.
Yucca schidigera extract (YSE) is a green feed additive that is known to reduce toxic gas emissions and promote intestinal health in animal production. This study investigated the potential of dietary YSE supplementation to mitigate the negative effect of Clostridium perfringens and coccidia infection on productive performance and gut health in laying hens. A total of 48 Lohmann gray laying hens (35 wk of age) were randomly allotted to 1 of 2 groups (n = 24) fed with either a basal diet or a YSE-supplemented diet for 45 d. From d 36 to 45, half of the hens in each group were orally administrated with Clostridium perfringens type A and coccidia. This challenge impaired productive performance and egg quality (P < 0.05), destroyed jejunal morphology and functions (P < 0.05), induced jejunal epithelial cell apoptosis (P < 0.05), and downregulated the antioxidant capacity and Nrf2 pathway expression of jejunal mucosa (P < 0.05) in laying hens. Supplementing YSE in the laying hen diet, to some extents, improved productive performance and egg quality (P < 0.05), and alleviated the effect of challenge on morphology, functions, cell apoptosis, and antioxidant capacity in the jejunum (P < 0.05). Overall, the results suggested that dietary YSE supplementation might mitigate the negative effects of Clostridium perfringens and coccidia infection on gut health, and thereby improve the productive performance and egg quality of laying hens, possibly through enhancing the antioxidant capacity of the jejunum.


Effect of ageing on the retinal vascular responsiveness to flicker light in glaucoma patients and in ocular hypertension.
To evaluate the effect of ageing on the retinal vascular responsiveness to flicker light in glaucoma and ocular hypertension (OHT). Retinal vascular response to flicker was measured with the retinal vessel analyser in 56 healthy subjects (59 ± 9 years), 50 primary open-angle glaucoma (POAG) (60 ± 10 years) and 46 OHT patients (62 ± 9 years). In the glaucoma group, the less damaged eye; in the OHT group, the eye with the higher intraocular pressure; and in healthy controls, one randomly selected eye was considered. Parametric and non-parametric linear regression analysis, as well as a model of covariance analysis (ANCOVA) was used to evaluate the effect of age on the vascular response. In all three groups (N=152) absolute (Pearson R: -0.19, p<0.019; Spearman R: -0.22, p<0.006) and relative change (Pearson R: -0.18, p<0.027; Spearman R: -0.21, p<0.010) were statistically associated with age. The ANCOVA showed no difference between the three groups in this regard (absolute change: p=0.43; relative change: p=0.51). Vascular responsiveness to flicker light decreases with age in healthy individuals, in glaucoma patients and in OHT patients. This effect seems to be comparable between the tested groups, and age-related change in vascular responsiveness to flicker light seems an unlikely risk factor for glaucoma.


Injecting drugs alone during an overdose crisis in Vancouver, Canada.
Settings throughout Canada and the USA continue to experience crises of overdose death due to the toxic unregulated drug supply. Injecting drugs alone limits the potential for intervention and has accounted for a significant proportion of overdose deaths, yet the practice remains understudied. We sought to examine the practice of injecting alone among people who inject drugs (PWID) in Vancouver, Canada. Data were derived from two prospective cohorts of people who use drugs between June 2016 and November 2018. This analysis was restricted to participants who, in the previous 6 months, reported any injection drug use. Rates of injecting alone were categorized as always, usually, sometimes, or occasionally. We fit a multivariable generalized linear mixed model to identify factors associated with injecting drugs alone. Among 1070 PWID who contributed 3307 observations, 931 (87%) reported injecting alone at least once during the study period. In total, there were 729 (22%) reports of always injecting alone, 722 (21.8%) usually, 471 (14.2%) sometimes, 513 (15.5%) occasionally, and 872 (26.4%) never. In a multivariable model, factors positively associated with injecting drugs alone included male sex (adjusted odds ratio [AOR] 1.69; 95% confidence interval [CI] 1.20-2.37), residence in the Downtown Eastside neighbourhood (AOR 1.43; 95% CI 1.08-1.91), binge drug use (AOR 1.36; 95% CI 1.08-1.72), and experiencing physical or sexual violence or both (AOR 1.43; 95% CI 1.00-2.03). Protective factors included Indigenous ancestry (AOR 0.71; 95% CI 0.52-0.98) and being in a relationship (AOR 0.30; 95% CI 0.23-0.39). We observed that injecting alone, a key risk for overdose mortality, was common among PWID in Vancouver. Our findings underline the need for additional overdose prevention measures that are gender-specific, culturally appropriate, violence- and trauma-informed, and available to those who inject alone.


Protein folding disorders: toward a basic biological paradigm.
Mechanistic 'physics' models of protein folding fail to account for the observed spectrum and rate of protein folding and aggregation disorders in human populations, showing that more appropriately in vivo paradigms reflecting biological and other embedding contexts are needed for understanding the etiology, prevention, and treatment of these diseases. Here, a topological rate distortion analysis is applied to the problem that is analogous to Tlusty (2007) elegant exploration of the genetic code. A 'developmental' perspective sees the rate distortion function as a temperature analog in a spontaneous symmetry breaking argument, and permits incorporation of external factors as catalysts, driving the system to different possible outcomes via a nonequilibrium empirical Onsager treatment, viewed as a kind of dynamic regression equation. The formalism produces large-scale, quasi-equilibrium 'resilience' states representing normal and pathological protein folding. Generalization to long times produces diffusion models of protein folding disorders in which epigenetic or life history factors determine the rate of onset of dysfunction.


[The reaction of imidates with isocyanates].
Derivatives of isocyanates were prepared by reaction with imidates. Fragmentation reactions and behaviour in a simple biological test were examined.


A comparison of behavioral and traditional treatment for middle-income problem drinkers.
Groups of middle-income outpatient problem drinkiers were randomly assigned to one of two treatments: a multicomponent positive reinforcement procedure emphasizing moderation, or "traditional" denial-confrontation therapy emphasizing abstinence. There were no significant differences between participants assigned to the two procedures with respect to pretreatment characteristics. Participants reduced their alcohol consumption significantly in both treatments. Behavioral participants reduced alcohol consumption significantly during therapy, whereas traditional participants reduced significantly prior to therapy. Significantly more traditional participants dropped out of therapy than did behavioral. The data suggested that the effects of traditional therapy were mixed, helping those participants who were receptive, driving out those who were not; moreover, reduced consumption seemed to be more the result of compliance with initial therapist demands (made during the screening period) than the effect of denial-confrontation in subsequent therapy. Behavioral treatment was more successful in several indicators of outcome; the improvement observed seemed to be attributable to the active therapeutic techniques employed.


Hartmann Stahelin (1925-2011) and the contested history of cyclosporin A.
The aims of this study are twofold: (i) to pay tribute to Hartmann Stahelin for his scientific research on cyclosporin A; and (ii) to consider possible lessons for future pharmacological innovation by revisiting Stahelin's personal struggles to obtain fair recognition for his contribution to transplantation medicine.


Investigation of the causal relationship between ALS and autoimmune disorders: a Mendelian randomization study.
Epidemiological studies have reported an association between amyotrophic lateral sclerosis (ALS) and different autoimmune disorders. This study aims to explore the causal relationship between autoimmune disorders and ALS using Mendelian randomization (MR). To test the genetically predicted effects of liability towards immune-related outcomes on ALS risk, we used summary statistics from the largest European genome-wide association studies (GWAS) for these disorders in a two-sample MR setting. To do this, we extracted single nucleotide polymorphisms (SNPs) from the GWAS, which strongly associated with the 12 traits, and queried their effects in a large European ALS GWAS (27,265 cases and 110,881 controls). To avoid bias in our MR instruments related to the complex linkage disequilibrium structure of the human leukocyte antigen (HLA) region, we excluded SNPs within this region from the analyses. We computed inverse-variance weighted (IVW) MR estimates and undertook sensitivity analyses using MR methods robust to horizontal pleiotropy. We also performed a reverse MR analysis testing the causal effects of ALS on the above autoimmune traits. After applying Bonferroni correction for multiple testing, our MR analyses showed that the liability to autoimmune disorders does not affect ALS risk. Our reverse MR analysis also did not support the effects of liability to ALS on other autoimmune disorders. The results of the main IVW MR analyses were generally supported by our sensitivity MR analyses. The variance in the exposures explained by the sets of SNPs used as MR instruments ranged from 8.1 × 10-4 to 0.31. Our MR study was well-powered to detect effects as small as an odds ratio (OR) of 1.045 for ALS in the main MR and as small as an OR of 1.32 in the reverse MR. Our MR study does not support a relationship between liability to autoimmune disorders and ALS risk in the European population. The associations observed in epidemiological studies could be partly attributed to shared biology or environmental confounders.


Genetic variation in the interleukin-8 gene promoter and vaginal concentrations of interleukin-8 are not associated with bacterial vaginosis during pregnancy.
Interleukin-8 (IL-8) may play a role in the activation of the vaginal immune system during bacterial vaginosis. However, contradictory results were obtained regarding the involvement of IL-8 in the immunological response during bacteria vaginosis. These apparently contradictory results could be due to different genetic variations of the study groups. Since some gene polymorphisms may affect the level of IL-8 production, the aim of this study was to determine whether the frequency IL-8 promoter alleles and levels of IL-8 in vaginal fluid are associated with bacterial vaginosis during pregnancy. Genotyping for IL-8 polymorphisms in the promoter region of the gene was performed in 34 pregnant women with asymptomatic bacterial vaginosis matched for gestational age with 38 pregnant women without vaginosis. Additionally, vaginal IL-8 levels were assayed by the dual monoclonal antibody sandwich enzyme-linked immunosorbent assay technique. The frequencies of the three polymorphisms were not significantly different between control women and women with bacterial vaginosis. In addition, there was no linkage disequilibrium between the polymorphisms. Furthermore, there was no statistical difference in median vaginal levels of IL-8 between both groups. Neither the frequencies of IL-8 polymorphic alleles nor levels of IL-8 in vaginal fluid were associated with bacterial vaginosis.


Fractalkine signaling and Tau hyper-phosphorylation are associated with autophagic alterations in lentiviral Tau and Aβ1-42 gene transfer models.
Tau hyper-phosphorylation (p-Tau) and neuro-inflammation are hallmarks of neurodegeneration. Previous findings suggest that microglial activation via CX3CL1 promotes p-Tau. We examined inflammation and autophagic p-Tau clearance in lentiviral Tau and mutant P301L expressing rats and used lentiviral Aβ1-42 to induce p-Tau. Lentiviral Tau or P301L expression significantly increased caspase-3 activity and TNF-α, but CX3CL1 was significantly higher in animals expressing Tau compared to P301L. Lentiviral Aβ1-42 induced p-Tau 4 weeks post-injection, and increased caspase-3 activation (8-fold) and TNF-α levels. Increased levels of ADAM-10/17 were also detected with p-Tau. IL-6 levels were increased but CX3CL1 did not change in the absence of p-Tau (2 weeks); however, p-Tau reversed these effects, which were associated with increased microglial activity. We observed changes in autophagic markers, including accumulation of autophagic vacuoles (AVs) and p-Tau accumulation in autophagosomes but not lysosomes, suggesting alteration of autophagy. Taken together, microglial activation may promote p-Tau independent of total Tau levels via CX3CL1 signaling, which seems to depend on interaction with inflammatory markers, mainly IL-6. The simultaneous change in autophagy and CX3CL1 signaling suggests communication between microglia and neurons, raising the possibility that accumulation of intraneuronal amyloid, due to lack of autophagic clearance, may lead microglia activation to promote p-Tau as a tag for phagocytic degradation.


Molecular biology of prostate cancer.
Development of any cancer reflects a progressive accumulation of alterations in various genes. Oncogenes, tumour suppressor genes, DNA repair genes and metastasis suppressor genes have been investigated in prostate cancer. Here, we review current understanding of the molecular biology of prostate cancer. Detailed understanding of the molecular basis of prostate cancer will provide insights into the aetiology and prognosis of the disease, and suggest avenues for therapeutic intervention in the future.


Toll-like receptors: mammalian "taste receptors" for a smorgasbord of microbial invaders.
In Drosophila, the Toll family of proteins is responsible for the recognition of bacteria and fungi. In mammals, Toll-like receptors (TLRs) are able to recognize and respond to microbial pathogens. Recent findings have defined the relationship between many TLRs and their microbial ligands, as well as the effect of TLR ligation on host defense. These findings have also provided a framework for determining how TLRs may by used to therapeutically modulate immune responses to infection.


Standardized electronic health record data modeling and persistence: A comparative review.
With the extensive adoption of electronic health records (EHRs) by several healthcare organizations, more efforts are needed to manage and utilize such massive, various, and complex healthcare data. Databases' performance and suitability to health care tasks are dramatically affected by how their data storage model and query capabilities are well-adapted to the use case scenario. On the other hand, standardized healthcare data modeling is one of the most favorable paths for achieving semantic interoperability, facilitating patient data integration from different healthcare systems. This paper compares the state-of-the-art of the most crucial database management systems used for storing standardized EHRs data. It discusses different database models' appropriateness for meeting different EHRs functions with different database specifications and workload scenarios. Insights into relevant literature show how flexible NoSQL databases (document, column, and graph) effectively deal with standardized EHRs data's distinctive features, especially in the distributed healthcare system, leading to better EHR.


Modulation of sphingolipid biosynthesis in primary cultured neurons by long chain bases.
Sphingolipid biosynthesis was studied in cultured murine cerebellar cells in the absence and presence of exogenous sphingosine homologues with different alkyl chain lengths (12, 18, and 24 carbon atoms). Labeling of cells with [14C]serine for 24 h indicated that endogenous sphingosine biosynthesis with incorporation of radiolabeled serine was inhibited by these long chain bases (0.5-50 microM) in a concentration-dependent manner; the inhibition was fully reversible after removal of the long chain bases from the culture medium. Metabolic labeling of neurons with [14C]galactose provided strong evidence that the cells were able to use the exogenous sphingosine homologues, irrespective of their alkyl chain length, as substrates for the biosynthesis of glycosphingolipids. When the biosynthetically inert sphingoid, azidosphingosine (5-50 microM), was fed to the cells, de novo sphingosine and glycosphingolipid biosynthesis were both strongly inhibited.


11q trisomy detected by fluorescence in situ hybridization.
A patient with psychomotor developmental delay, multiple minor anomalies, congenital heart disease and left inguinal hernia is reported. His karyotype was 45,X/46,X,+mar (3:37 cells), and the marker chromosome was identified as t(Y;11)(q12;q14?) using fluorescence in situ hybridization and fluorescent chromosome painting. He was diagnosed as mosaic for de novo 11q trisomy.


The Use of a Vascular Roadmap at Surgery Evens out Surgeons Expectations on Operating Time, Blood Loss, Lymph Nodes Harvest and Operative Difficulty when Performing Right Colectomy with Extended D3 Mesenterectomy.
To determine how individual vascular road-mapping impacts the surgeonsâ?? expectations in difficulty in D3 right colectomy for cancer, and compare these expectations to the results previously published. Aim/summary background data:Literature still lacks data on surgeons expectations using preoperative 3D roadmap of the vascular system. Surgeons filled out a survey asking expectations about operation time, estimated blood loss, amount of lymph nodes harvested and difficulty. The patients were classified into 4 groups and 2 subgroups according to the crossing pattern of the ileocolic artery and the jejunal veins. SPSS was used for statistical analysis. Results: Twelve surgeons were included. Eight of them expected type 2 anatomy to be least time consuming while 11/12 indicated anatomy group 4 to be the most. Five surgeons expected low blood loss in group 2 anatomy patients while 10/12 expected higher blood loss in group 4 anatomy patients. Three anticipated that group 2 would generate the highest lymph node yield and while 2/12 surgeons expected the lowest in anatomy group 4. Eight surgeons perceived group 2 as the least challenging while 10/12 experienced group 4 as the most difficult. Compared to previously published results only group 4b operating time met surgeons expectations. Using a vascular roadmap at surgery evens out surgeons expectations in operation time, blood loss, lymph node harvested and difficulty. Comparing expectations to previously published data shows operating time in one anatomy group as the only factor where these expectations were met.


Sustained major molecular response on interferon alpha-2b in two patients with polycythemia vera.
Quantitative assessment of the JAK2 V617F allele burden during disease evolution and ongoing myelosuppressive treatment is likely to be implemented in the future clinical setting. Interferon alpha has demonstrated efficacy in treatment of both chronic myeloid leukemia and the Philadelphia chromosome negative chronic myeloproliferative disorders. Reductions in the JAK2 V617F allele burden in patients treated with pegylated interferon alpha-2a (Peg-IFN-2a) have been demonstrated, although follow-up was relatively short. We report here the first profound and sustained molecular responses with a JAK2 V617F allele burden below 1.0% in two patients with polycythemia vera treated with interferon alpha-2b (IFN-2b). Discontinuation of IFN-2b in one of the patients was followed by a sustained long-lasting (12 months of follow-up) major molecular response.


The time course of peritoneal transport kinetics in continuous ambulatory peritoneal dialysis patients who develop sclerosing peritonitis.
The time course of measurements of peritoneal solute transport in four continuous ambulatory peritoneal dialysis (CAPD) patients who developed sclerosing peritonitis is described. Loss of fluid removal capacity was found in all of them. In three, this loss was associated with an increase in peritoneal absorption of glucose from the dialysate and an increase in the transperitoneal transport rates of low-molecular-weight solutes and proteins. In the other patient a decrease in all these parameters was found. This seems to imply that the effective peritoneal surface area was increased in three patients and decreased in one. Peritoneal permeability to macromolecules remained unchanged as judged by the ratio between the clearance of IgG and albumin. Among the possible factors that contribute to the development of sclerosing peritonitis, some are likely to lead to a larger effective peritoneal surface area, like prostacyclin and the formation of new capillaries in poorly vascularized parts of the peritoneum. Others, such as extensive formation of collagen, could lead to a smaller effective surface area. Individual differences in susceptibility to these factors may lead to an increase or decrease in peritoneal solute transport rates. Follow-up measurements of peritoneal solute kinetics are necessary to identify those patients who are at risk.


Anxiolytic properties of the antipsychotic alkaloid alstonine.
Anxiolytic properties may be a crucial feature of newer antipsychotics associated with the improvement of negative symptoms in schizophrenic patients. The indole alkaloid alstonine acts as an atypical antipsychotic in behavioral models, but differs in its dopamine and serotonin binding profile. The purpose of this study was to verify if alstonine possesses anxiolytic properties in mice. The hole-board and light/dark models were used; moreover, the participation of D(1), 5-HT(2), NMDA and gamma-aminobutyric acid (GABA) receptors was likewise investigated. Alstonine clearly behaves as anxiolytic in both hole-board and light/dark situations. Pretreatment with the 5-HT(2A/2C) serotonin receptor antagonist ritanserin reverted the effects of alstonine in both the hole-board and light/dark models, suggesting the involvement of these receptors in the alstonine mechanism of action. The involvement of glutamate NMDA receptors should also be considered, given that alstonine partially reversed the increase in locomotion induced by MK-801 in the hole board, as well as MK-801-induced hyperlocomotion in motor activity apparatus.


Ultrasound treatment of frozen crayfish with chitosan Nano-composite water-retaining agent: Influence on cryopreservation and storage qualities.
The synergistic impact of ultrasound and Nano-water retaining agent on the cryoprotective effect on crayfish during frozen storage was investigated. The samples soaked in water-retaining agent (WRA), ultrasonic 60 W treatment combined with water-retaining agent (WRA-US60W) and ultrasonic 80 W treatment combined with water-retaining agent (WRA-US80W) were frozen storage at -18 °C. The indices of frozen storage in 0, 7, 14, 21, 28, 35 and 42 days were measured. The results showed that there was a significant difference in the soaking weight gain, thawing loss, water content and water activity between control group and WRA groups (P < .05). The ultrasound combined with WRA treatment showed better water retention effect. The water holding capacity of heat induced gel decreased continuously during the frozen storage period, and the WRA-US60W group exhibited significantly higher values than that of other treatment groups (P < .05). The texture characteristics of hardness, elasticity and chewiness had a significant change (P < .05). The development of total volatile base nitrogen content, myofibrillar protein content and Ca2+-ATPase activity of muscle protein were significantly delayed by WRA-US60W treatment, maintaining the integrity of tissue structure. Therefore, WRA-US60W treatment was found effectively improving the quality of crayfish during frozen storage.


Study of the propensity for hemorrhage in Hispanic Americans with stroke.
Multiple sources document a higher proportion of intraparenchymal hemorrhage (HEM) in Hispanic (HIS) than white (WHI) patients with stroke. We sought an explanation for this phenomenon through analysis of multiple variables in our hospital-based stroke population. We performed univariate and multivariate analysis of risk factors in our HIS and WHI patients with stroke to identify differences that might account for a greater propensity for HEM in HIS patients. Multivariate analysis disclosed that the risk of HEM correlated significantly with untreated hypertension (HTN), HIS ethnicity, and heavy alcohol intake. A negative correlation was found for hyperlipidemia and diabetes. Our HIS patients with stroke had a greater prevalence of untreated HTN and heavy alcohol intake, with HIS men being at greatest risk. HIS patients with stroke in our hospital-based population appear relatively more prone to HEM than do WHI patients. This risk correlates with a greater likelihood of having untreated HTN and heavy alcohol intake, more so for HIS men. The explanation appears to be a relative lack of health awareness and involvement in our health care system. The possibility that HIS ethnicity itself constitutes a biological risk factor for HEM remains a matter of speculation. Validation of this work with community data should lead to remediation through a community-based effort.


Advances in insulin therapy for insulin-dependent diabetic children.
During the last two decades new forms of insulin and a better understanding of the physiological insulin secretion profile have led to great changes in insulin therapy. New insulin regimens mimicking the normal insulin secretory pattern, called intensive insulin therapy, and new insulin-delivery systems have been introduced. Self-monitoring of blood glucose levels and the use of glycosylated hemoglobin determination for objective evaluation of long-term control have made the achievement of near normoglycemia a practical goal for most patients taking insulin. 1. New forms of insulin: Beef and pork insulin were replaced by monocomponent pork insulin and now monocomponent human insulin is most popularly used. 2. Intensive insulin therapy: Intensified conventional insulin therapy, that is a multiple injection regimen and a twice a-day insulin regimen using a mixture of intermediate- and short-acting insulins has been commonly accepted. New devices such as pen-type injectors and jet-injectors have also been introduced for simplifying the multiple injection regimen. Continuous subcutaneous insulin injection (CSII) has also been adopted by adolescents and young adults.


In-depth transcriptomic and proteomic analyses of the hippocampus and cortex in a rat model after cerebral ischemic injury and repair by Shuxuetong (SXT) injection.
There is a lack of systematic descriptions and characterization of strokes and their effects in both the cerebral hippocampus and cortex. Shuxuetong (SXT) injection was reported to have good therapeutic effects in the clinic; therefore, it was selected as a drug intervention method for cerebral ischemia repair in rat models. The aim of this study was to understand the features of molecules and pathways and to reveal key processes of SXT repair. Evaluation of neurological deficit and infarct volume measurement was used to estimate the pharmacological effects of SXT injection on Ischemia-reperfusion(I/R) model rats. LC-MS/MS and RNA-Seq analysis were used to analyze the proteins and mRNA expression in the cerebral hippocampus and cortex 6 h and 24 h after ischemic injury and repair. A label-free approach (IBAQ) for proteomics analysis and FPKM based on gene read count for transcriptomics analysis were used to quantify the differences among the three experimental groups (Sham, Model and SXT-treated groups). Transcriptomics and proteomics analyses were verified by RT-qPCR and western blotting. By combining LC-MS/MS and RNA-Seq, eight larger datasets (two time points and two tissues) were confidently identified in more than three biological replicates. An average of 4500 unique proteins and 8200 protein-coding genes were confidently identified. By combining the subcellular localization, hierarchical clustering, pathway enrichment analysis in the injury and repair phase, six core proteins and related genes that were significantly expressed were verified as candidates for cerebral ischemic injury by western blotting and quantitative real-time PCR. Meanwhile, the results indicated that there was better expression in the 6 h group by significant proteomics analysis during the development and progression of cerebral ischemia. Two primary co-enriched pathways, the PI3K-AKT and MAPK signaling pathways, and six related core candidates may play key roles in molecular mechanisms related to cerebral ischemic injury and repair by SXT injection. Our data not only identified six core candidates and two key signaling pathways for cerebral ischemic injury and verification but also provided evidence for the explanation, prevention and treatment of cerebral ischemia by SXT injection. The results of the present study provide evidence for the explanation, prevention and treatment of cerebral ischemia by SXT injection.