Decontamination efficacy of sodium hypochlorite solutions for poliovirus.
Effective decontamination procedures are critical to the successful manufacture and control of poliovirus vaccines to minimize the risk to personnel and the environment. Polio viruses have been reported to be more resistant to disinfectants than many other viruses. We assessed the efficacy of sodium hypochlorite-containing disinfectants for decontamination for three poliovirus serotypes to implement decontamination procedures that are fully compliant with the WHO GAP III and Health authorities' requirements. A 10.4 log reduction was observed with a 0.63% sodium hypochlorite solution in a suspension with high protein and high poliovirus concentrations diluted 10-fold compared with a 6 log reduction in an undiluted sample. Treatment efficacy increased with sodium hypochlorite content and decreased with sample protein content. The surface tests showed that two 1-min treatments, 5-min apart, with a 0.63% Chl sodium hypochlorite solution effectively reduced the concentration of all poliovirus serotypes by 10 log10, irrespective of the protein and virus concentration in the sample. Sodium hypochlorite solutions lower than 0.52% were less effective for complete inactivation of poliovirus. In conclusion, we demonstrated that a high level of virus reduction (>10 log10) can be achieved with sodium hypochlorite solutions with poliovirus in suspension and dried on surfaces.


Interrupted oligomerization revisited: simple and efficient one-pot multicomponent approach to versatile synthetic intermediates.
A novel multicomponent reaction allowing for a one-pot formation of three carbon-carbon bonds has been developed. It is based on in situ generation and anionic dimerization of methylenedithiane and produces a versatile synthetic equivalent of 4-hydroxy-1,3-alkanediones which, among other things, offers expeditious one-pot access to 3(2H)-furanones.


Retracted: Innovative Application of Artificial Intelligence in the Field of Innovation and Entrepreneurship of College Students in Internet Colleges and Universities.
[This retracts the article DOI: 10.1155/2022/3538755.].


Pluripotent Stem Cells for the Treatment of Retinal Degeneration: Current Strategies and Future Directions.
Stem cells have been part of the biomedical landscape since the early 1960s. However, the translation of stem cells to effective therapeutics have met significant challenges, especially for retinal diseases. The retina is a delicate and complex architecture of interconnected cells that are steadfastly interdependent. Degenerative mechanisms caused by acquired or inherited diseases disrupt this interconnectivity, devastating the retina and causing severe vision loss in many patients. Consequently, retinal differentiation of exogenous and endogenous stem cells is currently being explored as replacement therapies in the debilitating diseases. In this review, we will examine the mechanisms involved in exogenous stem cells differentiation and the challenges of effective integration to the host retina. Furthermore, we will explore the current advancements in trans-differentiation of endogenous stem cells, primarily Müller glia.


Salience of self-identity roles in persons with dementia: differences in perceptions among elderly persons, family members and caregivers.
In this study, we explored perceptions of the salience of self-identity in persons suffering from dementia as perceived by the participants themselves, by family, and by staff caregivers. Four types of role-identity were explored: professional, family role, hobbies/leisure activities, and personal attributes. Participants were 104 persons with dementia, 48 of whom attended six adult day care centers while 56 resided in two nursing homes in the Washington, DC metropolitan area. Participants, relatives, and staff members were interviewed to obtain information about past and present self-identity roles of participants and attitudes toward these roles. Findings demonstrate that the importance of role identities decreases over time and with the progression of dementia. The family role was found to be the most important and salient role identity according to all the informant groups. The professional role was the one that showed the steepest decline in importance from past to present. Gender differences were detected for the importance of professional role identity. Participants rated their roles in the past as less important and those in the present as more important compared to family members. Family members reported greater decline in the importance of role identities for those participants with greater cognitive impairment. Participants with moderate cognitive impairment reported greater decline in the importance of role identities than did the participants with severe cognitive impairment. Understanding the past and present self-identities of persons with diminished cognitive abilities is crucial in the effort to provide individualized care and enhance participant experiences.


Chemical sphincterotomy in posthemorrhoidectomy pain relief: a meta-analysis.
This study aims to evaluate the pain relief function of chemical sphincterotomy in patients undergoing haemorrhoid surgery and compare, through a meta-analysis, the different drugs used to treat this condition. We conducted a search in databases including PubMed, EMBASE and Web of Science. The methodological quality was evaluated using the Revised Cochrane risk-of-bias tool for randomized trials (ROB2). The pain score was assessed using a visual analogue scale (VAS) on day 1, day 2, and day 7, and a meta-analysis was conducted based on the use of random effects models. In addition, the subgroup analysis was evaluated based on the kind of experimental drugs. Heterogeneity and publication bias were assessed. Fourteen studies with a total of 681 patients were included in this meta-analysis, and all studies were randomized controlled trials RCTs. Chemical sphincterotomy showed better pain relief function than placebo on day 1 (SMD: 1.16, 95% CI 0.52 to 1.80), day 2 (SMD: 2.12, 95% CI 1.37 to 2.87) and day 7 (SMD: 1.97, 95% CI 1.17 to 2.77) after surgery. In the subgroup meta-analysis, we found that different drugs for chemical sphincterotomy provided different pain relief. Chemical sphincterotomy effectively relieves pain after haemorrhoidectomy, and calcium channel blockers have the best effect.


Developmental effects of perinatal exposure to bisphenol-A and diethylstilbestrol on reproductive organs in female mice.
Reproductive tract development is influenced by estrogen. The aim of this study was to determine the effects of an environmental estrogenic chemical bisphenol-A (BPA) on prenatal and postnatal development of female mouse reproductive organs. In the prenatal treatment group, BPA or the synthetic estrogen diethylstilbestrol (DES) were given by subcutaneous (s.c.) injections to pregnant mice during gestational days 10-18. Some offspring treated prenatally with 10 and 100 mg/kg bw BPA or 0.67 and 67 microg/kg bw DES were ovariectomized at 30 days and sacrificed at 40 days of age. Vaginal smears were examined in the remaining offspring, then these offspring were mated with normal males. Prenatal exposure to 10 mg/kg BPA reduced the number of mice with corpora lutea compared to sesame oil controls at 30 days, but more than 80% of mice from either prenatally exposed BPA group were fertile at 90 days. Mice exposed prenatally to maternal doses of 67 microg/kg DES were sterile and showed ovary-independent vaginal and uterine epithelial stratification; however, mice exposed prenatally to BPA did not show ovary-independent vaginal and uterine changes. The number of offspring and litter sex ratio from mice exposed prenatally to BPA (10 or 100 mg/kg) or 0.67 microg/kg DES were not different compared to controls. In postnatal treatment group, female mice were given s.c. injections of BPA (15 or 150 microg/pup) or DES (0.3 or 3 microg/pup) for 5 days from the day of birth, then some mice were ovariectomized at 30 days and examined at 40 and 90 days. In the remaining mice, vaginal smears were examined from 61 to 90 days and ovarian histology was evaluated at 90 days. Mice exposed postnatally to 150 microg BPA exhibited ovary-independent vaginal epithelial stratification. Postnatal DES (0.3 and 3 microg) treatment also induced ovary-independent vaginal stratification. Polyovular follicles having more than one oocyte in a follicle were induced by postnatal injections of BPA (150 microg) or DES (0.3 or 3 microg) at 30 days. These findings indicate for the first time that a large dose of BPA can induce ovary-independent vaginal epithelial changes when given postnatally but not prenatally.


In silico and in vitro screening for carcinogenic potential of angiotensin-converting enzyme inhibitors and their degradation impurities.
According to some clinical observations, the use of angiotensin-converting enzyme inhibitors (ACEI) may be associated with an increased risk of cancer. The aim of the present study was to screen for the potential carcinogenicity, mutagenicity and genotoxicity of these drugs using in silico methodology. Delapril, enalapril, imidapril, lisinopril, moexipril, perindopril, ramipril, trandolapril, spirapril were thereby analyzed. In parallel, the corresponding degradation impurities, the diketopiperazine (DKP) derivatives, were also investigated. (Q)SAR computer software (VEGA-GUI and Lazar), available in the public domain, was employed. The obtained predictions suggested that none of the compounds tested (from the group of ACE-Is and DKPs) was mutagenic. Moreover, none of the ACE-Is was carcinogenic. The reliability of these predictions was high to moderate. In contrast, in the DKP group, ramipril-DKP and trandolapril-DKP were found to be potentially carcinogenic, but the reliability of this prediction was low. As for the genotoxicity screening, all compounds tested (ACE-I and DKP) were predicted to be active and genotoxic, with moexipril, ramipril, spirapril, and all DKP derivatives within the highest risk group. They were prioritized for experimental verification studies to confirm or exclude their toxic activity. On the other hand, the lowest risk of carcinogenicity was assigned to imidapril and its DKP. Then, a follow-up in vitro micronucleus assay for ramipril was performed. It showed that this drug was genotoxic via aneugenic activity, but only at concentrations exceeding real-life levels. At concentrations found in human blood after standard dose, ramipril was not genotoxic in vitro. Therefore, ramipril was considered safe for human use with a standard dosing regimen. The other compounds of concern (spirapril, moexipril and all DKP derivatives) should be subjected to analogous in vitro studies. We also concluded that the adopted in silico software was applicable for ACE-I toxicity prediction.


Elevated levels of immunoreactive prostacyclin metabolite in babies who develop intraventricular haemorrhage.
Measurement of 6-ketoprostaglandin F1-alpha by radioimmunoassay was made during the first three days of life in a group of 48 preterm neonates at risk of intraventricular haemorrhage. The babies who developed haemorrhage had significantly higher levels than those who did not, and failed to show the falling levels seen over the first three days of life in the nonhaemorrhage group. It is suggested that high levels of prostacyclin in low birthweight babies may be one factor which contributes to the alterations of cerebral blood flow and capillary bleeding time which predispose to intraventricular haemorrhage.


Nuclear receptors: a rendezvous for chromatin remodeling factors.
Nuclear receptors (NRs) are a large family of ligand-induced transcription factors that include the vitamin D receptor. The recent discovery of WINAC, a novel ATP-dependent chromatin remodeling complex, has shed new light on the molecular mechanisms by which the vitamin D receptor controls gene expression with unexpected clinical implications.


Quantitative Assessment of Levonorgestrel Binding Partner Interplay and Drug-Drug Interactions Using Physiologically Based Pharmacokinetic Modeling.
Levonorgestrel (LNG) is the active moiety in many hormonal contraceptive formulations. It is typically coformulated with ethinyl estradiol (EE) to decrease intermenstrual bleeding. Due to its widespread use and CYP3A4-mediated metabolism, there is concern regarding drug-drug interactions (DDIs), particularly a suboptimal LNG exposure when co-administered with CYP3A4 inducers, potentially leading to unintended pregnancies. The goal of this analysis was to determine the impact of DDIs on the systemic exposure of LNG. To this end, we developed and verified a physiologically-based pharmacokinetic (PBPK) model for LNG in PK-Sim (version 8.0) accounting for the impact of EE and body mass index (BMI) on LNG's binding to sex-hormone binding globulin. Model parameters were optimized following intravenous and oral administration of 0.09 mg LNG. The combined LNG-EE PBPK model was verified regarding CYP3A4-mediated interaction by comparing to published clinical DDI study data with carbamazepine, rifampicin, and efavirenz (CYP3A4 inducers). Once verified, the model was applied to predict systemic LNG exposure in normal BMI and obese women (BMI ≥ 30 kg/m2 ) with and without co-administration of itraconazole (competitive CYP3A4 inhibitor) and clarithromycin (mechanism-based CYP3A4 inhibitor). Total and free LNG exposures, when co-administered with EE, decreased 2-fold in the presence of rifampin, whereas they increased 1.5-fold in the presence of itraconazole. Although changes in total and unbound exposure were decreased in obese women compared with normal BMI women, the relative impact of DDIs on LNG exposure was similar between both groups.


Clinical value of histologic endometrial dating for personalized frozen-thawed embryo transfer in patients with repeated implantation failure in natural cycles.
Displacement of the window of implantation (WOI) has been proposed as an important factor contributing to repeated implantation failure (RIF). However, the use of histologic endometrial dating as a diagnostic tool of endometrial receptivity has been questioned. This study is a prospective intervention trial that enrolled 205 infertile patients from July 2017 to December 2017. Endometrial biopsies from 50 patients with good prognoses were conducted on day 3 (n = 6), 5 (n = 6), 7 (n = 26), 9 (n = 6), or 11 (n = 6) post-ovulation (PO + 3/5/7/9/11) of the previous natural cycle before their conventional frozen-thawed embryo transfer (FET) cycle. We conducted endometrial biopsies for 155 RIF patients on day PO + 7. The verification of the Noyes criteria for endometrial dating was conducted at different times (PO + 3/+ 5/+ 7/+ 9/+ 11) on 41 patients with good prognoses who achieved an ongoing pregnancy in their first conventional FET cycle after endometrial biopsy. The agreement between two pathologists determining endometrial biopsy dating results in infertile patients was determined to be acceptable (weighted kappa = 0.672, P < 0.001). The rate of out-of-phase dating on day PO + 7 was significantly higher in RIF patients than in good- prognosis patients (31.6% vs. 3.8%, P = 0.003). pFET was performed in 47 RIF patients diagnosed to be out of phase, and the cumulative live-birth rate was 61.7%. Histologic endometrial dating of RIF patients in natural cycles may be a biomarker for a receptive endometrium in diagnosing WOI displacement. NCT03312309 Registered 17 October 2017. NCT03222830 Registered 19 July 2017.


What is the minimum length of gltA gene required for phylogenetic analyzes in Bartonella?
Bartonellosis is an emerging serious diseases of zoonotic relevance caused by an expanding number of recently discovered species of Bartonella. Many studies use partial gltA gene sequencing as the method of choice for species attribution, and a plethora of studies have utilized only this gene to describe Bartonella diversity. We observe a lack of correspondence between the phylogenies constructed using the complete gltA gene sequences and the small gene fragment usually used in phylogenetic analyzes. Everything indicates that important changes occurred by using larger fragments. Therefore, it is of great importance to define a minimum gltA fragment length to be used in future phylogenetic analyzes, besides the use of other genes.


Complete Genome Sequences of Two Flavobacterium ammonificans Strains and a Flavobacterium ammoniigenes Strain of Ammonifying Bacterioplankton Isolated from Surface River Water.
Flavobacterium ammonificans and Flavobacterium ammoniigenes are ammonifying freshwater bacterioplankton. Here, we report the complete genome sequences of two F. ammonificans strains (SHINM13T and GENT11) and one F. ammoniigenes strain (GENT5T) that were isolated from surface river water in Japan.


Longitudinal Analysis of COVID-19 Impacts on Mobility: An Early Snapshot of the Emerging Changes in Travel Behavior.
The COVID-19 pandemic has caused a huge disruption worldwide with direct and indirect effects on travel behavior. In response to extensive community spread and potential risk of infection, during the early stage of the pandemic many state and local governments implemented non-pharmaceutical interventions that restricted non-essential travel for residents. This study evaluates the impacts of the pandemic on mobility by analyzing micro panel data (N = 1,274) collected in the United States via online surveys in two periods, before and during the early phase of the pandemic. The panel makes it possible to observe initial trends in travel behavior change, adoption of online shopping, active travel, and use of shared mobility services. This analysis intends to document a high-level overview of the initial impacts to spur future research to dive deeper into these topics. With the analysis of the panel data, substantial shifts are found from physical commutes to teleworking, more adoption of e-shopping and home delivery services, more frequent trips by walking and biking for leisure purposes, and changes in ridehailing use with substantial variations across socioeconomic groups. The social and environmental implications of these findings are discussed and suggestions for effective policy and directions for future research are made in the conclusion.


Knowledge and attitudes of orthopedic surgeons regarding prosthesis joint infection.
Periprosthetic joint infection (PJI) is a critical complication after joint arthroplasty and is accompanied by increasing rates of morbidity and mortality. Several studies have aimed at preventing PJI. To research the knowledge level and attitudes of orthopedic surgeons, who play a key role in both preventing and managing PJI. We conducted a web-based survey to evaluate orthopedic surgeons' knowledge level and attitudes regarding PJI. The Likert scale survey utilized consisted of 30 questions which were prepared based on the "Proceedings of the International Consensus on Periprosthetic Joint Infection". A total of 264 surgeons participated in the survey. Their average age was 44.8, and 173 participants (65.5%) had more than 10 years of experience. No statistically significant relationship was found between the PJI knowledge of the surgeons and their years of experience. However, participants who worked in training and research hospitals demonstrated higher levels of knowledge than the ones in the state hospitals. It was also noticed that surgeons' knowledge concerning the duration of antibiotic therapy and urinary infections was not consistent with their attitudes. Even though orthopedic surgeons have adequate knowledge about preventing and managing PJI, their attitudes might contradict their knowledge. Future studies are required to examine the causes and solutions of the contradictions between orthopedic surgeons' knowledge and attitudes.


Incorporating hematopoietic cell transplantation (HCT) into the management of adults aged under 60 years with acute myeloid leukemia (AML).
Current strategies for incorporating hematopoietic cell transplantation into the treatment of adults with AML are based predominantly on pre-treatment patient, donor and disease characteristics. These strategies, while useful, have significant shortcomings in that they recommend deferred transplantation for many patients who would benefit from earlier intervention and, at the same time, direct other patients who would be cured with chemotherapy alone to the more risky and toxic approach of early transplantation. Here we review the currently accepted indications for transplantation and raise the possibility that alternative approaches to incorporating transplantation into the management of adults with AML that rely predominantly on the measurement of minimal residual disease (MRD) could save additional lives without any major advance in chemotherapy or transplant technologies.


Environmental influences on photosynthesis within the crown of a white oak.
Photosynthesis, leaf conductance, xylem pressure potential as well as six environmental factors were measured within the crown of a dominant, 18.9 m, white oak tree (Quercus alba L.) during the summers of 1974 and 1975. Photosynthesis was measured with a 14CO2 apparatus which enabled a description of the within crown and with leaf variations to be made. Photosynthesis averaged 7.0, 5.6 and 4.6 mgCO2 dm-2 h-1 for top, middle and bottom crown positions. High leaf temperatures and mid-day stomatal closure appeared to limit photosynthesis in the upper crown while light appeared limiting in the lower. Under conditions of a moderate drought, the lower crown's photosynthethic activity approached that of the upper crown. Seasonal shifts in photosynthesis were noted and these were related to shifts in leaf conductance associated with temperature or drought or both pre-conditioning. For example, the xylem pressure potential threshold for stomatal closure varied from-18.9 to-26.1 bars depending upon drought history. With the 14CO2 technique, photosynthetic activity was statistically uniform over the entire leaf surface; thus sampling location within a white oak leaf was not a matter of concern. Similarly, no statistically significant within-leaf variation was found with respect to leaf conductance.


Development of the Idiopathic Toe Walking Outcome (iTWO) proforma: A modified delphi study and online parent survey for measurement consensus.
Idiopathic toe walking (ITW) is an exclusionary diagnosis given when children toe walk without a medical reason. Treatment effectiveness studies rarely collect data other than ankle range of motion or presence of toe walking. To develop a set of outcome measures identified by health professionals for use when providing treatment with children who have ITW, to understand if parents agreed with this set, and if parents believed they could perform these measures in clinician absence. Study 1 developed consensus and agreement on outcome measures for children receiving treatment for ITW through the modified Delphi technique with 10 expert health professionals. Parents of children who toe walked were invited to participate in an online survey for the second study, in which they were asked to rate the importance of these measures and if they believed they may be able to collect the data about their child without the health professional being present. Ten health professionals developed nine questions and assessments through consensus and agreement over the three rounds. There were 34 parents providing information about satisfaction with toe walking assessments and treatments. Of these, 27 provide detailed responses about the outcome questions and assessments. The majority (91 % of 24 parents) in support of the outcome measures identified by experts. Parents expressed a willingness to self-complete questions or be taught assessments to monitor their child's progress. Use of these clinically based measures may enable consistent data collection regardless of the setting and provide the foundation for large data pooling in future treatment research.


The distribution and morphologic variation of hyaline deposits in odontogenic lesions.
The deposits of homogeneous hyaline substances present in epithelium-containing odontogenic lesions were evaluated in 201 tumors. The material was evaluated to establish the types of odontogenic lesions capable of producing the substance, its frequency of occurrence, its microscopic variation, and the different morphologic relationships of the substance to the odontogenic epithelium present in the lesions. The deposits were found in 40.3 percent of the 201 odontogenic tumors and frequently in several other nonneoplastic odontogenic lesions. It was most consistent in odontomas but was found to some extent in all types of epithelium-containing odontogenic tumors. It was present either in a basement membrane location or as a diffuse deposit in the connective tissue. In the latter location, the deposits commonly contained enclaved islands of odontogenic epithelium and had a distinct tendency to calcify. The study also suggests that since some odontogenic tumors may contain large amounts of the hyaline deposits, multiple sections through different parts of the tumor may be required to find the epithelial elements necessary for the correct diagnosis.


Cell cycle time determinations based on liquid scintillation counting of 3H-TdR labeled mitotic cells.
Following a 10 min pulse labeling with 3H-TdR, flasks of asynchronous monolayer cultures of Chinese hamster ovary cells were subjected to mitotic selection at 2 hr intervals. The mitotic index of the selected populations was always greater than 90%. Counts per min per cell obtained by liquid scintillation counting were plotted versus time after the pulse label. Comparisons were made between cycle times obtained by the mitotic-scintillation counting method and by the standard per cent labeled mitosis technique. The resulting curves were used for calculations of the cell cycle times and the lengths of G1, S, G2 and M phases of the cell cycle. There was less than 2% difference in the cell cycle times obtained using the scintillation method as compared to times calculated from autoradiographic data obtained from individual petri dishes. The mitotic-scintillation counting technique is simple, accurate and rapid and allows the calculation of the cell kinetics parameters within 1 hr of the end of the experiment.


Effective stiffness of qPlus sensor and quartz tuning fork.
Quartz tuning forks (QTFs) have been extensively employed in scanning probe microscopy. For quantitative measurement of the interaction in nanoscale using QTF as a force sensor, we first measured the effective stiffness of qPlus sensors as well as QTFs and then compared the results with the cantilever beam theory that has been widely used to estimate the stiffness. Comparing with the stiffness and the resonance frequency in our measurement, we found that those calculated based on the beam theory are considerably overestimated. For consistent analysis of experimental and theoretical results, we present the formula to calculate the stiffness of qPlus sensor or QTF, based on the resonance frequency. We also demonstrated that the effective stiffness of QTF is twice that of qPlus sensor, which agrees with the recently suggested model. Our study demonstrates the use of QTF for quantitative measurement of interaction force at the nanoscale in scanning probe microscopy.


Synthesis of alpha-aryl N-adamant-1-yl nitrones and using them for spin trapping of hydroxyl radicals.
alpha-Aryl N-adamant-1-yl nitrones were synthesized and evaluated with respect to the stability of the hydroxyl radical adduct. The polarity and water solubility of nitrones were altered with changing the alpha-aryl groups. Introduction of adamantane ring instead of tert-butyl group resulted in a reasonable good stability of hydroxyl radical adduct for biological measurements.


A stimulating effect of guanyl nucleotides on the rat-liver soluble cyclic GMP high-affinity phosphodiesterase activity.
The high affinity (low Km) cyclic GMP phosphodiesterase (PDE) is activated by GTP, while the cyclic AMP PDE is not. GTP and its hydrolysis-resistant analogue, guanylylimidodiphosphate (GppNHp), display a half-maximal stimulating effect at almost the same concentration (5 X 10(-6) M). The GTP stimulating effect is not observed when the socalled cyclic GMP low affinity (high Km) PDE is operative. GTP cooperates with the increase of the substrate concentration on removing the IBMX inhibitory effect. The isolation through a classical chromatographic procedure on a DEAE-cellulose column, of a PDE fraction specific for cyclic GMP, results in the loss of the GTP stimulating effect.


Surface adsorption and vesicle formation of dilauroylphosphatidylcholine in room temperature ionic liquids.
Surface chemical properties of a phospholipid, dilauroylphosphatidylcholine (DLPC), in two ionic liquids (ILs), 1-butyl-3-methylimidazolium tetrafluoroborate (bmimBF(4)) and hexafluorophosphate (bmimPF(6)), were investigated by means of surface tension, dynamic light-scattering, and freeze-fracture transmission electron microscopy. It was found that DLPC shows finite solubility in the ILs and spontaneously forms vesicles with size distribution around 400 nm in diameter above the critical vesicular concentration (CVC) of 0.040 wt.% (in bmimBF(4)) and approx. 0.08 wt.% (in bmimPF(6)). Other than the CVC value, anion specificity of the ILs was also seen in the temperature effect on the vesicular aggregation; that is, a temperature-induced reversible aggregation was observed in bmimPF(6), but not in bmimBF(4). The differences in the vesicular stability against the temperature-induced aggregation could be attributed to differences in the interaction between anion species of the ILs and zwitterionic phosphatidylcholine head groups. The apparent molecular area occupied by DLPC at the air/solution interface was estimated to be 0.37 nm(2) in bmimBF(4) and 0.20 nm(2) in bmimPF(6) by applying the Gibbs adsorption equation. These values are much smaller than the molecular area of 0.69 nm(2) reported for the hydrated DLPC bilayer of lamellar liquid-crystalline phase. This result is not consistent with the traditional Gibbs adsorption model, but can be interpreted in terms of a picture for the surface adsorption of soluble amphiphiles proposed by Moroi et al. Differential scanning calorimetric study is also reported regarding the phase transition behavior of DLPC bilayer solvated by the ILs.


Maturational changes in the respiratory rhythm generator of the mouse.
The changes in motor activity of the respiratory rhythm generator were quantitatively analysed in mice (from birth to at least 56 days old) in both awake and anaesthetized preparations, as well as in vitro to define the age at which the respiratory network is mature. In awake and anaesthetized spontaneously breathing mice respiratory-related thoracic movements were recorded and revealed an age-dependent increase in both inspiratory time (45%) and cycle length (22%) over the first 15 days of life. Similarly, the pattern of phrenic nerve activity recorded from anesthetized animals also changed from a short, rapid onset and offset burst, without a post-inspiratory phase (0-10 days old), to a discharge of longer duration which included both ramp and post-inspiratory components (> 15 days). This pattern was comparable to that seen in adult mice (> 56 days old). A recently developed tilted-sagittal brainstem slice preparation containing an isolated, but functionally intact, medullary respiratory network was employed in our in vitro studies. Since this preparation generates respiratory rhythmic activity spontaneously in both neonatal and mature mice (> 56 days old) it has permitted a direct comparison of the respiratory motor output pattern, recorded from the hypoglossal (XII) motor nucleus, during post-natal development in similar preparations. Consistent with our in vivo findings there was an age-dependent change in the motor pattern. The rhythmic burst of XII neurones recorded from slices of neonates (0-10 days old) was short in duration and decremented whereas a longer discharge (increase of 625% compared to neonate) containing a plateu component was seen in animals more than 15 days old. In addition, the cycle length of rhythmic XII neurones increased (143%) and, together with the changes in burst duration, reached a steady-state value over a similar time course to the maturational changes in phrenic nerve activity recorded in vivo.


Intubating conditions and onset of neuromuscular block of rocuronium (Org 9426); a comparison with suxamethonium.
The intubating conditions and neuromuscular blocking profile following 600 micrograms.kg-1 rocuronium (Org 9426) have been investigated in patients under various experimental conditions. They were compared with conditions following 1.5 mg.kg-1 suxamethonium, preceded by a precurarising dose (10 mg) of gallamine, and with those in a control group in the absence of a muscle relaxant. Rocuronium produced good to excellent intubating conditions at 60 as well as at 90 s after administration, even though there was only a partial blockade of the adductor pollicis muscle. Intubating conditions following suxamethonium were comparable with those after rocuronium. Half of the control patients could be intubated. The clinical duration and the recovery time of 600 micrograms.kg-1 of rocuronium were 24(4) and 9(3) min (mean(s.d.)), respectively. Rocuronium may have a major advantage over existing non-depolarising muscle relaxants due to the early presence of excellent intubating conditions. The results indicate that rocuronium may replace suxamethonium in procedures in which rapid sequence induction is required.


Antimycobacterial and nitric oxide production inhibitory activities of limonoids isolated from Trichilia lepidota subsp. schumanniana (Harms) T.D.Penn.
Six previously undescribed intact limonoids together with four known compounds were isolated from the seeds of Trichilia lepidota subsp. schumanniana (Harms) T.D.Penn. Their structures were characterized based on one- and two-dimensional nuclear magnetic resonance spectra, infrared, ultraviolet, mass spectroscopy results, and optical rotation. All compounds were evaluated for their ability to inhibit nitric oxide production in cultures of RAW 264.7 macrophages stimulated by lipopolysaccharide, cytotoxicity and growth of Mycobacterium tuberculosis strains H37Rv and M299. The compounds 7-deacetyl-11β,12α-diacetoxy-14,15-epoxyazadirone (5) and walsurin E (9) were the most potent in inhibiting nitric oxide production, although the compounds 1-deshydroxy-12α-acetoxymunronin N (1) and 6α,12α-dihydroxyazadirone (6) also showed controlled potential of this mediator, in addition to being potent growth inhibitors of Mycobacterium tuberculosis H37RV and M299, without cytotoxicity interference. Ring intact limonoids isolated from Trichilia lepidota subsp. schumanniana seeds are a new source of bioactive substances that may be used in the future against diseases such as tuberculosis and other processes related to inflammation.


Depression and cardiovascular disease events among patients with type 2 diabetes: A systematic review and meta-analysis with bias analysis.
To provide updated systematic and quantitative summary of the association between depression and the risk of CVD events among individuals with type 2 diabetes. We also aimed to examine the sensitivity of the association to uncontrolled confounding. Data sources included Medline, Embase, and PsycInfo through September 2019. Two independent reviewers selected cohort studies that evaluated the association between depression and fatal or non-fatal CVD events among individuals with type 2 diabetes. Bias analysis was performed using the bias formula approach. Of 2527 citations screened, 17 eligible studies with a total of 1,033,131 participants were identified. Based on random-effects meta-analysis, depression was associated with higher risks of non-fatal CVD events (relative risk 1.35, 95% confidence interval [CI] 1.20 to 1.53) and fatal CVD event (relative risk 1.47, 95% CI 1.21 to 1.77). Bias analysis indicated that unmeasured confounders alone may not explain the observed association between depression and CVD events among individuals with type 2 diabetes. Depression was associated with a higher risk of non-fatal and fatal CVD events among individuals with type 2 diabetes. Our findings provide updated and robust evidence about the association between depression and CVD events among individuals with type 2 diabetes.


The Effect of Fingolimod on Conversion of Acute Gadolinium-Enhancing Lesions to Chronic T1 Hypointensities in Multiple Sclerosis.
Brain lesions converting to chronic T1 hypointensities ("chronic black holes" [CBH]), indicate severe tissue destruction (axonal loss and irreversible demyelination) in multiple sclerosis (MS). Two mechanisms by which fingolimod could limit MS lesion evolution include sequestration of lymphocytes in the periphery or direct neuroprotective effects. We investigated the effect of fingolimod on the evolution of acute gadolinium-enhancing (Gd+) brain lesions to CBH in patients with MS. This was a retrospective nonrandomized comparison of patients with Gd+ brain lesions at the time of starting oral fingolimod [.5 mg/day, n = 26, age (mean ± SD) 39.2 ± 10.6 years, Expanded Disability Status Scale (EDSS) score - median (range): 1.75 (0, 6.5)] to those on no therapy [n = 30, age 41.7 ± 9.3 years; EDSS 1.0 (0, 6)]. Each lesion was classified by whether it converted to a CBH in the year following treatment. In the fingolimod group, 99 Gd+ baseline lesions (mean ± SD, range: 3.8 ± 5.1; 1, 21 per patient) were identified of which 25 (25%) evolved to CBH (1.0 ± 2.0; 0, 10 per patient). The untreated group had 62 baseline Gd+ lesions (2.1 ± 2.3; 1, 13), 26 (42%) of which evolved to CBH (.9 ± 1.4; 0, 7) (P = .063). Thirteen patients (50%) receiving fingolimod and 17 untreated patients (57%) developed CBH (P = .79). This pilot study shows a trend of fingolimod on reducing the conversion rate from acute to chronic destructive MS lesions. Such an effect awaits verification in larger randomized prospective studies.


Habituation of P300 to target stimuli.
Two experiments examined the effects on N100, N200, and P300 of 1) repeated target presentation, 2) interblock intervals, 3) knowledge of session end, and 4) reversal of targets and nontargets. In the first experiment, subjects (N = 40) performed an oddball task across six test blocks (35 targets per block). Statistical analyses showed that repeated target presentation resulted in P300 amplitude decreases (habituation) and P300 latency increases within and across test blocks (11.3 microV to 5.4 microV, 330 msec to 348 msec), and also resulted in N200 amplitude increases within blocks and N200 latency increases within and across blocks. Interblock intervals resulted in partial recovery of these habituation effects. Knowledge of session end increased P300 amplitude, while reversal of targets and nontargets had no effect. The latencies of N200 and P300 were positively correlated (r .55), while the amplitudes were not. The second experiment demonstrated P300 habituation at multiple scalp sites (Fz, Cz, Pz). Two factors that may relate to habituation of the P300 are decreased arousal level and degree of involvement in the task.


Esophageal Apoplexy.
Oesophageal apoplexy or intramural haematoma of the oesophagus (IHE) is a rare condition with a pattern of presentation that can mimic sinister pathologies. Diagnosis requires a high index of suspicion, and the exclusion of an oesophageal perforation or oesophageal malignancy is important. Investigations include computer topography (CT) and contrast swallow studies as well as a gastroscopy. Management is mainly supportive with resolution of symptoms typically occurring rapidly. We present two cases of this rare condition, with accompanying images.


Role of angiotensin II in hyperinsulinemia-induced hypertension in rats.
To investigate the role of angiotensin II in the pathogenesis of hyperinsulinemia-induced hypertension in rats. Chronic hyperinsulinemia was achieved by infusing insulin (3 mU/kg per min) subcutaneously by an osmotic minipump for 6 weeks. An angiotensin converting enzyme inhibitor (fosinopril, 10 mg/kg per day) was added in drinking water and the angiotensin II subtype 1 receptor antagonist losartan (3.5 microg/kg per min) was co-infused via the minipump. Control rats were administered the vehicle only. The rats were housed in individual metabolic cages and fed a sodium-controlled diet. Food and water intake and urine output were measured daily. Systolic blood pressure and heart rate were measured by the tail-cuff method twice a week. By the end of weeks 4 and 6 of the sustained insulin infusion, systolic blood pressure had increased significantly (P < 0.05), from 134+/-1 to 157+/-2 and 158+/-2 mmHg, respectively, and the heart rate had increased significantly (P< 0.05), from 380+/-9 to 423+/-7 and 426+/-6 beats/min, respectively. The plasma insulin concentration increased by 2-2.5 times but no significant changes in plasma glucose and triglyceride levels were noted. Concomitant treatment with fosinopril prevented the rises in systolic blood pressure and heart rate in the insulin-infused rats. When the insulin-induced hypertension had become established (systolic blood pressure increased from 132+/-3 to 155+/-2 mmHg 4 weeks after the infusion, P< 0.05 ), subsequent fosinopril or losartan treatment for 2 weeks reversed the elevated systolic blood pressure and heart rate to the control levels. There were no significant differences in water intake, urine flow, sodium gain and body weight gain between the control and the insulin-infused rats. Angiotensin converting enzyme inhibition or angiotensin II type 1 receptor antagonism can prevent and reverse insulin-induced hypertension in rats, suggesting that angiotensin II itself or an angiotensin II-dependent mechanism has an etiological influence in the pathogenesis of this hypertension model.


Perils of rib fractures.
Rib fractures (RF) are noted in 4 to 12 per cent of trauma admissions. To define RF risks at a Level 1 trauma center, investigators conducted a 10-year (1995-2004) retrospective analysis of all trauma patients. Blunt chest trauma was seen in 13 per cent (1,475/11,533) of patients and RF in 808 patients (55% blunt chest trauma, 7% blunt trauma). RF were observed in 26 per cent of children (< 18 years), 56 per cent of adults (18-64 years), and 65 per cent of elderly patients (> or = 65 years). RF were caused by motorcycle crashes (16%, 57/347), motor vehicle crashes (12%, 411/3493), pedestrian-auto collisions (8%, 31/404), and falls (5%, 227/5018). Mortality was 12 per cent (97/808; children 17%, 8/46; adults 9%, 46/522; elderly 18%, 43/240) and was linearly associated with a higher number of RF (5% 1-2 RF, 15% 3-5 RF, 34% > or = 6 RF). Elderly patients had the highest mortality in each RF category. Patients with an injury severity score > or = 15 had 20 per cent mortality versus 2.7 per cent with ISS < 15 (P < 0.0001). Increasing age and number of RF were inversely related to the percentage of patients discharged home. ISS, age, number of RF, and injury mechanism determine patients' course and outcome. Patients with associated injuries, extremes of age, and > or = 3 RF should be admitted for close observation.


Usefulness of Intravenous Sodium Nitrite During Resuscitation for the Treatment of Out-of-Hospital Cardiac Arrest.
It is hypothesized that intravenous (IV) sodium nitrite given during resuscitation of out-of-hospital cardiac arrest (OHCA) will improve survival. We performed a phase 1 open-label study of IV sodium nitrite given during resuscitation of 120 patents with OHCA from ventricular fibrillation or nonventricular fibrillation initial rhythms by Seattle Fire Department paramedics. A total of 59 patients received 25 mg (low) and 61 patients received 60 mg (high) of sodium nitrite during resuscitation from OHCA. Treatment effects were compared between high- and low-dose nitrite groups, and all patients in a concurrent local Emergency Medical Services registry of OHCA. Whole blood nitrite levels were measured in 97 patients. The rate of return of spontaneous circulation (48% vs 49%), rearrest in the field (15% vs 25%), use of norepinephrine (12% vs 12%), first systolic blood pressure (124 ± 32 vs 125 ± 38 mm Hg), survival to discharge (23.7% vs 16.4%), and neurologically favorable survival (18.6% vs 11.5%) were not significantly different in the low and high nitrite groups. There were no significant differences in these outcomes among patients who received IV nitrite compared with concurrent registry controls. We estimate that 60 mg achieves whole blood nitrite levels of 22 to 38 μM 10 minutes after administration, whereas 25 mg achieves a level of 9 to 16 μM 10 minutes after delivery. In conclusion, administration of IV nitrite is feasible and appears to be safe in patients with OHCA, permitting subsequent evaluation of the effectiveness of IV nitrite for the treatment of OHCA.


A scoping review: virtual patients for communication skills in medical undergraduates.
Communication is an essential competence for medical students. Virtual patients (VP), computerized educational tools where users take the role of doctor, are increasingly used. Despite the wide range of VP utilization, evidence-based practical guidance on supporting development of communication skills for medical students remains unclear. We focused this scoping review on VP affordance for student learning especially important in the current environment of constrained patient access. This scoping review followed Arksey & O'Malley's methodology. We tested and used a search strategy involving six databases, resulting in 5,262 citations. Two reviewers independently screened titles, full texts (n= 158) and finally performed data extraction on fifty-five included articles. To support consideration of educational affordance the authors employed a pragmatic framework (derived from activity theory) to map included studies on VP structure, curricular alignment, mediation of VP activity, and socio-cultural context. Findings suggest that not only the VP itself, but also its contextualization and associated curricular activities influence outcomes. The VP was trialled in the highest proportion of papers as a one-off intervention (19 studies), for an average duration of 44.9 minutes (range 10-120min), mainly in senior medical students (n=23), notably the largest group of studies did not have VP activities with explicit curricular integration (47%). There was relatively little repeated practice, low levels of feedback, self-reflection, and assessment. Students viewed VPs overall, citing authenticity and ease of use as important features. Resource implications are often omitted, and costings would facilitate a more complete understanding of implications of VP use. Students should be provided with maximal opportunity to draw out the VPs' full potential through repeated practice, without time-constraint and with curricular alignment. Feedback delivery enabling reflection and mastery is also key. The authors recommend educators to explicitly balance computerized authenticity with instructional design integrated within the curriculum.


Safety of a picosecond laser with diffractive lens array (DLA) in the treatment of Fitzpatrick skin types IV to VI: A retrospective review.
Laser therapy in patients with skin of color is associated with an increased rate of complications. The 755-nm picosecond laser with the diffractive lens array (DLA) has been used for the treatment of scars, striae, and rejuvenation. By delivering high energy to focused areas, the DLA minimizes complications. This study explores the adverse events associated with treatment with the 755-nm picosecond laser with DLA in individuals with Fitzpatrick skin type IV to VI. A retrospective chart review of patients treated with the 755-nm picosecond laser with DLA with a standardized spot size of 6 mm, fluence of 0.71 J/cm(2), and pulse width of 750 to 850 picoseconds was performed. Standard clinical photographs were obtained before treatment and at follow-up. Treatment sites were assessed for dyspigmentation, erythema, edema, and herpetic lesions. A total of 56 patients with Fitzpatrick skin type IV to VI, atrophic and hypertrophic scars, and pigmented lesions or striae were included. Ten patients (17.9%) were lost to follow-up. Transient adverse events, most commonly erythema and hyperpigmentation, were reported after therapy; these resolved in all cases. Retrospective design is a limitation. The 755-nm picosecond laser with the DLA device may be a safe therapeutic alternative for unwanted scars, pigmented lesions, and striae in patients with skin of color.


The impact of HLA A, B, and DR blood transfusions and immune responder status on cardiac allograft recipients treated with cyclosporine.
From July 1982 to August 1986, 137 patients received heart allografts at our transplant (Tx) center. Recipients were treated postoperatively with cyclosporine (CsA) and prednisone (Pred), with a minority of patients receiving CsA, Pred, and azathioprine (Aza) as immunosuppression. The impact of pre-Tx immune factors on survival was evaluated, including HLA A, B, and DR mismatches (MM), blood transfusions (BT), immune responder status, crossmatch results, and donor and recipient AIDS-virus (human immunodeficiency virus, HIV-1) status. The overall patient survivals were 75%, 68%, and 62% at one, two, and three years respectively. Pre-Tx, 15/137 (11%) recipient sera and 5/137 (3.6%) donor sera were HIV-1 reactive in both enzyme immunoassay (EIA) and Western blot antibody assays. Two of the 5 recipients of HIV-1 (+) donor allografts are alive 11 and 29 months post-Tx, whereas the other 3 recipients died at 1, 31, and 36 months post-Tx from diseases unrelated to AIDS. All 5 were pre-Tx HIV-1 nonreactive. The survivals for the 15 recipients who tested pre-Tx HIV-1 (+) were 87%, 87%, and 69% at 1, 2, and 3 years, respectively, comparable to the overall group survivals. Pre-Tx strong and weak immune responders had comparable 12-month survivals of 73% and 80%, respectively. Six patients displayed a positive pre-Tx donor crossmatch, two were attributed to autoantibody, and 4 were attributed to donor T cell reactivity. Five of the six patients presently survive 14, 16, 30, 36, and 44 months post-Tx. Recipients treated pre-Tx with 1-4 BTs displayed significantly better 12-month survival (81% vs. 69%, P less than 0.05) and fewer rejections (1.3 +/- 0.9 vs. 1.9 +/- 1.0, P less than 0.05) than untransfused recipients. Recipients of a 0-1 vs. 2 DR donor antigen-mismatch experienced fewer rejections (1.3 +/- 1.0 vs. 1.8 +/- 1.1, P less than 0.05). Evaluation of the combined influence of HLA DR as well as pre-Tx BTs suggested a significantly improved survival (80% vs. 61%, P less than 0.05) and fewer rejection episodes (1.4 +/- 0.9 vs. 2.0 +/- 1.1, P less than 0.05) for 29 well-matched, transfused (0-1 DR MM and 1-4 BT) compared with 43 poorly matched, untransfused (2 DR MM and 0-BT) heart allograft recipients. Moreover, the benefit of DR matching was only observed in untransfused, but not transfused, cardiac recipients.


Perinatal psychotropic dispensing: A descriptive population-based study in New Zealand.
Decisions about using psychotropics during pregnancy are complex as risks of untreated illness are balanced against risks of fetal exposure to medication. The objective was to describe perinatal psychotropic dispensing patterns in New Zealand. Nationwide data from the New Zealand National Maternity Collection between January 1, 2011 and December 31, 2017 identified 399 715 pregnancies. These were linked with dispensing records to determine the proportion of pregnancies during which at least 1 psychotropic was dispensed. Proportions were calculated separately for each class, year, pregnancy period, and across maternal characteristics. The pattern of dispensing (including discontinuations) was also determined for the 25 841 women who were dispensed at least 1 psychotropic drug prior to pregnancy. From the 399 715 pregnancies in the study cohort, 6.6% were dispensed at least 1 psychotropic during pregnancy. Antidepressants (5.1%) were the most dispensed, followed by hypnotics (1.2%), anxiolytics (0.7%), and antipsychotics (0.7%). From the 25 841 pregnancies during which a psychotropic was dispensed pre-pregnancy, 91% and 90% discontinued hypnotics and anxiolytics respectively, prior to or during pregnancy. This was followed by lithium (71%), antipsychotics (66%), and antidepressants (66%). Dispensing of psychotropics during pregnancy occurs in approximately 6.6% of pregnancies in New Zealand. Two-thirds of women (66%) on antidepressants or antipsychotics discontinue dispensing before or during pregnancy. This may have implications for maternal mental health, suggesting there is a need to investigate how healthcare providers and women are making decisions about psychotropic use during pregnancy.


Effect of HCH contamination of diet on the growth performance and immune and antioxidant ability in growing/finishing pigs.
The effects of hexachlorocyclohexane (HCH) on growth performance and immune and oxidative stress in growing/finishing pigs were studied. Seventy-two pigs, with equal numbers of barrows and gilts, of the same genotype (Duroc x Landrace x Large White), were randomly assigned to three groups receiving the same basal diet, exposed to 0, 0.4 and 0.8 mg/kg technical HCH, respectively, for 90 days. Six pigs from each group were randomly picked out and slaughtered on a finishing feeding trial. The result showed that addition of HCH did not affect the growth performance significantly but increased the weight of kidney and thymus significantly. Total serum IgG and IgM were elevated significantly, but there were no significant differences in serum IgA, C3 and C4 among the groups. Addition of HCH to feedstuff reduced superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) activities in liver, reduced serum catalase (CAT) activity, and increased serum malondialehyde (MDA). Moreover, the activities of serum alanine aminotransferase and alkaline phosphatase were increased significantly. Addition of 0.4 mg/kg or 0.8 mg/kg HCH did not affect the growth performance but affected the immune and antioxidant potential.


Mechanism of formation of 3-chloropropan-1,2-diol (3-MCPD) esters under conditions of the vegetable oil refining.
3-MCPD esters are contaminants that can form during refining of vegetable oils in the deodorization step. It was experimentally shown that their content in the vegetable oil depends on the acid value of the vegetable oil and the chloride content. 3-MCPD esters form approximately 2-5 times faster from diacylglycerols than from monoacylglycerols. It has been proved that the higher fatty acids content in the oil caused higher 3-MCPD esters content in the deodorization step. Neutralization of free fatty acids in the vegetable oil before the deodorization step by alkaline carbonates or hydrogen carbonates can completely suppress the formation of 3-MCPD esters. Potassium salts are more effective than sodium salts.


Obstruction increases activation in the right inferior frontal gyrus.
The right inferior frontal gyrus (IFG) is involved in intention understanding during interpersonal interactions. To examine how prior experience of cooperation and competition affects one's right IFG activation in the subsequent interaction, using near-infrared spectroscopy (NIRS) we simultaneously measured paired participants' bilateral IFG activations during a turn-taking game. Participant pairs were assigned to either one of two roles: a Builder taking the initial move to copy a target disk-pattern on monitor and the Partner taking the second move to aid in (cooperation) or to obstruct (competition) the Builder. The experiment consisted of two sessions. One participant (B-P) played as a Builder (B-) in session 1 and changed the role to the Partner (-P) in session 2, and vice versa for the paired participant (P-B). NIRS data in competition demonstrated that the Builder (B-) being obstructed in session 1 showed higher right IFG activation when (s)he took a role of obstructor (-P) in session 2 (the obstructed effect), whereas "the cooperated effect" was not revealed in cooperation. These results suggest that prior experience of being obstructed may facilitate understanding of the Builder and/or the obstructor's tactical move, thereby increasing his/her right IFG activation when one is meant to obstruct in subsequent competitions.


Photobiomodulation activates the PI3K/AKT pathway in diabetic fibroblast cells in vitro.
Photobiomodulation (PBM) has been known to facilitate the healing of numerous ailments including diabetic wounds. PBM is not broadly acknowledged largely due to scepticism regarding its mechanism of action, including the specific molecular targets and the effects rendered at a tissue, cellular and molecular level. Diabetes mellitus (DM) reduces cellular signalling, including the phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signalling pathway that is critical during wound healing. In DM, wound chronicity is common and may lead to non-traumatic limb amputation. This study investigated the hypothesis that PBM at 660 nm activates PI3K/AKT and downstream signalling proteins in fibroblast cells in vitro. Cells were incubated for 24 and 48 h after PBM (660 nm and 5 J/cm2), followed by evaluation of activated PI3K/AKT and downstream mammalian target of rapamycin (mTOR) and glycogen synthase kinase-3 beta (GSK3β) signalling proteins using western blotting and ELISA. Irradiated cell models displayed increased activation of PI3K/AKT and downstream mTOR and GSK3β signalling proteins. Our findings suggest that the therapeutic effects of PBM in stressed cells are through activation of the PI3K/AKT cell signalling pathway and downstream GSK3β and mTOR signalling proteins. This study provides a novel understanding into one of the probable molecular mechanisms in which PBM at a wavelength of 660 nm (5 J/cm2) enhances therapeutic activities in diabetic wound healing.


The Frequency of Medication-related Osteonecrosis of the Jaw and its Associated Risk Factors.
This article provides the best current frequency estimate of medication-related osteonecrosis of the jaws (MRONJ), and identifies factors associated with the risk of developing osteonecrosis of the jaw (ONJ) among patients exposed to relevant medications (ie, antiresorptive or antiangiogenic agents). MRONJ is a rare but serious complication of cancer treatment or osteoporosis management. This review confirms that antiresorptive medications such as oral or intravenous bisphosphonates and denosumab are the most common risk factors for developing ONJ. The risk of MRONJ is greater in patients with cancer than in those receiving antiresorptive treatments for osteoporosis by a factor of 10.


Cyclooxygenase-2 expression correlates with diminished survival in invasive breast cancer treated with mastectomy and radiotherapy.
To evaluate the relationship between cyclooxygenase-2 (COX-2) expression and pathologic features and outcome in invasive breast cancer. Formalin-fixed, paraffin-embedded tumor specimens from 23 women with invasive breast cancer were stained for COX-2 expression. All women underwent mastectomy and locoregional radiotherapy. The distribution (percentage of positive staining cells) and intensity of COX-2 expression within the tumor cells were compared with clinical factors, including stage, grade, lymph node involvement, and outcome. For invasive breast cancer, the distribution and intensity of COX-2 tumor expression correlated significantly with diminished overall survival. The 5-year overall survival rate was 100% for patients with <75% of breast cancer cells expressing COX-2 compared with 49% for patients with > or =75% (p = 0.044). The 5-year overall survival rate was 100% for patients with COX-2 intensity <80 compared with 60% for patients with COX-2 intensity > or =80 (p = 0.018). The percentage and intensity of COX-2 expression also correlated significantly with disease-free survival. The percentage of cells expressing COX-2 was significantly greater in women <40 years old than in women > or =40 years old (81% vs. 59%, respectively, p = 0.04). Both the distribution and the intensity of COX-2 expression correlated significantly with disease-free and overall survival in patients with invasive breast cancer. Younger patients with invasive breast cancer may have a greater percentage of COX-2 expression in their tumors.


Actions of prostaglandin precursors and other unsaturated fatty acids on conduction time and refractory period in the cat heart in situ.
1 The effect of arachidonic, dihomo-gamma-linolenic, linoleic, alpha-linolenic and oleic acid, given by intravenous infusion, on conduction time and functional refractory period have been studied in the cat heart in situ. 2 The prostaglandin precursors, arachidonic acid and dihomo-gamma-linolenic acid, prolonged the conduction time and the functional refractory period. Linoleic acid was also effective but to a lesser degree. alpha-Linolenic acid and oleic acid showed no or only a weak effect in thie respect. 3 Pretreatment was indomethacin diminished or abolished the actions of the three effective fatty acids but not those of prostaglandin E2. 4 The results suggest that the effects of prostaglandin prostaglandin precursors on conduction time and refractory period are responsible for their antiarrhythmic effectiveness and that these effects are attributable to their endogenous conversion into prostaglandins.


Congenital labial mucocele: rare presentation of a common disease.
Oral mucoceles are common lesions characterized by accumulation of mucus following rupture of a minor salivary gland duct. However, congenital mucoceles are a rare and distinctive oral condition observed in newborns. This case report details the features of a congenital labial nodule diagnosed as congenital mucocele. These lesions are rare in the oral cavity and should be diagnosed in the delivery room, but many cases are referred for further evaluation. Management is simple, and recurrence is not expected.


Novel universal approach for preimplantation genetic diagnosis of beta-thalassaemia in combination with HLA matching of embryos.
Beta-Thalassaemia results from co-inheritance of two mutant beta-globin alleles. Allogeneic cord blood cell transplantation (CBT) from an HLA-identical sibling donor is an excellent treatment option for beta-thalassaemia. In families with an affected child and willing to have another child, IVF followed by preimplantation genetic diagnosis (PGD) can be applied to exclude affected embryos. Furthermore, healthy embryos could be HLA matched with the affected child so that cord blood from the future newborn can be used to transplant the affected sibling. We developed an indirect single-cell HLA typing technique based on the use of a bank of seven microsatellite markers within the HLA locus from which four informative and evenly distributed markers were selected. The methodology was validated in three beta-thalassaemia families having six ovarian stimulation cycles in view of IVF and PGD. Six PGD cycles were performed in two families. On 58 embryos tested, the combined PCR was successful in 54 (93%). Two transfers were done and one clinical pregnancy was obtained. Using confirmatory analysis on 50 embryos, the accuracy for HLA typing was 100%. This strategy offers a new therapeutic option for patients with beta-thalassaemia and other monogenic diseases that can be cured with CBT.


Decidual extracts suppress antibody response in vitro.
Extracts of decidual tissue produced in pseudopregnant rats were found to suppress in vitro antibody response to alpha-2,4-dinitrophenyl-polylysine. The peak levels of both the total antibody response and the 2-mercaptoethanol-resistant fraction were reduced. Extracts prepared in a similar manner from uteri of normal untreated or pseudopregnant rats did not exert such an effect.


Emerging chemicals of concern: pharmaceuticals and personal care products (PPCPs) in Asia, with particular reference to Southern China.
In many western nations, pharmaceuticals and personal care products (PPCPs) are present in aquatic environments, raising concerns amongst chemists and toxicologists regarding their potential environmental fates and effects. However, there are few published reports of PPCPs in environmental samples from Southeast Asia. Whilst the environmental toxicology of PPCPs is not well understood, several effects cause concern, such as feminisation or masculinisation by hormones and xenoestrogens, synergistic toxicity from complex mixtures at low concentrations, potential creation of resistant strains in natural bacterial populations, and other potential concerns for human health. Whilst both the presence and distributions of PPCPs in Southeast Asia and China are not well known, observations elsewhere suggest that they may be important contaminants in the aquatic environment. This is particularly emphasised by the enormous production and widespread use of many PPCPs in China, particularly antibiotics utilised in human and veterinary medicine applications. This Viewpoint presents a general description of the issue, characterises the current status of PPCP analyses and reporting in the Southeast Asian region, and proposes a recommended approach for monitoring and chemical assessment of one group of PPCPs, antibiotics, in the aquatic environments of Hong Kong and the Pearl River Delta.


Rat strain differences in the potentiation of morphine-induced analgesia by stress.
Restraint stress has been shown to increase the magnitude and duration of morphine-induced analgesia; however, this phenomenon has only been investigated using the Sprague-Dawley rat strain. The purpose of this study was to determine if other rat strains would also exhibit a potentiated analgesic response to morphine compared to their unrestrained controls. Dose-response and time course curves for the analgesic effect of morphine (1.0, 3.0, 5.6, 10 mg/kg) were generated in adult, male Wistar, Lewis, Fischer 344, Long-Evans Hooded, and Sprague-Dawley rats either unrestrained or restrained in Plexiglas cylinders, using the tail flick assay. Morphine produced dose-dependent increases in tail flick latencies, and this effect was potentiated by restraint stress in the Sprague-Dawley, Wistar, Lewis, and Fischer 344 strains, but not in the Long-Evans Hooded rats. Because Sprague-Dawley and Wistar rats displayed the most robust stress effect, the use of either of these rat strains is appropriate in studying the mechanisms of stress-induced potentiation of analgesia. The differences among rat strains demonstrated in this study may serve as a basis for correlation with opioid function.


Liposarcoma of the cord presenting at vasectomy counselling.
A case of liposarcoma of the cord is reported in a patient presenting for vasectomy. This paper discusses such tumours and illustrates the importance of a careful clinical examination during counselling.


Correction: Efficacy, Effectiveness, and Quality of Resilience-Building Mobile Health Apps for Military, Veteran, and Public Safety Personnel Populations: Scoping Literature Review and App Evaluation.
[This corrects the article DOI: 10.2196/26453.].


Analysis of iodinated amino acids by microemulsion electrokinetic chromatography using aliphatic amine as a cosurfactant.
A novel microemulsion electrokinetic chromatography (MEEKC) was established for the separation and determination of iodinated amino acids using n-butylamine as a novel cosurfactant. By optimizing the type of oil phase, the type and concentration of surfactant, the concentration of cosurfactant and the type and concentration of buffer in the microemulsion system, the optimal conditions for the separation of organic iodines were determined to be 0.5% ethyl acetate, 0.6% SDS, 1.2% n-butylamine and 10 mM sodium borate. The efficient and rapid separation of the five analytes (3-iodo-L-tyrosine (MIT), 3, 5-Diiodo-L-tyrosine (DIT), 3, 5-Diiodo-L-thyronine (T2), 3, 3', 5-Triiodo-L-thyronine (T3) and L-Thyroxine (T4)) was achieved under the optimal conditions. The reliability of the method was verified by measuring the precision, LOD, LOQ and recovery. The practicality of the MEEKC method was demonstrated by applying it to the determination of two iodotyrosines, MIT and DIT, in kelp. The analytical method established in this experiment will provide a reference for the study of iodotyrosines in other natural plants and food.


Treatment of fulminant liver failure by transplantation of microencapsulated primary or immortalized xenogeneic hepatocytes.
The aim of this study was to evaluate in vitro and in vivo functions of isolated hepatocytes after immortalization, cryopreservation, encapsulation and xenotransplantation into mice with fulminant liver failure (FLF). Rat and human hepatocytes were isolated from normal liver tissue by collagenase digestion. Human hepatocytes were immortalized using lentiviral vectors coding for SV 40 large T antigen, Bmi-1 and telomerase. Rat and immortalized human hepatocytes (IHH) were encapsulated in 400 micron alginate-PLL-alginate membranes and cryopreserved using a computerized device. In vitro, encapsulated hepatocytes (cryopreserved or freshly isolated) were cultured in albumin-free medium and albumin production was measured by enzyme-linked immunosorbent assay (ELISA). In vivo, a model of FLF was established in C57/BL6 mice by acetaminophen administration (700 mg/kg i.p.) followed 15 h later by a 30% hepatectomy. Microencapsulated (cryopreserved or freshly isolated) hepatocytes were transplanted intraperitoneally to mice with FLF and the following experimental groups were performed: group 1 (n = 10) Tx of empty capsules; group 2 (n = 12) Tx of free primary rat hepatocytes; group 3 (n = 12) Tx of cryopreserved encapsulated rat hepatocytes; group 4 (n = 10) Tx of fresh encapsulated rat hepatocytes; group 5 (n = 9) Tx of cryopreserved encapsulated IHH; group 6 (n = 10) Tx of fresh encapsulated IHH. Animals were killed at regular intervals and histopathology of microcapsules and liver tissue was obtained. In vitro, cryopreserved or fresh encapsulated rodent hepatocytes showed a progressively decreasing albumin secretion over 1 week in culture. In contrast, cryopreserved or fresh encapsulated IHH showed minimal, but stable albumin secretion. In vivo, FLF was achieved by combination of acetaminophen with 30% hepatectomy, resulting in a reproducible survival of 23% +/- 5%. In groups 1 and 2, survival rates were not improved significantly compared with untreated mice. In groups 3 and 4, Tx of cryopreserved or fresh encapsulated rat hepatocytes significantly increased survival rate to 66% and 80%, respectively (P < 0.01). In groups 5 and 6, Tx of cryopreserved or fresh encapsulated IHH improved survival to 50% and 55%, respectively (P < 0.05). Histopathology revealed that encapsulated hepatocytes were viable up to 2 weeks post-Tx. Primary rodent hepatocytes maintained synthetic functions after encapsulation and cryopreservation short-term. IHH showed minimal albumin secretion in the absence of encapsulation and cryopreservation, suggesting that hepatocytes loose specific functions after immortalization. After induction of FLF in mice, intraperitoneal Tx of encapsulated (primary or immortalized, fresh or cryopreserved) xenogeneic hepatocytes significantly improved survival. These results indicate that naïve and genetically modified hepatocytes can successfully be encapsulated, stored using cryopreservation, and be transplanted into xenogeneic recipients with liver failure and sustain liver metabolic functions.


Influence of sex hormones on free erythrocyte protoporphyrin response to lead in rats.
Following oral administration of lead a difference in free erythrocyte protoporphyrin (FEP) increase was found between adult male, adult female and suckling rats: young animals are more susceptible than adult female rats which in turn exhibit a greater FEP increase than adult male animals. This observation parallels that made previously in humans. Possible difference in iron metabolism does not appear to explain the sex-linked difference in FEP response to lead. Sex hormones mainly progesterone, seem to play a role but their interaction with lead on the FEP response is restricted to female rats and apparently is not mediated through changes in delta-aminolevulinic acid synthetase activity.


Future teachers' perception of the usefulness of SketchUp for understanding the space and geometry domain.
This article reflects the opinion of future Early Childhood Education teachers at the Universidad de Cádiz on the usefulness and degree of satisfaction of SketchUp, a 3D modelling software programme, after they participated in a workshop for didactic-mathematical training. They had to use the software to design and model their ideal nursery school in 3D, supported by clearly stated and well-defined educational pillars. This study aims to ascertain the students' perceptions of the use of this resource with the intention of assessing its suitability to offer more appropriate initial training regarding mathematics education. It seeks to make the most of using the software programme and minimise the obstacles encountered. Opinions were collected from a sample of 203 students who responded to two questionnaires designed ad hoc. The results are organised around a SWOT analysis and show a satisfactory global evaluation.


Utility of the immunohistochemical detection of FLI-1 expression in round cell and vascular neoplasm using a monoclonal antibody.
FLI-1 nuclear transcription factor has been proposed as a useful tool in the differential diagnosis of small round cell sarcomas. Recently, FLI-1 has been reported as the first nuclear marker of endothelial differentiation. However, its clinical use has been hampered by major interpretation problems, due to the presence of background staining as well as staining variation between different lots of the same antiserum. In this study, a novel monoclonal antibody raised against the carboxyl terminal of the FLI-1 protein (clone GI146-222, BD Pharmingen) was tested in a series of small round cell and vascular neoplasms. Furthermore, in order to assess FLI-1 specificity, we analyzed its expression in a series of common epithelial and nonepithelial malignancies. In total, 15 Ewing's sarcomas, 10 rhabdomyosarcomas, 5 desmoplastic small round cell tumors, 10 synovial sarcomas, 10 high-grade pleomorphic sarcomas, 10 malignant melanomas, 5 Merkel's carcinomas, 10 colonic adenocarcinomas, 10 breast carcinomas, 10 lung adenocarcinomas, 20 angiosarcomas, 5 epithelioid hemangioendotheliomas, 10 Kaposi's sarcomas and 10 benign hemangiomas, were stained. A strong FLI-1 immunoreactivity was detected in all Ewing's sarcomas and vascular neoplasms, highlighting the high sensitivity of FLI-1 monoclonal antibody. However, 2/5 Merkel's carcinomas and 1/10 malignant melanomas showed a strong nuclear immunostaining, suggesting that FLI-1 may not be so helpful in the differential diagnosis of cutaneous Ewing's sarcoma. In addition, a weak immunoreactivity was found in 3/5 Merkel cell carcinomas, 3/10 synovial sarcomas, 5/10 malignant melanomas, 6/10 lung adenocarcinomas and in 1/10 breast carcinomas. In contrast, all the rhabdomyosarcomas, desmoplastic small round cell tumors, high-grade pleomorphic sarcomas and colonic adenocarcinomas tested were negative. Importantly, in contrast with previous studies, no background staining was observed. Our results indicate that FLI-1 monoclonal antibody can be reliably applied to the differential diagnosis of small round cell neoplasms of soft tissue, and confirm its important role as nuclear marker of endothelial differentiation, mainly helpful in those cases in which technical artifacts are seen by using the traditional membranous and cytoplasmic endothelial markers.


Rhinoplasty: image and reality.
The rhinoplasty surgeon must convert a mental image into a surgical reality through aesthetics, anatomy, and analysis. This article attempts to provide a reasoned solution to the recurrent difficulty of progressing from image to reality.


Pharmacological Elevation of Circulating Bioactive Phosphosphingolipids Enhances Myocardial Recovery After Acute Infarction.
Acute myocardial infarction (AMI) triggers mobilization of bone marrow (BM)-derived stem/progenitor cells (BMSPCs) through poorly understood processes. Recently, we postulated a major role for bioactive lipids such as sphingosine-1 phosphate (S1P) in mobilization of BMSPCs into the peripheral blood (PB). We hypothesized that elevating S1P levels after AMI could augment BMSPC mobilization and enhance cardiac recovery after AMI. After AMI, elevating bioactive lipid levels was achieved by treating mice with the S1P lyase inhibitor tetrahydroxybutylimidazole (THI) for 3 days (starting at day 4 after AMI) to differentiate between stem cell mobilization and the known effects of S1P on myocardial ischemic pre- and postconditioning. Cardiac function was assessed using echocardiography, and myocardial scar size evolution was examined using cardiac magnetic resonance imaging. PB S1P and BMSPCs peaked at 5 days after AMI and returned to baseline levels within 10 days (p < .05 for 5 days vs. baseline). Elevated S1P paralleled a significant increase in circulating BMSPCs (p < .05 vs. controls). We observed a greater than twofold increase in plasma S1P and circulating BMSPCs after THI treatment. Mechanistically, enhanced BMSPC mobilization was associated with significant increases in angiogenesis, BM cell homing, cardiomyocytes, and c-Kit cell proliferation in THI-treated mice. Mice treated with THI demonstrated better recovery of cardiac functional parameters and a reduction in scar size. Pharmacological elevation of plasma bioactive lipids after AMI could contribute to BMSPC mobilization and could represent an attractive strategy for enhancing myocardial recovery and improving BMSC targeting. Acute myocardial infarction (AMI) initiates innate immune and reparatory mechanisms through which bone marrow-derived stem/progenitor cells (BMSPCs) are mobilized toward the ischemic myocardium and contribute to myocardial regeneration. Although it is clear that the magnitude of BMSPC mobilization after AMI correlates with cardiac recovery, the molecular events driving BMSPC mobilization and homing are poorly understood. The present study confirms the role of bioactive lipids in BMSPC mobilization after AMI and proposes a new strategy that improves cardiac recovery. Inhibiting sphingosine-1 phosphate (S1P) lyase (SPL) allows for the augmentation of the plasma levels of S1P and stem cell mobilization. These findings demonstrate that early transient SPL inhibition after MI correlates with increased stem cell mobilization and their homing to the infarct border zones. Augmenting BMSPC mobilization correlated with the formation of new blood vessels and cardiomyocytes and c-Kit cell proliferation. These novel findings on the cellular level were associated with functional cardiac recovery, reduced adverse remodeling, and a decrease in scar size. Taken together, these data indicate that pharmacological elevation of bioactive lipid levels can be beneficial in the early phase after cardiac ischemic injury. These findings provide the first evidence that a carefully timed transient pharmacological upregulation of bioactive lipids after AMI could be therapeutic, because it results in significant cardiac structural and functional improvements.


Transfer of hygromycin resistance into Brassica napus using total DNA of a transgenic B. nigra line.
The successful transfer of a marker gene (hpt gene) from Brassica nigra into B. napus via direct gene transfer was demonstrated. Total DNA was isolated from a hygromycin-resistant callus line, which contained three to five copies of the hpt gene. This line had been produced via direct gene transfer with the hygromycin resistance-conferring plasmid pGL2. The treatment of B. napus protoplasts with genomic DNA of B. nigra (HygR) resulted in relative transformation frequencies of 0.1-0.4%. Similar transformation rates were obtained in direct gene transfer experiments using B. napus protoplasts and plasmid pGL2.


Immigration Status and Sex Differences in Primary Cardiovascular Disease Prevention: A Retrospective Study of 5 Million Adults.
Background We evaluated whether immigration status modified the association between sex and the quality of primary cardiovascular disease prevention in Ontario, Canada. Methods and Results We used a population-based administrative database-derived cohort of community-dwelling adults (aged ≥40 years) without prior cardiovascular disease residing in Ontario on January 1, 2011. In the preceding 3 years, we evaluated screening for hyperlipidemia and diabetes in those not previously diagnosed; diabetes control (HbA1c <7%); and medication use to control hypertension, hyperlipidemia, or diabetes in those with previous diagnosis. We calculated the absolute prevalence difference (APD) between women and men for each metric stratified by immigration status and then determined the difference-in-differences for immigrants compared with long-term residents. Our sample included 5.3 million adults (19% immigrants), with receipt of each metric ranging from 55% to 90%. Among immigrants, women were more likely than men to be screened for hyperlipidemia (APD, 10.8%; 95% CI, 10.5-11.2) and diabetes (APD, 11.5%; 95% CI, 11.1-11.8) and to be treated with medications for hypertension (APD, 3.5%; 95% CI, 2.4-4.5), diabetes (APD, 2.1%; 95% CI, 0.7-3.6) and hyperlipidemia (APD, 1.8%; 95% CI, 0.5-3.1). Among long-term residents, findings were similar except poorer medication use for diabetes (APD, -2.8%; 95% CI, -3.4 to -2.2) and hyperlipidemia (APD, -3.5%; 95% CI, -4.0 to -3.0]) in women compared with men. Conclusions The overall quality of primary preventive care can be improved for all adults, and future research should evaluate the impact of observed equal or better care in women than men, irrespective of immigration status, on cardiovascular disease incidence.


Photoelastic stress analysis of supporting alveolar bone as modified by nonrigid connectors.
A two-dimensional photoelastic model was constructed to represent the mandible with a missing first premolar and first molar. The model contained a canine, second premolar, and second molar as abutment teeth supported by simulated periodontal ligament and photoelastic bone. Six FPDs were constructed, one of rigid design and five of nonrigid design with varying location and orientation of the nonrigid connector. Each of the six prostheses was subjected to six different loading conditions. Patterns of stress for each loading condition were recorded photographically and evaluated. This study indicated that the rigid FPD distributed stresses vertically and evenly. The nonrigid D of canine and nonrigid M of molar designs distributed stresses almost as well as the rigid FPD. They also resisted rotational movements and resultant horizontal stress better than other nonrigid designs. Compared with the other designs, prostheses with nonrigid connectors at the pier exhibited greater apical and horizontal stress particularly with one-point loading on the pier. Considering the limitations of this study, the following conclusions were drawn: 1. The pattern of stress is dependent on incorporation and location of a nonrigid connector. 2. The pattern of stress reflected the condition of loading. 3. The pattern of stress is independent of the orientation of the nonrigid connector at the distal aspect of the pier abutment. 4. The placement of a nonrigid connector at the mesial surface of the pier is least desirable.


[Assertive care as new treatment perspective for Austria].
Although intensive, assertive treatment options in child and adoledcent psychiatry have been successfully evaluated and established in several countries, this development is just beginning in Austria. As part of the so called home-treatment, care is provided by a multiprofessional team to patients with severe mental disorders, who would otherwise be treated in an inpatiet setting at their own home. This opens up the opportunity for a better generalizability of therapeutic progress and an intensive work with the family system. Alternative models for inpatient care like home-treatment, show the potential for intensive therapeutic options independent of building structures. Further development of this therapeutic option based on evaluated model projects is desirable within the Austrian health care system.


GC-MS determination of amphetamines in serum using on-line trifluoroacetylation.
An extraction and determination method of most important amphetamine derivatives in serum has been developed. The procedure comprises liquid-liquid extraction with tert-butyl methyl ether of the sample under basic conditions, centrifugation, formation of hydrochloric salts after the separation of organic phase, vacuum evaporation of the organic solvent at 60 degrees C, and trifluoroacetylation by on-line flash injection with MBTFA. GC analysis was performed by electron impact GC-MS in SIM mode. In this way satisfactory identification of 12 amphetamine derivatives could be obtained. Amphetamine, methamphetamine, MDA, MDMA and MDEA could be analyzed by using pentadeuterated analogs as internal standards. Low limits of detection 2.5-6.9 ng/mL could be reached. The assay was linear within the 5-100 ng/mL range with a regression coefficient greater than 0.999 for each compound. Our derivatization method is of low cost since only 1 microL of MBTFA is used for each flash trifluoroacetylation.


Impact of micropapillary urothelial carcinoma variant histology on survival after radical cystectomy.
The role of micropapillary urothelial carcinoma (MUC) variant histology as an independent prognostic factor for survival after radical cystectomy has not been studied. Our aim was to examine the impact of MUC on survival. A retrospective analysis of prospectively collected data from the University of Southern California (USC) Bladder Cancer Database was performed. Between 1985 and 2008, 1,380 patients underwent radical cystectomy and superextended pelvic lymph node dissection for bladder cancer. All surgical specimens underwent central pathologic review by dedicated genitourinary pathologists. Histologic type was categorized as urothelial carcinoma (UC; n = 1,347) or MUC (n = 33). The outcomes were overall survival (OS) and recurrence-free survival (RFS). The Kaplan-Meier method and Cox proportional regression models were used to analyze survival data. The median follow-up duration was 10 years (range, 0-25 years). Baseline characteristics were similar between histologic types except MUC was associated with advanced clinical (cTanyN1-3: 2% vs. 9%, P = 0.03) and pathologic (pTanyN1-3: 22% vs. 46%, P = 0.01) TNM stage, multifocality (38% vs. 58%, P = 0.02), and high nuclear grade (83% vs. 97%, P = 0.03). The predicted 5-year OS (61% and 67%, Log rank P = 0.96) and RFS (69% and 58%, Log rank P = 0.33) rates did not differ between patients with UC and MUC. Multivariable analysis showed that histologic type was not independently associated with OS (HR 0.91, 95% CI 0.55-1.49, P = 0.70) or RFS (HR 0.97, 95% CI 0.55-1.73, P = 0.92). Outcomes of radical cystectomy for patients with MUC are similar to those with UC when controlling for other clinical and pathologic factors.


Dissociative state and competence.
This report presents the results of forensic evaluation of the civil competence of a case of alleged dissociative identity disorder (DID) and discusses whether such dissociative states substantially jeopardize civil competence. A 40-year-old woman claimed that she had had many personalities since her college days. From the age of 37 to 40, she shopped excessively, which left her with millions of dollars of debt. She ascribed her shopping to a certain identity state, over which she had no control. (In this article, we use the term identity state to replace personality as an objective description of a mental state.) She thus raised the petition of civil incompetence. During the forensic evaluation, it was found that the identity states were relatively stable and mutually aware of each other. The switch into another identity state was sometimes under voluntary control. The subject showed consistency and continuity in behavioral patterns across the different identity states, and no matter which identity state she was in, there was no evidence of impairment in her factual knowledge of social situations and her capacity for managing personal affairs. We hence concluded that she was civilly competent despite the claimed DID. Considering that the existence and diagnosis of DID are still under dispute and a diagnosis of DID alone is not sufficient to interdict a persons civil right, important clinical and forensic issues remain to be answered.


Errors in identifying and expressing emotion in facial expressions, voices, and postures unique to social anxiety.
The purpose of the present study was to see if 7-10-year-old socially anxious children (n = 26) made systematic errors in identifying and sending emotions in facial expressions, paralanguage, and postures as compared with the more random errors of children who were inattentive-hyperactive (n = 21). It was found that socially anxious children made more errors in identifying anger and fear in children's facial expressions and anger in adults' postures and in expressing anger in their own facial expressions than did their inattentive-hyperactive peers. Results suggest that there may be systematic difficulties specifically in visual nonverbal emotion communication that contribute to the personal and social difficulties socially anxious children experience.


Phospholipase Cgamma2 is essential in the functions of B cell and several Fc receptors.
Many receptors activate phospholipase Cgamma1 or -gamma2. To assess the role of PLCgamma2, we derived enzyme-deficient mice. The mice are viable but have decreased mature B cells, a block in pro-B cell differentiation, and B1 B cell deficiency. IgM receptor-induced Ca2+ flux and proliferation to B cell mitogens are absent. IgM, IgG2a, and IgG3 levels are reduced, and T cell-independent antibody production is absent. The similarity to Btk- or Blnk-deficient mice demonstrates that PLCgamma2 is downstream in Btk/Blnk signaling. FcRgamma signaling is also defective, resulting in a loss of collagen-induced platelet aggregation, mast cell FcepsilonR function, and NK cell FcgammaRIII and 2B4 function. The results define a signal transduction pathway broadly utilized by immunoglobulin superfamily receptors.


Value of digital volume tomography in patients with conductive hearing loss.
Digital volume tomography (DVT) is an extension of panoramic tomography. With this diagnostic technique, characterized by high resolution, a narrow section width (0.125 mm) and three-dimensional display, small pathological processes can be well visualized. Twenty-five patients with the history of a progressive hearing loss were examined with DVT (Accu-I-tomo, Morita, Japan). The results were compared with pre- and intraoperative findings to evaluate the diagnostic value of DVT in cases of erosion of the ossicular chain. With high resolution and artifact-free demonstration of the middle ear and the ossicular chain, it was possible to define its continuity preoperatively by DVT in all 25 cases. An intact ossicular chain was found by DVT in 13 cases and was later confirmed by surgery. The predicted erosion of the ossicles was verified in 12 patients, and a tympanoplasty type III was performed. Digital volume tomography is an excellent technique to examine the middle ear cleft and inner ear, and expands the application of diagnostic possibilities in the lateral skull base. Therefore, improvement in preoperative diagnosis is achieved along with more accurate planning of the surgical procedure. Digital volume tomography delivers a small radiation dose with a high resolution and a low purchase price for the equipment.


Identification and validation of an m6A-related gene signature to predict prognosis and evaluate immune features of breast cancer.
Breast cancer is the most prevalent cancer, and it is accompanied by high heterogeneity. N6-methyladenosine (m6A) modification significantly contributes to breast cancer tumorigenesis and progression. However, how m6A-related genes affect the clinical outcomes and tumor immune microenvironment (TIME) of breast cancer is largely unknown. Our study developed an m6A-related gene signature on the basis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The m6A-related gene signature was constructed using univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses. Breast cancer patients were classified into low- and high-risk groups depending on the median risk score. The reliability and efficiency of the signature were validated using Kaplan-Meier analysis, receiver operating characteristic (ROC) curves, and principal component analysis (PCA). The risk score was validated as an independent indicator associated with overall survival, and a nomogram model was created to estimate the overall survival of patients with breast cancer. Functional annotation suggested that the risk score had a strong relationship with immune-related pathways. Different proportions of immune cell infiltration between the two groups were evaluated using various algorithms. The high-risk group had higher immune checkpoint expression levels. We discovered that one of the 6 prognostic genes, TMEM71, was downregulated in breast cancer tissues. In vitro experiments indicated that overexpression of TMEM71 suppressed breast cancer cell proliferation and migration. In conclusion, the m6A-related gene signature may be a sensitive biomarker for overall survival prediction and guide the individualized treatment for breast cancer patients.


The BTB/POZ-ZF transcription factor dPLZF is involved in Ras/ERK signaling during Drosophila wing development.
In Drosophila, broad complex, tramtrack, bric à brac (BTB)/poxvirus and zinc finger (POZ) transcription factors are essential regulators of development. We searched the Drosophila genome for BTB/POZ-ZF domains and discovered an unknown Drosophila gene, dPLZF, which encodes an orthologue of human PLZF. We then characterized the biological function of the dPLZF via genetic interaction analysis. Ectopic expression of dPLZF in the wing induced extra vein formation during wing development in Drosophila. Genetic interactions between dPLZF and Ras or extracellular signal-regulated kinase (ERK) significantly enhanced the formation of vein cells. On the other hand, loss-of-function mutations in dPLZF resulted in a dramatic suppression of the extra and ectopic vein formation induced by elevated Ras/ERK signaling. Moreover, dPLZF activity upregulated the expression of rhomboid (rho) and spitz, which perform crucial functions in vein cell formation in the developing wing. These results indicate that dPLZF is a transcription factor controlled by the Ras/ERK signaling pathway, which is a prominent regulator of vein cell formation during wing development in Drosophila.


Identifying freezing of gait in Parkinson's disease during freezing provoking tasks using waist-mounted accelerometry.
Freezing of gait (FOG) is a common and debilitating phenomenon in Parkinson's disease (PD). Wearable accelerometers might help to assess FOG in the research setting. Here, we evaluate whether accelerometry can detect FOG while executing rapid full turns and while walking with rapid short steps (the two most common provoking circumstances for FOG). We included 23 PD patients, who all had objective FOG. Participants performed several walking tasks, including walking rapidly with short steps and rapid full turns in both directions with a triaxial linear waist-mounted accelerometer. Two independent experts identified FOG episodes using off-line video-analysis (gold standard). A validated algorithm [ratio between pathological freezing (3-8 Hz)-and normal locomotor frequencies (0.5-3 Hz)] was applied on the accelerometer data to detect FOG episodes. Clinically, FOG was most often observed during full rapid turns (81% of all episodes), followed by walking with short rapid steps (12% of all episodes). During full rapid turns, accelerometry yielded a sensitivity of 78% and specificity of 59%. A sensitivity of 64% and specificity of 69% was observed during walking rapidly with small steps. Combining all tasks rendered a sensitivity of 75% and specificity of 76%. Our results suggest that FOG can be detected from a single lumbar accelerometer during several walking tasks, including full rapid turns and walking with short steps rapidly, with reasonable sensitivity and specificity. This approach holds promise for possible implementation as complementary objective outcome in a research setting, but more work remains needed to improve the sensitivity and specificity.


Associations between serum lipoprotein(a) levels and the severity of coronary and aortic atherosclerosis.
To elucidate the associations between Lp(a) levels and coronary and aortic atherosclerosis, we performed aortic MRI in 143 patients undergoing coronary angiography. Severity of aortic atherosclerosis was represented as plaque scores. Of the 143 patients, 104 had coronary artery disease (CAD). Thoracic and abdominal aortic plaques were found in 89 and 131 patients. Lp(a) levels increased stepwise with the number of stenotic coronary vessels: 15.7 (CAD(-)), 21.2 (1-vessel), 21.4 (2-vessel), and 22.9 mg/dl (3-vessel) (P<0.05). For aortic atherosclerosis, 143 patients were divided into quartiles by plaque scores. Lp(a) did not differ among quartiles of thoracic plaques: 17.1, 19.0, 23.5, and 21.2 mg/dl (P=NS), whereas Lp(a) increased stepwise with quartiles of abdominal plaques: 17.1, 19.2, 19.1, and 24.0 mg/dl (P<0.05). Lp(a) was an independent factor for CAD and abdominal aortic plaques, but not thoracic plaques. Thus, Lp(a) levels were associated with aortic atherosclerosis, especially in abdominal aorta, as well as coronary atherosclerosis.