Addition of pyridoxine to prednisolone in the treatment of infantile spasms: A pilot, randomized controlled trial.
West syndrome is a catastrophic epilepsy syndrome characterized by infantile spasms, hypsarrhythmia, and developmental arrest or regression. The aim of this study was to explore the role of pyridoxine in the management of infantile spasms. This was a pilot, randomized, open-label trial conducted at a tertiary level hospital from November 2012 to March 2014. Children aged 3 months to 3 years presenting with infantile spasms in clusters (at least 1 cluster/day) with hypsarrhythmia or its variants on electroencephalogram (EEG) were enrolled. The study participants were randomized to receive either oral prednisolone (4 mg/kg/day) alone or 30 mg/kg/day of pyridoxine with oral prednisolone. The primary outcome measure was the proportion of children who achieved spasm freedom for 48 h on day-14 after treatment initiation, as per parental reports, in both the groups. The adverse effects were also monitored. The study was registered with clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT01828437). Sixty-two children were randomized into the two groups with comparable baseline characteristics. The proportion of children with spasm cessation on day-14 was similar in the two groups (39 vs. 37%, P = 0.98). The adverse effects were comparable in both the groups. The combination of pyridoxine with oral prednisolone was not found to be a beneficial therapy as compared to prednisolone alone in the treatment of infantile spasms in this pilot study. However, high dose pyridoxine may be safe in children with infantile spasms.


Pulmonary edema due to upper airway obstruction in adults.
A report of pulmonary edema following acute upper airway obstruction in an adult is presented, and the literature involving 25 additional cases is reviewed. This form of pulmonary edema appears to be related to markedly negative intrathoracic pressure due to forced inspiration against a closed upper airway resulting in transudation of fluid from pulmonary capillaries to the interstitium. Postanesthetic laryngospasm is the most common cause of pulmonary edema in adults (11/26 cases). The edema usually clears rapidly with supportive care. Aggressive diagnostic and therapeutic interventions may be avoided if the syndrome is recognized. Maintenance of oxygenation and a patent airway are the mainstays of treatment.


Regional odontodysplasia: a case report.
This patient presents with a regional odontodysplasia in the mixed dentition with the upper right quadrant being affected from the anomaly. The upper right first primary molar was extracted because of a periapical abscess and examined scanning electron microscopically. The aim of this article is to discuss the clinical and ultrastructural features of the anomaly and revise the other odontodysplasia cases reported in the literature.


Prognostic significance of Fas expression in retinoblastoma.
The loss of Fas is believed to enhance metastatic spread in diverse human tumors. We studied the expression of Fas by immunohistochemistry in retinoblastomas and correlated the results clinicopathologically. Archival specimens of 76 retinoblastomas were included in this study. The tumors were divided into three groups: Group A (n = 21) comprising tumors with no invasion; Group B (n = 46) tumors with invasion of choroid (diffuse), optic nerve (post-laminar), and orbit; and Group C (n = 9) tumors with both invasion and metastasis. Sections were immunostained with monoclonal antibody CD95 (APO-1/Fas) and the immunoreactivity was assessed. Negative immunoreactivity of Fas was observed in Group B and Group C tumors (p < 0.001). Poorly differentiated retinoblastomas showed a decreased Fas expression (p = 0.006). Decreased expression of Fas is seen in aggressive tumors and tumors that are poorly differentiated. This preliminary observation deserves further investigation, which may then shed more light on the immune escape mechanisms of this tumor and thus enable novel therapeutic strategies.


Test-Retest Reliability and Minimal Detectable Change for the 10-Meter Walk Test in Older Adults With Parkinson's disease.
Measurement of gait performance in individuals with Parkinson's disease (PD) can be challenging because of the daily fluctuations in performance and the progressive nature of the condition. The 10-Meter Walk Test (10MWT) is commonly used to measure gait speed of individuals with gait limitations. Existing research on the 10MWT in individuals with PD controls for many variables inherent to this condition, rendering the results of this test in settings where these variables are not controlled questionable. The purpose of this study was to estimate under commonly encountered clinical conditions the test-retest reliability and the minimal detectable change (MDC) of gait speed and step frequency determined during the 10MWT in individuals with PD. The 10MWT was administered by 2 testers, on 35 participants, across 2 sessions, separated by 5 to 14 days. Gait speed was measured using a hand-held stopwatch, and step frequency was assessed through visual observation. Test-retest reliability was calculated using the intraclass correlation coefficient (ICC) and the MDC was calculated using the standard error of measurement (SEM). Comfortable and fast gait speeds demonstrated excellent reliability between sessions (ICC = 0.92 and 0.96, respectively). The corresponding MDCs were 0.22 and 0.23 m/s, respectively. The test-retest reliability for step frequency was moderate for comfortable gait speed and good for fast gait speeds (ICC = 0.73 and 0.82, respectively). The corresponding MDCs were 15.1 and 17.4 steps per minute for comfortable and fast step frequency, respectively. Under both comfortable and fast conditions, measurements of gait speed and step frequency during the 10MWT are reliable between sessions in individuals with PD.


Menopausal hormone therapy use and long-term all-cause and cause-specific mortality in the Long Island Breast Cancer Study Project.
Previous studies have observed a reduced mortality risk associated with menopausal hormone therapy (MHT) use among breast cancer survivors. We sought to clarify whether such association could be explained by tumor heterogeneity, specific causes of death, confounding from comorbidities or health behaviors, and a comparison group of women without breast cancer. We interviewed 1508 women newly diagnosed with first primary breast cancer in 1996 to 1997 (~3 months after diagnosis), and 1556 age-matched women without breast cancer, about MHT use history. The National Death Index was used to ascertain vital status after a median of 17.6 years of follow-up (N = 597 deaths for breast cancer subjects). Multivariable-adjusted Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) for all-cause mortality, and cause-specific HR (cHR) for breast cancer and cardiovascular disease (CVD). The Fine-Gray model was used to account for competing causes of death. Among women with breast cancer, ever vs never MHT use was inversely associated with all-cause (HR = 0.77, 95%CI = 0.62-0.95), breast cancer-specific (cHR = 0.69, 95%CI = 0.48-0.98), and CVD-specific mortality (cHR = 0.57, 95%CI = 0.38-0.85). Difference of the association was observed in breast cancer-specific mortality according to hormone receptor status (negative tumors: cHR = 0.44, 95%CI = 0.19-1.01; positive tumors: cHR = 0.96, 95%CI = 0.60-1.53). Among the comparison group, we observed similar, but more modest inverse associations for all-cause and CVD-specific mortality. MHT use was inversely associated with mortality after breast cancer, even after accounting for competing causes of death and multiple confounders, and was evident among women without breast cancer. Potential heterogeneity by hormone receptor status requires more study.


Pneumomediastinum complicating Pneumocystis carinii pneumonia in a patient with AIDS.
The destructive potential of Pneumocystis carinii infection in patients with AIDS has been amply documented. This report describes a homosexual man with P. carinii pneumonia (PCP) complicated by pneumatocoeles and pneumomediastinum. The pneumomediastinum almost completely resolved with successful antimicrobial therapy. Pneumomediastinum, like pneumothorax, should be anticipated in patients with AIDS and PCP.


Physicochemical characteristics, antioxidant potential, and shelf stability of developed roselle-fig fruit bar.
Fruit bars are prepared by combining different ingredients which are wholesome and nutrient rich. The current study was designed to develop roselle-fig (different proportions) fruit bars and further investigate their physicochemical characteristics and antioxidant potential. Moreover, the prepared fruit bars were scrutinized for microbial and sensory characteristics to assess the appropriateness of ingredients during storage (up to 90 days). It was observed that there was gradual increase in moisture content with the passage of time, while ash, fat, fiber, and protein contents did not change significantly during storage. The pH and total soluble solid contents of these fruit bars during storage were 3.54-4.07 and 1.71-1.86 Brix, respectively. According to the mean values for sensory evaluation, T 2 was preferred over other treatments. The bars received an acceptable sensory evaluation, demonstrating that they were suitable for 90 days of storage. Phytochemical quantities significantly increased in subsequent treatments, but decreased during storage in all the treatments. Similar trend was observed regarding total antioxidant and DPPH radical scavenging activities. The mineral contents increased significantly among the treatments. The microbial analysis of fruit bars exposed that the fruit were microbiologically safe. Hence, on the basis of the results obtained in this study, it may be concluded that the developed roselle-fig fruit bar would be acceptable and nutritious regarding physicochemical characteristics, microbiological quality, and antioxidant potential.


High Aspect Ratio β-Ga2O3 Fin Arrays with Low-Interface Charge Density by Inverse Metal-Assisted Chemical Etching.
β-Ga2O3, with a bandgap of ∼4.6-4.9 eV and readily available bulk substrates, has attracted tremendous interest in the wide bandgap semiconductor community. Producing high aspect ratio β-Ga2O3 3D nanostructures without surface damage is crucial for next-generation power electronics. However, most wet etching methods can only achieve very limited aspect ratios, while dry etch usually damages the surface due to high energy ions. In this work, we demonstrate the formation of β-Ga2O3 fin arrays on a (010) β-Ga2O3 substrate by metal-assisted chemical etching (MacEtch) with high aspect ratio and sidewall surfaces with excellent quality. The etching was found to be strongly crystal orientation dependent, and three kinds of vertical structures were formed after MacEtch. The Schottky barrier height (SBH) between Pt and various MacEtch-produced β-Ga2O3 surfaces and sidewalls was found to decrease as the aspect ratio of the β-Ga2O3 vertical structure increased. This could be attributed to the different amount of oxygen lost at the surface after etching, as indicated by the XPS and TEM examination. Very little hysteresis was observed in the capacitance-voltage characteristics for the 3D Pt/Al2O3/β-Ga2O3 MOS capacitor structures, and the extracted interface trap density was as small as 2.73 × 1011 cm-2 eV-1, comparable to or lower than that for unetched planar β-Ga2O3 surfaces.


Repeated bronchoconstriction attenuates the cough response to bronchoconstriction in naïve guinea pigs.
Cough variant asthma (CVA) is recognized as a precursor of bronchial asthma (BA). However, the cough response to bronchoconstriction differs between these similar diseases. Repeated bronchoconstriction and the resulting imbalance of endogenous lipid mediators may impact the cough response. We investigated the influence of repeated bronchoconstriction on the cough response to bronchoconstriction using naïve guinea pigs. Bronchoconstriction was induced for 3 consecutive days and changes in the cough response and lipid mediators, such as PGE2, PGI2, and cysteinyl-LTs (Cys-LTs), in BAL fluid (BALF) were assessed. We investigated the effect of endogenous PGI2 on the cough response by employing a PGI2 receptor antagonist. In order to investigate the cough response over a longer period, we re-evaluated the cough response 2 weeks after repeated bronchoconstriction. The number of coughs induced by bronchoconstriction were significantly decreased by repeated bronchoconstriction. The levels of PGE2, PGI2, and Cys-LTs, and the ratio of PGI2/PGE2 were significantly increased, following repeated bronchoconstriction. This decrease in the cough response was suppressed by pretreatment with a PGI2 receptor antagonist. Two weeks after repeated bronchoconstriction, the cough response returned to the same level as before repeated bronchoconstriction along with a concomitant return of lipid mediators, such as PGE2, PGI2, and Cys-LTs and the ratio of PGI2/PGE2. Our results suggest that repeated bronchoconstriction and the resulting imbalance of endogenous lipid mediators contribute to the difference in cough responses to bronchoconstriction in CVA and BA.


Tracing the locality of prisoners and workers at the Mausoleum of Qin Shi Huang: First Emperor of China (259-210 BC).
The mausoleum complex of the First Emperor of China, Qin Shi Huang (259-210 BC), is one of the most famous and important archaeological sites in China, yet questions remain as to how it was constructed and by whom. Here we present isotopic results of individuals from the Liyi (n = 146) and Shanren sites (n = 14), both associated with the mausoleum complex. Those buried at Liyi represent the local workers/inhabitants of the Qin population, and the δ(13)C (-8.7 ± 1.5%) and δ(15)N (10.3 ± 0.7%) values indicate that they consumed predominately millet and/or domestic animals fed millet. In contrast, the Shanren individuals were prisoners forced to construct the mausoleum (found buried haphazardly in a mass grave and some in iron leg shackles), and their δ(13)C (-15.4 ± 2.9%) and δ(15)N (8.0 ± 0.6%) results indicate a more mixed C3/C4 diet, with possibly less domestic animals and more wild game protein consumed. This pattern of decreased millet consumption is also characteristic of archaeological sites from southern China, and possible evidence the Shanren prisoners originated from this region (possibly the ancient Chu state located in modern day Hubei Province and parts of Hunan and Anhui Provinces). Further, this finding is in agreement with historical sources and is supported by previous ancient DNA evidence that the mausoleum workers had diverse origins, with many genetically related to southern Chinese groups.


Binge drinking and alcohol-related problems among U.S.-born Asian Americans.
Binge drinking (five drinks or more in a 2-h sitting for men or four or more drinks in a 2-h sitting for women) and alcohol-related problems are a growing problem among Asian American young adults. The current study examines the sociocultural (i.e., generational status and ethnic identity) determinants of binge drinking and alcohol-related problems across U.S.-born, young-adult, Asian American ethnic groups. Data were collected from 1,575 Asian American undergraduates from a public university in Southern California. Chinese Americans consisted of the largest Asian ethnicity in the study, followed by Vietnamese, Filipino, Korean, South Asian, Japanese, Multi-Asian, and "other Asian American." Participants completed a web-based assessment of binge drinking, alcohol-related problems, ethnic identity, descriptive norms (i.e., perceived peer drinking norms), and demographic information. An analysis of variance was used to determine potential gender and ethnic differences in binge drinking and alcohol-related problems. Negative binomial regression was selected to examine the relationship between the predictors and outcomes in our model. There were no gender differences between Asian American men and women in regards to binge drinking; however, men reported more alcohol-related problems. Japanese Americans reported the highest number of binge-drinking episodes and alcohol-related problems, followed by Filipino and Multi-Asian Americans (e.g., Chinese and Korean). Living off-campus; higher scores in descriptive norms; Greek status; and belonging to the ethnic groups Japanese, Filipino, Multi-Asian, Korean, and South Asian increased the risk of engaging in binge drinking. Quantity of alcohol consumed, Greek status, gender, Filipino, South Asian, other Asian, and lower ethnic identity scores were related to alcohol-related problems. Using one of the largest samples collected to date on sociocultural determinants and drinking among U.S.-born Asian American young adults, the findings highlight the significant variability in drinking patterns among Asian American ethnic groups.


5-Hydroxymethyl-2-Furfural Oxidation Over Au/CexZr1-xO2 Catalysts.
A series of gold catalysts supported on pure CeO2, ZrO2, and two different Ce-Zr mixed oxides have been prepared and tested in the 5-hydroxymethyl-2-furfural oxidation reaction. All catalysts show high catalytic activity (100% conversion) and important selectivity (27-41%) to the desired product i.e., 2,5-furandicarboxylic acid at low base concentration. Products selectivity changes with the support nature as expected, however, the observed trend cannot be related neither to gold particle size, nor to catalyst reducibility and oxygen mobility. An important relation between the FDCA selectivity and the support textural properties is observed, conducing to the general requirement for optimal pore size for this reaction.


Clarithromycin mediated the expression of polymorphonuclear granulocyte response against streptococcus pneumoniae strains with different patterns of susceptibility and resistance to penicillin and clarithromycin.
There is an urgent need for antibiotics that can be used in the therapy of infections caused by penicillin-resistant Streptococcus pneumoniae, the incidence of which is often associated with considerable morbidity and mortality. Antibiotics that can interact positively with the immune response and that also possess microbicidal properties might significantly contribute to improving the outcome of S. pneumoniae infections. Therefore, in the present study we investigated the effect of clarithromycin, an extended spectrum macrolide currently used in the treatment of respiratory tract infections, on the in vitro interaction between human polymorphonuclear granulocytes (PMN) and three strains of S. pneumoniae with different susceptibility or resistance patterns to both penicillin and clarithromycin. At a concentration of one-half the minimal inhibitory concentration (MIC), clarithromycin significantly enhanced human PMN functions, particularly intracellular bactericidal activity, against all the S. pneumoniae strains, including resistant ones. This finding may help to explain clarithromycin activity in vivo despite apparent resistance in vitro. Preexposure of PMNs to one-half the MIC of clarithromycin had no effect on either phagocytosis or intracellular killing, ruling out a direct antibiotic action on PMNs. Preexposure of streptococci to clarithromycin increased the susceptibility of S. pneumoniae to the bactericidal mechanisms of human PMNs compared with untreated bacteria, indicating that this macrolide may partly reduce bacterial virulence via changes in S. pneumoniae.


Thermal injury and recovery of Salmonella enterica serovar enteritidis in ground chicken with temperature, pH, and sodium chloride as controlling factors.
Cells of Salmonella enterica serovar Enteritidis were grown at 25 and 35 degrees C, heat injured (55, 60, and 62.5 degrees C), and recovered in tryptic soy broth (TSB) at various NaCl concentrations (2.0 and 3.5%) and pH levels (5.5 and 6.5). To assess the interactions of growth temperature, heating temperature, NaCl concentration and pH on the thermal injury and recovery of Salmonella Enteritidis in ground chicken, a randomized design with each experimental combination was used. When a logistic equation for nonlinear survival curves was used, D-values of cells of Salmonella Enteritidis grown at 25 degrees C were 7.60, 5.73, and 4.81 min at 55, 60, and 62.5 degrees C, respectively. For cells grown at 35 degrees C, the D-values were 12.38, 7.45, and 5.70 min at 55, 60, and 62.5 degrees C. The influence of tryptic soy agar and double modified lysine agar (DMLIA) on the recovery of heat-injured cells was determined. Recovery was significantly reduced on DMLIA at increased pH levels and NaCl concentrations. Higher numbers of cells were recovered in TSB with 2.0% NaCl than in TSB with 3.5% NaCl. It was observed that the rate of recovery of heat-injured cells was similar at each pH. Therefore, a pH range of 5.5 to 6.5 does not have a major inhibitory effect on the recovery of Salmonella Enteritidis.


Investing in the future of young people.
Atrocious events seem to have multiplied in frequency recently. Sometimes it feels as if we have become almost inured to their obscenity. No sooner has the impact and aftermath of one event receded into the past than along comes another to test our reserves.


Kaposi sarcoma of the stomach: a case report.
A 60-year-old man presented with persistent dysphagia and weight loss of 2-months duration. An upper GI endoscopy revealed mycotic oesophagitis and chronic gastritis with two ulcers of the gastric body and antrum. Repeat endoscopy was performed after medical treatment failed, and histological examination on new biopsy samples led to a diagnosis of Kaposi sarcoma of the stomach. HIV infection was not known at this time; however, the patient was tested after the diagnosis of Kaposi sarcoma was made and found to be HIV positive. An adequate biopsy sampling was required for histological diagnosis and the use of immunohistochemical markers, especially human herpesvirus 8 (HHV8) antibodies, supplied valid diagnostic support. This case underlines the importance of an accurate evaluation of vascular proliferation in gastrointestinal biopsies even in patients without clinical evidence of HIV-related pathology.


Cloning: revisiting an old debate.
The debate about cloning that took place 25 years ago, although directed toward a different sort of cloning, elucidates fundamental issues currently at stake in reproductive technologies and research. Paul Ramsey and Joseph Fletcher were participants in this early debate. The differences between Ramsey and Fletcher about the meaning and sufficiency of freedom, the understanding and weighing of good and evil, the connection between embodiment and personhood, the relationship of humans with nature, and the meaning of parenthood suggest both a broader agenda for the debate about cloning and a cautious move forward in the development of embryo-splitting.


[When the throug is reached].
The only option for a patient suffering from severe chronic obstructive pulmonary disease (COPD) despite fully developed medical therapy inclusive eventually supplemental oxygen is either lung transplantation or lung-volume-reduction surgery (LVRS). Indication for LVRS is based on the results of a large prostective controlled clinical trial and patients are selected for this intervention based on particular functional and radiomorphologic criteria. We report a patient with far advanced COPD, no longer able to walk to the toilette without support. Based on clinical reasoning and our experience with other unique cases the patient underwent unilateral LVRS despite a lack of scientific evidence that she might profit from this intervention. Luckily, the perioperative course was uneventful and she experienced an impressive subjective and objective improvement. This case illustrates, that in desperate situations it may be necessary to reach a therapeutic decision outside scientifically based evidence.


Hierarchically patterned protein scaffolds with nano-fibrillar and micro-lamellar structures modulate neural stem cell homing and promote neuronal differentiation.
Biophysical factors are essential in cell survival and behaviors, but constructing a suitable 3D microenvironment for the recruitment of stem cells and exerting their physiological functions remain a daunting challenge. Here, we present a novel silk fibroin (SF)-based fabrication strategy to develop hierarchical microchannel scaffolds for biomimetic nerve microenvironments in vitro. We first modulated the formation of SF nanofibers (SFNFs) that mimic the nanostructures of the native extracellular matrix (ECM) by using graphene oxide (GO) nanosheets as templates. Then, SFNF-GO systems were shaped into 3D porous scaffolds with aligned micro-lamellar structures by freeze-casting. The interconnected microchannels successfully induced cell infiltration and migration to the SFNF-GO scaffolds' interior. Meanwhile, the nano-fibrillar structures and the GO component significantly induced neural stem cells (NSCs) to differentiate into neurons within a short timeframe of 14 d. Importantly, these 3D hierarchical scaffolds induced a mild inflammatory response, extensive cell recruitment, and effective stimulation of NSC neuronal differentiation when implanted in vivo. Therefore, these SFNF-GO lamellar scaffolds with distinctive nano-/micro-topographies hold promise in the fields of nerve injury repair and regenerative medicine.


Astrophysical processes on the sun.
Over the past two decades, there have been a series of major solar space missions, namely Yohkoh, SOHO, TRACE, and in the past 5 years, STEREO, Hinode and SDO, studying various aspects of the Sun and providing images and spectroscopic data with amazing temporal, spatial and spectral resolution. Over the same period, the type and nature of numerical models in solar physics have been completely revolutionized as a result of widespread accessibility to parallel computers. These unprecedented advances on both observational and theoretical fronts have led to significant improvements in our understanding of many aspects of the Sun's behaviour and furthered our knowledge of plasma physics processes that govern solar and other astrophysical phenomena. In this Theme Issue, the current perspectives on the main astrophysical processes that shape our Sun are reviewed. In this Introduction, they are discussed briefly to help set the scene.


Preparation and characterization of cornstalk microspheric hydrochar and adsorption mechanism of mesotrione.
In this study, cornstalk was pyrolysed to obtain hydrochar (HC), which was used to remove mesotrione from aqueous solutions. HC characterization and batch experiments were conducted to investigate mesotrione adsorption and the underlying mechanism. The characterization revealed microspheres on the HC surface. FT-IR spectra showed that the HC contained a large number of -OH groups, C=C bonds of aromatic rings, C-H groups in aromatic rings and phenolic C-O bonds. The adsorption results showed that the mesotrione adsorption ability gradually increased as the HC preparation temperature increased. The quasi-second-order kinetic equation (R2 ≥ 0.9860, p < 0.05) agreed well with the mesotrione adsorption process. The maximum monolayer adsorption capacity, which was obtained at pH 7 and 45°C with HC prepared at 240°C, was 3181.7 mg kg-1 with the Langmuir isotherm model (R2 ≥ 0.9491, p < 0.05). Van der Waals and dipole forces and hydrogen bonds were inferred as the main adsorption mechanisms. HC has potential as an effective and energy-saving adsorbent for mesotrione to reduce environmental pollution.


The low-density lipoprotein receptor-related protein 5 (LRP5) 4037C>T polymorphism: candidate for susceptibility to type 1 diabetes mellitus.
The present study has investigated the association between low-density lipoprotein receptor-related protein 5 (LRP5) 4037C>T polymorphism and type 1 diabetes mellitus (T1DM) susceptibility in a Brazilian population. A total number of 134 T1DM patients and 180 normoglycemic individuals (NG) aged 6-20 years were studied. Glycated hemoglobin and glucose levels were determined. Genotyping of LRP5 4037C>T (rs3736228) was performed. T1DM patients showed poor glycemic control. Genotypes in the codominant (CT: OR = 2.99 [CI 95%: 1.71-5.24], p < 0.001; TT: OR = 5.34 [CI 95%: 1.05-2702], p < 0.001), dominant (CT + TT: OR = 3.16 [CI 95%: 1.84-5.43], p < 0.001) and log-additive (OR = 2.78 [CI 95%: 1.70-4.52], p < 0.001) models, and LRP5 4037T allele (OR = 2.88, [CI 95%: 1.78-4.77], p < 0.001) were associated with an increased risk of developing T1DM. LRP5 4037CT and CT+TT carriers in T1DM group showed higher concentrations of serum glucose and glycated hemoglobin when compared with CC carriers. The LRP5 4037C>T may represent a candidate for T1DM susceptibility, as well as poor glycemic control.


Spectral decomposition of intracellular complex fluorescence using multiple-wavelength phase modulation lifetime determination: technical approach and preliminary applications.
Lifetime-based spectral decomposition using a frequency-domain phase/modulation technique is developed on a microspectrofluorimeter prototype. In a fluorescent mixture with strongly overlapping components, such measurements enable us to not only obtain excited state lifetimes of each fluorescent component but also determine the specific spectral contribution of each species without the use of any model spectra. Examples of such applications are first given for complex mixtures of highly overlapping fluorescent components in solution. Preliminary results concerning cellular applications are also reported. This allows us to follow the cellular uptake and intracellular stability of fluorescent labeled modified oligonucleotides in the context of antisense strategy studies. Indeed, the intracellular signal from the fluorescent label bound to oligonucleotides can be distinguished from those of the free label by its specific excited state lifetime.


Effects of melatonin on the proliferation and apoptosis of sheep granulosa cells under thermal stress.
The cross-talk between oocyte and somatic cells plays a crucial role in the regulation of follicular development and oocyte maturation. As a result, granulosa cell apoptosis causes follicular atresia. In this study, sheep granulosa cells were cultured under thermal stress to induce apoptosis, and melatonin (MT) was examined to evaluate its potential effects on heat-induced granulosa cell injury. The results demonstrated that the Colony Forming Efficiency (CFE) of granulosa cells was significantly decreased (heat 19.70% ± 1.29% vs. control 26.96% ± 1.81%, p < 0.05) and the apoptosis rate was significantly increased (heat 56.16% ± 13.95% vs. control 22.80% ± 12.16%, p < 0.05) in granulosa cells with thermal stress compared with the control group. Melatonin (10⁻⁷ M) remarkably reduced the negative effects caused by thermal stress in the granulosa cells. This reduction was indicated by the improved CFE and decreased apoptotic rate of these cells. The beneficial effects of melatonin on thermal stressed granulosa cells were not inhibited by its membrane receptor antagonist luzindole. A mechanistic exploration indicated that melatonin (10⁻⁷ M) down-regulated p53 and up-regulated Bcl-2 and LHR gene expression of granulosa cells under thermal stress. This study provides evidence for the molecular mechanisms of the protective effects of melatonin on granulosa cells during thermal stress.


Ultrasensitive electrochemical detection of proteins by amplification of aptamer-nanoparticle bio bar codes.
An ultrasensitive label-free bioelectrochemical method for rapid determination of thrombin has been developed by directly detecting the redox activity of adenine (A) nucleobases of anti-thrombin aptamer using a pyrolytic graphite electrode. The bioelectrochemical protocol involves a sandwich format. Thrombin, captured by immobilzed anti-thrombin antibody on microtiter plates, is detected by anti-thrombin aptamer-Au nanoparticle bio bar codes. A systematic optimization of the parameters has been carried out via ELAA (enzyme linked aptamer assay) performance. The adenine nucleobases were released by acid or nuclease from Au nanoparticles bound on microtiter plates. Differential pulse voltammetry was employed to investigate the electrochemical behaviors of the purine nucleobases. Well-defined adenine signal was observed at about 0.85 V in pH 5.9 acetate buffer. Because the nanoparticle carries a large number of aptamers per thrombin binding event, there is substantial amplification and thrombin can be detected at a very low level of detection (0.1 ng/mL). This method has been used to detect thrombin in complex matrix such as fetal calf serum with minimum background interference.


Interaction of catechol and gallic acid with titanium dioxide in aqueous suspensions. 1. Equilibrium studies.
The adsorption isotherms of catechol (1,2-dihydroxybenzene) and gallic acid (3,4,5-trihydroxybenzoic acid) onto titanium dioxide (Degussa P-25) were measured at various pH values and room temperature using attenuated total reflection Fourier transform infrared (FTIR-ATR) data, processed by singular value decomposition. The affinity is largely pH independent, although the deprotonatation of the carboxylic group in gallic acid might produce a slight increase in the affinity. Catechol was shown to form two complexes, with Langmuir stability constants log K of 4.66 (strong mode) and 3.65 (weak mode). Both complexes have the same spectral signature, and mononuclear and binuclear chelate structures are proposed for them. Gallic acid chemisorbs by complexation through two -OH groups and forms one complex only, log K = 4.70. The third -OH and the pendant carboxylate do not influence much the stability of the surface complex. Comparison with literature data demonstrates that the affinity of 4-chlorocatechol is also similar, whereas 2,3-dihidroxynaphthalene and 4-nitrocatechol form more stable complexes, probably because of the solvation contribution to the overall Gibbs adsorption energy. All quoted constants refer to the surface complexation equilibria written as follows: ([triple bond]Ti-OH)2 + H2L = ([triple bond]Ti)2-L + 2H2O, i.e., as electroneutral processes. The FTIR-ATR spectra of the surface complexes are also discussed.


An Unusual Outbreak of Chlamydiosis in Commercial Turkeys Involving the Nasal Glands.
An unusual outbreak of chlamydiosis was diagnosed in 15,000, 13-wk-old organically grown turkeys housed in a semiconfinement housing system. The disease was characterized by unilateral or bilateral swelling above the eye due to mild-to-severe inflammation of the nasal glands in 3%-5% of the birds. Except for a slight drop in feed and water consumption, the birds did not exhibit any respiratory signs, morbidity, and mortality. Chlamydiosis in the turkeys was confirmed by immunofluorescence, immunohistochemistry, and PCR assay of the nasal glands. Other samples such as conjunctiva, lungs, air sacs, heart, liver, spleen, and feces were negative for chlamydia by florescence antibody test in birds submitted over several weeks. Chlamydia psittaci strain B was isolated in chicken egg embryos and typed by multilocus sequence variable number of tandem repeats analysis, multilocus sequence typing, and ompA gene sequencing as a CP3-like strain. This is the first report of a naturally occurring chlamydiosis affecting the nasal glands in turkeys.


Circulating fibrocytes: a potent cell population in antigen-presenting and wound healing.
Fibrocytes are bone marrow-derived mesenchymal progenitors that co-express hematopoietic cell antigens and markers of monocytic lineage as well as fibroblast products. During wound healing, fibrocytes have been found to possess the ability of antigen-presentation to naive T cells in the inflammatory phase. Moreover, they can promote the endothelial cell proliferation, migration and angiogenesis by secreting several proteins. Fibrocytes can further differentiate into mature mesenchymocyte lineage, such as fibroblasts, myofibroblasts and adipocytes, and they may represent the systemic source of myofibroblasts that exert a contractile force required to close tissue wounds. A deep understanding of the mechanism involved in fibrocyte migration and differentiation may lead to the development of a novel theory of normal physiology and pathology.


Skeletal muscle changes following stroke: a systematic review and comparison to healthy individuals.
Despite extensive study of the impact of stroke on muscle and functional performance, questions remain regarding the extent to which changes are due to the neurological injury vs. age-related loss of morphology and force production. To synthesize available evidence describing post-stroke changes in lower extremity muscle size and strength compared to healthy adults. Scientific literature was searched up to April 2016 to identify studies that included lower extremity muscle size and strength measures in individuals with chronic stroke. Lower extremity muscle size and strength data from healthy controls were sought for comparison. Relative differences were calculated between paretic, nonparetic, and control limbs. Fifteen studies with 375 participants (61% male; age = 62 ± 5 years; time since stroke = 60 ± 42 months) were included. The paretic limb exhibited deficits of ~13% in thigh muscle size, ~5% in lower leg muscle size, and ~8% in lean leg mass compared to the nonparetic limb. Paretic plantarflexor and knee extensor strength were 52 and 36% lower, respectively, compared to the nonparetic limb. When compared to age-matched control data, both paretic and nonparetic limbs showed deficits in muscle size and strength. Age-related differences support the impact of stroke-related sarcopenia as a contributor to hemiparetic muscle dysfunction. Understanding these muscular changes is necessary for designing appropriate exercise interventions aimed at restoring muscle function.


Pachyonychia congenita with woolly hair in a ten month old infant.
A 10-month-old female presented with severe progressive wedge-shaped thickening and discoloration of all twenty nails. Further evaluations revealed palmoplantar keratoderma along with recurrent acral blisters causing residual crusted ulcers which were present during the past six months. Other findings included scalp kinky hair and dental caries. Past medical and family history had remarkable findings such as natal teeth and similar skin lesions in her older brother since his infancy. The patients' clinical presentations and history are compatible with pachyonychia congenita presenting with concomitant features of both subtypes 1 and 2.


OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF CHOROIDAL NEOVASCULARIZATION ASSOCIATED WITH CHOROIDAL NEVUS.
To describe the imaging features of choroidal neovascularization (CNV) associated with choroidal nevus using optical coherence tomography angiography (OCT-A) imaging. Retrospective observational case series. Patients with CNV secondary to choroidal nevus underwent full imaging examination including fundus photography, fluorescein angiography, indocyanine green angiography, spectral domain OCT, and OCT-A. The OCT-A features were analyzed and correlated with conventional angiography findings and spectral domain OCT. There were 11 eyes from 11 patients (6 men and 5 women, mean age of 65 ± 20.4 years) included in the analysis. Fluorescein angiography and indocyanine green angiography disclosed CNV in 90% and 83%, respectively. Optical coherence tomography angiography displayed CNV network in 11 eyes (100%) and the pattern was classified as "sea-fan" in 8 (73%) and "long filamentous linear vessels" in 3 (27%) eyes. Distinct from CNV, intrinsic vasculature within the nevus was observed in six eyes (55%), corresponding to those with chronic retinal pigment epithelium changes. Optical coherence tomography angiography is a useful imaging technique to disclose CNV associated with choroidal nevus. Despite the presence of intraretinal or subretinal fluid and hemorrhage, OCT-A revealed the CNV in all cases, results noninferior to indocyanine green angiography. This imaging modality can be useful for analysis of long-standing nevi with related exudation.


Down syndrome cell adhesion molecule (DSCAM) associates with uncoordinated-5C (UNC5C) in netrin-1-mediated growth cone collapse.
In the developing nervous system, neuronal growth cones explore the extracellular environment for guidance cues, which can guide them along specific trajectories toward their targets. Netrin-1, a bifunctional guidance cue, binds to deleted in colorectal cancer (DCC) and DSCAM mediating axon attraction, and UNC5 mediating axon repulsion. Here, we show that DSCAM interacts with UNC5C and this interaction is stimulated by netrin-1 in primary cortical neurons and postnatal cerebellar granule cells. DSCAM partially co-localized with UNC5C in primary neurons and brain tissues. Netrin-1 induces axon growth cone collapse of mouse cerebellum external granule layer (EGL) cells, and the knockdown of DSCAM or UNC5C by specific shRNAs or blocking their signaling by overexpressing dominant negative mutants suppresses netrin-1-induced growth cone collapse. Similarly, the simultaneous knockdown of DSCAM and UNC5C also blocks netrin-1-induced growth cone collapse in EGL cells. Netrin-1 increases tyrosine phosphorylation of endogenous DSCAM, UNC5C, FAK, Fyn, and PAK1, and promotes complex formation of DSCAM with these signaling molecules in primary postnatal cerebellar neurons. Inhibition of Src family kinases efficiently reduces the interaction of DSCAM with UNC5C, FAK, Fyn, and PAK1 and tyrosine phosphorylation of these proteins as well as growth cone collapse of mouse EGL cells induced by netrin-1. The knockdown of DSCAM inhibits netrin-induced tyrosine phosphorylation of UNC5C and Fyn as well as the interaction of UNC5C with Fyn. The double knockdown of both receptors abolishes the induction of Fyn tyrosine phosphorylation by netrin-1. Our study reveals the first evidence that DSCAM coordinates with UNC5C in netrin-1 repulsion.


The expression of cysteine-rich secretory protein 2 (CRISP2) and its specific regulator miR-27b in the spermatozoa of patients with asthenozoospermia.
Cysteine-rich secretory protein 2 (CRISP2) is an important sperm protein and plays roles in spermatogenesis, modulation of flagellar motility, acrosome reaction, and gamete fusion. Clinical evidence shows a reduced CRISP2 expression in spermatozoa from asthenozoospermic patients, but the molecular mechanism underlying its reduction remains unknown. Herein, we carried out a study focusing on the CRISP2 reduction and its roles in asthenozoospermia. Initially, through analyzing CRISP2 expression and methylation on CRISP2 promoter activity in sperm, we observed a decreased expression of CRISP2 protein rather than its mRNA in the ejaculated spermatozoa from asthenozoospermic patients and no methylation in the CRISP2 promoter, suggesting CRISP2 expression may be regulated in the sperm at the posttranscriptional level. Subsequently, we found that microRNA 27b (miR-27b), predicted as a candidate regulator of CRISP2 using bioinformatics, was highly expressed in the ejaculated spermatozoa from asthenozoospermic patients. Luciferase reporter assay and transfection experiments disclosed that this microRNA could target CRISP2 by specifically binding its 3' untranslated region, suppressing CRISP2 expression. Extended clinical observation further confirmed a highly expressed miR-27b and its obviously negative correlation with CRISP2 protein expression in ejaculated spermatozoa samples from asthenozoospermic patients. Finally, we conducted a retrospective follow-up study to support that either high miR-27b expression or low CRISP2 protein expression was significantly associated with low sperm progressive motility, abnormal morphology, and infertility. Thus, this study provides the first preliminary insight into the mechanism leading to the reduced CRISP2 expression in asthenozoospermia, offering a potential therapeutic target for treating male infertility or for male contraception.


Robustness properties of apoptosis models with respect to parameter variations and intrinsic noise.
Analyses of different robustness aspects for models of the direct signal transduction pathway of receptor-induced apoptosis is presented. Apoptosis is a form of programmed cell death, removing unwanted cells within multicellular organisms to maintain a proper balance between cell reproduction and death. Its signalling pathway includes an activation feedback loop that generates bistable behaviour, where the two steady states can be seen as 'life' and 'death'. Inherent robustness, widely recognised in biological systems, is of major importance in apoptosis signalling, as it guarantees the same cell fate for similar conditions. First, the influence of the stochastic nature of reactions indicating a role for inhibition reactions as noise filters and justifying a deterministic approach in the further analyses is evaluated. Second, the robustness of the bistable threshold with respect to parameter changes is evaluated by statistical methods, showing the need to balance both the forward and the back part of the activation loop. These analyses can also discriminate between the models favouring the model consistent with novel biological findings. The parameter robustness analyses are also applicable to other signal transduction networks, as several have been shown to display bistable behaviour. These methods therefore have a range of possible applications in systems biology not only to measure robustness, but also for model discrimination.


Suppression of cortical TRPM7 protein attenuates oxidative damage after traumatic brain injury via Akt/endothelial nitric oxide synthase pathway.
Neuronal death after traumatic brain injury (TBI) is a complex process resulting from a combination of factors, many of which are still unknown. Transient receptor potential melastatin 7 (TRPM7) is a transient receptor potential channel that has been demonstrated to mediate ischemic and traumatic neuronal injury in vitro. In the present study, TRPM7 was suppressed in the rat cerebral cortex by intracortical injections of viral vectors bearing shRNA specific for TRPM7 to investigate its potential role in an in vivo TBI model. We found that TRPM7 suppression significantly reduced brain edema, brain contusion volume and motor functional deficits, which was sustained for at least 2 weeks after the insult. These protective effects were accompanied by inhibited apoptosis in injured cortex. Also, TRPM7 suppression attenuated lipid peroxidation, decreased the expression of protein carbonyl, and preserved the endogenous antioxidant enzyme activities. The results of western blot analysis showed that TRPM7 suppression markedly increased the phosphorylation of Akt and endothelial nitric oxide synthase (eNOS). In addition, blocking Akt/eNOS pathway activation by the specific inhibitor LY294002 (LY, 10 μL, 10 mmol/L) or L-NIO (0.5 mg/kg) partially reversed the protective effects of TRPM7 suppression and its anti-oxidative activities. Taken together, these findings demonstrated that regional inhibition of TRPM7 in cerebral cortex exerts neuroprotective effects against TBI through activation of Akt/eNOS pathway. Thus, TRPM7 might represent a potential drug development target for the treatment of TBI.


[Isolation and properties of neurospecific proteins 14-3-2, 14-3-3 and 10-40-4].
A procedure for isolation of three neurospecific proteins 14-3-2, 14-3-3 and 10-40-4 from human brain is proposed. This procedure includes successive ammonium sulphate precipitation, ion-exchange chromatography on DEAE-cellulose, gel filtration through Sephadex G-150 and ion-exchange chromatography on DEAE-Sephadex A-50. Specific antisera raised against these antigens were used to prove their neurospecificity and to study their species-specificity. Some physico-chemical properties of the isolated proteins were investigated. The 14-3-2 protein--neurospecific enolase, appeared to be much more stable at high temperatures than the non-neuronal enzyme isoform.


ROS and ABA signaling are involved in the growth stimulation induced by low-dose gamma irradiation in Arabidopsis seedling.
It has been well established that gamma rays at low doses have stimulatory effects on plant growth and development. However, our knowledge regarding the molecular mechanism underlying the growth stimulation remains limited. In this study, we report the role of reactive oxygen species (ROS) and abscisic acid (ABA) in the growth stimulation using irradiated Arabidopsis seeds. The results indicated that 50 Gy gamma irradiation presented maximal beneficial effects on germination index, root length, and fresh weight. The contents of hydrogen peroxide (H2O2) and activities of antioxidant enzymes under gamma irradiation were markedly higher than those of controls. ROS scavenging significantly suppressed the growth of the irradiated plants. Furthermore, endogenous ABA was induced under low-dose gamma irradiation. The growth stimulation and elevated H2O2 level were affected in the irradiated ABA-deficient mutant aba2-1 compared with the mutant control. Transcriptional expression analysis of selected genes revealed that several genes for ABA biosynthesis were upregulated, and the genes for ABA catabolic pathway and transport were differentially regulated in response to low-dose gamma irradiation. Our results suggest that ROS and ABA signaling play an essential role in the stimulatory effects of low-dose gamma irradiation and that ROS, as secondary molecules, mediate ABA signal transduction under irradiation in response to stress factors during plant growth.


Cracking Behavior and Stress Field Evolution in Coal Specimens Containing Bedding under Uniaxial Compression.
During the underground mining process, various coal seams with different bedding structures are often encountered. The presence of bedding structures is one of the primary factors that influence the strength and deformation characteristics of the coal seam and then affect gas extraction and gas disaster prevention. However, there is still a lack of mechanical properties of coal rock with structural anisotropy influenced by bedding structures. In this study, numerical models were established by using the particle flow code method to simulate coal specimens containing bedding with varying inclination angles. The results demonstrate the impact of the bedding inclination angle on the mechanical properties, crack propagation patterns, and the temporal and spatial evolution of the stress field in coal specimens with bedding during the loading process. Furthermore, three crack initiation patterns were investigated for coal specimens with different bedding angles. Additionally, the quantitative relationship between the mechanical properties and the fractal dimension was analyzed. The numerical simulation results were effectively validated through laboratory tests.


Pulse methylprednisolone in SLE.
Insufficient information is available about the effectiveness of high-dose intravenous corticosteroid treatment in non-renal SLE to determine whether it provides better management of the disease. Issues of steroid preparation, dose and frequency have not been addressed. Significant short-term complications appear to be minimal; the question of long-term effects on avascular necrosis may not be answerable since most patients also receive oral corticosteroids at some time during their course. No large randomized controlled trial of pulse IV-MP in lupus nephritis is available. Ideally, such a trial would include randomization with stratification according to important prognostic variables. Previous studies of other agents have been hampered by lack of agreement about both the identification of relevant prognostic variables and the selection of 'significant' measures of outcome. The observation that patients with recent deterioration in glomerular filtration rate are more likely to improve after IV-MP may form the basis for stratification in a controlled trial of the comparative efficacy of IV-MP and other forms of treatment. However, lack of improvement in glomerular filtration rate among patients without recent deterioration in function may reflect the inadequacy of our outcome measures rather than a true lack of beneficial effect for the patient.


Surveying the youth-to-senior transition landscape in Major League Soccer: a new frontier.
The aim of this study was to survey Major League Soccer stakeholders' attitudes and perspectives on the youth-to-senior transition with a particular interest in the league's evolving club structures, specifically the reserve team and youth academy entities. The survey assessed various stakeholders' views on clubs' organisational aims and structure, the capabilities of club entities to prepare players for the first team, and the transition process to the first team within MLS. A total of 80 participants working in various 'player operation' roles for MLS clubs in the United States and Canada voluntarily completed the online survey. The predominant aim for both reserve teams and academies in MLS is to develop players for the first team. The organisational structure and governance of reserve teams are varied across the league, but an overarching feature is their function as a development team. When players are transitioning, communication between staff may or may not be clear and effective. Finally, for players within an MLS club's talent pathway, a variety of support strategies are made available during the transition into the first team, but psychological support in particular may be limited or unavailable. Similar to European soccer, the aim of MLS reserve teams and youth academies is to develop first team players for the club. However, while players are transitioning into the first team, communication may or may not be clear and effective, and psychological support may be absent, which may impair player development initiatives.


A look into hemostatic characteristics during pediatric liver transplantation using the thromboelastometry (ROTEM® ) test.
There is a paucity of evidence about the coagulation profile regarding the complexity of children undergoing liver transplantation (LT). This study aimed to investigate intraoperative hemostatic changes during pediatric LT according to the etiology for LT and examine the ability of rotational thromboelastometry (ROTEM® , TEM International GmbH, Munich, Germany) as a point-of-care monitoring method. We evaluated 106 patients aged 3 months to 17 years undergoing LT for acute liver failure (ALF) and chronic liver disease, which consists of patients with cholestatic disease, metabolic/genetic disease, and cancer. A total of 731 ROTEM® measurements, including 301 ellagic acid to initiate clotting via the intrinsic pathway, 172 tissue factor to initiate the extrinsic clotting cascade (EXTEM), and 258 cytochalasin D to inhibit platelet activity reflecting fibrinogen (FIBTEM), were analyzed at predetermined time points (the preanhepatic, anhepatic, and postreperfusion phases). We simultaneously conducted conventional coagulation tests. In children with ALF, preanhepatic measurements of conventional coagulation tests and ROTEM® showed a more hypocoagulable state than other diseases. During LT, the coagulation profile was deranged, with a prolonged clotting time and reduced clot firmness, changes that were more profound in the cholestatic disease group. Maximum clot firmness (MCF) on EXTEM and FIBTEM were well correlated with the platelet count and fibrinogen concentration (r = 0.830, p < 0.001 and r = 0.739, p < 0.001, respectively). On the EXTEM, MCF with 30 mm predicted a platelet count <30,000/mm3 (area under the curve, 0.985), and 6 mm predicted a fibrinogen concentration <100 mg/dl on the FIBTEM (area under the curve, 0.876). However, the activated partial thromboplastin time and prothrombin time were significant but only weakly correlated with the clotting time on the ROTEM® . In children undergoing LT, coagulation profiles depend on the etiology for LT. During LT, ROTEM® parameters could help detect thrombocytopenia and hypofibrinogenemia and guide transfusion therapy as a point-of-care monitoring method.


Entanglement of formation for symmetric Gaussian states.
We show that for a fixed amount of entanglement, two-mode squeezed states are those that maximize Einstein-Podolsky-Rosen-like correlations. We use this fact to determine the entanglement of formation for all symmetric Gaussian states corresponding to two modes. This is the first instance in which this measure has been determined for genuine continuous variable systems.


Psilocybin-assisted therapy for major depressive disorder: An exploratory placebo-controlled, fixed-order trial.
Several early phase studies have demonstrated that psilocybin-assisted therapy has rapid-acting and persisting antidepressant effects from just one or two doses. However, methodological limitations (e.g., placebo-control, blinding) limit interpretability of the existing literature. In an exploratory placebo-controlled, within-subject, fixed-order study, individuals with moderate to severe major depressive disorder were administered placebo (n = 19) followed by psilocybin (0.3 mg/kg) (n = 15) 4 weeks later. Dosing sessions were embedded within an manualized course of psychotherapy. Enhanced blinding procedures were used. Depression, anxiety, and quality of life were measured over a 16-week study period. Depression and anxiety significantly improved following both placebo and psilocybin with no significant difference in the degree of change between the two conditions. However, antidepressant effect sizes were larger after psilocybin (d' = 1.02-2.27) than after placebo (d' = 0.65-0.99) and there were high rates of response (66.7%) and remission (46.7%) following psilocybin administration. Antidepressant effects following psilocybin persisted, on average, for 2 months and there were persisting improvements in mood-related quality of life domains. The strength of mystical-type experience during psilocybin dosing was not correlated with subsequent antidepressant effects. The results of this exploratory study highlight the complex interplay between expectancy, therapy effects, and drug/placebo effects in psychedelic-assisted psychotherapy studies. Nonetheless, the acute and persisting clinical improvements observed following psilocybin support further study of its potential in the treatment of major depression. Future studies should more explicitly mitigate and measure expectancy effects and assess the impact of repeated dosing and different forms of psychotherapeutic support.


Mucinous neoplasms of the appendix: a current comprehensive clinicopathologic and imaging review.
Mucinous neoplasms of the appendix are a heterogeneous group of neoplasms ranging from simple mucoceles to complex pseudomyxoma peritonei. Considerable controversy exists on their pathologic classification and nomenclature. Clear understanding of the histopathologic diversity of these neoplasms helps in establishing proper communication between the radiologist, the pathologist and the surgeon. In this article, we present a brief discussion of the current taxonomy and nomenclature of mucinous neoplasms of the appendix followed by a review of their imaging features. Important points including the significance of identifying extra-appendiceal mucin at imaging, the new classification of pseudomyxoma peritonei into low- and high-grade varieties and the significance of simultaneous ovarian and appendiceal neoplasms are highlighted.


Induction of intrinsic apoptosis in leukaemia stem cells and in vivo zebrafish model by betulonic acid isolated from Walsura pinnata Hassk (Meliaceae).
Leukaemia stem cells (LSC) have been associated with disease relapse and chemotherapy resistance. Betulonic acid (BA), a pentacyclic lupane-type triterpenoid, was reported to exhibit cytotoxicity toward various cancer cells and to be capable of inducing intrinsic apoptosis in solid tumours. However, the in vitro and in vivo apoptotic effects of BA against LSC remain unknown. We aimed to determine whether BA isolated from bark of Walsura pinnata Hassk (Meliaceae) has pro-apoptotic effects on LSC in in vitro and in vivo models. The population of high purity LSC was isolated from the Kasumi-1 cell line using magnetic sorting and characterised by flow cytometry. Cell viability was assessed using the MTS assay to examine dose- and time-dependent effects. The colony formation assay was performed in MethoCult® H4435 enriched media. Apoptosis was analysed using Annexin-V and propidium iodide staining, mitochondrial transmembrane potential was studied using JC-1 staining, and expression of apoptosis related genes (BAX, Bcl-2 and survivin) was evaluated by real time-polymerase chain reaction (RT-PCR). Caspase 3/7 and 9 activities were monitored through Promega Caspase-Glo® over a period of 24h. The in vivo antileukaemia activity was evaluated using LSC xenotransplanted zebrafish, observed for DNA fragmentation from apoptosis by TUNEL assay. BA maintained its potency against the LSC population in comparison to parental Kasumi-1 cells (fold differences ≤ 1.94) over various treatment time points and significantly inhibited the formation of colonies by LSC. Apoptosis was triggered by BA through the upregulation of BAX and suppression of Bcl-2 and survivin genes with the loss of mitochondrial transmembrane potential, leading to the activation of caspase 9 followed by downstream caspase 3/7. BA was able to suppressed leukaemia formation and induced apoptosis in LSC xenotransplanted zebrafish. The results demonstrate that BA inhibited the proliferative and colonogenic properties of LSC. BA induced apoptosis in LSC through the mitochondria pathway and was effective in the in vivo zebrafish model. Therefore, BA could be a lead compound for further development into a chemotherapy agent against LSC.


Rarecare: A policy perspective on the burden of rare diseases on caregivers in Latin America.
In Latin America (LA), 40-50 million people live with rare diseases (RDs) that require constant monitoring, care, and attention. Caregivers help them with their basic life activities and medication administration, which they would otherwise be unable to perform. Family caregivers complement healthcare and social security systems; however, their unpaid work is often underappreciated and under-protected. Recognizing the need to address these unrecognized and undervalued women, the Americas Health Foundation (AHF) convened a panel of LA experts on caregiving for people with RDs to provide recommendations to support the undervalued family caregivers. A panel of LA experts in caregiving for RDs were given questions to address the challenges faced by family caregivers of people with RDs in LA. During a 3-day conference, the panelists' responses were discussed and edited until the panel agreed on recommendations to address the challenges. The identified challenges for caregivers included physical, emotional, and economical areas. Caregivers, primarily women, experienced physical pain, and social isolation, and were forced to pay substantial out-of-pocket expenses in their caregiving roles. Brazil and Colombia are at the forefront of policies to protect caregivers and their experiences in attempting to provide for this group are outlined as case studies for what is possible in LA. Finally, recognizing that caregivers must be included in formulating, executing, and evaluating care policies for people living with RDs and that the caregivers themselves require social assurances, the panel suggested policy objectives aimed at protecting caregivers of people living with RDs. The recommendations ranged from recognizing the role of the family caregiver as an essential supplement to the formal healthcare system to providing financial assistance, training, and workplace protection, among others. Finally, monitoring and evaluating the impact of policies is necessary to ensure that LA is moving forward in caring for family caregivers for people with RDs.


[Acute coronary syndromes with ST-segment elevation and anomalous connections of the coronary arteries].
Acute coronary syndrome with ST-segment elevation associated with an anomalous connection of a coronary artery, when the latter is the culprit, may be problematic. Anatomic and radiologic knowledge of major congenital coronary abnormalities and some catheterization skills can help the operators not to delay a beneficial coronary reperfusion. The relationship between acute coronary syndromes with ST-segment elevation and anomalous connections of the coronary arteries needs to be analyzed with a large number of cases because the coronary artery disease frequency may vary with the type of coronary anomaly.


16S ribosomal RNA sequence-based identification of veterinary clinical bacteria.
This study evaluated 16S rRNA gene sequence analysis methods as tools for identification of 22 phenotypically difficult to identify veterinary clinical bacterial isolates in a veterinary diagnostic laboratory. The study compared 16S rRNA gene sequencing and conventional phenotypic identification methods. Using 16S rRNA full-gene sequencing, 95% (21/22) of the isolates were identified to the genus level and 86% (19/22) to the species level. The conventional or commercially available manual identification phenotypic characterization methods presumptively identified 91% (20/22) of the isolates to the genus level and 1 isolate to the species level. However, only 55% (12/22) or 4.5% (1/22) of the phenotypic identifications were correct at the genus or species level when they were compared with the 16S rRNA full-gene sequencing. This study also compared 16S rRNA full-gene and partial-gene sequencing. The results demonstrated that the best 16S rRNA gene-sequencing approach is full-gene sequencing because it gives the most precise species identification. Sequencing of the variable regions 1, 2, and 3 of the 16S rRNA gene could be used for tentative identification because the ability of this sequencing to identify bacteria to the genus level is similar to that of the 16S rRNA full-gene sequencing. This method identified only 14% (3/22) isolates differently to the species level compared with the 16S rRNA full gene sequence. Sequencing of the variable regions 7, 8, and 9 is not recommended because it gives more ambiguous identifications. The cost of a 16S RNA full-gene-sequencing analysis was Can 160 dollars and Can 60 dollars for a partial 16S rRNA gene sequence, i.e., sequencing of variable regions 1, 2, and 3 or variable regions 7, 8 and 9.


[Methods for the detection of ventricular late potentials. High amplification ECG, signal averaging technic, frequency analysis and intracardiac mapping].
Circumscribed areas of injured myocardium which lead to late ventricular depolarization represent the pathologic-anatomic substrate for reentry mechanisms potentially capable of propagating ventricular tachycardia at the ventricular level. If the myocardial area from which delayed ventricular depolarization and, consequently, late potentials eminate, exceeds a critical minimal size, documentation of such signals can not only be achieved with direct endocardial mapping or catheter mapping but also by means of special high-resolution ECG techniques from the body surface. Since high amplification of the conventional ECG results in registration of noise signals in amplitude of up to 50 microV, late potentials with their amplitudes at the body surface ranging from 5 to a maximum of 20 microV, can only be discriminated after substantial enhancement of the signal-to-noise ratio. The noise arises from no less than three sources: physiologic noise, for example, from muscle activity; electronic noise from amplifiers and background noise of 50 or 60 Hz, respectively. To improve the signal-to-noise ratio, currently three methods are employed: sequential or temporal signal averaging, spatial signal averaging and fast Fourier transformation analysis of the frequency spectrum of the highly-amplified ECG. Temporal signal averaging has the purpose of smoothing randomly-occurring background noise and, at a specified point in time of the ECG cycle, to sum the signal incurred. The effectivity of this technique, however, is subject to certain conditions: the signal to be registered and the background noise must be independent from each other, the noise must be stationary and show normal random distribution, the signal of interest must be periodic and/or coupled with a fixed interval to a point in the ECG cycle which can be used as a trigger. The quality of the averaged signal is dependent on trigger stability. There are three approaches to trigger processing: voltage threshold determination, slope detection and the pattern matching technique, the accuracy, reliability and time-consumption of which increases in the order listed. A trigger stability of +/- 0.5 ms is necessary to detect ventricular late potentials with sufficient sensitivity and without meaningful deformation or attenuation of their form and temporal extent. Intercurrently, a number of commercially-acquirable signal averaging computers have been made available which differ with respect to registration and analysis.(ABSTRACT TRUNCATED AT 400 WORDS)


Biased learning affects mate choice in a butterfly.
Early acquisition of mate preferences or mate-preference learning is associated with signal diversity and speciation in a wide variety of animal species. However, the diversity of mechanisms of mate-preference learning across taxa remains poorly understood. Using the butterfly Bicyclus anynana we uncover a mechanism that can lead to directional sexual selection via mate-preference learning: a bias in learning enhanced ornamentation, which is independent of preexisting mating biases. Naïve females mated preferentially with wild-type males over males with enhanced wing ornamentation, but females briefly exposed to enhanced males mated significantly more often with enhanced males. In contrast, females exposed to males with reduced wing ornamentation did not learn to prefer drab males. Thus, we observe both a learned change of a preexisting mating bias, and a bias in ability to learn enhanced male ornaments over reduced ornaments. Our findings demonstrate that females are able to change their preferences in response to a single social event, and suggest a role for biased learning in the evolution of visual sexual ornamentation.


Pulmonary blastoma.
Pulmonary blastoma is now accepted as a distinctive neoplasm. It remains rare, and only 28 cases have been reliably recorded. A further two cases are now reported, and the previous literature is reviewed. There are no specific clinical or radiological features of pulmonary blastoma. The presentation can be that of any other pulmonary tumour although a peripheral situation is usual and a large size is often attained before detection. Pulmonary blastoma is a mixed tumour with malignant epithelial and connective tissue components with a distinctive resemblance to fetal lung. The treatment of choice is surgical excision but the overall prognosis is poor. It is doubtful whether the tumour has a true blastomatous origin.


[Bulbar subconjunctival tumor secondary to periocular schistosome granuloma].
Schistosomiasis, a parasitic disease, is endemic in many areas in the world. Schistosome eggs can be found in human tissues or organs, including the eye. These eggs can produce inflammatory granuloma. We report a unique and exceptional clinical case of periocular localization of schistosome granuloma. A 12-year-old girl, living in a schistosomiasis-endemic region, presented an inflammatory subconjunctival tumor in one eye. This tumor regressed but did not completely disappear with treatment. Complementary tests showed a slight eosinophilia (500/mm(3)) in the blood and S. mansoni ova in the stools. A biopsy was performed, revealing an inflammatory granuloma with epithelioid and giant cells rich in eosinophilic polynuclear. The immunohistochemical study showed no cells with anti-CD1 and anti-CD30, excluding histocytosis X type lesion. Although considered as exceptional, periocular localization of schistosome granuloma must be proposed, based on epidemiological, clinical and paraclinical results. Schistosomiasis may be considered as an origin of an inflammatory subconjunctival tumor found in endemic areas.


Ferromagnetic ordering correlated strong metal-oxygen hybridization for superior oxygen reduction reaction activity.
The efficiency of transition-metal oxide materials toward oxygen-related electrochemical reactions is classically controlled by metal-oxygen hybridization. Recently, the unique magnetic exchange interactions in transition-metal oxides are proposed to facilitate charge transfer and reduce activation barrier in electrochemical reactions. Such spin/magnetism-related effects offer a new and rich playground to engineer oxide electrocatalysts, but their connection with the classical metal-oxygen hybridization theory remains an open question. Here, using the MnxVyOz family as a platform, we show that ferromagnetic (FM) ordering is intrinsically correlated with the strong manganese (Mn)-oxygen (O) hybridization of Mn oxides, thus significantly increasing the oxygen reduction reaction (ORR) activity. We demonstrate that this enhanced Mn-O hybridization in FM Mn oxides is closely associated with the generation of active Mn sites on the oxide surface and obtaining favorable reaction thermodynamics under operating conditions. As a result, FM-Mn2V2O7 with a high degree of Mn-O hybridization achieves a record high ORR activity. Our work highlights the potential applications of magnetic oxide materials with strong metal-oxygen hybridization in energy devices.


[Prognostic factors of prostate cancer: usefulness of Ki-67 expression in preoperative biopsies].
To evaluate the usefulness of Ki-67 expression in preoperative diagnostic biopsies to predict prostate cancer biochemical relapse after radical prostatectomy. We analyze the expression of Ki-67 in ultrasound guided biopsies of 103 patients who underwent radical prostatectomy. Mean follow-up was 3.4 years (1.3-8.8 yr.). We correlated biochemical progression with traditional prognostic factors such as PSA (> 10/< or = 10), Gleason (> or = 7/< 7), pT classification (pT3/pT 0-2), and the immunohistochemical prognostic factor Ki-67 (> 3%/< or = 3%). 71/103 (69%) patients did not have progression and 32 (31%) had biochemical progression. Mean preoperative PSA was 10.7 ng/ml in patients without progression and 20.90 ng/ml in patients with biochemical progression (p = 0.0001). Mean Gleason score was 6.03 in patients without progression and 6.75 in patients with biochemical progression (p = 0.0001). Ki-67 expression was 3.95% in patients without progression in comparison to 5.05% of patients with biochemical progression. 12/67 (17.9%) of pT 0-2 tumors and 20/36 (55.6%) pT3 tumors progressed (p = 0.0001). Multivariate analysis indicates that there is not relationship between Ki-67 (> 3% < or = 3%) in preoperative biopsy specimens and prostate cancer biochemical progression after radical prostatectomy (p = 0.204). The immunohistochemical prognostic factor Ki-67 (> 3%/< or = 3%) in preoperative biopsies is less effective than classic factors, PSA (> 10/< or = 10), Gleason score (> or = 7/< 7) and pT classification (pT3/pT 0-2), to predict prostate cancer biochemical progression after radical prostatectomy.


Synovial tissue quantitative proteomics analysis reveals paeoniflorin decreases LIFR and ASPN proteins in experimental rheumatoid arthritis.
Rheumatoid arthritis (RA) is a common worldwide public health problem, which causes a chronic, systemic inflammatory disorder of synovial joints. Paeoniflorin (PA) has achieved positive results to some extent for the treatment of RA. This study aimed to reveal the potential druggable targets of PA in an experimental RA model using quantitative proteomics analysis. Thirty Sprague-Dawley rats were randomly divided into a normal group, model group and PA group. PA (1 mg/kg) was used to treat collagen-induced arthritis (CIA) rats for 42 days. We used isobaric tags for relative and absolute quantitation-based quantitative proteomics to analyze the synovial tissue of rats. Ingenuity pathway analysis (IPA) software was applied to process the data. The proteins that were targeted via IPA software were verified by Western blots. We found that PA caused 86 differentially expressed proteins (≥1.2-fold or ≤0.84-fold) compared with the CIA group. Of these varied proteins, 20 significantly changed (p<0.05) proteins referred to 41 CIA-relative top pathways after IPA pathway analysis. Thirteen of the PA-regulated pathways were anchored, which intervened in 24 biological functions. Next, network analysis revealed that leukemia inhibitory factor receptor (LIFR) and asporin (ASPN), which participate in two significant networks, contributed the most to the efficacy of PA treatment. Additionally, Western blots confirmed the aforementioned druggable targets of PA for the treatment of RA. The results reveal that PA may treat RA by decreasing two key proteins, LIFR and ASPN. Our research helps to identify potential agents for RA treatment.


Recurrent events of acute coronary syndrome in young adult patients after Kawasaki disease.
I encountered three adult patients with major coronary artery occlusion after Kawasaki disease in childhood, who had developed again acute coronary syndrome of adults in the peripheral branches, such as the 4th segments, the atrioventricular node artery, and the posterior descending artery, of the right coronary artery. I reviewed their clinical course and coronary angiograms. Their age at onset of acute coronary syndrome ranged from 29 to 33 years. The male patient with a previous anteroseptal myocardial infarction in children had a symptomatic occlusion of the branch of the 4th posterior descending artery at 32 years of age. Acute coronary syndrome occurred in the area of 4th atrioventricular node artery in two female patients. The collateral arteries from the circumflex artery to the 4th atrioventricular node arteries were not clearly injected. It was suspected that they had developed bilateral giant aneurysms after acute Kawasaki disease. Two patients had an acute myocardial infarction due to thrombotic occlusion in a giant aneurysm of the right coronary artery or the left anterior descending artery, and one patient had an asymptomatic coronary occlusion of the right coronary artery and left anterior descending artery in children. Occlusion of peripheral coronary arteries in adulthood can occur in patients with multi-vessel disease caused by Kawasaki disease. Recurrent events of acute coronary syndrome can occur in adults, although its prevalence may be low. Careful follow-up in adults is also needed in this population.


Thermophobicity of liquids: heats of transport in mixtures as pure component properties--the case of arbitrary concentration.
We have measured Soret coefficients of a large number of binary mixtures of 23 different organic solvents. The present analysis is based on 77 equimolar mixtures and strongly supports the thermophobicity concept previously developed for the heats of transport of originally 10 different substances [S. Hartmann, G. Wittko, W. Köhler, K. I. Morozov, K. Albers, and G. Sadowski, Phys. Rev. Lett. 109, 065901 (2012)]. Among the investigated compounds, cis-decalin is the most thermophobic, hexane the most thermophilic one. In addition to the equimolar mixtures, we have also analyzed the composition dependence of the Soret coefficients and the heats of transport for 22 selected binary mixtures. Both the interpretation of the heats of transport in equimolar mixtures as pure component thermophobicities and the composition dependence of the Soret coefficient can be understood on the basis of the thermodiffusion theory developed by Morozov [Phys. Rev. E 79, 031204 (2009)], according to which the composition dependence is determined by the excess volume of mixing.


Transition from Doublet to Triplet Excitons in Single Perovskite Nanocrystals.
Lead halide perovskite nanocrystals (NCs) have emerged as novel semiconductor nanostructures possessing great potential for optoelectronic, photovoltaic, and quantum information processing applications. Success in these applications requires a comprehensive understanding of the perovskite NCs' electronic structures, which mysteriously exhibit either doublet or triplet peaks of exciton luminescence at the single-particle level. Here we show that the transition from doublet- to triplet-exciton peaks can be triggered in single CsPbI3 NCs from the same batch of samples when they are stored in the ambient environment. We propose theoretically that the doublet-exciton peaks originate from two in-plane dipole moments, while the optical transition arising from the out-of-plane dipole moment becomes prominent only after the crystal-field splitting is strongly reduced by the structural transformation in the deterioration process. Furthermore, the quantum-confinement effect is strongly reinforced in the single CsPbI3 NCs with a triplet-exciton configuration, leading to enhanced Auger recombination and allowing us to extract the emission-energy dependence of the exciton-energy-level fine structure.


Food security and women's roles in Moroccan Berber (Amazigh) society today.
Traditionally, the Berber diet was part of a semiautarkic economy. The suitability of the diet to the regional ecosystem has guaranteed food security for the Berber tribes of Morocco and other countries of North Africa. As part of a patriarchal model, Berber dietary patterns are historically embedded in a social system where women's and men's roles are complementary at all stages of food production, processing, and conservation. Women have played a dominant role in the conservation of Berber dietary patterns through the preservation of biodiverse seeds and local varieties, the transmission of the Berber language through generations, and the sharing of knowledge on food, medicinal plants, and cultural practices related to diet and food security. Political, social, demographic, economic, and cultural factors have affected the Berber dietary model and the role of women in its preservation. The shift from a semiautarkic traditional model to a model within a market economy has led to food importation, the erosion of culinary components such as wild edible plants and dietary homogenization. Despite these changes and the associated nutrition transition, the Berber diet remains a cultural heritage because of its rich diversity. Berber women play a crucial role in the preservation and sustainability of Berber culinary heritage and food security.


"It's Like Moving the Titanic:" Community Organizing to Address Food (In)Security.
Health communication scholars are uniquely positioned to examine the ways in which individuals organize to address current and future exigencies related to social ills. In particular, organizations are key sites in understanding our health decisions related to food choice. From a young age, children develop habits of eating that stay with them throughout their life. More specifically, food insecurity impacts childhood nutrition. Children from low-income homes experience disproportional negative health outcomes. Appalachian Ohio is an area within the United States that experiences severe poverty. In 2013, community members in a small public school district in Appalachian Ohio formed the Appalachian Nutrition Advisory Council to address the nutritional needs of students in schools. This project stories the ways in which community members creatively organized to supplement existing structures in place designed to address school nutrition and food security.


Overproduction of cellulase by Trichoderma reesei RUT C30 through batch-feeding of synthesized low-cost sugar mixture.
Cellulase is a prerequisite for the bioconversion of lignocellulosic biomass, but its high cost presents the biggest challenge. In this article, low-cost mixture was produced from glucose through the transglycosylation reaction catalyzed by β-glucosidase for cellulase overproduction by Trichodema reesei RUT C30. As a result, cellulase titer of 90.3FPU/mL, which was more than 10 folds of that achieved with lactose as inducer, was achieved at 144h. Meanwhile, cellulase productivity was drastically increased to 627.1FPU/L/h, at least 3-5 folds higher than previously reported by the fungal species. The crude enzyme was further tested by hydrolyzing NaOH-pretreated corn stover with 15% solid loading, and 96.6g/L glucose was released with 92.6% sugar yield at 96h and 44.8g/L ethanol was obtained.


Insight on mutation-induced resistance to anaplastic lymphoma kinase inhibitor ceritinib from molecular dynamics simulations.
Ceritinib, an advanced anaplastic lymphoma kinase (ALK) next-generation inhibitor, has been proved excellent antitumor activity in the treatment of ALK-associated cancers. However, the accumulation of acquired resistance mutations compromise the therapeutic efficacy of ceritinib. Despite abundant mutagenesis data, the structural determinants for reduced ceritinib binding in mutants remains elusive. Focusing on the G1123S and F1174C mutations, we applied molecular dynamics (MD) simulations to study possible reasons for drug resistance caused by these mutations. The MD simulations predict that the studied mutations allosterically impact the configurations of the ATP-binding pocket. An important hydrophobic cluster is identified that connects P-loop and the αC-helix, which has effects on stabilizing the conformation of ATP-binding pocket. It is suggested, in this study, that the G1123S and F1174C mutations can induce the conformational change of P-loop thereby causing the reduced ceritinib affinity and causing drug resistance.


Approximate Methods for State-Space Models.
State-space models provide an important body of techniques for analyzing time-series, but their use requires estimating unobserved states. The optimal estimate of the state is its conditional expectation given the observation histories, and computing this expectation is hard when there are nonlinearities. Existing filtering methods, including sequential Monte Carlo, tend to be either inaccurate or slow. In this paper, we study a nonlinear filter for nonlinear/non-Gaussian state-space models, which uses Laplace's method, an asymptotic series expansion, to approximate the state's conditional mean and variance, together with a Gaussian conditional distribution. This Laplace-Gaussian filter (LGF) gives fast, recursive, deterministic state estimates, with an error which is set by the stochastic characteristics of the model and is, we show, stable over time. We illustrate the estimation ability of the LGF by applying it to the problem of neural decoding and compare it to sequential Monte Carlo both in simulations and with real data. We find that the LGF can deliver superior results in a small fraction of the computing time.


Methods, strengths, weaknesses, and limitations of bioequivalence tests with special regard to immunosuppressive drugs.
Within the field of solid organ transplantation, the patents for a number of immunosuppressive drugs have expired in the last few years. Tacrolimus, cyclosporine, and mycophenolate mofetil are now available as generic drugs. In some countries, the market penetration of these generic formulations is as high as 70%, whereas in some other countries, this figure is below 10%. Several professional societies have published position papers on the risks and benefits of generic substitution of immunosuppressive drugs. It often appears that transplant professionals are not fully aware of the requirements for registration of generic drugs. This article describes the registration requirements with a focus on bioequivalence testing, the strengths and weaknesses in this process, and the differences between Europe and the US.


The pathway of collagen secretion.
COPII vesicles mediate export of secretory cargo from the endoplasmic reticulum (ER). However, a standard COPII vesicle with a diameter of 60-90 nm is too small to export collagens that are composed of rigid triple helices of up to 400 nm in length. How do cells pack and secrete such bulky molecules? This issue is fundamentally important, as collagens constitute approximately 25% of our dry body weight and are essential for almost all cell-cell interactions. Recently, a potential mechanism for the biogenesis of mega-transport carriers was identified, involving packing collagens and increasing the size of COPII coats. Packing is mediated by TANGO1, which binds procollagen VII in the lumen and interacts with the COPII proteins Sec23/Sec24 on the cytoplasmic side of the ER. Cullin3, an E3 ligase, and its specific adaptor protein, KLHL12, ubiquitinate Sec31, which could increase the size of COPII coats. Recruitment of these proteins and their specific interactors into COPII-mediated vesicle biogenesis may be all that is needed for the export of bulky collagens from the ER. Nonetheless, we present an alternative pathway in which TANGO1 and COPII cooperate to export collagens without generating a mega-transport carrier.


Neuroanesthesiology update.
We provide a review of both clinical and basic science literature from 2012 relevant to care of the patient with neurological disease. Our review addresses the following major areas: general neurosurgical procedures, stroke, traumatic brain injury, spine surgery, anesthetic neurotoxicity, neuroprotective strategies, electrophysiological monitoring, history, and graduate medical education. We have focused on research describing new and innovative concepts and recurring themes. This review is intended to be of interest to those working in the clinical arena and also to neuroscientists.


[Quantitative equilibrium radionuclide ventriculography at rest in the evaluation of the severity of coronary disease].
The results of examining 373 patients with a quantitative equilibrium radionuclide ventriculography were stored in a data bank and evaluated statistically. The following left ventricular parameters were evaluated: global and regional ejection fractions ( gEF , rEF1 - rEF5 ) and volume parameters (EDV, ESV, stroke volume, cardiac output, heart index). It appeared that in stages I and II of coronary heart disease evaluation of gEF , EDV and ESV under resting conditions does not sufficiently discriminate diseased patients from normals. Significant changes (p less than 0.025) of these parameters (vs. normal) were found only in CHD III and IV or in patients with a history of old myocardial infarction. The additional evaluation of the regional fraction yields, however, a significant increase (CHD I and II: +25%) of the sensitivity of the equilibrium radionuclide ventriculography in the diagnosis of coronary heart disease.


Methotrexate and beta-carotene loaded-lipid polymer hybrid nanoparticles: a preclinical study for breast cancer.
This work was intended to investigate the targeting potential of fructose-tethered lipid-polymeric hybrid nanoparticles (F-BC-MTX-LPHNPs) co-loaded with beta carotene (BC) and methotrexate (MTX) in breast cancer therapeutics and find out the possible protective role of BC on MTX-induced toxicity. F-BC-MTX-LPHNPs were fabricated using self-assembled nano-precipitation technique. Fructose was conjugated on the surface of the particles. The in vitro cytotoxicity, sub-cellular localization and apoptotic activity of F-BC-MTX-LPHNPs were evaluated against MCF-7 breast cancer cells. The antitumor potential of F-BC-MTX-LPHNPs was further studied. Outcomes suggested that F-BC-MTX-LPHNPs induced the highest apoptosis index (0.89) against MCF-7 cells. Following 30 days of treatment, the residual tumor progression was assessed to be approximately 32%, in animals treated with F-BC-MTX-LPHNPs. F-BC-MTX-LPHNPs are competent to selectively convey the chemotherapeutic agent to the breast cancers. Beta carotene ameliorated MTX-induced hepatic and renal toxicity.


[Goodpasture's syndrome].
Goodpasture s syndrome (GS) is an auto-immune disease that is part of the pulmonary-renal syndrome spectrum. It is characterized by the linear deposition of anti-glomerular basement membrane antibodies (anti-GBM) in glomerular and alveolar basement membrane resulting in alveolar hemorrhage and progressive glomerulonephritis. An early diagnosis is important to decrease clinical morbidity. In the present work we illustrate a GS case initially diagnosed as Wegener s granulomatosis. The patient showed favorable clinical evolution with corticosteroid therapy associated with plasmapheresis and cyclophosphamide.


Autism: Common, heritable, but not harmful.
We assert that one of the examples used by Keller & Miller (K&M), namely, autism, is indeed common, and heritable, but we question whether it is harmful. We provide a brief review of cognitive science literature in which autistics perform superiorly to non-autistics in perceptual, reasoning, and comprehension tasks; however, these superiorities are often occluded and are instead described as dysfunctions.


Natural history of tuberculosis. Epidemiology.
This Symposium honours the achievements of Dr Karel Styblo. In this presentation, specific epidemiologic insights are reviewed. Studies of the epidemiology of tuberculosis in Eskimos showed a picture of tuberculosis at the height of the epidemic. Very high incidence was observed in young people who experienced a high fatality rate. Application of specific control measures were accompanied by rapid decline in rates, greater than observed in any other human population, demonstrating that tuberculosis could be brought under control by specific intervention. Studies of the natural trend of tuberculosis in South India showed that, even in the absence of intervention, a decline was observed in the rates of this disease. In the absence of chemotherapy, 50 per cent of cases die within 5 years, 30 per cent recover spontaneously and 20 per cent remain sputum positive. Studies of the efficacy of BCG in Madras, enabled to study the impact of efficient case-finding associated with poor treatment results showing that such a situation multiplies the number of surviving, infectious cases in the community and, thus, actually deteriorates the epidemiological situation. These various basic studies have shown both how to create success and how to create failure in tuberculosis programmes.


Sticky Floor, Broken Ladder, and Glass Ceiling in Academic Obstetrics and Gynecology in the United States and Canada.
Objective To evaluate the gender proportion in academic obstetrics and gynecology faculty across the United States and Canada and further assess any gender differences in academic ranks, leadership positions, and research productivity. Methods Obstetrics and gynecology programs were searched from the Fellowship and Residency Electronic Interactive Database (FREIDA) (n=145) and the Canadian Resident Matching Service (CaRMS) (n=13) to compile a database of gender and academic profiles of faculty physicians with Medical Doctorate (MD) or Doctors of Osteopathic Medicine (DO) degrees. Elsevier's Scopus was used to gather individual research metrics for analysis, and the data were analyzed using Strata v14.2 (StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX: StataCorp LP). Results Among 3556 American and 689 Canadian Obstetrics and Gynaecology physicians, women comprised 60.9% and 61.4%, respectively. Among physicians with professorships, women physicians comprised 36.2% and 35.8% in the United States and Canada, respectively. When examining the gender proportion of physicians in leadership roles, women comprised 52.2% and 56.1% in the United States and Canada, respectively. The h-index between men and women physicians showed a significant difference overall in both the United States (p<0.001) and Canada (p<0.001), indicating that men have higher academic output. Conclusion Although the overall proportion of women academic staff physicians in Obstetrics and Gynaecology is higher than the proportion of men, there are more men who had a full professor rank. Men also had higher academic productivity.


Complication Severity Score for Growth-friendly Surgery Has Strong Interrater and Intrarater Agreement.
Growth-friendly surgery has high complication rates. The Complication Severity Score for growth-friendly surgery was developed to maintain consistency while reporting complications as part of research in this rapidly evolving field. This study evaluates the interrater and intrarater reliability of this complication classification system. After Institutional Review Board approval, complications during treatment for early onset scoliosis were identified from a prospectively collected database. Previous validation studies and a 10-case pilot survey determined that 60 cases were needed to represent a minimum of substantial agreement. In total, 63 of 496 cases were selected randomly to evenly represent each severity classification. The cases comprised an internet survey for classification sent to faculty and research coordinators involved in early onset scoliosis research, 3 weeks apart, with questions shuffled between iterations. Fleiss Kappa and Cohen Kappa were used to assess interrater and intrarater agreement, respectively. A total of 20 participants, 12 faculty and 8 research assistants, completed the survey twice. The overall Fleiss Kappa coefficient for interrater agreement from the second round of the survey was 0.86 (95% confidence interval, 0.86-87), which represents substantial agreement. Reviewers agreed almost perfectly on categorizing complications as Device I (0.85), Disease I (0.91), Disease II (0.94), Device IIB (0.92), and Disease IV (0.98). There was substantial agreement for categorizing Device IIA (0.73) and Device III (0.76) complications. Disease III and Device IV were not evaluated in this survey since none of these occurred in the database. There was almost perfect intrarater agreement among faculty (0.87), research coordinators (0.85), and overall (0.86). There is strong interrater and intrarater agreement for the published complications classification scheme for growing spine surgery. The complication classification system is a reliable tool for standardizing reports of complications with growth-friendly surgery. Adoption of this classification when reporting on growth-friendly surgery is recommended to allow for comparison of complications between treatment modalities. Level I-diagnostic study.