Melatonin influences the early growth stage in Zoysia japonica Steud. by regulating plant oxidation and genes of hormones.
Zoysia japonica is a commonly used turfgrass species around the world. Seed germination is a crucial stage in the plant life cycle and is particularly important for turf establishment and management. Experiments have confirmed that melatonin can be a potential regulator signal in seeds. To determine the effect of exogenous melatonin administration and explore the its potential in regulating seed growth, we studied the concentrations of several hormones and performed a transcriptome analysis of zoysia seeds after the application of melatonin. The total antioxidant capacity determination results showed that melatonin treatment could significantly improve the antioxidant capacity of zoysia seeds. The transcriptome analysis indicated that several of the regulatory pathways were involved in antioxidant activity and hormone activity. The hormones concentrations determination results showed that melatonin treatment contributed to decreased levels of cytokinin, abscisic acid and gibberellin in seeds, but had no significant effect on the secretion of auxin in early stages. Melatonin is able to affect the expression of IAA (indoleacetic acid) response genes. In addition, melatonin influences the other hormones by its synergy with other hormones. Transcriptome research in zoysia is helpful for understanding the regulation of melatonin and mechanisms underlying melatonin-mediated developmental processes in zoysia seeds.


Recent advances in Baijiu analysis by chromatography based technology-A review.
Baijiu, a conventional fermented beverage with thousands history, plays a crucial part in physical health of people and social culture in China. The application of high-throughput screening and confirmation of flavor components in the field of authenticity identification and potential function has attracted more and more attention and interest of researchers. With more attention to health, pesticides residues, phthalates, biogenic amines and other hazardous substances remained in Baijiu have also become the quality parameters concerned by consumers. This review aims to present updated and critical overview on the substances analysis of Baijiu by means of hyphenated chromatographic techniques based on various pretreatment approaches in recent years. Subsequently, the advance and main direction of Baijiu composition analysis were evaluated and prospected.


Acute non lymphoid leukemia following CMF treatment as adjuvant therapy in positive node breast cancer. Case report.
The CMF regimen as an adjuvant therapy for breast cancer with axillary node involvement has become "standard therapy" at least for some subsets of patients (according to the Second Consensus Development Conference on Adjuvant Chemotherapy for Breast Cancer). The acute toxicity of such a regimen is usually mild and well tolerated; the late toxicity is mainly represented by amenorrhea. Here a case of acute non-lymphoid-leukemia (ANLL) after six CMF cycles is reported.


Two new bamboo-feeding species of the planthopper genus Bambusicaliscelis Chen & Zhang, 2011 (Hemiptera, Fulgoromorpha, Caliscelidae) from China.
Two new species of the Chinese caliscelid planthopper genus Bambusicaliscelis Chen & Zhang, 2011, B.bibulbussp. nov. from Fujian Province and B.clavatussp. nov. from Jiangxi Province, are described and illustrated. The genus now known to include six described species. A checklist and identification key to Bambusicaliscelis species are provided.


[Development of multicentric invasive cancer of the esophagus against a background of epithelial dysplasia and preinvasive cancer].
Two observations of squamous cell carcinoma of the oesophagus developing in the presence of multiple confluent areas of dysplasia (degree II and III) and multiple foci of preinvasive carcinoma are described. The authors claim that their observations confirm the concept of a tumourous field on the basis of which dysplastic changes and neoplastic growth develop.


Effect of chronic mucus hypersecretion on treatment responses to inhaled therapies in patients with chronic obstructive pulmonary disease: Post hoc analysis of the IMPACT trial.
Chronic mucus hypersecretion (CMH) is a clinical phenotype of COPD. This exploratory post hoc analysis assessed relationship between CMH status and treatment response in IMPACT. Patients were randomized to once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 μg, FF/VI 100/25 μg or UMEC/VI 62.5/25 μg and designated CMH+ if they scored 1/2 in St George's Respiratory Questionnaire (SGRQ) questions 1 and 2. Endpoints assessed by baseline CMH status included on-treatment exacerbation rates, change from baseline in trough forced expiratory volume in 1 second, SGRQ total score, COPD Assessment Test (CAT) score, proportion of SGRQ and CAT responders at Week 52 and safety. Of 10,355 patients in the intent-to-treat population, 10,250 reported baseline SGRQ data (CMH+: 62% [n = 6383]). FF/UMEC/VI significantly (p < 0.001) reduced on-treatment moderate/severe exacerbation rates versus FF/VI and UMEC/VI in CMH+ (rate ratio: 0.87 and 0.72) and CMH- patients (0.82 and 0.80). FF/UMEC/VI significantly (p < 0.05) reduced on-treatment severe exacerbation rates versus UMEC/VI in CMH+ (0.62) and CMH- (0.74) subgroups. Similar improvements in health status and lung function with FF/UMEC/VI were observed, regardless of CMH status. In CMH+ patients, FF/VI significantly (p < 0.001) reduced on-treatment moderate/severe and severe exacerbation rates versus UMEC/VI (0.83 and 0.70). FF/UMEC/VI had a favourable benefit: risk profile versus dual therapies irrespective of CMH status. The presence of CMH did not influence treatment response or exacerbations, lung function and/or health status. However, CMH did generate differences when dual therapies were compared and the impact of CMH should be considered in future trial design.


Maintenance of white adipose tissue in man.
Obesity is increasing in an epidemic manner in most countries and constitutes a public health problem by enhancing the risk for diseases such as diabetes, fatty liver disease and atherosclerosis. Together these diseases form a cluster referred to as the metabolic syndrome. Despite the negative health consequences associated with excess adipose tissue, very little is known about the origin and maintenance of white adipose tissue in man. In this review we discuss what is known about the turnover of adult human adipocytes and their precursors, as well as adipose tissue heterogeneity, plasticity and developmental origins. The focus of this review is human tissue, however in many cases human data are missing and are inferred from animal studies. As such, reference to animal studies are made where human data is not available. This article is part of a directed issue entitled: Regenerative Medicine: the challenge of translation.


Caring for migrant farm workers on medical-surgical units.
Over 3 million migrant farm workers are employed in the United States. Many factors place them at risk for work-related disease and injury. Knowledge of workers' health issues can prepare medical-surgical nurses to anticipate and meet the needs of this underserved population.


3D variable flip angle T1 mapping for differentiating benign and malignant liver lesions at 3T: comparison with diffusion weighted imaging.
Different methods have been used to improve the imaging diagnosis of focal liver lesions (FLL). Among them, magnetic resonance imaging (MRI) has received more attention since it provides significant amount of information without radiation exposure. However, atypical imaging characteristics of FLL on MRI may complicate the differential diagnosis between benign and malignant FLL. This study aimed to compare the diagnostic value of T1 mapping and diffusion-weighted imaging (DWI) for differentiating of benign and malignant FLLs. This retrospective study enrolled 294 FLLs, including 150 benign and 144 malignant lesions. Whole liver T1 mapping sequences were obtained before and 2 min after the administration of Gd-DTPA to acquire native T1 and enhanced T1 and ΔT1%. Additionally, DWI sequence was conducted to generate apparent diffusion coefficient (ADC) maps. These quantitative parameters were compared using one-way analysis of variance, and the diagnostic accuracy of T1 mapping and ADC for FLLs was calculated by area under the curve (AUC). Significant differences were observed regarding the native T1, enhanced T1, ΔT1%, and ADC between benign and malignant FLLs. Furthermore, the sensitivity and specificity of the parameters are as follows: native T1 0.797/0.702 (cut off value 1635.5 ms); enhanced T1, 0.911/0.976 (cutoff value 339.2 ms); ΔT1%, 0.901/0.905 (cutoff value 70.8%); and ADC, 0.975/0.952 (cutoff value 1.21 × 10-3 mm2/s). The ideal cutoff values for native T1 and ADC in identifying cyst and haemangioma were 2422.9 ms (AUC 0.990, P < 0.01) and 2.077 × 10-3 mm2/s (AUC 0.949, P < 0.01), respectively, with a sensitivity and specificity of 0.963/1 and 0.852/0.892, respectively. ADC was significantly positively correlated with T1 and ΔT1%, and significantly negatively correlated with enhanced T1. The 3D Variable flip angle T1 mapping technique with Gd-DTPA has a high clinical potential for identifying benign and malignant FLLs. The enhanced T1 and ΔT1% values have similar diagnostic accuracy compared with DWI in evaluating FLLs. Native T1 shows better performance than DWI in distinguishing benign liver lesions, specifically, cysts, and haemangioma.


Recent Insights into Escherichia coli and Vibrio spp. Pathogenicity and Responses to Stress.
The ubiquitous presence of microorganisms is largely attributed to their tremendous capacity to successfully adapt and survive in highly adverse environments [...].


Paediatric and neonatal sepsis and inflammation.
Sepsis has a huge impact on global mortality and has been declared as a priority by the World Health organisation the WHO.1 Children have a high incidence of sepsis especially in the neonatal with an estimated 3 million babies affected worldwide and mortality ranges from 11 to 19%.2 In addition, long-term neurodevelopmental outcomes are affected but this is largely unquantified. However, challenges remain in the early recognition, diagnosis and standardised management of sepsis. This series on Sepsis and inflammation in children reviews the conundrums of diagnostic criteria, biomarkers, management and future strategies to improve outcomes.


Changing academic culture to improve undergraduate STEM education.
Improving undergraduate science, technology, engineering, and math (STEM) education requires faculty with the skills, resources, and time to create active learning environments that foster student engagement. Current faculty hiring, promotion, and tenure practices at many universities do not measure, reward, nor encourage faculty pursuit of these skills. A cultural change is needed to foster improvement.


Role of semen in HIV-1 transmission: inhibitor or facilitator?
Sexual transmission of human immunodeficiency virus type 1 (HIV-1) accounts for 60-90% of new infections, especially in developing countries. During male-to-female transmission, the virus is typically deposited in the vagina as cell-free and cell-associated virions carried by semen. But semen is more than just a carrier for HIV-1. Evidence from in vitro and in vivo studies supports both inhibitory and enhancing effects. Intrinsic antiviral activity mediated by cationic antimicrobial peptides, cytotoxicity, and blockage of HIV-dendritic cell interactions are seminal plasma properties that inhibit HIV-1 infection. On the contrary, neutralization of vaginal acidic pH, enhanced virus-target cell attachment by seminal amyloid fibrils, opsonization by complement fragments, and electrostatic interactions are factors that facilitate HIV-1 infection. The end result, i.e., inhibition or enhancement of HIV mucosal infection, in vivo, likely depends on the summation of all these biological effects. More research is needed, especially in animal models, to dissect the role of these factors and establish their relevance in HIV-1 transmission.


Research Models of the Nanoparticle-Mediated Drug Delivery across the Blood-Brain Barrier.
Brain diseases and damages come in many forms such as neurodegenerative diseases, tumors, and stroke. Millions of people currently suffer from neurological diseases worldwide. While Challenges of current diagnosis and treatment for neurological diseases are the drug delivery to the central nervous system. The Blood-Brain Barrier (BBB) limits the drug from reaching the targeted site thus showing poor effects. Nanoparticles that have advantage of the assembly at the nanoscale of available biomaterials can provide a delivery platform with potential to raising brain levels of either imaging therapeutic drugs or imaging. Therefore, successful modeling of the BBB is another crucial factor for the development of nanodrugs. In this review, we analyze the in vitro and in vivo findings achieved in various models, and outlook future development of nanodrugs for the successful treatment of brain diseases and damages.


Epstein-Barr virus-associated lymphoepithelioma-like gastric carcinoma presenting as a submucosal mass: CT findings with pathologic correlation.
A lymphoepithelioma-like carcinoma, characterized by a carcinoma with heavy lymphocyte infiltration, is one of the histological patterns observed in patients with Epstein-Barr virus (EBV)-associated gastric carcinoma. Less than half of invasive carcinomas with lymphoepithelioma-like histology can grow to make a submucosal mass. These tumors generally have a better prognosis than conventional adenocarcinomas. We report a case of an EBV-associated lymphoepithelioma-like gastric carcinoma that presented as a submucosal mass on multi-detector (MD) CT and correlate them with the pathology.


A simple qualitative scale for diagnosis of laryngopharyngeal reflux: high correlations with pH measurements and disease severity. The usefulness of the Warsaw Scale in LPR diagnostics compared to other diagnostic tools.
Diagnosis and monitoring of laryngopharyngeal reflux (LPR) is a constant challenge in otolaryngological practice, chiefly because there are no specific symptoms characteristic of the disease. In this paper, we present the validation of a simple, 6-level qualitative scale to gauge the clinical findings of LPR. It has been previously published in Polish as the Warsaw Scale. In the study, we enrolled 100 patients with voice problems who had registered in our clinic, and we performed an extended battery of diagnostic tests for LPR, together with 24-h pH monitoring. The Warsaw Scale significantly outperformed other instruments in both predicting LPR status and correlating with pH measurements. Moreover, the rating provided by the scale showed a strong association with patient-reported symptoms. The data indicate that the Warsaw Scale could be used as an affordable, consistent, and effective diagnostic and monitoring tool for LPR.


Association of Albumin-Bilirubin Grade and Myosteatosis with its Prognostic Significance for Patients with Colorectal Cancer.
The albumin-bilirubin (ALBI) grade is a useful prognostic and predictive marker for patients with liver disease. Its clinical significance has been limited to patients with colorectal cancer (CRC). Furthermore, the association between the ALBI grade and skeletal muscle-related indices is unclear. This study enrolled 1015 patients who underwent computed tomography (CT) scans within 31 days before surgery. The prognostic value of the ALBI grade in predicting overall survival (OS) was assessed using the Cox proportional hazards model. The correlation between the ALBI grade and the skeletal muscle index or radiodensity (myosteatosis) was evaluated. The predictive accuracy of ALBI alone and in combination with myosteatosis was compared using Harrell's concordance index (C-index). The significant prognostic factors for OS identified in the multivariable analysis were the ALBI group (low vs high: hazard ratio [HR], 1.566; 95 % confidence interval [CI], 1.174-2.089; p = 0.002) and myosteatosis (low vs. high: HR, 0.648; 95 % CI, 0.486-0.865; p = 0.003). The rate of low-grade myosteatosis increased as the ALBI grade increased. The C-index of combined ALBI and myosteatosis (0.650; 95 % CI, 0.618-0.683) was superior to that of ALBI alone (0.603; 95 % CI, 0.575-0.631; bootstrap incremental area under the curve [iAUC] mean difference, 0.047; 95 % CI, 0.012-0.070) and myosteatosis alone (0.608; 95 % CI, 0.577-0.640; bootstrap iAUC mean difference, 0.042; 95 % CI, 0.023-0.064). The ALBI grade is significantly associated with myosteatosis. The ALBI grade is a significant prognostic factor, and the combination of ALBI and myosteatosis show an additive value in discriminating survival of patients with CRC.


[Factors determining irregular attendance to follow-up visits among human immunodeficiency virus patients: results of the hospital survey of patients infected with human immunodeficiency virus].
To describe the occurrence of non-regular attendance to follow-up visits among HIV patients and to analyze the determining factors. One-day survey carried out annually (2002-2012) in public hospitals. Epidemiological, clinical and behavioral data are collected in all HIV-infected inpatients and outpatients receiving HIV-related care on the day of the survey. "Non-regular attendance to a follow-up visit" was defined as sporadic attendance to the medical appointments, according to the judgment of the attending physician. Descriptive and bivariate analyses were performed, and factors associated to non-regular attendance to follow-up visits were estimated using logistic regression. A total of 7,304 subjects were included, of whom 13.7% did not attend medical appointments regularly. Factors directly associated with non-regular attendance were: age between 25-49 years; birth in Sub-Saharan Africa or Latin-America; low educational level; being homeless or in prison; living alone or in closed institutions; being unemployed or retired; being an intravenous drug user; not using a condom at last sexual encounter, and injecting drugs in the last 30 days. Conversely, HIV diagnosis within the last year and being men who have sex with men were factors inversely associated with non-regular attendance to follow-up visits. In spite of health care beings free of charge for everyone in Spain, social factors can act as barriers to regular attendance to medical appointments, which, in turn, can endanger treatment effectiveness in some population groups. This should be taken into account when planning HIV policies in Spain.


Inflammatory markers in postoperative cognitive dysfunction for patients undergoing total hip arthroplasty: a meta-analysis.
Postoperative cognitive dysfunction (POCD) is a poorly understood disorder, very common even after total hip arthroplasty (THA). It is widely considered that inflammation response play a role in the pathogenesis of POCD. The aim of the present study was to investigate whether inflammation cytokine concentrations could serve as biomarkers for POCD in patients undergoing THA. A systematic search of databases was conducted to retrieve publications measuring circulating inflammatory markers of patients with and without POCD after THA. Inflammatory markers identified in more than two studies were pooled. The standardized mean difference (SMD) and the 95% confidence interval (95% CI) were calculated for each outcome. Fail-safe N statistics was calculated to estimate possible publication bias. The pooled incidence rate of POCD after THA by combining 11 cohort studies was 31%. A total of five inflammatory markers, CRP, S-100B, IL-1β, IL-6 and TNF-α, were assessed. Significantly higher pre-operative CRP (P = 0.012) and S-100B (P < 0.0001) as well as post-operative CPR (P = 0.005) and IL-6 (P < 0.0001) at 6 h were found in POCD compared with non-POCD patients undergoing THA. Fail-safe N statistics revealed that these results are robust. The current evidence suggests that some of the inflammatory markers, including CRP, S-100B, and IL-6, were correlated with the occurrence of POCD after THA. Monitor of inflammatory markers might help early diagnosis of POCD after THA and development of preventive strategies.


Considering difference: clinician insights into providing equal and equitable burns care for Aboriginal and Torres Strait Islander children.
To better understand issues driving quality in burn care related to equity of outcomes and equality of provision for Aboriginal and Torres Strait Islander children. Seventy-six interviews with team members who provide care for Aboriginal and Torres Strait Islander children in six paediatric burn units across five Australian jurisdictions were completed. Interface research methodology within a qualitative design guided data collection and analysis. Three themes were identified: i) Burn team members who identify the requirement to meet the specific needs of Aboriginal and Torres Strait Islander children and deliver differential care; ii) Burn team members who believe in equal care, but deliver differential care based on the specific needs of Aboriginal and Torres Strait Islander children; and iii) Burn team members who see little need for provision of differential care for Aboriginal and Torres Strait Islander children and rather, value the provision of equal care for all. Burn team members conflate equitable and equal care, which has implications for the delivery of care for Aboriginal and Torres Strait Islander children. Equitable care is needed to address disparities in post-burn outcomes, and this requires clinicians, healthcare services and relevant system structures to work coherently and intentionally to reflect these needs. Implications for public health: Changes in health policy, the embedding of Aboriginal and Torres Strait Islander liaison officers in burn care teams and systems that prioritise critical reflexive practice are fundamental to improving care.


Reduction of ferric green rust by Shewanella putrefaciens.
To reduce carbonated ferric green rust (GR*) using an iron respiring bacterium and obtain its reduced homologue, the mixed Fe(II)-Fe(III) carbonated green rust (GR). The GR* was chemically synthesized by oxidation of the GR and was incubated with Shewanella putrefaciens cells at a defined [Fe(III)]/[cell] ratio. Sodium methanoate served as the sole electron donor. The GR* was quickly transformed in GR (iron reducing rate = 8.7 mmol l(-1) h(-1)). Ferric green rust is available for S. putrefaciens respiration as an electron acceptor. The reversibility of the GR redox state can be driven by bacterial activity. This work suggests that GRs would act as an electronic balance in presence of bacteria. It provides also new perspectives for using iron reducing bacterial activity to regenerate the reactive form of GR during soil or water decontamination processes.


Reasons for leaving nursing care and improvements needed for considering a return: a study among Swedish nursing personnel.
Based on two research projects in Sweden during the 1990s, the aim of this study was to identify former nursing personnel's main reasons for leaving nursing care, and to find out under what circumstances they would consider returning. Two open-ended questions in a questionnaire were analysed. The results showed that different aspects of working conditions, mainly working schedule, management and status of profession were the dominating reasons both for leaving and considering a return. The findings indicate that interventions required for retaining personnel in nursing care need to be addressed both at the political and at the local level.


High performance, environmentally friendly and sustainable nanofiber membrane filter for removal of particulate matter 1.0.
Particulate matter (PM) air pollution is becoming more and more serious and dangerous to public health, especially in developing countries where industrialization is accelerating. The use of electrospun membrane-based materials for air filtration is a widespread and effective way to help individuals avoid air pollution. However, most electrospun membrane preparation processes require the use of organic solvents, resulting in secondary environmental pollution. In this study, an environmentally friendly polyvinyl alcohol (PVA) - tannic acid (TA) composite nanofiber membrane filter was prepared by the green electrospinning and the physical cross-linking method. The filtration efficiency of the membrane filter for PM1.0 reached 99.5%, and the pressure drop was only 35 Pa. In addition, due to the existence of intermolecular hydrogen bond between PVA and TA, the mechanical properties of the nanofiber membrane were improved to meet the requirements of practical application of the filter. Therefore, the PVA-TA composite nanofiber membrane is expected to provide a solution for the development of efficient and environmentally friendly air filter.


Continuous motor sequence learning: cortical efficiency gains accompanied by striatal functional reorganization.
The acquisition and generation of action sequences constitute essential elements of purposeful human behavior. However, there is still considerable debate on how experience-driven changes related to skill learning are expressed at the neural systems level. The current functional magnetic resonance imaging (fMRI) study focused on changes in the neural representation of continuous movement sequences as learning evolved. Behavioral and neural manifestations of nonvisual motor practice were studied both within the time frame of a single scanning session, as well as after several days of extended practice. Based on detailed behavioral recordings which enabled the continuous characterization of the ongoing learning process at the single subject level, sequence-specific decreases in activation throughout a learning-related network of cortical areas were identified. Furthermore, the spatial layout of this cortical network remained largely unchanged after extensive practice, although further decreases in activation levels could be observed as learning progressed. In contrast, the posterior part of the left putamen showed increased activation levels when an extensively trained sequence needed to be recalled. Overall, these findings imply that continuous motor sequence learning is mainly associated with more efficient processing in a network of consistently recruited cortical areas, together with co-occurring activation pattern changes at the subcortical level.


The effect of zinc in the form of erythromycin-zinc complex (Zineryt lotion) and zinc acetate on metallothionein expression and distribution in hamster skin.
The occurrence of zinc-induced synthesis of metallothionein in skin after topical application of the anti-acne drug Zineryt lotion was investigated in hamster ears. The dinitrophenyl hapten-sandwich immunohistochemical method involving a monoclonal anti-metallothionein (MT) antibody (E9) was used to detect and localize zinc-binding MT in the 'treated' and untreated hamster skin. Atomic absorption spectrophotometry and dithizone histochemistry indicated that zinc penetrated the skin more readily, and accumulated more efficiently within the sebaceous glands, when applied to the skin surface as the organo-zinc complex, rather than as the inorganic zinc salt. MT and zinc had similar distributions in hamster skin exposed to the metal. Thus, MT immunoreactivity was especially intense in the sebaceous glands of Zineryt lotion-treated skin, with evidence of nuclear distribution in some cells. Zinc delivered to the sebaceous glands, and released from the organo-complex under the prevailing aqueous conditions, certainly induced MT synthesis; the cysteine-rich protein may protect the pilosebaceous units during the inflammatory phase of acne by scavenging generated oxyradical species.


Contemporary Assessment of Long-Term Survival Rates in Patients With Stage I Nonseminoma Germ-Cell Tumor of the Testis: Population-Based Comparison Between Surveillance and Active Treatment After Initial Orchiectomy.
Historical data demonstrated similar survival outcomes in patients with stage I nonseminoma germ-cell tumor of the testis (NSGCTT) subjected to either surveillance or active treatment (AT) after orchiectomy. However, data with long-term follow-up are unavailable. We tested contemporary treatment rates and their effect on cancer-specific mortality (CSM) and other-cause mortality (OCM) relative to surveillance, as well as after stratification between chemotherapy (CHT) versus retroperitoneal lymph node dissection (RPLND). We identified patients with stage I NSGCTT with initial orchiectomy within the Surveillance, Epidemiology, and End Results (SEER) database (1988-2015). Subsequent surveillance versus CHT versus RPLND use rates were reported. Cumulative incidence plots and multivariable competing-risks regression (CRR) models were used after propensity score (PS) matching. These tests first compared surveillance versus AT (CHT vs. RPLND) and subsequently CHT versus RPLND. Of 5034 patients with stage I NSGCTT, 61.2%, 24.9%, and 13.9%, respectively, underwent surveillance, CHT, and RPLND. Between 1988 and 2015, surveillance (estimated annual percentage change [EAPC]: +1.1%, P < .001) and CHT (EAPC: +2.3%, P < .001) rates increased. RPLND rates decreased (EAPC: -5.7%; P < .001). After PS matching, CRR models failed to identify AT as an independent predictor of lower mortality relative to surveillance. However, after PS matching, CRR models identified RPLND as an independent predictor of lower CSM (hazard ratio, 0.26; P = .002) relative to CHT. No difference in OCM rates was recorded (hazard ratio, 1.25; P = .2). Surveillance and CHT use rates increased while RPLND decreased in the last two decades. Virtually the same outcomes were recorded between surveillance and AT. However, within AT, RPLND was associated with lower CSM than CHT.


Staphylococcus aureus Colonization and Nosocomial Infections: Implications for Prevention.
Colonization with Staphylococcus aureus is a risk factor for invasive S. aureus infections. Intranasal mupirocin has effectively eradicated S. aureus colonization and appears to prevent S. aureus nosocomial infections in some patient populations. In hospitals and communities where mupirocin use has been widespread, resistance to the drug has emerged. New strategies and agents are needed if we want to significantly decrease the risk of S. aureus infections.


Laparoscopic Lymphadenectomy and Vaginal Radical Hysterectomy for the Treatment of Cervical Cancer
The choice of treatment (surgery, radiotherapy) for cervical carcinoma depends on surgical staging. The noninvasive approach for node evaluation is not very accurate; therefore lymph node metastasis has to be determined surgically. Seventeen women with cervical cancer underwent bilateral laparoscopic lymphadenectomy with dissection of the common iliac, hypogastric, and external iliac vessels and the obturator nerve. The average number of lymph nodes sampled was 14 (range 12-24 nodes). The mean duration of lymphadenectomy was 60 minutes (range 50-90 min). Based on preoperative evaluation and on the pathology report, a radical vaginal hysterectomy (Schauta-Amreich) was performed in all women at the end of laparoscopy. All laparoscopies and radical hysterectomies were uneventful. Based on this preliminary experience, laparoscopic lymphadenectomy may play an important role in reviving radical vaginal hysterectomy in women with cervical cancer. Followed by vaginal radical hysterectomy, it may be the treatment of choice in early disease, avoiding an abdominal incision.


2D Semiconductor Nanomaterials and Heterostructures: Controlled Synthesis and Functional Applications.
Two-dimensional (2D) semiconductors beyond graphene represent the thinnest stable known nanomaterials. Rapid growth of their family and applications during the last decade of the twenty-first century have brought unprecedented opportunities to the advanced nano- and opto-electronic technologies. In this article, we review the latest progress in findings on the developed 2D nanomaterials. Advanced synthesis techniques of these 2D nanomaterials and heterostructures were summarized and their novel applications were discussed. The fabrication techniques include the state-of-the-art developments of the vapor-phase-based deposition methods and novel van der Waals (vdW) exfoliation approaches for fabrication both amorphous and crystalline 2D nanomaterials with a particular focus on the chemical vapor deposition (CVD), atomic layer deposition (ALD) of 2D semiconductors and their heterostructures as well as on vdW exfoliation of 2D surface oxide films of liquid metals.


Molecular requirements of the active sites of the cholinergic receptors. XVI - Synthesis and cholinergic activity of 2- or 5-alkyl or 5-phenyl-4-methyl-3-oxo-1-dimethylaminomethylcyclopentane methiodide.
In order to study the cholinergic receptor through affinity chromatography, some derivatives of deoxamuscarone (I a) incorporating alkyl and phenyl substituents at the positions 2 and 5 were synthesized as model compounds. However, the sharp drop in activity and the lack of discrimination between nicotinic and muscarinic receptors exhibited by the compounds discourage their further development as affinity reagents.


Single cell activity in chronic unit recording: a quantitative study of the unit amplitude spectrum.
The ratio of standard deviation to mean, of the amplitude spectrum of well resolved single units, is shown to scale exponentially. This scaling is explained on the basis of a consideration of the relationship of extracellular voltage to voltage gradient, in a dendritic neuron model. A method is then advanced to extract, from multi-unit data, normally distributed amplitude spectra which are indistinguishable from those of well resolved single units. This method is suggested as a means of characterizing, in general, the unit activity obtained from chronically implanted preparations.


Harnessing oxidative stress for anti-glioma therapy.
Glioma cells use intermediate levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) for growth and invasion, and suppressing these reactive molecules thus may compromise processes that are vital for glioma survival. Increased oxidative stress has been identified in glioma cells, in particular in glioma stem-like cells. Studies have shown that these cells harbor potent antioxidant defenses, although endogenous protection against nitrosative stress remains understudied. The enhancement of oxidative or nitrosative stress offers a potential target for triggering glioma cell death, but whether oxidative and nitrosative stresses can be combined for therapeutic effects requires further research. The optimal approach of harnessing oxidative stress for anti-glioma therapy should include the induction of free radical-induced oxidative damage and the suppression of antioxidant defense mechanisms selectively in glioma cells. However, selective induction of oxidative/nitrosative stress in glioma cells remains a therapeutic challenge, and research into selective drug delivery systems is ongoing. Because of multifactorial mechanisms of glioma growth, progression, and invasion, prospective oncological therapies may include not only therapeutic oxidative/nitrosative stress but also inhibition of oncogenic kinases, antioxidant molecules, and programmed cell death mediators.


Long-term memory of acute postsurgical pain.
The long-term memory of acute postoperative pain intensity was evaluated in a population of patients who had undergone the removal of impacted third molar teeth. The results suggest a positive correlation between experienced and remembered intensities of postsurgical pain for up to 3 years after surgery. They also suggest that males and females do not differ significantly in their reports of postsurgical pain intensity, nor do they differ significantly in their memories of pain intensity. Pain recall using verbal pain descriptors was more reliable than recall with visual analog scales. Patient reports of intensity of past postsurgical acute pain, particularly those reports obtained with verbal descriptors, may be useful in the planning of treatment and in the selection and evaluation of analgesic regimens.


Cold-stable microtubules in the cytoplasm of mouse embryo fibroblasts.
Treatment of cultured mouse embryo fibroblasts with Triton X-100 after prolonged incubation at 0 degrees C reveals a network of microtubules in the cytoplasm of cooled cells. This network of cold-stable microtubules was demonstrated by immunofluorescence microscopy, using a monospecific antibody against tubulin and by electron microscopy. The cold-stable microtubules, as well as the ordinary cytoplasmic microtubules, were sensitive to Ca ions and were not observed in the cells pre-treated with colchicine or vinblastine. The cold-stable microtubules do not seem to be in equilibrium with the pool of depolymerized tubulin at 0 degrees C.


The felt-presence experience: from cognition to the clinic.
The felt presence experience is the basic feeling that someone else is present in the immediate environment, without clear sensory evidence. Ranging from benevolent to distressing, personified to ambiguous, felt presence has been observed in neurological case studies and within psychosis and paranoia, associated with sleep paralysis and anxiety, and recorded within endurance sports and spiritualist communities. In this Review, we summarise the philosophical, phenomenological, clinical, and non-clinical correlates of felt presence, as well as current approaches that use psychometric, cognitive, and neurophysiological methods. We present current mechanistic explanations for felt presence, suggest a unifying cognitive framework for the phenomenon, and discuss outstanding questions for the field. Felt presence offers a sublime opportunity to understand the cognitive neuroscience of own-body awareness and social agency detection, as an intuitive, but poorly understood, experience in health and disorder.


Orthorexia among patients with eating disorders, student dietitians and general population: a pilot study.
Orthorexia is a recent construct describing an unhealthy and extreme concern for healthy food. To date, its relationship with other eating disorders (EDs) remains unclear, and little is known about the development of this condition. Current literature suggests that a thorough knowledge about nutrition and alimentation, as in the case of experts in the field of dietetics, could foster the development of orthorexic tendencies. The aim of this study was to compare orthorexia between ED patients, student dietitians and general population. A total of 90 female participants (age: 18-29 years) were recruited: 30 ED patients, 30 student dietitians and 30 control subjects, matched for age and sex. Orthorexia, ED-specific and general psychopathology were evaluated using self-report questionnaires (ORTO-15, Eating Disorder Examination Questionnaire and Symptom Checklist-90-Revised). Eating disorder patients had significantly higher orthorexic tendencies than other groups (p < 0.001), while student dietitians and general population showed no difference between each other (p = 0.96). Moreover, orthorexia positively correlated to ED psychopathology in ED patients (p = 0.004), but not in control groups. Our data do not confirm previous suggestions that experts in the field of dietetics may display a higher level of orthorexia. Level IV, cross-sectional observational study (case series).


Transcriptional and epigenetic effects of deleting large regions, alone or in combination, from their natural context in the chicken Ig-β gene.
Previously, we used homologous recombination to delete six groups of cell-type-specific DNase I hypersensitive sites (DHSs), potential transcriptional and epigenetic regulators, scattered in and around the Ig-β gene from their natural context in B-lymphocyte-derived chicken DT40 cells. Simultaneous deletion of all six groups completely shut down transcription and epigenetic regulation of the Ig-β gene; therefore, the cooperation of the scattered regulatory regions was essential for transcription and epigenetic regulation. In this study, we regrouped the cell-type-specific DHSs of Ig-β, those in the original six deletions and three additional ones, into three larger regional groups-the long upstream region, the intron, and the long downstream region-and deleted these groups individually or in combination. Combinatorial deletion of all three regional groups decreased Ig-β mRNA levels to 0.4% of the control, which was significantly higher than <0.1%, the level resulting from deletion of all six smaller groups. Histone H3 and H4 acetylation and H3K4 dimethylation levels at the Ig-β promoter were low in cells carrying deletions of all six smaller groups, but intermediate levels of acetylation and enhanced H3K4 dimethylation were observed in cells carrying deletions of all three larger groups. While CG methylation was definitely present at the Ig-β promoter in cells carrying all six smaller deletions, it was nearly absent from the Ig-β promoter in cells carrying all three larger deletions. Thus, combinatorial deletion of larger regulatory regions had less effect on transcription and epigenetic regulation at the chicken Ig-β gene than combinatorial deletion of shorter ones. Analysis of several combinatorial deletions, where combinations included two larger deletions and one smaller deletion, revealed the relative effects of each deletion on transcription of the Ig-β gene. Investigation of the CG methylation status at the Ig-β promoter in one combinatorial deletion demonstrated that USI was involved in the maintenance of CG methylation.


Functional and Allergenic Properties Assessment of Conalbumin (Ovotransferrin) after Oxidation.
Conalbumin (CA) is an iron-binding egg protein that has various bioactivities and causes major allergenicity in humans. This study investigated how oxidation affects the multiple functional properties of CA. The lipid peroxidation method was used to prepare treated CA [2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH)-CA and acrolein-CA] complexes. CA induced structural changes through oxidation. These changes enhanced the digestibility, rate of endocytosis in dendritic cells, and emulsifying and foaming properties of CA. ELISA and immunoblot analysis showed that the complexes reduced the IgE-binding ability of CA through lipid oxidation. KU812 cell assays showed that modification by AAPH and acrolein caused the release of IL-4 and histamine to decline. In conclusion, oxidation treatment modified the functional and structural properties of CA, reducing allergenicity during processing and preservation.


The behavioral dynamics of clinical trials.
Two ways of approaching the design of long-term clinical trials are presented and contrasted. The first, termed the "static" view, emphasizes close adherence to formal rules of study design. The second, termed the "dynamic" view, emphasizes the behavioral aspects of patient participation in trials of long duration. The dynamic view is discussed in detail, with discussion of how recruitment of participants, random assignment to conditions, compliance with protocol, and measurement of outcomes are affected by behavioral dynamics. Data from a recently completed tamoxifen toxicity trial are used to illustrate the points and to focus the discussion of behavioral dynamics on the design of a chemoprevention trial for breast cancer using tamoxifen.


Psychometric properties of Functional Assessment of Cancer Therapy-Prostate (FACT-P) in Chinese patients with prostate cancer.
The aim of the study was to assess the validity, reliability and sensitivity of the FACT-P (version 4) in Chinese males with prostate cancer. Construct validity was assessed using Spearman's correlation test against the 12-item Short Form Health Survey (SF-12v2). Internal consistency and test-retest reliability were assessed using Cronbach's α coefficient and intra-class correlation coefficient, respectively. Sensitivity was determined by performing known-group comparisons by independent t test. FACT-P subscale scores had a moderate correlation with the corresponding SF-12v2 domain score that conceptually measures the similar construct providing evidence for adequate construct validity. Internal consistency was acceptable (α: 0.687-0.900) for all subscales aside from the Prostate Cancer Subscale (α: 0.505) and Trial Outcome Index (α: 0.562). FACT-P subscale and total scores showed good test-retest reliability (range 0.753-0.913). All total scales and most of the subscales were sensitive in detecting differences between patients with different levels of functional impairment but not different cancer stages or levels of prostate-specific antigen. The measure is a valid and reliable measure to assess the health-related quality of life of Chinese males with prostate cancer. The FACT-P is sensitive to detect difference between patients with varying functional status.


Nonalcoholic fatty liver disease (NAFLD): Diagnosis, pitfalls, and staging.
Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and strongly associated with obesity, diabetes and the metabolic syndrome, not only in the Western societies, but also in most regions of the world in the 21st century. The spectrum of its histopathology ranges from steatosis to nonalcoholic steatohepatitis (NASH), with risk for progressive fibrosis that may lead to cirrhosis and hepatocellular carcinoma (HCC). Benign and malignant liver tumors have also been more frequently reported with the increasing prevalence of obesity and diabetes. This review addresses the pathology of NAFLD and NASH, and their diagnostic features, diagnostic pitfalls, grading and staging, and clinical correlation.


The effects of right hemisphere damage on the pragmatic interpretation of conversational remarks.
The ability to interpret conversational utterances was assessed in a group of 12 male patients with unilateral right hemisphere brain damage (RHD) and 12 non-brain-damaged, age-matched male control subjects. Subjects listened to short vignettes which described both the affective tone of the relationship between a speaker and an actor, and the actor's performance on a task. Each vignette concluded with the speaker characterizing the actor's performance. In half of the items, the speaker's utterance was literally true; in the other half, the utterance was literally false and invited a nonliteral interpretation. Results showed no appreciable differences in the performance of control subjects and RHD patients when interpreting literally true utterances. In contrast, the two groups differed reliably when interpreting the pragmatic intent of nonliteral utterances: Control subjects used information about both the actor's performance and the speaker-actor relationship, while RHD patients demonstrated difficulty in using the information about the speaker-actor relationship. Results have implications for patients' understanding of essential elements of conversations, such as characters' internal states and their intentions in employing different forms of literal and nonliteral language.


Methods in endogenous steroid profiling - A comparison of gas chromatography mass spectrometry (GC-MS) with supercritical fluid chromatography tandem mass spectrometry (SFC-MS/MS).
In various fields of endocrinology, the determination of steroid hormones synthesised by the human body plays an important role. Research on central neurosteroids has been intensified within the last years, as they are discussed as biomarkers for various cognitive disorders. Their concentrations in cerebrospinal fluid (CSF) are considered to be regulated independently from peripheral fluids. For that reason, the challenging matrix CSF becomes a very interesting specimen for analysis. Concentrations are expected to be very low and available amount of CSF is limited. Thus, a comprehensive method for very sensitive quantification of a set of analytes as large as possible in one analytical aliquot is desired. However, high structural similarities of the selected panel of 51 steroids and steroid sulfates, including numerous isomers, challenges achievement of chromatographic selectivity. Since decades the analysis of endogenous steroids in various body fluids is mainly performed by gas chromatography (GC) coupled to (tandem) mass spectrometry (MS(/MS)). Due to the structure of the steroids of interest, derivatisation is performed to meet the analytical requirements for GC-MS(/MS). Most of the laboratories use a two-step derivatisation in multi-analyte assays that was already published in the 1980s. However, for some steroids this elaborate procedure yields multiple isomeric derivatives. Thus, some laboratories utilize (ultra) high performance liquid chromatography ((U)HPLC)-MS/MS as alternative but, even UHPLC is not able to separate some of the isomeric pairs. Supercritical fluid chromatography (SFC) as an orthogonal separation technique to GC and (U)HPLC may help to overcome these issues. Within this project the two most promising methods for endogenous steroid profiling were investigated and compared: the "gold standard" GC-MS and the orthogonal separation technique SFC-MS/MS. Different derivatisation procedures for gas chromatographic detection were explored and the formation of multiple derivatives described and confirmed. Taken together, none of the investigated derivatisation procedures provided acceptable results for further method development to meet the requirements of this project. SFC with its unique selectivity was able to overcome these issues and to distinguish all selected steroids, including (pro-)gestagens, androgens, corticoids, estrogens, and steroid sulfates with appropriate selectivity. Valued especially in the separation of enantiomeric analytes, SFC has shown its potential as alternative to GC. The successful separation of 51 steroids and steroid sulfates on different columns is presented to demonstrate the potential of SFC in endogenous steroid profiling.


Hierarchy of evidence and appraisal of limitations (HEAL) grading system.
Despite more than 30 years of effort that has been dedicated to the improvement of grading systems for evaluating the quality of research study designs considerable shortcomings continue. These shortcomings include the failure to define key terms, provide a comprehensive list of design flaws, demonstrate the reliability of such grading systems, properly value non-randomized controlled trials, and develop theoretically-derived systems for penalizing and promoting the evidence generated by a study. Consequently, in light of the importance of grading guidelines in evidence-based medicine, steps must be taken to remedy these deficiencies. This article presents two methods--a grading system and a measure of methodological bias--for evaluating the quality of evidence produced by an efficacy study.


Splenic artery aneurysm rupture in pregnancy with maternal and fetal survival. A case report.
A splenic artery aneurysm occurred at 30 weeks, 3 days' gestation. Both the mother and fetus survived.


Mortality after endophthalmitis following contemporary phacoemulsification cataract surgery.
To determine if endophthalmitis following cataract surgery is linked to increased mortality. Increased mortality has been linked to patients with cataract and cataract surgery. We tested the hypothesis that post-cataract endophthalmitis has a greater risk of death than pseudophakes who do not develop this complication. Case-control study conducted in a tertiary public hospital. The study group comprised 50 consecutive patients with post-cataract endophthalmitis, and these were matched with selected controls. Patients with endophthalmitis following cataract surgery were identified from a prospective electronic surgical database. Subsequently, it was determined if the patient was deceased at the time of sequestration (September 2015), and the date of death was recorded. A previously described population who had undergone cataract surgery in the same facility was selected as a control group, and the population was case-matched in terms age, gender, presence or absence of diabetes and/or hypertension. The median survival rates were determined for the control group and the patients with post-cataract endophthalmitis. Fifty patients were identified as undergoing endophthalmitis post-cataract surgery, and 48 (n = 48) met inclusion criteria (mean age 72 years ±12 SD with 30:18 F:M); 17% were diabetic, and 50% had systemic hypertension. No statistically significant difference in median survival between the study and control cases was identified (100 months (95% confidence interval 86-114) vs. 106 months (95% confidence interval 66-146), respectively, P = 0.756). Post-cataract endophthalmitis was not associated with an increased rate of mortality in this study.


Electrophoretic build-up of multi nanoparticle array for a highly sensitive immunoassay.
One of the challenges in shrinking immunoassays to smaller sizes is to immobilize the biological molecules to nanometer-scaled spots. To overcome this complication, we have employed a particle-based immunoassay to create a nanostructured platform with a regular array of sensing elements. The technique makes use of an electrophoretic particle entrapment system (EPES) to immobilize nanoparticles that are coated with biological reagents into wells using a very small trapping potential. To provide useful information for controlling the trapping force and optimal design of the nanoarray, electrophoretic trapping of a nanoparticle was modeled numerically. The trapping efficiency, defined as the fraction of wells occupied by a single particle, was 91%. The performance of the array was demonstrated with a competitive immunoassay for a small molecule analyte, 3-phenoxybenzoic acid (214.2 g mole(-1)). The limit of detection determined with a basic fluorescence microscope was 0.006 μg l(-1) (30 pM); this represented a sixteen-fold improvement in sensitivity compared to a standard 96-well plate-based ELISA; the improvement was attributed to the small size of the sample volume and the presence of light diffraction among factors unique to this structure. The EPES/nanoarray system promises to offer a new standard in applications that require portable, point-of-care and real-time monitoring with high sensitivity.


Aortoenteric fistula after endovascular stent grafting for an abdominal aortic aneurysm: report of a case.
We report a case of an aortoenteric fistula (AEF) developing after endovascular stent grafting (EVSG) for an abdominal aortic aneurysm (AAA). A 69-year-old male patient with a history of panperitonitis caused by rectal perforation underwent EVSG for an AAA. A follow-up contrast-enhanced computed tomography (CT) scan, done 12 months after the EVSG, confirmed shrinkage of the AAA with no endoleak. However, 19 months postoperatively, an AEF developed between the AAA and the jejunum. Although there was no endoleak on a subsequent CT scan, we noted enlargement of the AAA and inflammatory changes in the surrounding tissue. The patient was treated surgically and discharged in good health 74 days postoperatively. Thus, one should consider the possibility of this devastating complication, even in patients without an endoleak, after EVSG for AAA.


"Mycobacterium tilburgii," a newly described, uncultivated opportunistic pathogen.
Molecular methods are increasingly used to identify pathogens that are difficult to cultivate. We report a case of disseminated infection with "Mycobacterium tilburgii," a proposed species that has never been cultivated. The case illustrates the diagnostic utility of sequence analysis of the 16S rRNA gene directly from clinical specimens.


Comprehensive comparison of bismuth and silver functionalized nickel foam composites in capturing radioactive gaseous iodine.
Developing an efficient and cheap iodine sorbent is of great practical significance in the modern nuclear industry. In this work, novel bismuth and silver functionalized Ni foam composites as iodine sorption materials (Bi-Ni foam and Ag-Ni foam) were successfully prepared via a simple solvothermal method. Through a series of iodine sorption experiments and characterization methods, iodine capture properties and corresponding sorption mechanism were comprehensively compared and thoroughly revealed. The results show that the core-sheath structure formed by the solvothermal reaction can supply more active sites (Bi0 or Ag0 particles) for the contact of radioactive iodine gas, thereby improving the sorption capacity of sorbents. Compared with Ag-Ni foam (456 mg/g), Bi-Ni foam exhibits a higher iodine capture capacity (658 mg/g), whereas silver-based material has a faster sorption kinetics. Such excellent sorption performances were attributed to the chemical reaction between Bi0/Ag0 particles and iodine gas, generating stable BiI3/AgI. In addition, this type of sorbents inherits the external structure of the Ni foam skeleton, decreasing the physically sorbed iodine, and can be prepared in different shapes and sizes, which is of great practical significance.


The unilateral nigral lesion induces dramatic bilateral modification on rat brain monoamine neurochemistry.
6-Hydroxydopamine (6-OHDA) is a neurotoxic compound commonly used to induce dopamine (DA) depletion in the nigrostriatal system, mimicking Parkinson's disease (PD) in animals. The aim of the present study was to evaluate the 7-day effect of unilateral nigral lesion on rat brain monoamine neurochemistry. Five brain regions were examined: the brain stem, cerebellum, hippocampus, striatum, and cortex. 6-OHDA-unilateral lesion dramatically modified DA, serotonin (5-HT) and their metabolites contents in both sides of the different brain nuclei. Furthermore, unilateral 6-OHDA lesion reduced DA and 5-HT contents and produced a robust inversion of their turnover in the nonlesioned side compared to sham-operated rats. These data suggest that 6-OHDA unilateral nigral lesion produces bilateral monoamine level modifications, and this piece of evidence should be taken into account when one interprets data from animal models of unilateral PD.


Hemostasis in anterior supine intermuscular total hip arthroplasty: pilot study comparing standard electrocautery and a bipolar sealer.
Previous studies have demonstrated that using a bipolar sealer device for hemostasis in hip and knee arthroplasty results in a decreased blood loss and transfusion requirement. The anterior supine intermuscular total hip arthroplasty is a minimally invasive approach with a faster initial recovery compared with more traditional hip replacement surgery. A retrospective consecutive series of 100 anterior supine total hip arthroplasties performed by one surgeon was reviewed. In the first 50 cases, traditional electrocautery was used. In the second 50 cases, a bipolar sealer device was used. No significant differences with operative times, intraoperative blood loss, postoperative hemoglobin levels, and length of hospitalization were demonstrated between the two groups. There was a lower rate of intraoperative and postoperative transfusions in the bipolar sealer group.


Effects of tumor necrosis factor-β (TNF-β) 252A>G polymorphism on the development of migraine: a meta-analysis.
Genetic factors including TNF-β have been considered as important components in the aetiology of migraine. Many studies have investigated the association between TNF-β 252A>G polymorphism and migraine risk, with debatable results. This study was designed to examine whether the TNF-β 252A>G polymorphism confers genetic susceptibility to migraine in diverse populations. Studies eligible for this meta-analysis were searched in the PubMed, Embase, and CNKI by using the keywords "tumor necrosis factor", "TNF", "252A>G", "rs909253", "polymorphism", "polymorphisms", "variant", "SNP", combined with "migraine" or "migraine with aura (MA)" or "migraine without aura (MO)". Pooled ORs and 95% CI were appropriately calculated using the fixed-effect model. We finally included a total of seven studies, providing 5 557 migraineurs and 20 543 unrelated healthy controls. Meta-analysis results showed no statistical evidence of a significant association between TNF-β 252A>G polymorphism and overall migraine risk. Stratified analyses by type of migraine and gender revealed similar results. Interestingly, an OR with 95% CI representing an increased migraine risk was indicated in Asians under the recessive model (GG vs. AG + AA: OR, 1.38; 95%CI, 1.04-1.84; P for heterogeneity, 0.665). Our findings appear to support the hypothesis that genetic variability of 252A>G polymorphism in TNF region may modulate risk of migraine in the population of Asian ancestry.


Gasdermin and Gasdermin-Like Pore-Forming Proteins in Invertebrates, Fungi and Bacteria.
The gasdermin family of pore-forming proteins (PFPs) has recently emerged as key molecular players controlling immune-related cell death in mammals. Characterized mammalian gasdermins are activated through proteolytic cleavage by caspases or serine proteases, which remove an inhibitory carboxy-terminal domain, allowing the pore-formation process. Processed gasdermins form transmembrane pores permeabilizing the plasma membrane, which often results in lytic and inflammatory cell death. While the gasdermin-dependent cell death (pyroptosis) has been predominantly characterized in mammals, it now has become clear that gasdermins also control cell death in early vertebrates (teleost fish) and invertebrate animals such as corals (Cnidaria). Moreover, gasdermins and gasdermin-like proteins have been identified and characterized in taxa outside of animals, notably Fungi and Bacteria. Fungal and bacterial gasdermins share many features with mammalian gasdermins including their mode of activation through proteolysis. It has been shown that in some cases the proteolytic activation is executed by evolutionarily related proteases acting downstream of proteins resembling immune receptors controlling pyroptosis in mammals. Overall, these findings establish gasdermins and gasdermin-regulated cell death as an extremely ancient mechanism of cellular suicide and build towards an understanding of the evolution of regulated cell death in the context of immunology. Here, we review the broader gasdermin family, focusing on recent discoveries in invertebrates, fungi and bacteria.


Interaction between the HCV NS3 protein and the host TBK1 protein leads to inhibition of cellular antiviral responses.
The persistent nature of hepatitis C virus (HCV) infection suggests that HCV encodes proteins that enable it to overcome host antiviral responses. Toll-like receptor 3 (TLR3)-mediated signaling, which recognizes the double-stranded RNA that is produced during viral replication and induces type I interferons, including interferon beta (IFN-beta), is crucial to the host defense against viruses. Recent studies suggest that a TIR domain-containing adaptor protein, TRIF, and two protein kinases, TANK-binding kinase-1 (TBK1) and IkappaB kinase-epsilon (IKKepsilon), play essential roles in TLR3-mediated IFN-beta production through the activation of the transcriptional factor interferon regulatory factor 3 (IRF-3). We report that the HCV NS3 protein interacts directly with TBK1, and that this binding results in the inhibition of the association between TBK1 and IRF-3, which leads to the inhibition of IRF-3 activation. In conclusion, these results suggest the mechanisms of the inhibition of the innate immune responses of HCV infection by NS3 protein.


Cytoplasmic 8 S glucocorticoid receptor binds to actin filaments through the 90-kDa heat shock protein moiety.
The glucocorticoid receptor exists in the cytoplasm of hormone-untreated cells as a complex with the 90-kDa heat shock protein (HSP90). Glucocorticoids induce dissociation of the glucocorticoid binding protein from HSP90 and translocation of the receptor to the nucleus. HSP90 binds to actin filaments, and calmodulin or tropomyosin inhibits the binding. We present here evidence that the HSP90-containing glucocorticoid receptor complexes (8 S receptor) bind to filamentous actin in vitro while the HSP90-free form of the receptor does not. The binding was detectable for both the crude cytosolic fractions and the partially purified 8 S glucocorticoid receptor. Purified HSP90 or tropomyosin completely abolished the binding. Calmodulin also inhibited the binding in a Ca(2+)-dependent manner. From these results, we conclude that the glucocorticoid receptor complex is able to bind actin filaments via the HSP90 moiety. The binding may provide an anchoring mechanism for the glucocorticoid receptor in the cytoplasm.


Situation testing: the case of health care refusal.
Situation testing to assess physicians' refusal to provide healthcare is increasingly used in research studies. This paper aims to explain the relevance and limits of this method. Conducted in 2008-2009, this study was designed to assess the rate of healthcare refusal among several categories of private practitioners toward patients covered by the French public means-tested complementary health insurance (CMUc) when they requested a first appointment by phone. The other objectives were to study the determinants of healthcare refusal and assess the method. The study was conducted on a representative sample of Paris-based dentists and physicians in five categories: general practitioners, medical gynecologists, ophthalmologists, radiologists, and dentists. The method was based on two protocols. In the first scenario, an actor pretended to be a CMUc beneficiary and, in the second one, he did not give information about his health coverage but hinted at a low socioeconomic status. The two protocols were compared and procedures checking the relation between refusal and CMUc coverage were implemented in each of them. In the scenario in which the patient declared being a CMUc beneficiary, the results showed different refusal rates depending on the type of practitioner, physician, or dentist, their specialty, and whether or not, they charge more than the standard set fee. In the second scenario, refusal rates were much lower. The comparison of the two protocols seems to confirm the existence of discrimination based on CMUc affiliation rather than patients' socioeconomic status. The discussion presents the limits of situation testing, which remains an experimental instrument because it does not observe reality but reveals behaviors in situation. The findings cannot be extrapolated and are limited in time. The statistical analysis is only valid if the procedure followed is precise and applied consistently using a preset scenario. In addition, the discriminatory nature of the refusal (CMUc coverage) must be confirmed by a validation procedure (unless clearly stated by the interlocutor).


Ring-shaped calcification of renal mass.
A case of peripherally calcified renal mass is presented which was interpreted as being a benign, calcified, developmental nephrogenic cyst. A differential diagnosis of calcified renal masses is presented.


Tyrosine phosphorylation-dependent localization of TmaR that controls activity of a major bacterial sugar regulator by polar sequestration.
The poles of Escherichia coli cells are emerging as hubs for major sensory systems, but the polar determinants that allocate their components to the pole are largely unknown. Here, we describe the discovery of a previously unannotated protein, TmaR, which localizes to the E. coli cell pole when phosphorylated on a tyrosine residue. TmaR is shown here to control the subcellular localization and activity of the general PTS protein Enzyme I (EI) by binding and polar sequestration of EI, thus regulating sugar uptake and metabolism. Depletion or overexpression of TmaR results in EI release from the pole or enhanced recruitment to the pole, which leads to increasing or decreasing the rate of sugar consumption, respectively. Notably, phosphorylation of TmaR is required to release EI and enable its activity. Like TmaR, the ability of EI to be recruited to the pole depends on phosphorylation of one of its tyrosines. In addition to hyperactivity in sugar consumption, the absence of TmaR also leads to detrimental effects on the ability of cells to survive in mild acidic conditions. Our results suggest that this survival defect, which is sugar- and EI-dependent, reflects the difficulty of cells lacking TmaR to enter stationary phase. Our study identifies TmaR as the first, to our knowledge, E. coli protein reported to localize in a tyrosine-dependent manner and to control the activity of other proteins by their polar sequestration and release.


Increased lncRNA AFAP1-AS1 expression predicts poor prognosis in gastric cancer: Evidence from published studies and followed up verification.
The purpose of this study was to clarify the influence of long non-coding RNA actin fiber-associated protein-1 antisense RNA 1 (lncRNA AFAP1-AS1) on the prognosis of gastric cancer (GC). Based on meta-analysis, the association between the expression of AFAP1-AS1 and the prognosis of GC was estimated. GC tissue and non-cancer tissues from 136 patients were determined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and verified by Gene Expression Profiling Interactive Analysis (GEPIA). Kaplan-Meier and Cox proportional hazards models were conducted to analyze the correlation between AFAP1-AS1 expression and GC prognosis. The pooled analysis from five studies revealed that the AFAP1-AS1 expression was significantly associated with GC overall survival (hazard ratio (HR) = 2.49 and 95% confidence interval (95% CI): 2.02-3.08, p < 0.001). Compared with non-cancer tissues, AFAP1-AS1 expression level of GC tissues were significantly upregulated (p < 0.001), which was confirmed by the results of GEPIA. The area under the receiver-operating characteristic (ROC) curve was 0.893, and the high expression of AFAP1-AS1 was correlated with poor prognosis in patients with GC (p = 0.005). Clinical grade (HR = 1.912, 95% CI: 1.246-2.934, p = 0.003), pathologic tumor node metastasis (pTNM) (HR = 2.393, 95% CI: 1.431-4.033, p = 0.001), log odds of positive lymph nodes (LODDS) (HR = 2.910, 95% CI: 1.787-4.793, p < 0.001) and AFAP1-AS1 expression (HR = 2.393, 95% CI: 1.869-3.064, p < 0.001) were independent prognostic factors for GC revealed by multivariate Cox-regression analysis. This study demonstrated that the AFAP1-AS1 may be a novel biomarker for the diagnosis and prognosis of GC.


Susceptibility of chicks to experimental infections with Neisseria gonorrhoeae.
Chicks were given intracerebral inoculations of Neisseria gonorrhoeae of colony types 1 or 2 one to two days after hatching. Small numbers ofN. gonorrhoeae initiated lethal infection provided that the body temperature of the animals was not maintained at levels harmful to the microbes per se. The disease process, which appeared to be localized intracranially rather than disseminated by bacteremia, merits further investigation as a model for the study of pathogenetic and immunologic mechanisms in gonococcal infection.


Reactor design and selection for effective continuous manufacturing of pharmaceuticals.
Pharmaceutical production remains one of the last industries that predominantly uses batch processes, which are inefficient and can cause drug shortages due to the long lead times or quality defects. Consequently, pharmaceutical companies are transitioning away from outdated batch lines, in large part motivated by the many advantages of continuous manufacturing (e.g., low cost, quality assurance, shortened lead time). As chemical reactions are fundamental to any drug production process, the selection of reactor and its design are critical to enhanced performance such as improved selectivity and yield. In this article, relevant theories, and models, as well as their required input data are summarized to assist the reader in these tasks, focusing on continuous reactions. Selected examples that describe the application of plug flow reactors (PFRs) and continuous-stirred tank reactors (CSTRs)-in-series within the pharmaceutical industry are provided. Process analytical technologies (PATs), which are important tools that provide real-time in-line continuous monitoring of reactions, are recommended to be considered during the reactor design process (e.g., port design for the PAT probe). Finally, other important points, such as density change caused by thermal expansion or solid precipitation, clogging/fouling, and scaling-up, are discussed.


Endogenous angiotensin II but not atrial natriuretic peptide modulates the effect of nicardipine on extracellular fluid partition in the rat.
Both atrial natriuretic peptide (ANP) and the dihydropyridine derivative nicardipine lower arterial pressure and induce a shift of plasma fluid from the vascular towards the interstitial compartment. Because some calcium antagonists increase the plasma concentration of ANP, and the effect of ANP on transcapillary fluid shift requires the presence of angiotensin II, we examined the consequences of blocking the ANP and renin-angiotensin systems on the hypotensive and haemoconcentrating effects of nicardipine. We evaluated the effects of 45-min 0.1 or 1 micrograms/kg per min nicardipine infusion on arterial pressure and haematocrit in anaesthetized, acutely binephrectomized Sprague-Dawley rats. Infusion of nicardipine resulted in a dose-dependent decrease in arterial pressure. Haematocrit increased by an amount corresponding to the decrease in plasma volume calculated for the relevant dose. In the presence of monoclonal anti-ANP antibodies the nicardipine-induced changes in haematocrit and arterial pressure were not affected. In rats pretreated for 2 weeks with the angiotensin converting enzyme inhibitor enalapril, as well as in rats receiving the angiotensin II receptor antagonist losartan acutely, the nicardipine-induced increase in haematocrit was abolished. In enalapril-treated rats the increase in haematocrit was entirely restored when angiotensin II was infused at a subpressor dose. The nicardipine-induced decrease in arterial pressure was not affected by pharmacological blockade of the renin-angiotensin system. These results demonstrate that the transcapillary shift of fluid induced by nicardipine is independent of ANP and requires the presence of a functional renin-angiotensin system, whereas its hypotensive action is independent of both ANP and angiotensin II.


On the accuracy of one-way approximate models for nonlinear waves in soft solids.
Simple strain-rate viscoelasticity models of isotropic soft solid are introduced. The constitutive equations account for finite strain, incompressibility, material frame-indifference, nonlinear elasticity, and viscous dissipation. A nonlinear viscous wave equation for the shear strain is obtained exactly and corresponding one-way Burgers-type equations are derived by making standard approximations. Analysis of the travelling wave solutions shows that these partial differential equations produce distinct solutions, and deviations are exacerbated when wave amplitudes are not arbitrarily small. In the elastic limit, the one-way approximate wave equation can be linked to simple wave theory and shock wave theory, thus, allowing direct error measurements.


Inhibitors of ubiquitin E3 ligase as potential new antimalarial drug leads.
Protein ubiquitylation is an important post-translational regulation, which has been shown to be necessary for life cycle progression and survival of Plasmodium falciparum. Ubiquitin is a highly conserved 76 amino acid polypeptide, which attaches covalently to target proteins through combined action of three classes of enzymes namely, the ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2) and ubiquitin-protein ligase (E3). Ubiquitin E1 and E2 are highly conserved within eukaryotes. However, the P. falciparum E3 ligase is substantially variable and divergent compared to the homologs from other eukaryotes, which make the E3 ligase a parasite-specific target. A set of selected E3 ubiquitin ligase inhibitors was tested in vitro against a chloroquine-sensitive P. falciparum D6 strain (PfD6) and a chloroquine-resistant P. falciparum W2 strain (PfW2). The inhibitors were also tested against Vero and transformed THP1 cells for cytotoxicity. The lead antimalarial E3 ubiquitin ligase inhibitors were further evaluated for the stage-specific antimalarial action and effects on cellular development of P. falciparum in vitro. Statistics analysis was done by two-way ANOVA followed by Tukey and Sidak multiple comparison test using GraphPad Prism 6. E3 ligase inhibitors namely, JNJ 26854165, HLI 373 and Nutlin 3 showed prominent antimalarial activity against PfD6 and PfW2. These inhibitors were considerably less cytotoxic to mammalian Vero cells. JNJ 26854165, HLI 373 and Nutlin 3 blocked the development of P. falciparum parasite at the trophozoite and schizont stages, resulting in accumulation of distorted trophozoites and immature schizonts. Interruption of trophozoites and schizont maturation by the antimalarial E3 ligase inhibitors suggest the role of ubiquitin/proteasome functions in the intraerythrocytic development of malaria parasite. The ubiquitin/proteasome functions may be critical for schizont maturation. Further investigations on the lead E3 ligase inhibitors shall provide better understanding regarding the importance of E3 ligase functions in the malaria parasite as a potential new antimalarial drug target and a new class of antimalarial drug leads.


Influence of rice bran stearin on stability, properties and encapsulation efficiency of polyglycerol polyricinoleate (PGPR)-stabilized water-in-rice bran oil emulsions.
In the present study, rice bran stearin was used to improve the physical stability and encapsulation efficiency of water-in-oil (W/O) emulsions fabricated from rice bran oil and polyglycerol polyricinoleate ester (PGPR). In the absence of rice bran stearin, the emulsions were highly unstable to phase separation with an oil layer forming on their surfaces. Phase separation was delayed by increasing the PGPR concentration because this reduced the water droplet size. Phase separation could be completely inhibited by replacement of 30 to 45wt% of rice bran oil with rice bran stearin due to the formation of a semi-solid fat crystal network that prevented droplet movement. Moreover, addition of rice bran stearin delayed the release of ferrous sulfate from the W/O emulsions. These results demonstrate that rice bran stearin can be used to improve the stability and encapsulation efficiency of W/O emulsions and reduce the level of PGPR required to stabilize them.


[Clinical Significance of Total Pancreatectomy for Multiple Pancreatic Metastases from Renal Cancer].
With the progress of replacement therapy for pancreatic endocrine and exocrine functions, the indications for a total pancreatectomy are expanding, and reports of multiple pancreatic metastases of renal cancer are on the rise. In the present, we investigated the utility of a total pancreatectomy for multiple pancreatic metastases of renal cancer. The subjects were 8 patients who underwent a total pancreatectomy for multiple pancreatic metastases of renal cancer between 2012 and 2021. The median, postoperative observation period was 31(3-92)months. Six of 8 patients survived without cancer, and one survived with chemotherapy(pazopanib plus axitinib)plus radiation therapy(maintaining stable disease). The one, remaining patient died of hypoglycemia. Of the 8 patients, 4 survived for 2 years or more, and 2 survived for more than 5 years. Postoperative, support for endocrine and exocrine functions is indispensable, but a total pancreatectomy for multiple pancreatic metastases of renal cancer promises to be a viable treatment option owing to its favorable long-term prognosis.


The role of total and high-molecular-weight complex of adiponectin in vascular function in offspring whose parents both had type 2 diabetes.
Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. We studied the role played by total adiponectin and by the bioactive high-molecular-weight (HMW) oligomeric complexes of adiponectin in vascular function in offspring whose parents both had type 2 diabetes, a population at high risk of diabetes and atherosclerosis. Total and %HMW adiponectin, the cytokines C-reactive protein, interleukin-6 and plasminogen activator inhibitor-1 (PAI-1), as well as lipid profiles were assayed in 19 offspring, each with two type 2 diabetic parents. Subjects underwent OGTTs and IVGTTs. Endothelium-dependent vasodilation (EDV) was assessed by brachial artery ultrasonography. There was a significant relationship between %HMW and total adiponectin levels (r=0.72, p=0.001). Despite an expected strong positive correlation between HDL-cholesterol and adiponectin levels (r=0.52, p=0.04), as well as HDL-cholesterol and EDV (r=0.56, p<0.02), there was no significant relationship between either total adiponectin or % HMW adiponectin and EDV. Adiponectin was inversely associated with PAI-1 (r=0.50, p=0.05), but did not correlate with the inflammatory markers C-reactive protein or interleukin-6. In offspring of diabetic parents, a population at high risk of diabetes and atherosclerotic disease, there is no relationship between total or %HMW adiponectin and endothelium-dependent vasodilation. However, low adiponectin was associated with impaired fibrinolysis as manifested by increased levels of plasminogen activator inhibitor-1.


Comparison of serum Lp-PLA2 levels in ischemic stroke patients with H-type hypertension or non-H-type hypertension.
Increased serum Lp-PLA2 levels have been reported in patients who experienced an ischemic stroke; however, the relationship between Lp-PLA2 and H-type hypertension in patients with ischemic stroke remains unclear. In the present study, we investigated the correlation between serum Lp-PLA2 and H-type hypertension in patients with ischemic stroke. A total of 135 patients who experienced acute ischemic stroke were enrolled in Tianjin Huanhu Hospital during October 2015 to May 2016. The demographic characteristics of the patients were collected, and biochemical parameters were detected. Among the 135 patients, 111 patients had essential hypertension, including 41 patients with H-type hypertension and 70 with non-H-type hypertension. There were higher proportions of males and patients with diabetes mellitus in the H-type hypertension group compared with the non-H-type hypertension group (P < .05). Lp-PLA2, glucose, and LDL-C levels were higher in the H-type hypertension group than in the non-H-type hypertension group (P < .05). Multivariate logistic regression showed that Lp-PLA2 levels >208.46 mg/L were independently associated with H-type hypertension in patients with ischemic stroke (OR: 2.560, 95% CI: 1.085-6.040, P = .032). The area under the ROC curve of Lp-PAL2 levels in the H-type hypertension group was 0.665 (95% CI: 0.561-0.768, P = .004). Synergetic effects of H-type hypertension and Lp-PLA2 levels were noted in the pathogenesis of ischemic stroke.


Implementing electronic health record-based National Diabetes Prevention Program referrals in a rural county.
Since 2016, public health professionals in a rural, Midwest county have collaborated with competing health care organizations to establish electronic health record (EHR)-based systems for identifying patients with prediabetes and referring them to National Diabetes Prevention Program (NDPP) classes. The purpose of this program evaluation was to identify barriers and best practices learned from implementation in two rural health care organizations. A purposively selected program coordinator from each organization and a primary care provider and information technology administrator from one of the organizations provided perspectives on initiating the referral process. Data were collected using open-ended questions in electronic survey format. Content analysis was used to identify themes. Two barrier themes were identified: Timely, clear communication is challenging; and More education is needed for both patients and providers. Best practice themes included Start small with one provider champion; Create a referral process that doesn't exceed resources; and Providers should be actively involved in referral discussions and decisions. Retrospective queries are a feasible way to initially establish EHR-based referral programs in rural areas. PHNs can facilitate this system change among competing health care organizations by leading partnerships, identifying common goals and timelines, and providing space for sharing challenges and best practices.


Versatile offset-free 16-QAM single dual-drive IQ modulator driven by binary signals.
A customized IQ modulator driven by equal-amplitude binary signals for generating offset-free 16-quadrature amplitude modulation (QAM) is proposed and validated through simulations. The incorporation of tunable splitters demonstrates the feasibility of the transmitter and enables more efficient constellations such as hexagonal 16-QAM.


Melatonin antagonizes interleukin-18-mediated inhibition on neural stem cell proliferation and differentiation.
Neural stem cells (NSCs) are self-renewing, pluripotent and undifferentiated cells which have the potential to differentiate into neurons, oligodendrocytes and astrocytes. NSC therapy for tissue regeneration, thus, gains popularity. However, the low survivals rate of the transplanted cell impedes its utilities. In this study, we tested whether melatonin, a potent antioxidant, could promote the NSC proliferation and neuronal differentiation, especially, in the presence of the pro-inflammatory cytokine interleukin-18 (IL-18). Our results showed that melatonin per se indeed exhibited beneficial effects on NSCs and IL-18 inhibited NSC proliferation, neurosphere formation and their differentiation into neurons. All inhibitory effects of IL-18 on NSCs were significantly reduced by melatonin treatment. Moreover, melatonin application increased the production of both brain-derived and glial cell-derived neurotrophic factors (BDNF, GDNF) in IL-18-stimulated NSCs. It was observed that inhibition of BDNF or GDNF hindered the protective effects of melatonin on NSCs. A potentially protective mechanism of melatonin on the inhibition of NSC's differentiation caused IL-18 may attribute to the up-regulation of these two major neurotrophic factors, BNDF and GNDF. The findings indicate that melatonin may play an important role promoting the survival of NSCs in neuroinflammatory diseases.


Influence of the carbon/nitrogen/phosphorus ratio on polycyclic aromatic hydrocarbon degradation by Mycobacterium and Sphingomonas in soil.
Biodegradation of polycyclic aromatic hydrocarbons (PAHs) in the environment is often limited due to unfavorable nutrient conditions for the bacteria that use these PAHs as sole source of carbon and energy. Mycobacterium and Sphingomonas are 2 PAH-degrading specialists commonly present in PAH-polluted soil, but not much is known about their specific nutrient requirements. By adding different inorganic supplements of nitrogen (N) and phosphorus (P), affecting the overall carbon/nitrogen/phosphorus ratio of soil in soil slurry degradation tests, we investigated the impact of soil inorganic N and P nutrient conditions on PAH degradation by PAH-degrading Sphingomonas and Mycobacterium strains. The general theoretically calculated C/N/P ratio of 100/10/1 (expressed in moles) allowed rapid PAH metabolization by Sphingomonas and Mycobacterium strains without limitation. In addition, PAH-degradation rate and extent was not affected when ca. ten times lower concentrations of N and P were provided, indicating that Sphingomonas and Mycobacterium strains are capable of metabolizing PAHs under low nutrient conditions. Nor does PAH-degradation seem to be affected by excesses of N and P creating an imbalanced C/N/P ratio. However, supplements of N and P salts increased the salinity of soil slurry solutions and seriously limited or even completely blocked biodegradation.


Leukoreduction makes a difference: A pair proteomics study of extracellular vesicles in red blood cell units.
Prestorage filtration of blood to remove contaminating donor leukocytes and platelets has substantially increased the safety level of transfusion therapy. We have previously shown that leukoreduction has a mitigating effect on the storage lesion profile by lowering the extent of hemolysis and of RBC aging and removal phenotypes, including surface signaling and microvesiculation. Even though protein composition may determine the fate of EVs in the recipient, the probable effect of leukoreduction on the EV proteome has been scarcely investigated. In the present paired study, we characterized the proteome of EVs released in prestorage leukoreduced (L) and nonleukoreduced (N) RBC units prepared from the same donors, by immunoblotting and qualitative proteomics analyses at two storage intervals. Apart from common proteofrms typically associated with the established EV biogenesis mechanisms, the comparative proteomics analyses revealed that both leukoreduction and storage duration affect the complexity of the EV proteome. Membrane and cytoskeleton-related proteins and regulators, metabolic enzymes and plasma proteins exhibited storage duration dependent variation in L- and N-EVs. Specific proteoforms prevailed in each EV group, such as transferrin in L-units or platelet glycoproteins, leukocyte surface molecules, MHC HLA, histones and tetraspanin CD9 in N-units. Of note, several unique proteins have been associated with immunomodulatory, vasoregulatory, coagulatory and anti-bacterial activities or cell adhesion events. The substantial differences between EV composition under the two RBC preparation methods shed light in the underlying EV biogenesis mechanisms and stimuli and may lead to different EV interactions and effects to target cells post transfusion.


Risk factors for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs): a three-centric case-control study.
Risk factors for sporadic GEP-NENs are still not well defined. To identify the main clinical risk factors represents the aim of this study performed by three Italian referral centers for NENs. We performed a retrospective case-control study including 148 consecutive sporadic GEP-NENs and 210 age- and sex-matched controls. We collected data on clinical features, cancer family history and other potential risk factors. Mean age was 58.3 ± 15.8 years; 50% males, primary site was pancreas (50.7%), followed by ileum (22.3%). The 62.8% and 29.1% of cases were G1 and G2, respectively; the 40% had locally advanced or metastatic disease at diagnosis. Independent risk factors for GEP-NENs were: family history of non-neuroendocrine GEP cancer (OR 2.16, 95% CI 1.31-3.55, p = 0.003), type 2 diabetes mellitus (T2DM) (OR 2.5, 95% CI 1.39-4.51, p = 0.002) and obesity (OR 1.88, 95% CI 1.18-2.99, p = 0.007). In the T2DM subjects, metformin use was a protective factor (OR 0.28, 95% CI 0.08-0.93, p = 0.049). T2DM was also associated with a more advanced (OR 2.39, 95% CI 1.05-5.46, p = 0.035) and progressive disease (OR 2.47, 95% CI 1.08-5.34, p = 0.03). Stratifying cases by primary site, independent risk factors for pancreatic NENs were T2DM (OR 2.57, 95% CI 1.28-5.15, p = 0.008) and obesity (OR 1.98, 95% CI 1.11-3.52, p = 0.020), while for intestinal NENs family history of non-neuroendocrine GEP cancer (OR 2.46, 95% CI 1.38-4.38, p = 0.003) and obesity (OR 1.90, 95% CI 1.08-3.33, p = 0.026). This study reinforces a role for family history of non-neuroendocrine GEP cancer, T2DM and obesity as independent risk factors for GEP-NENs and suggests a role of metformin as a protective factor in T2DM subjects. If confirmed, these findings could have a significant impact on prevention strategies for GEP-NENs.


The metabolic activation of benzo(a)pyrene and 9-hydroxybenzo(a)pyrene by liver microsomal fractions.
A rat liver microsome-mediated bacterial mutagenicity test showed 9-hyroxybenzo(a)pyrene to be significantly more effective as a pre-mutagen than benzo(a)pyrene. Experiments measuring the ability of these compounds to be metabolically activated to moieties that alkylate exogenous DNA demonstrated that 9-hydroxybenzo(a)pyrene was almost six times more effective than benzo(a)pyrene itself. Addition of trichloropropene-2,3-oxide to the reaction mixture enhanced the mutagenicity and DNA alkylation by benzo(a)pyrene but had little or no effect on the 9-hydroxybenzo(a)pyrene-mediated mutagenicity and alkylation. On the other hand, 7,8-benzoflavone inhibited the microsome-mediated mutagenicity and DNA alkylating activity of both hydrocarbons.


The prefrontal "cortex" in the pigeon catecholamine histofluorescence.
The prefrontal cortex of mammals is densely innervated with dopaminergic fibers. We report a comparable, dense network of catecholamine (probably dopamine)-containing fluorescent fibers in the posterodorsolateral neostriatum of the pigeon. This region is clearly separable from paleostriatum augmentatum, lobus parolfactorius, posterior archistriatum, posteromedial corticoid and septum, all of which also show strong catecholamine fluorescence. Parallel biochemical, anatomical and neurobehavioral data support the suggestion that posterodorsolateral neostriatum in the pigeon may be comparable to the mammalian prefrontal cortex. Thus the telencephalic tissue represented as the prefrontal cortex in mammals and the posterodorsolateral neostriatum in the pigeon, may turn out to be a phylogenetically ancient neural device.


Synthesis and antifungal evaluation of 6-hydroxy-1H-carbazole-1,4(9H)-diones.
6-Hydroxy-1H-carbazole-1,4(9H)-diones were synthesized and tested for in vitro antifungal activity against two pathogenic strains of fungi. Among them tested, many compounds showed good antifungal activity. The results suggest that 6-hydroxy-1H-carbazole-1,4(9H)-diones would be potent antifungal agents.


Mutual information analysis and detection of interictal morphological differences in interictal epileptiform discharges of patients with partial epilepsies.
The purpose of this paper is to compare the morphological features of interictal epileptiform discharges (IED) in patients with benign epilepsy of childhood with centrotemporal spikes to IED of those with symptomatic localization related epilepsies using information theory. Three patients from each clinical group were selected. Two-second epochs centered at the peak negativity of the sharp waves were analyzed from a referential montage during stage I sleep. The epochs from the two groups were compared using parametric and information theory analysis. Information analysis determined the likelihood of correctly identifying the clinical group based on the IED. Standard parametric, morphological and spectral analyses were also performed. We found no significant difference in the morphology of the sharp wave between the two groups. The after-going slow wave contained the greatest information that separated the two groups. This result was supported by morphological and spectral differences in the after-going slow wave. Greater distinguishing information is held in the after-going slow wave than the sharp wave for the identification of clinical groups. Information analysis may assist in differentiating clinical syndromes from EEG signals.


Critical flicker fusion in patients with epilepsy under antiseizure medication.
Critical flicker frequency (CFF) and flicker frequency (FF) are used as indicators for the neurotoxic adverse events of drugs in pharmacology. In this pilot study, we investigated whether patients with epilepsy (PWE) treated with various antiseizure medications (ASM) had significantly different CFFs compared to healthy controls. In addition, we investigated the appropriateness of CFF as an objective measurement tool in PWE who reported adverse events according to the adverse event profile (AEP). Patients receiving regular antiseizure treatment at our center, along with healthy controls, were included in this study. Clinical neurotoxic symptoms, AEP scores, and serum ASM levels were assessed in the PWE group. We used a CFF device that produced a red-black, green-black, blue-black, or white-black flicker. CFF and FF were compared between PWE and healthy controls. In PWE, the correlation of alterations in CFF and FF with AEP results and trough ASM serum concentrations was calculated. A total of 33 PWE and 20 healthy controls participated in the study. Except for two light modalities, CFF and FF were significantly reduced in PWE compared to controls. CFF and FF did not differ significantly between PWE with AEP scores > 44 points and those with lower scores. CFF and FF levels did not correlate with changes in AEP scores, serum concentrations, or doses. CFF and FF distinguished PWE with ASM from healthy controls. No clinically relevant differentiation was detected in the heterogenous PWE group. To investigate whether CFF and FF may serve as subtle indicators of neurotoxicity or specific modes of action, additional studies are needed in more homogenous PWE groups.


Geometric morphology and population genomics provide insights into the adaptive evolution of Apis cerana in Changbai Mountain.
Exploration of adaptive evolution of organisms in response to environmental change can help to understand the evolutionary history of species and the underlying mechanisms of adaptation to local environments, thus guiding future conservation programmes. Before the introduction of Apis mellifera in China, eastern honey bees (Apis cerana) were the only species used for beekeeping in this region. In the mountains of Changbai, populations of A. cerana are considered a distinct ecotype of the species which formed through the distinct selective pressures in this area over time. We performed a measure of 300 wing specimens of eastern honey bees and obtained the geometric morphological variation in the wing of A. cerana in Changbai Mountain. A total of 3,859,573 high-quality SNP loci were yielded via the whole-genome resequencing of 130 individuals in 5 geographic regions. Corresponding geometric morphology and population genomics confirmed the particularity of the A. cerana in Changbai Mountain. Genetic differentiation at the subspecies level exists between populations in Changbai Mountain and remaining geographic regions, and a significant reduction in the effective population size and an excessive degree of inbreeding may be responsible for a substantial loss of population genetic diversity. Candidate genes potentially associated with cold environmental adaptations in populations under natural selection were identified, which may represent local adaptations in populations. Our study provided insights into the evolutionary history and adaptation of A. cerana in Changbai Mountain, as well as its conservation.