Interval-based features of auditory ERPs for diagnosis of early Alzheimer's disease.
It has been demonstrated that event-related potentials (ERPs) mirror the neurodegenerative process of Alzheimer's disease (AD) and may therefore qualify as diagnostic markers. The aim of this study was to explore the potential of interval-based features as possible ERP biomarkers for early detection of AD patients. The current results are based on 7-channel ERP recordings of 95 healthy controls (HCs) and 75 subjects with mild AD acquired during a three-stimulus auditory oddball task. To evaluate interval-based features as diagnostic biomarkers in AD, two classifiers were applied to the selected features to distinguish AD and healthy control ERPs: RBFNN (radial basis function neural network) and MLP (multilayer perceptron). Using extracted features and a radial basis function neural network, a high overall diagnostic accuracy of 98.3% was achieved. Our findings demonstrate the great promise for scalp ERP and interval-based features as non-invasive, objective, and low-cost biomarkers for early AD detection.


PEEP and "reverse mismatch". A case where less PEEP is best.
A V/Q lung scan was obtained in a patient with LLL collapse who was receiving IPPV and PEEP. This revealed absent ventilation and hyperperfusion to the collapsed lobe. After a reduction in PEEP from 12 to 5 cm H2O, a repeat V/Q scan showed a more even distribution of pulmonary perfusion. Arterial hypoxemia improved.


Spatial localization precedes temporal determination in visual perception.
The temporal order of two spots of light successively appearing in the dark, just before a saccade, influences their perceived spatial relation. Both spots are mislocalized in the saccade direction--the second more so than the first--because mislocalization grows as time elapses from stimulus to saccade onset. On the other hand, the perceived order of the two spots may be altered if the second spot is at the focus of spatial attention. How would these illusory perceptions of space and time interact when they are brought to play together? Could they be independent or could one perception depend on the other? Here we show that perceived location of stimuli is not affected by illusory temporal order, whereas perceived temporal order is affected by misperceived location. The results suggest that the brain processes spatial location of visual stimuli before processing their temporal order.


Achieving educational excellence: a strategic initiative to enhance orthopedic resident academic performance.
Orthopedic resident training involves not only the hands-on learning of surgery but also should equally involve instructing the core knowledge of musculoskeletal medicine. Our program has developed a strategy that enhances resident educational performance; the educational curriculum entails conferences daily. Conferences include gross and surgical anatomy, orthopedic basic science, multidisciplinary trauma, radiology, pathology, journal club, and orthopedic subspecialty conferences. The primary purpose of the conference schedule is to provide the residents with a comprehensive education in orthopedic surgery. It is not geared toward taking the Orthopaedic In-Training Examination (OITE). The OITE is administered annually by the American Academy of Orthopaedic Surgeons (AAOS) and serves as an objective measure of knowledge acquisition. There has been a scientifically validated correlation between performance on the OITE and passage of the American Board for Orthopaedic Surgery Part I Examination. As a collective program, we have achieved at or above the 98th percentile nationally from 2004 to 2009. This academic success has not impacted the total surgical case volume negatively or interfered with Residency Review Committee (RRC) policies.


Wastewater and greywater reuse on irrigation in centralized and decentralized systems--an integrated approach on water quality, energy consumption and CO2 emissions.
Wastewater and greywater have different scales of end-uses in irrigation in Portugal. Wastewater is treated in a central wastewater treatment plant and reused in public/private large areas of irrigation, like agriculture, public gardens and golf courses. On the contrary, greywater reuse is generally applied in in situ small scales, treated and used in the same place, generally in the production site. The main aim of this paper is to compare the two types of systems: a wastewater centralized reuse system (WWCRS) and a greywater decentralized reuse system (GWDRS) in terms of water quality, energy consumption and CO2 emissions. In this paper, the main characteristics of both streams are presented and the degree of treatment required in each stream is analyzed. The advantages and disadvantages of its reuse in different scales, in terms of water quality, energy consumption and CO2 emissions are discussed. A methodology to calculate the energy consumptions and CO2 emissions related to wastewater treatment that may be applied in different cases is presented. A hypothetical example of the two systems: one referring to a WWCRS and the other to a GWDRS is presented. The energy consumption and the CO2 emissions are analyzed and compared. The WWCRS needs a higher degree of treatment and so it spends more energy and leads to more CO2 emissions to the environment than the GWDRS that consumed between 11.8 and 37.5% of the energy consumed in the WWCRS considering the same number of inhabitants served.


Lutetium-177 Labelled PSMA Targeted Therapy in Advanced Prostate Cancer: Current Status and Future Perspectives.
Patients suffering from metastatic castration-resistant prostate cancer (mCRPC) have a poor prognosis. As a further treatment option 177Lutetium (Lu) prostate-specific membrane antigen (PSMA) radioligand therapy gained a significant interest of many investigators. Several publications showed great response and prolonged survival with limited adverse events. However, to this point, it still remains unclear which patients benefit the most from 177Lu-PSMA therapy, and how to improve the treatment regimen to achieve best outcome while minimizing potential adverse events. The efficacy for mCRPC patients is a given fact, and with the newly published results of the VISION trial its approval is only a matter of time. Recently, investigators started to focus on treating prostate cancer patients in earlier disease stages and in combination with other compounds. This review gives a brief overview of the current state and the future perspectives of 177Lu labelled PSMA radioligand therapy.


A blood analog for laser-induced photochemical anemometry.
A transparent viscoelastic blood analog fluid was developed for use with Laser-Induced Photochemical Anemometry. To provide solubility of the photochemical tracer, 1', 3', 3'-trimethyl-6-nitroindoline-2-benzopyran (TNSB dye, Kodak Chemicals), the analog solvent needed to be nonpolar, thus currently available aqueous blood analogs were not suitable. An analog consisting of 0.04% ethylhydroxyethylcellulose dissolved in gamma-butyrolactone produced a pseudoplastic steady shear response with low elasticity in unsteady shear, while being compatible with the photochemical tracer.


Comprehensive Management of Daily Living Activities, behavioral and Psychological Symptoms, and Cognitive Function in Patients with Alzheimer's Disease: A Chinese Consensus on the Comprehensive Management of Alzheimer's Disease.
Alzheimer's disease (AD) is the most common cognitive disorder in the elderly. Its main clinical manifestations are cognitive decline (C), behavioral and psychological symptoms (B), and a decline in the activities of daily living (A), also known as ABC symptoms. Early identification and evaluation of ABC symptoms are helpful for establishing the accurate diagnosis, comprehensive treatment, and prognosis of AD. To guide Chinese clinical practice for optimization of the comprehensive management of AD, in 2018, The Academy of Cognitive Disorder of China gathered 22 neurologists and gerontologists in China to build a consensus on the comprehensive management of AD. Based on a review of the evidence, the consensus summarizes the pathogenesis, pathological changes, clinical manifestations, evaluation, diagnosis, drug and non-drug treatment, and patient care for AD. Focus group discussion was used to establish a flowchart of comprehensive ABC management for AD patients. The new consensus provides a feasible AD management process for clinicians.


Adenovirus and protein kinase C have distinct molecular requirements for regulating epidermal growth factor receptor trafficking.
The ligand-activated tyrosine kinase receptor for epidermal growth factor (EGF) is down-regulated by an integral membrane protein coded for by the E3 early transcription unit of group C adenoviruses. The E3 protein appears to block recycling of constitutively internalized receptors, causing them instead to traffic to lysosomes where they are degraded. Expression of functional EGF receptors is also regulated by protein kinase C (PKC), which directly phosphorylates the EGF receptor at Thr-654. The goal of this study was to determine potential interactions between PKC and the E3 protein, since membrane-bound PKC activity is elevated by the adenovirus E1A protein. Our results show that although tumor promoters which activate PKC cause a coordinate induction of E3 protein synthesis and EGF receptor degradation, the E3 protein-induced pathway for receptor down-regulation functions independently of PKC and other kinases that are inhibited by staurosporine. This suggests that in contrast to other mechanisms that modulate receptor expression (i.e., ligand and PKC), the E3 protein is not regulated by phosphorylation but is constitutively active. We also report that adenovirus-mediated degradation is the preferred pathway in infected cells stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA) to induce receptor recycling.


Understanding the Relationship Between Tourists' Consumption Behavior and Their Consumption Substitution Willingness Under Unusual Environment.
Understanding the relationship between tourists' consumption behavior and their willingness to substitute consumption in unusual environments can promote tourists' sustainable consumption behavior. This study explores the internal relationship between tourists' willingness to engage in sustainable consumption behavior and the substitution of tourism consumption willingness in an unusual environment and the related factors. Through qualitative and quantitative mixed research, this study first invited 32 interviewees related to the tourism industry to conduct in-depth and focus group interviews and extracted a research model based on the push-pull theoretical model (PPM) through three rounds of coding of grounded theory. Then, through questionnaire design, pre-release, and formal release, 268 valid questionnaires were collected using a convenience sampling method, and the hypothesis and its mediating effect were verified using a structural equation model. Further quantitative analysis and verification showed that being in an unusual environment had a positive effect on tourists' perception of crisis awareness, safety risk, and willingness to engage in sustainable consumption behavior. However, the results did not support the unusual environment positively affecting the substitution of tourism consumption willingness, the psychological transformation cost, and the fixed consumption habit negatively affecting the substitution of tourism consumption willingness. In this study, two mediating variables were used to verify the indirect effect of being in an unusual environment and the substitution of tourism consumption willingness. The results showed that the mediating effect was significant. This study explored an action mechanism model aimed at guiding tourists' willingness for sustainable consumption, based on the environment and consumption behavior, and provided relevant countermeasures for the government and business decision-makers, enterprises, and investors in the tourism sector.


Quining diet qualia.
This paper asks whether we can identify a neutral explanandum for theories of phenomenal consciousness, acceptable to all sides. The 'classic' conception of qualia, on which qualia are intrinsic, ineffable, and subjective, will not serve this purpose, but it is widely assumed that a watered-down 'diet' conception will. I argue that this is wrong and that the diet notion of qualia has no distinctive content. There is no phenomenal residue left when qualia are stripped of their intrinsicality, ineffability, and subjectivity. Thus, if we reject classic qualia realism, we should accept that all that needs explaining are 'zero' qualia - our dispositions to judge that our experiences have classic qualia. Diet qualia should, in Dennett's phrase, be quined.


Clinically relevant concentrations of dexmedetomidine may reduce oxytocin-induced myometrium contractions in pregnant rats.
Recently, there have been some trials to use dexmedetomidine in the obstetric field but concerns regarding the drug include changes in uterine contractions after labor. We aimed to evaluate the effects of dexmedetomidine on the myometrial contractions of pregnant rats. In a pilot study, the contraction of the myometrial strips of pregnant Sprague-Dawley rats in an organ bath with oxytocin at 1 mU/ml was assessed by adding dexmedetomidine from 10-6 to 10-2 M accumulatively every 20 min, and active tension and the number of contractions were evaluated. Then, changes in myometrial contractions were evaluated from high doses of dexmedetomidine (1.0 × 10-4 to 1.2 × 10-3 M). The effective concentrations (EC) for changes in uterine contractions were calculated using a probit model. Active tension and the number of contractions were significantly decreased at 10-3 M and 10-4 M dexmedetomidine, respectively (P < 0.05). A complete loss of contractions was seen at 10-2 M. Dexmedetomidine (1.0 × 10-4 to 1.2 × 10-3 M) decreased active tension and the number of contractions in a concentration-dependent manner. The EC95 of dexmedetomidine for inhibiting active tension and the number of contractions was 5.16 × 10-2 M and 2.55 × 10-5 M, respectively. Active tension of the myometrium showed a significant decrease at concentrations of dexmedetomidine higher than 10-3 M. Thus, clinical concentrations of dexmedetomidine may inhibit uterine contractions. Further research is needed for the safe use of dexmedetomidine in the obstetrics field.


Sharing best practices through online communities of practice: a case study.
The USAID-funded Capacity Project established the Global Alliance for Pre-Service Education (GAPS) to provide an online forum to discuss issues related to teaching and acquiring competence in family planning, with a focus on developing countries' health related training institutions. The success of the Global Alliance for Nursing and Midwifery's ongoing web-based community of practice (CoP) provided a strong example of the successful use of this medium to reach many participants in a range of settings. GAPS functioned as a moderated set of forums that were analyzed by a small group of experts in family planning and pre-service education from three organizations. The cost of the program included the effort provided by the moderators and the time to administer responses and conduct the analysis. Family planning is still considered a minor topic in health related training institutions. Rather than focusing solely on family planning competencies, GAPS members suggested a focus on several professional competencies (e.g. communication, leadership, cultural sensitivity, teamwork and problem solving) that would enhance the resulting health care graduate's ability to operate in a complex health environment. Resources to support competency-based education in the academic setting must be sufficient and appropriately distributed. Where clinical competencies are incorporated into pre-service education, responsible faculty and preceptors must be clinically proficient. The interdisciplinary GAPS memberships allowed for a comparison and contrast of competencies, opportunities, promising practices, documents, lessons learned and key teaching strategies. Online CoPs are a useful interface for connecting developing country experiences. From CoPs, we may uncover challenges and opportunities that are faced in the absorption of key public health competencies required for decreasing maternal mortality and morbidity. Use of the World Health Organization (WHO) Implementing Best Practices Knowledge Gateway, which requires only a low bandwidth connection, gave educators an opportunity to engage in the discussion even in the most Internet access-restricted places (e.g. Ethiopia). In order to sustain an online CoP, funds must come from an international organization (e.g. WHO regional office) or university that can program the costs long-term. Eventually, the long-term effectiveness and sustainability of GAPS rests on its transfer to the members themselves.


Effects of pentobarbital and d-amphetamine on the repeated acquisition of response sequences by pigeons.
Pigeons were trained to acquire a new 4-response sequence in each session by pecking three keys in a predetermined order. The key color varied for each step under the chained schedule, but there was only one key color under the tandem schedule. Under the reset contingency, incorrect responses produced a reset of the 4-response sequence to its beginning and a short timeout. In the non-resent contingency, only the timeout was produced by incorrect responses. Under both contingencies of both schedules, low doses (3-10 mg/kg) of pentobarbital increased the response rate and the total number of errors, although the rate increases usually occurred at lower doses than did the increases in errors. A dose of 17.5 mg/kg pentobarbital eliminated almost all responding. Injection of low doseas (0.1 -0.3 mg/kg) of d-amphetamine decreased the total number of errors under both contingencies of both the chained and the tandem schedules. Higher doses of d-amphetamine sometimes increased the total number of errors and decreased the response rate.


Review of the effects of polycystic ovary syndrome on Cognition: Looking beyond the androgen hypothesis.
Polycystic-ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age, and many features associated with PCOS - such as elevated androgens, insulin resistance and inflammation - are known to affect cognition. However, effects of PCOS on cognition are not well-understood. Here we review the current literature on PCOS and cognition, note the extent of PCOS symptomatology studied in relation to cognitive outcomes, and identify key research gaps and common methodological concerns. Findings indicate a pattern of worse performance across cognitive domains and brain measures in women with PCOS relative to non-PCOS controls, as well as a lack of evidence for the common assumption that women with PCOS will have higher performance on tasks with a demonstrated male-advantage due to high testosterone levels. We suggest strategies for moving beyond the focus on elevated androgens, in favor of research practices that account for the nuances and heterogeneity of PCOS symptoms.


The importance of input data on landslide susceptibility mapping.
Landslide detection and susceptibility mapping are crucial in risk management and urban planning. Constant advance in digital elevation models accuracy and availability, the prospect of automatic landslide detection, together with variable processing techniques, stress the need to assess the effect of differences in input data on the landslide susceptibility maps accuracy. The main goal of this study is to evaluate the influence of variations in input data on landslide susceptibility mapping using a logistic regression approach. We produced 32 models that differ in (1) type of landslide inventory (manual or automatic), (2) spatial resolution of the topographic input data, (3) number of landslide-causing factors, and (4) sampling technique. We showed that models based on automatic landslide inventory present comparable overall prediction accuracy as those produced using manually detected features. We also demonstrated that finer resolution of topographic data leads to more accurate and precise susceptibility models. The impact of the number of landslide-causing factors used for calculations appears to be important for lower resolution data. On the other hand, even the lower number of causative agents results in highly accurate susceptibility maps for the high-resolution topographic data. Our results also suggest that sampling from landslide masses is generally more befitting than sampling from the landslide mass center. We conclude that most of the produced landslide susceptibility models, even though variable, present reasonable overall prediction accuracy, suggesting that the most congruous input data and techniques need to be chosen depending on the data quality and purpose of the study.


Sleep disruption as a correlate to cognitive and adaptive behavior problems in autism spectrum disorders.
Sleep problems associated with autism spectrum disorders (ASD) have been well documented, but less is known about the effects of sleep problems on day-time cognitive and adaptive performance in this population. Children diagnosed with autism or pervasive developmental disorder-not otherwise specified (PDD-NOS) (N = 335) from 1 to 10 years of age (M = 5.5 years) were evaluated for the relationships of Behavioral Evaluation of Disorders of Sleep (BEDS; Schreck, 1998) scores to measures of intelligence and adaptive behavior. Results suggested that children who slept fewer hours per night had lower overall intelligence, verbal skills, overall adaptive functioning, daily living skills, socialization skills, and motor development. Children who slept fewer hours at night with waking during the night had more communication problems. Breathing related sleep problems and fewer hours of sleep related most often to problems with perceptual tasks. The results indicate that quality of sleep--especially sleep duration--may be related to problems with day-time cognitive and adaptive functioning in children with autism and PDD-NOS. However, future research must be conducted to further understand these relationships.


Impact of curing protocol on the selected properties of a model bis-GMA/TEGDMA dental resin composite.
This study investigated the impact of different photo-activation protocols on selected properties of a model composite formulated using bis-GMA/TEGDMA (1:1 mass ratio), camphorquinone/amine (1:2 mass ratio) and 75% of fillers. The protocols tested were: high-intensity continuous (HIC-500 mW cm(-2) for 20 s), medium-intensity continuous (MIC-250 mW cm(-2) for 40 s), low-intensity continuous (LIC-100 mW cm(-2) for 100 s) and pulse-delay-1 min or 3 min (PD-1 min/3 min-100 mW cm(-2) for 5 s + 1 or 3 min interval + 500 mW cm(-2) for 19 s). Degree of conversion (DC) was evaluated using infrared spectroscopy. Flexural strength (FS) and modulus (FM) were measured in three-point bending mode. Cross-link density was estimated by calculating the swelling coefficient (alpha) after immersion in chloroform. All methods showed similar values for DC except for PD-1 min, which showed lower DC. HIC and MIC showed similar FS, but were both different than all of the other methods. All curing methods showed similar FM, except for HIC, which presented a different modulus. PD-3 min showed a different swelling than all of the remaining groups, while HIC showed the lowest swelling. A significant relationship was observed between swelling and both FS and FM. In conclusion, the HIC activation protocol generated polymers with properties at least similar, and sometimes improved, in comparison with the alternative protocols.


Security of a kind of quantum secret sharing with entangled states.
We present a new collusion attack to a kind of quantum secret sharing schemes with entangled states. Using this attack, an unauthorized set of agents can gain access to the shared secret without the others' cooperation. Furthermore, we establish a general model for this kind of quantum secret sharing schemes and then give some necessary conditions to design a secure quantum secret sharing scheme under this model.


[Protein crystals and tubuli bundles in yeast cells. V. Enrichment of crystal and tubuli proteins during O2 limitation and anaerobiosis].
Cells of Saccharomyces carlsbergensis contain proteins assembling to crystals and bundles of tubules (tb) in the cyto- and karyoplasm by osmotic shock with hypertonic solutions. The cellular concentration of these proteins is regulated by oxygen pressure during growth. In cells grown at optimal aeration the protein level is low and crystals and tb cannot be induced. After a short period of O2-limitation or anerobic growth conditions the protein concentration increases and induction of crystals and tb is possible.


Generalized robust loss functions for machine learning.
Loss function is a critical component of machine learning. Some robust loss functions are proposed to mitigate the adverse effects caused by noise. However, they still face many challenges. Firstly, there is currently a lack of unified frameworks for building robust loss functions in machine learning. Secondly, most of them only care about the occurring noise and pay little attention to those normal points. Thirdly, the resulting performance gain is limited. To this end, we put forward a general framework of robust loss functions for machine learning (RML) with rigorous theoretical analyses, which can smoothly and adaptively flatten any unbounded loss function and apply to various machine learning problems. In RML, an unbounded loss function serves as the target, with the aim of being flattened. A scale parameter is utilized to limit the maximum value of noise points, while a shape parameter is introduced to control both the compactness and the growth rate of the flattened loss function. Later, this framework is employed to flatten the Hinge loss function and the Square loss function. Based on this, we build two robust kernel classifiers called FHSVM and FLSSVM, which can distinguish different types of data. The stochastic variance reduced gradient (SVRG) approach is used to optimize FHSVM and FLSSVM. Extensive experiments demonstrate their superiority, with both consistently occupying the top two positions among all evaluated methods, achieving an average accuracy of 81.07% (accompanied by an F-score of 73.25%) for FHSVM and 81.54% (with an F-score of 75.71%) for FLSSVM.


Therapeutic potential of stem cell extracellular vesicles for ischemic stroke in preclinical rodent models: a meta-analysis.
Extracellular vesicles derived from stem cells (SC-EVs) have been proposed as a novel therapy for ischemic stroke. However, their effects remain incompletely understood. Therefore, we conducted this meta-analysis to systematically review the efficacy of SC-EVs on ischemic stroke in preclinical rodent models. Using PubMed, EMBASE, and the Web of Science, we searched through studies published up to August 2021 that investigated the treatment effects of SC-EVs in a rodent ischemic stroke model. Infarct volume was the primary outcome. Neurological severity scores (mNSS) were the secondary outcome. The standard mean difference (SMD) and the confidence interval (CI) were calculated using a random-effects model. R and Stata 15.1 were used to conduct the meta-analysis. Twenty-one studies published from 2015 to 2021 met the inclusion criteria. We also found that SCs-EVs reduced infarct volume by an SMD of - 2.05 (95% CI - 2.70, - 1.40; P < 0.001). Meanwhile, our results revealed an overall positive effect of SCs-derived EVs on the mNSS with an SMD of - 1.42 (95% CI - 1.75, - 1.08; P < 0.001). Significant heterogeneity among studies was observed. Further stratified and sensitivity analyses did not identify the source of heterogeneity. The present meta-analysis confirmed that SC-EV therapy could improve neuron function and reduce infarct volume in a preclinical rodent ischemic stroke model, providing helpful clues for human clinical trials on SC-EVs.


Caring for anxiety among adults in the face of COVID-19: A cross-sectional online survey.
The outbreak of COVID-19 poses a challenge to psychological resilience. The aim of this study was to evaluate the prevalence of anxiety and identify risk and protective factors associated with the presence of anxiety symptoms in the face of COVID-19 among adults. A cross-sectional online survey was conducted in adults from March 2nd to March 16th 2020. The self-rating anxiety scale (SAS) was used to measure the status of anxiety. Unconditional multivariate logistic regression was performed to identify the factors associated with anxiety. Among the 7144 respondents, 9.3% met the criteria for anxiety risk based on the SAS. Symptoms of anxiety were more prevalent among farmer (OR=1.43, 95%CI: 1.03-1.99), respondents lived in urban out of Beijing during the COVID-19 outbreak (OR=1.73, 95%CI: 1.14-2.63), and slept less than six hours per day (OR=2.64, 95%CI: 1.96-3.57). Compared to participants who didn't exercise, a lower risk of anxiety was observed in those exercised 30-60 minutes/day (OR=0.62, 95%CI: 0.41-0.94) and more than 60 minutes/day (OR=0.57, 95%CI: 0.37-0.88). And compared with participants whose knowledge and perceptions of COVID-9 scores in lower quartile, the OR (95%CI) for the second, third and upper quartile were 0.58 (0.46, 0.73), 0.48 (0.37, 0.61) and 0.42(0.33, 0.52), respectively. No diagnostic interview for mental disorders was administered in the original studies limiting analysis of sensitivity and specificity of the Swahili PHQ-9. There was a high level of anxiety in the face of COVID-19 among adults. The results point to characteristics of adults in particular need for attention to anxiety and suggest possible targets for intervention such as strengthening of physical activity and knowledge and perceptions of COVID-19.


The role of cuticle in fruit shelf-life.
Ensuring the availability of high-quality fresh fruits requires the development of strategies to maintain prolonged shelf-life. The plant cuticle is a modification of the outer epidermal cell wall and, as such, acts as a barrier with the environment. Understanding how the cuticle naturally changes during postharvest is crucial to address the potential effect of different storage conditions on the cuticle biophysical properties. The impact of different cuticle traits in fruit water loss, its relevance in several fruit-skin disorders, and its participation in postharvest decay caused by pathogens are discussed. Future challenges to study in vivo the physicochemical properties of the cuticle are also addressed.


LKB1 Down-Modulation by miR-17 Identifies Patients With NSCLC Having Worse Prognosis Eligible for Energy-Stress-Based Treatments.
Preclinical models recently unveiled the vulnerability of LKB1/KRAS comutated NSCLC to metabolic stress-based treatments. Because miR-17 is a potential epigenetic regulator of LKB1, we hypothesized that wild-type LKB1 (LKB1WT) NSCLC with high miR-17 expression may be sensitive to an energetic stress condition, and eligible for metabolic frailties-based therapeutic intervention. We took advantage of NSCLC cell lines with different combinations of KRAS mutation and LKB1 deletion and of patient-derived xenografts (PDXs) with high (LKB1WT/miR-17 high) or low (LKB1WT/miR-17 low) miR-17 expression. We evaluated LKB1 pathway impairment and apoptotic response to metformin. We retrospectively evaluated LKB1 and miR-17 expression levels in tissue specimens of patients with NSCLC and PDXs. In addition, a lung cancer series from The Cancer Genome Atlas data set was analyzed for miR-17 expression and potential correlation with clinical features. We identified miR-17 as an epigenetic regulator of LKB1 in NSCLC and confirmed targeting of miR-17 to LKB1 3' untranslated region by luciferase reporter assay. We found that miR-17 overexpression functionally impairs the LKB1/AMPK pathway. Metformin treatment prompted apoptosis on miR-17 overexpression only in LKB1WT cell lines, and in LKB1WT/miR-17 high PDXs. A retrospective analysis in patients with NSCLC revealed an inverse correlation between miR-17 and LKB1 expression and highlighted a prognostic role of miR-17 expression in LKB1WT patients, which was further confirmed by The Cancer Genome Atlas data analysis. We identified miR-17 as a mediator of LKB1 expression in NSCLC tumors. This study proposes a miR-17 expression score potentially exploitable to discriminate LKB1WT patients with NSCLC with impaired LKB1 expression and poor outcome, eligible for energy-stress-based treatments.


Impedance cardiography used to assess patterns of cardiovascular response to behavioral stressors.
This paper presents two examples of how impedance cardiography may be used to interpret the hemodynamic influences on blood pressures measured during behavioral stress. In Study 1, blood pressure changes which were similar during two tasks were shown to have important differences in their cardiac output and vascular resistance components. During work on a reaction time task having aversive incentives compared with a neutral task, the blood pressure changes were seen to be associated with lowered vascular resistance and raised cardiac activity, a "fight-flight" pattern. In Study 2, blood pressure response differences between two subject groups working on an identical task were found to have blood pressure changes differing in their underlying cardiac and vascular components as measured by impedance. Such uses impedance cardiography have widespread potential application in psychophysiological research with humans.


Dysregulation of prostaglandine E2 and BDNF signaling mediated by estrogenic dysfunction induces primary hippocampal neuronal cell death after single and repeated paraquat treatment.
Paraquat (PQ) produces hippocampal neuronal cell death and cognitive dysfunctions after unique and continued exposure, but the mechanisms are not understood. Primary hippocampal wildtype or βAPP-Tau silenced cells were co-treated with PQ with or without E2, N-acetylcysteine (NAC), NS-398 (cyclooxygenase-2 inhibitor), MF63 (PGES-1 inhibitor) and/or recombinant brain-derived neurotrophic factor (BDNF) during one- and fourteen-days to studied PQ effect on prostaglandin E2 (PGE2) and BDNF signaling and their involvement in hyperphosphorylated Tau (pTau) and amyloid-beta (Aβ) protein formation, and oxidative stress generation, that lead to neuronal cell loss through estrogenic disruption, as a possible mechanism of cognitive dysfunctions produced by PQ. Our results indicate that PQ overexpressed cyclooxygenase-2 that leads to an increase of PGE2 and alters the expression of EP1-3 receptor subtypes. PQ induced also a decrease of proBDNF and mature BDNF levels and altered P75NTR and tropomyosin receptor kinase B (TrkB) expression. PQ induced PGE2 and BDNF signaling dysfunction, mediated through estrogenic disruption, leading to Aβ and pTau proteins synthesis, oxidative stress generation and finally to cell death. Our research provides relevant information to explain PQ hippocampal neurotoxic effects, indicating a probable explanation of the cognitive dysfunction observed and suggests new therapeutic strategies to protect against PQ toxic effects.


Explicating Filipino student nurses' preferences of clinical instructors' attributes: A conjoint analysis.
The role of clinical instructor in student nurses' preparation for the professional nursing practice cannot be underestimated. The extent to which such role is achieved depends highly on the instructors' ability to realize the desired qualities expected of them. While a number of empirical studies have qualitatively explored the attributes of an effective clinical instructor, no attempt has ventured yet on the power of experimental vignettes for conjoint analysis in explicating the preferences of a select group of Filipino student nurses relative to their clinical instructors' attributes. Junior and senior nursing students (n=227), recruited from one of the comprehensive universities in the Philippines, were asked to sort out orthogonal cards generated by Sawtooth Software. As shown, the full-profile conjoint analysis was considerably fit for this study: Pearson's R=0.988, (p<0.05) and Kendall's t=0.944, (p<0.05). Results indicated that the student nurses are one in terms of their most preferred clinical instructor attribute, which was clinical teaching capacity (38.14%) followed by interpersonal relationship and caring behavior (33.17%). In regard to the clinical teaching capability, a clinical instructor who parallels clinical teaching skills with the students' understanding and experience (0.089) was the highest part-worth. As for the interpersonal relationship and caring behavior, the highest part-worth was a clinical instructor who respects a student nurse as an individual and cares about him/her as a person (0.114). Findings of this study can be a basis for clinical instructors as to which qualities to cultivate best to facilitate a first-rate clinical nursing instruction. Likewise, the results of this study can inform current practices of clinical instructors by making them aware of how they can nurture a pedagogical approach consistent with the student nurses' preferences.


Serum levels of luteinizing and follicle-stimulating hormones in normal and poor-responding patients undergoing ovarian stimulation with urofollitropin after pituitary downregulation.
We were interested in the degree of downregulation in women with poor response to in vitro fertilization (IVF) treatment. Ten women who were poor-responders, arbitrarily defined as having fewer than three follicles with diameter > 14 mm on days 9 and 10 of urofollitropin therapy, were compared with ten women who were not poor-responders, in a standard IVF program. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol after pituitary down-regulation did not differ between the two groups. The daily dose and the serum level of FSH were higher in poor-responders and there was a significant correlation between the dose of urofollitropin and the serum FSH level. There was no difference in serum LH level during ovulation stimulation between the groups. The clinical pregnancy rate was similar in the two groups although fewer embryos were transferred in the poor-response group. In conclusion, there was no difference with regard to pituitary suppression in normal-responders and poor-responders.


Imported Salmonella Enteritidis cases: a multiphage outbreak among Austrian vacationers in Turkey, 2008.
An outbreak of Salmonella Enteritidis infection among high school graduates was associated with the 2008 three-week Summer Splash event in Turkey. A similar outbreak, caused by Salmonella Enteritidis PT6, affected 70 of 2879 graduates attending the 2007 Summer Splash event. A total of 103 cases of Salmonella Enteritidis were identified by passive and active case finding among the 8914 participants of the 2008 event. A case series investigation was performed. The cases originated from eight of the nine Austrian provinces. Among 59 laboratory-confirmed S. Enteritidis cases, the most commonly identified phage type was PT21 (72.9%), followed by PT6 (18.6%), PT7 and PT3 (3.4% each). To our knowledge, none of the published outbreaks of salmonellosis in the past 10 years has involved multiple phage types. Among the three hotels within the resort complex, the highest number of outbreak cases was identified among the students who stayed at Hotel A (n = 37), followed by Hotel B (n = 33) and Hotel C (n = 32). Eggs and egg-containing products frequently offered at meals in all three hotels were hypothesized as the source of infection. Reliable findings from investigation of imported outbreaks enable the appropriate response measures in the country of origin. As a consequence of the effective programs for reducing salmonella in domestic animals intended for human consumption in Austria, the number of imported cases will gain importance in the coming years, and salmonellosis will increasingly appear as traveler's diarrhoea.


Risk of cancer in migrants and their descendants in Israel: I. Leukaemias and lymphomas.
Cancer registrations among young individuals (under age 30 years) for the 30-year period 1960-1989 were used to investigate the risk of leukaemia and lymphoma in migrants to Israel, and in their offspring, relative to Israel-born individuals with Israel-born parents. Relative risks by the father's continent of origin, and odds ratios by continent of origin of mother or both parents, adjusted for age, sex and period, were estimated. The leukaemias showed little variation in risk by birthplace, and no change between generations. For non-Hodgkin lymphoma, however, there were quite large differences in incidence, with relatively high rates in migrants from Asia and Africa. These persisted to some degree into the second generation, suggesting that inherited susceptibility may underlie some of the variation.


Evaluating function in the hallux valgus foot following a 12-week minimalist footwear intervention: A pilot computational analysis.
Hallux valgus is a foot pathological condition showing a lateral deviation of the first phalange and medial deviation of the first metatarsal. The purpose of the current study was to evaluate a longitudinal effect of minimalist footwear running protocol for a mild/moderate hallux valgus patient. The computer tomography (CT) images from a male hallux valgus (HV) patient were respectively scanned pre and post 12-week minimalist footwear running intervention. The pre and post -intervention foot finite element (FE) models were developed from the foot three-dimensional geometries manually segmented via the MIMICS 21.0. The post-process with SolidWorks 2019 was conducted for model assembly, consisting of 24 bones, 22 cartilages, five plantar fascia, and lumped encapsulated soft tissue. The foot FE models were solved in ANSYS Workbench 2020 R1 package. The FE models were validated against the plantar pressure (pre: 0.146 MPa vs 0.155 MPa, and post: 0.156 MPa vs 0.17 MPa) and vertical displacements (pre: 2.6 mm vs 2.4 ± 0.4 mm, and post 1.1 mm vs 1.3 ± 0.4 mm) of navicular measured from experiments. The first metatarsophalangeal joint showed varus realignment and the von Mises stress in the first metatarsal and the second metatarsal decreased 72.1% and 51.2% compared with pre-intervention (M1: 4.41 MPa and M2: 4.18 MPa). This framework investigated the shape adjustment and functional recovery in the mild/moderate HV deformity, which may provide references and implications for future studies with a larger cohort.


Relaxin-3/INSL7 regulates the stress-response system in the rat hypothalamus.
Relaxin-3 (RLN3) is a neuropeptide belonging to the insulin-relaxin superfamily. RLN3-expressing neurons are predominantly located in the dorsal pons known as the nucleus incertus, and project their axons to the forebrain including the hypothalamus. RLN3 has been suggested to be involved in the stress response. In the present study, we investigated the hypothalamic action of RLN3 in the stress-response system by intracerebroventricular (icv) administration of RLN3. Compared with saline icv injection, 1 nmol icv RLN3 injection induced c-Fos expression in the paraventricular nucleus of the hypothalamus (PVN) at 1 h after administration. Some RLN3-induced c-Fos-positive cells in the PVN were also corticotropin-releasing factor (CRF)-expressing neurons. CRF and c-fos mRNA levels in the PVN were increased at 2 h after RLN3 administration. Plasma adrenocorticotropic hormone (ACTH) levels were also increased after RLN3 administration. These results suggest that RLN3 is able to stimulate the hypothalamopituitary CRF-ACTH system during the acute response.


Mutated human embryonic stem cells for the study of human genetic disorders.
Human embryonic stem cells (HESCs) are of great interest in biology and medicine due to their ability to grow indefinitely in culture while maintaining their ability to differentiate into all different cell types in the human body. In addition, HESCs can be used for better understanding the key developmental processes and can, therefore, serve for studying genetic disorders for which no good research model exists. Preimplantation genetic diagnosis of in vitro derived embryos results in affected-spare blastocysts with specific known inherited mutations.These affected blastocysts can be used for the derivation of disease-bearing HESCs, which would serve for studying the molecular and pathophysiological mechanisms underlying the genetic disease for which they were diagnosed. This chapter describes the methods to derive HESCs carrying mutations for inherited disorders.


In vitro biomineralization potential in simulated wound fluid and antibacterial efficacy of biologically-active glass nanoparticles containing B2O3/ZnO.
In the present study, SiO2-CaO-B2O3-ZnO (SCBZ), SiO2-CaO-B2O3 (SCB), SiO2-CaO-ZnO (SCZ) and SiO2-CaO (SC) silicate-based glasses were synthesized by the sol-gel method to elucidate the influence of B2O3 and ZnO substitution on glass characteristics aiming to further use in wound healing applications. The amorphous nature, spherical-shaped morphology and nano-sized primary particles of glasses were revealed by XRD and SEM analysis. Moreover, investigating the antibacterial activity of glasses against E.coli and S.aureus bacteria indicated the improved antibacterial properties of SCBZ glass against both bacterial strains compared with SCB and SCZ glasses. Assessment of ion release revealed that the incorporation of zinc induces a more stable glass network with a lower tendency to dissolution contrary to the incorporation of boron, which facilitated the dissolution of glass by the formation of more reactive SiOB and BO bonds. Glasses were immersed in Simulated Wound Fluid (SWF) to predict their mineralization susceptibility. Morphological studies and FTIR analysis showed the formation of cauliflower-like hydroxy-carbonated apatite on the surface of SCB and SC glasses after 14 days. In contrast, the presence of Zn in SCBZ and SCZ glasses inhibited the formation of crystalline apatite and induced the deposition of spherical-shaped amorphous apatite. Our study suggests that the co-incorporation of B and Zn in SCBZ glass make this material a potential multifunctional candidate for accelerating the healing of skin wounds.


Inorganic nanoparticle-based contrast agents for molecular imaging.
Inorganic nanoparticles (NPs) including semiconductor quantum dots (QDs), iron oxide NPs and gold NPs have been developed as contrast agents for diagnostics by molecular imaging. Compared with traditional contrast agents, NPs offer several advantages: their optical and magnetic properties can be tailored by engineering the composition, structure, size and shape; their surfaces can be modified with ligands to target specific biomarkers of disease; the contrast enhancement provided can be equivalent to millions of molecular counterparts; and they can be integrated with a combination of different functions for multimodal imaging. Here, we review recent advances in the development of contrast agents based on inorganic NPs for molecular imaging, and also touch on contrast enhancement, surface modification, tissue targeting, clearance and toxicity. As research efforts intensify, contrast agents based on inorganic NPs that are highly sensitive, target-specific and safe to use are expected to enter clinical applications in the near future.


[Causes of death from tuberculosis in children under the present-day conditions].
Analysis of the causes of death from tuberculosis in 15 children in one of the central regions of Russia has indicated that in the past 14 years, the territorial childhood mortality rates have been 0.10-0.20 per 100,000 children. The main cause of death is tuberculous meningoencephalitis (n = 10); caseous pneumonia (n = 3), and generalized tuberculosis with severe concomitant diseases (n = 2) were less common. Tuberculous meningoencephalitis was postmortally diagnosed in 4 children who had received intensive nonspecific therapy using large doses of corticosteroid hormones. This led to the development of severe pyonecrotic meningoencephalitis with great brain edema and hemorrhoidal portions, which was early known as steroid-induced tuberculosis.


Reversed-phase high-performance liquid chromatographic method for the determination of peptidoglycan monomers and structurally related peptides and adamantyltripeptides.
The reversed-phase HPLC method using UV detection was developed for the determination of (a) immunostimulating peptidoglycan monomers represented by the basic structure GlcNAc-MurNAc-L-Ala-D-isoGln-meso-DAP(omegaNH(2))-D-Ala-D-Ala (PGM) and two more lipophilic derivatives, Boc-Tyr-PGM and (Ada-1-yl)-CH(2)-CO-PGM, (b) two diastereomeric immunostimulating adamantyltripeptides L- and D-(adamant-2-yl)-Gly-L-Ala-D-isoGln and (c) peptides obtained by the enzyme hydrolyses of peptidoglycans and related peptides. The enzymes used, N-acetylmuramyl-L-alanine amidase and an L,D-aminopeptidase are present in mammalian sera and are involved in the metabolism of peptidoglycans and related peptides. Appropriate solvent systems were chosen with regard to structure and lipophilicity of each compound. As well, different gradient systems within the same solvent system had to be applied in order to achieve satisfactory separation and retention time. HPLC separation was developed with the aim to use this method for the study of the stability of the tested compounds, the purity during preparation and isolation and for following the enzyme hydrolyses.


Geriatric assessment of a giant splenic artery aneurysm accidentally diagnosed.
Giant splenic artery aneurysms (GSAAs) larger than 8 cm in diameter have rarely been reported, particularly in older people. They are clinically important lesions, often asymptomatic and related to an increased risk of complications such as abrupt rupture, requiring emergency surgical treatment. Comprehensive geriatric assessment (CGA), originally developed for multidimensional clinical evaluation in several geriatric settings, was recently proposed as a fundamental preoperative aid for treatment planning of older patients undergoing elective surgery and preventing adverse post-operative outcomes. We present the first case of an asymptomatic 9-cm partially thrombosed GSAA, accidentally diagnosed during abdominal ultrasound in a 63-year-old woman from the Apulia region in Southern Italy. She successfully underwent aneurysmectomy, highlighting the usefulness of CGA in elective surgical patients.


Incidence and characteristics of metastatic intracranial lesions in stage III and IV melanoma: a single institute retrospective analysis.
The study aimed to describe the brain metastases (BM) incidence, at diagnosis and follow-up, in patients initially presenting with stage III or IV melanoma and characterize their metastatic brain lesions. We also sought to describe the association of common genetic mutations and immunotherapy with BM development in advanced melanoma. Using our institution's tumor registry, we identified patients with initial diagnoses of stage III and stage IV melanoma. In this cohort, we obtained BM incidence at diagnosis and follow-up, characterized the metastatic brain lesions and primary tumor's genetic profile. During the follow-up period, 22.9% of patients with an initial diagnosis of stage III developed BM. In this cohort, the median time for BM occurrence was 20 months; [95% CI (14-29)]. Likewise, 37.7% of patients with Stage IV melanoma presented with BM at the time of diagnosis, and 22.7% of remaining patients developed BM at follow-up over a median duration of 6 months [95% CI (4-11)]. Therefore, suggesting an overall incidence of 51.9% in stage IV melanoma. Next, we observed that the incidence of BM development during the follow-up period significantly decreased from 2012 to 2017 (p < 0.001). Lastly, we found a significantly higher frequency of mutational BRAF in the primary tumor of patients with BM (68.7% vs. 31.2%; p = 0.02). While the overall incidence of BM remains high, the decreasing incidence of BM over the follow-up period is promising. Similar BM incidence in patients with an initial diagnosis of stage III or stage IV warrants appropriate imaging surveillance regimen for stage III patients.


Tenofovir is Associated With Higher Risk of Kidney Function Decline Than Entecavir in Patients With Chronic Hepatitis B.
Of the antiviral agents currently available to patients with chronic hepatitis B (CHB), entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are 2 of 3 first-line agents.1-3 Given the well-known renal and bone toxicity associated with TDF,4 major international hepatitis B virus treatment guidelines recommend ETV over TDF in patients with predisposing factors to kidney function decline.1-3 However, as evidenced by recent studies, nephrotoxicity of antiviral agents is still an issue under debate.5-7 Therefore, we investigated the differences in the risk of kidney function decline in patients with treatment-naive CHB who were treated with ETV or TDF.


A passage retrieval method based on probabilistic information retrieval model and UMLS concepts in biomedical question answering.
Passage retrieval, the identification of top-ranked passages that may contain the answer for a given biomedical question, is a crucial component for any biomedical question answering (QA) system. Passage retrieval in open-domain QA is a longstanding challenge widely studied over the last decades. However, it still requires further efforts in biomedical QA. In this paper, we present a new biomedical passage retrieval method based on Stanford CoreNLP sentence/passage length, probabilistic information retrieval (IR) model and UMLS concepts. In the proposed method, we first use our document retrieval system based on PubMed search engine and UMLS similarity to retrieve relevant documents to a given biomedical question. We then take the abstracts from the retrieved documents and use Stanford CoreNLP for sentence splitter to make a set of sentences, i.e., candidate passages. Using stemmed words and UMLS concepts as features for the BM25 model, we finally compute the similarity scores between the biomedical question and each of the candidate passages and keep the N top-ranked ones. Experimental evaluations performed on large standard datasets, provided by the BioASQ challenge, show that the proposed method achieves good performances compared with the current state-of-the-art methods. The proposed method significantly outperforms the current state-of-the-art methods by an average of 6.84% in terms of mean average precision (MAP). We have proposed an efficient passage retrieval method which can be used to retrieve relevant passages in biomedical QA systems with high mean average precision.


Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1.
Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse. Utilizing single-cell RNA-Seq, ChiP-Seq, ATAC-Seq, RNA-Seq, RPPA, and mass cytometry (CyTOF) analyses, present pre-clinical studies elucidate gene-expression correlates of MI efficacy in AML cells harboring MLL1-r or mtNPM1. Notably, MI-mediated genome-wide, concordant, log2 fold-perturbations in ATAC-Seq and RNA-Seq peaks were observed at the loci of MLL-FP target genes, with upregulation of mRNAs associated with AML differentiation. MI treatment also reduced the number of AML cells expressing the stem/progenitor cell signature. A protein domain-focused CRISPR-Cas9 screen in MLL1-r AML cells identified targetable co-dependencies with MI treatment, including BRD4, EP300, MOZ and KDM1A. Consistent with this, in vitro co-treatment with MI and BET, MOZ, LSD1 or CBP/p300 inhibitor induced synergistic loss of viability of AML cells with MLL1-r or mtNPM1. Co-treatment with MI and BET or CBP/p300 inhibitor also exerted significantly superior in vivo efficacy in xenograft models of AML with MLL1-r. These findings highlight novel, MI-based combinations that could prevent escape of AML stem/progenitor cells following MI monotherapy, which is responsible for therapy-refractory AML relapse.


A real-world assessment of mycophenolate mofetil for remission induction in eosinophilic granulomatosis with polyangiitis.
Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of ANCA-associated vasculitis (AAV). Clinical trials demonstrating the efficacy of mycophenolate mofetil (MMF) for remission induction in AAV excluded patients with EGPA. Despite this, MMF is commonly used in these patients. The objective of this study was to evaluate, for the first time, the effectiveness and tolerance of MMF in EGPA remission induction. A retrospective, two-center, real-world study was conducted in patients with EGPA who received MMF in addition to prednisolone for newly diagnosed or relapsing disease between 2009 and 2019. Baseline, 3-, 6- and 12-month outcome data were extracted from electronic health records. The primary outcome was disease remission, defined as a Birmingham Vasculitis Activity Score of 0 at 6 months. Secondary outcomes included disease relapse, median prednisolone dose at 12 months and drug tolerance. In total, 15 patients (73% male, median age 57) with EGPA (11 newly diagnosed/4 relapsing) were identified. At 6 months, 67% had achieved disease remission. At 12 months, this was maintained (66.7%) and 4 patients had relapsed. All but one patient remained on MMF at study completion and all patients tolerated MMF. Our real-world data suggest that MMF is an effective and well-tolerated agent for achieving disease remission in EGPA. A future randomized controlled trial of MMF in this neglected orphan disease is now warranted.


Efficacy of cotrimoxazole (Sulfamethoxazole-Trimethoprim) as a salvage therapy for the treatment of bone and joint infections (BJIs).
Cotrimoxazole (Sulfamethoxazole-Trimethoprim, SXT) has interesting characteristics for the treatment of bone and joint infection (BJI): a broad spectrum of activity with adequate bone diffusion and oral and intravenous formulations. However, its efficacy and safety in BJIs are poorly documented and its use remains limited. We conducted a retrospective study in 2 reference centers for BJIs from 2013 to 2018 among patients treated with SXT for a BJI. Data were collected from patient's medical charts. Outcomes and adverse events were evaluated at day (D)7, D45 and D90. We analyzed 51 patients with a mean age of 60 ± 20 (SD) years of which 76% presented with an orthopedic device infection (ODI). Gram-negative bacilli (GNB) were involved in 47% of BJIs (n = 24). Moreover, they were often polymicrobial infections (41%). Doses of SXT ranged from 800/160mg bid (61%; n = 31) to 800/160mg tid (39%; n = 20). Median SXT treatment duration was 45 days (IQR 40-45). SXT was part of a dual therapy in 84% of patients (n = 43), associated mainly with fluoroquinolones (n = 17) or rifampicin (n = 14). Outcome was favorable at D7 in 98% (n = 50), at D45 in 88.2% (n = 45) and at D90 in 78.4% (n = 40). The second agent combined with SXT was not an independent factor of favorable outcome (p = 0.97). Adverse events were reported in 8% (n = 4) of patients, with a median of 21 days (IQR 20-30) from SXT initiation and led to discontinuation (n = 3). SXT appears to be effective for treatment of BJIs as a salvage therapy, even in GNB or polymicrobial infection, including ODI. Further data are needed to confirm SXT efficacy as an alternative oral regimen in BJIs.


Antitumor monoclonal antibodies for radioimmunodetection of tumors and drug targeting.
Developments in hybridoma technology leading to the production of monoclonal antibodies recognizing tumor-associated antigens are providing new approaches for the radioimmunodetection of, and drug targeting to, metastases. These developments are illustrated in a series of studies on the in vivo localization of an antihuman-osteogenic sarcoma monoclonal antibody (791T/36) in human tumor xenografts maintained in immunodeprived mice. 131I-labelled 791T/36 antibody localized specifically in osteogenic sarcomas but not in xenografts of other tumors, such as bladder carcinoma T24, which do not express the antigen identified by this antibody. Developing from these studies, various parameters influencing antibody localization in tumors were examined including the kinetics of antibody uptake, the relationship between tumor size and antibody binding, and the site of antibody deposition. This provides a basis for considering the potential of antitumor monoclonal antibodies for targeting antitumor agents. Of particular importance here is the observation that antibody is principally located at the periphery of tumors since this will influence the population of cells within a tumor which can be attacked by antibody-drug or antibody-toxin conjugates. Experiments with human tumor xenografts demonstrate tumor localization of radioisotope-labelled 791T/36 monoclonal antibody. Tumor localization by external gamma camera imaging of osteogenic sarcoma xenograft-bearing mice was also demonstrated. These studies illustrate the potential of antitumor monoclonal antibodies for imaging primary and metastatic tumors. This approach is further emphasized by the radioimmunodetection of primary and metastatic colorectal carcinomas.


[Pronostic value of parenchyma renal invasion of pT3 upper tract urinary carcinoma].
Upper tract urinary carcinoma (UTUC) pT3 tumors are a heterogeneous entity including tumors invading the renal parenchyma, tumors with peripelvic fat invasion or peri-ureteral fat invasion. The aim of this study was to evaluate the prognostic significance of these three different groups of pT3 tumors. Between 1998 and 2012, 205 patients with UTUC were operated in two centers, including 52 patients with pT3 tumor stage. pT3 tumors were divided into three groups: peri-ureteral fat invasion (pT3U, n = 16), peripelvic fat invasion (pT3G, n = 21), and renal parenchyma invasion (pT3P, n = 15). The prognostic significance of the type of tumor infiltration was evaluated on specific and disease-free survival. Median follow-up was 18.9 months [6-133.4]. In univariate analysis, renal parenchyma invasion was associated with a better prognostic in both specific (P = 0.026) and disease-free survival (P = 0.031) compared with peripelvic or peri-ureteral fat invasion. Mutivariate analysis retained the pT3 subgroup as an independant prognostic factor in both specific and disease-free survival (P = 0.02). pT3 tumors with renal parenchyma invasion had a better prognosis than those with peripelvic or peri-ureteral fat invasion. The heterogeneity of the pT3 group should be taken into account to improve the care of patients.


Association between polymorphisms in the XRCC1 gene and male infertility risk: A meta-analysis.
X-ray repair cross-complementing group 1 (XRCC1) single nucleotide polymorphisms (SNPs) might correlate with male infertility susceptibility. This association has been described; however, the findings remain inconsistent. Consequently, this meta-analysis was conducted to characterize the relationship between XRCC1 SNPs and male infertility susceptibility. Studies were systematically searched in databases to evaluate the association between SNPs of XRCC1 and infertility in males. The effect measures chosen were the 95% confidence intervals (95% CIs) and odds ratios (ORs). A total of 7 studies, including 6 case-controlled studies on XRCC1 Arg399Gln and 3 case-controlled studies on XRCC1 Arg194Trp, were included. Ultimately, the results of this analysis revealed that XRCC1 Arg399Gln SNPs were significantly associated with infertility in males in homozygote comparisons (GG vs GA+AA: OR = 0.614, 95% CI: 0.40-0.937, P = .024). This meta-analysis did not demonstrate a relationship between XRCC1 Arg194Trp and male infertility risk. Our study indicated that XRCC1 Arg399Gln polymorphism was associated with a significantly decreased male infertility risk, but not XRCC1 Arg194Trp.


Reporting after sexual violence: The influence of victim, assault and perpetrator characteristics.
Sexual violence is a worldwide public health concern. Care for victims has improved with the development of sexual assault centres, which have served to professionalise and tailor care and to get different services to improve collaboration. Nonetheless, reporting rates remain low, causing perpetrators to walk free without prosecution. We aimed to investigate, firstly, the influence of victim, perpetrator and assault characteristics on the reporting rate, and, secondly, the reasons why victims did not report to the police. Data of a Dutch sexual assault centre was used in this cross-sectional study. All victims who attended the centre between January 2016 and January 2019 were included. Logistic regression analysis was used to assess the relation of certain characteristics with reporting. Forty per cent of the victims reported to the police. Age and injuries were significantly related to reporting. Victims of 26 years or over were less likely to report than victims under 18 years old. Victims with objectified injuries reported to the police more often. Contrary to previous research, no relation between the perpetrator being well-known to the victim and a lower reporting rate was found. Victims mainly refrained from reporting as they experienced conflicting emotions, followed by their feeling discouraged by the police. Other reasons were fear of the perpetrator and defamation, wanting to move on with their life and wanting to spare the perpetrator. Our findings will serve to further optimise care for victims of sexual violence and increase reporting rates.


The expression of ribonuclear protein IMP3 in laryngeal carcinogenesis.
The aim of the study was to investigate the expression of ribonuclear protein IMP3 in laryngeal carcinogenesis, together with other biomarkers of carcinogenesis (Ki-67, p53 and cyclin D1), and to evaluate their predictive values. The study included 153 patients divided into three groups: 68 operated for primary invasive laryngeal squamous cell carcinoma (LSCC); 41 with precancerous lesions of atypical and abnormal hyperplasia; 44 with hyperplastic laryngeal nodule without atypia. Tissue microarray technique was used for immunohistochemical analysis. All markers showed statistically significant differences between the three groups. The percentage of IMP3 positive cells is statistically significantly higher in LSCC group in comparison to precancerosis and control group. The percentage of Ki-67 positive cells is statistically significantly higher in LSCC group in comparison to precancerosis and control group. The percentage of p53 positive cells in LSCC group is statistically significantly higher than the control group and higher, but not statistically significant, than the precancerosis group. The percentage of cyclin D1 positive cells is statistically significantly higher in LSCC group than in precancerosis group and higher, but not statistically significant, than in the control group. All analyzed markers have good predictive values (AUC > 0.6), but the percentage of IMP3 positive cells is the only statistically significant marker in predicting whether the patient has LSCC or not. Expression of Ki-67 and pronouncedly IMP3 generally follow the same pattern where control and precancerosis are similar and LSCC significantly differs, as opposed to p53 and cyclin D1. IMP3 expression increase possibly has an important diagnostic, therapeutic (in terms of the need for additional therapy after surgery) and prognostic value. Further studies on the exact molecular mechanisms behind it are, of course, needed.


Dietary level of protein regulates glyceraldehyde-3-phosphate dehydrogenase content and synthesis rate in mouse liver cytosol.
The content of liver cytosolic proteins was studied in mice subjected to protein depletion followed by refeeding with a normal diet. Depletion elicited either the accumulation or the decrease of several polypeptides, being the early increase of a M(r) 36,000 polypeptide the most pronounced change observed. The refeeding with a normal diet for 2 days caused a return of the cytosol protein composition to that of normally fed animals. The M(r) 36,000 polypeptide was identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Its molecular weight, the sequence of its first twenty amino acid residues, its amino acid composition and its antigenic properties were found to be similar with those of GAPDH from different mammalian cells. During the first 2 days of protein depletion, both the GAPDH polypeptide content and activity increased. Thereafter, the enzymatic activity of GAPDH decreased, whereas GAPDH protein mass decreased in a lesser extent. The accumulation of GAPDH and other particular polypeptides in the cytosols of protein depleted mice was associated with an increased synthesis. The refeeding with a normal diet caused an immediate return to the synthesis pattern of normal livers.


Predictors of sedation period for critical illness patients focusing on early rehabilitation on the bed.
There are various interventions of rehabilitation on the bed, but these are time-consuming and cannot be performed for all patients. The purpose of this study was to identify the patients who require early mobilization based on the level of sedation. We retrospectively evaluated the data of patients who underwent physical therapy, ICU admission of > 48 h, and were discharged alive. Sedation was defined as using sedative drugs and a Richmond Agitation-Sedation Scale score of < - 2. Multiple regression analysis was performed using sedation period as the objective variable, and receiver operating characteristic (ROC) curve and Spearman's rank correlation coefficient were performed. Of 462 patients admitted to the ICU, the data of 138 patients were analyzed. The Sequential Organ Failure Assessment (SOFA) score and non-surgery and emergency surgery cases were extracted as significant factors. The ROC curve with a positive sedation period of more than 3 days revealed the SOFA cutoff score was 10. A significant positive correlation was found between sedation period and the initial day on early mobilization. High SOFA scores, non-surgery and emergency surgery cases may be indicators of early mobilization on the bed in the ICU.


The Use of Death Certificate Data to Characterize Mortality Associated With Respiratory Syncytial Virus, Unspecified Bronchiolitis, and Influenza in the United States, 1999-2018.
Death certificate data can improve our understanding of the mortality burden associated with respiratory syncytial virus (RSV) and influenza. We used International Classification of Diseases, Tenth Revision codes listed on death certificates to characterize deaths from 1999 to 2018 as RSV, influenza, and unspecified bronchiolitis. We described the distribution of each cause of death by age, sex, race/ethnicity, place of death, and contributing causes of death. Over the 20-year study period, RSV, bronchiolitis, and influenza were listed as the underlying causes of death on 932, 1046, and 52 293 death certificates, respectively. Children <1 year of age accounted for 39% of RSV and bronchiolitis deaths, while 72% of influenza deaths were in adults ≥65 years. Children <1 year were more likely to die outside of the hospital from RSV, bronchiolitis, or influenza compared to all causes (P < .01), and black infants had the highest mortality rate for all 3 causes. Most infants dying from RSV did not have a high-risk condition listed on the death certificate. Death certificates captured 20%-60% of estimated excess RSV-attributable mortality in infants and <1% in seniors. Thorough reporting on death certificates is an important public health goal, especially as new therapeutics become available. Infants had higher odds of dying out of hospital from respiratory pathogens compared to other causes, and race/ethnicity alone did not explain this disparity.


Upper dorsal sympathectomy.
Over a 20 year period, 60 patients underwent 76 procedures for upper dorsal sympathectomy, usually with a transaxillary approach but occasionally with an anterior approach. Procedures in male patients and in those that were carried out on the right side were most frequent. There were few simultaneous procedures. The extent of sympathectomy included resection of the lower half of the stellate ganglion through the fourth thoracic ganglion. The results were satisfying for patients with vasospastic disorders and hyperhidrosis and quite acceptable for those with causalgia and vaso-occlusive disorders. Complication rates and the incidence of postoperative Horner's syndrome were low. There were prominent differences in results among the various age groups. In addition, female patients and those with bilateral procedures had less favorable results. Factors that did not appear to affect results included technique of surgical approach, extent of sympathectomy, presence of Horner's syndrome, or the addition of other procedures. Current indications for upper dorsal sympathectomy include cases of Raynaud's and Buerger's diseases refractory to drug therapy, causalgia, vaso-occlusive disorders, and hyperhidrosis.


Extracardiac birth defects in children with congenital heart defects.
To assess the proportion and pattern of extracardiac birth defects in children with congenital heart defects referred to a tertiary care institute. Cross-sectional observational study from January 2010 to June 2011. Out of 560 children with congenital heart defects, 98 (17.5%) had extracardiac birth defects. Fifty-six had multiple congenital defects; 36 were syndromic cases and 6 had laterality defects. A total of 386 extracardiac birth defects (103 major and 283 minor) were documented, with craniofacial and skeletal birth defects being the commonest. Extracardiac birth defects are common in children with congenital heart defects.


PlasmiR: A Manual Collection of Circulating microRNAs of Prognostic and Diagnostic Value.
Only recently, microRNAs (miRNAs) were found to exist in traceable and distinctive amounts in the human circulatory system, bringing forth the intriguing possibility of using them as minimally invasive biomarkers. miRNAs are short non-coding RNAs that act as potent post-transcriptional regulators of gene expression. Extensive studies in cancer and other disease landscapes investigate the protective/pathogenic functions of dysregulated miRNAs, as well as their biomarker potential. A specialized resource amassing experimentally verified, circulating miRNA biomarkers does not exist. We queried the existing literature to identify articles assessing diagnostic/prognostic roles of miRNAs in blood, serum, or plasma samples. Articles were scrutinized in order to exclude instances lacking sufficient experimental documentation or employing no biomarker assessment methods. We incorporated information from more than 200 biomedical articles, annotating crucial meta-information including cohort sizes, inclusion-exclusion criteria, disease/healthy confirmation methods and quantification details. miRNAs and diseases were systematically characterized using reference resources. Our circulating miRNA biomarker collection is provided as an online database, plasmiR. It consists of 1021 entries regarding 251 miRNAs and 112 diseases. More than half of plasmiR's entries refer to cancerous and neoplastic conditions, 183 of them (32%) describing prognostic associations. plasmiR facilitates smart queries, emphasizing visualization and exploratory modes for all researchers.


Neural progenitor cell death is induced by extracellular ATP via ligation of P2X7 receptor.
Neural progenitor cells (NPCs) are capable of self-renewal and differentiation into neurons, astrocytes and oligodendrocytes, and have been used to treat several animal models of CNS disorders. In the present study, we show that the P2X7 purinergic receptor (P2X7R) is present on NPCs. In NPCs, P2X7R activation by the agonists extracellular ATP or benzoyl ATP triggers opening of a non-selective cationic channel. Prolonged activation of P2X7R with these nucleotides leads to caspase independent death of NPCs. P2X7R ligation induces NPC lysis/necrosis demonstrated by cell membrane disruption accompanied with loss of mitochondrial membrane potential. In most cells that express P2X7R, sustained stimulation with ATP leads to the formation of a non-selective pore allowing the entry of solutes up to 900 Da, which are reportedly involved in P2X7R-mediated cell lysis. Surprisingly, activation of P2X7R in NPCs causes cell death in the absence of pore formation. Our data support the notion that high levels of extracellular ATP in inflammatory CNS lesions may delay the successful graft of NPCs used to replace cells and repair CNS damage.


Quality of Life and Associated Factors Among Patients with Epilepsy Attending Outpatient Department of Saint Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia, 2019.
Epilepsy is strongly associated with an impaired quality of life. Patients suffering from epilepsy have a poorer quality of life than both the general population and many other chronic disease sufferers. However, attention is not given on the quality of life of people with epilepsy other than focusing on symptom reduction. This increases the frequency of seizures, impacts on the ability to perform and increases health-related costs. The aim of this study was to assess quality of life and associated factors among patients with epilepsy attending the outpatient department of Amanuel Mental Specialized Hospital, Addis Ababa, Ethiopia. An institution-based cross-sectional study design was conducted between May and June 2019 at Amanuel Mental Specialized Hospital. A systematic random sampling technique was used to get a total number of 447 samples. Data on quality of life was assessed through interviews using the World Health Organization Quality of Life-Brief (WHOQOL-BREF) Version. The collected data were coded, entered into EpiData 3.1, and analyzed by using SPSS version 20. Simple and multiple linear regression analysis models were fitted and the unstandardized β coefficient at 95% confidence interval was employed. The statistical significance was accepted at p-value <0.05. The mean score of quality of life was 61.1±11.6 (95%CI: 59.05, 61.23). Perceived stigma (β=-2.13, 95%CI:-2.96, -1.30), frequent seizure (β=-3.16, 95%CI: -4.27, -2.04), AED adherence (β=1.24, 95%CI: 1.10, 1.30), antiepileptic drug side effect (β=-0.32, 95%CI: -0.38, -0.26), anxiety (β-1.91, 95%CI: -2.95, -0.86), depression (β=-3.59, 95%CI: -4.67, -2.52), poor social support (β=-2.51, 95%CI: -3.62, -1.40) and moderate social support (β=-1.60, 95%CI: -2.58, -0.62) were significantly associated factors with quality of life. The finding from this study indicated that quality of life of patients with epilepsy were moderate. Perceived stigma, frequent seizure, comorbid depression and anxiety, antiepileptic drug nonadherence, antiepileptic drug side effect and poor social support were the predictors of quality of life.


A Contemporary Analysis of Urethral Recurrence following Radical Cystectomy.
Oncologic outcomes following urethral recurrence (UR) remain incompletely described, with reports limited by small cohort sizes. We evaluated risk factors for UR as well as cancer-specific survival (CSS) and overall survival (OS) among patients with UR. We reviewed our institutional radical cystectomy (RC) registry to identify patients with UR. Cox proportional hazards regression was used to assess risk factors for UR. Kaplan-Meier and Cox models were used to assess the relationship between UR and CSS/OS as well as to compare outcomes following symptomatic vs asymptomatic presentation of UR. Overall, 2,930 patients underwent RC from 1980 to 2018, with a median postoperative followup of 7.1 years (IQR 2.8-13.1), of whom 144 (4.9%) were subsequently diagnosed with UR. Carcinoma in situ (HR 1.98, 95% CI 1.30-3.04), multifocal disease (HR 1.59, 95% CI 1.07-2.36) and prostatic urethral involvement at RC (HR 3.01, 95% CI 1.98-4.57) were associated with increased risk of UR. UR was associated with decreased CSS (HR 7.30, 95% CI 5.46-9.76) and OS (HR 1.86, 95% CI 1.54-2.24). A total of 63/144 patients were diagnosed with UR based on symptoms, while 104/144 patients with UR underwent urethrectomy. Patients with symptomatic UR had higher tumor stage at urethrectomy (≥pT2 in 13.1% vs 3.1%, p=0.007), while patients with asymptomatic UR experienced longer median CSS (12.1 vs 6.1 years) and OS (8.30 vs 4.82 years; p=0.05 for both). We identified pathological risk factors for UR after RC and report adverse subsequent survival outcomes for these patients. Presentation with symptomatic UR was associated with higher tumor stage and poorer prognosis, supporting a value to continued urethral surveillance after RC.


Baicalin attenuated Mycoplasma gallisepticum-induced immune impairment in chicken bursa of fabricius through modulation of autophagy and inhibited inflammation and apoptosis.
Mycoplasma gallisepticum (MG) is the primary etiologic agent of chronic respiratory disease in poultry. However, the mechanism underlying MG-induced immune dysregulation in chicken is still elusive. Baicalin shows excellent anti-bacterial, anti-inflammatory, anti-carcinogenic and anti-viral properties. In the present study, the preventive effects of baicalin against immune impairment in chicken bursa of fabricius (BF) were studied in an MG infection model. Histopathological examination showed increased inflammatory cell infiltrations and fragmented nuclei in the model group. Ultrastructural analysis revealed the phenomenon of apoptosis in bursal cells, along with the deformation of mitochondrial membrane and swollen mitochondria in the model group. However, these abnormal morphological changes were partially alleviated by baicalin. Meanwhile, baicalin treatment attenuated the level of proinflammatory cytokines, and suppressed nuclear factor-kappa B expression at both protein and mRNA level. Terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling assay showed extensive apoptosis in BF in the model group. The mRNA and protein expression levels of apoptosis-related genes were upregulated in BF, while baicalin treatment significantly alleviated apoptosis in BF. In addition, alterations in mRNA and protein expression levels of autophagy-related genes and mitochondrial dynamics proteins were significantly alleviated by baicalin. Moreover, baicalin treatment significantly attenuated MG-induced decrease in CD8+ cells and reduced bacterial load in chicken BF compared to the model group. These results suggested that baicalin could effectively inhibit MG-induced immune impairment and alleviate inflammatory responses and apoptosis in chicken BF. © 2020 Society of Chemical Industry.


A single cDNA encodes all three Aedes leucokinins, which stimulate both fluid secretion by the malpighian tubules and hindgut contractions.
A cDNA encoding preproleucokinin was isolated from a cDNA library of the mosquito Aedes aegypti. The deduced amino acid sequence of Aedes preproleucokinin contains a putative signal peptide of 18 amino acid residues and a 210-amino acid residue proleucokinin. Within the proleucokinin are encoded one copy each of the Aedes leucokinins 1, 2, and 3 isolated previously from this species (Veenstra, J. A. (1994) Biochem. Biophys. Res. Commun. 202, 715-719). All three Aedes leucokinins depolarize the transepithelial voltage of the malpighian tubule in concentrations of less than 10(-9) M and increase the frequency of hindgut contractions at concentrations above 10(-8) M. At higher concentrations the Aedes leucokinins 1 and 3 but not Aedes leucokinin 2 are also able to increase the rate of fluid secretion by the malpighian tubules. The differences of the three Aedes leucokinins in their potencies to induce fluid secretion or depolarizations in the malpighian tubules suggest that there may be more than one type of leucokinin receptor in this tissue.


Decentralisation and its implications for reproductive health: the Philippines experience.
Decentralisation is one of the most common health sector reforms initiated in developing countries in the 1980-90s. Although decentralisation is often politically driven, it can significantly improve health sector performance. However, the early phase of the Philippines experience indicates that decentralisation in and of itself does not always improve the efficiency, equity and effectiveness of the health sector. Instead, it can exacerbate inequities, weaken local commitment to priority health issues and decrease the efficiency and effectiveness of service delivery by disrupting the referral chain. Such effects pose a particularly serious threat to accessibility and delivery of reproductive health services, some of which (e.g. family planning) are controversial and thus susceptible to local pressures, and others of which (e.g. emergency obstetric care) require a functioning and effective health system. Moreover, those undertaking decentralisation need to take account of the impacts of non-health factors as well as other reforms that interact with decentralisation to affect accessibility, affordability and quality of services, including for reproductive health. The Philippines experience also demonstrates that authority should be shared between the centre and local units in order to achieve national health objectives and respond to local health needs. Adjustments must be made during implementation to correct for both emerging and pre-existing problems.


Comparison of Clinicopathologic and Oncological Outcomes Between Transurethral En Bloc Resection and Conventional Transurethral Resection of Bladder Tumor: A Systematic Review, Meta-Analysis, and Network Meta-Analysis with Focus on Different Energy Sources.
Introduction: It has been hypothesized that transurethral en bloc (TUEB) of bladder tumor offers benefits over conventional transurethral resection of bladder tumor (cTURBT). This study aimed to compare disease outcomes of TUEB and cTURBT with focus on the different energy sources. Methods: A systematic search was performed using PubMed and Web of Science databases in June 2021. Studies that compared the pathological (detrusor muscle presence), oncological (recurrence rates) efficacy, and safety (serious adverse events [SAEs]) of TUEB and cTURBT were included. Random- and fixed-effects meta-analytic models and Bayesian approach in the network meta-analysis was used. Results: Seven randomized clinical trials (RCTs) and seven non-RCTs (NRCT), with a total of 2092 patients. The pooled 3- and 12-month recurrence risk ratios (RR) of five and four NRCTs were 0.46 (95% CI 0.29-0.73) and 0.56 (95% CI 0.33-0.96), respectively. The pooled 3- and 12-month recurrence RRs of four and seven RCTs were 0.57 (95% CI 0.25-1.27) and 0.89 (95% CI 0.69-1.15), respectively. The pooled RR for SAEs such as prolonged hematuria and bladder perforation of seven RCTs was 0.16 (95% CI 0.06-0.41) in benefit of TUEB. Seven RCTs (n = 1077) met our eligibility criteria for network meta-analysis. There was no difference in 12-month recurrence rates between hybridknife, laser, and bipolar TUEB compared with cTURBT. Contrary, laser TUEB was significantly associated with lower SAEs compared with cTURBT. Surface under the cumulative ranking curve ranking analyses showed with high certainty that laser TUEB was the best treatment option to access all endpoints. Conclusion: While NRCTs suggested a recurrence-free benefit to TUEB compared with cTURBT, RCTs failed to confirm this. Conversely, SAEs were consistently and clinically significantly better for TUEB. Network meta-analyses suggested laser TUEB has the best performance compared with other energy sources. These early findings need to be confirmed and expanded upon.


Endoscopic treatment of juvenile nasopharyngeal angiofibromas: our experience and review of the literature.
The endoscopic resection of juvenile nasopharyngeal angiofibroma (JNA) emerges as an alternative approach to open procedures due to reduced morbidity and comparable recurrence rates. The purpose of this study was to present our experience with the endoscopic management of JNA using retrospective chart review of ten male patients (mean age 15.7 years) with JNA who were treated endoscopically at our institution between the years 2003 and 2010. According to the Radkowski's system, one patient was at stage Ia, two at stage Ib, one at stage IIa, two at stage IIb, two at stage IIc (infratemporal fossa invasion) and two at stage IIIa (clivus erosion). Six patients underwent preoperative embolization. The endoscopic treatment involved total ethmoidectomy, middle meatal antrostomy, sphenoidotomy, clipping of the sphenopalatine artery and its branches and drilling of the pterygoid basis. All patients underwent magnetic resonance imaging 3 months postoperatively and then if indicated clinically. Mean follow-up was 23.7 months (range 3-70). All but one patient were free of macroscopic disease. A patient with stage IIb JNA developed a recurrence after 9 months. The residual tumor was resected endoscopically and the sphenopalatine foramen widened by drilling. The patient is free of disease 25 months postoperatively. The intra-operative blood loss was not excessive (200-800 ml, mean: 444 ml) and no patient required a blood transfusion. Patients were discharged after 4-8 days (mean 5 days). One patient developed postoperative infraorbital nerve hypoesthesia. Results showed that endoscopic treatment of stage I and IIa/b JNA is a valid alternative to external approaches. For select tumors with limited infratemporal fossa invasion and skull base erosion, the endoscopic approach may also be indicated. It is a safe and effective treatment modality due to the lack of external scars, minimal bone resection and blood loss and low recurrence rate.


Mathematical modelling of haemorrhagic transformation after ischaemic stroke.
With an increasingly elderly population globally, the impacts of cerebrovascular diseases, such as stroke and dementia, become increasingly significant. Haemorrhagic transformation (HT) is one of the most common complications of ischaemic stroke that is caused by dysfunction of endothelial cells in the blood-brain barrier (BBB) and that can be exacerbated by thrombolytic therapy. Recent studies also suggest that HT can lead to an increase in intracranial pressure (ICP) and result in capillary compression. The aim of this study is to develop a mathematical model that can be used to simulate the consequence of HT over a range of vasculature length scales. We use a 2D vasculature model to investigate the severity of HT with different vascular geometry. The resulting model shows that the haematoma radius is approximately constant across different length scales (100-1000μm) and in good agreement with the available experimental data. In addition, this study identified that the effects of capillary compression do appear to have a significant impact on the leakage fraction of blood and hence act to restrain the development of a haematoma.


Dpp signalling orchestrates dorsal closure by regulating cell shape changes both in the amnioserosa and in the epidermis.
During the final stages of embryogenesis, the Drosophila embryo exhibits a dorsal hole covered by a simple epithelium of large cells termed the amnioserosa (AS). Dorsal closure is the process whereby this hole is closed through the coordination of cellular activities within both the AS and the epidermis. Genetic analysis has shown that signalling through Jun N-terminal Kinase (JNK) and Decapentaplegic (Dpp), a Drosophila member of the BMP/TGF-beta family of secreted factors, controls these activities. JNK activates the expression of dpp in the dorsal-most epidermal cells, and subsequently Dpp acts as a secreted signal to control the elongation of lateral epidermis. Our analysis shows that Dpp function not only affects the epidermal cells, but also the AS. Embryos defective in Dpp signalling display defects in AS cell shape changes, specifically in the reduction of their apical surface areas, leading to defective AS contraction. Our data also demonstrate that Dpp regulates adhesion between epidermis and AS, and mediates expression of the transcription factor U-shaped in a gradient across both the AS and the epidermis. In summary, we show that Dpp plays a crucial role in coordinating the activity of the AS and its interactions with the LE cells during dorsal closure.


Echocardiographic Evaluation of Left and Right Ventricular Function in Patients with Coronary Slow Flow Syndrome: A Comparative Study.
The Coronary Slow Flow Phenomenon is a syndrome of normal coronary anatomy and delayed progression of contrast medium through the coronary vessels. This research attempts to analyze and compare the systolic and diastolic function of the left and right ventricle in primary Slow Flow and Normal Coronary Flow.Two groups of primary Slow Coronary Flow (33 people) and Normal Coronary Flow (11 people) were included and the systolic and diastolic function of the ventricles was analyzed and compared between them.In the control group 18% of patients had mild and in the case group 24.2% mild, and 3.1% had moderate left ventricular diastolic dysfunction (P >0.05). The frequency distribution of the left and right ventricular systolic dysfunction was similar in the two groups.There was no statistically significant difference between two groups and in the association of cardiac dysfunction, it may be reasonable to investigate other causes.


[Applications of functional materials-based solid phase microextraction technique in forensic science].
Sample extraction is a crucial step in forensic analysis, especially when dealing with trace and ultra-trace levels of target analytes present in various complex matrices (e. g., soil, biological samples, and fire debris). Conventional sample preparation techniques include Soxhlet extraction and liquid-liquid extraction. However, these techniques are tedious, time-consuming, labor-intensive and require large amounts of solvents, which poses a threat to the environment and health of researchers. Moreover, sample loss and secondary pollution can easily occur during the preparation procedure. Conversely, the solid phase microextraction (SPME) technique either requires a small amount of solvent or no solvent at all. Its small and portable size, simple and fast operation, easy-to-realize automation, and other characteristics thus make it a widely used sample pretreatment technique. More attention was given to the preparation of SPME coatings by using various functional materials, as commercialized SPME devices used in early studies were expensive, fragile, and lacked selectivity. Examples of those functional materials include metal-organic frameworks, covalent organic frameworks, carbon-based materials, molecularly imprinted polymers, ionic liquids, and conducting polymers, all widely used in environmental monitoring, food analysis, and drug detection. However, these SPME coating materials have relatively few applications in forensics. Given the high potential of SPME technology for the in situ and efficient extraction of samples from crime scenes, this study briefly introduces functional coating materials and summarizes the applications of SPME coating materials for the analysis of explosives, ignitable liquids, illicit drugs, poisons, paints, and human odors. Compared to commercial coatings, functional material-based SPME coatings exhibit higher selectivity, sensitivity, and stability. These advantages are mainly achieved through the following approaches: First, the selectivity can be improved by increasing the π-π, hydrogen bonds, and hydrophilic/hydrophobic interactions between the materials and analytes. Second, the sensitivity can be improved by using porous materials or by increasing their porosity. Third, thermal, chemical, and mechanical stability can be improved by using robust materials or fixing the chemical bonding between the coating and substrate. In addition, composite materials with multiple advantages are gradually replacing the single materials. In terms of the substrate, the silica support was gradually replaced by the metal support. This study also outlines the existing shortcomings in forensic science analysis of functional material-based SPME techniques. First, the application of functional material-based SPME techniques in forensic science remains limited. On one hand, the analytes are narrow in scope. As far as explosive analysis is concerned, functional material-based SPME coatings are mainly applied to nitrobenzene explosives, while other categories, such as nitroamine and peroxides, are rarely or never involved. Research and development of coatings is insufficient and the application of COFs in forensic science has not yet been reported. Second, functional material-based SPME coatings have not been commercialized as they don't yet have inter-laboratory validation tests or established official standard analytical methods. Therefore, some suggestions are proposed for the future development of forensic science analyses of functional material-based SPME coatings. First, research and development of functional material-based SPME coatings, especially fiber coatings with broad-spectrum applicability and high sensitivity, or outstanding selectivity for some compounds, is still an important direction for SPME future research. Second, a theoretical calculation of the binding energy between the analyte and coating was introduced to guide the design of functional coatings and improve the screening efficiency of new coatings. Third, we expand its application in forensic science by expanding the number of analytes. Fourth, we focused on the promotion of functional material-based SPME coatings in conventional laboratories and established performance evaluation protocols for the commercialization of functional material-based SPME coatings. This study is expected to serve as a reference for peers engaged in related research.