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Using numerical continuation software with parameter values estimated from phage-microbe systems, we obtain two parameter bifurcation diagrams that divide parameter space into regions with different dynamical outcomes. We thus investigate how varying different parameters, including how the time spent in the eclipse phase, can influence whether or not the virus survives.

Histopathological or intracoronary image assessment of healed plaques (HPs) has been reported. However, the lesion characteristics of HPs remains undetermined yet. We assessed the healed plaque components in patients with coronary artery lesions using multiple imaging modalities.

We enrolled 33 stable angina pectoris (SAP) patients with 36 native coronary culprit lesions with angiography severe stenosis and without severe calcification undergoing pre-intervention optical coherence tomography (OCT) and coronary angioscopy (CAS). HPs were defined as layered phenotype on OCT. Lesion morphologies and plaque characteristics of HPs were assessed using OCT and CAS.

HPs were observed in 19 lesions (52.8%). HP lesions had higher frequent B2/C lesions (89.4% vs. 52.9%, p = 0.02), worse pre-PCI coronary flow (corrected thrombolysis in myocardial infarction count 21.6 ± 13.5 vs. 13.8 ± 6.2, p = 0.047) and greater lumen-area stenosis (79.6 ± 10.6% vs. 68.0 ± 21.6%, p = 0.047) than non-HP lesions. HP lesions had higher prevalence of OCT-thin-cap fibroatheroma (TCFA) (31.6% vs. 0.0%, p = 0.02), OCT-macrophage (89.5% vs. 41.2%, p = 0.004), and CAS-red thrombus (89.5% vs. 41.2%, p = 0.004) than non-HP lesions. The combination of 3 features including OCT-TCFA, macrophages, and CAS-red thrombus showed higher predictive valuer for HPs on OCT than each single variable. Post-PCI irregular tissue protrusion was more frequently observed in lesions with HPs than in those without (52.6% vs. 13.3%, p = 0.03).

SAP lesions with HPs might have more frequent vulnerable plaques with intraplaque inflammation and thrombus than those without, suggesting that layered phenotype on OCT might reflect not only healing process but also potential risks for future coronary events.

SAP lesions with HPs might have more frequent vulnerable plaques with intraplaque inflammation and thrombus than those without, suggesting that layered phenotype on OCT might reflect not only healing process but also potential risks for future coronary events.Stent implantation in bifurcated coronary lesions is technically challenging so that procedural refinements are continuously investigated. Novel procedure modeling and intracoronary imaging techniques may offer critical insights on stent deformations and stent-wall interactions during bifurcation stenting procedures. Thus, we assessed coronary bifurcation stenting techniques using multimodal imaging and 3D modeling in reanimated swine hearts. Harvested swine hearts were reanimated using Visible Heart® methodologies and (under standard fluoroscopic guidance) used to test 1-stent (provisional and inverted provisional) and 2-stent (culotte, TAP and DK-crush) techniques on bifurcations within various coronary vessels using commercially available devices. Intracoronary angioscopy and frequency-domain optical-coherence-tomography (OCT) were obtained during the procedures. 3D OCT reconstruction and micro-computed tomography 3D modeling (post heart fixations) were used to assess stent deformations and stent-wall interactions. We conducted multiple stenting procedures and collected unique endoscopic and OCT images (and subsequent computational models from micro-CT) to assess stent deformations and device/wall interactions during different steps of bifurcation stenting procedures. Endoscopy, micro-CT and virtual reality processing documented that different 1- and 2-stent techniques, practiced according to experts' recommended steps, achieve optimal post-intervention stent conformation. As compared with intra-procedural endoscopy, software-generated 3D OCT images accurately depicted stent deformations during 1-stent techniques. On the opposite, during more complex 2-stent techniques, some defects were appreciated at 3D OCT reconstruction despite optimal 2D OCT images. This study provided unique insights regarding both stent deformations occurring in the course of bifurcation stenting and the efficacy of OCT to visualize them.Mitogen-activated protein kinases (MAPKs) are evolutionarily conserved signaling proteins involved in the regulation of most eukaryotic cellular processes. They are downstream components of essential signal transduction pathways activated by the external stimuli, in which the signal is conveyed through phosphorylation cascades. The excellent genetic and biochemical tractability of simple eukaryotes such as Saccharomyces cerevisiae has significantly contributed to gain fundamental information into the physiology of these key proteins. The budding yeast MAPK Slt2 was identified 30 years ago and was later revealed as a fundamental element of the cell wall integrity (CWI) pathway, one of the five MAPK routes of S. cerevisiae. As occurs with other MAPKs, whereas Slt2 displays the core typical structural traits of eukaryotic protein kinases, it also features conserved domains among MAPKs that allow an exquisite spatio-temporal regulation of their activity and binding to activating kinases, downregulatory phosphatases, or nuclear transcription factors. Additionally, Slt2 bears a regulatory extra C-terminal tail unique among S. cerevisiae MAPKs. Here, we review the structural and functional basis for the signaling role of Slt2 in the context of the molecular architecture of this important family of protein kinases.The years 2020 and 2021 have witnessed a COVID-19 pandemic caused by the SARS-CoV-2 virus. However, these years have also witnessed certain remarkable scientific achievements. Researchers across the globe have been trying extremely hard and accomplished in bringing vaccines a great variety of COVID-19 vaccines. Though the route of administration for the majority of these vaccines has been the intramuscular route (invasive), some laboratories are developing formulations intended for transmucosal and transcutaneous (non-invasive) administration, which are in the early phases of pre-clinical and clinical development. This short report discusses these unconventional formulations against COVID-19, in brief, to stress the importance of research in the field of drug delivery.Cenobamate is one of the latest antiseizure medications (ASMs) developed for the treatment of focal onset seizures in adult patients. The recommended starting dose is 12.5 mg/day, titrated gradually to the target daily dose of 200 mg, which may be increased to a maximum of 400 mg/day based on clinical response. Although the high rate of seizure freedom observed in randomized, placebo-controlled clinical trials has resulted in exciting expectations, further clinical studies are needed to better define its clinical profile. Cenobamate is characterized by a peculiar pharmacology regarding both pharmacodynamics and pharmacokinetics. The mechanism of action has only partly been described, with the drug acting on voltage-gated sodium channels through a pronounced action on persistent rather than transient currents. Cenobamate also acts as a positive allosteric modulator of GABAA receptors independently from the benzodiazepine binding site. The bioavailability of cenobamate is not influenced by other drugs, except pntriguing and not fully understood mechanism of action; pharmacokinetic issues need to be considered in clinical practice.

Malignant melanoma is the third most common primary in the diagnosis of brain metastases. Stereotactic radiosurgery (SRS) is a well-established treatment option in limited brain disease. We analyzed outcomes of SRS with a particular focus on the graded prognostic assessment (GPA, melanoma molGPA), prognostic factors, and toxicity.

We evaluated 173 brain metastases in 83 patients with malignant melanoma. All were treated with SRS median dose of 20Gy prescribed to the 80 or 100% isodose line between 2002 and 2019. All patients were followed-up regularly, including contrast-enhanced brain imaging as well as clinical examination, initially 6weeks after treatment, then in quarterly follow-up.

The median age was 61years (range 27-80); 36 female and 47 male patients were treated. After a median follow-up of 5.7months, median OS (overall survival) was 9.7months 95%-KI 4.7-14.7). LC (local control) at 6months, 12, 24months was 89%, 86%, and 72%, respectively (median was not reached). Median DBC (distant brain coshould be considered.Organic cation transporters 1-3 (OCT1-3, SLC22A1-3) and the plasma membrane monoamine transporter (PMAT, SLC29A4) play a major role in maintaining monoaminergic equilibrium in the central nervous system. With many psychoactive substances interacting with OCT1-3 and PMAT, a growing literature focuses on characterizing their properties via in vitro and in vivo studies. In vitro studies mainly aim at characterizing compounds as inhibitors or substrates of murine, rat, and human isoforms. The preponderance of studies has put emphasis on phenylalkylamine derivatives, but ketamine and opioids have also been investigated. Studies employing in vivo (knockout) models mostly concentrate on the interaction of psychoactive substances and OCT3, with an emphasis on stress and addiction, pharmacokinetics, and sensitization to psychoactive drugs. The results highlight the importance of OCT3 in the mechanism of action of psychoactive compounds. Concerning in vivo studies, a veritable research gap concerning OCT1, 2, and PMAT exists. This review provides an overview and summary of research conducted in this field of research.Bistable switch-like behavior is a ubiquitous feature of gene regulatory networks with decision-making capabilities. Type II toxin-antitoxin (TA) systems are hypothesized to facilitate a bistable switch in toxin concentration that influences the dormancy transition in persister cells. However, a series of recent retractions has raised fundamental questions concerning the exact mechanism of toxin propagation in persister cells and the relationship between type II TA systems and cellular dormancy. Through a careful modeling search, we identify how sp bistablilty can emerge in type II TA systems by systematically modifying a basic model for the RelBE system with other common biological mechanisms. Our systematic search uncovers a new combination of mechanisms influencing bistability in type II TA systems and explores how toxin bistability emerges through synergistic interactions between paired type II TA systems. Our analysis also illustrates how Descartes' rule of signs and the resultant can be used as a powerful delineator of bistability in mathematical systems regardless of application.Designing new types of drugs with preferred properties against cancer is a great issue for scientists dealing with synthesis and study of biological activity. Several organometallic compounds used in chemotherapy reveal side effects. Peptides from edible sources having no side effects may play a transport role in the delivery of anticancer metal ions into targeted tumor cells. For the last two decades, peptide-metal complexes have been considered as potential anticancer agents. In this work, oxovanadium complexes of peptides from Chickpea (Cicer arietinum L.) seeds' protein hydrolysate were investigated. The albumin fraction of Chickpea seeds protein was hydrolyzed with a combination of enzymes papain, trypsin, and alcalase. The hydrolysate was combined with vanadyl ions and obtained oxovanadium complexes were studied by FTIR, SEM-EDX, and TG-DSC analyses, and cell inhibition activity against A549 cells was detected by MTT Assay. In a result, activity of the complexes (IC50 = 14.39 µg/mL) increased 1.7-fold compared to the activity of inorganic salt of vanadium (IC50 = 24.75 µg/mL) against A549 cells. The complexes (CPH-V) were fractionated through Sephadex G-15, and the second active fraction, named CPH-V G15-II was studied by nano-Q-TOF LC/MS. Nine peptides with a molecular mass range of 437-1864 Da were identified. Seven of them were theoretically considered as cell-penetrating peptides. These results could serve first steps for deeper fundamental research on food-derived peptide-vanadium complexes.In recent years, the incidence of fatigue has been increasing, and the effective prevention and treatment of fatigue has become an urgent problem. As a result, the genetic research of fatigue has become a hot spot. Transcriptome-level regulation is the key link in the gene regulatory network. The transcriptome includes messenger RNAs (mRNAs) and noncoding RNAs (ncRNAs). MRNAs are common research targets in gene expression profiling. Noncoding RNAs, including miRNAs, lncRNAs, circRNAs and so on, have been developed rapidly. Studies have shown that miRNAs are closely related to the occurrence and development of fatigue. MiRNAs can regulate the immune inflammatory reaction in the central nervous system (CNS), regulate the transmission of nerve impulses and gene expression, regulate brain development and brain function, and participate in the occurrence and development of fatigue by regulating mitochondrial function and energy metabolism. LncRNAs can regulate dopaminergic neurons to participate in the occurrence ze the relationship between miRNAs, lncRNAs and circRNAs in ncRNAs and fatigue, and focus on exploring the regulatory role of the miRNA-centered ceRNA regulatory network in the occurrence and development of fatigue, in order to gain a comprehensive, in-depth and new understanding of the essence of the fatigue gene regulatory network.

Photoacoustic tomography (PAT) is a novel imaging technique that can spatially resolve both morphological and functional tissue properties, such as vessel topology and tissue oxygenation. While this capacity makes PAT a promising modality for the diagnosis, treatment, and follow-up of various diseases, a current drawback is the limited field of view provided by the conventionally applied 2D probes.

In this paper, we present a novel approach to 3D reconstruction of PAT data (Tattoo tomography) that does not require an external tracking system and can smoothly be integrated into clinical workflows. It is based on an optical pattern placed on the region of interest prior to image acquisition. This pattern is designed in a way that a single tomographic image of it enables the recovery of the probe pose relative to the coordinate system of the pattern, which serves as a global coordinate system for image compounding.

To investigate the feasibility of Tattoo tomography, we assessed the quality of 3D image reconstruction with experimental phantom data and in vivo forearm data. The results obtained with our prototype indicate that the Tattoo method enables the accurate and precise 3D reconstruction of PAT data and may be better suited for this task than the baseline method using optical tracking.

In contrast to previous approaches to 3D ultrasound (US) or PAT reconstruction, the Tattoo approach neither requires complex external hardware nor training data acquired for a specific application. It could thus become a valuable tool for clinical freehand PAT.

In contrast to previous approaches to 3D ultrasound (US) or PAT reconstruction, the Tattoo approach neither requires complex external hardware nor training data acquired for a specific application. It could thus become a valuable tool for clinical freehand PAT.

Psychological distress is common in patients with cancer, and oncology providers are often tasked with utilizing psychotropic medications to treat such symptoms.

This study aims to characterize how oncology providers prescribe psychotropic medications and to assess their comfort level with prescribing these medications.

A cross-sectional survey was sent to oncology medical doctors, nurse practitioners, and physician assistants who prescribe psychotropic medications to patients with cancer at a large academic medical center in the Mountain West. The survey included questions regarding provider subspecialty, degree, comfort with prescribing psychotropic medications, and factors that informed their prescribing.

Oncology providers (n = 65) reported equal proportions of comfort and discomfort with prescribing psychotropic medications. The medication class with the most prescribers was benzodiazepines, with 89.2% (n = 58) of the respondents prescribing those medications. The least prescribed category was moal training and continued education throughout their oncology careers. A clinical pathway for prescribing psychotropic medications with resources to connect patients to long-term mental health care may also increase prescribing comfort.

The aim of this study was to investigate the therapies administered to Italian adolescents with primary herpetic gingivostomatitis (PHGS) METHODS The medical records of 74 adolescents with PHSG were reviewed. The following data were recorded age, gender, day of onset, type of treatment, lesions' severity, pain scoring, eating, and drinking ability. The oral examination was performed at the first evaluation (T0) and after one week (T1).

All patients showed up at the first visit at least 48h after the onset of symptoms. No patient was prescribed an antiviral therapy. An antibiotic therapy was prescribed in order to prevent secondary bacterial infections. Fifteen patients had been treated with non alcoholic chlorhexidine rinses (group A), 29 patients with non alcoholic chlorhexidine rinses plus hyaluronic acid gel (group B); 30 patients with non alcoholic chlorhexidine rinses plus Mucosyte® (group C). A significant improvement of the pain scoring and lesions' severity was noted in group C.

In Italian adolescents, PHGS is diagnosed at least 48h after onset and the antibiotic therapy is widely prescribed in order to prevent overinfections. Among topical therapies, an association of verbascoside and sodium hyaluronhate seems to favour a faster healing.

In Italian adolescents, PHGS is diagnosed at least 48 h after onset and the antibiotic therapy is widely prescribed in order to prevent overinfections. Among topical therapies, an association of verbascoside and sodium hyaluronhate seems to favour a faster healing.

The National Institute for Clinical Excellence recommends the use of tumour profiling tests to guide adjuvant chemotherapy in breast cancer. The Oncotype DX™ score (Genomic Health) has superseded more traditional tools such as PREDICT in appropriate patients (ER + ve, HER2-ve, lymph node negative and with a Nottingham Prognostic Index [NPI] ≥ 3.4). The aim of this study was to see whether the introduction of Oncotype DX within our institution resulted in an overall reduction in rates of chemotherapy.

Data was collected retrospectively using the Somerset Cancer Register, Pathology department databases and the institution's own online medical records system. Two groups were compared (1) pre-oncotype (Jan 2012-Dec 2014) and (2) post-oncotype (Jan 2016-July 2018).

During the pre-oncotype period, 28/82 (34%) patients who would have been eligible for testing (patients who were ER + ve, HER2-ve, and a NPI ≥ 3.4) received chemotherapy compared to 34/135 (25%) who were sent for oncotype during the second study pn patients who will derive little benefit.

The incidence of obstructive sleep apnea (OSA) immediately after surgery in patients with dentofacial deformities without previous OSA remains unknown. We aimed to perioperatively evaluate factors associated with oxygen desaturation index (ODI) during sleep, 7days after bilateral splitting ramus osteotomy (BSSRO) in patients without previous OSA.

Fifty-one patients (15 males, 36 females) with dentofacial deformities, scheduled to undergo BSSRO, were included. Polysomnography was performed before orthognathic surgery. Perioperative OSA was evaluated with peripheral arterial tonometry on the day of surgery and 1, 2, 3, 4, and 7days postoperatively. Rapid eye movement (REM) sleep periods and the ODI were measured. Factors associated with perioperative ODI after surgery were statistically analyzed.

REM sleep periods were significantly decreased on the day of surgery and significantly increased at 4 and 7days postoperatively, compared to the preoperative period. ODI increased on the day of surgery, decreased after 1day, and increased again at 4 and 7days postoperatively. ODI on the day of surgery was significantly increased due to increased preoperative ODI, overjet, and SN-MP angle and decreased SNA and SNB angle. ODI at 7days postoperatively was significantly increased due to increased REM sleep periods and decreased SN-MP and gonial angle. ODI was increased in response to REM sleep periods 7days after BSSO.

Airway management in patients with dentofacial deformity should be given more attention by preoperative assessment for OSA, even in the absence of previous OSA, until 7days postoperatively due to REM rebound.

Airway management in patients with dentofacial deformity should be given more attention by preoperative assessment for OSA, even in the absence of previous OSA, until 7 days postoperatively due to REM rebound.Polycystic ovary syndrome (PCOS) is an endocrine disorder and affects 5-10% of reproductive-age women. Chronic anovulation, polycystic ovaries, and hyperandrogenism are the important features of this syndrome. Furthermore, hyperinsulinemia and central obesity are frequent in PCOS women. In recent years, noncoding RNAs detection provided new ideas to explain the etiology of female reproductive disorders. Long noncoding RNAs (lncRNAs) as a subset of noncoding RNAs are associated with the pathogenesis of manifold reproductive-related disorders. Various investigations emphasized the potential involvement of lncRNAs in PCOS development. Therefore, in this paper, we will summarize the function of numerous lncRNAs in the apoptosis and proliferation of granulosa cells (GCs), insulin resistance (IR), and steroidogenesis in PCOS.Psychotic experiences can occur in autism spectrum disorders (ASD). Some of the ASD individuals with these experiences may fulfil Clinical High-Risk for Psychosis (CHR-P) criteria. A systematic literature search was performed to review the information on ASD and CHR-P. A meta-analysis of the proportion of CHR-P in ASD was conducted. The systematic review included 13 studies. The mean age of ASD individuals across the included studies was 11.09 years. The Attenuated Psychosis Syndrome subgroup was the most frequently reported. Four studies were meta-analysed, showing that 11.6% of CHR-P individuals have an ASD diagnosis. Symptoms of prodromal psychosis may be present in individuals with ASD. The transition from CHR-P to psychosis is not affected by ASD.Scientific evidence suggests that Saharan dust intrusions in Southern Europe contribute to the worsening of multiple pathologies and increase the concentrations of particulate matter (PM) and other pollutants. However, few studies have examined whether Saharan dust intrusions influence the incidence and severity of COVID-19 cases. To address this question, in this study we carried out generalized linear models with Poisson link between incidence rates and daily hospital admissions and average daily concentrations of PM10, NO2, and O3 in nine Spanish regions for the period from February 1, 2020 to December 31, 2020. The models were adjusted by maximum daily temperature and average daily absolute humidity. Furthermore, we controlled for trend, seasonality, and the autoregressive nature of the series. The variable relating to Saharan dust intrusions was introduced using a dichotomous variable, NAF, averaged across daily lags in ranges of 0-7 days, 8-14 days, 14-21 days, and 22-28 days. The results obtained in this study suggest that chemical air pollutants, and especially NO2, are related to the incidence and severity of COVID-19 in Spain. Furthermore, Saharan dust intrusions have an additional effect beyond what is attributable to the variation in air pollution; they are related, in different lags, to both the incidence and hospital admissions rates for COVID-19. These results serve to support public health measures that minimize population exposure on days with particulate matter advection from the Sahara.The bacterial leaf blight in rice caused by Xanthomonas oryzae pv. oryzae (Xoo) affects crop losses worldwide. In spite of developing resistant varieties by introgressing different Xa genes, the occurrence of diseases is evident. Here we report identification of several genes that are associated with improved plant immunity against Xoo in a resistant genotype BPT-5204 in comparison with susceptible genotype TN-1. The RNA sequencing information was developed to identify the genes that could provide durable resistance in rice. Xoo-resistant rice genotype BPT-5204 with Xa 5, 13 and 21 genes is compared with sensitive Taichung Native 1 (TN-1) to identify the genetic pathways and gene networks involved in resistance mechanisms. The higher levels of salicylic acid resulted in upregulation of many pathogenesis-related (PR) and redox protein encoding transcripts which resulted in higher hypersensitive response in BPT-5204. Many Serine/threonine protein kinase, leucine-rich repeat (LRR) transmembrane protein kinase, protein kinase family genes, Wall-associated kinase (WAK) were upregulated that resulted in activation of bZIP, WRKY, MYB, DOF and HSFs transcription factors that are associated with improved plant immunity. The study provided roles of many genes and their associated plant immunity pathways that can be used for developing resistant rice cultivars.Hydrocortisone is used in preterm infants. However, early disruption of growth velocities was observed in infants exposed to hydrocortisone. This retrospective study aimed to explore the postnatal brain growth of extremely preterm infants requiring hydrocortisone treatment as well as its association with perinatal factors. Extremely preterm infants exposed to hydrocortisone from 2011 to 2016 who survived up to 12 months were included. Each of them was matched with two infants not treated with hydrocortisone exhibiting similar gestational ages and nearly similar birth head circumferences. The outcome variables were brain tissue areas on MRIs performed at term-equivalent age and postnatal head circumference growth up to a corrected age of 12 months. Univariate and multiple regression analyses were performed. Infants treated with hydrocortisone (n=20) were matched with 40 infants not exposed to hydrocortisone. The infants exposed to hydrocortisone exhibited a lower birth weight (p=0.04) and a longer duration of e conditions did not show independent effect on brain growth up to the corrected age of 12 months. However, a different effect of hydrocortisone according to sex can't be excluded and needs further explorations. • Perinatal factors as birth weight and duration of mechanical ventilation were determinant for the subsequent brain growth.Sociodemographic factors and lifestyle behaviours were evidenced as correlates of self-reported 24-hour movement behaviours in high-income settings. However, it is unclear how these relations occur in a middle-income country setting, with unique cultural and social characteristics. This study aimed to examine the association between sociodemographic, dietary, and substance use factors with accelerometer-measured 24-hour movement behaviours in Brazilian adolescents. Information on sex, age, socioeconomic status (SES), family structure, dietary behaviours, and history of substance use were collected by a questionnaire. Sleep duration, sedentary behaviour, and light- and moderate-to-vigorous physical activity (LPA and MVPA) were measured using wrist-worn accelerometers. On average, females slept more (β = 21.09, 95%CI 13.18; 28.98), engaged in more LPA (β = 17.60, 95%CI 8.50; 27.13), and engaged in less sedentary behaviour (β = -16.82, 95%CI -30.01; -4.30) and MVPA (β = -4.76, 95%CI -7.48; -1.96) than males. Agers. What is New • Sex, age, and dietary behaviours were associated with the 24-hour movement behaviours. • No associations were found between socioeconomic status and substance use with the 24-hour movement behaviours.We found mycoheterotrophic seedling growth (initial mycoheterotrophy) of Gentiana zollingeri, a spring-flowering photosynthetic species of Gentianaceae family. Small seeds (about 300 µm in length) were buried in a habitat by using seed packets, and development of the subterranean seedlings to form shoots, more than 3 cm in length, was observed in symbiosis with arbuscular mycorrhizal (AM) fungi in the dark (i.e., underground of a field). Hyphal coils and their degenerations were observed in the root cortical cells of the subterranean seedlings as well as those of adult plants. Among the mycobionts identified on the basis of partial small subunit rDNA sequences, it was found that AM fungi of a lineage in Glomeraceae dominantly colonized, and the AM fungi were also dominant in adult individuals of G. zollingeri in three habitats separated one another by 17.2, 34.7, and 49.6 km. Though initial mycoheterotrophy in symbioses with AM fungi has been observed in some pteridophytes, this is the first study to demonstrate this type of symbiosis in a photosynthetic seed plant. The mycoheterotrophy means that an energy distribution occurs through the hyphal bridges of AM fungi among different photosynthetic seed plants, which may be important in constructing plant species diversity in some ecosystems.

In this manuscript, we present recent findings concerning concordance and discrepancy between biological measures and self-reports of these three outcomes of HIV programs HIV status, adherence to antiretroviral medications (ARVs) and use of and adherence to pre-exposure prophylaxis medication (PrEP), and condom use/unprotected sex.

Recent studies suggest that three successive rapid HIV tests (for those whose first test in positive) might be reasonably inexpensive and valid biological data to collect to combine with self-reports of HIV status, dried blood spots sufficiently affordable to combine with self-reports of adherence to ARVs and use of or adherence to PrEP, and that the discrepancy between self-reports of condom use and biomarkers of unprotected sex may be relatively small in high-income countries. Additional work on assessment of incorrect condom usage and breakage, standardized self-report measures of condom use, and more private data collection methodologies in low-income settings might reduce ncome countries. Our results suggest that more careful assessment of incorrect condom use and breakage as reasons other than intentional misreporting should be investigated more carefully and that more private data collection methods such as audio, computer-assisted self-interviewing (ACASI) might be employed more often in low-resource settings to reduce this discrepancy in those settings further. In addition, further analysis of the discrepancy between self-reports of condom use and biomarkers should be conducted of published studies using the correct calculation methods to be more certain of these findings.

Implantation is essential for a successful pregnancy. Despite the increasing number of studies, implantation is still an unknown process. This study aimed to determine whether sirtuin-1 has a role in embryo implantation in oxidative stress-induced mice.

Pregnant mice were separated into 5 groups control, vehicle, paraquat, SRT1720, and SRT1720+Paraquat. Paraquat is a herbicide and is used to induce oxidative stress. SRT1720 is a specific sirtuin-1 activator. Implantation and inter-implantation sites were removed in the morning of the 5th day of pregnancy after Chicago blue injection was performed. Sirtuin-1 and Forkhead box O1 (FoxO1) were detected by immunohistochemistry and Western blot while acetylated lysine was evaluated by Western blot analysis. Reactive oxygen and nitrogen species (ROS/RNS) and superoxide dismutase (SOD) activity were determined by fluorometric and spectrometric methods, respectively.

Although there was no embryo implantation in paraquat-treated mice, 5 out of 9 SRT1720+Paraquat-treated mice had implantation sites which were significantly higher compared to the paraquat-treated group. Sirtuin-1 and FoxO1 expressions were increased at implantation sites of SRT1720-treated mice. ROS/RNS levels were decreased, while deacetylated FoxO1 levels and SOD activity were increased in SRT1720-treated mice.

Our findings suggest that sirtuin-1 may play a role in embryo implantation against oxidative stress through FoxO1-SOD signaling.

Our findings suggest that sirtuin-1 may play a role in embryo implantation against oxidative stress through FoxO1-SOD signaling.

Chronic intermittent hypoxia (CIH) plays a key role in the complications of obstructive sleep apnea (OSA), which is strongly associated with retinal and optic nerve diseases. Additionally, the brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling pathway plays an important protective role in neuronal injury. In the present study, we investigated the role of 7,8-dihydroxyflavone (7,8-DHF) in regulating CIH-induced injury in mice retinas and rat primary retinal ganglion cells (RGCs).

C57BL/6 mice and in vitro primary RGCs were exposed to CIH or normoxia and treated with or without 7,8-DHF. The mice eyeballs or cultured cells were then taken for histochemistry, immunofluorescence or biochemistry, and the protein expression of the BDNF/TrkB signaling pathway analysis.

Our results showed that CIH induced oxidative stress (OS) in in vivo and in vitro models and inhibited the conversion of BDNF precursor (pro-BDNF) to a mature form of BDNF, which increased neuronal cell apoptosis. 7,8-DHF reduced the production of reactive oxygen species (ROS) caused by CIH and effectively activated TrkB signals and downstream protein kinase B (Akt) and extracellular signal-regulated kinase (Erk) survival signaling pathways, which upregulated the expression of mature BDNF. ANA-12 (a TrkB specific inhibitor) blocked the protective effect of 7,8-DHF.

In short, the activation of the BDNF/TrkB signaling pathway alleviated CIH-induced oxidative stress damage of the optic nerve and retinal ganglion cells. 7,8-DHF may serve as a promising agent for OSA related neuropathy.

In short, the activation of the BDNF/TrkB signaling pathway alleviated CIH-induced oxidative stress damage of the optic nerve and retinal ganglion cells. 7,8-DHF may serve as a promising agent for OSA related neuropathy.

Diagnosis and treatment of obstructive sleep apnea are traditionally performed in sleep laboratories with polysomnography (PSG) and are associated with significant waiting times for patients and high cost. We investigated if initiation of auto-titrating CPAP (APAP) treatment at home in patients with obstructive sleep apnea (OSA) and subsequent telemonitoring by a homecare provider would be non-inferior to in-lab management with diagnostic PSG, subsequent in-lab APAP initiation, and standard follow-up regarding compliance and disease-specific quality of life.

This randomized, open-label, single-center study was conducted in Germany. Screening occurred between December 2013 and November 2015. Eligible patients with moderate-to-severe OSA documented by polygraphy (PG) were randomized to home management or standard care. All patients were managed by certified sleep physicians. The home management group received APAP therapy at home, followed by telemonitoring. The control group received a diagnostic PSG, follprocedures, and facilitates faster access to therapy.

Use of a home-based telemonitoring strategy for initiation of APAP in selected patients with OSA managed by sleep physicians is feasible, appears to be non-inferior to standard sleep laboratory procedures, and facilitates faster access to therapy.Two new compounds, podogigants A (1) and B (2), were isolated from the culture broth of Podostroma giganteum. This is the first report on the identification of secondary metabolites in P. giganteum. The structures of 1 and 2 were elucidated through spectroscopic analysis, including 2D NMR spectroscopy assisted by chemical derivatization, which revealed the presence of farnesyl- and geranyl-hydroquinone structures, respectively. Compounds 1 and 2 exhibited no antifungal activity even at a concentration of 64 μg/mL, whereas they potentiated amphotericin B (AmB) activity against several species of fungi. In particular, 1 potentiated AmB activity against C. albicans and R. oryzae by up to 32-fold (MIC value of AmB decreased from 1.0 to 0.032 µg/mL), while 2 potentiated AmB activity against C. albicans by up to 16-fold.

Although the value of video-assisted thoracic surgery for acute pyothorax is becoming widely recognized, the optimal timing of surgery has not been established. Therefore, we aimed to determine the optimal timing of video-assisted thoracic surgery in acute pyothorax.

We retrospectively reviewed 38 consecutive video-assisted thoracic surgeries performed for acute pyothorax between January 2013 and December 2017 at our institution. Data were analyzed using the independent samples t test and Mann-Whitney U test. A receiver-operating characteristic curve was used to identify the optimal time for intervention.

The average time from disease onset to surgery was 17.9days, and the average preoperative drainage period was 8.3days. The operation was completed in all patients with video-assisted thoracic surgery curettage and drainage under general anesthesia; single lung ventilation was administered, and one or two thoracic drains were placed. The average postoperative drainage period was 10.8days. Intraoperative complications were observed in two cases; no perioperative death occurred. Additional surgery was performed in four cases because of poor treatment response. There was no recurrence of pyothorax over a mean postoperative follow-up period of 42.5months. A receiver-operating characteristic curve showed that the cut-off time from disease onset to surgery was 21.0days; complication rates were 14.3% and 25.0% for patients operated on before and after 21days, respectively.

Thoracoscopic surgery for acute pyothorax is safe and curative, and should be performed within 21days of disease onset to avoid postoperative complications.

Thoracoscopic surgery for acute pyothorax is safe and curative, and should be performed within 21 days of disease onset to avoid postoperative complications.The effectiveness of bullying prevention programs has led to expectations that these programs could have effects beyond their primary goals. By reducing the number of victims and perpetrators and the harm experienced by those affected, programs may have longer-term effects on individual school performance and prevent crime. In this paper, we use Norwegian register data to study the long-term impact of the Olweus Bullying Prevention Program (OBPP) on academic performance, high school dropout, and youth crime for the average student, which we call population-level effects. The OBPP program is widely acknowledged as one of the most successful programs reducing school-level bullying; yet, using a difference-in-difference design, no statistically significant population-level effects of the OBPP were found on any of the long-term outcomes in this study. When studied at the population level, as in the current project, the base rate prevalence of bullying is a major explanatory factor for these results. Earlier studies have shown that OBPP reduces bullying prevalence by 30-50%. This decrease translates into absolute reductions in bullying victimization and perpetration at the population level of "only" four and two percentage points, respectively. Our results suggest the average causal effects of school bullying involvement are too small to translate this reduction in bullying into a sizeable population-level impact on students' long-term outcomes. However, a limited potential of anti-bullying programs to prevent population-level adversity can very well be compatible with substantial program effects for individual bullies and victims. Further, our results do not speak to the main objective of anti-bullying programs of limiting childhood abuse and safeguarding children's human rights.Peritoneal adhesion represents a severe complication following surgery. Punica granatum (pomegranate) possesses several anti-oxidative and anti-inflammatory properties. Pomegranate peel extract (PPEx) can alleviate the production of various inflammatory factors and cytokines. Thus, we sought to evaluate the anti-adhesion effects of pomegranate in rats. Thirty male Wistar rats (6-week-old, 220 ± 20 g) were divided into five groups (n = 6) normal group without any surgical procedures, control group, and experimental groups receiving 2 ml of 1%, 2%, and 4% w/v PPEx, respectively. Peritoneal adhesions were examined macroscopically. Furthermore, we evaluated inflammatory cytokines levels [interleukin 6 (IL-6), and tumour necrosis factor-α (TNF-α)], growth factors [transforming growth factor- β1 (TGF-β1), and vascular endothelial growth factor (VEGF)], and oxidative stress parameters [nitric oxide metabolites (NO), and malondialdehyde (MDA), and glutathione (GSH)] using biochemical methods. Our results showed that the adhesion score and IL-6, TNF-α, TGF-β1, VEGF, NO, and MDA levels were increased in the control group. In contrast, the GSH level was diminished in the control group compared with the normal group (P  less then  0.001). PPEx (1 and 2% w/v) markedly reduced all measured parameters compared with the control group (P  less then  0.001-0.05). PPEx may reduce peritoneal adhesion by alleviating adhesion formation, IL-6, TNF-α, TGF-β1, VEGF, NO, and MDA, and stimulating anti-oxidative factors. Therefore, PPEx may be considered an appropriate candidate for the treatment of postoperative peritoneal adhesion.

Postoperative pneumonia is a serious prognostic problem that can appear after esophagectomy in patients with esophageal cancer. The past reports have considered the usefulness of perioperative culture examinations for predicting postoperative pneumonia; however, the direct relationship between these examinations and postoperative complications remains unclear.

This study retrospectively analyzed esophageal cancer patients who underwent esophagectomy followed by sputum culture on the first postoperative day. The bacterial species that frequently cause hospital-acquired pneumonia were chosen as the target species in this study. The relationship between culture examination and postoperative pneumonia within one week (7days) after esophagectomy was investigated.

Sputum cultures on the first postoperative day were investigated in 238 patients who underwent esophagectomy for esophageal cancer. Forty-one patients developed pneumonia within one week after surgery. The target bacterial species were detected in 2ys after surgery. Prospective studies for the prevention of early postoperative pneumonia using sputum culture on the first postoperative day can be considered.

In the phase II ATTRACTION-1 study, nivolumab demonstrated a promising antitumor activity among Japanese patients with treatment-refractory advanced esophageal cancer. Here, we report the follow-up results of ATTRACTION-1 of > 5years.

We enrolled patients with esophageal cancer that was refractory or intolerant to a standard chemotherapy. Then, nivolumab (3mg/kg) was administered every 2weeks. The primary endpoint was a centrally assessed objective response rate.

Nivolumab was administered to 65 patients with esophageal squamous-cell carcinoma (ESCC). The centrally assessed objective response rate was 17.2%. The overall survival rates at 3 and 5years were 10.9% and 6.3%, respectively. Three-year survivors tended to have more reduced target lesions. A total of 63.1% of the patients exhibited treatment-related adverse events, and no new safety signal was observed. Patients with select adverse events tended to have better overall survival than those without. No apparent chronological order was observed between the first response and the onset of select adverse events.

Our follow-up analysis of more than 5years is currently the longest and is the first to demonstrate that nivolumab has long-term efficacy and safety for advanced ESCC.

Our follow-up analysis of more than 5 years is currently the longest and is the first to demonstrate that nivolumab has long-term efficacy and safety for advanced ESCC.We recently investigated the presence of enteroviruses (EVs) in non-human primates (NHPs) in Northern Nigeria and documented the presence of EV-A76 of South-East Asian ancestry in an NHP. In this study, we go further to ask if we could also find EVs in NHPs indigenous to the forested South-south Nigeria. Fresh faecal samples were collected from the floor of 10 cages housing NHPs in Cross River Nigeria, re-suspended in PBS and subjected to RNA extraction, cDNA synthesis, PanEnt 5'-UTR and PanEnt VP1 PCR assays. None of the samples was positive for the PanEnt VP1 assay, but one sample was positive for PanEnt 5'-UTR PCR. This sample was subsequently inoculated into RD cell line, produced CPE and the isolate analysed by PCR assays, next-generation whole genome sequencing and passage in four different cell lines showing replication in two of them. Analysis of the complete genome of the isolate identified it as an Echovirus 11 (E11) and revealed a recombinant genomic structure. Phylogenetic analysis showed that the E11 NHP strain was related to human clinical isolates suggesting a zoonotic behaviour. We describe the first isolation and complete genome characterization of an E11 obtained from an NHP in Nigeria having zoonotic potential.Progress in unraveling the complex biology of cancer, novel developments in radiochemistry, and availability of relevant α-emitters for targeted therapy have provided innovative approaches to precision cancer management. The approval of 223Ra dichloride for treatment of men with osseous metastatic castrate-resistant prostate cancer unleashed targeted α-therapy as a safe and effective cancer management strategy. While there is currently active research on new α-therapy regimens for prostate cancer based on the prostate-specific membrane antigen, there is emerging development of radiopharmaceutical therapy with a range of biological targets and α-emitting radioisotopes for malignancies other than the prostate cancer. This article provides a brief review of preclinical and first-in-human studies of targeted α-therapy in the cancers of brain, breast, lung, gastrointestinal, pancreas, ovary, and the urinary bladder. The data on leukemia, melanoma, myeloma, and neuroendocrine tumors will also be presented. It is anticipated that with further research the emerging role of targeted α-therapy in cancer management will be defined and validated.Tracking control of specific variables is key to achieve a proper fermentation. This paper analyzes a fed-batch bioethanol production process. For this system, a controller design based on linear algebra is proposed. Moreover, to achieve a reliable control, on-line monitoring of certain variables is needed. In this sense, for unmeasurable variables, state estimators based on Gaussian processes are designed. Cell, ethanol and glycerol concentrations are predicted with only substrates measurement. Simulation results when the controller and estimators are coupled, are shown. Furthermore, the algorithms were tested with parametric uncertainties and disturbances in the control action, and are compared, in all cases, with neural networks estimators (previous work). Bayesian estimators show a performance improvement, which is reflected in a decrease of the total error. Proposed techniques give reliable monitoring and control tools, with a low computational and economic cost, and less mathematical complexity than neural network estimators.The partial denitrification (PD) is a very promising process developed in the last decade, to study the comprehensive influence of influent carbon to nitrogen (C/N) on the activated sludge system under PD, six sequencing batch reactors (SBRs) were operated in parallel at C/N of 2.75, 3.30, 4.13, 5.50, 8.25 and 16.50, the nitrogen removal, phosphorus removal and sludge settleability of PD were investigated. The results showed that PD was observed treating synthetic wastewater in all the six SBRs, and the nitrite accumulation rate (NAR) was highest at C/N of 5.50 (NAR of 82.30%). However, due to the alternate inhibition of NO2--N and free nitrous acid (FNA) produced by a limited carbon source, both the sludge settleability and phosphorus removal deteriorated. The average SVI at C/N of 8.25 was 130% lower than C/N of 3.30, and the average amount of PO43--P released at C/N of 16.5 was 189% higher than C/N of 2.75. Kinetic analysis showed that the denitrification kinetics of PD and complete denitrification were similar, and the nitrite accumulation was caused by the difference between nitrate reduction rate and nitrite reduction rate. Variations of on-line parameters (pH and ORP) revealed that nitrite accumulation could be indicated by judging the nitrate turning point and nitrite turning point on pH and ORP curves, which provided guidance for the setup of PD.

Aurora kinases are overexpressed or amplified in numerous malignancies. This study was designed to determine the safety and tolerability of the Aurora A kinase inhibitor alisertib (MLN8237) when combined with weekly irinotecan.

In this single-center phase 1 study, adult patients with refractory advanced solid tumors received 100mg/m

irinotecan intravenously on day 1 and 8 of a 21-day cycle. Alisertib at planned escalating dose levels of 20-60mg was administered orally twice per day on days 1-3 and 8-10. Patients homozygous for UGT1A1*28 were excluded. The primary objective was the safety of alisertib when combined with irinotecan to determine the maximum tolerated dose (MTD). Secondary objectives included overall response rate by RECIST and pharmacokinetics in a planned expansion cohort of patients with colorectal cancer treated at the MTD.

A total of 17 patients enrolled at three dose levels. Dose-limiting toxicities included diarrhea, dehydration, and neutropenia. The MTD of alisertib combined with weekly irinotecan was 20mg twice per day on days 1-3 and 8-10. One fatal cardiac arrest at the highest dose level tested was deemed possibly related to drug treatment. One partial response in 11 efficacy evaluable patients (9%) occurred in a patient with small cell lung cancer. The study was terminated prior to the planned expansion in patients with colorectal cancer.

In contrast to prior results in a pediatric population, adult patients did not tolerate alisertib combined with irinotecan at clinically meaningful doses due to hematologic and gastrointestinal toxicities. The study was registered with ClinicalTrials.gov under study number NCT01923337 on Aug 15, 2013.

In contrast to prior results in a pediatric population, adult patients did not tolerate alisertib combined with irinotecan at clinically meaningful doses due to hematologic and gastrointestinal toxicities. The study was registered with ClinicalTrials.gov under study number NCT01923337 on Aug 15, 2013.