Ballardfriedrichsen2615

7%), GAD65 (7.7%), NMDAr (3.8%), Ma2 (3.8%) and Hu (3.8%) Ab. Cases with LGI1 Ab showed a good response to immunotherapy.

The prevalence of IP in our LE cohort was of 13.3%, higher than expected. According to the literature review, most cases were associated with LGI1 Ab and showed a good response to immunotherapy. With the contribution of our cases, GAD65 emerged as the second most frequently detected Ab, showing a poor outcome. Our findings widen the spectrum of IP-associated Ab, with the respective prognostic implications.

The prevalence of IP in our LE cohort was of 13.3%, higher than expected. According to the literature review, most cases were associated with LGI1 Ab and showed a good response to immunotherapy. With the contribution of our cases, GAD65 emerged as the second most frequently detected Ab, showing a poor outcome. Our findings widen the spectrum of IP-associated Ab, with the respective prognostic implications.

Recent position papers and guidelines encourage women with epilepsy (WWE) to exclusively breastfeed their infants because the benefits to their infants outweigh the potential adverse effects caused by exposure to antiseizure medications (ASMs).

The objectives of this review were to evaluate concentrations of ASMs in breastmilk of lactating WWE, qualitatively synthesize evidence that can be used to estimate theoretical doses as estimated daily intake (EDI) and relative infant dose (RID) of ASMs, and to evaluate potential risks to infants as a result of exposure to ASMs from breastmilk.

This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) as CRD42020223645. The databases MEDLINE/PubMed, EMBASE, CINAHL/EBSCO, COCHRANE, SpringerLink, ScienceDirect, Summon, WHO International Clinical Trials Registry Platform, and SCOPUS were systematically searched. A qualitative synthesis was adopted in this study.

A total of 15 records were included in this systn the safety of breastfeeding while taking ASMs.

For NSCLC patients with complete resection, the prognostic role of EGFR mutation for recurrence, especially for CNS metastasis, is still controversial. In this study, we aimed to identify the characteristics of the recurrence pattern of lung adenocarcinoma based on EGFR mutation status.

Overall, 888 patients with completely surgically resected LUAD who underwent EGFR mutation status analysis from two Chinese institutions were included. Sites and data of initial recurrence were recorded. The recurrence patterns according to EGFR mutation status were estimated by Kaplan-Meier analysis, and hazard rate curves were generated.

245 (27.6%) of 888 patients suffered from recurrence. Before and after PSM, there were no statistically significant differences between the EGFR mutation and EGFR WT groups for all types of recurrence, including CNS metastasis. Multivariable Cox analysis revealed that EGFR status was not a risk factor for all types of recurrence, including CNS metastasis (HR 0.88, 95% CI 0.54-1.46, p=0.632). The CNS metastasis hazard curve in the EGFR mutation group showed that the first peak occurred at approximately 24-26months after surgery, which was 10months later than that in the EGFR WT group. In addition, the second peak time in the EGFR mutation group was approximately 2years later than that in the EGFR WT group.

EGFR mutation was not an independent prognostic factor for postoperative recurrence. EGFR-mutated LUADs did not have a clinical course with a higher incidence of CNS metastasis. However, the peak hazards for recurrence of CNS metastasis occur at a later time point in the EGFR mutant group compared with the EGFR wild type group.

EGFR mutation was not an independent prognostic factor for postoperative recurrence. EGFR-mutated LUADs did not have a clinical course with a higher incidence of CNS metastasis. However, the peak hazards for recurrence of CNS metastasis occur at a later time point in the EGFR mutant group compared with the EGFR wild type group.

Parkinson's disease (PD) is associated with structural alterations of the retina. However, it remains unknown whether these changes are present in PD with mild cognitive impairment (MCI). The purpose of the study was to evaluate the retinal microvasculature using optical coherence tomography angiography (OCTA) to assess possible retinal microvascular impairments associated with PD and PD with MCI.

This study included 83 eyes of 45 PD patients and 83 eyes of 42 healthy controls. All subjects underwent complete neurological and ophthalmological examinations before measurements. Cognitive function was also measured in PD patients. Retinal microvasculature was evaluated with OCTA. Vessel density in the superficial capillary plexus (SRCP), deep capillary plexus (DRCP), and radial peripapillary capillaries (RPC) and intraretinal layer thickness in the peripapillary retinal nerve fibre layer (RNFL) and ganglion cell complex (GCC) were analysed. Correlations between vessel density and cognitive function were analysed in the PD group.

Parafoveal vessel density in the SRCP and DRCP were lower in the eyes of PD patients than healthy controls (P<0.05). However, there were no significant differences in the RPC (P=0.120), RNFL (P=0.303) or GCC (P=0.375) between PD patients and healthy controls. Lower executive function scores were associated with lower vessel density in the DRCP of PD patients (P<0.05, 95% CI [0.133,1.342]).

OCTA revealed lower macular microvascular density in PD patients and microvascular impairments in the deep retinal capillary layer in PD patients with executive dysfunction. These parameters might have potential utility as early disease diagnostic biomarkers.

OCTA revealed lower macular microvascular density in PD patients and microvascular impairments in the deep retinal capillary layer in PD patients with executive dysfunction. These parameters might have potential utility as early disease diagnostic biomarkers.Human visual perception is efficient, flexible and context-sensitive. The Bayesian brain view explains this with probabilistic perceptual inference integrating prior experience and knowledge through top-down influences. Advances in machine learning, such as Artificial Neural Networks (ANNs), have enabled considerable progress in computer vision. Unlike humans, these networks do not yet adaptively draw on meaningful and task-relevant contextual cues and prior knowledge. We propose ideas to better align human and computer vision, applied to facial expression recognition. We review evidence of knowledge-augmented and context-sensitive face perception in humans and approaches trying to leverage such sources of information in computer vision. We discuss how both fields can establish an epistemic loop Redesigning synthetic systems with inspiration from the Bayesian brain-framework could make networks more flexible and useful for human-machine interaction. In turn, employing ANNs as scientific tools will widen the scope of empirical research into human knowledge-augmented perception.The multifunction antibacterial hemostatic materials can reduce blood loss, infection and wound complications, which probably decrease morbidity and health care costs. However, the contradictory relationship between antibacterial ability and biocompatibility, and the unnecessary blood loss restricts the practical application of hydrophilic cationic antibacterial hemostatic materials. Herein, a multifunctional temperature-triggered antibacterial hemostatic fluorocopolymer aggregate coating was developed. After self-assembly and quaternization process, the quaternized poly(N,N-dimethylaminoethylmethacrylate)-b-poly(1H,1H,2H,2H-heptadecafluorodecyl acrylate) block copolymers (PDMA-b-PFOEMA) aggregate coating consisting of fluoropolymer and quaternary ammonium salt were built. The synergistic effect on fluorinated block with low surface energy and quaternary ammonium salt block with bactericide activity severs the way of initial bacterial attachment and proliferation, while the migration of fluorinated block greatly promotes the biocompatibility and anti-adhesion performance in response to the switch from room temperature to physiological temperature. Furthermore, the fluorocopolymer aggregate coating with hydrophobic properties possessed the property of rapid coagulation, low blood loss, minor secondary bleeding and least bacteria infiltration. The multifunctional temperature-triggered fluorocopolymer aggregate coating with antifouling, antibacterial and hemostatic properties may have a great potential in the biomedical application.

The association between chronic obstructive pulmonary disease (COPD) and functional gastrointestinal disorders (FGIDs) remains unclear.

Using Taiwan's National Health Insurance Research Database, we conducted a nationwide population-based study to explore the relationship of COPD and future FGIDs development. The COPD cohort consisted of 4107 patients with COPD between 2000 and 2005. For a comparison cohort, 12,321 age- and gender-matched patients without COPD were randomly selected. The two cohorts were tracked for 5 year and observed for occurrence of FGIDs. The operational definition of COPD in the Korean Health Insurance Review and Assessment Service database was used to validate the results. The validation study confirmed the accuracy of definitions of COPD (83.5% sensitivity).

The adjusted hazard ratios (aHR) of FGIDs in patients with COPD was higher (aHR 1.63; 95% confidence interval (CI) 1.45-1.83; P<.001) than that of the comparison patients. In our secondary analysis in which FGIDs was divided into gastroesophageal reflux disease, irritable bowel syndrome and functional dyspepsia. Patients with COPD also had higher risk for all three subtypes of FGIDs irritable bowel syndrome (aHR 1.55; 95% confidence interval (CI) 1.27-1.90; P<.001), gastroesophageal reflux disease (aHR 2.10; 95% confidence interval (CI) 1.76-2.49; P<.001), and functional dyspepsia (aHR 1.34; 95% confidence interval (CI) 1.11-1.62; P=.003). The results in validated COPD group were consistent with those in unvalidated COPD group.

Patients with COPD appeared to be at higher risk for future FGIDs.

Patients with COPD appeared to be at higher risk for future FGIDs.

We examined the prevalence of comorbid depression and anxiety in patients with chronic obstructive pulmonary disease (COPD) and their response to eight-weeks of pulmonary rehabilitation (PR).

Seven hundred thirty four patients with clinically stable COPD completed an eight-week outpatient multidisciplinary PR, comprising 2-h (1-h exercise and 1-h education) per/week. Depression and anxiety, exercise capacity, quality of life (QOL), and dyspnea were measured pre- and post-PR by the incremental shuttle walk test (ISWT), St. George's Respiratory Questionnaire (SGRQ), and modified Medical Research Council (mMRC) scale, respectively. The Depression Anxiety Stress Scale (DASS-21) was completed and patients classified as having clinically significant comorbid anxiety and depression, anxiety alone, depression alone, or with neither.

The mean (SD) age of patients was 71 (8.8) years, and 51% were men. Prevalence of pre-PR comorbid depression and anxiety was 34%, anxiety alone 20%, depression alone 5% and neither 41%. The prevalence of stress was 59%. In patients with anxiety and depressive symptoms, total SGRQ score improved from 64.9 (13.8) pre-PR to 50.1 (17.2) post PR (p<0.001), mMRC score improved from 3.4(1.0) pre-PR to 2.8 (1.1) post PR (p<0.001), and ISWT distance walked increased from 188.6 (117.6) pre-PR to 248.6 (149.1) post PR, p<0.001.

One in three patients with COPD suffer from comorbid depression and anxiety with a high level of disease burden, reflected by symptoms of elevated dyspnea and impaired QOL. PR improves QOL and exercise capacity, and reduces dyspnea in patients with COPD and comorbid depression and anxiety.

One in three patients with COPD suffer from comorbid depression and anxiety with a high level of disease burden, reflected by symptoms of elevated dyspnea and impaired QOL. PR improves QOL and exercise capacity, and reduces dyspnea in patients with COPD and comorbid depression and anxiety.

Although a full course of coronavirus disease 2019 (COVID-19) vaccine is effective in cancer patients, the duration of the protection and the efficacy of a booster dose against the new variants remain unknown. We prospectively evaluated the immunogenicity of the third dose of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) BNT162b2 messenger RNA vaccine in cancer patients undergoing active treatment.

Patients with solid cancer, vaccinated with a booster dose during active treatment, were enrolled in this study. Patients were classified into SARS-CoV-2 naïve (without previous COVID-19 infection) and SARS-CoV-2 experienced (with previous COVID-19 infection). Neutralizing antibody (NT Ab) titer and total anti-Spike immunoglobulin G (IgG) concentration were quantified in serum. Heparinized whole blood samples were used for SARS-CoV-2 Interferon Gamma Release Assay (IGRA). The primary endpoint was to assess the increase of IgG antibody level between baseline and 3 weeks after the booster.

Onts of concern seem to confirm the lower vaccine activity.

The third dose is able to trigger both the humoral and the cell-mediated immune response in cancer patients on active treatment. Our preliminary data about the neutralization of the SARS-CoV-2 vaccine against variants of concern seem to confirm the lower vaccine activity.

The coronavirus disease 2019 (COVID-19) pandemic has disrupted clinical practice, research and teaching. During peaks, virtual courses were implemented but these changes are poorly described, especially for oncology postgraduate students and faculty teachers.

We administered two surveys from June 2021 to October 2021 to students and faculty teachers (250 and 80 responses, respectively) who registered at Gustave Roussy School of Cancer Sciences (Université Paris-Saclay) during 3 consecutive university years (October 2018 to October 2021), where a major shift to e-learning was associated with COVID-19 pandemic.

Most students were female (53%), attending physicians (50%), aged 30-39 years (54%) and 2020-2021 (66.4%) was the main year of training. Most faculty teachers were male (58%), aged 40-50 years (44%) and had participated in training for at least 3 years (83%). More than half of the students received 100% virtual training [55% versus 45% face-to-face/mixed teaching modalities; online (84%) versus rem are required.

COVID-19 accelerated the transition toward novel practices. Students and faculty teachers agreed on the need for future mixed (≤50% e-learning) teaching modalities. Adequate formation and the use of codified best newer virtual practices are required.

The aim of this study was to examine the evaluation of ultra-high-resolution computed tomography angiography (UHR CTA) images in moyamoya disease (MMD) reconstructed with hybrid iterative reconstruction (Hybrid-IR), model-based iterative reconstruction (MBIR), and deep learning reconstruction (DLR).

This retrospective study with institutional review board approval included patients with clinically suspected MMD who underwent UHR CTA between January 2018 and July 2020. CTA images were reconstructed with three reconstruction methods. Qualitative visualization was evaluated in comparison with digital subtraction angiography. Quantitative evaluation included assessment of edge sharpness, full width at half maximum (FWHM), vessel contrast, and tissue signal-to-noise ratio (SNR

). One-way analysis of variance was used to analyze differences. In addition, reconstruction time were assessed.

Qualitative evaluation of CTA for 33 sides did not differ significantly between reconstruction methods. In quantitative evaluation for 54 patients, edge sharpness for right and left cortical segments of the middle cerebral artery was significantly higher for Hybrid-IR than for other reconstructions. No significant difference was seen between MBIR and DLR. Edge sharpness for STA-MCA bypass was significantly higher for Hybrid-IR than for MBIR, but no significant difference was seen between Hybrid-IR and DLR. FWHM for STA-MCA showed no significant difference between the three reconstruction methods. DLR displayed the highest SNR

. The time required for reconstruction was 40s for Hybrid-IR, 2580s for MBIR, and 180s for DLR.

UHR CTA with DLR adequately visualized vessels in patients with MMD within a clinically feasible reconstruction time.

UHR CTA with DLR adequately visualized vessels in patients with MMD within a clinically feasible reconstruction time.Oxygenated polycyclic aromatic hydrocarbons (OPAHs) have been ubiquitously detected in atmospheric, soil, sediment, and water environments, some of which show higher concentrations and toxicities than the parent polycyclic aromatic hydrocarbons (PAHs). The occurrence, source, fate, risks and methods of analysis for OPAHs in the atmosphere, soil, and the whole environment (comprising the atmosphere, soil, water, and biota) have been reviewed, but reviews focusing on OPAHs in the water environment have been lacking. Due to the higher polarity and water solubility of OPAHs than PAHs, OPAHs exist preferentially in water environments. In this review, the occurrence, ecological toxicity and source of OPAHs in surface water environments are investigated in detail. Most OPAHs show higher concentrations than the corresponding PAHs in surface water environments. OPAHs pose non-ignorable ecological risks to surface water ecosystems. Wastewater treatment plant effluent, atmospheric deposition, surface runoff, photochemical and microbiological transformation, and sediment release are possible sources for OPAHs in surface water. This review will fill important knowledge gaps on the migration and transformation of typical OPAHs in multiple media and their environmental impact on surface water environments. Further studies on OPAHs in the surface environment, including their ecotoxicity with the co-existing PAHs and mass flows of OPAHs from atmospheric deposition, surface runoff, transformation from PAHs, and sediment release, are also encouraged.Why is it rational for scientists to pursue multiple models of a phenomenon at the same time? The literatures on mechanistic inquiry and scientific pursuit each develop answers to a version of this question which is rarely discussed by the other. The mechanistic literature suggests that scientists pursue different complementary models because each model provides detailed insights into different aspects of the phenomenon under investigation. The pursuit literature suggests that scientists pursue competing models because alternative models promise to solve outstanding empirical and conceptual problems. Looking into research on visual processing as a case study, we suggest an integrated account of why it is rational for scientists to pursue both complementary and competing models of the same mechanism in scientific practice.

To investigate whether and how global O-linked N-Acetylglucosamine modification (O-GlcNAcylation), a prevalent nutrient-sensitive post-translation modification, regulates odontogenic differentiation and mineralization in human dental pulp cells (hDPCs).

First, immunostaining assays on sections of dental pulp tissue were performed to detect the distributions of O-GlcNAcylation and its exclusive enzyme set O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Then global O-GlcNAcylation was determined by anti O-linked N-Acetylglucosamine (RL2) Western blot during odontogenesis of hDPCs. Further, inhibition or knockdown of OGT and OGA were achieved by specific inhibitors or siRNA in vitro, respectively. The odonto-induction effect of O-GlcNAcylation ex vivo was investigated by a subcutaneous transplantation experiment. Moreover, the O-GlcNAc modification of RAPTOR was confirmed by immunoprecipitation. Odontogenic differentiation assays also investigated the indispensable role of RAPTOR during enhanced global O-GlcNAcylation.

The signals of O-GlcNAc became more enriched in the odontoblasts compared to pulp fibroblasts. During odontogenesis of hDPCs, global O-GlcNAcylation was significantly increased. An increase or decrease of O-GlcNAcylation significantly boosted or blunted odontogenic differentiation, respectively. The fluctuation of O-GlcNAcylation continuously impacted the downstream targets of mTORC1. Consistently, RAPTOR was modified by O-GlcNAcylation, which was necessary for inducing odontogenesis.

Global O-GlcNAcylation participated in and affected the odontogenic differentiation of hDPCs, which was mediated by the mTORC1 pathway. Thus, targeting O-GlcNAcylation might be a potential therapeutic intervention for pulp repair and regeneration.

Global O-GlcNAcylation participated in and affected the odontogenic differentiation of hDPCs, which was mediated by the mTORC1 pathway. Thus, targeting O-GlcNAcylation might be a potential therapeutic intervention for pulp repair and regeneration.The possible damaging effects on human health of inhaled radon and its decay products are of interest to workers and the public. In particular, radon in thermal environments often occurs in high concentrations. Therefore, investigations and remedial actions are important to reduce activity concentration values and associated risk. This work concerns the analysis of two surveys of radon gas activity concentration carried out in 2006/2007 and 2019/2020 at twenty thermal spas on the island of Ischia (Italy). Annual measurements were carried out in workplaces located in the basement and ground floor using passive CR-39 detectors. In the spas involved in both surveys, the effectiveness of the remedial actions, implemented by the owners, was assessed obtaining an average percentage reduction of 74%. Considerations were made about the annual effective dose, and the location of the spas taking into account the geological setting of the volcanic nature of the island.

Frontline immune checkpoint inhibitors (ICI)-based regimens in non-oncogene-addicted non-small-cell lung cancer (NSCLC) have been deeply investigated. To rank the available therapeutic options, we carried out a systematic review and Bayesian meta-analysis.

A comprehensive search for randomized controlled trials (RCTs) of ICI regimens, and a pairwise and a network meta-analysis (NMA) with an all-comers and a stratified strategy were conducted. Endpoints were overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (TRAEs).

Nineteen RCTs involving 17 treatment regimens were included. For the all-comers population, pembrolizumab/chemotherapy (CT) and cemiplimab were most likely the best treatments. For programmed death-ligand 1 (PD-L1) <1% nivolumab/ipilimumab with/without CT, for PD-L1 >1% and 1%-49% pembrolizumab/CT and for PD-L1 >50% cemiplimab ranked first for OS. In non-squamous (NSQ), pembrolizumab with/without CT ranked firstferent ICI treatments rank differently in specific NSCLC settings (histology, biomarker and clinical presentation) offering a novel challenging scenario for clinical decision making and research planning.

The SAKK 17/16 study showed promising efficacy data with lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma. Here, we evaluated long-term outcome and analyzed the impact of lurbinectedin monotherapy on the tumor microenvironment at the cellular and molecular level to predict outcomes.

Forty-two patients were treated with lurbinectedin in this single-arm study. Twenty-nine samples were available at baseline, and seven additional matched samples at day one of cycle two of treatment. Survival curves and rates between groups were compared using the log-rank test and Kaplan-Meier method. Statistical significance was set at P value <0.05.

Updated median overall survival (OS) was slightly increased to 11.5 months [95% confidence interval (CI) 8.8-13.8 months]. Thirty-six patients (85%) had died. The OS rate at 12 and 18 months was 47% (95% CI 32.1% to 61.6%) and 31% (95% CI 17.8% to 45.0%), respectively. Median progression-free survival was 4.1 months (95% CI 2.6-5.5 months). No new safety signals were observed. Patients with lower frequencies of regulatory T cells, as well as lower tumor-associated macrophages (TAMs) at baseline, had a better OS. Comparing matched biopsies, a decrease of M2 macrophages was observed in five out of seven patients after exposure to lurbinectedin, and two out of four patients showed increased CD8+ T-cell infiltrates in tumor.

Lurbinectedin continues to be active in patients with progressing malignant pleural mesothelioma. According to our very small sample size, we hypothesize that baseline TAMs and regulatory T cells are associated with survival. Lurbinectedin seems to inhibit conversion of TAMs to M2 phenotype in humans.

Lurbinectedin continues to be active in patients with progressing malignant pleural mesothelioma. According to our very small sample size, we hypothesize that baseline TAMs and regulatory T cells are associated with survival. Lurbinectedin seems to inhibit conversion of TAMs to M2 phenotype in humans.

PD-1/PD-L1 inhibitors do not show activity in mismatch repair proficient (MMRp) colorectal cancer. Inhibition of C-C motif chemokine receptor 5 (CCR5) leads to an antitumoral activation of macrophages, affecting immune cell infiltrates. PICCASSO is a phase I trial exploring safety and efficacy of pembrolizumab and maraviroc in refractory MMRp CRC.

Twenty patients received pembrolizumab and maraviroc (core period, eight cycles), followed by pembrolizumab monotherapy. Primary endpoint was the feasibility rate (patients without treatment-related grade ≥3 immune-related adverse events, treatment-related grade ≥4 adverse events, or any toxicity-related premature withdrawal of treatment). Secondary endpoints included safety/toxicity, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Optional biopsies of liver metastases were performed for analyses of the micromilieu.

The feasibility rate was 94.7% [90% CI 77.4-99.7%], with one grade 4 hyperglycemia and no additional≥gradacy of poststudy salvage treatment and OS was higher than expected in this heavily pretreated population. THIS TRIAL IS REGISTERED AT CLINICALTRIALS.GOV NCT03274804.

The echocardiogram is a useful method for monitoring the cardiovascular complications of chronic obstructive pulmonary disease (COPD), but it is not clear if morphological and functional cardiac variables are able to identify patients with unfavorable COPD progression.

The aim of this study was to investigate morphological and functional echocardiographic variables associated with exacerbation of the disease, pulmonary function parameters and functional capacity evaluation in COPD patients.

A longitudinal observational study including 91 patients diagnosed with COPD, who were stratified in two groups according to their basal right ventricle diastolic diameter (RVDD) measuring greater and less than 35mm. They underwent clinical evaluation, echocardiography, spirometry and 6-minute walking-test (6MWT).

The study found that patients with RVDD greater than 35mm showed worse functional capacity in the 6MWT (p=0.05) and more exacerbation of the disease during the one-year follow-up (p=0.05). There were correlations of greater RVDD vs forced vital capacity (R=-0.27; p=0.02) and distance in the 6MWT (R=0.55; p=0.03) in patients with exacerbation. In the univariate regression analysis, the RVDD was responsible for 55% of the variation in distance in the 6MWT (-0.75m) in COPD patients.

The RV dilation is associated with unfavorable prognostic markers in COPD, such as the worsening of the functional capacity and more frequent exacerbations. The echocardiogram may be a useful tool to identify patients who need more aggressive strategies to control the evolution of the disease with potential impact in pulmonary rehabilitation.

The RV dilation is associated with unfavorable prognostic markers in COPD, such as the worsening of the functional capacity and more frequent exacerbations. The echocardiogram may be a useful tool to identify patients who need more aggressive strategies to control the evolution of the disease with potential impact in pulmonary rehabilitation.Chlorine dioxide (ClO2) is commonly used as an alternative disinfectant to chlorine because it has a high bactericidal effect and may produce limited concentrations of halogenated disinfection byproducts (DBPs). However, previous studies have reported that free available chlorine (FAC) was produced when ClO2 reacted with some compounds, such as phenol, leading to the formation of halogenated DBPs. In this study aliphatic amines was found to react rapidly with ClO2 to form significant amount of FAC and its related DBPs. This study investigated the formation of FAC when ClO2 reacts with six model aliphatic amines (including primary amines, secondary amines and tertiary amines). FAC was formed immediately as ClO2 was added to the precursor solution. The maximum yield of FAC even reached 45% (based on consumed ClO2) when ClO2 reacted with 20 μM methylamine at a dose of 10 μM, which is close to a realistic maximum dose (about 0.8 mg/L) in the U.S.. The reactivity of amines to result FAC follows the sequence tertiary amines less then secondary amines less then primary amines. It was verified that the addition of aliphatic amines may enhance the formation of FAC during ClO2 oxidation in actual water samples. Organic chloramines and other chlorinated DBPs, such as cyanogen chloride, were detected when ClO2 was used as the sole oxidant of real water samples. This study demonstrated that chlorine-related byproducts may also be formed in the presence of organic amines during ClO2 treatment.Microplastic fibers (MFs), as the most frequently detected microplastic shape in sewage sludge, have posed emerging concern for sludge treatment and disposal. However, the effect of MFs on antibiotic resistance genes (ARGs), especially extracellular ARGs (eARGs) during sludge treatment remains far from explicit. Therefore, this study investigated the potential impact of MFs on eARGs during sludge anaerobic digestion (AD), a commonly used sludge treatment method, through long-term operation. The qPCR results showed that both absolute and relative abundances of eARGs increased with the MFs exposure during sludge AD. The average absolute and relative abundances of eight tested eARGs in the AD reactor with the highest MFs dosage (170 items/gTS) were 1.70 and 2.15 times higher than those in the control AD reactor. The metagenomics results further comfirmed the increase of eARGs abundance during sludge anaerobic digestion after MFs exposure and the enhancement did not show significant selectivity. The identification of the potential hosts of eARGs suggested the host numbers of eARGs also increased with MFs exposure, which may suggest enhanced horizonal transformation as a result of increased eARGs. Further exploring the mechansims showed that the genes involved in type IV secretion system was upregulated after MFs exposure, suggesting the active release of eARGs was enhanced with MFs exposure. In contrast, the MFs may not affect the passive release of eARGs as its impact on cell membrance damage was insignificant. The enhanced eARGs in sludge AD process may further accelerate the transport of ARGs in environment, which should be considered during sludge treatment and disposal.Antibiotic resistance genes (ARGs) have become an important public health concern. Particularly, although several ARGs have been identified in wastewater treatment plants (WWTPs), very few studies have characterized their impacts on reactor performance. Therefore, our study sought to investigate the effect of a representative conjugative transfer plasmid (RP4) encoding multidrug resistance genes on ammonia oxidation. To achieve this, we established sequencing batch reactors (SBRs) and a conjugation model with E. coli donor strains carrying the RP4 plasmid and a typical ammonia-oxidating (AOB) bacterial strain (Nitrosomonas europaea ATCC 25978) as a recipient to investigate the effect of conjugative transfer of plasmid RP4 on AOB. Our findings demonstrated that the RP4 plasmid carried by the donor strains could be transferred to AOB in the SBR and to Nitrosomonas europaea ATCC 25978. In SBR treated with donor strains carrying the RP4 plasmid, ammonia removal efficiency continuously decreased to 71%. Once the RP4 plasmid entered N. europaea ATCC 25978 in the conjugation model, ammonia removal was significantly inhibited and nitrite generation was decreased. Furthermore, the expression of several functional genes related to ammonia oxidation in AOB was suppressed following the transfer of the RP4 plasmid, including amoA, amoC, hao, nirK, and norB. In contrast, the cytL gene encoding cytochrome P460 was upregulated. These results demonstrated the ecological risk of ARGs in WWTPs, and therefore measures must be taken to avoid their transfer.Due to the sheer number of contaminated sites, bioavailability-based measurement and modeling of toxicity is used to triage response; despite advances, both remain relatively cumbersome. Cadmium (Cd) and lead (Pb) are two of the most toxic and globally prevalent pollutants, disproportionately impacting disadvantaged communities. Here we demonstrate the use of high throughput lights-on bioreporter technology to measure both speciation and toxicity. The organism's response is fit-for-purpose to parameterize the Biotic Ligand Model used in risk assessment of aquatic ecotoxicity and setting environmental Water Quality Criteria. Toxicity endpoints for analogous Cd and Pb models reported in literature average 71st and 44th rank-percentile sensitivity of Genus Mean Acute Values for acute toxicity (i.e., insensitive) in comparison to the bioreporter, the unique dual-mode measurement ability of which can predict toxicity endpoints from below the 5th percentile up to the 50th rank-percentile. These results are extensible to other reporters, paving the way to cost-efficient environmental risk assessment of aquatic ecotoxicity for a wide range of priority toxic pollutants.Free nitrous acid (FNA, i.e. HNO2) has been demonstrated to have broad biocidal effects on a range of microorganisms, which has direct implications for wastewater management. However, the biocidal mechanisms still remain largely unknown. This study aims to test the hypothesis that FNA will induce cell lysis via cell membrane perforations, and consequently cause cell death via proteolysis, through the use of two model organisms namely Escherichia coli K12 and Pseudomonas putida KT2440. A combination of analytical techniques that included viability assays, atomic force microscopy (AFM), protein abundance assays and proteomic analysis using Quadruple-Orbitrap™ Mass spectrometry was used to evaluate the extent of cell death and possible cell lysis mechanisms. FNA treatment at 6.09 mg/L for 24 h (conditions typically applied in applications) induced 36 ± 4.2% and 91 ± 3.5% cell death/lysis of E. coli and P. putida, respectively. AFM showed that the lysis of cells was observed via perforations in the cell membrane; cells also appeared to shrink and become flat following FNA treatment. By introducing a reactive nitrogen species (RNS) scavenger to act as a treatment control, we further revealed that it was the nitrosative decomposition species of FNA, such as .NO that caused the cell lysis through the destruction of protein macromolecules found in the cell membrane (proteolysis). Subsequently, the RNS went on to cause the destruction of protein macromolecules within the cells. The death of these model organisms E. coli and P. putida following exposure to FNA treatment provides insights into the use of FNA as an antimicrobial agent in wastewater treatment.Recently, graph theoretical analysis based on resting-state functional magnetic resonance imaging has provided a means of investigating the complex brain connectome in obsessive-compulsive disorder (OCD) patients. However, these studies have been restricted to spontaneous blood oxygen level-dependent (BOLD) signals with frequency bands between 0.01 and 0.08 Hz, and the parameters from graph theory across multiple frequency bands have seldom been studied. Here, we calculated global metrics (small-worldness, global efficiency and modularity) and nodal metrics (degree centrality, betweenness centrality, nodal clustering coefficient and shortest path) at four different frequency bands (slow-2 (0.199-0.25 Hz), slow-3 (0.074-0.198 Hz), slow-4 (0.027-0.073 Hz) and slow-5 (0.01-0.027 Hz), from 0.01 to 0.25 Hz) in seventy-three OCD patients and ninety healthy controls. The analyses were also calculated in traditional low-frequency bands (0.01-0.08 Hz) for reference. For the global metrics, the OCD patients showed increased small-worldness and modularity only in the slow-3 band. For the local metrics, we observed a frequency-dependent characteristic, with the main significant differences in regions including the right precentral gyrus, occipital region, right anterior cingulum cortex and fusiform cortex. Our results suggested frequency-specific abnormalities of the brain connectome in OCD and the future studies may need to consider different frequency bands when measuring spontaneous activity in the brain.Social mentalizing refers to the ability to understand the intentions, causes, emotions and beliefs of another person or the self and is crucial for interpersonal understanding. Disturbances in this process may lead to aggressive and violent behaviors. Literature has shown that male perpetrators convicted for intimate partner crime (IPVAW) present alterations in different measures related to social mentalizing, in particular, they present more irrational thoughts toward women and difficulties in emotional recognition and empathy processes. However, the brain mechanisms underlying this process are still unknown. The aim of this study is to examine the resting-state functional connectivity of the cerebellar Crus II area, as a core component of social mentalizing in male perpetrators, and to explore if this connectivity is associated with social mentalizing processes. To achieve these objectives, we compared the resting-state connectivity of 25 men convicted for an IPVAW crime (male perpetrators) with 29 men convicted for other crimes (other offenders) and 28 men with no criminal records (non-offenders) using a seed-based whole brain analysis. Subsequently, correlations were performed to explore the association between the significant connectivity networks and social mentalizing measures only in male perpetrators of IPVAW. Analyses showed that male perpetrators of IPVAW exhibit hyperconnectivity between Crus II and posterior areas of the default mode network, frontoparietal and limbic areas compared to other offenders and non-offenders. In addition, the greater connectivity found between the Crus II and the posterior default mode network was related to a greater number of distorted thoughts about women and less affective empathy in male perpetrators of IPVAW. These results show that connectivity between the cerebellum and the default mode network may underlie the social processes that are at the basis of intimate partner violence perpetration.

Leptin, a hormone related to satiety, has been studied because of its association with obesity and sleep apnea. The distribution of leptin receptors in the brain stem, and in the hypoglossal nucleus, has not yet been described. The stimulation of these muscles has been studied in the treatment of sleep apnea.

to detail the presence of leptin receptors in the nuclei of these nerves to enable studies of stimulation of this region through leptin.

the brains of five cadavers, removed during necropsy, collected at the Death Verification Service were included. An informed consent was signed by a family member (wife, mother or son/daughter) who answered specific questionnaire concerning comorbities. Anthropometric measurements were recorded. The medulla oblongata and pons fragments were identified. Immunohistochemical staining analysis was performed to identify the location of the leptin receptors.

In the immunohistochemical analysis an intense staining signal of the brownish coloration of neurons was evidenced in the hypoglossal nerve nucleus, moderate in the olivary nucleus and mild in the dorsal nucleus of the vagus and trigeminal nucleus. In motor neurons, more intense brown pigmentation can be observed in the nucleus and cytoplasm when compared to sensory neurons.

The immunoexpression of leptin receptor was demonstrated in the motor neurons of the human hypoglossal nucleus. These results may contribute to unravel details of the pathophysiology of neuromuscular control of airway collapse during sleep and to the development of new drugs capable of improving the neuromuscular tone of upper airway in apneic individuals.

The immunoexpression of leptin receptor was demonstrated in the motor neurons of the human hypoglossal nucleus. These results may contribute to unravel details of the pathophysiology of neuromuscular control of airway collapse during sleep and to the development of new drugs capable of improving the neuromuscular tone of upper airway in apneic individuals.Pancreatic cancer (PaCa), a common and highly lethal malignant cancer, is often insensitive to radio- and/or chemotherapy. Therefore, effective treatment regiments are still lacking. Herein, we found that an extract of Ficus carica fruit (EFCF) exerted anti-tumor effects on PaCa cells. EFCF induced cell viability inhibition and apoptotic cell death in two PaCa cell lines in a dose- and time dependent manner. EFCF effectively suppressed the migration, metastasis, invasion, and colony formation of PaCa cells. Mechanistically, EFCF stimulated an increase in intracellular ROS to promote cell death and senescence. EFCF treatment also triggered autophagy, and autophagy inhibition enhanced EFCF-induced cell death. We found that EFCF decreased mitochondrial membrane potential and promoted lipid peroxidation. Moreover, intragastric administration of EFCF effectively suppressed xenograft PaCa growth inhibition by activating cell death. EFCF had no apparent toxicity to normal pancreatic epithelial cells. Together, these findings suggest that EFCF may be a potential treatment for PaCa.Dupuytren disease (DD) is a hand-localized fibrotic disorder characterized by a scar-like, collagen-rich cord. Treatment usually comprises surgical removal of the cord, but is associated with a high relapse rate, in some cases requiring finger amputation. There is currently no consensual medical approach for treating DD. Numerous preclinical studies have highlighted antifibrotic properties of metformin, and the aim of this study was to assess a potential antifibrotic role of metformin in DD. Fibroblasts from DD cords (DF) and phenotypically normal palmar fascia (PF) were extracted from surgical specimens and cultured. The fibrotic status of DF and PF was compared at baseline, and under profibrotic (TGF-β stimulation) and antifibrotic (metformin stimulation) conditions, using quantitative RT-PCR, western blot, immunocytochemistry, and a functional fibroblast contraction assay. At baseline, DF showed higher levels of fibrotic markers and contraction capacity compared with PF. Both types of fibroblasts responded to TGF-β stimulation. Treatment of DF and PF with metformin did not affect basal levels of fibrotic markers and contraction but largely prevented their induction by TGF-β. In conclusion, our data show that metformin inhibits TGF-β-induced expression of fibrotic markers and contraction in hand-derived fibroblasts. This supports the case for a clinical trial to assess the repurposing of metformin as an adjuvant to surgery, to prevent, reduce, or delay recurrence in at-risk DD patients.AHCC® is a standardized extract of cultured mushroom (Lentinula edodes) mycelia with a wide variety of therapeutic effects including anti-inflammatory, antitumor and antiviral effects. Trichinellosis, a food-borne parasitic zoonosis is caused by the nematode Trichinella spp. Infection with Trichinella is characterized by the induction of a Th1-type response at the beginning of the intestinal phase, followed by a dominant Th2-type response which is essential for parasite expulsion. The aim of this study was to evaluate the immunomodulatory effect of AHCC® in a murine model of Trichinella spiralis infection. Swiss CD1 mice were infected with T. spiralis larvae and treated with AHCC®. Standard treatment with albendazole (ABZ) was used as control in the assessment of parasite burden. The small intestine was taken out and the proximal segment was evaluated for several parameters gene expression of immune and stress-reticulum mediators, histological damage score, goblet cell count and Mucin 2 (Muc2) gene expression. AHCC® modulated expression levels of both Th1 and Th2 cytokines and reduced histological damage score. In addition, AHCC® diminished the number of adults of T. spiralis in treated animals. AHCC® treatment anticipates T. spiralis expulsion and increases goblet cell number and Muc2 gene expression.Nowadays, about 30% of magnetic resonance imaging (MRI) exams need contrast agents (CAs) to improve the sensitivity and quality of the images for accurate diagnosis. Here, a multifunctional nano-agent with ring-like vortex-domain iron oxide as core and gadolinium oxide as shell (vortex nanoring Fe3O4 @Gd2O3, abbreviated as VNFG) was firstly designed and prepared for highly enhanced T1-T2 dual-modality magnetic resonance imaging (MRI)-guided magnetic thermal cancer therapy. After thorough characterization, the core-shell structure of VNFG was confirmed. Moreover, the excellent heat generation property (SAR=984.26 W/g) of the proposed VNFG under alternating magnetic fields was firmly demonstrated. Furthermore, both in vitro and in vivo studies have revealed a good preliminary indication of VNFG's biological compatibility, dual-modality enhancing feature and antitumor efficacy. This work demonstrates that the proposed VNFG can be a high-performance tumor diagnosis and theranostic treatment agent and may have great potential for clinical application in the future.

Astragalus and Safflower are commonly used in the treatment of stroke. Studies have shown that their two active components, hydroxysafflor yellow A (HSYA) and calycosin (CA), have protective effects on cerebral ischemia-reperfusion injury (I/R). However, the pharmacokinetic-pharmacodynamic (PK-PD) modeling study of the combination of the two components has not been reported in rats. The study aimed to perform combined PK-PD modeling of HSYA and CA in normal and cerebral ischemia model rats to explain quantitatively their time-concentration-effect relationship.

To make the middle cerebral artery occlusion (MCAO) model. SD rats were randomly divided into normal treated group (NTG) (n=6), model group (MDG) (n=6) and model treated group (MTG) (n=6). Plasma was collected from the mandibular vein after 0, 2, 5, 10, 15, 20, 30, 45, 60, 75, 90, 120, 180, and 240min after intravenous administration. Rats in NTG and MTG were administered the same dose of HSYA (5mg/kg) and CA (8mg/kg) by tail vein injection. HPLC-VWion of HSYA and CA was successfully established in rats, and the differences in pharmacodynamic and pharmacokinetic properties between the normal and cerebral ischemic rats were evaluated. Based on comprehensive data analysis, we found that the combination of HSYA and CA may exert protective effects against I/R injury in rats via anti-apoptotic and anti-inflammatory pathways. The study provided additional insights into the development of drugs for ischemic stroke as well as the design of appropriate dosing regimens.For understanding the significance of tidal pumping for driving submarine groundwater discharge (SGD), two time series observations were conducted over tidal cycles in typical mariculture areas of Sanmen Bay, China. Based on 224Ra and dissolved silicon (DSi), the tide-driven SGD fluxes showed significant negative correlations with tidal height, and were 16.4 ± 5.6 cm d-1 and 21.7 ± 13.9 cm d-1 at two coastal sites of the Sanmen Bay, highlighting the potential of DSi in SGD calculation when coastal waters are on short time scales. Furthermore, nutrient fluxes through tidally influenced SGD were estimated to be 11.5-26.5 mmol m-2 d-1 for dissolved inorganic nitrogen, 0.06-0.34 mmol m-2 d-1 for dissolved inorganic phosphorus and 11.5-32.1 mmol m-2 d-1 for DSi, which were higher than those from surface loadings, revealing that tide-driven SGD with large amounts of nutrient and high NP ratios may significantly contribute to the development of marine aquaculture.This editorial presents results of the MANA (MANagement of Atolls) project compiled in the form of a Marine Pollution Bulletin collection of 14 articles. MANA is a project funded by the French Agence National pour la Recherche that specifically addresses the development of knowledge and management tools for pearl farming atolls, with a focus on the spat collecting activity in French Polynesia. The 14 papers cover the range of thematic tasks described in the initial project, including atoll geomorphology and bathymetry, climate forcing, atoll lagoon and rim hydrodynamics, typology of atolls, evaluation of remote sensing data for monitoring atoll lagoons, and development of numerical models and spatially-explicit tools that altogether have contributed to the applied objectives. In addition, this editorial draws an update on the pearl farming industry in French Polynesia with the latest statistics, and discusses the next targeted priorities for research programs focusing on pearl farming atolls.As global ecological disasters, green tide outbreaks have been observed in the Southern Yellow Sea (SYS) of China since 2007, resulting in considerable economic losses and environmental damage to the coastal cities of Jiangsu and Shandong Provinces. Therefore, prevention of green tides is crucial. Previous studies have revealed that a relatively small green tide outbreak scale in the SYS was observed in 2018 and 2020, with the green tides covering areas of 193 km2 and 192 km2 and durations of 91 days and 64 days, respectively. Killing green macroalgae attached to cultivation ropes in Neopyropia aquaculture areas, which has been considered a primary source of the blooms, early removal of Neopyropia aquaculture rafts, and green tide prevention in the SYS are the key reasons for the decrease in green tides in 2018 and 2020. Furthermore, to address the challenges associated with the current green tide source prevention measures, we proposed a comprehensive control method that combines ecological farming, early green tide prevention, and resource utilization.