Results show the limitations faced by environmental managers in relation to the use of Remote Sensing technologies and the shortcomings associated with a purely technology driven approach to the development of satellite missions. Through the introduction of this flexible and user centred approach instead, this paper provides a clear overview of agro-environmental user requirements and represents the basis for the definition of an integrated agricultural service.In this study, we investigated the feasibility on the utilization of coffee husk as biosorbents for the removal of heavy metal ions such as Pb2+ and Cd2+ from wastewater. Biochar was produced from coffee wastes and modified with sodium hydroxide to create functional groups on the surface and increase the specificic surface area. The resultant products were characterized by using various analytical methods such as scanning electron microscopy, specific area, surface functional group and zeta potential analysis. The as-prepared materials were employed as adsorbent to remove Pb2+ and Cd2+ ions from wastewater. The maximum sorption capacities of biosorbents were measured to be 116.3 and 139.5 mg g-1 for Cd2+ and Pb2+, respectively, which is comparable to the conventional adsorbents. Kinetic studies showed that the sorption of Pb2+ and Cd2+ on biosorbents can be described by the Freundlich isotherm and second-order kinetic model. The coffee husk-derived biosorbent was capable of removing 89.6% of Pb2+ and 81.5% Cd2+ ions from wastewater, and therefore can be considered as low-cost and efficient adsorbent to remove heavy metal ions from wastewater.Food is often exposed to multiple types of contaminants, and the coexistence of contaminants may have antagonistic, additive or synergistic effects. This study investigated the combinatorial toxicity of the three most widespread exogenous contaminants, decabrominated diphenyl ether (BDE-209), bisphenol A (BPA), and acrylamide (ACR) to HepG2 cells. A mathematical model (Chou-Talalay) and high-content analysis (HCA) were used to probe the nature of the contaminants’ interactions and their cytotoxicity mechanisms, respectively. The results highlighted that for the individual pollutants, the cytotoxicity order was BDE-209> BPA > ACR, and varying combinations of contaminants exhibited additive/synergistic effects. In general, combining multiple contaminants significantly increased intracellular reactive oxygen species (ROS), Ca2+ flux, DNA damage and Caspase-3, and decreased mitochondrial membrane potential (MMP) and nucleus roundness, indicating that the additive or synergistic mechanism of the combined contaminations was disturbance to multiple organelles. This study emphasizes the complexity of human exposure to food contaminants and provides a scientific basis for formulating strict regulatory standards.Municipal wastewaters are abundant low-strength streams that require adequate treatment and disposal to ensure public and environmental health. This study aims to provide a comprehensive summary of municipal wastewater research in Europe in the 2010s in the form of bibliometric analysis. The work was based on the Science Citation Index Expanded (Web of Science) and carried out using the R-package bibliometrix for bibliometric data analysis and the software VOSviewer for science mapping. Analysing a dataset of 5645 publications, we identified the most influential journals, countries, authors, institutions, and publications, and mapped the co-authorship and keyword co-occurrence networks. Spain had produced the most publications while Switzerland had the highest average citations per publication. China was the most collaborative country from outside of Europe. Analysis of the most cited articles revealed the popularity of micropollutant removal in European municipal wastewater research. The keyword analysis visualized a paradigm shift from pollutant removal towards resource recovery and circular economy. We found that current challenges of resource recovery from municipal wastewater come from both technical and non-technical (e.g., environmental, economic, and social) aspects. We also discussed future research opportunities that can tackle these challenges.Aluminum (Al)1 is ubiquitously present in the environment, and human exposure to Al is common. Al has been reported to be involved in various human diseases and adverse pregnancy outcomes, including neural tube defects (NTDs). This study aimed to examine the association between prenatal Al exposure and the risk for NTDs using Al concentrations in maternal serum and placental tissue. The subjects were recruited from six counties/cities in the Shanxi province of northern China from 2003 to 2016. Al concentrations in both types of specimens were assessed using inductively coupled plasma-mass spectrometry. In the maternal serum cohort (200 cases and 400 controls), compared to the lowest tertile concentration of Al, the highest Al tertile was associated with 2.42-fold (95% confidence interval, 1.23-4.87) increased risk after adjustment for confounding factors. In the placental tissue cohort (408 cases and 593 controls), the highest tertile of Al also tended to be associated with an elevated risk for NTDs [adjusted odds ratio, 1.60 (0.94-2.70)]. When analyzed by NTD subtypes, the highest Al tertile was associated with an increased risk for anencephaly in both cohorts after adjustment for confounders [odds ratio, 1.97 (1.15-3.48) in the maternal serum cohort; odds ratio, 4.75 (2.01-12.00) in the placental tissue cohort]. Taken together, using concentrations of Al in maternal serum and placental tissue as exposure markers, we found that prenatal exposure to higher levels of Al is a risk factor for fetal NTDs, especially for the anencephaly subtype.Probiotic supplementation is effective to modulate the metabolic disorders caused by perfluorobutanesulfonate (PFBS). However, the underlying mechanisms remain unclear. To this end, the present study exposed adult zebrafish to PFBS (0 and 10 μg/L), probiotics, or their binary combinations for 40 days. After the exposure, the nutritional stores, intestinal organization, and metabolic activities along the gut-liver axis were investigated. The results showed that PFBS exposure decreased the nutrient reserves significantly, especially the lipid content, which was alleviated by the probiotic administration. Intestinal mucus secretion was promoted remarkably in the presence of the probiotic, which enhanced epithelial protection against PFBS damage. Metagenomic analysis showed that PFBS alone induced gut microbial dysbiosis, which was efficiently antagonized by the probiotic bacteria. Intestinal metabolomic profiling revealed that ferroptosis occurred because of the unrestricted lipid peroxidation following PFBS exposure. However, probiotic administration prevented the ferroptotic symptoms induced by PFBS, further highlighting the beneficial effects of the probiotic on the host. In PFBS-exposed livers, high levels of bile acid metabolites (e.g., taurochenodeoxycholic acid) accumulated, implying the induction of cholestasis. Notably, probiotic addition recovered the metabolomic homeostasis under PFBS stress, probably resulting from the activation of detoxification pathways based on the pentose and glucuronate interconversion. Overall, the present study provides systematic evidence of the antagonistic interaction between PFBS and the probiotic regarding the metabolic activities along the microbe, gut and liver axis, highlighting the application values of probiotic recipe in aquaculture industry and ecological reservation.Mobilizable colloids from reservoir sediment contain nutrients and contaminants, thus may affect water quality once being released. A major obstacle to evaluate the quantity and quality of mobilizable colloids in natural system is the using of appropriate method for colloid extraction from sediment and their separation from dissolved and particulate phases. This work evaluates the role of different extraction methods (agitation, sonication at sediment pH, and sonication at alkaline pH) on the characteristics (mass, size, shape and composition) of water-mobilizable colloids from sediment of Champsanglard dam reservoir (France). Attention has been paid to phosphorus (P), an important element in controlling eutrophication. Recovered colloids were highly affected on both quantity and quality according to the different applied protocols. The less aggressive agitation liberated low-energy water-dispersible colloids without physical damage and with less modification in colloidal chemical composition and shape, whereas sonication released 10-20 times higher colloid quantity but in lower size, due to physically disruption of fragile sediment structure or aggregated/chained colloids. In contrast, alkaline pH intensified colloid release by fortified repulsive forces between colloids and dissolution of organic coat. Concerning phosphorus, competition with hydroxide ions for sorption site or dissolution of phosphate minerals in alkaline pH caused release of dissolved P to solution and decrease of P content in recovered colloids. A special care should be paid to method selection according to the aim of the study and when comparing data from experiments conducted with different colloid extraction methods.The aim of the study was to investigate the effect of iron coagulant (IC), aluminum coagulant (AC) and lanthanum modified bentonite (LMB) on the embryogenesis of pike. Physicochemical indicators of the water were determined according to the methods recommended by APHA (1999). The applied precipitating agents (IC, AC, LMB) at appropriate concentrations were sprayed on the surface of water in aquariums with the pike eggs placed on nets. The eggs were observed under a microscope, documenting their development using digital photography NIS Elements Br software. The number of fertilized eggs, embryo survival, and the percentage of malformed larvae were determined. The pike eggs and hatched larvae were recorded and measured. The percentage of fertilized eggs was found to be the highest in the control sample (LW) and in the IC sample (94% and 93.3%, respectively), 85.9% in the AC sample and 81.8% in the LMB sample. The pace of pike embryogenesis in the samples was identical – the embryos in both the control and other samples reached individual stages of embryonic development with an equal number of degree days (DD). The IC group hatched the earliest, and the control sample was the last to hatch (LW). In the control sample, the hatched larvae were the longest and had the lowest percentage of malformed individuals. The control sample also had the highest rate of embryo survival (85.9%), while the lowest was in the LMB sample (68.6%). These results indicate that the application of precipitating measures to improve water quality should not coincide with the periods of fish reproduction.Cyanobacteria produce numerous volatile organic compounds (VOCs) that show a lytic activity against other cyanobacteria. We found the lytic phenomenon under natural conditions and during densification experiments, and also observed the species change of the cyanobacteria during the lysis processes, in which Microcystis finally became dominant. The species change of the cyanobacteria was strongly suggested to depend on the susceptibility of the cyanobacteria toward the VOCs. To verify this suggestion, the susceptibility of the species was evaluated by the minimal inhibitory concentration (MIC) using axenic cyanobacterial strains against β-cyclocitral, its oxidation products and β-ionone with the aid of log D. It was found that the difference depended on the susceptibility of the cyanobacteria toward the VOCs, in which β-cyclocitral played a crucial role and Microcystis had a significantly protective ability compared to the other cyanobacteria. In addition, the species change of cyanobacteria was consistent with the cyanobacterial seasonal succession in Lakes Sagami and Tsukui, based on data that had been accumulated for 10 years. Conventionally, although this phenomenon could be explained by nutrient availability or the physical structure of the environment, the results of this study revealed that it was controlled by the VOCs, particularly β-cyclocitral produced by the cyanobacteria.Some cyanobacteria produce toxins that threaten the aquatic ecosystem and human health. To prevent serious consequences, this study suggests a potential means of reducing microalgal toxins, microcystins (MCs) by applying non-thermal plasma (NTP) process. Quantified MC-RR, -LR, and -YR were drastically degraded and removed as much as 99.9% by reactive species generated by NTP. Results further demonstrate that NTP uses less energy based on estimated energy per order (EEO kWh m-3 order-1) than other advanced oxidation processes and requires relatively less time to remove the MCs. As a result, NTP may be a viable management option for effective MC control during severe surface water blooms.The aqueous extract synthesized using the biomass, Ziziphus spina-christi, was applied to protect the surface of aluminium under acidic environment. The influence of extract concentration (0-0.14 mg/ml), contact time (2-8 h) and temperature (303.15-313.15 K) on the inhibition efficiency was studied. Langmuir isotherm fitted well to the experimental observations (R2 > 0.960) confirmed the monolayer attachment of inhibitors. The values of activation energy observed in this study suggests that the inhibition process to be surface interaction-based process. Thermodynamic parameters confirmed the process as feasible and exothermic. Potentiodynamic polarization and Electrochemical impedance spectroscopy studies are conducted to study the mechanism of corrosion. The electrochemical corrosion kinetics was studied using current density-potential curves and the Tafel constants (βa and βc) were calculated as 154.42 and 128.35 mV, at 0.14 mg/mL of inhibitor concentration. The biomass-based corrosion inhibitor was characterized using scanning electron microscope and attenuated total reflection techniques.Membrane bioreactor technology includes the integration of biological wastewater treatment and physical separation by membrane filtration. When analyzing the system performance, efficiency of biological processes, physical separation and membrane fouling must be taken into consideration. Over the years, mathematical modelling of wastewater treatment has evolved and is being used extensively to optimize the performance of treatment systems. A Number of attempts have been made towards the development of mathematical models for membrane bioreactors and most of these models have not considered the effect of soluble microbial products on membrane fouling. Also the effect of periodic membrane cleaning was neglected. In this study, an integrated mathematical model was developed for the membrane bioreactor. A biological model based on activated sludge processes (extended with biopolymer kinetics) and a physical model with cake layer kinetics and membrane fouling have been combined. In order to overcome the drawbacks of previous attempts of modelling, the influence of soluble microbial products and extracellular polymeric substances are considered in the model integration. Further, the physical processes of the sludge removal and membrane cleaning which have strong influence on membrane fouling are considered in the model. „AQUASIM”, a computer program for the identification and simulation of aquatic systems, was used for solving the processes. Calibrated and validated model enables the prediction of the system performance and membrane fouling under different operating conditions.3D-particulate and 1D-fiber structures of multiferroic bismuth ferrite (BiFeO3/BFO) and their composites with 2D-graphene oxide (GO) have been developed to exploit the different scheme of interfacial engineering as 3D/2D and 1D/2D systems. Particulates and fibers of BFO were developed via sol-gel and electrospinning fabrication approaches respectively and their integration with GO was performed via the ultrasonic-assisted chemical reduction process. The crystalline and phase formation of BiFeO3 and GO was confirmed from the XRD patterns obtained. The electron microscopic images revealed the characteristic integration of 3D particulates (with average size of 100 nm) and 1D fibers (with diameter of ~150 nm and few μm length) onto the 2D GO layers (thickness of ~27 nm). XPS analysis revealed that the BFO nanostructures have been integrated onto the GO through chemisorptions process, where it indicated that the ultrasonic process engineers the interface through the chemical modification of the surface of these 3D/2D and 1D/2D nanostructures. The photophysical studies such as the impedance and photocurrent measurements showed that the charge separation and recombination resistance is significantly enhanced in the system, which can directly be attributed to the effective interfacial engineering in the developed hetero-morphological composites. The degradation studies against a model pollutant Rhodamine B revealed that the developed nanocomposites exhibit superior photocatalytic activity via the effective generation of OH radicals as confirmed by the radical analysis studies (100% degradation in 150 and 90 min for 15% GO/BFO particulate and fiber composites, respectively). The developed system also demonstrated excellent photocatalytic recyclability, indicated their enhanced stability.This study aimed to produce a clean energy, hydrogen, and to remove pollutants simultaneously in water by photoelectrochemical (PEC) method. The photo-anode of cuprous oxide modified titanate nanotube arrays (Cu2O/TNTAs) was synthesized by using lactic acid, green tea, and coffee as reductants individually. The characterizations of Cu2O/TNTAs were performed by ultraviolet-visible diffuse reflectance spectroscopy (UV-vis DRS), field emission scanning electron microscope (FE-SEM), X-ray photoelectron spectroscopy (XPS), and X-ray diffraction (XRD) to investigate the physical and chemical properties such as structure, crystallization, element contents, and optical performance. The electrochemical analyses of Cu2O/TNTAs showed the photo-current of Cu2O/TNTAs-t (using green tea as reductant) was 2.4 times higher than pure TNTAs, illustrating the effective separation of electron-hole pairs after Cu2O modification. The photoelectrochemical performances of Cu2O/TNTAs-t and Cu2O/TNTAs-c (using coffee as the reductant) were better than Cu2O/TNTAs-L (using lactic acid as the reductant) in terms of photo-current density, Ibuprofen degradation, and hydrogen generation, implying that depositing Cu2O on TNTAs can significantly improve the electron mobility by reducing the recombination rate of electron-hole pairs, which is beneficial to simultaneously ibuprofen degradation and hydrogen production.Arsenic oxyanions are toxic chemicals that impose a high risk to humans and other living organisms in the environment. The present study investigated indigenous heterotrophic bacteria in the tailings dam effluent (TDE) of a gold mining factory. Thirty-seven arsenic resistant bacteria were cultured on Reasoner’s 2A agar supplemented with arsenic salts through filtration. One strain encoded as PMS5 with the highest resistance to 140-mM sodium arsenite and 600-mM sodium arsenate in tryptic soy broth was selected for further investigations. According to phenotypic examinations and 16S rDNA sequence analysis, PMS5 belonged to the genus Alishewanella and was sensitive to most of the examined antibiotics. The biosorption and bioaccumulation abilities of arsenic salts were observed in this isolate based on Scanning Electron Microscopy (SEM) with Energy Dispersive X-Ray Analysis (EDX) and biosorption and bioaccumulation data. PMS5 was also found to cause the volatilization and biotransformation of arsenic oxyanions through their oxidation and reduction. Moreover, the contribution of PMS5 to arsenic (3+, 5+) bioprocessing under oligotrophic conditions was confirmed in fixed-bed reactors fed with the TDE of the gold factory (R1) and synthetic water containing As5+ (R2). According to biofilm assays such as biofilm staining, cell count, detachment assay and SEM, the arsenic significantly reduced the biofilm density of the examined reactors compared to that of the control (R3). Arsenate reduction and arsenite oxidation under bioreactor conditions were respectively obtained as 75.5-94.7% and 8%. Furthermore, negligible arsenic volatilization (1.2 ppb) was detected.The fall of 2020 brought several new variants of SARS-CoV-2 circulating across the globe, and the steadily increasing COVID-19 cases are responsible for the emergence of these variants. All the SARS-CoV-2 variants reported to date have multiple mutations in the spike (S) protein, specifically in the receptor-binding domain (RBD). Here, we employed an integrated computational approach involving structure and sequence based predictions to study the effect of naturally occurring variations in the S-RBD on its stability and ACE2 binding affinity. The hotspot stabilizing residue mutations N501I, N501Y, Q493L, Q493H and K417R, strengthen the RBD-ACE2 complex by modulating the interaction statistics at the interface. Thus, we report here some critical mutations that could increase the binding affinity of the SARS-CoV-2 RBD with ACE2, increasing the viral infectivity and pathogenicity. Understanding the effect of these mutations will help in developing potential vaccines and therapeutics.Snoring is the most direct symptom of obstructive sleep apnea hypopnea syndrome (OSAHS) and implies a lot of information about OSAHS symptoms. This paper aimed to identify OSAHS patients by analyzing acoustic features derived from overnight snoring sounds. Mel-frequency cepstral coefficients, 800 Hz power ratio, spectral entropy and other 10 acoustic features were extracted from snores, and Top-6 features were selected from the extracted 10 acoustic features by a feature selection algorithm based on random forest, then 5 kinds of machine learning models were applied to validate the effectiveness of Top-6 features on identifying OSAHS patients. The results showed that when the classification performance and computing efficiency were taken into account, the combination of logistic regression model and Top-6 features performed best and could successfully distinguish OSAHS patients from simple snorers. The proposed method provides a higher accuracy for evaluating OSAHS with lower computational complexity. The method has great potential prospect for the development of a portable sleep snore monitoring device.

Sleep disturbances are features of Parkinson’s disease (PD), that can already occur before PD diagnosis. The most investigated prodromal PD sleep disorder is REM sleep behavior disorder (RBD). The relation between other polysomnographic (PSG) alterations and the prediagnostic stages of PD, however, is less clear.

We performed a retrospective case-control study to characterize polysomnographic alterations in PD and prediagnostic PD. We included 63 PD subjects (33 subjects that underwent a video-PSG before PD diagnosis [13 with and 20 without RBD] and 30 subjects that underwent a PSG after PD diagnosis) and 30 controls. PSGs were analyzed for sleep stages, different RSWA variables, body position, arousals, periodic limb movements, and REM density.

Higher subscores of all RSWA variables were observed in subjects with PD and prediagnostic PD (with and without RBD). Total RSWA, tonic RSWA and chin RSWA severity were significant predictors for all PD and prediagnostic PD groups. Our study also shows a higher percentage of nocturnal supine body position in all PD and prediagnostic PD groups. Supine body position percentage is the highest in the PD group and has a positive correlation with time since diagnosis.

These findings suggest that increased total, tonic and chin RSWA as well as nocturnal supine body position are already present in prediagnostic PD, independently of RBD status. Prospective longitudinal studies are necessary to confirm the additional value of these PSG abnormalities as prodromal PD biomarkers.

These findings suggest that increased total, tonic and chin RSWA as well as nocturnal supine body position are already present in prediagnostic PD, independently of RBD status. Prospective longitudinal studies are necessary to confirm the additional value of these PSG abnormalities as prodromal PD biomarkers.This study aimed to investigate the effects of pre-bedtime blue-light exposure on ratio of deep sleep and sleep quality. In this study, 11 healthy young men were exposed to three conditions for 1 h before bedtime 1) incandescent light, 2) blue-light, or 3) blue light-blocking glasses on. The following morning, subjective sleep quality was measured using the Oguri-Shirakawa-Azumi Sleep Inventory. Sleep time, ratio of sleep, ratio of deep sleep, and body movements during sleep were measured using a mat sleep-scan (sleep scan, SL- 504; TANITA Corp., Japan) and an ambulatory portable sleep study system (LS-140; Fukuda Denshi Co. Ltd., Japan). Ratio of deep sleep was significantly decreased in the blue-light exposure group compared to the groups with incandescent light and blue light-blocking glasses (p less then 0.01), There were no differences noted in sleep time or body movements among the three groups. These results suggest that blue-light exposure to affects sleep quality by reducing the ratio of deep sleep.

Social jetlag has been reported to predict obesity-related indices, independent of sleep duration, with associations in female adolescents but not males. However, such sex-specific relationships have not been investigated in pre-adolescents.

To examine (i) the relationships between sleep characteristics, including social jetlag, and obesity-related outcomes during childhood, and (ii) whether these relationships are moderated by sex.

This cross-sectional study included 381 children aged 9-11 years (49.6% female). Average sleep duration, social jetlag, and physical activity were assessed via wrist-worn accelerometry. Sleep disturbances were quantified from the Children’s Sleep Habits Questionnaire. Obesity-related outcomes included age-specific body mass index Z-scores (zBMI) and waist-to-height ratio. Additionally % fat, total fat mass, and fat mass index were assessed via bioelectrical impedance analysis. Linear mixed models that nested children within schools were used to identify relationships among sleep characteristics and obesity-related outcomes.

Positive associations between social jetlag with zBMI, % fat, and fat mass index were seen in univariable and unadjusted multivariable analyses. Following adjustments for known confounders, social jetlag remained significantly associated with zBMI (β=0.12, p=0.013). Simple slopes suggested a positive association in girls (β=0.19, p=0.006) but not in boys (β=0.03, p=0.703).

Obesity prevention efforts, particularly in girls, may benefit from targeted approaches to improving the consistency of sleep timing in youth.

Obesity prevention efforts, particularly in girls, may benefit from targeted approaches to improving the consistency of sleep timing in youth.The Green Revolution of the 1960s boosted cereal crop yields in part through widespread adoption of semi-dwarf plant varieties, many of which were later found to have mutations in either gibberellins (GAs) homeostasis or DELLA proteins. GA is essential for plant growth and developmental regulation and plays an important role in improving crop plant architecture for enhanced grain yield under high nitrogen conditions. A complex regulatory network governs the spatially and temporally controlled genes expression through integrative GA signaling in response to multiple endogenous and environmental cues. In this review, we summarize current advances in understanding the molecular mechanisms of DELLA-dependent and DELLA-independent GA signaling pathways and their contributions to plant developmental and metabolic adaptations to changes in nitrogen availability. The progress in molecular understanding of the plant growth-metabolic coordination will facilitate breeding strategies for future sustainable agriculture and a new Green Revolution.

Immune checkpoint inhibitors (ICIs) have led to a paradigm change in the management of metastatic renal cell carcinoma (mRCC). Prospective trials have focused on ICI treatment in the first or second line. The aim of this analysis is to evaluate the benefit of ICI across different treatment lines.

This is a single-center retrospective study that included mRCC patients who received ICIs in various treatment lines. Objective response rates (ORR), progression-free survival (PFS) and overall survival (OS) were evaluated.

Ninety-four patients were eligible for full evaluation. Patients were classified as International mRCC Database Consortium (IMDC) risk group categorization as good, intermediate and poor risk in 26.8%, 61.6% and 14.8% of cases, respectively. They were treated with ICI monotherapy, dual ICI therapy and ICI+ tyrosine kinase inhibitor in 59%, 20% and 21% of cases, respectively. ORR, median PFS and OS for the entire cohort was 39.4%, 9.67 months [95% confidence interval (CI) 6.9-12.4 months] and 23.6 months (95% CI 13.3-33.9 months), respectively. The ORR by treatment line was 33% in first, 40.4% in the second, 35% in the third and 43.5% in the fourth line and beyond. Median PFS by treatment line was 8.6, 10.3, 7.9 and 7.23 months, respectively. The median OS was not reached in first-line treatment and was 26.2, 18.1 and 20.7 months in the second, third and fourth line and beyond, respectively.

ICIs or ICI combinations are active in all treatment lines and should also be offered in heavily pretreated patients. Patient selection based on tumor and patient factors allows for maximal benefit from ICI-based therapies.

ICIs or ICI combinations are active in all treatment lines and should also be offered in heavily pretreated patients. Patient selection based on tumor and patient factors allows for maximal benefit from ICI-based therapies.The gut-brain axis plays a critical role in the maintenance of the gastrointestinal tract homeostasis. Several enteric pathogens have developed strategies to sense neurochemical molecules to regulate their virulence in the gut. Additionally, there is growing evidence that gut dysbiosis can strongly affect host brain responses. Here we review different mechanisms that have been proposed to mediate gut-brain axis communication using Citrobacter rodentium, a natural murine enteric pathogen and one of the most widely used small animal models for studying host-microbe interactions. We highlight studies that have identified-specific pathways used by C. rodentium to sense host neurochemicals during colonization as well as behavioral responses and brain pathologies affected by pathogen colonization of the gut.

PD-L1 expression on tumor cells (TCs) or immune cells (ICs) may be used as a prognostic marker for survival in patients with NSCLC. We characterized PD-L1 expression on TCs or ICs in a patient cohort with NSCLC to determine associations between PD-L1 expression and overall survival (OS), according to EGFR and KRAS mutation status.

Danish patients aged >18 years diagnosed with NSCLC before 2014 on first- (N = 491), second- (N = 368), or third-line (N = 498) therapy were included. Data were extracted from population-based medical registries. Tumor samples from pathology archives were tested for biomarkers. High PD-L1 expression was defined as expression on ≥25 % of TCs or ICs based on first diagnostic biopsy or surgical resection. KRAS and EGFR mutation status were tested using PCR-based assays. Cox regression analysis was used to compute adjusted HRs and associated 95 % CIs.

PD-L1 TC and IC ≥ 25 % were observed in 24.3 %-31.0 % and 11.7-14.7 % of patients, respectively. EGFR and KRAS mutations were detected in 4.7 %-8.8 % and 26.5 %-30.7 % of patients, respectively. PD-L1 TC ≥ 25 % was not associated with survival advantage in first- (HR = 0.96, 95 % CI 0.75-1.22), second- (1.08, 0.81-1.42), or third-line (0.94, 0.74-1.20) therapy. PD-L1 IC ≥ 25 % was associated with survival advantage in second-line (HR = 0.56, 95 % CI 0.36-0.86) and third-line (0.69, 0.49-0.97) but not first-line (1.00, 0.70-1.41) therapy.

No association was observed between PD-L1 TC ≥ 25 % and OS in any therapy line. PD-L1 IC ≥ 25 % may confer survival benefit among some patients who reach second-line therapy.

No association was observed between PD-L1 TC ≥ 25 % and OS in any therapy line. PD-L1 IC ≥ 25 % may confer survival benefit among some patients who reach second-line therapy.Cases of child abuse and homicide are amongst the biggest challenges investigators face, with complex evidence bases often strongly contested and reliant on specialist interpretation of the medical evidence. In many cases, this medical evidence includes examination of the deceased’s skeleton using different macroscopic and microscopic imaging methods. Rib fractures are a common concern when examining suspicious cases and much research has been conducted on their causes. The role of CPR in particular has been controversial and therefore a clear assessment of the fracture distribution is crucial. Recent studies have shown the benefit of imaging techniques such as Computed Tomography, although the gold standard remains histology. This paper presents three cases of suspected non-accidental rib fractures of infants which had been examined using micro-CT and histology. Micro-CT has been shown to be superior to medical CT as it achieves a greater resolution, making it effective for paediatric post-mortem imaging. Micro-CT observations were compared retrospectively to the histology, which demonstrated that micro-CT found 69% of the fractures identified histologically as well as an additional 22% not identified through histology. As well as complimenting histological analysis, the extent to which micro-CT can enhance the overall examination of paediatric non-accidental injuries is also discussed.Circular stepped-plates are often chosen to generate continuous waves in air due to their transmission efficiency, directive radiation patterns and capability to generate high-intensity airwave emission. Such features can be suitable for an acoustic radiator intended for the generation of harmonic radiation force, if the narrow bandwidth of the piezoelectric power transducer is not an obstacle to the application. This force has been used as the excitation source in noncontact modal analysis of mechanical devices, since it offers some advantages over the traditional impact method and the use of shakers. In this study, a directional stepped-plate ultrasonic device driven by a bolt-clamped Langevin-type transducer is used to excite the first flexural mode of a clamped-free beam by means of harmonic radiation force. The harmonic component was generated using an amplitude-modulated electrical input signal. The radiator design was done by solving a parametric optimization problem of finding a plate with the desired vibrational behavior using the genetic algorithm. Finite element analysis was used to obtain the dynamic behavior of the device and the airwave propagation was modeled using linear acoustic theory. Modal and harmonic analyses were conducted to obtain some of the electroacoustic parameters of the transducer. The acoustic field generated by the prototype is estimated by solving the Rayleigh integral and the obtained results are compared to experimental measurements.We use optical tweezers to characterize the ability of Caffeine (Caf) to modulate the intercalation of drugs into the DNA double-helix at the single molecule level. When previously bound to the double-helix, Caf hinders ethidium bromide (EtBr) intercalation, decreasing its effective equilibrium binding constant with DNA. The dominant mechanism of such singular ability is a direct binding of Caf to the intercalating drugs in solution, which decreases the effective concentration of such compounds available to interact with DNA. When EtBr intercalation into the DNA double-helix occurs firstly, on the other hand, the measured cooperativity between Caf molecules interacting with DNA can be modulated, a feature also correlated to the Caf-EtBr interaction in solution. The results achieved here unveil many peculiarities about the details of such interactions at the molecular level and provide new insights on the use of Caf in therapeutic applications.

CDK4/6 inhibitors modulate immune response in breast cancer. This phase I/II trial was designed to test the safety and efficacy of palbociclib, pembrolizumaband letrozole in women with hormone receptor positive (HR

) human epidermal growth factor receptor 2 negative (HER2

) metastatic breast cancer (MBC).

Women with stage IV HR

HER2

MBC were enrolled and treated with palbociclib, pembrolizumaband letrozole. Primary end-points were safety, tolerabilityand efficacy.

Between November 2016 and July 2020, 23 patients were enrolled with 20 evaluable for response, including 4 patients in cohort 1 and 16 patients in cohort 2. Cohort 1 median age was 48 years (33-70) and cohort 2 median age was 55 (37-75). Cohort 1 closed early due to limited accrual. Grade III-IV adverse events were neutropenia (83%), leucopaenia (65%), thrombocytopenia (17%) and elevated liver enzymes (17%). In cohort 1, 50% achieved a partial response (PR) and 50% had stable disease (SD). In cohort 2, 31% achieved complete response (CR), 25% had PRand 31% had SD by Response Evaluation Criteria in Solid Tumours version 1.1. Median progression-free survivalwas 25.2 months (95% confidence interval [CI] 5.3, not reached) and median overall survival was 36.9 months (95% CI36.9, not reached) in cohort 2 with a median follow-up of 24.8 months (95% CI 17.1, not reached). A correlative immune biomarker analysis was published separately.

The combination of palbociclib, pembrolizumaband letrozole is well tolerated, and a complete response rate of 31% was identified in HR

MBC patients who received this combination as front-line therapy. Confirmatory trials are required to better understand the immune-priming effects of CDK4/6 inhibitors.

The combination of palbociclib, pembrolizumab and letrozole is well tolerated, and a complete response rate of 31% was identified in HR+ MBC patients who received this combination as front-line therapy. Confirmatory trials are required to better understand the immune-priming effects of CDK4/6 inhibitors.Indigenous chicken breeds are considered to be more disease tolerant than exotic chicken breeds especially for the bacterial diseases. Nicobari and Vanaraja chicken were evaluated for the survivability/mortality patterns and host immune response after experimental infection with P. multocida A1 isolate. The birds were inoculated with 1.9 × 105 CFU/mL through intraperitoneal (I/P) and intranasal (I/N) routes at 2 different age groups viz., 12 wk and 18 wk. Symptoms, mortality rates, lesions in dead birds were observed; Serum from surviving birds of different groups from both breeds were collected at 5, 14, 21, 28, 35 and 42nd d and specific antibody titers were measured by indirect ELISA. At 12 wk of age, the mortality rates were 100% and 16% in birds inoculated by I/P and I/N routes respectively in Vanaraja birds; whereas the mortality rates were 50% and 16% I/P and I/N routes respectively in Nicobari birds. At 18 wk of age the mortality rates were 16% and 50% for I/P routes in Nicobari and Vanaraja birds respectively. The mortality rates were 16% for I/N route in both Nicobari and Vanaraja birds. Lesions such as necrotic foci on liver, congestion in the liver were observed in dead birds. Serum titers were significantly (P less then 0.05) higher in surviving Nicobari birds inoculated through I/P route followed by I/N route. The peak titers were reached on 14th d postinfection and declined thereafter. However, no significant difference was found in I/N route of inoculation between 2 breeds. Nicobari chicken breed showed significantly higher survivability and longer mean death time than Vanaraja germplasm to experimental Pasteuralla infection at both the ages however the survivability rate in both breeds improved at later ages.Effects of the in ovo injection of vitamin D3 (D3) and 25-hydroxyvitamin D3 (25OHD3) on the immunity and small intestine morphology of broilers fed calcium and phosphorus-restricted diets were investigated. At 18 d of incubation (doi), live embryonated Ross 708 broiler hatching eggs were in ovo-injected with a 50 μL solution of one of the following treatments using an Inovoject multiegg injector 1) diluent (control); diluent containing either 2) 2.4 μg D3; 3) 2.4 μg 25OHD3; or 4) 2.4 μg D3 + 2.4 μg 25OHD3. At hatch, 18 randomly selected male broilers belonging to one of the 4 in ovo injection treatments were placed in each of 12 floor pens and were fed either a commercial diet or a diet restricted by 20% in calcium and available phosphorus (ReCaP) content for the starter, grower and finisher dietary phases. Concentrations of plasma IgG and IgM at 14 d of age (doa) and α-1-acid glycoprotein at 40 doa were determined. Bursa, liver, spleen, duodenum, jejunum, and ileum weights were recorded at 7, 14, and 40 doa and small intestine histology was evaluated at 14 and 40 doa. Blood and organ samples were randomly collected from 1 bird in each of the 6 replicate pens within each of the 8 (4 in ovo x 2 dietary) treatment groups. Plasma IgG levels were higher in 25OHD3 than in diluent or D3 in ovo-injected birds. At 14 doa, a higher jejunal villus length (VL) to crypt depth (CD) ratio (RVC) was observed in birds that were in ovo-injected with 25OHD3 alone as compared to all other in ovo injection treatments. At 40 doa, ileal VL increased and jejunal CD decreased in commercial diet-fed birds compared to ReCaP diet-fed birds. In conclusion, the in ovo injection of 25OHD3 alone increased the immune response and improved the small intestine morphology and subsequent nutrient uptake of Ross 708 broilers. However, a ReCaP diet was observed to be detrimental to their small intestine morphology.The present study investigated the effect of different dietary levels of calcium (Ca) and non-phytate phosphorus (P) on the growth performance, carcass characteristics, and blood components of growing geese. A total of 120, 4-wk-old Egyptian goslings with similar body weights were randomly distributed to four groups in a 2 × 2 factorial arrangement, which included 2 levels of Ca (0.85% and 0.70%) and 2 levels of non-phytate P (0.45% and 0.35%). Each group was subdivided into 6 replicates of five birds. The experiment lasted 8 wk, from 4 to 12 wk of age. Results show that dietary Ca level had no significant effect on any of the studied growth performance traits over the full experimental period. Dietary P level also had no significant impact on these traits, with the exception of daily body weight gain and feed conversion ratio at 8 to 12 wk of age; these improved significantly with the low P diet. Geese received a diet containing 0.70% Ca + 0.45% P had the lowest body weight values at 12 wk of age and the lowary Ca and P combinations. In conclusion, dietary Ca and P levels can be simultaneously reduced without negative impacts on growth performance, carcass characteristics, or blood biochemical components. We advise to avoid increasing the dietary Ca P ratio, as it leads to negative effects on growth performance and blood biochemistry in growing geese. So, the findings of the current study recommended the low levels of Ca (0.70%) and non-phytate P (0.35%) for the performance of Egyptian geese during the fattening period.Antifreeze proteins (AFP) have the potential for improving sperm cryopreservation. We have applied Type III antifreeze protein (AFP3) on the cryopreservation of spermatozoa from broiler breeder roosters, aiming to enhance post-thawing quality and fertility. Semen was extended at 37°C in Lake’s extender containing AFP3 at 0.01, 0.1, 1, 5, and 10 µg/mL (no AFP3 as control). Post-thawing sperm assessment included sperm motility (CASA), morphology, membrane functionality by hypoosmotic swelling test (HOST), lipoperoxidation as malondialdehyde (MDA) production, and sperm viability, early apoptosis (phosphatidylserine exposure as annexin V-positive staining in viable spermatozoa), and mitochondrial activity by flow cytometry. Fertility was assessed after artificial insemination (30 hens/treatment). Total and progressive motility, membrane functionality, and mitochondrial activity increased in 0.1 and 1 µg/mL AFP, compared to control and other concentrations, whereas apoptosis was significantly lower. VAP, VSL, and viability were significantly higher for 1 µg/mL AFP3 than with the other treatments except for 0.1 µg/mL (which was not always significantly different from the control or other concentrations), and with abnormal forms being significantly lower. The proportion of fertilized and hatched eggs was also higher for 1 µg/mL AFP3, with 0.1 µg/mL also showing significantly higher results than the control, and no differences with other concentrations). In conclusion, 1 µg/mL AFP3 could improve the post-thawing results of rooster spermatozoa frozen in Lake’s extender. According to our results, concentrations between 1 and 0.1 µg/mL could be similarly efficient.Stem cell therapy is promising for neural repair in devastating traumatic brain injury (TBI). However, the low survival and differentiation rates of transplanted stem cells are main obstacles to efficient stem cell therapy in TBI. Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 are key factors that regulate the survival, recruitment, and differentiation of stem cells. Herein, we synthesized a sodium alginate (SA)/collagen type I (Col)/SDF-1 hydrogel and investigated whether the SA/Col/SDF-1 hydrogel loaded with bone marrow-derived mesenchymal stem cells (BMSCs) had therapeutic effects on a TBI model. Our results showed that the SA/Col/SDF-1 scaffold could stably release SDF-1 and provide biocompatible and biodegradable microenvironment for the survival, migration, and neuronal differentiation of BMSCs in vitro. In a rat model of TBI, the SA/Col/SDF-1 hydrogel loaded with BMSCs significantly ameliorated motor and cognition dysfunction and relieved anxiety and depressive-like behaviors. In addition, migration and neuronal differentiation of BMSCs in vitro. In addition, the SA/Col/SDF-1 hydrogel loaded with BMSCs significantly ameliorated neurological deficits, mitigated neuroinflammation, promoted the recruitment of BMSCs and enhanced neurogenesis in TBI partly by activating the SDF-1/CXCR4-mediated FAK/PI3K/AKT pathway. Our results may serve as an alternative neural regeneration strategy for brain injury.Mycoplasma hyorhinis (Mhr) is a commensal of the upper respiratory tract that can be shed by nasal secretions and transmitted by direct contact in neonatal and nursery pigs. Lesions associated with Mhr infection include polyserositis and arthritis; however, systemic Mhr disease pathogenesis is not well characterized. This study aimed to investigate the immunopathogenesis and bacterial dissemination pattern of Mhr using single and multiple inoculation approaches in a caesarian-derived colostrum-deprived (CDCD) pig model. Animals in three treatment groups were inoculated once (Mhr 1; n = 12) or four (Mhr 2; n = 8) times with Mhr or sham-inoculated (NC group; n = 3) nasally and by tonsillar painting. Inoculum consisted of a triple cloned Mhr field isolate (4.5 × 107 CFU/mL) in Friis medium. Clinical signs were evaluated daily during the study. Serum and oral fluid antibody (IgA and IgG) response and cellular immune response were assessed using a recombinant chimeric VlpA-G-based indirect ELISA and by ELISpot, reical natural infection in the field. In addition, the humoral and transient cellular response did not result in bacterial clearance. Based on these results, animals would have to be exposed multiple times to mount a detectable immune response.

Health care professionals (HCPs) (eg, nurses, doctors) play a key role in vaccine uptake. Few studies describe HCP influenza vaccine communication with parents of hospitalized children.

This study included English- and Spanish-speaking parents of influenza vaccine-eligible children hospitalized at a tertiary care pediatric hospital between October 2018 and May 2019. A survey was completed online or via telephone 2 to 15 weeks (median 4 weeks) after discharge. It examined parental intent to vaccinate their child during hospitalization and parent-reported inpatient HCP communication practices (eg, vaccine recommendation strength, format for initiating the recommendation). Multivariable logistic regression examined the associations between HCP communication practices and influenza vaccination during hospitalization, adjusting for demographic, clinical, and visit characteristics.

Parents (n=194; 63.0% response rate) were mostly white (66.8%) and English-speaking (97.4%). Their children were primarily 5 thro hospitalized children.Paralysis of the muscles around the shoulder is a debilitating condition that continues to be a very challenging problem. It leads to an inability to position one’s hand in space. This greatly compromises the function of the upper limb and can lead to chronic shoulder pain due to inferior glenohumeral subluxation. Management of these complex problems has two main objectives (i) stabilize the glenohumeral joint to decrease pain related to inferior glenohumeral subluxation; (ii) restore active range of motion in external rotation, abduction, and internal rotation. All the shoulder muscles contract in a coordinated and complex manner to allow the shoulder to move through a complete range of motion. Understanding how the different muscle groups coordinate their contractions and the basic biomechanical principles of tendon transfers is paramount before considering doing a tendon transfer around the shoulder. To function properly, a tendon transfer should have a similar line of pull (similar moment arm), similar tension and similar excursion to that of the muscle it replaces; one tendon transfer should replace only one function and the donor (transferred) muscle should have normal muscle strength (at least M4).Ulnar paralysis has multiple clinical presentations, which are due to partial recovery or to anatomical variations between the ulnar and median nerves. The main sequelae of ulnar nerve paralysis are the loss of hand strength with impairment of all intrinsic functions of the fingers and some of the thumb’s functions. Weakness of the adductor pollicis and flexor pollicis brevis muscles may manifest as weak key pinch with automatic flexion of the thumb interphalangeal joint when gripping. Indications for palliative surgery have decreased due to advances in peripheral nerve surgery. However, palliative surgery still has a significant role to play when nerve repair techniques are not indicated or do not provide satisfactory results. The principle is to reinforce metacarpophalangeal flexion while stabilizing the thumb’s interphalangeal joint, thus supplementing the action of the flexor pollicis brevis. This is generally done by transferring the flexor digitorum superficialis tendon of the fourth finger to the distal insertion of the superficial thenar muscles and the extensor pollicis longus.