The response of salt tolerant wheat genotype (Kharchia 65), and sensitive cultivars (HD2687, HD2009, WL711) to vegetative stage salinity stress (for 4 weeks) were studied at 1.1 (control), 9.1 (S1) and 14.2 (S2) dSm-1 salinity levels. Based on relative change in Membrane stability, PSII efficiency, retention of chlorophyll and carotenoid contents, Kharchia 65 showed better tolerance to salinity than other genotypes considered. To understand the role of different component mechanisms, expression of genes involved in ion exclusion, antioxidant defence and compatible osmolyte synthesis were analysed. Expression of SOS1 (plasma membrane Na+/H+ antiporter), NHX (vacuolar Na+/H+ antiporter), Ionic (sodium exclusion) and tissue tolerance (Sodium compartmentation, compatible solute accumulation and antioxidant defence) mechanisms were analysed in leaves of the genotypes after 4 weeks of salinity stress. Expression assay and the content of respective constituents indicated that apart from the well-known ion exclusion ability, Kharchia 65 also showed high level of tissue tolerance resulting in high early vigour and maintenance of growth rate afterwards. In Kharchia 65, sensing of salinity stress at plasma membrane activates NADPH Oxidase (RBOH) genes and generate ROS at apoplast. Apoplastic ROS triggers calcium influx and activates calcium signaling genes of SOS pathway (SOS1 and NHX). ROS generated from organelles chloroplast, peroxisome and mitochondria triggers cellular oxidative burst. ROS and calcium activates MAPK genes and downstream transcription factors, NAC and bZIP. MAPK signaling induces cellular antioxidant and compatible osmolyte biosynthesis and imparts tissue tolerance to salinity.

(1) Background: Although manual therapy for pain relief has been used as an adjunct in treatments for chronic low back pain (CLBP), there is still the belief that a single session of myofascial release would be effective. This study aimed to investigate whether a single session of a specific technique reduces pain and disability. (2) Methods: This was a crossover clinical trial in which 41 participants over 18 years old with CLBP were randomly enrolled into 3 situations - experimental, placebo, control, in a balanced and cross-over manner. The subjects underwent a single session of myofascial release on thoracolumbar fascia and compare it with the control and placebo. Outcome were pain and functionality, evaluated using the numerical pain rating scale (NPRS), pressure pain threshold (PPT) and Oswestry (ODI). (3) Results: There was no effects between-, within-tests, and interaction for all the outcomes, i.e., NPRS (η 2 = 0.32, F = 0.48, p = 0.61), PPT (η2 = 0.73, F = 2.80, p = 0.06), ODI (η 2 = 0.02, F = 0.02, p = 0.97). (4) Conclusion: A single trial of thoracolumbar myofascial release technique was not enough to reduce pain and disability in subjects with CLBP.

This research is aimed at evaluating two different scenarios, firstly, appraising the impacts of employing the concepts of Total Quality Management (TQM) to the construction projects in Saudi Arabia. The results of the study were obtained through utilization of a descriptive analytical approach, where 300 questionnaires were distributed to engineering firms and companies with a response rate of 200 questionnaires, hence achieving the study sample for this research. The data gathered was analyzed by applying the Statistical Package for Social Science (SPSS) program and calculating the Relative importance index (RII) and the mean values. From the research conducted, the outcomes showed that the management’s ability to commit using TQM while applying BIM obtained a relative importance of (0.717), while the relative importance for the management’s ability to commit using TQM without the application of BIM is (0.552). The results showed that construction projects in Saudi Arabia still sustain setbacks from applying TQM concepts and suffer from the lack of administrative, scientific and technical applications. In a second scenario, a hybridized support vector regression (SVR) Harris-hawks optimization (HHO) (i.e., SVR-HHO) were used to predict the TQM. The performance accuracy of the models was checked through three different evaluation metrics namely; mean square error (MSE), correlation co-efficient (CC) and Nash-Sutcliffe efficiency (NSE). the hybridized emerging SVR-HHO outperformed the other two data driven approaches in both the training and testing stages based on the employed evaluation metrics. Overall, the obtained results showed that both the machine learning and metaheuristic approaches were capable of predicting TQM.

Solidification microstructure is formed under high cooling rates and temperature gradients in powder-based additive manufacturing. In this study, a non-equilibrium multi-phase field method (MPFM), which was based on a finite interface dissipation model proposed by Steinbach et. al., coupled with a CALPHAD database was developed for a multicomponent Ni alloy. A qua-si-equilibrium MPFM was also developed for comparison. Two-dimensional equiaxed micro-structural evolution for the Ni (Bal.)–Al–Co–Cr–Mo–Ta–Ti–W–C alloy was performed at various cooling rates. The temperature–γ fraction profiles obtained under 10^5 K/s using non- and qua-si-equilibrium MPFMs were in good agreement with each other. Over 10^6 K/s, the differences between non- and quasi-equilibrium methods grew as the cooling rate increased. The non-equilibrium solidification was strengthened over a cooling rate of 10^6 K/s. Colum-nar-solidification microstructural evolution was performed under cooling rates from 5×10^5 K/s to 1×10^7 K/s at various temperature gradient values under the constant interface velocity (0.1 m/s). The results showed that as the cooling rate increased, the cell space decreased in both methods, and the non-equilibrium MPFM agreed well with experimental measurements. Our results show that the non-equilibrium MPFM can simulate solidification microstructure in powder bed fusion additive manufacturing.

Ammonia produced using renewable hydrogen is being viewed as a promising media for the export of energy from locations rich in renewable energy sources. Solid oxide fuel cells (SOFCs) are efficient devices for converting such exported ammonia back into electricity at the point of use, however investigations on materials and operating regime for direct ammonia fuelled SOFCs are limited. The studies on fuel electrodes tailored specifically for ammonia fuel are limited. In this work, we evaluated the direct ammonia SOFC performance with Silver-Lanthanum Strontium Cobalt Ferrite (Ag-LSCF) composite anode and a novel Palladium (Pd) nanoparticle decorated Silver-Lanthanum Strontium Cobalt Ferrite (Pd-Ag-LSCF) composite anode in the temperature range of 500 °C to 800 °C. It is hypothesized that Palladium nanoparticles in the anode provide hydrogen dissolution and shift the ammonia decomposition reaction towards the right. The cell performance was evaluated with both hydrogen and ammonia as fuels and a clear-cut improvement in the performance was observed with the addition of Pd for both the fuels. The results showed a performance enhancement by 20% and 43% with hydrogen and ammonia fuels respectively from the Pd addition of Ag-LSCF anode. Open circuit voltage (OCV) values of the cells with hydrogen and ammonia fuel recorded over the temperature range of 500 °C to 800 °C indicated the possibility of direct electro-oxidation of ammonia in SOFCs.

Abstract: Background: Intensity modulated radiotherapy (IMRT) is still a standard of care for radiotherapy in locally advanced head and neck cancer (LA-HNSCC). Simultaneous integrated boost (SIB) and moderate hypofractionation offer an opportunity for individual dose painting and a reduction in overall treatment time. We present retrospective data on toxicity and locore-gional control of a patient cohort with LA-HNSCC treated with an IMRT-SIB concept in compar-ison to normofractionated 3D-conformal radiotherapy (3D-RT) after a long-term follow-up. Methods: Between 2012 and 2014, n=67 patients with HNSCC (stages III/IV without distant me-tastases) were treated with IMRT-SIB either definitively (single/total doses: 2.2/66 Gy, 2.08/62.4 Gy, 1.8/54 Gy in 30 fractions) or in the postoperative setting (2.08/62.4 Gy, 1.92/57.6 Gy, 1.8/54 Gy). These patients' clinical courses were matched (for sex, primary, and treatment concept) as part of a matched-pair analysis with patients treated before mid-2012 with normofractionated 3D-CRT (definitive: 2/50 Gy followed by a sequential boost up to 70 Gy; postoperative: 2/60-64 Gy). Chemotherapy/ immunotherapy was given concomitantly in both groups in the definitive situation (postoperative dependent on risk factors). The primary endpoints were acute and late toxicity; the secondary endpoint was locoregional control (LRC). Results: Sixty-seven patients treated with IMRT-SIB (n = 20 definitive, n = 47 adjuvant) were matched with 67 patients treated with 3D-RT. There were minor imbalances between the groups concerning nonmatching variables such as extracapsular extension (ECE) and chemotherapy in IMRT-SIB. Significantly less toxicity was found in favor of IMRT-SIB concerning dysphagia, ra-diation dermatitis, xerostomia, fibrosis, and lymphedema. After a median follow-up of 63 months, the median LRC was not reached (IMRT-SIB) vs. 69.5 months (3D-RT) (p=0.63). Conclusions: This moderately hypofractionated IMRT-SIB concept was shown to be feasible with less toxicity than conventional 3D-RT in this long-term follow-up observation.

Hepato-renal dysfunctions associated with hyperlipidemia necessitates continuous search for natural remedies. This study thus, evaluated the effect of dietary chitosan on diet-induced hyperlipidemic rats. Thirty male Wistar rats (90 ± 5.2) g were randomly allotted into six (6) groups (n=5): Normal diet, High-fat diet (HFD), Normal diet + 5% chitosan. The three other groups received HFD, supplemented with 1%-, 3%-, and 5% of chitosan. The feeding lasted for 8 weeks, after which the rats were sacrificed. The liver and kidneys were harvested for Analyses. Hepatic alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activity, and renal biomarkers (ALT, AST, urea, and creatinine) were assayed spectrophotometrically. Additionally, expression of hepatic and renal CD43 and p53 was estimated immunohistochemically. Hyperlipidemia caused a significant (p<0.05) decrease in the hepatic (AST, ALT, and ALP) and renal (AST and ALT) activities, while renal urea and creatinine increased. Furthermore, the HFD group showed an elevated level of hepatic and renal CD43 while p53 expression decreased. However, groups supplemented with chitosan showed improved hepatic and renal biomarkers, as well as corrected the aberrations in the expressions of p53 and CD43. Conclusively, dietary chitosan could effectively improve kidney and liver functionality via abatement of inflammatory responses.

Attackers are perpetually modifying their tactics to avoid detection and frequently leverage legitimate credentials with trusted tools already deployed in a network environment, making it difficult for organizations to proactively identify critical security risks. Network traffic analysis products have emerged in response to attackers’ relentless innovation, offering organizations a realistic path forward for combatting creative attackers. Additionally, thanks to the widespread adoption of cloud computing, Device Operators (DevOps) processes, and the Internet of Things (IoT), maintaining effective network visibility has become a highly complex and overwhelming process. What makes network traffic analysis technology particularly meaningful is its ability to combine its core capabilities to deliver malicious intent detection. In this paper, we propose a novel darknet traffic analysis and network management framework to real-time automating the malicious intent detection process, using a weight agnostic neural networks architecture. It is an effective and accurate computational intelligent forensics tool for network traffic analysis, the demystification of malware traffic, and encrypted traffic identification in real-time. Based on Weight Agnostic Neural Networks (WANNs) methodology, we propose an automated searching neural net architectures strategy that can perform various tasks such as identify zero-day attacks. By automating the malicious intent detection process from the darknet, the advanced proposed solution is reducing the skills and effort barrier that prevents many organizations from effectively protecting their most critical assets.

Stroke is one of the leading cause of adult disability and the second leading cause of death worldwide. The immune system actively participates in the pathobiological process of AIS, during the index event and during the repair process despite the limited attention drawn to this aspect in the existing stroke guidelines globally. The similar clinical course and similar circulating innate and adaptive immune cell counts in AIS and COVID-19 has created a renewed interest in these easily available biomarkers innate and adaptive immunological changes in AIS with potential diagnostic, prognostic, and therapeutic implications. The current scoping review aimed to assess the significance of circulating neutrophil and lymphocyte counts and their ratio (NLR) in AIS and explore their association with post-stroke recovery trajectory. The Arksey and O'Malley methodological framework was employed to review the published papers on the neutrophil-lymphocyte ratio (NLR) and AIS in late November 2020. Only studies published in English from 2000-2020 were included in this scoping review. Fifty-three published papers were reviewed. This review's key finding is that a canonical inflammatory response occurs in AIS just as in the case of COVID-19 and neurological involvements well described in the recent literature. An excessive circulating innate immune cells (neutrophils) and reduced circulating adaptive immune cells (lymphocytes ) are associated with poorer outcomes during the acute interventions ( reperfusion therapies) as well as the recovery trajectory. Main representatives of innate and adaptive immunity follow a canonical course in AIS and COVID-19. Exaggerated circulating innate ( elevated neutrophils and elevated NLR) and reduced adaptive immune response (lymphopenia) correlate with the worse outcome in AIS and COVID-19. This scoping review's findings make the strongest case for a systems biology-based approach to the standard operating procedures in stroke care urgently.

One of the most used markers of cancer stem cells in several cancers, including colorectal cancer and breast cancer, is CD44. CD44 is a glycoprotein that traverses the cell membrane and binds to many ligands including hyaluronan resulting in activation of signaling cascades. Several reports have shown conflicting data on the expression of CD44 and that the expression depends on modes of investigations and subtypes of cancers. In addition, the correlation between CD44 expression and drug resistance, immune infiltration, EMT, metastasis and patients prognosis in several cancer types remains unclear. This study investigated CD44 expression in several cancers and explored its relationship with tumorigenesis using various publicly available databases, including The Cancer Genome Atlas, GEPIA, Oncomine, Genomics of Drug Sensitivity in Cancer and Tumor Immune Estimation Resource. Our analysis reveals that CD44 is differentially expressed in different cancers. CD44 expression is significantly associated with cancer patients’ survival in gastric, pancreatic and colorectal cancers. In addition, CD44 expression is closely linked with immune infiltration and immune suppressive features in pancreatic, colon adenocarcinoma and stomach cancer. High CD44 expression was significantly correlated with the expression of drug resistance-, EMT- and metastasis- linked genes. Tumors expressing high CD44 have higher mutation burden and afflict older patients than tumors expressing low CD44. Cell lines expressing high CD44 are more resistant to anti-cancer drugs compared to those expressing low CD44. Protein-protein interaction investigations and functional enrichment analysis showed that CD44 interacts with gene products related to cell-substrate adhesion, migration, platelet activation, and cellular response to stress. KEGG pathway analysis revealed that these genes play key roles in biological adhesion, cell component organization, locomotion, G-α-signaling and the response to stimulus. Overall, this investigation reveals that CD44 play significant roles in tumorigenesis, can be used as a prognostic biomarker in several cancers and can be therapeutically targeted in cancer therapy.

Land and property development process include a series of multifaceted activities ranging from purchasing to converting it for development purposes and everything in between. The process itself encompasses multiple stakeholders, drivers, and contributions from diversified public and private actors and transaction cost arises out of their complex interaction. Transaction costs incurred during any kind of human interactions (i.e. transactions). Every actor involved in the process wishes to maximize his achievement under various constraints and hence institutional arrangement (i.e. set of humanly devised rules to administer the constraints) is necessary for efficient management of the development process. Therefore, to devise an optimum outcome out of economic and social transactions in the property development process, cooperative and competitive relationships between individuals should be understood from a broader socio-political and governance structure. In this research, it is critically argued that land and property development process should implicate a multifaceted set of formal and informal rules or institutional arrangement to govern the intrinsic interaction, action and thereby reducing the related transaction cost. The argument is further reproachfully evaluated and implicated in the urban development process through the myopic lens of Transit-oriented development (TOD) pathway. A vigilant combination of descriptive and explanatory research approach is adopted to analyze the connection between theory and practice.

The COVID-19 pandemic had profound negative effects on millions of couples affected by infertility and in need to resort to assisted reproductive technologies. There is no consensus over the optimal way and moment of screening triage-negative asymptomatic patients and staff. We present SARS-CoV-2 antibodies’ (IgM, IgG) seroprevalence in 516 triage-negative patients and 30 fertility care providers. The sampling for SARS-CoV-2 serological assays took place from the lockdown release throughout the second half of 2020 (17.05 - 01.12.2020). It revealed an increased seroprevalence of antibodies that closely followed the local epidemiology of COVID-19, with the highest rate of seropositivity coincident with the peak of the second wave. From 546 triage-negative individuals whose blood samples were assessed for SARS-CoV-2 antibodies, 6% yielded positive results. The overall seroconversion rate was 2.8% for IgG and 5.1% for IgM. In the group with positive IgM, we observed a negative predictive value for IgM of 98.36% (95% CI: 88.79 – 99.78%), which is clinically meaningful. Serological testing of triage-negative patients up to seven days prior to the actual fertility procedure might avoid the more expensive and not more sensitive molecular testing currently being used for patient screening in most fertility units.

Chikungunya virus is an Alphavirus belonging to the family Togaviridae that is transmitted to humans by an infected Aedes mosquito. Patients develop fever, inflammatory arthritis, and rash during the acute stage of infection. Although the illness is self-limiting, atypical and severe cases are not uncommon, and 60% may develop chronic symptoms that persist for months or even for longer durations. Having a distinct periodical epidemiologic outbreak pattern, chikungunya virus reappeared in Thailand in December 2018. Here, we describe a cohort of acute chikungunya patients who had presented to the Bangkok Hospital for Tropical Diseases during October 2019. Infection was confirmed by real-time RT-PCR using serum collected at presentation to the Fever Clinic. Other possible acute febrile illnesses such as influenza, dengue, and malaria were excluded. We explored the sequence of clinical manifestations at presentation during the acute phase and associated the viral load with the clinical findings. Most of the patients were healthy individuals in their forties. Fever and arthralgia were the predominant clinical manifestations found in this patient cohort, with a small proportion of patients with systemic symptoms. Higher viral loads were associated with arthralgia, and arthralgia with the involvement of the large joints was more common in female patients

The enterohemorrhagic Escherichia coli (EHEC) O157: H7 EspF is known to be a multifunctional effector that triggers several damage processes in the host cells. However, in the process of EHEC O157: H7 infection, the interactions between EspF, its N- or C-terminus, and host proteins are still unclear. In this work, we use co-immunoprecipitation combined with mass spectrometry (CoIP-MS) to screen the interactions between EspF/EspF-N/EspF-C terminus and host proteins. A total of 311 host proteins are analyzed. The N-terminus of EspF is found to interact with 192 proteins, whereas 205 proteins interact with the C-terminus. These proteins are mainly involved in RNA splicing, endoplasmic reticulum stress, and a variety of metabolic signaling pathways. Surprisingly, MS results reveal that EspF can also phosphorylate H2AX, suggesting that EspF may directly mediate DNA damage. Here, by western blot and immunofluorescence (IF), we verified that EspF can cause phosphorylation of H2AX and mediates cell multi-nuclearation and cell hypertrophy. Furthermore, we verify here for the first time that SMC1 interacts with EspF -C-terminus, and provide evidence that EspF increases p-SMC1 levels. p-SMC1 is known to influence S-phase cell cycle arrest and usually increases during periods of DNA damage. Our work revealed a novel interaction between EspF and the host protein SMC1 and lays a foundation for further research on EspF-mediated host DNA damage, apoptosis, and even colorectal carcinogenesis.

Wheat blast caused by the hemibiotroph fungal pathogen Magnaporthe oryzae Triticum (MoT) pathotype, is a destructive disease of wheat in South America and Bangladesh. Generation of reactive oxygen species (ROS) is one of the defense responses in plants during the infection process by a pathogen. However, empirical evidence on regulation of ROS in wheat and other host and non-host plants towards MoT is limited. This study aimed to determine the susceptibility of some major cereals and weeds of Bangladesh and compare the antioxidant enzyme activities in host and non-host plants in response to artificial inoculation by MoT. Seedlings of wheat, maize, barley and swamp rice grass were susceptible to MoT and produced considerable number of conidia on infected leaves (host). Rice seedlings showed a resistant response in our laboratory conditions (non-host). The activities of ROS-detoxifying enzymes; catalase (CAT), ascorbate peroxidase (APX), Glutathione peroxidase (GPX), Glutathione S-transferase (GST), Peroxidase (POX) increased in all plants after inoculation by MoT with a few exceptions. Interestingly, an early and very high accumulation of CAT was observed within 24 hours of inoculation (hai) in wheat, barley, maize and swamp rice grass while H2O2 concentration was low during that time and immediately after that (24-48 hai). In contrast, an early and high accumulation of H2O2 was observed in rice at 48 hai with little CAT activity only at a late stage. The APX, GST and POD activity was also increased due to the inoculation of MoT at the early stage of infection in rice but were very high at the disease progression stage in wheat, barley, maize and swamp rice grass. GPX activity gradually decreased with the increase of time in rice. Taken together, our results suggest that a robust and late induction of most of the antioxidant enzyme activities occurs in susceptible/host plants whereas an early induction of antioxidant enzyme activities occurs in resistant/ non-host plant but with slow kinetics.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is pandemic. Prevention and control strategies require an improved understanding of SARS-CoV-2 dynamics. We did a rapid review of the literature on SARS-CoV-2 viral dynamics with a focus on infective dose. We sought comparisons of SARS-CoV-2 with other respiratory viruses including SARS-CoV-1 and MERS-CoV. We examined laboratory animal, and human studies. The literature on infective dose, transmission, and routes of exposure was limited specially in humans, and varying endpoints were used for measurement of infection. We propose the minimum infective dose of COVID-19 in humans, is higher than 100 particles, possibly slightly lower than the 700 particles estimated for H1N1 influenza. Despite variability in animal studies, there was some evidence that increased dose at exposure correlated with higher viral load clinically, and severer symptoms. Higher viral load measures did not reflect COVID-19 severity. Aerosol transmission seemed to raise the risk of more severe respiratory complications in animals. An accurate quantitative estimate of the infective dose of SARS-CoV-2 in humans is not currently feasible and needs further research. Further work is also required on the relationship between routes of transmission, infective dose, co-infection, and outcomes.

By the use of the tertiary amine A327 and 1 M HCl solution as precursors, the ionic liquid A327H+Cl- was generated and used to investigate its performance in the transport of Au(III) form hydrochloric acid medium. The influence of the stirring speed (600-1800 min-1), ionic liquid concentration (1.25-50% v/v) in the membrane phase and gold concentration (0.01-0.15 g/L) in the feed phase on metal transport have been investigated. An equation which included both equilibrium and kinetics parameters was derived, and the membrane diffusional resistance (Δm) and feed phase diffusional resistance (Δf) was estimated as 9.5x106 s/cm and 307 s/cm, respectively. At carrier concentrations in the 5-50% v/v range and gold concentrations in the 0.01-0.15 g/L range, metal transport is controlled by diffusion of metal species through the feed boundary layer, whereas at the lowest carrier concentrations, membrane diffusion is predominant. From the receiving solutions, gold can be recovered as gold nanoparticles.

This study takes as a starting point the importance and dependence of the media (Ball-Rokeach & DeFleur, 1976) to obtain information about the pandemic. The dependency theory of the media system was developed in the 1970s when mass media were the dominant source of information. Today, at a time when media choices have become abundant, studies are needed to understand the phenomenon of media dependence in light of new dimensions made important by the transformations that have taken place in the social and media fields - where the coexistence of mass media with social media platforms stands out. As large-scale crises rarely occur and the media environment changes rapidly, it is important to analyze how media dependence relates to choose and trust in different media (traditional media vs. social media) in times of crisis. Several questions arise. What is the trust attributed by individuals to social media as sources of information about the COVID-19? How well informed are the individuals who choose these sources as the main sources of information? From a questionnaire administered to 240 individuals in Portugal, during the first week of the state of emergency (March 2020), this research seeks to identify how people gained access to information about the COVID-19, how they acted critically towards the various sources and how they assess the reliability of different media. Finally, it analyzes the association between the type of medium chosen and adherence to misinformation content about the virus. The results reveal the existence of a phenomenon of dependence on the media, with a strong exposure (both active and accidental) to informative content, with conventional media being privileged as the main source, and positively distinguished in terms of confidence. Finally, a statistically significant association of a positive sign was identified between the use of social media as the main source and the acceptance of misinformation.

Repeated air pollution exposure is one of the major threats to skin health. Air pollution causes skin damage and accelerates skin ageing mainly through oxidative stress mechanisms. Since it is difficult to minimize skin exposure from air pollutants, especially in urban areas, strategies to protect the skin are needed. On the other hand, plant phenolic compounds have been found to be effective in attenuating cellular oxidative stress and inflammation induced by different air pollutants. Therefore, we conducted a 12-week randomized, placebo-controlled, double blind study to assess the efficacy of a polyphenol-enriched dietary supplement (comprised of olive leaf, lemon verbena, rosemary and Sophora japonica extracts) in reducing pollution-induced oxidative stress and in improving different skin parameters related to skin ageing of Caucasian and Asian volunteers living in a polluted urban European area (Milan). One hundred healthy women were recruited and randomized in the placebo or in the test dietary supplement treatment arms. To assess the efficacy of the dietary supplement, the total antioxidant capacity on saliva (FRAP) was determined, as well as the oxidative damage on skin (lipoperoxides content), the skin moisture (corneometry), the trans-epidermal water loss (Tewameter), the skin radiance and the skin colour, (spectrophotometry), the skin elasticity (cutometry), the skin sebum content (sebumeter), and the skin roughness (image analysis). As a result, both inter-group and intra-group analysis proved that the dietary supplement improved all clinical and biochemical monitored parameters, in both Caucasian and Asian individuals. In conclusion, the results of the study indicate a reduced oxidative stress-induced skin damage in both Asian and Caucasian women living in a polluted urban area.

Major depression is accompanied by increased IgM-mediated autoimmune responses to oxidative specific epitopes (OSEs). Nevertheless, these responses have not been examined in bipolar disorder type 1 (BP1) and BP2. IgM responses to malondialdehyde (MDA), phosphatidinylinositol, oleic acid, and azelaic acid were determined in 35 healthy controls, and 101 mood disorder patients, namely 47 major depressed (MDD), 29 BP1, and 25 BP2 patients. We also measured serum total peroxides, IgG to oxidized LDL (oxLDL), IgM to nitroso-adducts, and IgM/IgA directed to lipopolysaccharides (LPS). IgM responses to OSEs were significantly higher in MDD and BP1 as compared with controls and higher in MDD than in BP2. Partial Least Squares (PLS) analysis showed that 57.7% of the variance in the clinical phenome of mood disorders was explained by number of episodes, IgM directed to OSEs and nitroso-adducts, IgG to oxLDL, and peroxides. There were significant specific indirect effects of IgA/IgM to LPS on the clinical phenome, which were mediated by peroxides, IgM OSEs, and IgG oxLDL. Using PLS we have constructed a data-driven nomothetic network which ensembled causome (increased plasma LPS load), adverse outcome pathways (namely neuro-affective toxicity), and clinical phenome features of mood disorders in a data-driven model. Based on those feature sets, cluster analysis discovered a new diagnostic class characterized by increased plasma LPS load, peroxides, autoimmune responses to OSEs and nitroso-adducts, and increased phenome scores. Using the new nomothetic network approach, we constructed a mechanistically transdiagnostic diagnostic class indicating neuro-affective toxicity in 74.3% of the mood disorder patients.

This study to assess the Physical Land Suitability Analysis for Cultivation of Selected Cool Weather Cereal Crops, Misha District, Hadiya Zone, South Central Ethiopia of major cereal crops of barley and teff in Misha district. Each of the criteria was separately reclassified and analyzed for their suitability for supporting barley and teff crops based on the FAO crop requirements specified for them. The major data sources were climatic data, soil, LGP and topographic data as well as key informant interview, questioner observation of crop requirements which have been considered to undertake suitability assessments of the study area. The factor maps like land use /land cover, temperature, rain fall, soil type and altitude were classified based on suitability evaluation methods of FAO and experts’ opinion. At final stage these were reclassified and standardized in GIS software extension tools, which led to the preparation of suitability analysis map of the major crops plant suitability classes. As part of spatial MCDM, AHP pair wise comparison module was used to derive internal and external weights for each individual factors and parameters respectively. Consequently, suitability analysis was done and weighted overlay suitability map was visualized with integration of GIS. The findings show that among total area of land suitability maps for both barley and teff cops were using weighted overlay techniques. The suitability map of teff crop shows that 12,038.22 hectare of the investigated area are highly suitable (S1), 19,646.07 hectare moderately suitable (S2) and 4,501.71 hectare marginally suitable (S3) and 112 hectare not suitable. On the other hand, the suitability map of barley crop shows that 7,898.52 hectare of the investigated area are highly suitable (S1), 22,830.08 hectare moderately suitable (S2), and 5,466.4 hectare marginally suitable (S3) and 103 hectare not suitable for economic reasons (N1). This was done for barley and Teff crops separately. Results of the study revealed that most of the lands in the study area are suitable for the cultivation of the selected crops and other crops. Based on finding, it could be recommended that this work would be used as policy guide for planners; investment could be successful in the District, further suitability research works should be carried out in order to optimize the major crop cultivation and production.

Identified by the eponym “Edwards’ Syndrome,” trisomy 18 (T18) represents the second most common autosomal trisomy after T21. The pathophysiology underlying the extra chromosome 18 is a nondisjunction error, mainly linked with the advanced maternal age. More frequent in female fetuses, the syndrome portends high mortality, reaching a rate of 80% of miscarriages or stillbirths. The three-step evaluation includes first trimester screening for fetal aneuploidy using a combination of maternal age, fetal nuchal translucency thickness, fetal heart rate and maternal serum free ß-hCG and PAPP-A; followed by the research for fragments of fetal DNA in maternal blood; and, finally, invasive techniques leave to the established diagnosis. Starting with the first trimester scan, selected ultrasound findings should be investigated to define not only the impact of the genetic problem on the fetus, but also to address the prenatal counselling. Previous series underline that T18 is not uniformly lethal. An active dialogue on the choices in the management of infants with T18 has emerged, sustained by the transition from the comfort care to the intervention attitude. Survival rates for individuals with supposedly fatal conditions have increased. In this novel scenario, an ad hoc counselling is pivotal. To support it, a comparative analysis by pictorial assays between ultrasound and autopsy findings could be beneficial. We provide an illustrative tool from a clinical case managed in early second trimester, with the purpose to strive a balanced approach in the hard choice faced by couples of fetuses with T18.

To investigate the influence of supplemental lighting intensity on the production of cut gerbera during Canada’s supplemental lighting season (November to March), trials were carried out at a research greenhouse. Five supplemental LED light intensity (LI) treatments provided canopy-level photosynthetic photon flux densities (PPFD) ranging from 41 to 180 µmol·m-2·s-1. With a 12-h photoperiod, the treatments provided 1.76 to 7.72 mol·m-2·d-1 of supplemental light. Two cultivars of cut gerbera (Gerbera jamesonii H. Bolus ex Hook.f) were used to evaluate vegetative growth and flower production. Plugs of ‘Ultima’ were assessed for vegetative growth and rate of flower development. There were minor LI treatment effects on number of leaves and chlorophyll content index and flowers from plants under the highest vs. lowest LI matured 10% faster. Reproductively mature ‘Panama’ plants were assessed for flower yield and quality. ‘Panama’ flowers from the highest LI treatment had shorter stems than the three lowest LI treatments, flowers from the middle LI treatment had larger diameter than the other treatments. Flowers from the lowest LI treatment had lower fresh mass than the three highest LI treatments. There were linear relationships between LI and numbers of flowers harvested, with the highest LI treatment producing 10.3 and 7.0 more total and marketable flowers per plant than the lowest LI treatment. In general, increasing levels of supplemental light had only minor effects on vegetative growth (young plants) and size and quality of harvested flowers (mature plants) but flowers from plants grown under higher LIs were more numerous and matured faster.

We report the results of our study of approved drugs as potential treatments for COVID 19, based on the application of various bioinformatics predictive methods. The drugs studied include chloroquine, ivermectin, remdesivir, sofosbuvir, boceprevir, and α-difluoromethylornithine (DMFO). Our results indicate that these small molecules selectively bind to stable, kinetically active residues and residues adjoining them on the surface of proteins and inside protein pockets, and that some prefer hydrophobic over other active sites. Our approach is not restricted to viruses and can facilitate rational drug design, as well as improve our understanding of molecular interactions, in general.

Background: To examine the association between income levels and mortality rates in patients with chronic kidney disease. Methods: We analyzed data obtained from 3,172 patients with chronic kidney disease obtained from the Korean National Health Insurance claims database (2003–2009). Each patient was monitored until December 2010 or until death, whichever came first. Individual income was estimated from the national health insurance premium. Information on mortality was obtained from the Korean National Statistical Office. Cox proportional hazard models were used to compare mortality rates between different income groups after adjusting for possible confounding risk factors. Results: A low income was significantly associated with a high mortality rate after adjusting for covariates (adjusted HR 1.298 [1.082–1.556]). In addition, dialysis patients who had low incomes were more likely to have higher mortality rates compared to those in dialysis patients who had high incomes (adjusted HR 1.528 [1.122–2.082]). Conclusion: The findings of this study indicate that chronic kidney disease patients with low incomes have the highest mortality risk. Promotion of targeted policies and priority health services for patients with low incomes may help reduce the mortality rate in this vulnerable group.

The study of neurodegenerative diseases using pluripotent stem cells requires new methods to assess neurodevelopment and neurodegeneration of specific neuronal subtypes. The cholinergic system, characterized by its use of the neurotransmitter acetylcholine, is one of the first to degenerate in Alzheimer’s disease and is also affected in frontotemporal dementia. We developed a differentiation protocol to generate basal forebrain cholinergic neurons (BFCNs) from induced pluripotent stem cells (iPSCs) aided by the use of small molecule inhibitors and growth factors. Ten iPSC lines were successfully differentiated into BFCNs using this protocol. The neuronal cultures were characterised through RNA and protein expression, and functional analysis of neurons was confirmed by whole-cell patch clamp. We have developed a reliable protocol using only small molecule inhibitors and growth factors, while avoiding transfection or cell sorting methods, to achieve a BFCN culture that expresses the characteristic markers of cholinergic neurons.

Maslinic acid (MA) is a natural triterpene from Olea europaea whose pharmacological functions have been showed. The objective of this study was to examine MA effect on cell viability (by MTT assay), reactive oxygen species (ROS levels, by flow cytometry) and key anti-oxidant enzyme activities (by spectrophotometry) in murine skin melanoma (B16F10) cells compared to healthy cells (A10). MA induced cytotoxic effects in cancer cells (IC50 42 µM) whereas no effect was found in A10 cells treated with MA (up to 210 µM). In order to produce a stress situation in cells, 0.15 mM of H2O2 were added. Under stressful conditions, MA protected both cell lines against oxidative damage, decreasing intracellular ROS, being higher in B16F10 than in A10 cells. The treatment with H2O2 and without MA produced different responses in anti-oxidant enzymes activities depending on cell line. In A10 cells, all enzymes were up-regulated, but in B16F10 cells only superoxide dismutase, glutathione S-transferase and glutathione peroxidase increased their activities. MA restored the enzyme activities to similar levels than control group in both cell lines, highlighting that in A10 cells the highest MA doses induced values lower than control. Overall, these findings demonstrate the great anti-oxidant capacity of MA.

With the rising trends in elderly populations around the world, there is a growing interest in understanding how climate sensitivity is related to their thermal perception. Therefore, we analyzed the associations between mortality in the elderly due to cardiovascular (CVD) and respiratory diseases (RD) and meteorological variables, for three cities in the State of São Paulo, Brazil: Campos do Jordão, Ribeirão Preto and Santos, from 1996 to 2017. We applied the Autoregressive Model Integrated with Moving Average (ARIMA) and the Principal Component Analysis (PCA) in order to evaluate statistical associations. Results showed CVD as a major cause of mortality, particularly in the cold period, when a high mortality rate is also observed due to RD. The mortality rate was higher in Campos do Jordão and lower in Santos (and intermediate values in Ribeirão Preto). Campos do Jordão results indicate an increased probability of mortality from CVD and RD due to lower temperatures. In Ribeirão Preto, the lower relative humidity may be related to the increase in CVD and RD deaths. This study emphasizes that, even among subtropical climates, there are significant differences. Therefore, this can assist decision makers in the implementation of mitigating and adaptive measures.

BOLD-100, a ruthenium-based complex, sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (also known as IT-139, NKP1339 or KP1339), is a novel small molecule drug that demonstrated a manageable safety profile at the maximum tolerated dose and modest antitumor activity in a phase I clinical trial. BOLD-100 has been reported to inhibit the upregulation of the endoplasmic reticulum stress sensing protein GRP78. However, response to BOLD-100 varies in different cancer models and the precise mechanism of action in high-response versus low-response cancer cells remains unclear. In vitro studies have indicated that BOLD-100 induces cytostatic rather than cytotoxic effects as a monotherapy. To understand BOLD-100 mediated signaling mechanism in breast cancer cells, we used estrogen receptor positive (ER+) MCF7 breast cancer cells to obtain gene-metabolite integrated models. Particularly, BOLD-100 significantly reduced expression of genes involved in the DNA repair pathway. BOLD-100 also induced reactive oxygen species (ROS) and phosphorylation of histone H2AX, gH2AX (Ser139), suggesting disruption of proper DNA surveillance. In estrogen receptor negative (ER-) breast cancer cells, combination of BOLD-100 with a PARP inhibitor, olaparib, induced significant inhibition of cell growth and xenografts and increased gH2AX. Thus, BOLD-100 is a novel DNA repair pathway targeting agent and can be used with other chemotherapies in ER- breast cancer.

This study presents a novel technique utilizing high frequency vibration to shorten treatment time and preserve alveolar bone in challenging orthodontic cases treated with Invisalign® clear aligners. Four non-growing orthodontic patients (age range 14-47 years old) with Class II skeletal patterns (convex profiles with retrognathic mandibles) who sought correction of their crowded teeth and non-surgical correction of their convex profiles were included in this study. These patients were treated using Invisalign clear aligners together with high frequency vibration (HFV) devices (120 Hz) (VPro5™) that were used by all patients for five minutes per day during active orthodontic treatment. Vertical control and forward rotation of the mandible for each patient was achieved through pre-programming the Invisalign to produce posterior teeth intrusion. Successful forward rotation of the mandibles achieved in all patients led to improvement of their facial convex profiles (ANB improved 2.1 + 0.5 degrees; FMA improved 1.2 +1.1 degrees). Dental decompensation was achieved by lingual tipping of the lower incisors and palatal root torque of upper incisors. The use of HFV together with Invisalign facilitated achieving these results within a 12+6 month period. In addition, more bone labial to the lower incisors after their lingual movement was noted. In conclusion, the use of HFV concurrent with SmartTrack Invisalign aligners allowed complex tooth movement and forward projection without surgery in non-growing patients with skeletal Class II relationships. The clinical impact and implications of this case series is that the use of HFV facilitates complex orthodontic tooth movement including posterior teeth intrusion and incisor decompensation in addition to increased bone formation labial to lower incisors that may minimize future gum recession due to their labial inclination.

The coronavirus disease (COVID-19) pandemic is rapidly spreading across the world. In Democratic Republic of Congo (DRC), 11 out of 26 provinces have been affected on 19 June 2020. The purpose of this study was to assess the public views, attitudes and beliefs related to the COVID-19 pandemic among the population of an unaffected city.Methods: This is a descriptive observational study conducted in an unaffected city using a questionnaire. Findings: A total of 769 people participated. The average age was 36 ±14 years. The sex ratio (male: female) was 1.6. The majority of respondents (97%) is aware of the existence of the COVID-19 pandemic, it is well informed about the signs of the disease, its severity and barrier measures, however few of them have adopted the change in habit and behavior in respect of the barrier measures. Lack of water for handwashing is the most common difficulty in complying with barrier measures (71%). The COVID-19 is considered as an artificial virus designed to reduce the world population by 26%, God’s punishment (22%). Only 36% of the participants are in favor of vaccination against COVID-19. Vaccine is, a western conspiracy to spread COVID-19 in Africa (38%), testing it on Africans (35%), sterilize Africans’ people (12%).Conclusions: Cities not yet affected by COVID-19 in DRC are aware of the existence of the disease, but insufficiently prepared to deal with it. It is important to increase awareness on barrier measures, combating false information, and improving regular water supply for regular handwashing.

To obtain an accurate and reproducible experimental results in microbial fuel cell (MFC), it is important to know ‘anode maturation biofilm’ to produce a stable and maximum performance. For this purpose, four single chamber MFCs were tested in this study. The linear sweep voltammetry (LSV) polarization tests illustrated that maximum power densities of three MFCs became stable after 9 weeks. Although there were variations afterwards, such variations were negligible. Average maximum power densities from the 9th to the 17th week were 2,990 mW/m2 (MFC-4), 2,983 mW/m2 (MFC-2), 2,368 mW/m2 (MFC-3) and 837 mW/m2 (MFC-1). Polarization resistance shows that MFC-1 had much larger anode resistance (36.6-85.4 Ω) than the other MFCs (1.7-11.6 Ω). Anodic cyclic voltammetry (CV) shows that current production increased over time and MFC-1 had much smaller current production (24.4 mA) than the other MFCs (31.0-34.9 mA) at 17th week. The increased current production indicates anode biofilm became more mature over time, but overall cell performance did not increased accordingly. Possibly due to the bad inoculation, MFC-1 showed the lowest performance. However, its performance was restored to the initial performance and anode resistance was reduced by 47% at 17th week. This study shows that the optimum anode maturation time is 9 weeks and that bioanode performance is a key factor for MFC performance. This study also shows than LSV polarization and CV tests are accurate and non-destructive measurement methods for diagnosing anode performance.

Time-restricted feeding (TRF) showed a potent effect in preventing obesity and improving metabolic outcomes in several animal model of obesity; however, there is, as yet, scarce evidence about its effectiveness against obesogenic challenge that more accurately mimic the human Western diets, such as cafeteria diet. Moreover, the mechanism for its efficacy is poorly understood. White adipose browning has been linked to body weight loss. Herein, we tested whether TRF has the potential to induce browning of inguinal white adipose tissue (iWAT) and to attenuate obesity and associated dyslipidemia in cafeteria diet-induced obesity model. Male Wistar rats, fed normal laboratory chow (NC) or cafeteria diet (CAF) for 16 weeks, were subdivided into two groups that were subjected to either ad libitum (ad lib, A) or TRF (R) for 8 hours per day. Rats under TRF regimen had a lower body weight gain and adiposity compared with their diet-matched ad lib rats, despite equivalent levels of food intake and locomotor activity. In addition, TRF improved the deranged lipid profile [total cholesterol (TC); triglycerides (TG); high density lipoprotein (HDL-c); low density lipoprotein (LDL-c)] and atherogenic indices [atherogenic index of plasma (AIP); atherogenic coefficient (AC); coronary risk index (CRI)] in rats fed CAF diet. Remarkably, TRF resulted in decreased size of adipocytes and induced emergence of multilocular brown-like adipocytes in iWAT of NC- and CAF-fed rats. Protein expression of browning markers, such as uncoupling protein-1 (UCP1) and peroxisome proliferator activated receptor gamma coactivator 1-alpha (PGC1α) in iWAT were also up-regulated in time restricted NC- or CAF-fed rats. These findings suggest that TRF regimen is an effective strategy to improve obesity and associated dyslipidemia induced by CAF-diet, probably via a mechanism involving WAT browning process.

To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analysed its oral pharmacokinetics and its effects on a) the secretion of hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin and adiponectin), b) insulin signaling in the liver and c) the expression of glycolytic and neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted in its rapid absorption and distribution to plasma and liver compartments. Its administration reduced insulinemia and HOMA-IR, while maintaining glycaemia thanks to increased glucagon activity. In the liver, D-Pinitol reduced the key glycolytic enzyme pyruvate kinase and decreased the phosphorylation of the enzymes AKT and GSK-3. These observations were associate with an increase in ghrelin concentrations, a known inhibitor of insulin secretion. The profile of D-Pinitol suggests its potential use as a pancreatic protector decreasing insulin secretion through ghrelin upregulation while sustaining glycaemia through liver-based mechanisms of glycolysis control.

Oral cancer cells (TYS) and the signalling pathways involved in metastasis, in response to cancer-associated fibroblasts (CAFs, COM) and normal oral mucosal fibroblasts (MM1) was studied. Metastatic cell behaviour was observed by cell-scatter, 3D-collagen gel migration and 3D-spheroid invasion assays. Akt, MAPK, EGFR, TGFβRii and CXCR4 inhibitors were used to identify the signalling pathways involved. Signalling pathway protein expression and activation were assessed by SDS-PAGE and Western Blotting. COM-CM (conditioned medium) and MM1-CM stimulated cancer cell scattering, which was blocked only by the Akt inhibitor. COM-CM induced scattered cancer cells showed higher levels of Akt phosphorylation than the negative control and MM1-CM. Migration and invasion of TYS cells into the collagen gels from the spheroids was stimulated by CM from both sources, compared to the negative control. COM cells stimulated TYS, cancer cell invasion into the collagen more than MM1 and the control. Akt and EGFR inhibitors effectively blocked CM and COM cell-induced invasion. Akt-silenced cancer cells were not stimulated to migrate and invade by fibroblast-CM and did not survive addition of the EGFR inhibitor. This suggests that CAFs stimulate oral cancer cell migration and invasion in an Akt- dependent manner. EGFR and Akt are potential therapy targets in metastatic oral cancer.

The aim of this study was to introduce a new activity-based balance index by using accelerometer data. Twenty-seven junior soccer players from the Iranian premier league were selected. Four functional tests, consisting of one leg stance, dynamic Y balance, running and dribbling tests, were conducted to assess the players’ balance, activity and skill. During these four tests, besides their relative scores, the acceleration of their body center was also recorded. Activity-based balance index (ABI) was calculated using these acceleration data. The results showed positive correlations between ABI and both static and dynamic balance scores. Additionally, negative correlations were found between ABI and dribbling scores, which demonstrate the agility required for this skill. It seems that this new index achieves the evaluation of both the balance and the skill level of soccer players. Perhaps this is a new way of talent identification and also a re-development of balance tests from traditional to modern.

Citrus greening disease or huanglongbing (HLB) caused by Candidatus Liberibacter asiaticus (CLas) limits the citrus production worldwide. CLas is transmitted by the Asian citrus psyllid (ACP), Diaphorina citri (Hemiptera: Psyllidae) in a persistent-propagative manner. Application of insecticides to manage the psyllid vectors and disease is the most common practice. Understanding the molecular interaction between CLas and ACP and interrupting the interrelationship can provide an alternative to insecticides for managing citrus greening disease. Transcriptome analysis of ACP in response to CLas showed differential expression of 3911 genes (2196 up-regulated, and 1715 down-regulated) including the key genes of ACP involved in cytoskeleton synthesis and nutrition-related proteins. Majority of the differentially expressed genes were categorized under molecular function followed by cellular components and biological processes. KEGG pathway analysis showed differential regulation of carbohydrate, nucleotide and energy metabolic pathways, the endocytotic pathway and the defense-related pathways. Differential regulation of genes associated with the key pathways might favors CLas to become systemic and propagate in its insect vector. The study provides an understanding of genes involved in circulation of CLas in ACP. The candidate genes involved in key physiological processes and CLas transmission by ACP would be potential targets for sustainable management of ACP and CLas.

The objective of this study was to describe the overall pattern of morbidity and mortality of children seen at the Thai Binh Pediatric Hospital in Vietnam, with a focus on infectious diseases. A retrospective review of hospitalisation records was conducted from 1 January 2015 to 31 December 2019. Data were obtained from a total of 113,999 records. The median age of patients was 18 months, with 83.98% of patients aged <5 years. Infectious diseases accounted for 61.0% of all cases. The most prevalent diseases were lower respiratory tract infections (32.8%), followed by gastrointestinal infections (13.3%) and confirmed influenza (5.4%). Most infections were not microbiologically documented. A total of 81.4% patients received at least one antibiotic. Most patients (97.0%) were hospitalised for less than 15 days. Regarding outcomes, 87.8% patients were discharged home with a favourable outcome. 12.0% were transferred to the Vietnam National Children’s Hospital because their condition had worsened and 0.1% died. In total, infectious diseases accounted for 40.4% of deaths, followed by neonatal disorders (34.6%). Our data serves a basis for the identification of needs for diagnostic tools and for future evaluation of the effect of the targeted implementation of such facilities. Point-of-care tests, including real-time PCR assays to identify common pathogens should be implemented for more accurate diagnosis and more appropriate antibiotic use.

Background: Social skills deficits are present in 43.3% of major depressed patients and significantly impact health-related quality of life. However, studies concerning social deficits as state-dependent markers of depression are limited. Objective: To delineate the effects of severity of depression, personality characteristics, family support satisfaction and self-esteem on social skills in clinical depression. Methods: We recruited 150 patients with major depressive disorder or persistent depressive disorder and assessed 1) Beck Depression Inventory-II (BDI-II), 2) Social Skill Inventory (SSI), 3) Family Adaptation, Partnership, Growth, Affection, Resolve (APGAR) Questionnaire 4) Rosenberg Self-Esteem Scale (RSES) and 5) Maudsley Personal Inventory (MPI). Results: Social skills deficits were significantly associated with female gender, age < 40 years, depression severity, introvert / neurotic personality, and lowered family support satisfaction and self-esteem. A large part of the variance (47.2%) in social skills deficits was predicted by satisfaction of family support, introvert personality, and low self-esteem. Exploratory Factor Analysis showed that a bifactorial model best fitted the data with a) a general factor loading highly on BDI-II, SSI emotional and social, APGAR, RSES, MPI_introvert and MPI_neurotic scores, and b) a single-group factor loading on both SSI, RSES, and MPI introvert scores. Conclusion: In clinical depression, social skills deficits covary with increasing severity of depression and thus constitute a state marker of depression, and independently from severity of depression covary with introvert personality features. As such, remission of social skills deficits may emerge as a novel objective for the treatment of depression and prevention of new episodes.

Mutation in the ethionamide (ETH) activating enzyme, EthA, is the main factor determining resistance to this drug, used to treat TB patients infected with MDR and XDR Mycobacterium tuberculosis isolates. Many mutations in EthA of ETH resistant (ETH-R) isolates have been described but their roles in resistance remain uncharacterized, partly because structural studies on the enzyme are lacking. Thus, we took a two-tier approach to evaluate two mutations (Y50C and T453I) found in ETH-R clinical isolates. First, we used a combination of comparative modeling, molecular docking, and molecular dynamics to build an EthA model in complex with ETH that has hallmark features of structurally characterized homologs. Second, we used free energy computational calculations for the reliable prediction of relative free energies between the wild type and mutant enzymes. The ΔΔG values for Y50C and T453I mutant enzymes in complex with FADH₂-NADP-ETH were 3.34 (+/−0.55) and 8.11 (+/−0.51) kcal/mol, respectively, compared to the wild type complex. The positive ΔΔG values indicate that the wild type complex is more stable than the mutants, with the T453I complex being the least stable. These are the first results shedding light on the molecular basis of ETH resistance, namely reduced complex stability of mutant EthA.

The outbreak of 2019-novel coronavirus (SARS-CoV-2) that causes severe respiratory infection (COVID-19) has spread in China, and the world health organization declared it pandemic. However, no approved drug or vaccines are available, and treatment is mainly supportive and through a few repurposed drugs. In this urgency situation, development of SARS-CoV-2 based vaccines is immediately required. Immunoinformatic and molecular modelling are generally used time-efficient methods to accelerate the discovery and design of the candidate peptides for vaccine development. In recent years, the use of multiepitope vaccines is proved to be a promising immunization strategy against viruses and pathogens, which induce more comprehensive protective immunity. The current study demonstrated a comprehensive in-silico strategy to design stable multiepitope vaccine construct (MVC) from B-cell and T-cell epitopes of essential SARS-CoV-2 proteins with the help of adjuvants and linkers. The integrated molecular dynamics simulations analysis revealed the stability of MVC and its interaction with human Toll-like receptors (TLRs), which trigger an innate and adaptive immune response. Later, the in-silico cloning in a known pET28a vector system also estimated the possibility of MVC expression in E. Coli. Despite this study lacks validation of this vaccine construct in terms of its efficacy, the current integrated strategy encompasses the initial multiple epitope vaccine design concepts. After validation, this MVC can present to be a better prophylactic solution against COVID-19.

The importance of antibodies in health care and the biotechnology research and development demands not only knowledge of their experimental structures at high resolution, but also practical implementation of this knowledge for both effective and efficient design and production of antibody for its use in both medical and research applications. While the experimental wet-lab approach is usually costly, laborious and time-consuming, computational (dry-lab) approaches, in spite of their intrinsic limitations in comparison with its experimental (wet-lab) counterpart, provide a cheaper and faster alternative option. For the first time, this article reports a comprehensive set of structural electrostatic features extracted from experimentally determined antigen-antibody-related structures, including especially those structural electrostatic features at the interfaces of all experimentally determined antigen-antibody complex structures as of February 29, 2020, to facilitate effective and efficient machine learning-based computational antibody design using currently available experimental structures inside Protein Data Bank.

During December 2019, a novel coronavirus named as 2019-nCoV, has emerged in Wuhan, China. The human to human transmission of this virus has also been established. Untill now the virus has infected more than seven thousand people and has spread to fifteen countries. The World Health Organization (WHO) has declared 2019-nCoV as global health emergency due to its outburst well beyond China. There is need to develop some vaccines or therapeutics to control or prevent 2019-nCoV infections. The bottleneck with current conventional approaches is that these require longer time for vaccine development. However, computer assisted approaches help us to produce effective vaccine in short time compared with conventional methods. In this study, bioinformatics analysis was used to predict B cell and T cell epitopes of surface glycoprotein of 2019-nCoV that could be suitable to trigger significant immune response. The sequence of surface glycoprotein was collected from the database and analyzed to identify the immunogenic epitope. Both B cell and T cell epitopes were analyzed so the predicted epitopes can stimulate both cellular and humoral immune responses. We predicted 13 B cell and 05 T cell epitopes that later on were joined with GPGPG linker to make a single peptide. This computational approach to design a multi epitope peptide vaccine against emerging 2019-nCoV allows us to find novel immunogenic epitopes against the antigen targets of surface 2019-nCoV surface glycoprotein. This multi epitope peptide vaccine may prove effective to combat 2019-nCoV infections.

Ethnopharmacological relevance: Novel coronavirus disease (COVID-19) outbroke in Wuhan has imposed a huge influence onto the society in term of the public heath and economy. However, so far, no effective drugs or vaccines have been developed. Whereas, the Traditional Chinese Medicine (TCM) has been considered as a promising supplementary treatment for the disease owing to its clinically proven performance on many diseases even like severe acute respiratory syndrome (SARS). Meanwhile, many side-effect (SE) reports suggest the SE of the TCM prescriptions cannot be ignored in curing the COVID-19, especially because COVID-19 always simultaneously leads to dramatic degradation of the patients’ physical condition. How to evaluate the TCM regarding to their latent SE is a urgent challenge. Aim of the study: In this study, we use an ontology-based side-effect prediction framework (OSPF) developed in our previous work and Artificial Neural Network (ANN)-based deep learning to evaluate the TCM prescriptions that are officially recommended in China for novel coronavirus (COVID-19). Materials and methods: Firstly, we adopted the OSPF developed in our previous work, where an ontology-based model separate all the ingredients in a TCM prescription into two categories: hot and cold. Then, we established a database by converting each TCM prescription into a vector containing the ingredient dosage and the according hot/cold attribution as well as the safe/unsafe label. And, we trained the ANN model using this database, after which a safety indicator (SI), as the complementary percentage of side-effect (SE) possibility, is then given for each TCM prescription. According to the proposed SI from high to low, we re-organize the recommended prescription list. Secondly, by using this method, we also evaluate the safety indicators of some other famous TCM prescriptions that are not in the recommended list but are used traditionally to cure flu-like diseases for extending the potential treatments. Results: Based on the SI generated in the ANN model, FTS, PMSP, and SF are the safest ones in recommended list, which all own a more-than-0.8 SI. Whereas, JHQG, LHQW, SFJD, XBJ, and SHL are the prescriptions that are most likely unsafe, where the indicators are all below 0.2. In the extra list, the indicators of XC, XQRS, CC, and CHBX are all above 0.8, and at the meantime, XZXS, SJ, QW, and KBD’s indicators are all below 0.2. Conclusions: In total, there are seven TCM prescriptions which own the indicators more than 0.8, suggesting these prescriptions should be considered firstly in curing COVID-19, if suitable. We believe this work will provide a reasonable suggestion for the society to choose proper TCM as the supplementary treatment for COVID-19. Besides, this work also introduces a pilot and enlightening method for creating a more reasonable recommendation list of TCM to other diseases.

The article discusses determinants of living environment in Central and Eastern Europe. As an example, the city of Radzionkow was chosen, with 16 thousand inhabitants, located in the Silesia agglomeration in southern Poland, in the area where hard coal has been mined for almost two hundred years, which largely serves as a source of heating for houses and flats. 360 buildings in 6 groups of 60 buildings were examined in the selected city, which allowed to distinguish 3 different areas in terms of the quality of the living environment depending on the technical condition of buildings, the method of heating and location. To a large extent, determinants are the existing spatial and geophysical conditions of a given location. Many research and reports on the living environment do not take into account the factors mentioned, focusing only on the statistical data of pollution, excluding spatial factors. In the research presented, the author, taking into account location variables, shows differences in the measurements of air pollution in relation to the designated location zones depending on the morphological structure of the building, the degree of its modernization and the types of heating used in buildings.

Fatty acid desaturase 2 (Fads2) is the key enzyme of long chain polyunsaturated fatty acid (LC-PUFA) biosynthesis. Endogenous production of these biomolecules in vertebrates, if present, is insufficient to meet demand. Hence, LC-PUFA are considered as conditionally-essential. At present however, LC-PUFA are globally-limited nutrients due to anthropogenic factors. Attention of research is given therefore to find ways to maximize endogenous LC-PUFA production especially in production species, whereby deeper knowledge on molecular mechanisms of enzymatic steps involved is being generated. This review first briefly informs about the milestones in the history of LC-PUFA essentiality exploration before it focuses on the main aim – to highlight the fascinating Fads2 potential to play roles fundamental to adaptation to novel environmental conditions. Investigations are summarized, which elucidate the evolutionary history of fish Fads2 providing an explanation for the remarkable plasticity of this enzyme in fish. Further, structural implications of Fads2 substrate specificity are discussed and some relevant studies performed on organisms other than fish are mentioned in cases when such studies have so far not been conducted on fish models. The importance of Fads2 in the context of growing aquaculture demand and dwindling LC-PUFA supply is depicted and a few remedies in the form of genetic engineering to improve endogenous production of these biomolecules are outlined.

Water resource is considered as a significant factor in development of regional environment and society. Water consumption prediction can provide important decision basis for the regional water supply scheduling optimisations. According to the periodicity and randomness nature of the daily water consumption data, a Markov modified autoregressive moving average (ARIMA) model is proposed in this study. The proposed model, combined with the Markov chain, can correct the prediction error, reduce the continuous superposition of prediction error, and improve the prediction accuracy of future daily water consumption data. The daily water consumption data of different monitoring points are used to verify the effectiveness of the model, and the future water consumption is predicted, in the study area. The results show that the proposed algorithm can effectively reduce the prediction error compared to the ARIMA.

The aim of the study was to analyze the in ovo injection of chemically and biologically synthesized silver nano-particles (Ag NPs) using Brassica oleracea L. var capitate f. Rubra, (BOL) conjugation with L-Arginine (L-Arg) on the immune, muscle growth, survivability and hatchability of the broiler chickens. L-Arg (100 μg) with 1000 µg (BOL-Ag NPs) and L-Arg (100 μg) with 100 µg (C-Ag NPs) were injected into fertile eggs at 8, 14 and 18 of incubation. Survival and hatched chicks were calculated. Survivability and hatchability were unaffected by the injected dose of L-Arg (100 μg) with 1000 µg (BOL-Ag NPs) and L-Arg (100 μg) with 100 µg (C-Ag NPs) but it significantly improved when the eggs were injected on day 14 of incubation compared with those injected on days 8 or 18. Moreover, the protein expression of muscle development markers such as myogenin and myoD were significantly up-related in 14 d incubation whereas the heat shock proteins (HSPs) such as HSP-60 and HSP-70 were significantly up-regulated in 18 d incubation. In addition, the in ovo injection on 18 d significantly increased the serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) as well the immunoglobulin (IgM) levels were increased in 14-day incubation period in serum at the same concentration. Collectively, these results indicate that injecting L-Arg (100 μg) with 1000 µg of BOL-Ag NPs or L-Arg (100 μg) with 100 µg of C-Ag NPs to eggs at day 14 after incubation could improve their hatchability, survival rate, and muscle growth marker.

Chronic gastro-abdominal pain with altered bowel habits are associated with pathologies including gastroenteritis, autoimmune and inflammatory bowel disease, and irritable bowel syndrome (IBS). In IBS, diagnostic evidence of infection or inflammation are absent, yet symptoms nonetheless include chronic abdominal pain and alterations of stool frequency and consistency, with most common subtypes including diarrhea-predominant (IBS-D) or constipation predominant (IBS-C). [1, 2] IBS is a common clinical complaint in westernized nations, with females more frequently diagnosed than males [3]. Obesity is also associated with increased likelihood of chronic pain [4], and is associated with intestinal dysbiosis, and systemic inflammatory signatures [5]. Improving personalized medicine therefore requires patient stratification based on a combination of biological factors contributing to the individual’s symptom and biomarker spectrum. The “buffy coat” method isolates leukocytes and PBMCs from whole blood, comprises the immune cell population in peripheral blood. These cells are relatively inactive but are primed to respond to generalized and localized immune activation signals; they are under active investigation as diagnostic biomarkers [6]. Collection of buffy coat is a standard method in clinical laboratories; detection of immune activation via RNA expression biomarkers will be informative of differential biological response, and be tractable to collect in clinical settings. Results of differential expression, pathway analysis, and cell-type abundance analysis from buffy coat RNA, is presented here using variables for BMI, Gender, and IBS-subtype from publicly available Nanostring RNA expression and phenotypic data from the NCBI GEO database.

Indian pangolins are insectivorous mammals with less-known ecology. Due to the lack of sufficient literature on their dietary ecology, captive raring of this species has become problematic. This article describes data on dietary composition and foraging habitats of the Indian Pangolin (Manis crassicaudata) in a tropical lowland forest-associated landscape in Southwest Sri Lanka. Five different types of habitats were investigated in this study: Forest, rubber plantation, cinnamon cultivation, oil palm plantation, and tea-dominated home gardens. Foraging preference of the Indian pangolin for each habitat was assessed using signs of foraging activities. To further observe the foraging habitat utilization of pangolins, photographic evidences were collected using Infrared (IR) active camera traps located in all the studied habitats. Faecal samples collected from same habitats were further examined to identify the dietary composition of Indian Pangolins. As termites and ants are major prey organisms of Indian pangolins, the digestibility of different body parts –heads, mouthparts, abdomens, and legs of termites and ants was also scrutinized. The findings of the study with regard to dietary ecology will be important for both captive feed preparation and future conservation planning of the species

I demonstrate that the ionization energy (IE) and the electron affinity (EA) of organic molecular crystals can be predicted from first-principles. Here, I describe the induced electronic polarization and the electrostatic effects upon crystalline IE and EA. I also demonstrate that the electronic polarization mainly originates from the screened coulomb interaction inside the crystalline bulk phase, and that the electrostatic contribution to IE and EA crucially depends on the orientation of the molecule at the surface. The former is well described by the GW approximation, while the latter is reasonably estimated by the difference in frontier orbital energy between the gas phase and the surface at the level of a generalized gradient approximation to the density functional theory. The present methodology enables to demonstrate the impact of the electrostatic effect upon the energy level of the injected charge at a multi-monolayer surface of an organic semiconductor thin film.

Background: Sacubitril/valsartan has been shown to be superior to enalapril in reducing the risks of death and hospitalization for heart failure (HF). However the effect on cardiac performance remains unknown. We sought to evaluate the effects of sacubitril/valsartan on clinical, bioumoral and echocardiographic parameters in patients with HFrEF. Methods: Sacubitril/valsartan was administered to 205 HFrEF patients. Results: Among 230 patients (mean age 59 ± 10 years, 46% with ischemic heart disease) 205 (89%) completed the study. After a follow–up of 10.49 (2.93±18.44) months, the percentage of patients in NYHA class III changed from 40% to 17% (p<0.001). Median N–Type natriuretic peptide (Nt-proBNP) decreased from 1865 ± 2318 to 1514 ± 2205 pg/mL, (p=0.01). Furosemide dose reduced from 131.3 ± 154.5 to 120 ± 142.5 (p=0.047). Ejection fraction (from 27± 5.9% to 30 ± 7.7% (p<0.001) and E/A ratio (from 1.67 ± 1.21 to 1.42 ± 1.12 (p=0.002)) improved. Moderate to severe mitral regurgitation (from 30.1% to 17.4%; p=0.002) and tricuspid velocity decreased from 2.8 ± 0.55 m/sec to 2.64 ± 0.59 m/sec (p<0.014). CONCLUSIONS: Sacubitril/valsartan induce “hemodynamic reverse remodeling” and in association with Nt-proBNP concentrations lowering improve NYHA class despite a diuretic dose reduction.

In Sub-Saharan African Countries such as Nigeria with high prevalence rate, Child HIV/AIDs acquired through Mother-to-Child transmission (MTCT) can be largely prevented by using a well-established prevention programme and scheme. This study examined factors that can enhanced Prevention of Mother-to-Child transmission (PMTCT) in Nasarawa State. To achieve this, structured questionnaire were used to collect data from one hundred and sixteen (116) women attending two (2) primary facilities and two (2) secondary facilities in the State. This study utilized methods of Poisson Regression, Negative Binomial Regression and Logistic Regression Analyses. Results revealed that women with at least a secondary school education, women with husband in military and women with perceived confidentiality of their HIV status significantly enhanced PMTCT of HIV in Nasarawa State while significant proportion of the women attest to the fact that drugs are available in the facilities (p-value=0.0000<0.05) . Other factors include mother income level, willingness to continue with PMTCT programme and women in support group can also enhanced PMTCT though they are not significant. This study recommends that the factors identified should be explored by NGOs, Ministry of Health and, Support groups and other relevant agencies since they have the capacity to enhanced PMTCT of HIV in Nasarawa State, Nigeria.

PDEF is expressed in luminal epithelial cells of the prostate gland and associates with luminal phenotype. Hippo pathway regulates cell growth/proliferation, cellular homeostasis, and organ development by modulating phosphorylation of its downstream effectors. In previous studies, we observed decreased levels of PDEF during prostate cancer progression. In the present studies, we evaluated the effects of PDEF on total and phospho (Ser-127)YAP1 protein(a downstream effector of the Hippo pathway) levels in PC3 cells, a line of castrate resistant prostate cancer. We observed that the expression of PDEF in PC3 cells resulted in increased increased phospho(Ser127) -YAP1 protein levels. Our immunofluorescence analysis for YAP1 revealed an increased cytoplasmic/nuclear ratio of YAP1 in PDEF-PC3 cells as compared to VC-PC3 cells, suggesting PDEF may play a critical role in modulating YAP1 phosphorylation, and by extension in the regulation of the Hippo pathway. We also observed a decrease in YAP1 protein levels in prostate cancer tissues as compared to normal prostate tissues. Our analysis of multiple publicly available clinical cohorts revealed a gradual decrease in YAP1 mRNA expression during prostate cancer progression and metastasis. This decrease was similar to the decrease in PDEF levels which we reported earlier. In addition we observed further decreased in PDEF and YAP1 expression in Neuro-Endocrine Prostate Cancer (NEPC), and a direct correlation between PDEF and YAP1 expression. To the best of our knowledge, these results provide the first demonstration of modulation of YAP1 by PDEF in any system and suggest a cross-talk between PDEF and the Hippo pathway.

In the steeply inclined and extremely thick coal seams (SIETCS) mined using the horizontal sublevel top-coal caving (HSTCC) method, the uncertainty of gas emission is a safety threat to the mining operations. In order to reduce the occurrence of accidents, the determination of gas emission is crucial. In this paper, we first proposed a prediction model for workers at the floor coalbed to calculate gas emission on site. We then put forward a finite element numerical simulation for researchers to predict gas emission from the floor coalbed. At last, we measured gas emitted from the floor coalbed of SIETCS in Wudong Coal Mine in a specific mining period and used the data to verify the applicability and accuracy of these two gas-emission prediction methods. The results showed that the gas emission from Wudong Coal Mine was 1.08 m³/min calculated based on the prediction model and 1.07 m³/min obtained using the user-defined integration method. Both methods have their own advantages, disadvantages and applicable objects, and are important in predicting gas emission from SIETCS mined using HSTCC method.

Background: Glioblastoma (GBM), a malignant grade IV tumor, is the most malignant brain tumor due to its hyper-proliferative and apoptosis-evading characteristics. The signal transducer and activators of transcription (STAT) family genes, including STAT3 and STAT5A, have been indicated to play important roles in GBM progression. Increasing number of reports suggest that Garcinol, a polyisoprenylated benzophenone and major bioactive component of Garcinia indica contains potent anti-cancer activities. Material & Methods: The present study investigated the anti-GBM effects of garcinol, focusing on the STAT3/STAT5A activation, using a combination of bioinformatics, in vitro, and ex vivo assays. Results: Our bioinformatics analysis of TCGA - GBM cohort (n=173) showed that STAT3 and STAT5A are preferentially elevated in primary and recurrent GBM, compared to non-tumor brain tissues, and is significantly correlated with reduced overall survival. In support, our immunohistochemical staining of a GBM cohort (n=30) showed an estimated 5.3-fold (p<0.001) elevation in STAT3 and STAT5A protein expression in primary and recurrent GBM versus the non-tumor group. In vitro, garcinol treatment significantly suppressed the proliferative, invasive, and migratory potential of U87MG or GBM8401 cells, dose-dependently. In addition, garcinol anticancer effect significantly attenuated the GBM stem cell-like phenotypes, as reflected by diminished ability of U87MG or GBM8401 to form colonies and tumorspheres and suppressed expression of OCT4 and SOX2. Furthermore, analysis on GBM transcriptome revealed an inverse correlation between the level of STAT3/5A and hsa-miR-181d. Garcinol-mediated anti-GBM effects were associated with an increased hsa-miR-181d/STAT3 and hsa-miR-181d/5A ratio. Conclusion: We present evidence of anti-GBM efficacy of garcinol mediated by enhancing the hsa-miR-181d/STAT3 and hsa-miR-181d/5A ratios in GBM cells. Our findings suggest a potential new therapeutic agent for combating aggressive GBM.

Although urbanization has contributed to improving living conditions, it has had negative impacts on the natural environment in the urbanized areas. Urbanization has changed the urban landscape and resulted in increasing land surface temperature (LST). Thus, studies related to LST in various urban environments have become a popular research topic. However, few LST studies focusing on the mountain landscapes (i.e. hill stations) have been carried out. The primary objective of this study is to investigate changes in the landscape and their impacts on LST intensity (LSTI) in the tropical mountain city of Nuwara Eliya, Sri Lanka. The study utilized annual median temperatures extracted from Landsat data collected from 1996 to 2017 based on the Google Earth Engine (GEE) interface. The fractions of built-up (BL), forest (FL), and agricultural (AL) land were calculated using land use and cover maps based on the urban-rural zone (URZ) analysis. The urban-rural margin was demarcated based on the fraction of BL (<10%) and LSTI was measured using the mean LST difference in the urban-rural zone. In addition, the mixture of land use types was calculated using the AL/FL and BL/FL fraction ratios, and grid-based density analysis. The result shows that the BL in all URZ rapidly developed, while AL decreased during the period 1996 to 2017. There was minimal change in the forest area of the Nuwara Eliya owing to the government forest preservation policies. The fraction of the BL increased from 32.4% in 1996 to 58.7% in 2017 in the city center zone (URZ₁) resulting in increased mean LST by 4.7 °C. Furthermore, the increase of the BL/FL fraction ratio and the decrease of the AL/FL fraction ratio were positively correlated with the mean LST. Grid-based analysis showed an increasing positive relationship between mean LST and density of BL. This indicated that BL density has been a crucial element in increasing LST in the study area. The results of this study will be a useful indicator to introduce improved landscape and urban planning in the future to minimize the negative impact of LST on urban sustainability.

A multi-strand composite welding wire was applied to join high nitrogen austenitic stainless steel, and microstructures and mechanical properties were investigated. The electrical signals demonstrate that the welding process using a multi-strand composite welding wire is highly stable. The welded joints are composed of columnar austenite and dendritic ferrite and welded joints obtained under high heat input and cooling rate have a noticeable coarse-grained heat-affected zone and larger columnar austenite in weld seam. Compared with welded joints obtained under the high heat input and cooling rate, welded joints have the higher fractions of deformed grains, high angle grain boundaries, Schmid factor and the lower dislocation density under the low heat input and cooling rate, which indicate a lower tensile strength and higher yield strength. The rotated goss (G_RD) orientation of a thin plate and the cube (C) orientation of a thick plate are obvious after welding, but the S orientation at 65° sections of Euler’s space is weak. The δ-ferrite was studied based on the primary ferrite solidification mode. It is observed that low heat input and high cooing rate result in the increasing of δ-ferrite and high dislocation density was obtained in grain boundaries of δ-ferrite. M₂₃C₆ precipitates due to low cooling rate and heat input in weld seam and deteriorates the elongation of welded joints. The engineering stress-strain curves also show the low elongation and tensile strength of welded joints under low heat input and cooling rate, which is mainly caused by the high fraction of δ-ferrite and the precipitation of M₂₃C₆.

Major depression (MDD) is accompanied by higher serum IgM/IgA responses to LPS of Gram-negative bacteria, suggesting increased bacterial translocation and gut dysbiosis. Gut dysbiosis may occur in bipolar disorder (BD) and there are differences between MDD and BD type 1 (BP1) and -2 (BP2) in nitro-oxidative stress biomarkers associated with leaky gut. This study examines serum IgM/IgA responses directed to LPS of 6 Gram-negative bacteria in 29 BP1, 37 BP2, 44 MDD and 30 healthy individuals. MDD plus BD was best discriminated from controls by increased IgM/IgA responses to Pseudomonas aeruginosa. BP1 patients showed higher IgM responses to Morganella morganii as compared with MDD and BP2 patients. Patients with melancholia showed higher IgA responses to Citrobacter koseri as compared to controls and non-melancholic depression. The total score on the Hamilton Depression Rating Scale was significantly associated with IgA responses, especially C. koseri. IgG responses to oxidized low-density lipoprotein were significantly associated with signs of increased bacterial translocation. In conclusion, not only MDD but also BP1 and BP2 are accompanied by an immune response due to the increased load of plasma LPS of gut commensal bacteria while these aberrations in the gut-brain axis are most pronounced in BP1 and patients with melancholic features. Activated oxidative stress pathways and autoimmune responses to oxidative specific epitopes in mood disorders may be driven by a breakdown in gut paracellular, transcellular and/or vascular pathways. If replicated, drugs that protect the integrity of the gut barrier may offer novel therapeutic opportunities for BP1 and MDD.

In the implementation of thermal enhanced oil recovery (TEOR) techniques, the temperature impact on relative permeability in oil - water systems is of special concern. Hence, developing a fast and reliable tool to model the temperature effect on two-phase oil - water relative permeability is still a major challenge for precise studying and evaluation of TEOR processes. To reach the goal of this work, two promising soft-computing algorithms, namely Group Method of Data Handling (GMDH) and Gene Expression Programming (GEP) were employed to develop reliable, accurate, simple and quick to use paradigms to predict the temperature dependency of relative permeability in oil - water systems (K_rw and K_ro). To do so, a large database encompassing wide-ranging temperatures and fluids/rock parameters, including oil and water viscosities, absolute permeability and water saturation, was considered to establish these correlations. Statistical results and graphical analyses disclosed the high degree of accuracy for the proposed correlations in emulating the experimental results. In addition, GEP based correlations were found to be the most consistent with root mean square error (RMSE) values of 0.0284 and 0.0636 for K_rw and K_ro, respectively. Lastly, the comparison of the performances of our correlations against those of the preexisting ones indicated the large superiority of the introduced correlations compared to previously published methods. The findings of this study can help for better understanding and studying the temperature dependency of oil - water relative permeability in thermal enhanced oil recovery processes.

Structural perturbations in the Mn4CaO5 cluster site, an oxygen-evolving complex of photosystem II, such as those induced by Ca2+/Sr2+ exchanges or Ca/Mn-removal have been known to induce long-range positive shifts (+30 mV to +150 mV) in the redox potential of the primary quinone electron acceptor plastoquinone A (QA) located 40 Å distant from the OEC. Here, we reanalyzed the crystal structure of Sr-PSII solved at 2.1 Å and compare it with the native Ca-PSII of 1.9 Å with focus on the acceptor site and report on the possible long-range interactions between the donor, Mn4Ca(Sr)O5 cluster, and acceptor sites.

Bacterial wilt (BW), caused by Ralstonia solanacearum is one of the major biotic factors limiting tomato production in the humid tropics. Pyramiding of resistance genes through marker-assisted selection is an efficient way to develop durable BW resistant cultivars. Tomato line ‘Hawaii 7996’ (H7996) is a stable and robust resistance source against various R. solanacearum strains. Major BW resistance quantitative trait loci (QTLs) Bwr-12 and Bwr-6, and several minor or strain specific QTLs have been coarse-mapped in this line, but none has been fine-mapped and validated. The objective of the current study was to construct a high density genetic map using single-nucleotide polymorphism (SNP) markers derived from genotyping-by-sequencing, fine-map Bwr-12 and Bwr-6 and determine the effects of these QTLs using a near isogenic line (NIL) population. A high density genetic map using 1,604 SNP markers with an average distance of 0.82 cM was developed for 188 F9 recombinant inbred lines derived from the cross H7996 × WVa700. A total of seven QTLs associated with BW resistance to race 1-phylotype I or/and race 3-phylotype II strains were located on chromosomes 6 (Bwr-6.1, 6.2, 6.3 and 6.4) and 12 (Bwr-12.1, Bwr-12.2 and Bwr-12.3) with logarithm of odds (LOD) scores of 6.2-15.6 and 6.2-31.1, explaining 14.2-33.4% and 15.9-53.9% of the total phenotypic variation contributed from H7996, respectively. To validate the genetic effects of the two QTL regions, a set of 80 BC3F3 NILs containing different sections of Bwr-6 with or without Bwr-12 was phenotyped for disease severity after challenge with either race 1-phylotype I Pss4 or race 3-phylotype II Pss1632 BW strains over two seasons. Bwr-6.1 specific to Pss4 and Bwr-6.3 specific to Pss1632 were mapped to an interval of 5.0 cM (P < 0.05) between 6_33,444,000_SLM6-47 and 6_33,868,000_SLM6-124 SNP marker, and to 2.7 cM (P < 0.01) between positions 6_35,949,000 _SLM6-107 to 6_36,750,000_SLM6-82 marker, respectively. In addition, the specific effect of Bwr-12 for resistance to Pss4 (LOD score of 5.8-16.1, P < 0.01) was confirmed and markers for this QTL have already been made available previously.

The objective of this study was to develop an ultrasonic-assisted procedure for the extraction of total phenolics from Citrus aurantium L. blossoms (CAB) and evaluate the free radical scavenging activity, anti-HMG-CoA reductase activity of total phenolics. In this work, a Box-Behnken design based on the single-factor experiments was used to explore the optimum extraction process. Under the optimum conditions (extraction solvent 70.31% ethanol, extraction temperature 61.94 °C, extraction time 51.73 min and liquid-to-solid ratio 35.63 mL/g), the extraction yield of total phenolics was 95.84 mg gallic acid equivalents (GAE)/g dry matter (DM), which was highly consistent with the theoretical value (96.12 mg GAE/g DM). The total phenolic extract showed excellent free radical scavenging properties against DPPH·, ABTS+·, ·OH and ·O2-, with the IC50 values of 197.007, 83.878, 218.643 and 158.885 μg/mL, respectively, and the extracts also showed good inhibition of HMG-CoA reductase activity, with the IC50 value of 117.165 μg/mL. Total phenolics from CAB could be a potential source of natural free radical scavenger and HMG-CoA reductase inhibitor.

Mediterranean coastal lagoons and their peripheral areas often provide a collection of habitats for many species, and they often face significant threats from anthropogenic activities. Diverse human activities in such areas directly affect the spatio-temporal dynamic of surface water and its ecological characteristics. Monitoring the surface water dynamic, and understanding the impact of human activities are of great significance for coastal lagoon conservation. The Regional Natural Park of Narbonne includes a typical Mediterranean lagoon complex where surface water dynamic and its potential link with local diverse human activities has not yet been studied. In this context, based on all the available Landsat images covering the study area during 2002-2016, this study identified the water and non-water classes for each satellite observation by comparing three widely used water indices (i.e., NDVI, NDWI and MNDWI) and using the Otsu method. The yearly water frequency index was then computed to present the spatio-temporal dynamic of surface water for each year, and three water dynamic scenarios were also identified for each year: permanent water (PW), non-permanent water (NPW) and non-water (NW). The spatial and inter-annual variation in the patterns of the three water scenarios were characterized by computing the landscape metrics at scenario-level quantifying area/edge, shape, aggregation and fragmentation. Finally, the quantitative link between different land use and land cover (LULC) types derived from the LULC maps of 2003, 2012 and 2015 and the surface water dynamic scenarios was established in each of the 300 m x 300 m grid cells covering the study area to determine the potential impact of human activities on the surface water dynamic. In terms of the inter-annual variation during 2002-2016, PW presented an overall stability, and NPW occupied only a small part of the water surface in each year and presented an inter-annual fluctuation. NPW had a smaller patch size, with lower connectivity degree and higher fragmentation degree. In terms of spatial variation during 2002-2016, NPW often occurred around PW, and its configurational features varied from place to place. Moreover, PW mostly corresponded to natural lagoon, and salt marsh (as a part of lagoons), and NPW had a strong link with arable land (agricultural irrigation) and salt marsh (salt production), sand beach/dune, coastal wetlands and lagoon for the LULC maps of 2003, 2012 and 2015. However, more in-depth analysis is required for understanding the impact of sand beach/dune, coastal wetlands and lagoon on surface water dynamics. This study covers the long-term variations of surface water patterns in a Mediterranean lagoon complex having intense and diverse human activities, and the potential link between LULC types and the water dynamic scenarios was investigated on different dates. The results of the study should be useful for environmental management and protection of coastal lagoons.

Intercultural education can be seen as a cornerstone in the sustainability of the current culturally diverse society. In addition, through the establishment of policies and strategies to reverse situations of discrimination and exclusion, there is a consensus on the importance of the social inclusion of groups at risk of exclusion. In this context, actions are suggested to reverse high dropout rates and school failure within the Roma population. The aim of this systematic review in the educational context is to analyze investigations of programs and interventions that have been made to promote the educational inclusion of Roma students. Three databases are used, Scopus, Web of Science, and Eric, to examine 419 articles, which after a selection, based on an inclusion criterion which follows the guidelines given by the Declaration PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyzes), 17 articles were chosen for the analysis. The main findings shed light on data for programs and interventions developed mostly within the school setting and for students of elementary and secondary education. These programs provide answers for the molding of intercultural education and the policies for educational inclusion of Roma people.

The main objective of the study is to analyse time trends in excessive body weight (obesity, overweight) of Czech adolescents between 2002 and 2018 with regard to the socioeconomic status (SES) of adolescents’ families and to find SES-mediated correlates of adolescents’ obesity. A nationally representative sample of 29,879 adolescents (49.6% of them boys) aged 10.5-16.5 years was drawn from the Health Behaviour in School-aged Children cross-sectional, self-reported questionnaire surveys conducted in 2002, 2006, 2010, 2014, and 2018 in the Czech Republic. Across the quadrennial surveys from 2002 to 2018, we observed a clear increase in the prevalence of excessive body weight (overweight/obesity) in all SES categories of adolescents, which was most striking (p < 0.05) in adolescents with low SES (boys: +5.2/+7.5 percent points (p.p.); girls +6.3/+2.4 p.p.). When all the survey cycles were compared, the highest prevalence of overweight/obesity was evident in the low-SES adolescents in 2018, both in girls (14.9%/5.1%) and boys (20.4%/12.0%). The lower odds of obesity were significantly (p < 0.05) associated with regular vigorous physical activity, participation in organized sport. An unreasonable increase in the prevalence of obesity in adolescents with low SES suggests that national health-related and sports programmes have the least impact on children from low-SES families.

The Internet-of-Things (IoT) enables enterprises to obtain profits from data but triggers data protection questions and new types of cyber risk. Cyber risk regulations for the IoT however do not exist. The IoT risk is not included in the cyber security assessment standards, hence, often not visible to cyber security experts. This is concerning, because companies integrating IoT devices and services need to perform a self-assessment of its IoT cyber security posture. The outcome of such self-assessment needs to define a current and target state, prior to creating a transformation roadmap outlining tasks to achieve the stated target state. In this article, a comparative empirical analysis is performed of multiple cyber risk assessment approaches, to define a high-level potential target state for company integrating IoT devices and/or services. Defining a high-level potential target state represent is followed by a high-level transformation roadmap, describing how company can achieve their target state, based on their current state. The transformation roadmap is used to adapt IoT risk impact assessment with a Goal-Oriented Approach and the Internet of Things Micro Mart model.

In this paper, we study the convergence of new implicit iterations dealing with n-tupled fixed point results for nonlinear contractive-like mappings on W-hyperbolic metric spaces. Herein, we demonstrate that our newly implicit iteration schemes have faster rate of convergence than implicit S-iteration process, implicit Ishikawa and Mann type iteration processes. Furthermore, a numerical simulation to improve our theoretical results is obtained.

Background: Biomarkers are essential for identification of individuals at high risk of mild cognitive impairment (MCI) for potential prevention of dementia. We investigated DNA methylation in the ApoE gene and plasmatic apolipoprotein E (ApoE) levels as MCI biomarkers in Colombian subjects with MCI and controls. Methods: 100 participants were included (71% women, average age, 70 yrs., range 43-91). MCI was diagnosed by neuropsychological testing, medical and social history, activities of daily living, cognitive symptoms and neuroimaging. Multivariate logistic regression models adjusted by age and gender were performed to examine the risk association of MCI with plasma ApoE and APOE methylation Results: MCI was diagnosed in 41 subjects (average age, 66.5±9.6 yrs.) and compared with 59 controls. Elevated plasma ApoE and APOE methylation of CpGs 165, 190, and 198 were risk factors for MCI (P<0.05). Higher CpG-227 methylation correlated with lower risk for MCI (P=0.002). Only CpG-227 was significantly correlated with plasmatic ApoE levels (correlation coefficient=-0.665; P=0.008). Conclusion: Differential APOE methylation and increased plasma ApoE levels were correlated with MCI. These epigenetic patterns can be used as potential biomarkers to identify early stages of MCI.

Background: It is unknown whether lowered steady state levels of sex hormones coupled with changes in those hormones during the menstrual cycle could be associated with the presence and severity of premenstrual syndrome (PMS).Objective: To examine associations between levels of progesterone and oestradiol during the menstrual cycle and PMS severity considering different diagnostic criteria for PMS.Methods: Forty women aged 18-45 years with a regular menstrual cycle completed the Daily Record of Severity of Problems (DRSP) for all 28 consecutive days of the menstrual cycle. Blood was sampled at days 7, 14, 21 and 28 to assay oestradiol and progesterone. Results: We developed a new diagnosis of peri-menstrual syndrome, which is characterized by increased DRSP severity in pre and post-menstrual periods and increased scores on the major DRSP dimensions, i.e. depression, physio-somatic symptoms, breast tenderness and appetite, and anxiety. This new diagnosis performed better than classical diagnoses of PMS, including the one presented by the American College of Obstetricians and Gynecologists. Lowered steady state levels of progesterone, when averaged over the menstrual cycle, together with declining progesterone levels during the luteal phase predict severity of peri-menstrual symptoms. Steady state levels of oestradiol and declining oestradiol levels during the cycle are also related to DRSP severity although most of these effects appeared to be mediated by progesterone. Conclusion: A significant increase in menstrual-cycle related symptoms can best be conceptualized as “peri-menstrual syndrome” and may result from “corpus luteum insufficiency”, which may result from suboptimal pre-ovulatory follicular development. Future research should trial Clomiphene citrate (given the first 5 days of the cycle) and a mid-cycle injection of human Chorionic Gonadotrophin in subjects with peri-menstrual syndrome.

Introduction: Child undernutrition remains a challenge globally and in the geographically diverse country of Ethiopia. Improving dietary diversity and consumption of animal source foods are important for improving child nutrition and corresponding health outcomes. Objective: The objective of the study was to identify household and community factors associated with consumption of animal source foods among 6 to 36-month-old children from four regions of Ethiopia. Methods: A cross-sectional survey using multistage probability sampling in eight geographic zones and four regions of Ethiopia took place in 2015 with parents/caretakers of 6 to 36-month-old children. Data was collected on demographic information, proxy indicators of socioeconomic status, and food consumed by the child the day before the survey. Results: Increased child age, pastoral livelihood, Muslim religion, and participation in the Productive Safety Net Program were associated with increased consumption of animal source foods. Odds of animal source foods consumption increased 8% with each 3-month age increase. Children from pastoralist households were the most likely to have consumed animal source foods in the preceding 24 hours as compared with those in agro-pastoralist households (0.21 times as likely) or those in agriculturalist/farming households (0.15 times as likely). The odds of consumption of animal source foods for families with food aid or safety net support was 1.7 times greater among those receiving traditional support from the Productive Safety Net Program and 4.5 times greater for those in the direct support arm of the program. Conclusions: The findings illustrate the importance of accounting for local context and community characteristics, such as livelihood and religion, when undertaking programming designed to improve diversity of children’s diets through increasing animal source foods. In addition, the Productive Safety Net program may be a critical determinant of dietary diversity for young children in these regions.

This paper analyses the evolution of the internal damage in two types of steel that show different fracture behaviours, with one of them being the initial material used for manufacturing prestressing steel wires, which shows a flat fracture surface perpendicular to the loading direction, and the other one being a standard steel used in reinforced concrete structures, which shows the typical cup-cone surface. 3mm-diameter cylindrical specimens are tested with a tensile test carried out in several loading stages and, after each of them, unloaded and analysed with X-ray tomography, which allows detection of internal damage throughout the tensile test. In the steel used for reinforcement, damage is developed progressively in the whole specimen, as predicted by Gurson-type models, while in the steel used for manufacturing prestressing steel-wire damage is developed only in the very last part of the test. In addition to the experimental study, a numerical analysis is carried out by means of the finite element method by using a Gurson model to reproduce the material behaviour.

Although, staging models gained momentum to stage define affective disorders, no attempts were made to construct mathematical staging models using clinical and biomarker data in patients with major depression and bipolar disorder.The aims of this study were to use clinical and biomarker data to construct statistically-derived staging models, which are associated with early lifetime traumata (ELTs), affective phenomenology and biomarkers.In the current study, 172 subjects participated, 105 with affective disorders (both bipolar and unipolar) and 67 controls. Staging scores were computed by extracting latent vectors (LVs) from clinical data including ELTs, recurring flare ups and suicidal behaviors, outcome data such as disabilities and health-related quality of life (HR-QoL), and paraoxonase (PON)1 actvities and nitro-oxidative stress biomarkers.Recurrence of episodes and suicidal behaviors could reliably be combined into a LV with adequate composite reliability (the “recurrence LV”), which was associated with female sex, the combined effects of multiple ELTs, disabilities, HR-QoL and impairments in cognitive tests. All those factors could be combined into a reliable “ELT-staging LV” which was significantly associated with nitro-oxidative stress biomarkers. A reliable LV could be extracted from serum PON1 activities, recurrent flare ups, disabilities and HR-QoL.Our ELT-staging index scores the severity of a relevant affective dimension, shared by both major depression and bipolar disorder, namely the trajectory from ELTs, a relapsing course and suicidal behaviors to progressive disabilities. Patients were classified into three stages, namely an early stage; a relapse-regression stage; and a suicidal-regression stage. Lowered lipid-associated antioxidant defenses may be a drug target to prevent the transition from the early to the later regression stages.

The black timber bark beetle Xylosandrus germanus (Blandford) is an invasive ambrosia beetle originating from Southeastern Asia that has become successfully established within Europe and North America. Herein, we provide a review of the spread and distribution of this pest of trees and timber across Europe before and after 2000, along with a review of its habitat preferences. Since the spread of X. germanus across Europe has accelerated rapidly post-2000, emphasis is placed on this period. X. germanus was first recorded in Germany in 1951 and since then in 21 European countries along with Russia. Ethanol-baited traps were deployed in oak, beech, and spruce forest ecosystems in the Western Carpathians, Central Europe, Slovakia, to characterize the distribution and habitat preference of this non-native ambrosia beetle. Captures of X. germanus within Slovakia have been rising rapidly since its first record in 2010, and now this species dominates captures of native ambrosia beetles. X. germanus has spread throughout the whole Slovakia from the south-southwest to the north-northeast over the period of 5–10 years and has also spread vertically into higher altitudes within this country. While living but weakened trees in Europe and North America are attacked by X. germanus, the greatest negative impact within Slovakia is attacks on recently felled logs of oak, beech and spruce trees providing high quality timber/lumber. We suggest that the recent rapid spread of X. germanus in Central Europe is being facilitated by environmental changes, specifically global warming, and the increasing frequency of timber trade. Recommendations for management of X. germanus in forest ecosystems are proposed and discussed, including early detection, monitoring, sanitary measures, etc.

Polluted rivers are a primary problem in Changhua County, Taiwan, due to rapid and massive developments in agriculture and industry. In this study, samples consisted of water influent from the Yangzi-Cuo River, Ci-Tong Jiao, Changhua County. Ecology technology, a combination of gravel contact oxidation and surface flow constructed wetlands, was employed to enhance the water quality. Ecology technology is a useful and ordinary process that focuses on original treatment of pollution through chemical, physical, and biological procedures based on the mediums of soil, plant, water, and microorganisms from pure environments. Moreover, this study aimed to minimize the river pollution index (RPI) of the Yangzi-Cuo River by using combinations of gravel contact oxidation and surface flow constructed wetlands. The inflow volume of the water samples in situ was found to be 1534–2261 cubic meters per day (CMD). The pollution in the water sample mostly involved suspended solid (SS), ammoniacal nitrogen (NH₃–N), total phosphorus (TP), total nitrogen (TN), and biochemical oxygen demand (BOD), and the values of the above indexes were found to be 10.0–26.7 mg/L, 0.9–14.0 mg/L, 1.2–14.1 mg/L, 11.1–18.2 mg/L, and 0.5–3.6 mg/L, respectively. Efficiencies of pollution elimination in SS, NH₃–N, TP, TN, and BOD were found to be 24.2–93.1%, 58.3–86.2%, 5.2–85.0%, 59.4–77.2%, and 46.3–76.4%, correspondingly, after purification treatment via ecology technology. Thus, ecology technology is a valid means of purification treatment for polluted rivers.

We describe a selective and sensitive fluorescence platform for the detection of trinitrophenol (TNP) based on competitive host–guest recognition between pyridine-functionalized pillar[6]arene (PCP6) and probe (acridine orange, AO) that used PCP6-functionalized reduced graphene (PCP6-rGO) as the receptor. TNP is an electron-deficient and negative molecule which is captured by PCP6 via electrostatic interactions and π-π interactions. Therefore, a selective and sensitive fluorescence sensor for TNP detection is developed. It has a low detection limit of 0.0035 μM (S/N=3) and a wider linear response of 0.01−5.0 and 5.0−125.0 for TNP. The sensing platform is also used to test TNP in two water and soil samples with satisfying results. This suggests that this approach has potential applications for the determination of TNP.

Objective: The purpose of this study is to compare the effects of stretching methods for flexibility, muscle activation, and pressure pain threshold in ballet dancers, and to suggest an effective stretching method. Methods: Thirty-three ballet dancers were randomized to a static stretching group (n=11), muscle energy technique stretching group (n=11), and vibration-assisted stretching group (n=11). The angle of hip joint extension in arabesque, the activation of rectus femoris in Devéloppé, and the pressure pain threshold on rectus femoris in sitting position were measured to compare the effects of different stretching methods. Results: Hip joint extension angles increased in all stretching methods (p<0.05), however, vibration-assisted stretching and muscle energy technique stretching were more effective than static stretching (p<0.05). The activation of the rectus femoris decreased in all groups (p<0.05), but the muscle energy technique stretching group and the vibration-assisted stretching group showed a significant decrease compared to the static stretching group (p<0.05). The pressure pain threshold showed significant improvement only in the static stretching group (p<0.05), and the vibration-assisted stretching group (p<0.05). Conclusion: Vibration-assisted stretching compared to static stretching and muscle energy technique stretching is a beneficial method for flexibility, muscle activation, and pressure pain threshold in ballet dancers.

Phospholipase Dα1 (PLDα1) belongs to phospholipases, a large phospholipid hydrolyzing protein family. PLDα1 has a substrate preference for phosphatidylcholine leading to enzymatic production of phosphatidic acid, a lipid second messenger with multiple cellular functions. PLDα1 itself is implicated in biotic and abiotic stress responses. We present here a shot-gun differential proteomic analysis on roots of two pldα1 mutants compared to the Col-0 wild type. Our data suggest new roles of PLDα1 in endomembrane transport, mitochondrial protein import and protein quality control and glucosinolate biosynthesis. Thus, we identified proteins involved in endocytosis, endoplasmic reticulum-Golgi transport and attachment sites of endoplasmic reticulum and plasma membrane (V-type proton ATPases, protein transport protein SEC13 homolog A, vesicle-associated protein 1-2, vacuolar protein sorting-associated protein 29, syntaxin-32, all upregulated in the mutants), mitochondrial import and electron transport chain (mitochondrial import inner membrane translocase subunits TIM23-2 and TIM13, mitochondrial NADH dehydrogenases, ATP synthases, cytochrome c oxidase subunit 6b-1, ADP,ATP carrier protein 2, downregulated in the mutants) and glucosinolate biosynthesis (3-isopropylmalate dehydrogenases 1, 2 and 3, methylthioalkylmalate synthase 1, cytochrome P450 83B1, Glutathione S-transferase F9, indole glucosinolate O-methyltransferase 1, adenylyl-sulfate kinase 1, all upregulated in mutants). Our results suggest broader biological roles of PLDα1 as anticipated so far.

The fact that individuals are spatially close to each other in the urban environment increases the potential number of encounters between them. Thus, theoretically speaking, the probability of interaction and social intercourse among people increases as they get closer to each other spatially. This reduction in spatial distance and propensity for larger networks can offer advantages in lower communication and transaction costs. However, there is also the possibility of entropy in a single (organizational) urban subsystem, characterized by reduced spatial distances between individuals that can lead to more toxic outcomes and the possibility of generalized deconstruction in an urban system as a whole. The current paper considers, through a theoretical model and secondary data analysis, how reductions in spatial distance between individuals in urban business organizations can lead to withdrawals of energy through toxic forms of entropic citizenship behavior, and lead to the development of toxic organizations. Such toxic organizations can ‘infect’ the urban system and lead to systematic entropic urban deconstruction. Practical, implications for management of the theoretical explanatory heuristic of toxic forms of organizational entropy and toxic organizations are briefly discussed in the paper.

Citrus peel has been used in Asian traditional medicine for the treatment of cough, asthma, and bronchial disorders. However, the anti-inflammatory effect of quercetogetin (QUE), a polymethoxylated flavone isolated from the peel of citrus unshui is poorly understood. We investigated the anti-inflammatory effect and the molecular mechanisms of QUE in lipopolysaccharide (LPS)-induced RAW264.7 cells. QUE inhibited the production of NO and prostaglandin E2 by suppressing the LPS-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 at both the mRNA and protein levels. QUE suppressed the production of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. QUE also inhibited the translocation of the nuclear factor kappa B subunit, p65, into the nucleus by interrupting the phosphorylation of IκB-α in LPS-induced RAW 264.7 cells. Based on the finding that QUE significantly decreased p-ERK protein expression in LPS-induced RAW264.7 cells, we confirmed that suppression of the inflammatory process by QUE was mediated through the MAPK pathway. This is the first report on the strong anti-inflammatory effects of QUE, which is a compound that can potentially be used as a therapeutic agent for inflammatory diseases.

Abstract: Background and objective: Propofol is an anesthetic agent that is frequently used in anesthesia induction, maintenance and sedation. Propofol has severe side effects such as hypotension, bradycardia and respiratory depression. Although propofol is commonly used, there is no known antidote for its toxic effects. An approach to prevent toxic effects of propofol would be beneficial. The aim of this study was to assess the effects of intravenous lipid emulsion (ILE) therapy in the prevention of depressive effects of propofol on cardiovascular and respiratory systems. Materials and methods: Twenty-eight Sprague-Dawley adult rats were randomly divided into 4 groups. The saline-administered group was determined as the Control group. The second group was administered propofol (PP group); the third group was administered ILE (ILE group), and the fourth was administered propofol with ILE therapy (ILE+PP group). Systolic blood pressure (SBP), Diastolic blood pressure (DBP), Mean arterial blood pressure (MAP), Respiratory rate (RR), Heart rate (HR) and mortality were recorded at 10 points during 60 minutes. A repeated measures linear mixed-effect model with unstructured covariance was used to compare the groups. Results: In the PP group, SBP, DBP, MAP, RR and HR levels were declining steadily; all rats in this group died after 60 minutes. In the ILE+PP group, after a while, the decreased SBP, DBP, MAP, RR and HR levels increased SBP, DBP, MAP, RR and HR levels of the Propofol group were found to be significantly lower than those of the other groups (p<0.01). The mortality rate was 100% (surviving period, 60 min) for the PP group, whereas 0% for the ILE, ILE+PP and Control groups. Conclusion: Our results suggest that undesirable side effects that can be seen after propofol application such as hypotension, bradycardia and respiratory depression might be prevented by using ILE therapy.

Wingless-type MMTV integration site (Wnt) signaling is one of the most critical pathways in developing and adult tissues. In the brain, Wnt signaling contributes to different neurodevelopmental aspects ranging from differentiation, axonal extension, synapse formation, neurogenesis and neuroprotection. Canonical Wnt signaling is mediated mainly by the multifunctional β-catenin protein which is a potent co-activator of transcription factors such as Lymphoid Enhancer Factor (LEF) and T Cell Factor (TCF). Accumulating evidence points to dysregulation of Wnt/β-catenin signaling in major neurodegenerative disorders. Here I focus on a “Wnt/β-catenin-glial connection” in Parkinson’s disease (PD), the most common movement disorder characterized by the selective death of midbrain dopaminergic (mDAergic) neuronal cell bodies in the subtantia nigra pars compacta (SNpc) and gliosis. I will summarize the work of the last decade documenting that Wnt/β-catenin signaling in partnership with glial cells is critically involved in each step and at every levels in the regulation of nigrostriatal DAergic neuronal health, protection and regeneration in the MPTP mouse model of PD, focusing on Wnt/β-catenin signaling to boost a full neurorestorative program in PD.

The quick modernisation of Iceland, that rapidly took place from the first decades of the 20th century onwards, did not only bring fishing trawlers and cars into the country. Among all the techniques of modernity, concrete [steinsteypa] was to become the key material that changed the built landscape of the island and was soon adopted by the first Icelandic architects, such as Rögnvaldur Ólafsson (1874–1914) and Guðjón Samúelsson (1887–1950). Interestingly, the main supporter of this material was Guðmundur Hannesson (1866–1946), a medical doctor and town planner who wrote several articles and even a guidebook published in 1921 and titled Steinsteypa. Leiðarvísir fyrir alþýðu og viðvaninga [Concrete. Guidebook for Common People and Beginners]. In a country that was seeking an architectural self-representation, he understood the technical and formal possibilities that concrete could offer: he claimed, “people [...] were trying to change, to build out of a new material with a new form” (Guðmundur Hannesson 1926, 14). This essay aims thus to retrace the rhetoric of Guðmundur Hannesson and his role in writing an Icelandic chapter of the history of concrete, from its early stage of unmodern trial-and-error to the definition of a modern Icelandic architecture.

Literature is inconsistent as to how coffee affects the features of the metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. We aimed to compare the in-vivo effects of unfiltered coffee with a selected mixture of its compounds on diet-induced MetS. 24 male Sprague-Dawley rats were fed a high-fat (35% W/W) food plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water in a dosage equal to 4 cups/day in a human. Compared to the controls, only coffee supplementation decreased total food intake, weight gain, and estimated average plasma glucose. Surrogate measures of insulin resistance (fasting insulin, HOMA-IR, and oral glucose tolerance) were improved at endpoint in the coffee group. Circulating triglyceride levels were also reduced by coffee. Histopathological and quantitative measurements indicated lower grades of liver steatosis after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

Abstract: Unusual methane emission and spontaneous combustion of coal induced by the air leakage are both hazards during mining. The most common practice has been to improve mine safety is sealing the mining fractures. In this paper, the methane and geology, coal spontaneous combustion characteristics and the coexistence of methane emission and spontaneous combustion of coal were analyzed. The preparation system of inorganic solidified foam (ISF) in field applications is studied and the working principle of generating device consists of foam generator and mixer was expounded. The technical plan of site construction is that the foam fluids was injected to respectively seal the mining fractures behind hydraulic supports, the cavities of air return corner, and the fractures nearby the coal pillar. After the foam fluids injection, the two stress values in the coal pillar eventually maintained above 15.5Mpa and 13Mpa, respectively. It indicated that the ISF can enhance the bearing stress ability of the coal pillar by transforming the stress state from two dimensional to three dimensional. The methane concentration in the air return corner and air return roadway declined significantly to 0.63% and 0.25%. The differential pressure inside and outside of the 4301(1) goaf fluctuated between -100pa to 150pa and the concentration of CO and O2 declined to 9ppm and 6%. The CO concentration in the air return corner finally reached a stable level of 6ppm. What that all means, the foam fluids can seal the air leakage and inhibit spontaneous combustion of coal effectively.

A phenomenological constitutive model is developed to describe the uniaxial transformation ratcheting behaviors of super–elastic shape memory alloy (SMA) by employing a cosine–type phase transformation equation with the initial martensite evolution coefficient that can capture the feature of the predictive residual martensite accumulation evolution and the nonlinear hysteresis loop on a finite element (FE) analysis framework. The effect of the applied loading level on transformation ratcheting are considered in the proposed model. The evolutions of transformation ratcheting and transformation stresses are constructed as the function of the accumulated residual martensite volume fraction. The FE implementation of the proposed model is carried out for the numerical analysis of transformation ratcheting of the SMA bar element. The integration algorithm and the expression of consistent tangent modulus are deduced in a new form for the forward and reverse transformation. The numerical results are compared with those of existing model and the experimental results to show the validity of the proposed model and its FE implementation in transformation ratcheting. Finally, a FE modeling is established for a repeated preload analysis of SMA bolted joint

The proposed research methodology aims to design a generally implementable framework for providing a house owner/member with the immediate notification of an on-going theft (unauthorized access to their premises). For this purpose, a rigorous analysis of existing systems was undertaken to identify research gaps. The problems found with existing systems were that they can only identify the intruder after the theft, or cannot distinguish between human and non-human objects. Wireless Sensors Networks (WSNs) combined with the use of Internet of Things (IoT), Cognitive Internet of Things, Internet of Medical Things, and Cloud Computing are expanding smart home concepts and solutions, and their applications. The primary objective of the present research work was to design and develop IoT and cloud computing based smart home solutions. In addition, we also propose a novel smart home anti-theft system that can detect an intruder, even if they have partially/fully hidden their face using clothing, leather, fiber, or plastic materials. The proposed system can also detect an intruder in the dark using a CCTV camera without night vision facility. The fundamental idea was to design a cost-effective and efficient system for an individual to be able to detect any kind of theft in real-time and provide instant notification of the theft to the house owner. The system also promises to implement home security with large video data handling in real-time.

Technology then has become a mixed bag for the tourism industry. It creates a great deal of conveniences while at the same time has been used as a way to increase revenues and to lessen customer service, especially for the education of adults in the area of digital competence for the use for advertising the tourist offer of your own units. Modern Education Programs can be a great help in overcoming digital literacy and thus helping to choose a variety of offers that offer free internet advertising. The survey was conducted on the example of Okrug municipality on the Čiovo peninsula in the period from February 2017 to April 2017. 278 private renters participated. The aim of the research was to show that the Program for the Education of Foreign Languages, a specific English language that was organized by the Municipality, contributed to the advertising of its tourist units, thereby contributing to the revenue, ie the occupancy in the number of reservations. The paper used a quantization method, a questionnaire survey. point to the fact that it is necessary to invest in the Education Program so that the older population, in particular, acquires the general level of digital literacy and foreign language learning, for the purpose of finding an adequate media for advertising and strengthening the tourist capital of a municipality.

The emerging use of visualization techniques in pathology and microbiol- ogy has been accelerated by machine learning (ML) approaches towards image preprocessing, classification, and feature extraction in an increasingly complex series of datasets. Modern Convolutional Neural Network (CNN) architectures have developed into an umbrella of vast image reinforcement and recognition methods, including a combined classification-localization of single/multi-object featured images. As a subtype neural network, CNN cre- ates a rapid order of complexity by initially detecting borderlines, edges, and colours in images for dataset construction, eventually capable in mapping intricate objects and conformities. This paper investigates the disparities between Tensorflow object detection APIs, exclusively, Single Shot Detector (SSD) Mobilenet V1 and the Faster RCNN Inception V2 model, to sample computational drawbacks in accuracy-precision vs. real time visualization capabilities. The situation of rapid ML medical image analysis is theoretically framed in regions with limited access to pathology and disease prevention departments (e.g. 3rd world and impoverished countries). Dark field mi- croscopy datasets of an initial 62 XML-JPG annotated training files were processed under Malaria and Syphilis classes. Model trainings were halted as soon as loss values were regularized and converged.

In recent years, integration of electric vehicles (EVs) has increased dramatically due to their lower carbon emissions and reduced fossil fuel dependency. However, charging EVs could have significant impacts on the electrical grid. One promising method for mitigating these impacts is the use of renewable energy systems. Renewable energy systems can also be useful for charging EVs where there is no local grid. This paper proposes a new strategy for designing a renewable energy charging station consisting of wind turbines, a photovoltaic system, and an energy storage system to avoid the use of diesel generators in remote communities. The objective function is considered to be the minimization of the total net present cost, including energy production, components setup, and financial viability. The proposed approach, using stochastic modeling, can also guarantee profitable operation of EVs and reasonable effects on renewable energy sizing, narrowing the gap between real-life daily operation patterns and the design stage. The proposed strategy should enhance the efficiency of conventional EV charging stations. The key point of this study is the efficient use of excess electricity. The infrastructure of the charging station is optimized and modeled.

Agriculture is the backbone of Kenya’s economy, supporting up to 80% of the rural livelihoods. Kenya’s export horticulture is currently the leading Agriculture subsector in Kenya has evolved from small-holder farming to agro-industrial large-scale export farming dominated by multinational companies. It is regarded as an agro-industrial food system based on the economies of scale producing for mass markets outside of the production area. Much of the food consumed from this food system has undergone multiple transformations and been subject to a host of formal and informal insitutions (rules, regulations, standards, norms and values). An Anthropological study of export horticulture in Northwest Mount Kenya was carried out utilizing qualitative data collection methods in Northwest Mount Kenya region. Data was coded and analysed thematically based on grounded theory approach. The study described the institutional settings of export horticulture from an emic perspective as changing and defining the operations of the food system access and management of common pool resources, namely water and land. With the agro-industrial food system competing for these scarce resources in a semi-arid zone, there is potential for conflict and also reduced production and overall benefits to the different actors in the study area.

Structurally related 7-acetyl-2-aryl-5-bromoindoles 2a–d and the 7-acetamido-2-aryl-5-bromoindoles 4a–d as well as their corresponding 3-trifluoroacetyl–substituted derivatives 5a–d and 5e–h were evaluated for potential antigrowth effect in vitro against the human lung cancer (A549) and cervical cancer (HeLa) cells. All of the 3-trifluoroacetyl–substituted 7-acetamido-2-aryl-5-bromoindoles 5e–h were found to be more active against both cell lines when compared to the chemotherapeutic drug, Melphalan. The most active compound 5g induced apoptosis in a caspase dependent manner for both cell lines. Compounds 5e–h were found to significantly inhibit tubulin polymerization. Molecular docking of 5g into the colchicine-binding site suggests that the compounds bind to tubulin by different type of interactions including pi-alkyl, amide-pi stacked and alkyl interactions as well as hydrogen bonding with the protein residues to elicit anticancer activity.

Conservation Agriculture (CA) is capable of improving soil health and ecosystem functions. Soil carbon sequestration is one of the ecosystem processes that is of importance in sustainable land management involving reduction in greenhouse gas emissions and adaptation to climate change. In this study, we wanted to determine, during the first year of the process of establishing a CA cropping system in rain-fed areas in Madhya Pradesh state of India, which soil health indicators show measurable signs of improvement. Four field trials were selected, each comprising two neighboring plots. One plot (15×15 m) was managed conventionally under farmer practice and was tilled before sowing seeds, and in the adjacent plot Conservation Agriculture practices were applied. No mineral fertilizers or pesticides were applied in both treatments. Soil health indicators of soil aggregate stability, soil-atmosphere CO₂ fluxes, water infiltration, soil moisture, potentially mineralizable nitrogen, soil organic content and bulk density were measured. Results demonstrate that soil CO₂ emissions in CA soils decreased and soil aggregates stability improved in the first year. Generally, in CA soils, there were measurable improvements in all soil health indicators but only some of them were statistically significant.

Recently, the awareness of energy conservation, carbon emission reduction, and environmental protection in Taiwan has begun to gradually improve, and bicycles have become an important vehicle for residents. In 2009, Kaohsiung began promoting public bicycle sharing. The number of users in that year amounted to 140,000. By 2015, the accumulated number of users reached nine million. This study adopted the Theory of Planned Behavior (TPB) to explore the factors influencing the behavioral intentions of public bicycle users, including the three dimensions of attitude, subjective norm, and perceived behavioral control, and probed into the relationship between the factors influencing the behavioral intentions of public bicycle users in Kaohsiung City and the dimensions. This study used a questionnaire to collect data and SPSS & AMOS for statistical analysis. The empirical results demonstrated that the most prominent factors influencing the behavioral intentions of public bicycle users in Kaohsiung City included perceived behavioral control, attitude, and subjective norm, in order. Among the influencing factors in the three dimensions, personal interests, main groups, and self-competence had a positive and significant correlation. Administrators should provide more incentives related to the three influencing factors to encourage the public in Kaohsiung City to use public bicycles more frequently as their short-distance travel mode, so as to achieve the purposes of saving energy, reducing carbon emissions, and protecting the urban environment.

This article concerns the adoption of small-scale irrigation farming as a climate-smart agriculture practice and its influence on household income in the Chinyanja Triangle. Chinyanja Triangle is a region that experiences mid-season dry spells and an increase in occurrences of drought due to low and erratic rainfall patterns which is attributed largely to climate variability and change. This poses high agricultural production risks, which aggravate poverty and food insecurity. For this region, adoption of small-scale irrigation farming as a climate-smart agriculture practice is very important. Through a binary logistic and ordinary least squares regression, the article determines factors that influence the adoption of small-scale irrigation farming as a climate-smart agriculture practice and its influence on income among smallholder farmers. The results show that off-farm employment, access to irrigation equipment, access to reliable water sources and awareness of water conservation practices, such as rainwater harvesting have a significant influence on the adoption of small-scale irrigation farming. On the other hand, the farmer’s age, distance travelled to the nearest market and nature of employment negatively influenced the adoption of small-scale irrigation farming decisions. Ordinary least squares regression results showed that the adoption of small-scale irrigation farming as a climate-smart agriculture practice has a significant positive influence on agricultural income. We therefore conclude that to empower smallholder farmers to quickly respond to climate variability and change, practices that will enhance adoption of small-scale irrigation farming in the Chinyanja Triangle are critical as this will significantly impact on agricultural income.

Tourmalines are a group of minerals which may concentrate various accessory components, e.g. Cu, Ni, Zn, Bi, Ti, Sn. The paper presents fluor-elbaite and elbaite from a dyke of the Julianna pegmatitic system at Piława Górna, at the NE margin of the Bohemian Massif, SW Poland, containing up to 6.32 and 7.37 wt.% ZnO, respectively. Such high amounts of ZnO are almost two times higher than in the second most Zn-enriched tourmaline known to date. The compositions of the Zn-rich tourmalines from Piława Górna, studied by electron microprobe and Raman spectroscopy, correspond to the formulae: (Na0.73Ca0.01•0.25)Σ1(Al1.03Li0.79Zn0.76Fe2+0.33Mn0.09)Σ3Al6B3Si6O27(OH)3(F0.66OH0.34), and (Na0.78Ca0.01•0.21)Σ1(Al1.06Li0.87Zn0.88Fe2+0.10Mn0.09)Σ3Al6B3Si6O27(OH)3(OH0.84F0.16), respectively, with Zn as one of the main octahedral occupants. A comparison with other tourmalines and associated Zn-rich fluor-elbaite and elbaite from the pegmatite indicates that atypically high Zn-enrichment is not a result of Zn-Fe fractionation, but dissolution and reprecipitation induced by a late (Na,Li,B,F)-bearing fluid within the assemblage of gahnite spinel and primary schorl-type tourmaline. This strongly suggests Na-Li-B-F metasomatism of gahnite-bearing mineral assemblages as that is the only environment that can promote crystallization of a hypothetical Zn-dominant tourmaline. The compositions of the Zn-rich fluor-elbaite and elbaite suggest three possible end-members for such a hypothetical tourmaline species: NaZn3Al6B3Si6O27(OH)3(OH), •(Zn2Al)Al6B3Si6O27(OH)3(OH) and Na(Zn2Al)Al6B3Si6O27(OH)3O.

Watermelon fusarium wilt caused by Fusarium oxysporum f.sp. niveum (FON) is a destructive soil-borne disease throughout the world leading to serious economic losses and limit watermelon production. Cuminic acid, extracted from the seed of Cuminum cyminum L., belongs to benzoic acid analogues. In this study, the median effective concentration (EC₅₀) values for cuminic acid in inhibiting mycelial growth of FON was 22.53μg/mL. After treatment with cuminic acid, mycelial morphology was seriously influenced; cell membrane permeability and glycerol content were increased markedly, but pigment and mycotoxin (mainly fusaric acid) were significantly decreased. Synthesis genes of bikaverin and fusaric acid both were down regulated compared with the control confirmed by quantitative RT-PCR. In greenhouse experiments, cuminic acid at all concentrations displayed significant bioactivities against FON. Importantly, significant enhancement of activities of SOD, POD, CAT and decrease of MDA content after cuminic acid treatment in watermelon leaves were observed in vivo. These indicated that cuminic acid not only showed high antifungal activity, but also could enhance the self-defense system of the host plant. Above all, cuminic acid showed the potential as a biofungicide to control FON.

Nicaragua is preparing the construction of an interoceanic canal that will be the longest and largest canal on earth. An environmental and social impact assessment has been published in 2014 supporting a general viability of the canal. Nonetheless, several scientist and societal actors raised serious concerns regarding the social, economic and ecological sustainability. Despite an open dispute within the Nicaraguan society, no independent, transparent and scientifically sound assessment has been carried out. Only the environmental and social impact assessment, charged by the canal constructor, has so far been realized. The aim of this study is to contribute to an open scientific debate through an objective and independent quantification of land use and hydrological impacts. This article presents a transparently documented and comprehensible impact assessment investigation of the West Canal Segment of the Nicaragua Canal. Based on publically available data and scientifically sound and recognized methods land use, hydrological (water availability) and socio-economic impacts (streets, population) are described, quantified and compared with official declarations in the impact assessment. While some results support official declarations other do not. The number of affected population and the water use of the Brito Lock resulted much higher in this study, for instance. Hence, society and water availability could be affected much higher than estimated in the impact assessment.

1) Background: The Aicardi-Goutières syndrome (AGS) is a rare congenital disease which courses with severe psychomotor delay in neurodevelopment. We studied a 3-years and 4-months old child with very important growth and weight affectation, microcephaly and loss of his developmental skills from 16-months of age, in which previous metabolic and genetic studies discarded any abnormality. Therefore diagnosis was cerebral palsy of unknown etiology. He presented spastic paraparesia, poor fine motricity, cognitive impairment and absence of oral communication. One year after discharge, a de novo mutation was detected in a single nucleotide in the gene IFIH1: c.2317G>C, being then diagnosed of AGS. 2) Methods: Blood analysis showed very low IGF-1 and slightly elevated liver transaminases. Treatment consisted in GH (0.04 mg/kg/day), melatonin (20 mg/day, and after 3-months 50 mg/day), and daily intense neurorehabilitation (5 days/week). Tests for evaluating childhood developmental milestones (GMFM-88, BDIST and the WeeFim test) were carried out every 3-months. 3) Results: The equivalent age at admission (10-months) increased to 24-months at discharge. There were clear improvements in spasticity, fine motor function, swallowing, cognition and autonomy as well as in communication, growth and weight. 4) Conclusion: Most likely melatonin blocked or decreased the interferon signature, allowing GH and neurorehabiltation to act on neurodevelopment.

We previously reported that in multiple sclerosis (MS) patients with a progressive form of the disease, spinal cord periplaques extend distance away from plaque borders and are characterized by the co-occurrence of partial demyelination, astrocytosis and low-grade inflammation. However, transcriptomic analyses comparing periplaques to adjacent normal-appearing white matter (NAWM) areas did not allow providing a comprehensive view of molecular events in astrocytes vs oligodendrocytes. Here, we re-assessed our transcriptomic data with the aim of identifying functionally-relevant co-expression networks that would reflect astrocyte vs oligodendrocyte molecular signatures in periplaques. We identified an astrocytosis-related gene module comprising GFAP, the hub gene CX43/GJA1 and a set of transcripts forming a TGFB/SMAD1/SMAD2 genomic signature. Partial demyelination was characterized by a co-expression network which, besides myelin genes, comprised a highly significant number of translation/elongation-related genes. Interestingly, the main oligodendrocyte-related hub we identified was NDRG1, a gene previously shown to be specifically silenced in the NAWM of MS patients. This result indicated that NDRG1 down-regulation could be an important event in the process of periplaque partial demyelination. To establish a putative link between NDRG1 down-regulation and a cytokine/chemokine signature, we then sought to identify cytokine/chemokine genes whose mRNA levels inversely correlated with those of NDRG1. Following this approach we found 5 candidate immune-related genes whose up-regulation associated with NDRG1 down-regulation: TGFB1, PDGFC, IL-17D, IL-33, and IL-12A. From these results we propose that in the spinal cord of MS patients with progressive forms of the disease, TGFB1 may limit acute inflammation but concurrently induce astrocytosis and an alteration of oligodendrocytes terminal differentiation.