This retrospective study aimed to compare risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Baseline data from 30 pre-HD and 85 HD patients were analyzed, in-cluding iPTH, vitamin D, FGF-23, fetuin-A, sclerostin and VC scores (Adragao method). Preva-lence of VC was similar in both groups, but HD patients had more frequent VC scores ≥6. Pre-HD patients were older, with higher prevalence of hypertension and less frequent use of calcium phosphate binders. Both groups showed similar patterns of hyperphosphatemia, low vitamin D, and iPTH. Fetuin-A levels were higher in pre-HD, while FGF-23 was elevated in HD patients. Higher VC risk in pre-HD patients was associated with male gender, older age, lower fetuin-A and higher sclerostin, lower ferritin and no vitamin D treatment, while in HD patients with higher sclerostin, FGF23 and urea, and lower iPTH. Conclusion. Progression of CKD from the pre-HD to the HD stage is accompanied by a decreased effect of the inhibitor and an increase in the promoter VC. However, mineral imbalance, hormonal regulation, treatment options, and patient-specific fac-tors should be considered. Further studies are needed to elucidate the underlying pathways.

Sierra Madre Mountain Range (SMMR) is the backbone of Luzon Islands that contains high concentration of highly important ecological resources distributed among the 68 protected areas therewith. The present study aimed to assess the tree species composition and diversity in a secondary forest within the SMMR. A 2.25-km transect with 10 900-m2 was established to record tree species with a diameter at breast height of at least 10 cm. The findings revealed 148 individuals of trees from 38 morphospecies, 28 genera, and 20 families. Importance values unveiled the Aurora endemic Macaranga stonei Whitmore as the most important species in terms of the relative values of its abundance, frequency, and dominance. The area was also found to be home for 33 natives, 12 endemics, five IUCN threatened species, and nine Philippine threatened trees. Furthermore, the study site was also found to have a considerably high diversity with Shannon Weiner Index value of 3.269 and a relatively even distribution of individuals among species supported by the Simpson’s Evenness index value of 0.9453. Significant correlational relationships were also found among species richness, Shannon Weinder index, and Simpson’s Evenness index with correlation coefficients ranging from 0.881 to .934 all significant at p < .001. Lastly, the study was able to produce a distribution map necessary in implementing targeted conservation strategies. These findings provided valuable implications for future research and implementation of targeted and participatory biodiversity conservation and protection strategies.

Viruses frequently contain overlapping genes, which encode functionally unrelated proteins from the same DNA or RNA region but in different reading frames. Yet overlapping genes are often overlooked during genome annotation, in particular in DNA viruses. Here we looked for the presence of overlapping genes likely to encode a functional protein in human parvovirus B19 (genus erythroparvovirus), using an experimentally validated software, Synplot2. Synplot2 detected an open reading frame, X, conserved in all erythroparvoviruses, which overlaps the VP1 capsid gene, and is under highly significant selection pressure. In a related virus, human parvovirus (genus tetraparvovirus), Synplot2 also detected an open reading frame under highly significant selection pressure, ARF1, which overlaps the VP1 gene. X and ARF1 have exactly the same location (both overlap the region of VP1 encoding the phospholipase A2 domain), and encode proteins with similar predicted properties, such as a transmembrane region, strongly suggesting that they are homologous. These findings provide compelling evidence that the X protein must be expressed and functional. It is probably translated either from a polycistronic mRNA by a non-canonical mechanism, or from an unmapped monocistronic mRNA. Finally, we also discovered proteins predicted to be expressed from a frame overlapping VP1 in other species related to parvovirus B19: porcine parvovirus 2 (Z protein) and bovine parvovirus 3 (X-like protein).

Background: Accurate estimation of dietary intake is challenging. But whilst some progress has been made in high-income countries, low- and middle-income countries (LMICs) remain behind, contributing to critical nutritional data gaps. This study aimed to validate an objective, passive image-based dietary intake assessment method against weighed food records in London, UK for onward deployment to LMICs. Methods: Wearable camera devices were used to capture food intake of eating occasions in 18 adults and 17 children of Ghanaian and Kenyan origin living in London. Participants were provided pre-weighed meals of Ghanaian and Kenyan cuisine and camera devices to automatically capture images of the eating occasions. Food images were assessed for portion size, energy, and nutrient intake, and relative validity of the method compared to the weighed food records. Results: Pearson and Intra-class correlation coefficient of estimates of intakes of food, energy and 19 nutrients ranged from 0.60 to 0.95 and 0.67 to 0.90, respectively. Bland-Altman analysis showed good agreement between the image-based method and weighed food record. Under-estimation of dietary intake by the image-based method ranged from 4 to 23%. Conclusions: Passive food image capture and analysis provides an objective assessment of dietary intake comparable to weighed food records.

Background: This practice guideline was developed by the Chronic Kidney Disease (CKD) Task Force, which was composed of clinical and methodological experts. The Saudi Arabian Ministry of Health and its Health Holding Company commissioned this guideline project to support the realization of the Vision 2030's healthcare transformation pillar. Methods: The guideline synthesis was guided by the GRADE-ADOLOPMENT methodology. Results: The final adoloped guideline addressed 12 clinical questions on blood pressure management in patients with CKD through a set of recommendations and performance measures. The recommendations included antihypertensive agents in children, non-renin angiotensin system inhibition (Non-RASi) vs RASi in adults, intensive vs standard blood pressure targets, early vs late assessment for kidney replacement therapy (KRT), late vs early preparation strategy for KRT, CKD symptoms during assessment for KRT or conservative management, initiation of KRT in patients with deteriorating CKD, choice of KRT modality or conservative management in certain CKD patient groups, changing or discontinuing KRT modalities, review frequency for KRT or conservative management, and Information, education and support. Conclusions: These conditional recommendations were based on low to very low certainty of evidence that highlights the need for high-quality randomized trials comparing different antihypertensive agents in patients with CKD.

The aim of the study is to assess enjoyment and intensity of physical exercise while practicing physical activity (PA) in immersive virtual reality (IVR) using innovative training devices (omni-directional Omni treadmill and Icaros Pro flight simulator). The study also contains the results of subjective research on the usefulness of such a form of PA in the opinion of users. In total, 61 adults (10 women and 50 men) took part in the study. To assess the enjoyment level (EL) Interest/Enjoyment subscale of Intrinsic Motivation Inventory (IMI) was used. Exercise intensity was assessed during 10-minute sessions of active video games (AVGs) in IVR based on heart rate (HR). The average enjoyment level during physical exercise in IVR on the tested training devices was relatively high (Omni 5.74 points, Icaros 5.60 points). In the opinion of the majority of participants, AVGs on IVR training devices constitute a sufficiently useful form of movement to meet the needs of PA practiced in free time, and they can even replace some of the classic forms of movement. Intensity of PA during games on training devices was at the level recommended for health benefits for 92% (Omni) and 84% (Icaros Pro) of its duration. Based on the conducted research, it can be assumed that AVGs in IVR using a multi-directional treadmill and a flight simulator can be an effective tool for increasing participation in health-oriented PA.

The present work reports new mineralogical and whole rock geochemical data from the Breivikbotn silicocarbonatite (Seiland igneous province, North Norway), allowing conclusions to be drawn concerning its origin and the role of late fluid alteration. The rock shows a rare mineral association: calcite + pyroxene + amphibole + zeolite group minerals + garnet + titanite, with apatite, allanite, magnetite and zircon as minor and accessory minerals, and it is classified as silicocarbonatite. Calcite, titanite and pyroxene (Di36-46 Acm22-37 Hd14-21) are primarily magmatic minerals. Amphibole of hastingsitic composition has formed after pyroxene at a late-magmatic stage. Zeolite group minerals (natrolite, gonnardite, Sr-rich thomsonite-(Ca)) were formed during hydrothermal alteration of primary nepheline by fluids/solutions with high Si-Al-Ca activities. Poikilitic garnet (Ti-bearing andradite) has inclusions of all primary minerals, amphibole and zeolites, and presumably crystallized metasomatically during a late metamorphic event (Caledonian orogeny). Whole rock chemical compositions of the silicocarbonatite differs from the global average of calciocarbonatites by elevated silica, aluminium, sodium and iron, but show comparable contents of trace elements (REE, Sr, Ba). Trace element distributions indicate within-plate tectonic setting of the carbonatite. The spatial proximity of carbonatite and alkaline ultramafic rock (melteigite), the presence of “primary nepheline” in carbonatite together with the trace element distributions indicate that the carbonatite was derived from crystal fractionation of a parental carbonated foidite magma. The main prerequisites for the extensive formation of zeolite group minerals in silicocarbonatite are revealed.

Non-melanoma skin cancers (NMSCs) are the leading cause of skin cancer-related morbidity and mortality. Effective strategies are needed to control NMSC occurrence and progression. Non-toxic, plant-derived extracts have been shown to exert multiple anti-cancer effects. Graviola (Annona muricata), a tropical fruit-bearing plant, has been used in traditional medicine against multiple human diseases including cancer. The current study investigated the effects of graviola leaf and stem extract (GLSE) and its solvent-extracted fractions on two human NMSC cell lines, UW-BCC1 and A431. GLSE was found to: i) dose-dependently suppress UW-BCC1 and A431 cell growth, motility, wound closure, and clonogenicity; ii) induce G₀/G₁ cell cycle arrest by downregulating cyclin/cdk factors while upregulating cdk inhibitors, and (iv) induce apoptosis as evidenced by cleavage of caspases-3, -8 and PARP. Further, GLSE suppressed levels of activated hedgehog (Hh) pathway components Smo, Gli 1/2, and Shh while inducing SuFu. GLSE also decreased the expression of pro-apoptotic protein Bax while decreasing the expression of the anti-apoptotic protein Bcl-2. We determined that these activities were concentrated in an acetogenin/alkaloid-rich dichloromethane subfraction of GLSE. Our data identify graviola extracts and their constituents as promising sources for new chemopreventive and therapeutic agent(s) to be further developed for the control of NMSCs

Maxillary sinus augmentation with a lateral approach (MSA) is a well-established treatment. In this prospective study, we evaluated risk factors for postoperative bone-graft displacement and report the clinical application of long-term resorbable GMEM-B-2 (L-lactic acid/-caprolactone [P(LA/CL)]) as a barrier membrane to cover the open window in the lateral wall in MSA. Twenty-four patients underwent MSA according to the relevant criteria; CT data obtained before and 1 week (1W) and 5–6 months (5M) post-MSA, bone height changes, bone height reduction rates at 1W and 5M post-MSA, bone-graft displacement measurements, and risk factors were examined. All patients showed bone height increments (p &lt; 0.005). However, no difference was observed between 1W and 5M post-MSA. Bone-graft displacement was observed in eight patients; the reduction rate from 1W to 5M post-MSA was 8.38% ± 4.88%. Sex, septa, maxillary sinus floor–palatal bone distance, and maxillary sinus floor–natural mouth distance were associated with bone-graft displacement (p &lt; 0.05). Height from the maxillary sinus floor to the palatal bone and the sinus angle influenced the augmentation amount (p &lt; 0.05). The L-lactic acid/ε-caprolactone [P(LA/CL)] membrane compared favourably with other membranes and may be useful as a barrier membrane for the MSA open window.

Frailty syndrome, a significant contributor to morbidity and mortality in older adults, has traditionally been addressed through aerobic exercises. However, recent research has highlighted the importance of anaerobic and strength training activities in mitigating frailty. This article explores the shift from aerobic to anaerobic/strength training exercises, emphasizing the benefits of the latter in improving muscle strength, balance, and overall physical function. The discussion includes the physiological mechanisms underlying this shift, the evidence supporting strength training, and practical recommendations for implementation.

The research paper examines ‘aporia,’ ‘Différance,’ ‘binary oppositions’ in Ira Trivedi's "The Great Indian Love Story," and India in Love focusing on the characters Riya, Serena, and Permeet's experiences. Derrida’s deconstructive approach is applied to trace out ‘binaries’, ‘aporia’, and ‘Différance’ of sexuality and stigma in literary texts and real human life. It highlights how these characters seem/likely to challenge Indian societal norms and values, societal prejudices and discrimination that lead them to experiences of marginalization and exclusion of the self from other selves. It is observed that deconstruction is an apt approach to literature not a destructive approach.

Liraglutide, a glucagon-like peptide 1 analog used to treat type 2 diabetes and obesity, is a po-tential new treatment modality for bile acid (BA) diarrhea. Here, we show that administration of liraglutide significantly decreased total BAs, especially the primary BAs, including cholic acid, chenodeoxycholic acid, taurocholic acid, taurochenodeoxycholic acid, glycocholic acid, and β-muricholic acid, in the liver and feces. In addition, liraglutide significantly decreased trypto-phan metabolites, including L-tryptophan, serotonin, 5-hydroxy indole-3-acetic acid, L-kynurenine, and xanthurenic acid, in the colon, whereas it significantly increased in-dole-3-propionic acid. Moreover, the administration of liraglutide remarkably decreased the ex-pression of apical sodium-dependent bile acid transporter, which mediates BA uptake across the apical brush border member in the ileum, ileal BA binding protein, and fibroblast growth factor 15 in association with decreased expression of the BA-activated nuclear receptor farnesoid X receptor and the heteromeric organic solute transporter Ostα/β, which induces BA excretion, in the ileum. Liraglutide acutely decreased body weight and blood glucose levels in association with decreases in plasma insulin and serotonin levels in food-deprived mice. These findings suggest the potential of liraglutide as a novel inhibitor of primary BAs and serotonin in the colon, which may be in-volved in the improvement of BA diarrhea.

Volumetric models are a crucial tool for forest management. The study aimed to adjust the mixed model by Schumacher and Hall for estimating commercial volume in a dense ombrophilous forest situated in Ferreira Gomes, Amapá, Brazil. Cubage data from 100 sample trees of 5 species were used to adjust the Schumacher and Hall model in fixed and mixed non-linear forms with the diameter class as a random effect. In addition, the same model was also adjusted for each class to verify whether good equations will be generated by stratifying by diameter class. After analysis, it was found that most of the equations by diameter class do not present all significant parameters. On the other hand, the mixed models using class as a random effect showed good results. Finally, it can be seen that mixed models are a much better alternative than stratification by diameter class for volume estimation.

The aim of this cross-sectional study was to assess the influence of the maturity status on speed, explosive power and change of direction (COD) in 13-year-old football players. Ninety-eight male players (age: 13.1 ± 1.0 y) were divided into late, average, and early maturation groups. Physical fitness testing included the following variables: 10 and 30-meter sprint time and maximum speed in the 20-30 m segment of the 30-meter sprint test, the T-test time, countermovement jump height and horizontal distance in the triple jump. The data showed a significant effect of maturity status on performance in three parameters: in maximum speed in the 20-30 m section (p = 0,024), however, the only significant differences were found between the early-maturation group and average-maturation group (p = 0.033); in the COD (p = 0.024), where significant differences were confirmed between the late-maturation group and the average-maturation group (p = 0.033); in the unilateral triple jump distance of the dominant and non-dominant (p = 0,007 and p = 0.001, respectively) lower limb. For both limbs, significant differences between the late-maturation group and average maturation group (p = 0.005 and p = 0.013, respectively) as well as the late-maturation group and early-maturation group (p = 0.007 and p = 0.045, respectively) were proved. These results indicate that maximal speed, COD speed and unilateral lower limb reactive strength are moderated by biological age in football players aged 13 years.

We have been encouraging practicing gynecologists to adopt molecular diagnostics tests, PCR, and cancer biomarkers, as an alternative enabled by these platforms to traditional Papanicolaou and colposcopy tests, respectively. An aliquot of liquid-based cytology was used for the molecular test [high-risk HPV types, (HR HPV)], another for the PAP test and still one more for the p16/Ki67 dual stain cytology. A total of 4,499 laboratory samples were evaluated, and we found that 25.1% of low-grade samples and 47.9% of high-grade samples after PAP testing had a negative HR HPV-PCR result. In those cases, reported as Pap-negative, 22.1% got a positive HR HPV-PCR result. Dual staining with the p16/Ki67 biomarkers in samples was positive for HR HPV, and 31.7% were also positive for these markers. Of the PCR results positive for any of these high-risk HPV subtypes, n 68.3% we did not to find evidence for the presence of cancerous cells, highlighting the importance of performing dual staining with p16/Ki67 after PCR, to avoid unnecessary colposcopies. Encountered challenges are a deep-rooted social reluctance in Mexico to abandon traditional Pap smears and the opinion of many specialists, we still believe that colposcopy continues to be a preferred procedure over dual staining protocol.

Slimy sculpin (Uranidea cognata) inhabitat coldwater streams in southeastern Minnesota, USA, many of which were subjected to probable 2000-year flood events in August 2007. Floods scoured streambeds, created new stream channels, and greatly reduced benthic invertebrate communities that serve as the primary food resource for sculpin. Diets and Fulton condition of sculpin in Gilmore Creek (with moderate flooding) and Garvin Brook (with very severe flooding) had been examined just prior to flooding, and were re-examined two weeks after flooding to assess possible diet and condition changes. Diets, condition, and reproductive fitness of sculpin were examined seven months post-flood in these same two streams, plus nearby Trout run (also experienced very severe flooding). Sculpin condition declined significantly post-flood in Garvin Brook, but improved in Gilmore Creek. Prior to spring spawning, condition of Garvin Brook sculpin had improved, but Gilmore Creek fish condition worsened. Sculpin diets were more diverse before and after flooding in Gilmore Creek than in Garvin Brook, although diets of fish from both streams were dominated (>55%) by midge (Diptera: Chironomidae) larvae. Diets differed significantly before versus after flooding in the more severely flooded Garvin Brook, but not in Gilmore Creek. Prey number per sculpin stomach declined post-flood in Gilmore Creek, but not in Garvin Brook, although dry mass of prey/fish wet mass declined post-flood in both streams. Pre-spawn sculpin displayed no patterns in reproductive fitness (gonadosomatic index, hepatosomatic index, oocyte number) among the three streams that may have been related to flooding severity the previous summer. Although sculpin diets and condition were altered significantly immediately post-flood in the more severely flooded stream, food resource recovery apparently was rapid enough to prevent longer-term impacts on sculpin condition and reproductive fitness.

Leishmaniasis in wild canids is a vector-borne disease caused in Europe by the protozoan parasite Leishmania infantum. To date, there is limited information on clinical signs and laboratory abnormalities in wolves due to leishmaniasis. The current clinical case report described a female Iberian wolf (Canis lupus signatus) housed in semi-captivity conditions at the Centro del Lobo Ibérico “Félix Rodríguez de la Fuente”, in Robledo de Sanabria, Zamora (Spain) with an interdigital ulcerous wound at the right forepaw, hyper-gammaglobulinemia, and abnormal liver blood parameters. Definitive serodiagnosis of leishmaniasis was established using antileishmanial serum antibodies and PCR analysis of different biological samples. A gold standard anti-L. infantum treatment protocol consisting in intramuscular meglumine antimoniate and oral allopurinol combination was installed. However, the presence of pain at the site of injection due to meglumine antimoniate administration forced its substitution by oral miltefosine. A progressive reduction of the levels of anti-L. infantum serum antibodies and the concentrations of gamma-globulin fraction was detected after antileishmanial treatment as well as a decline of liver GPT. To our knowledge, this is the first case of leishmaniasis diagnosed in a wolf housed in semi-captivity conditions treated and successfully cured.

The identification of a new virus Kiparis-144 (KiparisV) in a half-fed tick I persulcatus, removed from a person in the south of the Russian Far East, determined the goal of further research - to study its role in human pathology and the characteristics of its behavior in the tick microbiome. An ELISA study of 439 blood samples from people affected by tick bites indicated a fairly frequent (up to 16.4±1.7%) encounter of people with the KiparisV virus in the territory of natural foci of the Primorsky Territory. It has been shown that this virus, when mono-infected, can cause clinical symptoms characteristic of acute respiratory diseases. During co-infection under the influence of the KiparisV, there was an increase in the activity of Borrelia spp. with the constant production of antibodies to them only of the IgM class and clinical symptoms of Lyme disease for one year (observation period). Electron microscopy of the KiparisV found in a tick removed from a patient showed a picture of the relationship of the KiparisV (up to 100 nm in size) with unknown representatives of the tick microbiome - pathogens of a viral or bacterial nature. In a comparative aspect, a similar electron microscopic picture of the interaction of the KiparisV virus with a known pathogen of viral nature, the ectromelia virus (ECTV), is presented. The importance of the electron microscopy method in describing the tick microbiome is shown. Thus, it has been established that when co-cultivated in the system the helper-virus KiparisV probably tends to use another pathogen of the tick microbiome for its reproduction, influencing its pathogenicity.

Food authorities aim to safeguard our food. This requires sensitive analyses to guarantee detection of both banned and regulated substances at low concentrations. At the same time, broad screening methods are needed to identify new emerging risks. For this purpose effect-based bioassays combined with mass spectrometric analyses offer an advantage. During the regular monitoring of dioxins in agricultural products, a discrepancy was observed between the results of the DR CALUX (Dioxin-Responsive Chemical Activated Luciferase gene Expression) bioassay and the confirmatory gas chromatographic high resolution mass spectrometric (GC-HRMS) analysis in egg and broiler fat samples. The response in the bioassay was high, suggesting a clear exceedance of the maximum limits of dioxins in these samples, yet regulated dioxins or dl-PCBs were not detected by GC/HRMS analysis . Ultimately, a broad screening analysis using GC-HRMS resulted in the identification of 2,3,7,8-tetrabromo-dibenzofuran (2,3,7,8-TBDF) in both egg and broiler fat. To investigate the potential; source of this brominated furan contaminant, different samples were analysed: bedding material, poultry feed, feed additives (choline chloride and L-lysine) and seaweed. The poultry feed and feed additives all contained 2,3,7,8-TBDF. Using a feed to food converter, it became clear that the poultry feed was probably the source of 2,3,7,8-TBDF in broilers and eggs through a feed additive like L-lysine or choline chloride. This study underlines the importance of using a combination of effect based screening assays with sensitive analytical methods to detect potential new and emerging risks.

Liver is structurally organized into zonation where LSECs endothelial cells play a crucial role during chronic liver injury and early stages of fibrosis. Fibrosis can be reversed if diagnosed early at molecular level in zonation before progressing to advanced stages like bridging fibrosis. This study identified zonation marker genes using scRNA-seq and spatial transcriptomics molecular profiling technologies in normal and diseased fibrotic human liver. DGE analysis is performed over LSECs and identified the top 20 expressed genes in periportal, perivenous, and intermediate acinar zones. Multi-omics and scRNA-seq analysis over Visium images and ECs liver cells figured out OIT3, DNASE1L3, CLEC4G, LYVE1, FCN2, CRHBP as commonly expressed mid-lobular zonation-specific genes. Also, this study detected STAB2, F8, AQP1, TEK, TIMP3, TIE1, CTSL genes as expressed in DILI and NASH ECs populations. The connection between LSECs marker genes in zone 2 and liver fibrosis holds significant promise for advancing our understanding in developing new therapeutic strategies for fibrosis reversal and designing computational molecular biomarkers in NASH and DILI fibrotic liver diseases.

The South Asian economy is on the rise but struggling with power shortages and heavy dependence on fossil fuels. For sustained growth, there is a need for access to readily available energy sources, such as electricity. Trading clean electrical energy among neighbouring countries can ensure access to readily available points. South Asia has a diverse range of energy sources, including hydropower, that are available in the region. However, sectorial barriers can impede energy trading. This study has attempted to assess the readiness and barriers to Nepal’s cross-border energy trade with India and Bangladesh using the Analytic Hierarchy Process (AHP). This study also recommends possible measures to strengthen preparedness and address the challenges in energy trade that can be tailored and applied to other cross-country situations.

This study aimed to assess the enhancement of physical fitness and quality of life through an 8 weeks strength program training in male adolescents soccer players. A lower body muscle groups intervention was performed, with 17 players in the experimental group (EG) and 15 in the control group (CG). The EG carried out soccer training complemented by specific strength work. Pre and post- intervention assessments included body composition, jump height, speed with change of direction, maximum speed in 20 m, movement velocity in back-squat, perceived fatigue effort, academic performance and quality of life. A general linear repeated measures model analysis was used considering for each variable, the interaction between groups (CG, EG) and time (basal, final), to analyze the differences between and within groups. The results showed reduction of fat in the upper limbs and trunk EG, improvements in jump height, maximum speed of 20 m, changes of direction and quality of life increased (p<0.05) in the EG too. It was concluded that a strength program could improve some components of physical performance in male adolescents soccer players.

Hepatitis D virus (HDV) infection represents the most severe form of chronic viral hepatitis. We have shown that the delivery of HDV replication-competent genomes to the hepatocytes using adenoassociated virus (AAV-HDV) as gene delivery vehicles offers a unique platform to investi-gate the molecular aspects of HDV and associated liver damage. Here, we generated HDV ge-nomes modified by site directed mutagenesis aimed to: i) prevent some post-translational modi-fications of HDV antigens (HDAgs) such as Large-HDAg (L-HDAg) isoprenylation or Short-HDAg (S-HDAg) phosphorylation ii) alter the localization of HDAgs within the subcellular compartments and iii) inhibit the right conformation of the delta ribozyme. First, the different HDV mutants were tested in vitro using plasmid-transfected Huh-7 cells and then in vivo in C57BL/6 mice using AAV vectors. We found that Ser 177 phosphorylation and the ribozymal ac-tivity are essential for HDV replication and HDAg expression. Mutation of the isoprenylation domain prevent the formation of infectious particles and increase cellular toxicity and liver dam-age. Finally, altering the intracellular localization od HDAg have a profound on viral replication in vivo but liver toxicity is maintained. Mutation in the nuclear export signal impair the for-mation of infectious viral particles. These findings contribute valuable insights into the intricate mechanisms of HDV biology and have implications for therapeutic considerations

Microfluidic systems offer precise control over physiological, biochemical, and mechanical stimuli in cell culture, allowing in vitro emulation of tissue or tumor microenvironments. This study aims to advance our understanding of tumor biology and contribute to personalized therapy development. Overcoming challenges in cell culture, including cell density and microfluidic device properties, is essential for this purpose. We designed a microfluidic system to facilitate the interaction of diverse cell lineages, incorporating human brain microvascular endothelial cells (HBEC5i), glioblastoma multiforme cells (U87MG), and astrocytes (ScienceCells 1800). Post-fabrication, we assessed the system's functionality and systematically evaluated cell inoculation conditions. Photographic acquisitions comprehensively captured cell culture and their interactions. The device successfully enabled assessment of cellular proliferation, invasion, and migration, supporting the growth of monolayers and tumor organoids. Importantly, each channel demonstrated independence in study processes while allowing cellular intercommunication, both physically and biochemically. In conclusion, the functional microfluidic device facilitated the study of cell migration, tumor invasion, and organoid growth, faithfully replicating biological features observed in a tumor microenvironment. This research contributes to advancing our understanding of tumor biology for the development of personalized therapies.

In the following article, it is presented an investigation of the determinants of Beds for High-Care Specialties-BHCS in the Italian regions in the context of Environmental, Social and Governance-ESG approach. Data from ISTAT-BES for 20 countries in the period 2004-2021 are been used. Different econometric techniques have been applied i.e.: Pooled Ordinary Least Squares, Panel Data with Fixed Effects, Panel Data with Random Effects, Dynamic Panel at 1 stage. Furthermore, a cluster analysis performed with a k-Means algorithm optimized with the Silhouette Coefficient indicated the presence of three clusters. Finally, eight different machine-learning algorithms are analysed to predict the future value of BHCS. The results show that the Artificial Neural Network-ANN algorithm is the best algorithm. The future value of BHSC is expected to growth on average of 4.88% for the analysed regions.

Although lymphoma is the most frequent malignancy in common variable immunodeficiency (CVID), solid tumors, especially under influence of oncogenic viruses, are not considered. Furthermore, in vitro genetic studies and cell cultures are not adequate for immune system and HBV interaction. We adopted previously introduced clinical model of host-virus interaction (i.e. infectious process in immunodeficiency) for analysis of B cells and specific IgG role (observational study of a CVID patient who received intravenous immunoglobulin (IVIG)) Suddenly, the patient deteriorated with positive result of HBs, HBV-DNA (369x106copies). In spite of lamivudine therapy and IVIG escalation (from 0.3 to 0.4g/kg), CT showed 11cm intrahepatic tumor (hepatocellular carcinoma). Anti-HBs had been positive in time-lapse analysis (range 111-220 IU/ml). Replacement therapy intensification was complicated by immune complex disease with renal failure. The fulminant HCC in CVID and the development of the tumor as the first sign is interesting. Unfortunately, treatment with hepatitis B immune globulins (HBIG) plays a major role in posttransplant maintenance therapy. Anti-HBs substitution has not been proven to be effective, oncoprotective nor safe. Therefore, immunosuppression in HBV-infected recipients should be carefully minimized, patient selection more precise with the exclusion of HBV-positive donors. Our clinical model show HCC pathway with important humoral host factors, contrary to epidemiological/cohort studies highlighting risk factors only (e.g. chronic hepatitis). Lack of cell cooperation, B cell deficiency observed in CVID plays a crucial role in high HBV replication, especially in carcinogenesis.

We investigated the prevalence and genetic diversity of Wolbachia pipientis strains in Aedes albopictus populations in Greece. Using a combination of PCR and Sanger sequencing techniques, we genotyped Wolbachia strains in 105 mosquitoes collected across eight different prefectures in 2021. We found a high prevalence of Wolbachia in both male (90%) and female (97%) mosquitoes. Among the infected samples, 84% had double infections with both wAlbA and wAlbB strains, while 16% had infections with only wAlbB. Our comparison of the Multi-Locus Sequence Typing (MLST) profile, employing gatB-coxA-hcpA-ftsZ-fbpA genotyping, revealed a single MLST profile for each wAlbA and wAlbB strain in Greek populations. The same MLST profiles were also reported in populations from China, Russia, and Argentina, suggesting low levels of global diversity in wAlbA and wAlbB strains. Furthermore, our results indicated a significant association between temperature and the prevalence of single infections (P = 6.498E-07), with higher temperatures correlating with an increased likelihood of single infections. Although male-bias showed a tendency towards single infections, the effect was marginally non-significant (P = 0.053). These results were confirmed using a bootstrap-with-replacement analysis approach. Overall, our findings offer novel insights into the distribution and species diversity of Wolbachia strains in Greek Ae. albopictus populations, emphasizing the importance of understanding the short-term plastic and adaptive responses of these organisms to environmental stressors and rapid climate change.

This study aimed to overcome the difficulty of conducting the horizontal-well cavity leaching test in the field and to investigate the long-term stability of the horizontal-well salt-cavity natural gas storage. The simulation test design is combined with the similarity theory to study the cavity expansion characteristics and the influence law of cavity leaching parameters. Through the design of a rubber hose connection, an integrated closed test system for multi-stage horizontal-well cavity leaching and brine drainage was built. The test system also realises the repeatable backward movement of the injection well during the test. A similarity simulation of the test design was carried out, and the test platform was constructed to carry out multi-stage horizontal-well leaching tests with a nitrogen cushion. In the horizontal-well leaching tests with a nitrogen cushion, the influence laws of the well spacing, flow rate and liquid level position on cavity expansion were investigated. Based on the morphological characteristics of the horizontal-well cavity, a numerical model of the horizontal-well salt cavity was developed, which reflects the real cavity morphology leached in the test. The long-term stability of the horizontal-well salt-cavity natural gas storage under different internal pressures was investigated through numerical simulation.

Chest trauma is one of the most serious and difficult injuries, with various complications that can lead to ventilation - perfusion (V/Q) mismatch and systemic hypoxia. We are presenting a case of 53 – year - old male with no comorbidities or chronic therapy, who was admitted to the Intensive Care Unit due to severe respiratory failure after chest trauma. He developed right - sided pneumothorax and then thoracic drain was placed. On admission, the patient was hemodynamically unstable and tachypneic. The patient was intubated and mechanically ventilated, febrile (38.9°C) and unconscious. A lung CT showed massive non-ventilated areas predominantly in the right lung. He was ventilated with PEEP of 10 cmH2O with a FiO2 of 0.6 – 0.8. Empirical broad-spectrum antimicrobial therapy was immediately initiated. Both high FiO2 and moderate PEEP were maintained and adjusted according to the current blood gas values and oxygen saturation. After Stenotrophomonas maltophilia was identified and treated with sulfamethoxazole/trimethoprim his general condition gradually improved, and he was weaned from mechanical ventilation. In conclusion, both ventilatory and antibiotic therapy were needed to improve oxygenation and outcome of the patient with pneumonia due to the resistant S. maltophilia with V/Q mismatch.

In the present work, a study has been carried out on the contamination of heavy metals in urban dust deposited on the roads of the city of Cartagena (Spain), in order to know the content of metals such as Ni, Zn, Pb, Cd, Cr and Cu. Likewise, the possible relationship of the concentration of heavy metals with the color of the sample, level of magnetism and traffic density was studied. Contamination was evaluated using several indices such as contamination factor (CF), enrichment factor (EF), geoacumulation index (Igeo), pollutant load index (PLI) and ecological risk index (RI). A total of 88 samples were taken in the urban area of Cartagena, and the metals were determined by acid digestion and measured by inductively coupled plasma mass spectrometry. The concentration of heavy metals in urban dust from Cartagena was Zn (672 mg/kg) &gt; Cu (248.9 mg/kg) &gt; Pb (227 mg/kg) &gt; Cr (82.7 mg/kg) &gt; Ni (47.7 mg/kg) &gt; Cd (4.1 mg/kg). Contamination levels were high in Pb, Zn, Cd and Cu, according to environmental indices. A correlation was found between magnetism and metal concentration, which was repeated for all metals except Cd. Dark-colored samples contained higher metal concentrations than light-colored samples. Meanwhile, streets with medium and low traffic intensity were found to have higher concentrations of heavy metals. This study's objective was to identify pollution hotspots caused by heavy metals in dust in the urban ecosystem of Cartagena city.

(1) Background: There is a need to assess the availability of essential antimicrobials as the availability of an antimicrobial is a critical element of its rational use. We aimed to assess the availability of antimicrobials listed in National List of Essential Medicines 2015, India (primary list) and a selected (secondary) list comprising of agents indicated for commonly encountered infectious illnesses in various healthcare settings and to identify the reasons for their non-availability. (2) Methods: A cross-sectional survey of 25 public, private, and other sector pharmacies was carried out in Rohtak, a district of North Indian state of Haryana, from April to June 2022. (3) Results: Most of the antimicrobials surveyed were optimally available in various sector pharmacies with the exception of benzathine benzyl penicillin, benzyl penicillin, cloxacillin, cefazolin, cefuroxime, cefadroxil, amphotericin B and antimalarials. Most frequent reasons for limited availability were low demand, no prescriptions and non-listing of drugs in state essential medicine list. (4) Conclusions: Enough evidence needs to be generated with respect to status of availability of essential antimicrobials from different regions of India as well as other lower-middle income countries to devise measures for ascertaining better availability of these agents especially antibiotics at regional, national and global scales.

There is currently no set of instruments or procedures to evaluate the effectiveness of cross-sectoral collaboration in the current CFC program. This study aimed to develop a tool for evaluating the cross-sectoral contributions to the CFC program. A paper-based questionnaire was developed by the research team after a preliminary qualitative procedure, and it was subsequently employed to collect data. This process resulted in 17 indicators (41 items) of cross-sectoral collaboration in the development of the CFC in Makassar. These indicators were categorized into five dimensions: governance, administration, autonomy, mutuality, and norms. There were 32 items remaining after several items that were determined not to correspond with the model were eliminated prior to the CFA analysis. According to the CFA results, the five-domain model corresponded to the data with standardized loading factor (SLF)<0.5, indicating that the convergent validity of SLF was acceptable. In addition, these results suggested that the items employed in the tool were really significant in reflecting these five domains. The developed and validated tool was expected to be beneficial in evaluating cross-sectoral collaboration in the CFC program developed in Makassar City. The findings of this study would serve as a benchmark indicator, enabling the assessment process to gauge the significance with which a city is developing with cross-sectoral restriction measures.

The effect of the melt cooling rate on the atomic ordering of austenite and, as a consequence, on the martensitic transformation of a nonstoichiometric alloy of the Ni-Mn-In system has been studied. In-situ TEM observations revealed differences in the mechanism of phase transformations of the alloy subjected to different cooling conditions. It is shown that during quenching a high density of antiphase boundaries (APB) is formed and the alloy is in the austenite-martensitic (10M and 14M) state up to a temperature of 120K. In a slowly cooled alloy, a lower APB density is observed, and a two-stage transformation L21/B2 → 10M → 14M occurs in the range of 150–120 K.

The phototransduction cascade allows the photoreceptor to avoid saturation and retain the ability to detect light over a very wide range of intensities. The main second messenger of the cascade is cGMP and the main regulatory mechanism is calcium feedback, however some experimental data suggest that cAMP may also be involved in the regulation of the phototransduction cascade. For this to be the case, cAMP would have to change on a time scale of seconds. Currently, there are no data on the dynamics of changes in intracellular cAMP levels on this time scale, largely due to the specificity of the sensory modality of photoreceptors, where it is practically impossible to use conventional experimental approaches based on fluorescence methods. In the present work, we used the method of rapid cryofixation of retinal samples after light stimulation and subsequent isolation of outer segment preparations. Levels of cAMP were measured using highly sensitive metabolomics approaches. PKA activity was also measured in these samples by Western blot. We show that when illuminated with near-saturating but still moderate light, cAMP levels rise transiently within approximately the first second and then return to pre-stimulus levels. The increase in cAMP activates PKA, leading to phosphorylation of PKA-specific substrates in frog retinal outer segments.

Nowadays, healthcare-associated infections (HAIs) represent a major global public health problem and the burden of these infections is high. In order to reduce the incidence of HAIs and to prevent the spread antibi-otics resistant organisms is mandatory to develop surveillance systems. We undertook a retrospective case-control study of all patients presenting HAIs admitted in Intensive Care Unit (ICU) in order to assess risk factors associated with death among patients with HAIs. Patients admitted to Intensive Care Unit who died were more likely to present an infection with a multidrug resistant bacteria, an infection with Acineto-bacter baumannii, and to suffer from acute myocardial infarction. Among the patients enrolled in the study, a higher probability of death was also observed in association with certain gram-negative pathogens: Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. The longer the patient remains admitted in ICU, the higher the risk of getting an infection that can often become fatal. Acquiring a noso-comial infection also increases the length of hospitalization which will lead to increased financial damage.

We assume that the current mathematical knowledge K is a finite set of statements from both formal and constructive mathematics, which is time-dependent and publicly available. Any theorem of any mathematician from past or present belongs to K. The set K exists only theoretically. Ignoring K and its subsets, sets exist formally in ZFC theory although their properties can be time-dependent (when they depend on K) or informal. In every branch of mathematics, the set of all knowable truths is the set of all theorems. This set exists independently of K. Algorithms always terminate. We explain the distinction between algorithms whose existence is provable in ZFC and constructively defined algorithms which are currently known. By using this distinction, we obtain non-trivial statements on decidable sets X⊆N that belong to constructive and informal mathematics and refer to the current mathematical knowledge on X. This and the next sentence justify the article title. For any empirical science, we can identify the current knowledge with that science because truths from the empirical sciences are not necessary truths but working models of truth about particular real phenomena.

Objective: To observe the effect of the combination of fluid-increasing decoction, low molecular heparin sodium and aspirin in the treatment of oligohydramnios in pregnancy. Methods: In this study, 114 pregnant women with oligohydramnios during pregnancy admitted to our hospital between May 2019 and March 2022 were selected as objects, and the pregnant women were equally divided into the observation group and the experimental group by random number table method, with 57 cases in each group. The observation group received conventional fluid infusion, low molecular heparin sodium and aspirin, while the experimental group was treated with fluid-increasing decoction on the basis of the observation group. The treatment effect, S/D level, amniotic fluid index, maximum vertical pocket (MVP), coagulation indexes (plasma prothrombin time (PT), plasma activated partial thromboplastin time (APTT), fibrinogen (FIB)), pregnancy outcome and adverse reactions were compared between the two groups. Results: The total effective rate of treatment was obviously better in the experimental group than that in the observation group (P＜0.05); the S/D level after treatment in the experimental group was remarkably lower than that in the observation group (P＜0.05). The amniotic fluid index and MVP were remarkably higher in the experimental group than in the observation group after treatment (P < 0.05). No significant differences in PT, APTT and FIB were found between the two groups before and after treatment (P > 0.05). The rate of oligohydramnios at delivery, cesarean section rate, neonatal weight status and preterm delivery rate were dramatically better in the experimental group than in the observation group (P < 0.05). Post-partum haemorrhage rate, neonatal asphyxia rate, amniotic fluid contamination rate and incidence of adverse events were not significantly different between the two groups of pregnant women (P > 0.05). Conclusion: The combination of fluid-increasing decoction, low molecular heparin sodium and aspirin is clinically effective and safe in the treatment of pregnant women with oligohydramnios during pregnancy. The combination is effective in reducing the S/D ratio of fetal umbilical blood flow, enhancing the amniotic fluid index and MVP in pregnant women with oligohydramnios during pregnancy, whilst not adversely influencing the coagulation function of the mother, thus contributing to a reduction in the risk of adverse pregnancy outcomes.

Cardiovascular diseases (CVDs) and type 2 diabetes mellitus (T2DM) are two of the four major chronic non-communicable diseases (NCDs), representing the leading cause of death worldwide. Several studies demonstrate that endothelial dysfunction (ED) plays a central role in the pathogenesis of these chronic diseases. Although it is well known that systemic chronic inflammation and oxidative stress are primarily involved in the development of ED, recent studies have shown that perivascular adipose tissue (PVAT) is implicated in its pathogenesis, also contributing to the progression of atherosclerosis and to insulin resistance (IR). In this review we describe the relationship between PVAT and ED, and we also analyse the role of PVAT in the pathogenesis of CVDs and T2DM, further assessing its potential therapeutic target with the aim of restoring normal ED and reducing global cardiovascular risk.

Due to similarities in genetics, cellular response, and behavior, Drosophila is used as a model organism in addiction research. A well described behavioral response examined in flies is the induced increase in locomotor activity after a single dose of volatilized cocaine (vCOC) and volatilized methamphetamine (vMETH) known as sensitivity, and the escalation of the locomotor response after the repeated dose, known as the locomotor sensitization. However, knowledge about how vCOC and vMETH affect different neurotransmitter systems over time is scarce. We used LC-MS/MS to systematically examine changes in the concentration of neurotransmitters, metabolites and non-metabolized COC and METH in the whole head homogenates of male flies one to seven hours after single and double vCOC or vMETH administrations. vMETH leads to complex changes in the levels of examined substances over time, while vCOC strongly and briefly increases concentrations of dopamine, tyramine and octopamine followed by a delayed degradation into N-acetyl dopamine and N-acetyl tyramine. The first exposure to psychostimulants leads to significant and dynamic changes in the concentrations relative to the second administration when they are more stable over several hours. Further investigations are needed to understand neurochemical and molecular changes post-psychostimulant administration.

This research explored the influence of spatiotemporal variations in phreatic levels and salinity on the patterns and interactions of soil mesofauna communities in a tropical urban coastal wetland. It delineated significant variations in phreatic levels and salinity, with distinct regimes characterizing different habitats and hydroperiods. A total of 120 mesofauna morphotypes across 42 taxa were identified, revealing habitat differences and similarities, and the ecosystem biodiversity. Moderate correlations were established between phreatic levels, salinity, and mesofauna richness and abundance, with habitat type and phreatic level emerging as significant predictors in the regression model. Our findings indicate that shallow phreatic levels in conjunction with oligohaline salinity conditions foster a more favorable abiotic environment, thereby promoting increased biodiversity. The study underscores the dynamic and adaptive nature of mesofauna communities in response to changing environmental conditions, offering valuable insights for effective costal urban wetland management, particularly in the context of multiple stressors such as global and regional climate change, sea level rise, and human activities. The bio-sensor capacity of soil mesofauna emerges as a vital tool for monitoring and facilitating adaptive ecosystem management, thereby ensuring their long-term health and sustainability.

Purpose: School-age children with autism spectrum conditions (ASC) often experience difficulties in speech-in-noise (SiN) perception, leading to increased listening effort that impacts their well-being and academic performance. This study aimed to investigate the SiN processing challenges faced by Mandarin-speaking children with ASC and its impact on their listening effort. Methods: Participants completed sentence recognition tests in both quiet and noisy conditions, with a steady-state noise masker presented at 0 dB signal-to-noise ratio in the noisy condition. We compared recognition accuracy and task-evoked pupil responses from 23 Mandarin-speaking children with ASC to 19 age-matched neurotypical (NT) counterparts to gauge their behavioral performance and listening effort during these auditory tasks. Results: The ASC group demonstrated notably decreased accuracy in noise compared to their NT peers, suggesting poorer SiN perception. Pupillometric data further revealed significantly larger peak dilations in the ASC group than in the NT group under comparable conditions. Importantly, the ASC group's peak dilation in quiet mirrored the NT group's in noise. However, the ASC group exhibited shorter peak latencies and reduced mean dilations than the NT group in similar conditions. Such patterns indicate the ASC group might initially experience a heightened cognitive load but utilize fewer cognitive resources as the task continued, indicating an atypical allocation of cognitive resources and a potential tendency towards relatively superficial and automated auditory processing. Conclusion: Our findings highlight the unique SiN processing challenges children with ASC face, underscoring the importance of a nuanced, individual-centric approach for interventions and support.

The SARS-CoV-2 infection is a cause of hypoxemic acute respiratory failure, leading to frequent intensive care unit (ICU) admission. Due to invasive organ support and immunosuppressive therapies, these patients are prone to nosocomial infections. Our aim was to assess the value of daily measurements of C-reactive protein (CRP) and Procalcitonin (PCT) in the early identification of ICU-acquired infections in COVID-19 patients Methods: We undertook a prospective observational cohort study (12 months). All adult me-chanically-ventilated patients admitted for ≥ 72 hours to the ICU with COVID-19 pneumonia were divided into an infected group (n=35) and a non-infected group (n=83). Day 0 was considered as the day of the diagnosis of infection (infected group) and day 10 of ICU stay (non-infected group). The kinetics of CRP and PCT were assessed from day -10 to day 10 and evaluated using a general linear model, univariate, repeated-measures analysis. Results: 118 patients (mean age 63 years, 74% males) were eligible for the analysis. The groups did not differ in patients' age, gender, CRP, and PCT serum levels at ICU admission. However, the infected group encompassed patients with a higher severity (SOFA score at ICU admission, p=0.009) and a higher 28-day mortality (p<0.001). Before D0, CRP kinetics showed a significant increase in infected patients, whereas in noninfected it remained almost unchanged (p<0.001), while PCT kinetics did not appear to retain diagnostic value to predict superinfection in COVID-19 patients (p=0.593). Conclusion: COVID-19 patients who develop ICU-acquired infections exhibited different biomarker kinetics before the diagnosis of those infections. Daily CRP monitoring and the recognition of the CRP kinetics could be useful in the prediction of ICU-acquired infections.

Logistics industry has been found to be among the key sources of carbon emission. In Vietnam logistics industry, there is a considerable difference between the number of foreign and Vietnamese firms as well as the proportion of markets that they are taking. This study is to research the low-carbon emission measures conducted by domestic and foreign invested logistics service providers (LSPs) and compare the results of the two groups. Both qualitative and quantitative approaches are applied. Literatures in relevant fields are reviewed and expert opinions are taken for structuring a questionnaire which was later distributed to 279 LSPs, with 166 returned and 159 being valid for data calculation. The results imply that there are differences in extension of applications of low-carbon practices between foreign and domestic firms. Except for transport mode switch and energy-saving lighting, the other practices witness that adoption levels of foreign LSPs are higher than their counterparts, which is possibly thanks to their global operation, more comfortable capital resources and awareness level of green initiative necessity. In conclusion, a comparison between the application conducted by foreign-invested firms and domestic ones, which has not been investigated before, was made.

Rapid proliferation of traditional gold mining sites in Kédougou a Southeast region in Senegal, led to mass population migration from the neighboring West African countries and rapid expansion of small mining villages with poor hygiene and sanitation conditions. An outbreak of hepatitis E was reported in 2014 with several cases of febrile jaundice among traditional mine workers. In this study, we analyzed both HEV IgM and IgG seroprevalence and the associated risk factors of infection by testing any suspected case and contacts collected from February 2012 to November 2014. RNA-negative sera from suspected cases and contacts were tested for anti-HEV IgM and anti-HEV IgG. A total of 799 sera were collected from 290 suspected cases, 470 contacts and 39 individuals with missing information. The median age of the cohort study was 19 years (1-88 years) with a male/female sex-ratio of 1.9. We found an overall prevalence of 43.68% (332/760) of anti-HEV IgM and 38.15% (290/760) of anti-HEV IgG sera. Our data provide new insights into the HEV epidemiology and point to the crucial need to estimate the disease’s burden in Kédougou and assess the viral mechanisms driving the disease’s severity in pregnant women.

(1) Background: Colon cancer is one of the leading causes of cancer morbidity and mortality globally. It is a multi-step process that involves genetic and epigenetic modifications leading to histological and morphological changes. Several complementary therapeutic options have been analyzed, shedding light on plant-based medication as a potential treatment for colon cancer. Flavonoids such as quercetin are known to have anti-cancer and anti-inflammatory properties. This in vitro study examines quercetin's anti-inflammatory, anti-apoptotic, anti-angiogenesis effects and antioxidant properties in colon cancer cells. (2) Methods: The antioxidant capacity of quercetin-treated cells was investigated using biochemical assays, and angiogenesis and cytokine levels were assessed using enzyme-linked immunosorbent assay (ELISA). The epigenetic modulation and differential expression of aging, apoptotic, and proliferation genes, and Histone deacetylases (HDACs) were also investigated. (3) Results: In this study, the quercetin-treated group significantly reduced the antioxidant enzymes, cytokines, and VEGF levels, altering the expression of epigenetic factors. Quercetin also induced significant senescence in colon cancer cells. Moreover, a considerable increase was observed in the apoptotic and hTERT genes. In contrast, a decrease in p53, proliferation genes, and HDACs was observed, providing a basis for the clinical use of quercetin in cancer treatment. (4) Conclusion: In vitro studies showed that quercetin treatment efficiently induces senescence and apoptosis in colon cancer cells. We also found that quercetin effectively modulated the expression of p53, Wnt1, CTNNB1, and HDACs, indicating that it could be used to treat colon cancer.

Objective: To evaluate the effect of care bundles on treatment compliance and intestinal barrier function in patients with refractory septic shock in the intensive care units (ICUs). Methods: In this retrospective study, the clinical data of 94 patients with refractory septic shock admitted to our hospital between June 2020 and April 2022 were collected. Patients with routine nursing were included in the routine group, and those with care bundles were assigned to the care bundles group, with 47 cases in each group. Outcome measures included nursing efficiency, treatment compliance, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, intestinal barrier function, inflammation factor level, treatment outcome and complications. Results: Care bundles resulted in significantly higher nursing efficiency and treatment compliance versus routine care (P<0.05). Patients receiving care bundles showed significantly higher SOFA scores and APACHE II scores than those receiving routine care (P<0.05). Intestinal fatty-acid binding protein (I-FABP), diamine oxidase (DAO), lactate, endotoxin, and intestinal dysfunction scores in the care bundles group were significantly lower than those in the conventional group after treatment (P<0.05). Care bundles were associated with significantly lower levels of procalcitonin (PCT) and hypersensitive C-reactive protein (hsCRP), shorter time to symptom relief, ICU treatment time, and duration of mechanical ventilation, and lower 28-d morbidity and mortality versus routine care (P<0.05). Patients in the care bundles group had a significantly lower incidence of complications than those in the routine group (P<0.05). Conclusion: Care bundles effectively enhance treatment compliance, improve intestinal barrier function and treatment outcomes, reduce the inflammatory response, and decrease the risk of SOFA score, APACHE II score, and complications in patients with refractory septic shock.

In this study, four experimental treatments were evaluated: (T1) alfalfa hay + concentrate, (50:50%, DM); (T2) alfalfa hay + Leucaena leucocephala + concentrate, (30:20:50%, DM); (T3) alfalfa hay + prickly pear + concentrate, (30:20:50%, DM); and (T4) alfalfa hay + Leucaena leucocephala + prickly pear + concentrate, (30:10:10:50%, DM). NH3-N concentrations in T2 and T4 decreased when replaced alfalfa hay in 20 and 10 %, respectively. Treatments did not affect the concentration of total volatile fatty acids (TVFA) between T3 and T4 (p>0.05); while the concentrations among T1 and T2 were different (P<0.05). T2 showed a reduction of 25.5 % in the methane production when compared to T1(p < 0.05).The lowest concentrations of protozoa were observed in T2 and T4, which contained Leucaena leucocephala (T2) and Leucaena leucocephala + prickly pear (T4) (p<0.05). The highest concentration of total methanogens was recorded in T1 and were different to T2, T3 and T4 (p<0.05). Leucaena leucocephala at a inclusion percentage of 20 % decreased the methane when compared to T1; whereas prickly pear there was not a positive effect the methane production.

Objective: To evaluate the effect of care bundles on treatment compliance and intestinal barrier function in patients with refractory septic shock in the intensive care units (ICUs). Methods: In this retrospective study, the clinical data of 94 patients with refractory septic shock admitted to our hospital between June 2020 and April 2022 were collected. Patients with routine nursing were included in the routine group, and those with care bundles were assigned to the care bundles group, with 47 cases in each group. Outcome measures included nursing efficiency, treatment compliance, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, intestinal barrier function, inflammation factor level, treatment outcome and complications. Results: Care bundles resulted in significantly higher nursing efficiency and treatment compliance versus routine care (P<0.05). Patients receiving care bundles showed significantly higher SOFA scores and APACHE II scores than those receiving routine care (P<0.05). Intestinal fatty-acid binding protein (I-FABP), diamine oxidase (DAO), lactate, endotoxin, and intestinal dysfunction scores in the care bundles group were significantly lower than those in the conventional group after treatment (P<0.05). Care bundles were associated with significantly lower levels of procalcitonin (PCT) and hypersensitive C-reactive protein (hsCRP), shorter time to symptom relief, ICU treatment time, and duration of mechanical ventilation, and lower 28-d morbidity and mortality versus routine care (P<0.05). Patients in the care bundles group had a significantly lower incidence of complications than those in the routine group (P<0.05). Conclusion: Care bundles effectively enhance treatment compliance, improve intestinal barrier function and treatment outcomes, reduce the inflammatory response, and decrease the risk of SOFA score, APACHE II score, and complications in patients with refractory septic shock.

In recent times, the process control network (PCN) of oil and gas installation has been subjected to amorphous cyber-attacks which include Denial-of-Service (DoS), Distributed-Denial-of-Service (DDoS), Man-in-the-Middle (MitM) attacks, and this may have been caused majorly by the integration of open network to Operation Technology (OT) as a result of low-cost network expansion. The connection of the OT to the internet for firmware updates, third-party support, or vendor interventions, has exposed the industry to attacks. The inability to detect these unpredictable cyber-attacks exposes the PCN and a successful attack can lead to devastating effects. This paper reviews the different forms of cyber-attacks in PCN of oil and gas installations and proposes the use of machine learning algorithms to monitor data exchanges between the sensors, controllers, processes, and the final control elements on the network so as to detect anomalies in such data exchanges. Python 3.0 Libraries, Deep-Learning Toolkit, MATLAB, and Allen Bradley RSLogic 5000 PLC Emulator software were used in the simulation of process control. The outcome of the experiments shows the reliability and functionality of the different machine-learning algorithms in detecting these anomalies with significant precise attack detections identified using a coarse tree algorithm.

Nurses and paramedics play a pivotal role when Mass Casualty Incidents (MCI) occur, yet they often feel unprepared for such events. Implementation strategies for training activities, including Virtual Reality (VR) and Augmented Reality (AR) simulations, offer realistic and immersive learning experiences, enhancing skills and competencies for nursing students. The aim of this work was to investigate the adopted tools in studies on VR&amp;AR simulations for training nursing and paramedic students in managing MCI. A scoping review was performed following the PRISMA-ScR statement, and the search strategy was conducted through five electronic databases from December 2022 to March 2023. Of 162 records identified, 27 full-text were screened and, six studies were included in this review. These studies involved students who were assigned to different training methods, including immersive VR simulation, written instruction, and traditional lecture. VR&amp;AR and immersive simulation generally show promising evidences in enhancing practical skills and knowledge in MCI management. VR&amp;AR showed to be promising in disaster education and preparedness training, offering different levels of immersiveness and engagement, encouraging active and experential learning. Further research is needed to determine their long-term effectiveness. The choice of training method should consider program goals, target population, and available resources.

Family Integrated Care (FICare) is associated with improved developmental outcomes and decreased parental mental health risks in stable preterm infants. However, less is known about its application in critically ill infants who are at greater risk for adverse outcomes. The objective of this study was to assess the safety and feasibility of implementation of FICare in critically ill infants in the first few weeks of life. In this prospective cohort study, 41 critically ill infants were enrolled: 17 in observational group receiving standard care (SC)and 24 in the FICare Plus group. Resources were developed for staff and parents to support earlier engagement in infant care. Outcomes were assessed using standardized questionnaires. The t-test or Wilcoxon Rank-Sum test were used to compare continuous variables, while Chi-square or Fisher exact test were used for categorical variables, respectively. Baseline maternal and infant characteristics were similar in both groups. The tools and procedures developed for FICare Plus successfully supported greater engagement in the care of their infant with no increase in adverse events and no increase in parent stress. Preliminary measures of infant efficacy were similar in both groups. Total anxiety scores were high among all parents at enrolment {83.1 (67-94) vs 77.3 (66-86); p-value 0.4}. However, the scores prior to discharge were lower in FICare Plus group {78 (71-90) vs 63 (52-74.5); p-value 0.02}. This pilot study showed that it is feasible and safe to implement family integrated care in critically ill infants.

CGT is composed of fiber residues, leaves, dust particles, soil and others derived during the ginning and yarn spinning process at processing industries,. In the cotton spinning industrial clusters, farmers are using CGT) as one of the alternative roughage feed for their sheep, mainly during forage shortages in the summer months. To have baseline information on farmers using gin and factors driving them to choose CGT as a roughage source, which need to be identified for future planning on the usage of CGT in sheep feeding. Considering the above facts, the present study was undertaken to assess socio-personal characteristics, managemental practices associated with farmers using cotton gin in the feeding of sheep and also identify the factors driving the choice of the CGT as the primary source of roughage in the cotton spinning industry cluster of Tamil Nadu. For this, a survey among 80 sheep farmers was carried out using a pre-tested in-terview schedule. The collected data was analysed using descriptive statistics and logit regres-sion. The results indicated that the majority of male, aged, and large-land farmers were involved in practicing CGT feeding during the summer and also indicated the non-availability of green fodder during the summer season. The coarse type of CGT preferred more than the fine type of CGT trash in that area due to quality perception and price. The replacement level of CGT as roughage ranged from 33 to 75% of the total roughage requirement per day. About 88 percent-age of farmers were highly satisfied with the results of using CGT and they also expressed that the presence of foreign particles and dust were the major problems with using CGT. The choice of CGT as primary roughage among sheep farmers was primarily influenced by selective farming contexts, namely landholding, access to labour, and feeding practices of other livestock with cotton gin. Further, research has to be focused on to improve the quality of CGT in the future, as it is being utilised largely by sheep farmers.

The hypothesis that health status is the highest-ranking concept, followed by respiratory symptoms and dyspnea as the lowest-ranking concepts in subjects with chronic obstructive pulmonary disease (COPD) was tested in a real clinical setting with 157 subjects with stable COPD. Spearman's rank correlation coefficients for scores of health status using the COPD assessment test (CAT), respiratory symptoms using the COPD Evaluating Respiratory Symptoms (E-RS) and dyspnea using the Dyspnoea-12 (D-12) between any two were 0.6 to 0.7. Upon categorizing the patients as "abnormal" or "normal" according to the threshold, it was found that 30 patients (19.1%) had dyspnea, respiratory symptoms, and impaired the health status. Dyspnea was considered an important part of respiratory symptoms though seven patients had dyspnea but no respiratory symptoms. There were 10 patients who had respiratory symptoms without dyspnea but without health status problems. Furthermore, there were six patients who had both dyspnea and respiratory symptoms but whose health status was classified as fine. Thus, the hypothesis was correct in approximately 85% of cases.

Chicken infectious anemia (CIA) poses a significant threat to the chicken industry in China. De-spite its non-specific symptoms, the disease is often overlooked. This study aimed to conduct a comprehensive analysis of the etiology and pathology of CIA in Guangxi Province, China. Three strains of the chicken infectious anemia virus (CIAV) were isolated from liver samples of diseased 20-week-old chickens. The complete genomes of these strains were sequenced, and experiments on specific pathogen-free (SPF) chicks revealed that the GX21121 strain exhibited high virulence. Histopathological examination of the deceased chicks showed liver cell necrosis, fibrous-serous exudation, inflammatory cell infiltration, hemorrhage in liver tissues, as well as congestion in lung and renal tissues. Phylogenetic analysis of the genome revealed that the three strains had a close genetic relationship to the Heilongjiang wild-type (GenBank KY486144). The genetic evolu-tion of their VP1 genes indicated that all three CIAV isolates belonged to genotype IIIc. In sum-mary, this study demonstrated the genomic diversity of three CIAV strains in adult layer hens. The isolation and characterization of the GX21121 strain as a highly virulent isolate provide val-uable information for further investigations into the etiology, molecular epidemiology, and viral evolution of CIAV.

Copper indium gallium diselenide, Cu(In,Ga)Se2, thin-film of about 1.2 μm has been deposited on Mo coated soda lime glass by thermal co-evaporation of Cu, In, Ga, and Se sources. The thin film CIGS was characterized by energy dispersive spectroscopy (EDS) and identified the elemental composition of Cu, In, Ga and Se in the film. A CIGS device was completed by the successive deposition of multiple layers; SLG/Mo/CIGS/CdS/ZnO/ITO which yielded the efficiency of 11%. External spectroscopic ellipsometry (ex-situ SE) was performed on the completed device and the device analysis was performed. Starting with the parameterized complex dielectric functions of the individual component layers, SE analysis was performed using a step-wise procedure that ranks the fitting parameters according to their ability to reduce the mean square error (MSE) of the fit. The resulting layer thicknesses and dielectric functions were used to simulate the external quantum efficiency (EQE) of the device assuming complete active layer collection. Electronic losses were identified by comparison of simulated EQE with the measured EQE. The ultimate goal of this work is the optimization of narrow band-gap CIGS-related solar cells for the bottom layer in tandem devices.

Background: Demographic aging is a reality in developed countries, which poses a social challenge of great responsibility. Thus, numerous studies have been developed in an attempt to understand which factors best predict healthy aging. The aim of this study was to investigate and systematize literature on intervention programs that simultaneously include cognitive stimulation and physical activity, understand the importance of the use of new technology in these programs, and understand their impact on cognitive function in older adults, giving indications about their contribution to healthy aging. Methods: A narrative approach was used for extraction and synthesis of the data. Relevant studies were identified from electronic databases such as PubMed, Scopus, Web of Science and Academic Search Complete. Results: Thirty-two articles, involving 2815 participants, were identified. All selected studies were randomized controlled studies. The studies were published between 2011 and 2020. All studies included a combination of cognitive and physical interventions. Many of the studies used technology to administer the cognitive stimulation program. Conclusions: Most of the analyzed studies use new technologies in physical and cognitive interventions, demonstrating that this new form of intervention exerts lasting and stable benefits in cognition.

Dubermatinib (DMB, TP-0903), a benzenesulfonamide, is an inhibitor of the tyrosine kinase AXL, which is a member of the TAM family, and can prevent GAS6-mediated activation of AXL in cancer cells. Patients with previously treated chronic lymphocytic leukemia are being studied in phase I/II clinical trials to determine its antineoplastic potential (CLL). In the current work, the reactive intermediates of DMB were studied using liquid chromatography-mass spectrometry (LC-MS). Human liver microsomes (HLMs) were exposed to dimethylbenzene in a laboratory setting, and the resulting metabolites were collected through protein precipitation. Intense reactivity toward nucleophilic macromolecules was seen in the metabolites of the piperazine and pyrimidine rings in DMB, iminium and 2,5-quinone-imine, respectively. To assess the toxicities of the possibly reactive metabolites, DMB was incubated with HLMs in the presence of 1.0 mM KCN and 1.0 mM glutathione. The DMB metabolites found by LC-MS/MS were seven in vitro phase I metabolites, three cyano adducts, and two GSH conjugates. Phase I in vitro metabolic reactions included N-demethylation, hydroxylation, and dechlorination. The in vitro metabolism of DMB and the metabolites it produces have not been studied before.

Epidemics of arboviruses in general, and dengue fever, in particular, are an increasing threat in areas where Aedes (Ae.) aegypti is present. The effectiveness of chemical control of Ae. aegypti is threatened by the increasing frequency of insecticide resistance. The aim of this study was to determine the susceptibility status of Ae. aegypti to public health insecticides and assess the underlying mechanisms driving insecticide resistance. Ae. aegypti eggs were collected in two study sites in the vicinity of houses for two weeks using Gravid Aedes Traps (GATs). After rearing mosquitoes to adulthood, female Ae. aegypti were exposed to the diagnostic doses of permethrin, deltamethrin and bendiocarb, using Centers for Disease Control and Prevention (CDC) bottle bioassays. Unexposed, un-engorged female Ae. aegypti were tested individually for mixed-function oxidase (MFO), glutathione-S-transferase (GST) and esterase activity. Finally, allele-specific PCR (AS-PCR) was used to detect kdr mutations (F1534C, S989P and V1016G) in the voltage-gated sodium channel gene in insecticide-exposed Ae. aegypti. Most traps were oviposition positive; 93.2% and 97% of traps contained Ae. aegypti eggs in the 10ème arrondissement of Cotonou and in Godomey-Togoudo, respectively. Insecticide bioassays assays detected resistance to permethrin and deltamethrin in both study sites and complete susceptibility to bendiocarb. By comparison to the insecticide-susceptibility Rockefeller strain, field Ae. aegypti populations had significantly higher levels of GSTs and significantly lower levels of  and  esterases; there was no significant difference between levels of MFOs. AS-PCR genotyping revealed the presence of the three kdr mutations (F1534C, S989P and V1016G) at high frequencies; 80.9% (228/282) of Ae. aegypti tested had at least one mutation, while the simultaneous presence of all three kdr mutations was identified in 13 resistant individuals. Study findings demonstrated phenotypic pyrethroid resistance, the overexpression of key detoxification enzymes and the presence of several kdr mutations in Ae. aegypti populations, emphasizing the urgent need to implement vector control strategies, targeting arbovirus vector species in Benin.

Aim: To investigate how much aerobic and resisted physical exercise affects the behavior of AST and ALT proteins in the NAFLD spectrum. Background: Non-alcoholic fatty liver disease (NAFLD) is a pathology resulting from the excessive accumulation of triglycerides in the liver. The pathophysiology of the disease comes from several mechanisms, among them, metabolic, environmental, and genetic. The measurement of liver enzymes, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) are essential to perform a differential diagnosis of NAFLD with other pathologies that affect the liver. The non-pharmacological treatment of NAFLD is based on aerobic and resisted physical exercise, and one of its aims is to reduce the inflammatory markers AST and ALT. Materials and Methods: Systematic review carried out in PubMed, Scopus, Embase, and Cochrane databases. Clinical trials that evaluated the effect of physical exercise on NAFLD on AST and ALT enzymes were included. Results: A total of 24 clinical trials met the inclusion criteria, with a sample size of 1141 participants, aged 20-82 years. The study protocol varied between aerobic exercise and resistance exercise with a weekly frequency between 2-6 times a week, a duration of 20-90 minutes for aerobics, and an intensity between 50-80% of peak VO2 and/or maximum HR for the resisted. Of the 24 studies included, only five showed improvements in both enzymes in the intervention group. Conclusion: Physical exercise cannot make significant changes in the behavior of AST and ALT liver parameters.

Multicellular organisms organize themselves according to two principles; first, the equilibrium between the driving force of unstable state cells and apoptosis or senescence; and second, the mutual equilibrium between the functional requirements of different types of cells. For the first principle, we deduce that stem cells at different levels have their own growth limits, which are determined by two factors: the ability of the stem cells to enter an unstable state (specifically, the ability of cells to divide and differentiate); and the rate of cellular senescence, loss of function, and finally, apoptosis. The superposition of stem cell limits at different levels over each other can amplify small differences at the genetic level. Moreover, the growth limits of different organs are different, which lead to different individuals having completely different appearances. The second principle is that the sum of the specific output functions of an organ must be equal to the overall demand for the function to be provided by the organ. If negative entropy input can meet this equilibrium, defects in certain genes will cause these defective individuals to become larger or develop other morphology.

The blood-brain barrier (BBB) is a selectively permeable boundary that separates the circulating blood from the extracellular fluid of the brain and is an essential component for brain homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes, being important to maintain the BBB integrity, can be functionally modified by GBM cells by inducing proliferation and cell motility via the TGF-β-mediated induction of central epithelial to mesenchymal transition (EMT) factors., We demonstrate that pericytes strengthen the integrity of the BBB in primary endothelial cell/pericyte co-cultures as in vitro BBB model, using TEER measurement of the barrier integrity. In contrast, this effect was abrogated by TGF-β or conditioned medium from TGF-β secreting GBM cells, finally leading to the disruption of a so far intact and tight BBB. TGF-β dramatically changed the metabolic behavior of pericytes, such as shutting down the TCA cycle, driving energy generation from oxidative phosphorylation towards glycolysis, and by shifting the cells towards the activation of pathways that are necessary to produce molecules used for proliferation and cell division. Furthermore, combined metabolomics and RNASeq analyses indicated that the observed functional changes of TGF-β-treated pericytes are closely connected with their behavior.

Forest plantations can substantially contribute to carbon sequestration and greenhouse gases (GHG) mitigation at the country and global scale. Forest fires (specially when combined with droughts) may significantly reduce such carbon sequestration capability. IPCC has global scale estimates for such losses, but they can vary widely depending on crops, climate, topography and management, among others. IPCC defines a factor for biomass loss as a consequence of forest fires, expressed as a fraction of total biomass. This methodology implies using aggregated data and the default emission factor, being only recommended for countries where wildfires are not a key category. In Chile, and over the last decade, there are between 5,000 to 8,000 wildfires annually (average 6,398 for the period 2011-2020), burning an average of 122,328 hectares each year. Countries may progress in the refinement of such factors depending on the availability and reliability of local values. This paper aims at estimating C_f values for the main forest plantation species in Chile: Pinus radiata, Eucalyptus nitens, and Eucalyptus globulus, across different age-classes and forest fire severities. To this aim we assessed the biomass loss after forest fires for a stratified sample of forest plots for the season 2018-2019. We fitted a model to predict the amount of biomass loss during fires, and in this way, predict the emissions associated to wildfires. The model employs very simple predictive variables, age and species, because statistics for burnt areas in plantations are only provided by age-classes and species, without details about productivity or management.

Background: The Ibizan Hound is a canine breed native to the Mediterranean region, where leishmaniasis is an endemic zoonosis. Several studies indicate a low prevalence of this disease in dogs, whereas other canine breeds present a high prevalence. However, the molecular underlaying mechanisms yet remains unknown. Methods: In this study, we analyze the haplotypes of genes encode cytokines related to immune response of Leishmania infantum infection in twenty-four Boxer and twenty-four Ibizan hound apparently healthy using CanineHD DNA Analysis BeadChip including 165,480 mapped positions. Results: The results show that several haplotypes of genes encoding Interleukin 6 (IL6) and Interferon gamma (IFNG) are related to Interferon gamma (IFN-γ), and Interleukins (IL) 2 and 18 serum levels. Our results indicate that the regulation of immune response is different in the two canine breeds analyzed and are related to the haplotype compositions of the genes encoding these cytokines. Conclusions: Future studies are needed to elucidate whether these differences and haplotypes are related to different phenotypes in immune response and expression gene regulation to L. infantum infection in dogs.

Malaria is one of the leading causes of illnesses and deaths in Africa at large and Nigeria in particular, especially amongst pregnant women and children under the age of five years. Our research revealed that though the government has deployed so many intervention systems to contend with this death-causing vector—the mosquitoes, malaria related deaths (MRDs) have continued to increase. This is because people have not sufficiently adopted those intervention systems to protect themselves. Further enquiries into the ineffective compliance of the people to the intervention systems revealed that the interventions are passive in nature. Based on these, we set up three measurable research outcomes to enable us to determine the appropriateness of persuasive technology in solving the malaria problem. We technically avoided a one-size-fits-all design approach and adopted Participatory System Design (PSD) and User-Centered Design (UCD) approaches in our system design methodologies. Well-structured questionnaires were used to extract information from the participants. The data obtained from the research survey was used in modeling the intervention system. The research was conducted in three phases: baseline, development and deployment of an intervention system—the Malaria Prevention and Control Support System (MPCSS), and an evaluation study to determine the performance of the intervention system. The research led to the following achievements: (1) encouraged an increase in the number of people who participated in malaria prevention and control activities by lowering the rate of malaria cases from 96.9% to 68.5% and increasing ownership of mosquito nets from 54% to 85.5%; (2) demonstrated that persuasive technology could be used to increase public awareness and knowledge of a given subject as noted in our evaluation result; and (3) demonstrated that persuasive technology is a veritable active intervention to combat malaria.

Hepatitis C virus (HCV) core protein is a multifunctional protein that is involved in proliferation, inflammation and apoptosis mechanism of hepatocytes. HCV core protein genetic variability has been implicated in various outcomes of HCV pathology and treatment. In the present study, we aimed to analyze the role of HCV core protein in tumor necrosis factor α (TNFα)-induced death under the viewpoint of HCV genetic variability. Immortalized hepatocytes (IHH), and not the Huh7.5 hepatoma cell line, stably expressing HCV subtype 4a and HCV subtype 4f core proteins showed that only HCV 4a core protein could increase sensitivity to TNFα-induced death. Development of two transgenic mice expressing the two different core proteins under the liver-specific promoter of transthyretin (TTR) allowed for the in vivo assessment of the role of core in TNFα-induced death. Using the TNFα-dependent model of lipopolysaccharide/D-galactosamine (LPS/Dgal) we were able to recapitulate the in vitro results in IHH cells in vivo. Transgenic mice expressing HCV 4a core protein were more susceptible to the LPS/Dgal model while mice expressing HCV 4f core protein had the same susceptibility as their littermate controls. Transcriptome analysis in liver biopsies from these transgenic mice gave insights into HCV core molecular pathogenesis, while linking HCV core protein genetic variability to differential pathology in vivo.

Worldwide, one of the main causes of death among young adults is multiple trauma. In these pa-tients hemorrhagic shock represents the leading cause for worsening of the clinical status and for increased morbidity and mortality. This is due to a multifactorial complex involving cellular, bi-ological, and biophysical mechanisms. The most important mechanisms affecting clinical out-come are oxidative stress, the augmentation of pro-inflammatory status, immune deficiency, dis-ruptions in the coagulation cascade, imbalances in electrolyte and acid-base homeostasis. Poly-trauma patients in hemorrhagic shock need adequate fluid management to ensure hemodynamic stability that must consider not only the maintenance of adequate blood pressure, but also the ad-equate oxygenation of tissues for optimal cellular function. In the current clinical practice, fluid resuscitation in polytrauma patients uses a variety of widely studied pharmacological products, such as crystalloids, colloids, blood transfusions, and the infusion of other blood products. Alt-hough these products exist, an agreement was not reached on a standard administration protocol that could be generally applied for all patients. Moreover, numerous studies have reported a se-ries of adverse events related to fluid resuscitation and to the inadequate use of these products. This review aims at describing the impact the administration of all the solutions used in fluid re-suscitation might have on the cellular and pathophysiological mechanisms in the case of poly-trauma patients suffering from hemorrhagic shock.

Michoacan state has a long history in plant domestication’s. Physalis ixocarpa is a native plant that growth associated to corn crops from this region. Such plants have similar fruits to Physalis philadelphica (husk tomate). Due to the domestication process includes the adaptation to environmental factors, we ask if 1) Does P. ixocarpa has the capacity of association with bacterial communities of the zone where it was domesticated?, and 2) Does the rhizobiome of this plant can increase the potential functions in the soil?. An experiment was established in a traditional milpa system. Samples of rhizobiome from corn, P. ixocarpa, P. philadelphica, and soil were sequenced using Next Generation Sequencing in the region 16S. The potential function, metabolic pathway reconstruction and participation of each bacteria genus was inferred using iVikodak platform. A total of 34 Phyla and 795 genera were identified. Purine metabolism's was the principal function, where all rizhobiomes showed similar metabolic pathways. However, the difference among plant species is the participation of the distinct genera in the purine metabolism. We conclude that rhizobiome of P. ixocarpa shows complementarity for the soil functions, and their utilization can be helpful in zones where the agricultural practices have degraded microbiological soil conditions.

Background. We investigated, for the first time, whether there are any sex differences in retrospective self-reported childhood maltreatment (CM) in Italian adult patients with major depressive disorder (MDD) or bipolar disorder (BD). Furthermore, the potential impacts of patients’ age on the CM self-report was investigated. Methods. This retrospective, cross-sectional study used the data documented in the electronic medical records of patients who were hospitalized for a 4-week psychiatric rehabilitation program. The CM was assessed using the 28-item Childhood Trauma Questionnaire (CTQ), which evaluates emotional, physical, and sexual abuse, as well as emotional and physical neglect. The linear and logistic regression models were used (α = 0.01). Results. Three hundred thirty five patients with MDD (255 women and 80 men) and 168 with BD (97 women and 71 men) were included. In both samples, considerable CM rates were identified, but no statistically significant sex differences were detected in the variety of CTQ-based CM aspects. There was a significant association, with no sex differences, between the increasing patients’ age and a decreasing burden of CM. Conclusion. Both women and men with MDD or BD experienced a similar and considerable CM burden. Our findings support the routine CM assessment in psychiatric clinical practice.

Human infections caused by the H5 highly pathogenic avian influenza virus (HPAIV) sporadically threaten public health. The susceptibility of HPAIVs to baloxavir acid (BXA), a new class of inhibitors for the influenza virus cap-dependent endonuclease, has been confirmed in vitro, but it has not yet been fully characterized. Here, the efficacy of BXA against HPAIVs, including recent H5N8 variants, was assessed in vitro. The antiviral efficacy of baloxavir marboxil (BXM) in H5N1 virus-infected mice was also investigated. BXA exhibited similar in vitro activities against H5N1, H5N6, and H5N8 variants tested in comparison with seasonal and other zoonotic strains. Compared with oseltamivir phosphate (OSP), BXM monotherapy in mice infected with the H5N1 HPAIV clinical isolate, the A/Hong Kong/483/1997 strain, also caused a significant reduction in viral titers in the lungs, brains, and kidneys, thereby preventing acute lung inflammation and reducing mortality. Furthermore, compared with BXM or OSP monotherapy, combination treatments with BXM and OSP using a 48-hour delayed treatment model showed a more potent effect on viral replication in the organs, accompanied by improved survival. In conclusion, BXM has a potent antiviral efficacy against H5 HPAIV infections.

Monascus pigments (MPs) have been used as food colorants for several centuries in Asian countries and nowadays in the whole world via Asian catering. The MPs biosynthetic pathway has been well-illustrated, however, the functions of a few genes including mrpigH in the MPs gene cluster of M. ruber M7 are still unclear. In current study, mrpigH was disrupted in Δmrlig4ΔmrpyrG, a highly efficient gene modification system, using mrpyrG as a selection marker, and ΔmrpigHΔmrlig4ΔmrpyrG::mrpyrG and ΔmrpigHΔmrlig4ΔmrpyrG have been obtained. Subsequently, their morphologies, biomasses, MPs and citrinin (CIT) production were analyzed, respectively. These results have revealed that the deletion of mrpigH has significant effects on the morphology and growth of M. ruber M7. Moreover, compared with M. ruber M7, the yields of MPs and CIT were drastically increased and decreased in mrpigH mutants, respectively.

Cryptosporidium is comprised an apicomplexan parasitic protist, which infects a wide range of hosts, causing cryptosporidiosis. In cattle farms, the incidence of cryptosporidiosis results in high mortality in calves leading to considerable economic loss in the livestock industry. Infected animals may also act as a major reservoir of Cryptosporidium spp., in particular C. parvum, the most common cause of cryptosporidiosis in calves. This poses a significant risk to other farms via breeding centres, to trading of livestock and to human health. This study, funded by the Interreg-2-seas programme, is a part of a global project aimed at strategies to tackle cryptosporidiosis. To reach this target, it was essential to determine whether prevalence was dependent on the studied countries or if the issue was borderless. Indeed, C. parvum occurrence was assessed across dairy farms in certain regions of Belgium, France and the Netherlands. At the same time, the animal-to-animal transmission of the circulating C. parvum subtypes was studied. To accomplish this, 1084 faecal samples, corresponding to 57 dairy-farms from all three countries, were analysed. Well-established protocols amplifying the 18S rDNA and gp60 genes fragments, followed by DNA sequencing, were used for the detection and subtyping C. parvum; the DNA sequences obtained were further characterised using a combination of bioinformatics and phylogenetics methods. Our results show 25.7%, 24.9% and 20.8% prevalence of Cryptosporidium spp. in Belgium, France and the Netherlands respectively. Overall, 93% of the farms were Cryptosporidium positive. The gp60 subtyping demonstrated a significant number of the C. parvum positives belonged to the IIa allelic family, which has been also detected in humans. Consequently, this study highlights how widespread is C. parvum in dairy farms and endorses cattle as a major carrier of zoonotic C. parvum subtypes, which subsequently pose a significant threat to human health.

Polyphosphate (polyP) accumulating organisms (PAOs) are the key agent to perform enhanced biological phosphorus removal (EBPR) activity, and intracellular polyP plays a key role in this process. Potential associations between EBPR performance and the polyP structure have been suggested, but are yet to be extensively investigated, mainly due to the lack of established methods for polyP characterization in the EBPR system. In this study, we explored and demonstrated that single-cell Raman spectroscopy (SCRS) can be employed for characterizing intracellular polyPs of PAOs in complex environmental samples such as EBPR systems. The results, for the first time, revealed distinct distribution patterns of polyP length (as Raman peak position) in PAOs in lab-scale EBPR reactors that were dominated with different PAO types, as well as among different full-scale EBPR systems with varying configurations. Furthermore, SCRS revealed distinctive polyP composition/features among PAO phenotypic sub-groups, which are likely associated with phylogenetic and/or phenotypic diversity in EBPR communities, highlighting the possible resolving power of SCRS at the microdiversity level. To validate the observed polyP length variations via SCRS, we also performed and compared bulk polyP length characteristics in EBPR biomass using conventional polyacrylamide gel electrophoresis (PAGE) and solution ³¹P nuclear magnetic resonance (³¹P-NMR) methods. The results are consistent with the SCRS findings and confirmed the variations in the polyP lengths among different EBPR systems. Compared to conventional methods, SCRS exhibited advantages as compared to conventional methods, including the ability to characterize in situ the intracellular polyPs at subcellular resolution in a label-free and non-destructive way, and the capability to capture subtle and detailed biochemical fingerprints of cells for phenotypic classification. SCRS also has recognized limitations in comparison with ³¹P-NMR and PAGE, such as the inability to quantitatively detect the average polyP chain length and its distribution. The results provided initial evidence for the potential of SCRS-enabled polyP characterization as an alternative and complementary microbial community phenotyping method to facilitate the phenotype-function (performance) relationship deduction in EBPR systems.

This article analyzes the assessment of the four development levels of the Digital Teaching Competence (DTC) to recognize the needs and formulation of challenges in training and educational innovation required in the pedagogical practices of university professors under the current context of the Covid-19 pandemic. The study used an empirical-analytical methodology with a non-experimental, transactional, descriptive design. The sample design was probabilistic, estimated with 95% confidence and 5% error among 252 teachers from various faculties of the University of La Guajira. The selected instrument corresponded to the rubric's application to evaluate the university professor's digital teaching competence in Latin America. Among the study's significant results, we highlight that the rubric presented a high Cronbach's alpha reliability (α: 0.947). In the general assessment of DTC development, it was estimated that 78.2% of teachers are in the first two levels of DTC development assessment (Beginning and Middle). The evaluation rubric allows identifying challenges and opportunities that teacher training must address to advance the professional development of professors.

In silico prediction of the in vivo efficacy of siRNA ionizable-lipid nanoparticles is desirable yet never achieved before. This study aims to computationally predict siRNA nanoparticles in vivo efficacy, which saves time and resources. A data set containing 120 entries was prepared by combining molecular descriptors of the ionizable lipids together with two nanoparticles formulation characteristics. Input descriptor combinations were selected by an evolutionary algorithm. Artificial neural networks, support vector machines and partial least squares regression were used for QSAR modeling. Depending on how the data set is split, two training sets and two external validation sets were prepared. Training and validation sets contained 90 and 30 entries respectively. The results showed the successful predictions of validation set log(dose) with R2val = 0.86 – 0.89 and 0.75 – 80 for validation sets one and two respectively. Artificial neural networks resulted in the best R2val for both validation sets. For predictions that have high bias, improvement of R2val from 0.47 to 0.96 was achieved by selecting the training set lipids lying within the applicability domain. In conclusion, in vivo performance of siRNA nanoparticles was successfully predicted by combining cheminformatics with machine learning techniques.

Gastric emptying rate (GER) may impact diabetes and obesity in humans and could provide a method to reduce canine weight gain. Starch, the most common source of carbohydrates (CHOs) in pet food, is classified as rapidly or slowly digestible, or resistant to digestion. This study investigated starch source effects in commercial extruded dog foods on the GER of 11 healthy adult Siberian Huskies (5.63±0.72 years; mean±SEM). Test diets were classified as traditional, grain-free, whole-grain, and vegan. Dogs received each diet once, a glucose control twice, and acetaminophen (Ac) as a marker for GER in a randomized, partially-replicated, 6x6 Latin square design. Pre- and post-prandial blood samples were collected at 16 timepoints from -15 to 480 minutes. Serum Ac concentrations were assessed via standard spectrophotometric assays and fitted with a mathematical model to estimate parameters of GER. Data was analyzed using a repeated measures ANOVA, followed by a Tukey-Kramer post-hoc test when significant (p<0.05). More total emptying (p= 0.0430) occurred at faster rate (p=0.0668) in dogs fed the grain-free diet, which contained the lowest total starch (34.03 ± 0.23%) and highest resistant starch (0.52 ± 0.007%). This research may benefit future diet formulations to reduce the prevalence of canine weight gain.

(1) Background: The Democratic Republic of the Congo (DRC) is heavily affected by malaria despite availability of effective treatments. Ignorance and unrecommended behaviour toward a suspected malaria case in households may contribute to this problem. (2) Method: In communities of one rural and one urban Health Centers in each of the 11 previous provinces of DRC, all households with a case of malaria in the 15 days prior to the survey were selected. The patient or caregiver (responder) were interviewed. Logistic regression was used to assess predictors of knowledge of recommended antimalarials and good behaviour in case of suspected malaria. (3) Results: 1,732 households participated; about 62% (1060/1721) of the responders were informed about antimalarials, 70.1% (742/1059) knew the recommended antimalarial and 58.6% (995/1699) resorted on self-medication. Predictors of knowledge of antimalarials were education to secondary school or university, information from media and smaller households. Predictors of good behaviour were catholic religion and smaller households. Receiving information from CHW failed to be determinants of knowledge or adequate attitude. (4) Conclusion: malaria control in DRC is hampered by ignorance and non-adherence to national recommendations. These aspects are influenced by unsuccessful communication, size of households and level of education.

Chromatin is dynamically remodeled to adapt to all DNA-related processes, including DNA damage responses (DDR). This adaptation requires DNA and histone epigenetic modifications, which are mediated by several types of enzymes; among them are lysine methyltransferases (KMTs). Methods: KMT inhibitors, chaetocin and tazemetostat (TZM), were used to study their role in the DDR induced by ionizing radiation or doxorubicin in two human sarcoma cells lines. The effect of these KMT inhibitors was tested by the analysis of chromatin epigenetic modifications, H4K16ac and H4K20me2. DDR was monitored by the formation of γH2AX, MDC1, NBS1 and 53BP1 foci, and the induction of apoptosis. Results: Chaetocin and tazemetostat treatments caused a significant increase of H4K16 acetylation, associated with chromatin relaxation; and increased DNA damage, detected by the labeling of free DNA-ends. These inhibitors significantly reduced H4K20 dimethylation levels in response to DNA damage and impaired the recruitment of 53BP1, but not of MDC1 and NBS1, at DNA damaged sites. This modification of epigenetic marks prevents DNA repair by the NHEJ pathway and leads to cell death. Conclusion: KMT inhibitors can function as sensitizers to DNA damage-based therapies and be used in novel synthetic lethality strategies for sarcoma treatment.

Around one billion people live in informal settlements, globally, including over half of Nairobi, Kenya’s three million residents. The purpose of this study was to explore women’s fear of victimization within Mathare, an informal settlement in Nairobi, Kenya and how fear of victimization influences behavior. Fifty-five in-depth interviews were conducted with women in 2016. A modified grounded theory approach guided data collection and analysis. Findings suggest fear of victimization is a serious concern in informal settlements. Women have found ways to adopt their behaviors that allow them to continue to function and protect their children despite fearing victimization, but at a potential cost to their health and well-being. Thus, there is a critical need for more research focused on social, economic, structural, community, infrastructure, technological, and individual strategies to prevent violence, enhance residents’ sense of safety, and, subsequently, minimize women’s fear of victimization in informal settlements.

An inclusive curriculum with a socio-cultural approach must include content on sustainability. This study raised the following problem: What is the presence of contents related to sustainability in the curricula of 24 degrees of Pedagogy of the Spanish state.? Through an explicit study, subjects directly related to sustainability were identified and analyzed through the qualitative data analysis program Atlas-ti. The categories of analysis used were those present in the Sustainability Thesaurus [4] to which the professional category was incorporated. The results showed, on the one hand, the low presence in these grades of subjects whose name indicates a direct link with sustainability and, on the other hand, On the other hand, the presence of professional competencies was detected, which were not subsequently specified in the corresponding learning outcomes or in the training content.

Background: Globally, infections are the third leading cause of neonatal mortality. Predominant risk factors for facility-born newborns are poor hygiene practices that span both the facility and home environments. Current improvement interventions focus on only one environment and tar-get limited caregivers, primarily birth attendants and mothers. To inform the design of a hand hygiene behaviour change intervention in rural Cambodia, a formative mixed-methods research study was conducted to investigate the context specific behaviours and determinants of hand-washing among healthcare workers, maternal and non-maternal caregivers along the early new-born care continuum. Methods: Direct observations of hygiene practices of all individuals providing care to 46 newborns across eight facilities and associated communities were completed and hand hygiene compliance assessed in analysis. Semi structured interactive interviews were subsequently conducted with 35 midwives and household members to explore the corresponding cognitive, emotional, and environmental factors influencing the observed key hand hygiene behaviours. Results: Hand hygiene opportunities during newborn care were frequent in both set-tings (n = 1319) and predominantly performed by mothers, fathers and non-parental caregivers. Compliance to hand hygiene protocol across all caregivers, including midwives, was inadequate (0%). Practices were influenced by the lack of accessible physical infrastructure, time, increased workload, low infection risk perception, nurture-related motives, norms and inadequate knowledge. Conclusion: Our findings indicate that an effective intervention in this context should be multi-modal to address the different key behaviour determinants and target a wide range of caregivers.

Familial adenomatous polyposis (FAP) is caused by germline mutations in the tumor suppressor gene APC. To date, nearly 2000 APC mutations have been described in FAP, most of which are predicted to result in truncated protein products. Mutations leading to aberrant APC splicing have rarely been reported. Here, we characterized a novel germline heterozygous splice donor site mutation in APC exon 12 (NM_000038.5: c.1621_1626+7del) leading to exon 12 skipping in an Italian family with the attenuated FAP (AFAP) phenotype. Moreover, we performed a literature me-ta-analysis of APC splicing mutations. We found that 123 unique APC splice site mutations, in-cluding the one described here, have been reported in FAP patients, 69 of which have been char-acterized at the mRNA level. Among these, only a small proportion (9/69) results in an in-frame protein, with 4 mutations causing skipping of exon 12 and/or 13 with loss of armadillo repeat 2 (ARM2) and 3 (ARM3), and 5 mutations leading to skipping of exon 5, 7, 8, and (partially) 9 with loss of regions not encompassing known functional domains. The APC splicing mutations considered in this study cluster with the AFAP phenotype and delineate a novel molecular mechanism of pathogenesis in FAP disease.

Inflammatory bowel diseases, familial adenomatous polyposis (FAP) and colorectal cancer (CRC) are associated with alterations of the intestinal microbiota. However, few data are available on the perpetuation of FAP and ulcerative colitis (UC) in relation to microbial dysbiosis. This study evaluated the UC and genetically confirmed FAP patients’ gut microbial balance in concordance to clinical outcome. Fecal materials (average mass of 0.54 g) were collected from three FAP and five UC patients to compare with healthy individuals as control group. Genomic materials of micro-biota were isolated for next generation sequencing of 16S rRNA that was performed by using QIAseq 16S/ITS panel in Illumina Miseq Platform. Data processing and bioinformatics analysis were performed via CLC Genomic Workbench bioinformatics tool. The comparison between FAP, UC and control group revealed an alteration in the intestinal microbial composition. More in details, relative abundance of class levels showed statistical significance differences among FAP, UC and control groups. Our preliminary data focused on the explanation of how dysbiosis can lead to inflammation and drive processes together with host genetic profile that leads to colorectal carcinogenesis.

Artificial sweeteners are widely used food ingredients in beverages and drinks to lower calorie intake which in turn prevent lifestyle diseases such as obesity. Epidemiological evidences suggest that an overdose of artificial sweeteners could result to adverse effects after consumption. Thus, our study aims to systematically explore the potential adverse effects of eight commercial artificial sweeteners, including acesulfame-K, alitame, aspartame, sodium cyclamate, dulcin, neotame, saccharin and sucralose on cardiac performances of zebrafish (Danio rerio) and Daphnia as model animals. Embryonic zebrafish and Daphnia were exposed to eight artificial sweeteners at 100 ppb concentrations and their cardiac performance (heart rate, ejection fraction, fractional shortening, stroke volume, cardiac output and heartbeat regularity) were measured and compared. Saccharin significantly increased the heart rate of zebrafish larvae while a significant decrease was observed in Daphnia. Significant increase was also noted in zebrafish heart rate variability after incubation in acesulfame K, dulcin, sodium cyclamate, and sucralose. However, a significant increase in Daphnia was only observed after incubation in dulcin. Based on Principal Component Analysis (PCA) and hierarchical clustering results, several artificial sweetener samples were species-specific to zebrafish and Daphnia. Our study demonstrates the potential adverse physiological effects of artificial sweeteners in cardiovascular systems of zebrafish larvae and Daphnia.

A cross-sectional study was carried out to determine the prevalence of subclinical mastitis (SCM) among medium to large scale household dairy farms in southwestern district, Jhenaidah, Bangladesh during July to December 2019. A total of 78 (n=100) lactating cows from household dairy farms (N=32) having three or more dairy cows were selected randomly as sampled populations. Milk samples were screened for SCM by using Surf Field Mastitis Test (SFMT). The prevalence of SCM varied among farm level [71.9% (95% CI: 53.3-86.3)], individual animal level [67.9% (95% CI: 56.4-86.3)] and quarter level [29.5% (95% CI: 24.5-34.9)]. Descriptive statistics represented the farmers and farm demography, characteristics of the sampled population, and overall management feature. Random Effect Logistic Regression identified, Body Condition Score (BCS) [OR=3.8 and 2.9, at cows level and quarter level respectively (BCS-2 vs. BCS-≥3)], and breed [OR=5.1 and 2.9, at cows level and quarter level respectively (HF× Sahiwal vs. HF × Local)] as potential risk factors. This study shows that SCM is highly prevalent in the study area, which is a major threat to the dairy industry's production performance. Regular screening by SFMT, proper hygiene, improve the management system, and farmer’s awareness is required to control the disease.

In this article we present a SCILAB implementation of algebraic iterative reconstruction methods for discretisation of inverse problems in imaging. These so-called row action methods rely on semi-convergence for achieving the necessary regularisation of the problem. We implement this method using SCILAB and provide a few simplified test problems: medical tomography, seismic tomography and walnut tomography.Numerical results show the capability of this method for the original and perturbed right-hand side vector.

Among the rust diseases, leaf rust of wheat caused by Puccinia triticina, is the most prevalent worldwide and causes significant yield losses. This study aimed to determine the genomic location of loci that control adult plant resistance (APR) to leaf rust in the pre-Green Revolution landrace accession, Aus27506, from the ‘Watkins Collection’. An Aus27506/Aus27229-derived F7 recombinant inbred (RIL) population was screened under field conditions across three cropping seasons and genotyped with the iSelect 90K Infinium SNP bead chip array. One QTL on each of chromosomes 1BL, 2B and 2DL explained most of the leaf rust response variation in the RIL population and were named QLr.sun-1BL, QLr.sun-2B and QLr.sun-2DL, respectively. QLr.sun-1BL and QLr.sun-2DL were contributed by Aus27506. QLr.sun-1BL is likely Lr46, while QLr.sun-2DL appeared to be a new APR locus. The alternate parent, Aus27229, carried the putatively new APR locus QLr.sun-2B. Comparisons of average severities among RILs carrying these QTL in different combinations indicated that QLr.sun-2B does not interact with either of the other two QTL; however, the combination of QLr.sun-1BL and QLr.sun-2DL reduced disease severity significantly. In-planta fungal quantification assays validated these results. The RILs carrying QLr.sun-1BL and QLr.sun-2DL did not differ significantly from parent Aus27506 in resistance. Aus27506 can be used as a source of adult plant leaf rust resistance in breeding programs.

The effect of proteolytic enzymes including Cathepsin K, a cysteine cathepsin, in onset and progression of cancers in human has been research intensive. Cathepsin K involves in many aspects and stages of cancers including apoptosis, cell proliferation, cancer immunology, inflammatory cell recruitment to tumors and aiding in the process of mobilization of normal healthy cells from their tissue compartments assisting in metastasis and angiogenesis. The objective of this review is to collect together and summarize and analyze the biochemical and physiological pathways of how cathepsin K is involved in onset and progression of cancers with more emphasis on breast and prostate cancers and cathepsin K regulated mechanisms underlying metastasis of such cancers to bones. Information for the review was gathered through published literature from global databases such as Google Scholar, PUBMED and NCBI on different studies on physiological interactions between enzymatic activity of cathepsin K with cancers and metastasis to bones. Analysis of published studies reveal that immunohistochemical studies of breast cancer cells indicate that they overexpress cathepsin K resulting in induction of aberrant mechanisms of cell signaling in breast cancers, creating a higher tendency for their metastasis to bones. Immunohistochemical, immunoprecipitation and fluorgenic assays of several studies done on the association of the same enzymatic activity on prostate cancers shows elevated levels of cathepsin K. Lesions derived from prostate cancer cell masses were observed to undergo increased bone formation and resorption levels. Such resorption levels cause secretion of biological factors promoting tumor expansion. In addition, studies indicate that Cathepsin K was observed to be a key component promoting higher bone resorption levels in patients suffering from cancer. Authors suggest that, to completely understand the association of cathepsin K on cancerous cells and their mechanism in metastasis, distributary patterns of cathepsin K in healthy human tissues needs to be extensively studied initially. It is also suggested that metastasis of breast and prostate cancers to bone could be terminated and overcome by successful production of efficient and precise inhibitory therapeutics targeting the enzymatic activity of Cathepsin K with minimum unintended adverse health effects.

Betadine (Providone-Iodine) solution is a topically applied antiseptic, which has been used for wound care and surgery for decades for the prevention and treatment of skin and wound infections. However, several studies have documented the ineffectiveness of Betadine solution. Other topical antimicrobial dressings, including those that contain silver, have been used in the management of infected wounds. The present study was undertaken to determine if the combination of 5% Betadine solutions and silver colloidal gel (Ag-gel), is more effective than the individual materials in inhibiting the growth of both Gram negative and Gram positive bacteria. These determinations were carried out by both the colony forming unit (CFU) assay, and confocal laser scanning microscopy (CLSM). Ag-gel showed complete inhibition on all the bacteria, except Klebsiella pneumoniae CI strain while 5% Betadine concentrations did not completely kill any of the tested bacteria. However, K. pneumoniae was completely eliminated in the presence of the combination of 5% Betadine solution plus Ag-gel. Confocal laser microscopy confirmed the CFU results. Thus this study demonstrated that while the individual treatments are not effective in killing all the bacteria tested, the combination of 5% Betadine solution and Ag-gel completely kill all bacteria tested, including K. penumoniae CI.

We develop a mathematical model to provide epidemic predictions for the 2019-nCov epidemic in Wuhan, China. We use reported case data up to January 31, 2020 from the Chinese Center for Disease Control and Prevention and the Wuhan Municipal Health Commission to parameterize the model. From the parameterized model we identify the number of unreported cases. We then use the model to project the epidemic forward with varying level of public health interventions. The model predictions emphasize the importance of major public health interventions in controlling 2019-nCov epidemics.

Background: the primary care service in Catalonia has operated an asynchronous teleconsulting service between GPs and patients since 2015 (eConsulta), which has generated some 500,000 messages. New developments in big data analysis tools, particularly those involving natural language, can be used to accurately and systematically evaluate the impact of the service. Objective: the study was intended to examine the predictive potential of eConsulta messages through different combinations of vector representation of text and machine learning algorithms and to evaluate their performance. Methodology: 20 machine learning algorithms (based on 5 types of algorithms and 4 text representation techniques)were trained using a sample of 3,559 messages (169,102 words) corresponding to 2,268 teleconsultations (1.57 messages per teleconsultation) in order to predict the three variables of interest (avoiding the need for a face-to-face visit, increased demand and type of use of the teleconsultation). The performance of the various combinations was measured in terms of precision, sensitivity, F-value and the ROC curve. Results: the best-trained algorithms are generally effective, proving themselves to be more robust when approximating the two binary variables "avoiding the need of a face-to-face visit" and "increased demand" (precision = 0.98 and 0.97, respectively) rather than the variable "type of query"(precision = 0.48). Conclusion: to the best of our knowledge, this study is the first to investigate a machine learning strategy for text classification using primary care teleconsultation datasets. The study illustrates the possible capacities of text analysis using artificial intelligence. The development of a robust text classification tool could be feasible by validating it with more data, making it potentially more useful for decision support for health professionals.

The present study uses the 3 years of data from a vertically pointed profile Radar (VPPR) at the mountain site (Huancayo at 3.2 km msl; HYO) in Peru to investigate the precipitation characteristics/patterns including diurnal variation, bright band (BB) characteristics and vertical structure of rain (VSR). VPPR provides continuous 1­min profiles of radar reflectivity (Ze), rain rate (RR), liquid water content (LWC) and Doppler velocity. At the same time, field campaign data are used to investigate the role of the surface and atmospheric variables in generating the rainfall and organization of the cloud systems over HYO. The precipitation shows the bimodal distribution; frequent and higher RR during afternoon and nighttime. The BB height also shows a diurnal pattern and BB height is higher during the afternoon and nighttime compared; and follows the diurnal heating of the Andes. More than 70% BB height lies between ~4.3­4.7 km and only 20% BB has altitude higher than 5 km. The austral summer monsoon (December to March months) have higher intense vertical profiles (higher Z e ) compared to pre monsoon seasons (September to November) and shows the nega­tive gradient for most of the altitude. The RR and LWC show the opposite characteristics, and both have a positive gradient below the 6 km altitude and then negative gradient above 6 km altitude. The raindrop size distribution (DSD) parameters show most of the variation below the freezing level, and a higher concentra­tion of large sized of hydrometeors are observed for higher RR, however the dominant modes of Dm are less than 1 mm. The changes in the VSR in DSD parameters are significant for the RR>20 mm/h, whereas for RR<2 mm/h the vertical structure in DSD parameters do not have much differences during monsoon and premonsoon seasons. Satellite and reanalysis data reveal the short periods of convective activity with higher ac­ cumulated rainfall over HYO compared to stratiform precipitation, which is more common in the nighttime and sustain for many hours. Wet spells (higher rainy days) have low pressure circulation, which favours the transport of moisture from the Amazon to the central Sierra of Peru, while the anticyclonic circulation at high levels favours the divergence at higher pressure levels and, enhances the convective in the region. During the dry spells, low level weaker circulation at the west of Brazil, restricts the transport of moisture to the central Sierra, while the circulation at high levels does not favor rain processes. The improved understanding of the tropical Andes precipitation would be very important for assessing climate variability and changes as well as to forecast precipitation using the numerical models.

The design, facilities and conditions inside a classroom play a significant role in the teaching and learning experience for both students and lecturers. Prior studies of primary schoolchildren indicate three design principles affecting student learning, namely: naturalness, individualisation and stimulation. The current study extends these investigations to Higher Education through a survey of undergraduate students and university lecturers aimed at determining the most critical factors in undergraduate classroom design. One-to-one interviews were conducted with students and lecturers (n. 31) at the University of Nottingham, Malaysia Campus. Interviewees were encouraged to express their opinions, comments, concerns and suggestions through open-ended questions. The interviews were recorded and then transcribed and coded using NVivo10. Results show a strong desire among lecturers and students for improved classroom equipment, greater flexibility in classroom arrangement, more attractive decoration and for the addition of natural elements to the classroom environment. Of the three design principles, individualisation and naturalness emerged most strongly from the interviews and appear to be more important factors for undergraduates than stimulation. These findings could make a novel and significant contribution to the physical aspects of classroom design in Higher Education settings. Educational institutions are increasingly employing non-traditional classroom designs, which are expected to provide for more flexible, collaborative, and active learning and teaching experiences. Taking into consideration the environmental psychology of teaching and learning, several of the reported design attributes can serve as benchmarks for upgrading current classroom design and facilities in the future, as institutions look to upgrade their physical infrastructures to meet the changing demands of teachers and learners arising from technological innovations and shifts in our understanding of the methods and purposes of Higher Education.

Because of the widespread use of bisphenol analogues (BPs) as the alternatives to bisphenol A (BPA), they have attracted considerable attention for health risk in aquatic ecosystems. The occurrence and distribution of six BPs were researched in soluble phase (< 5 kDa), colloidal phase (5 kDa to 1 µm) and suspended particulate matter (SPM > 1 µm) in a water diversion project of Nanjing, China. Except for bisphenol Z, all BPs were detected in the two or three phases, the total concentrations of detected BPs were 161-613 ng/L, 5.19-77.2 ng/L and 47.5-353 ng/g for the soluble phase, colloidal phase and SPM, respectively. Among the detected compounds, BPA still the dominant BPs in the soluble and colloidal phases, followed by BPS, while BPAF was the major contaminant in SPM, followed by BPA. The mean contribution proportions of colloids were 1-2 orders of magnitude higher than SPM, suggesting that colloids have an obvious impact on regulating BPs’ environmental behaviors. In terms of spatial distribution, although the water diversion project could reduce the pollution levels of BPs, which might further affect the ecological security of the Yangtze River.

Owing to the widespread use of bisphenol analogues (BPs) as bisphenol A (BPA) alternatives, they have been recognized to constitute a health risk for aquatic ecosystems. The occurrence and distribution of six BPs were investigated in the truly dissolved phase (< 5 kDa), colloidal phase (5 kDa to 1 µm) and suspended particulate matter (SPM > 1 µm) in a water diversion project of Nanjing, China. With the exception of bisphenol Z, all BPs were detected in at least two phases, the total concentrations of detected BPs were 161-613 ng/L, 5.19-77.2 ng/L and 47.5-353 ng/g for the truly dissolved phase, colloidal phase and SPM, respectively. Among the detected compounds, BPA still the dominant BPs in the truly dissolved phase and colloidal phase, followed by BPS, while BPAF was the major contaminant in SPM, followed by BPA. The mean contribution proportions of colloids were 1-2 orders of magnitude greater than that of SPM, suggesting that colloids play an important role in regulating the environmental behaviors of BPs. In terms of spatial distribution, although the water diversion project could reduce the pollution levels of BPs, which might further affect the ecological security of the Yangtze River.

High oxidative stress in cells due to inflammation process or excessive cell proliferation would produce oxidants or free radicals with biomarkers, one of which is malondialdehyde (MDA). Passion fruit seed’s contain high antioxidant and are expected to decrease the level of cholesterol and MDA. The objective is to identify the effect of passion fruit seed’s ethanol extract in Wistar rats that have been fed with atherogenic feed. The method was preclinical trial (post-test control group design) in rats, by administering passion fruit seed’s ethanol extract for 14 days. This study used 26 male rats aged two months, divided into 5 groups. The result showed significant difference in MDA level which was found in group that was given passion fruit seed extract 10mg/kg BW with positive control group that was given standard feed. Passion fruit seed’s extract showed significant difference in level of triglyceride, which was found in negative control group that was given atherogenic feed with group that was given passion fruit seed’s extract 5mg/kg BW (mean±standard deviation: 1.09±0.30 mg/dL vs 0.77±0.25mg/dL; p=0.048). This study showed that passion fruit seed’s ethanol extract had significant lowering effect in level of MDA, total cholesterol, and triglyceride for 14 days.

Best Management Practices (BMPs) are commonly used to control pollution in the river basins. Prioritization of BMPs helps improve the efficiency and effectiveness of pollution reduction, especially in Critical Source Areas (CSAs) that produce the highest pollution loads. Recently, the Dez River in Khuzestan, Iran, has become highly eutrophic from the overuse of fertilizers and pesticides. In this basin, dry and irrigated farming produce 77.34% and 6.3% of the Total Nitrogen (TN) load, and 83.56% and 4.3% of the Total Phosphorus (TP) load, respectively. In addition, residential, pasture, and forest land uses together account for 16.36% of the TN and 12.14% of the TP load in this area. The Soil and Water Assessment Tool (SWAT) was implemented to model the Dez River basin and evaluate the applicability of several BMPs, including point source elimination, filter strips, livestock grazing, and river channel management, in reducing the entry of pollution loads to the river. Sensitivity analysis and calibration/validation of the model was performed using the SUFI-2 algorithm in the SWAT Calibration Uncertainties Program (SWAT-CUP). The CSAs were identified using individual (sediment, TN, TP) and combined indices, based on the amount of pollution produced. Among the BMPs implemented, the 10 m filter strip was most effective in reducing TN load (42.61%), and TP load (39.57%).

Background Legionella pneumophila is one of the causes of legionellosis. Water environments serve as the natural habitat and the main sources of Legionella pneumophila. Objectives The aims of this study was to understand the differences of Legionella pneumophila serogroups distribution in well water, tap water, ice cubes, hospital and hotel water in East Java-Indonesia. Methods a total of 60 water samples in east java-Indonesia; from well water (n=25), tap water (n=5), ice cubes (n=5), water from the hospital (n=16), and hotel water (n=9) were detected using polymerase chain reaction with mip gene spesific primers and then it was analyzed by phylogenetic tree. Results For the 60 water samples collected in East Java, 12% of the samples (7/60) were positively contaminated by L. pneumophila. In details, there was 8% of the well water samples (2/25), 2% of the tap water samples (1/5), 2% of the ice cubes samples (1/5), 0% of the hospital water samples (0/16) and 33.33% of the hotel water samples (3/9). The phylogenetic tree showed that Legionella pneumophila contaminating well water isolate 1 from Surabaya and tap water isolate from Sidoarjo was closer to L.pneumophila serogroup 2, 4, 6, 8, 10, 12, isolates from Brazil, China, Spain and Australia. L.pneumophila contaminating the ice cubes from Sidoarjo was closer to serogroup 1, 2, 4, 7, 8, 11, 13, 14, while the bacteria contaminating well water isolate 2 from Sidoarjo as well as water in hotel of Surabaya (hotel water isolate 1, 2 and 3) classified into their own group. Conclusion There is a difference in the distribution of L. pneumophila serogroups between well water, tap water, ice cubes, and hotels.

The global demands for various grains including durum wheat (Triticum durum Desf.) are expected to increase substantially in the coming years due to ever-growing human population’s needs for food, feed and fuel. Thus, providing consistent or increased durum grain to the world market is one of the priorities for policy-makers, researchers, and farmers. What are the major achievements in agronomic advancement for durum wheat cultivation in recent decades? How might the current cropping systems be improved to increase crop yield and quality and improve resource use efficiencies while minimizing input costs and decreasing negative impact on the environment? Canada is one of the major durum wheat producers in the world, as Canada contributes about 50% to global trade of durum grain. Canada’s research achievements in durum wheat might serve as a guide for advancing the cultivation of the crop in other regions/countries on the planet. This review summarizes the major Canadian research findings in the aspects of durum wheat agronomics during the period 2001 to 2017 years. It highlights the main advancements in seeding and tillage, crop rotation and diversification, and use of pulse-induced microbiomes to improve soil health and feedback mechanism. The genetic gain and breeding for resistance against abiotic and biotic stresses are discussed. Finally, we identified main constraints and suggested some near-term research priorities. The research findings highlighted in this review will be of use for other areas on the planet to increase durum wheat productivity, improve soil fertility and health, and enhance long-term sustainability.

China’s transportation industry has made rapid progress, which has led to a mass of carbon emissions. However, it is still unclear how the carbon emission from transport sector is punctuated by shifts in underlying drivers. This paper aims to examine the process of China’s carbon emissions from transport sector as well as its major driving forces during the period of 2000 to 2015 at the provincial level. We firstly estimate the carbon emissions from transport sector at the provincial level based on the fuel and electricity consumption using a top-down method. We find that the carbon emission per capita is steadily increasing across the nation, especially in the provinces of Chongqing and Inner Mongolia. However, the carbon emission intensity is decreasing in most provinces of China, except in Yunnan, Qinghai, Chongqing, Zhejiang, Heilongjiang, Jilin, Inner Mongolia, Henan and Anhui. We then quantify the effect of socio-economic factors and their regional variations on the carbon emissions using panel data model. The results show that the development of secondary industry is the most significant variable in both the entire nation level and the regional level, while the effects of the other variables vary across regions. Among these factors, population density is the main motivator of the increasing carbon emissions per capita from transport sector for both the whole nation and the western region, whereas the consumption level per capita of residents and the development of tertiary industry are the primary drivers of per capita carbon emissions for the eastern and central region.

In South Western Indian ocean (IO), Extended-Spectrum β-Lactamase producing Enterobacteriaceae (ESBL) are a main public health issue. In livestock, ESBL burden was unknown. The aim of this study was estimating the prevalence of ESBL on commercial farms in Reunion, Mayotte and Madagascar and genes involved. Secondly, risk factors of ESBL occurrence in broiler, beef cattle and pig farms were explored. In 2016-2017, commercial farms were sampled using boot swabs and samples stored at 4°C before microbiological analysis for phenotypical ESBL and gene characterization. A semi-directive questionnaire was performed. Prevalences observed in all production types and territories were elevated, except for beef cattle in Reunion which differed significantly. The most common ESBL gene was the CTX-M-1 subtype. Generalized linear models explaining ESBL occurrence varied between livestock production sectors and allowed identifying main protective (e.g., water quality control and detergent use for cleaning) and risk factors (e.g., recent antibiotic use, other farmers visiting the exploitation, pet presence). This study is the first to explore tools for antibiotic resistance management in IO farms. It provides interesting hypothesis to explore about antibiotic use in IO and ESBL transmission between pig, beef cattle and humans in Madagascar.