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High-fat diet (HFD)-induced fatty liver disease is a deteriorating risk factor for Alzheimer’s disease (AD). Mitigating fatty liver disease has been shown to attenuate AD-like pathology in animal models. However, it remains unclear whether enhancing Aβ clearance through immunotherapy would in turn attenuate HFD-induced fatty liver or whether its efficacy would be compromised by long-term exposure to HFD. Here, the therapeutic potentials of an anti-Aβ antibody, NP106, was investigated in APP/PS1 mice by HFD feeding for 44 weeks. The data demonstrate that NP106 treatment effectively reduced Aβ burden and pro-inflammatory cytokines in HFD-fed APP/PS1 mice and ameliorated HFD-aggravated cognitive impairments during the final 18 weeks of the study. The rejuvenating characteristics of microglia were evident in APP/PS1 mice with NP106 treatment, namely enhanced microglial Aβ phagocytosis and attenuated microglial lipid accumulation, which may explain the benefits of NP106. Surprisingly, NP106 also reduced HFD-induced hyperglycemia, fatty liver, liver fibrosis, and hepatic lipids, concomitant with modifications in the expressions of genes involved in hepatic lipogenesis and fatty acid oxidation. The data further reveal that brain Aβ burden and behavioral deficits were positively correlated with the severity of fatty liver disease and fasting serum glucose levels. In conclusion, our study shows for the first time that anti-Aβ immunotherapy using NP106, which alleviates AD-like disorders in APP/PS1 mice, ameliorates fatty liver disease. Minimizing AD-related pathology and symptoms may reduce the vicious interplay between central AD and peripheral fatty liver disease, thereby highlighting the importance of developing AD therapies from a systemic disease perspective.

Intestinal dysbiosis is a major contributor to colorectal cancer (CRC) development, leading to bacterial translocation into the bloodstream. This study aimed to evaluate the presence of circulated bacterial DNA (cbDNA) in CRC patients (n = 75) and healthy individuals (n = 25). DNA extracted from peripheral blood was analyzed using PCR, with specific primers targeting 16S rRNA, Escherichia coli (E. coli), and Fusobacterium nucleatum (F. nucleatum). High 16S rRNA and E. coli detections were observed in all patients and controls. Only the detection of F. nucleatum was significantly higher in metastatic non-excised CRC, compared to controls (p < 0.001), non-metastatic excised CRC (p = 0.023), and metastatic excised CRC (p = 0.023). This effect was mainly attributed to the presence of the primary tumor (p = 0.006) but not the presence of distant metastases (p = 0.217). The association of cbDNA with other clinical parameters or co-morbidities was also evaluated, revealing a higher detection of E. coli in CRC patients with diabetes (p = 0.004). These results highlighted the importance of bacterial translocation in CRC patients and the potential role of F. nucleatum as an intratumoral oncomicrobe in CRC.

Extracellular HSP90α (eHSP90α) is a promoter of tumor development and malignant progression. Patients with malignancies, including pancreatic ductal adenocarcinoma (PDAC), have generally shown 5~10-fold increases in serum/plasma eHSP90α levels. In this study, we developed a humanized antibody HH01 to target eHSP90α and evaluated its anticancer efficacy. HH01, with novel complementarity-determining regions, exhibits high binding affinity toward HSP90α. It recognizes HSP90α epitope sites 235AEEKEDKEEE244 and 251ESEDKPEIED260, with critical amino acid residues E237, E239, D240, K241, E253, and K255. HH01 effectively suppressed eHSP90α-induced invasive and spheroid-forming activities of colorectal cancer and PDAC cell lines by blocking eHSP90α’s ligation with the cell-surface receptor CD91. In mouse models, HH01 potently inhibited the tumor growth of PDAC cell grafts/xenografts promoted by endothelial-mesenchymal transition-derived cancer-associated fibroblasts while also reducing serum eHSP90α levels, reflecting its anticancer efficacy. HH01 also modulated tumor immunity by reducing M2 macrophages and reinvigorating immune T-cells. Additionally, HH01 showed low aggregation propensity, high water solubility, and a half-life time of >18 days in mouse blood. It was not cytotoxic to retinal pigmented epithelial cells and showed no obvious toxicity in mouse organs. Our data suggest that targeting eHSP90α with HH01 antibody can be a promising novel strategy for PDAC therapy.

Dans le but de valoriser les espèces végétales à propriétés insecticides et la recherche des méthodes alternatives à l'utilisation des insecticides chimiques, il est impérieux de mettre en place de bio-pesticides, qui soient efficaces, moins coûteux, accessibles, faciles à manipuler par les paysans et respectueux de la santé humaine et de l’environnement. Pour ce faire, cette étude s’est fixée comme objectif de déterminer l’efficacité des extraits aqueux des graines de ricin (Ricinus communis L.) et de Neem (Azadiracta indica L.) sur les ravageurs de la culture de niébé dans les conditions écologiques de Mbujimayi (RDC). Un dispositif expérimental complètement randomisé a été installé, sur une superficie totale de 180 m², constitué de trois blocs et quatre traitements, à savoir, T0 (témoin), T1 (Deltamethrine (1,11 litre/m²), T2 (Extraits des graines de neem (1,11 litre/m²) et T3 (Extraits des graines de ricin (1,11 litre/m²). Après application des traitements, il a été noté que le nombre d’insectes d’Ootheca mutabilis, de Maruca vitrata, d’Aneplocnemis curvipes, de Riptortus dentipes, a varié et l’analyse de variance a dégagé une différence significative entre les traitements comparativement aux nombres d’insectes dénombrés avant application des produits phytosanitaires. Mot clés: Biopesticide, ricin, neem, niébé, Mbujimayi

ABSTRACTThe identification of immune correlates of protection against infectious pathogens will accelerate the design and optimization of recombinant and subunit vaccines. Systematic analyses such as immunoprofiling including serological, cellular, and molecular assessments supported by computational tools are key to not only identify correlates of protection but also biomarkers of disease susceptibility. The current study expands our previous cellular and serological profiling of vaccine-induced responses to a whole parasite malaria vaccine. The irradiated sporozoite model was chosen as it is considered the most effective vaccine against malaria. In contrast to whole blood transcriptomics analysis, we stimulated peripheral blood mononuclear cells (PBMC) with sporozoites and enriched for antigen-specific cells prior to conducting transcriptomics analysis. By focusing on transcriptional events triggered by antigen-specific stimulation, we were able to uncover quantitative and qualitative differences between protected and non-protected individuals to controlled human malaria infections and identified differentially expressed genes associated with sporozoite-specific responses. Further analyses including pathway and gene set enrichment analysis revealed that vaccination with irradiated sporozoites induced a transcriptomic profile associated with Th1-responses, Interferon-signaling, antigen-presentation, and inflammation. Analyzing longitudinal time points not only post-vaccination but also post-controlled human malaria infection further revealed that the transcriptomic profile of protected vs non-protected individuals was not static but continued to diverge over time. The results lay the foundation for comparing protective immune signatures induced by various vaccine platforms to uncover immune correlates of protection that are common across platforms.

In the United States, the political landscape is characterized by biannual changes in power between the two major political parties, the Democratic and Republican parties. The shift in power can lead to significant changes in the regulatory environment for businesses, with each party having different policies and priorities when it comes to business regulation. Our research investigates the impact of political power shifts on consumer perceptions of business ethics. We collected two sample datasets through telephone interviews, the first conducted before the November 2018 mid-term elections (N=1,003) and the second after the elections (N=1,009). Our findings were surprising. Despite the mid-term elections being a significant political event and a change in power, we found that they did not immediately impact consumer perceptions of business ethics. This study offers new insights into the relationship between political power shifts and consumer perceptions of business ethics in the United States and is the first to examine this issue. The results suggest that consumer perceptions of business ethics may be relatively stable despite changes in political power. The leniency or stringency of regulations imposed on businesses by political parties may not significantly alter consumers' perceptions of ethical behavior. It is an important finding for businesses as it highlights the importance of maintaining ethical practices and behavior, regardless of political circumstances. Our research sheds light on the complex relationship between political power shifts and consumer attitudes toward business ethics. It provides a starting point for future investigations into this topic, which is especially relevant in today's political climate. The findings have significant implications for businesses, as they underscore the importance of maintaining a strong ethical foundation and reputation, regardless of changes in the regulatory environment. By doing so, businesses can build trust and maintain consumer loyalty in the long run.

Background Accelerated population ageing is associated with an increasing prevalence of frailty. International guidelines call for systematic assessment and timely interventions for older persons requiring acute care. Checklists have been applied successfully in healthcare settings.Objective This study describes the implementation of a safety checklist for frailty in the acute medical unit (AMU) of a tertiary public hospital in Singapore. We explored the sustainability of processes up to 6 months after initial implementation. Additionally, we investigated process and system outcome benefits following the implementation of the checklist.Methods This retrospective observational study used case notes review of patients admitted to the AMU of a tertiary public hospital in Singapore from February to August 2019. Process outcomes measured to include compliance with AMU frailty checklist assessments and interventions at 24 hours of hospital admission. System and patient outcomes studied to include the length of hospital stay; 30-day emergency department reattendance rate; 30-day hospital readmission rate and inpatient mortality. Propensity scores were used to create balanced cohorts for comparison between those with complete and incomplete compliance with the checklist. Logistic regression was used to adjust for known confounders.Results Average weekly (all-or-nothing) compliance with the frailty checklist (14.7%) was sustained for 6 months. Where assessments detected high risk, appropriate interventions were appropriately triggered (44%–97.4%). While trends to benefit systems and patient outcomes were present, these were not statistically significant. Contextual patterns are discussed.Conclusion A safety checklist for frailty was feasibly implemented in the AMU. The checklist was a complex intervention. Full compliance with the checklist was challenging to achieve. Further research assessing optimal patient selection criteria and how checklists may shift team behaviour is a priority.

Background: Colon cancer surgery is a complex clinical pathway and traditional quality metrics may exhibit significant variability between hospitals and healthcare providers. The Textbook Outcome (TO) is a composite quality marker capturing the fraction of patients, in whom all desired short-term outcomes of care are realised. The aim of the present study was to assess the TO in a series of non-metastatic colon cancer patients treated with curative intent, with emphasis on long-term survival. Methods: Stage I–III colon cancer patients, who underwent curative colectomy following the Complete Mesocolic Excision principles, were retrospectively identified from the institutional database. TO was defined as (i) hospital survival, (ii) radical resection, (iii) no major complications, (iv) no reintervention, (v) no unplanned stoma and (vi) no prolonged hospital stay or readmission. Results: In total, 128 patients (male 61%, female 39%, mean age 70.7 ± 11.4 years) were included in the final analysis. Overall, 60.2% achieved a TO. The highest rates were observed for “hospital survival” and “no unplanned stoma” (96.9% and 97.7%), while the lowest rates were for “no major complications” and “no prolonged hospital stay” (69.5% and 75%). Older age, left-sided resections and pT4 tumours were factors limiting the chances of a TO. The 5-year overall and 5-year cancer-specific survival were significantly better in the TO versus non-TO subgroup (81% vs. 59%, p = 0.009, and 86% vs. 65%, p = 0.02, respectively). Conclusions: Outcomes in colon cancer surgery may be affected by patient-, doctor- and hospital-related factors. TO represents those patients who achieve the optimal perioperative results, and is furthermore associated with improved long-term cancer survival.

Abstract Background Chronic respiratory conditions are a prominent public health issue and thus, building a patient registry might facilitate both policy decision making and improvement of clinical management processes. Hellenic Registry of patients with Home Mechanical Ventilation (HR-HMV) was initiated in 2017 and a web-based platform is used to support patient data collection. Eighteen hospital departments (including sleep labs) across Greece participate in this initiative, focusing on recording data for both children and adult patients supported by mechanical ventilation at home, including patients with Sleep Apnea–Hypopnea Syndrome (SAHS) under Positive Airway Pressure (PAP) therapy. Methods The HR-HMV initiative ultimately aims to provide a database for evidence-based care and policy making in this specific domain. To this end, a web information system was developed and data were manually collected by clinics and hospital departments. Legal and privacy issues (such as General Data Protection Rule compliance and technical information security measures) have been considered while designing the web application. Based on the collected data, an exploratory statistical report of SAHS patients in Greece is presented. Results Eleven out of the eighteen participating clinics and hospital departments have contributed with data by the time of the current study. More than 5000 adult and children patient records have been collected so far, the vast majority of which (i.e., 4900 patients) diagnosed with SAHS. Conclusion The development and maintenance of patient registries is a valuable tool for policy decision making, observational/epidemiological research and beyond (e.g., health technology assessment procedures). However, as all data collection and processing approaches, registries are also related with potential biases. Along these lines, strengths and limitations must be considered when interpreting the collected data, and continuous validation of the collected clinical data per se should be emphasized. Especially for Greece, where the lack of national registries is eminent, we argue that HR-HMV could be a useful tool for the development and the update of related policies regarding the healthcare services for patients with home mechanical ventilation support and SAHS patients, which could be useful for related initiatives at a European level as well.

Environmental pollution is an issue of particular concern, specifically when industrial waste products are not subjected to appropriate treatment. Among various industries in the agri-food sector, the brewing industry holds a significant position in this context, given that beer stands as the predominant choice of consumers. Brewery waste generates significant quantities of organic substances, along with ammonium nitrogen and phosphorus. Among the various methods for their treatment, adsorption has received substantial attention due to its cost-effectiveness and operational simplicity. The present study investigates the adsorption capacity of two materials, zeolite and palygorskite, for the removal of ammonium nitrogen and brewery waste, using columns and batches. Simultaneously, desorption and regeneration experiments were conducted, and the effect of pH on their effectiveness was also examined. To understand the adsorption mechanisms, isotherm and kinetic models have been estimated. The results of the experiments have demonstrated a marked adsorption efficiency of the adsorbent materials, surpassing 90%. In comparison, zeolite has exhibited a better adsorption capacity in the removal of ammonium nitrogen, while palygorskite has shown greater aptitude for phosphorus removal. The purpose of these experiments was to investigate the adsorption capacity of these two materials as a potential medium for brewery wastewater treatment (e.g., as part of adsorption filter, trickling filters, and constructed wetlands).

Understanding farmers’ perceptions about climate change and adaptation strategies can help support their efforts and develop interventions more suited to the local context. This is particularly important for farmers who exploit fragile ecosystems such as marshlands.Using semi-structured questionnaires and interviews conducted with smallholder farmers in the marshlands of Kabare, this study compares the perception of men and women relating to climate change and uses the chi-square test and logistic regression to examine gendered differences in response to climate change and the determinants of farmers’ choice of sustainable practices. Meteorological data trends for three decades were also compared.Results showed that both men (77 %) and women (73 %) experienced climate change and this was illustrated by changes in temperature and rainfall patterns. Farmers’ climate change perceptions are consistent with the local historical climate data showing a slightly increasing trend of temperature and a decrease in rainfall for the last decade, particularly between 2013 and 2019. Although significant differences were observed between gender and sources of climate information (p

Bronchial provocation tests, such as the mannitol challenge, can be performed to identify and quantify the severity of bronchial hyperresponsiveness in asthmatic patients. Studies of the mannitol challenge as a monitoring tool in asthmatic children are limited. Our primary aim was to compare the bronchial hyperresponsiveness to mannitol in treatment-naive asthmatic children between baseline and three months after receiving the indicated asthma prophylaxis. Twenty-three asthmatic patients aged 4–16 years were analyzed in this prospective cohort study. All subjects underwent the mannitol challenge at baseline and after three months of treatment with budesonide ± formoterol. The difference in the provocative dose of mannitol to induce a 15% drop in FEV1 (PD15) between baseline and follow-up, as well as its association with the presence of exercise-induced or nocturnal asthma symptoms, were evaluated. The PD15 value increased significantly post-treatment (228.5 mg [4.50–458.15]; p = 0.04). Independently of the evaluation time point, the PD15 values were significantly lower in the presence of nocturnal asthma symptoms (490 mg [122–635] vs. 635 mg [635–635]; p = 0.03), whereas there was no association between the PD15 value and the presence of exercise-induced asthma (p = 0.73). These results suggest that bronchial hyperresponsiveness to mannitol may be a potential monitoring tool in the pediatric asthmatic population, reflecting therapy response in children receiving prophylactic treatment.

Background & AimsAgeing is a risk factor for diabetes mellitus (DM) and frailty. It is associated with body composition changes including increase in fat mass (FM), central fat distribution, decrease in fat free mass (FFM) and skeletal muscle which are risk factors for DM. This study aims to evaluate gender differences in body composition in pre-frail diabetics and association with physical performance, cognitive function and perceived health. In addition, we aim to explore the association of obesity, sarcopenia, sarcopenic obesity, and body composition in pre-frail older adults to DM status.MethodsCross-sectional study of 192 pre-frail community dwelling older adults (≥ 65 years). Data was collected on demographics, physical function, cognition, frailty, sarcopenia, perceived health and body composition using the InBody S10. Univariate and multivariate logistic regression were undertaken to explore the association of sarcopenic obesity, obesity, sarcopenia and body composition measures to DM status.ResultsThere were insignificant within-gender differences for physical function, cognition and body composition, except for a higher prevalence of obesity defined by body mass index (BMI) and body fat percentage (BF%), increased fat mass index(FMI) and fat free mass index(FFMI) in females with DM. There were significant between-gender differences for those with DM where females overall had lower education levels, lower perceived health, higher prevalence of depression and low mental vitality, lower overall physical function (low short physical performance battery scores, low gait speed and hand grip strength), lower cognitive scores, lower muscle mass and muscle quality with higher FMI, FM/FFM and visceral fat area(VFA). BMI, VFA>100 cm2, FMI and FFMI were found to be independently associated with DM status after multivariable adjustment.ConclusionWithin pre-frail DM vs non-DM, there were insignificant differences in body composition, physical function, cognition and perceived health within gender except for FMI, BF% and FFMI in females. There were significant differences between gender in pre-frail DM in muscle mass, quality, functional, cognitive and mental status. Further longitudinal studies are required to understand the pathogenesis, trajectory of DM and protective role of oral hypoglycemics in pre-frail older adults.

BackgroundBody mass index (BMI) is an inadequate marker of obesity, and cannot distinguish between fat mass, fat free mass and distribution of adipose tissue. The purpose of this study was twofold. First, to assess cross-sectional relationship of BMI with fat mass index (FMI), fat free mass index (FFMI) and ratio of fat mass to fat free mass (FM/FFM). Second, to study the association of FMI, FFMI and FM/FFM with physical function including sarcopenia, and cognition in pre-frail older adults.MethodsCross-sectional study of 191 pre-frail participants ≥ 65 years, 57.1% females. Data was collected on demographics, cognition [Montreal Cognitive Assessment (MoCA)], function, frailty, calf circumference, handgrip strength (HGS), short physical performance battery (SPPB) and gait speed. Body composition was measured using InBody S10. FMI, FFMI and FM/FFM were classified into tertiles (T1, T2, T3) with T1 classified as lowest and T3 highest tertile respectively and stratified by BMI.ResultsHigher FFMI and lower FM/FFM in the high BMI group were associated with better functional outcomes. Prevalence of low muscle mass was higher in the normal BMI group. FMI and FM/FFM were significantly higher in females and FFMI in males with significant gender differences except for FFMI in ≥ 80 years old. Small calf circumference was significantly less prevalent in the highest tertile of FMI, FM/FMI and FFMI. Prevalence of sarcopenic obesity and low physical function (HGS, gait speed and SPPB scores) were significantly higher in the highest FMI and FM/FFM tertile. Highest FFMI tertile group had higher physical function, higher MoCA scores, lower prevalence of sarcopenic obesity and sarcopenia, After adjustment, highest tertile of FFMI was associated with lower odds of sarcopenia especially in the high BMI group. Highest tertile of FM/FFM was associated with higher odds of sarcopenia. Higher BMI was associated with lower odds of sarcopenia.ConclusionFFMI and FM/FFM may be a better predictor of functional outcomes in pre-frail older adults than BMI. Cut-off values for healthy BMI values and role of calf circumference as a screening tool for sarcopenia need to be validated in larger population. Health promotion intervention should focus on FFMI increment.

We use the General Equilibrium Ecosystem Model (GEEM) parameterized to Wyoming sagebrush to explore the impact of two common simplifications in bio-economic policy frameworks on species conservation decisions. First, we compare conservation policies based on 2-species food web models to those based on a more complex food web. We find that using the simpler model can miss opportunities for more conservation benefits in the presence of species interactions. Second, we define the impact of species dispersal costs on population distributions in a heterogenous landscape and explore conservation policies to reduce those costs to enable species to move away from disturbed areas. Conservation actions that reduce dispersal costs for all species reflect species interactions and thresholds that determine which species disperse.

Background: Physical activity (PA) improves exercise capacity, slows the decline in lung function, and enhances Quality of Life (QoL) in patients with cystic fibrosis (pwCF). Objectives: The study aimed to evaluate PA and QoL among children with CF compared to healthy controls; the secondary aim was to assess the correlation between PA, QoL, and lung function (FEV1). Methods: Forty-five children and adolescents with CF and 45 age-matched controls completed two self-administered validated questionnaires: The Godin Leisure-Time Exercise Questionnaire (GLTEQ) and the DISABKIDS for QoL. Moreover, pwCF performed spirometry and multiple breath washout tests (MBW). In addition, weight, height, and BMI were recorded. The Godin Leisure-Time Exercise Questionnaire was used to evaluate physical activity; QOL was assessed using the DISABKIDS Questionnaire. The correlation of PA with QOL was assessed as well. Results: Mean age of the CF population was 13.22 (±4.6) years, mean BMI 19.58 (±4.1) kg/m2, mean FEV1% 91.15 ± 20.46%, and mean LCI 10.68 ± 4.08. 68% of the CF group were active, 27% were medium active, 5% were sedentary, while 83% of the control group were active and 17% were medium active. PwCF with higher PA scores showed significantly higher emotional health (r2: 0.414, p: 0.006) and total QOL score (r2: 0.372; p: 0.014). The PA score showed no significant correlation with FEV1% or LCI. Conclusions: The children with CF showed satisfactory PA levels, which positively correlated to their QoL. More research is needed on the effect of increased levels of habitual physical activity to establish the decline in pulmonary function among pwCF.

Introduction: Hospital-at-Home (HaH) programmes are well-established in Australia, Europe, and the United States. However, there is limited experience in Asia, where the hospital is traditionally seen as a safe and trusted space for healing. This cross-sectional study aimed to explore attitudes and perceptions among patients and caregivers in Singapore toward this care model.Methods: A quantitative study design was adopted to collect data among patients and their caregivers from medical wards within two acute hospitals in Singapore. Using a series of closed-ended and open-ended questions, the investigator-administered survey aimed to explore barriers and facilitators determining patients' and caregivers' responses. The study questionnaire was pretested and validated. Data were summarised using descriptive statistics, and logistic regression was performed to determine key factors influencing patients' decisions to enrol in such programmes.Results: Survey responses were collected from 120 participants (101 patients, 19 caregivers; response rate: 76%), of which 87 respondents (72.5%) expressed willingness to try HaH if offered. Many respondents valued non-quantifiable programme benefits, including perceived gains in quality of life. Among them, reasons cited for acceptance included preference for the comfort of their home environment, presence of family members, and confidence toward remote monitoring modalities. Among respondents who were unwilling to accept HaH, a common reason indicated was stronger confidence toward hospital care.Discussion: Most patients surveyed were open to having acute care delivered in their home environment, and concerns expressed may largely be addressed by operational considerations. The findings provide useful insights toward the planning of HaH programmes in Singapore.

Urine diversion toilets have become popular as a means of solving the challenges in sanitation. As a result, the source separated urine must be adequately treated so that it can be disposed of safely and valuable struvite can be extracted for use as fertiliser. Struvite crystallization has been investigated for this purpose, however, for the crystallization process to be viable and economical, a cost effective yet optimal magnesium source is required. Crystallisation must have optimal yield as well as crystal size and morphology (CSD). Crystal size is an important factor in crystallisation as it affects further processing steps such as washing and filtering, therefore CSD must be controlled in crystallisation processes. In this study, synthetic urine was prepared, and struvite crystallisation experiments carried out using Magnesium Nitrate (MgNO3). The effect of parameters on CSD were investigated. Residence time was found to be the parameter with the most effect on CSD. At residence time of 10, 30 and 60 minutes, mean particle sizes were 17, 34 and 53 µm showing that with higher residence times, larger crystal sizes can be achieved. SEM analysis of the crystal showed that the resultant crystals had the typical morphology of struvite crystals.

PurposeDue to the current practice on colorectal cancer (CRC) management, chemoresistance is most often recognized at the end of the treatment. Therefore, effective and easy-to-use prognostic biomarkers are needed.Experimental DesignWe evaluated the prognostic significance of two novel CRC biomarkers: a) micronuclei frequency (MNf) in 55 metastatic CRC (mCRC) and 21 locally advanced rectal cancer (laRC) patients using cytokinesis block micronucleus assay (CBMN assay) and b) telomerase activity (TA) in 23 mCRC and five laRC patients using TRAP-ELISA. Both biomarkers were evaluated in peripheral blood lymphocytes (PBLs) before, at the middle, and at the end of the therapy (approximately 0, 3, and 6 months) for mCRC patients before, at the end of the therapy, and after surgery for laRC patients.ResultsOverall, MNf demonstrated significant prognostic value since a decrease of MNf less than 29% between middle and initial MNf measurements can discriminate between progressive and stable/responsive disease with sensitivity of 36% and specificity of 87.0% while being able to identify responsive disease with sensitivity of 72.7% and specificity of 59.3%. On the other hand, TA presented a significant trend of increase (p = 0.07) in patients with progressive disease at the middle measurement.ConclusionsThe findings of this study suggest that the MN frequency may serve as a promising prognostic biomarker for the monitoring of the treatment response of patients with CRC, while TA should be evaluated in a larger group of patients to further validate its significance.

Abstract Background This study aims to present the feasibility of the open approach of hemilevator excision (HLE) as a promising alternative of the laparoscopic and/or robotic ones for the treatment of low rectal cancer extending to the ipsilateral puborectalis muscle. Methods A 60-year-old male patient with a high-grade differentiated rectal adenocarcinoma at the right side of the lower rectum invading puborectalis muscle. The proposed operation consists of a combination of extralevator abdomino-perineal excision (ELAPE), intersphicteric resection (ISR), and low anterior resection (LAR) since it resects the ipsilateral to tumor levator ani muscle (LAM) from its attachment at the internal obturator fascia and the deep part of ipsilateral external anal sphincter (EAS), while the distal part of dissection is completed in the intersphincteric space taking out the internal anal sphincter (IAS). At the contralateral side of the tumor, the dissection plane follows the classic route of LAR. Results Pathology proved the oncologic adequacy of resection. MRI at the fourth postoperative week showed clearly the right aspect of anorectal junction free of tumor. Anorectal manometry revealed a fair anorectal function which is in accordance with the findings of clinical assessment of patient after restoring large bowel continuity (post-op Wexner score, 7). Conclusion This is the first case of the open HLE that seems to be a good alternative compared to ELAPE or conventional APR, as it offers oncologic adequacy and a fair anorectal function.

Several studies have shown that patients with cystic fibrosis (CF), even at a young age, have pulmonary and cardiac abnormalities. The main complications are cardiac right ventricular (RV) systolic and/or diastolic dysfunction and pulmonary hypertension, which affects their prognosis. Exercise training (ET) is recommended in patients with CF as a therapeutic modality to improve physical fitness and health-related quality of life. However, questions remain regarding its optimal effective and safe dose and its effects on the patients’ cardiac function. The study aimed to provide a wearable activity tracker (WAT)-based ET to promote physical activity in CF patients and assess its effects on cardiac morphology and function. Forty-two stable CF individuals (aged 16.8 ± 3.6 years) were randomly assigned to either the intervention (Group A) or the control group (Group B). Group A participated in a 1-year WAT-based ET program three times per week. All patients underwent a 6-min walking test (6-MWT) and an echocardiographic assessment focused mainly on RV anatomy and function at the baseline and the end of the study. RV systolic function was evaluated by measuring the tricuspid annular plane systolic excursion (TAPSE), the systolic tricuspid annular velocity (TVS’), the RV free-wall longitudinal strain (RVFWSL), and the right ventricular four-chamber longitudinal strain (RV4CSL). RV diastolic function was assessed using early (TVE) and late (TVA) diastolic transtricuspid flow velocity and their ratio TVE/A. Pulmonary artery systolic pressure (PASP) was also estimated. In Group A after ET, the 6MWT distance improved by 20.6% (p < 0.05), TVA decreased by 17% (p < 0.05), and TVE/A increased by 13.2% (p < 0.05). Moreover, TAPSE, TVS’, RVFWSL, and RV4CSL increased by 8.3% (p < 0.05), 9.0% (p < 0.05), 13.7% (p < 0.05), and 26.7% (p < 0.05), respectively, while PASP decreased by 7.6% (p < 0.05). At the end of the study, there was a significant linear correlation between the number of steps and the PASP (r = −0.727, p < 0.01) as well as the indices of RV systolic function in Group A. In conclusion, WAT is a valuable tool for implementing an effective ET program in CF. Furthermore, ET has a positive effect on RV systolic and diastolic function.

As Cystic Fibrosis (CF) treatment advances, research evidence has highlighted the value and applicability of Lung Clearance Index and Cardiopulmonary Exercise Testing as endpoints for clinical trials. In the context of these new endpoints for CF trials, we have explored the use of these two test outcomes for routine CF care. In this review we have presented the use of these methods in assessing disease severity, disease progression, and the efficacy of new interventions with considerations for future research.

Frequent outbreaks of enterovirus A71 (EVA71) occur in the Asia-Pacific area, and these are closely associated with severe neurological symptoms in young children. No effective antiviral therapy is currently available for the treatment of EVA71 infection. The development of monoclonal antibodies (mAbs) has demonstrated promise as a novel therapy for the prevention and treatment of infectious diseases. Several medical conditions have been treated using bispecific or multi-specific antibodies that recognize two or more distinct epitopes simultaneously. However, bispecific or multi-specific antibodies often encounter protein expression and product stability problems. In this study, we developed an IgG-like bispecific antibody (E18-F1) comprising two anti-EVA71 antibodies: E18 mAb and llama-derived F1 single-domain antibody. E18-F1 was demonstrated to exhibit superior binding affinity and antiviral activity compared with E18 or F1. Additionally, E18-F1 not only improved survival rate, but also reduced clinical signs in human SCARB2 receptor (hSCARB2) transgenic mice challenged with a lethal dose of EVA71. Altogether, our results reveal that E18-F1 is a simple format bispecific antibody with promising antiviral activity for EVA71.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with a multifactorial etiology. A multitarget treatment that modulates multifaceted biological functions might be more effective than a single-target approach. Here, the therapeutic efficacy of combination treatment using anti-Aβ antibody NP106 and curcumin analog TML-6 versus monotherapy was investigated in an APP/PS1 mouse model of AD. Our data demonstrate that both combination treatment and monotherapy attenuated brain Aβ and improved the nesting behavioral deficit to varying degrees. Importantly, the combination treatment group had the lowest Aβ levels, and insoluble forms of Aβ were reduced most effectively. The nesting performance of APP/PS1 mice receiving combination treatment was better than that of other APP/PS1 groups. Further findings indicate that enhanced microglial Aβ phagocytosis and lower levels of proinflammatory cytokines were concurrent with the aforementioned effects of NP106 in combination with TML-6. Intriguingly, combination treatment also normalized the gut microbiota of APP/PS1 mice to levels resembling the wild-type control. Taken together, combination treatment outperformed NP106 or TML-6 monotherapy in ameliorating Aβ pathology and the nesting behavioral deficit in APP/PS1 mice. The superior effect might result from a more potent modulation of microglial function, cerebral inflammation, and the gut microbiota. This innovative treatment paradigm confers a new avenue to develop more efficacious AD treatments.

Mastic gum is a resinous sap produced by Pistacia lentiscus growing in the island of Chios (Greece) and has been recognized since Antiquity for its distinctive aroma as well as medical properties (antimicrobial, antioxidant, anti-inflammatory ones). The oral absorption of Chios Mastic gum (an insoluble polymer of poly-β-myrcene is among the most abundant contents) is poor due to its low water-solubility. We report in this study, two different Chios mastic gum extracts, the acidic mastic gum extract—AMGE—and the neutral one—NMGE, both prepared after removal of the contained polymer in order to ameliorate solubility and enhance in vivo activity. Liposomes are presented as a promising delivery system due to their physicochemical and biophysical properties to increase stability and absorption efficiency of the mastic gum extracts within the gastrointestinal (GI) tract. The aim of this study was to evaluate the stability in GI simulated conditions together with cytotoxic and antimicrobial activity of the two extracts (AMGE and NMGE) after encapsulation in a well characterized liposome formulation. Liposomes-AMGE complex showed an improved stability behavior in GI simulated conditions. Both assayed extracts showed significant dose dependent inhibition against the growth of liver cancer HepG2 cells and an interesting antimicrobial activity against several microorganisms. Conclusively, encapsulation could be evaluated as a beneficial procedure for further applications of mastic resin.

Productivity growth in the Canadian economy has been considerably slower in the post-2000 period than in the pre-2000 period, with important implications for the growth in the living standards of Canadians. Output per hour in the business sector in Canada advanced at a 0.9 per cent average annual rate from 2000 to 2016 compared to 1.6 per cent from 1981 to 2000. The objective of this article is to highlight the stylized facts of this important development. It first examines trends in both labour productivity and total factor productivity (TFP) at the aggregate level. It discusses growth accounting estimates of changes in the sources of labour productivity growth. Labour and total factor productivity estimates are provided for 15 industries, highlighting which industries experienced the largest slowdown in absolute terms and the industry contributions to the slowdown. Manufacturing is found to be the industry making the largest contribution to both the labour productivity and TFP slowdowns. Contributions of within-industry productivity growth and re-allocation effects to aggregate productivity growth are also examined.

The non-recurrent laryngeal nerve (nRLN) is a rare anatomic variation that every head and neck surgeon must be aware of, in order to avoid intraoperative injury which leads to postoperative morbidity. We are reporting a case of a nRLN in a 47 year old female patient with medullary thyroid carcinoma who was surgically treated with total thyroidectomy and lymph node dissection. Both two inferior laryngeal nerves were identified, fully exposed and preserved along their cervical courses. However, we found that the right inferior laryngeal nerve was non-recurrent and directly arised from the cervical vagal trunk, entered the larynx after a short transverse course and parallel to the inferior thyroid artery. The safety of thyroid operations is dependent on high index of suspicion, meticulous identification and dissection of laryngeal nerves either recurrent or non-recurrent. This leads to minimum risk of iatrogenic damage of the nerves. Complete knowledge of the anatomy of these neural structures, including all their anatomic variations is of paramount importance.

Background: Lipoblastoma is a rare, benign, fatty tissue tumor that occurs in infancy and early childhood. The most common tumor locations are the extremities and the torso. The location of this tumor in the chest wall and an intrathoracic extension is uncommon. Case report: We present a case of a 3-year-old boy with anterior chest wall lipoblastoma with an intrathoracic extension. Computed tomography was suggestive of lipoblastoma. The mass was completely excised through a right posterolateral thoracotomy. The histologic examination of the lesion confirmed the diagnosis of lipoblastoma. Conclusion: Although extremely rare, chest wall lipoblastoma should be included in the differential diagnosis of thoracic mass in childhood. Keywords: Lipoblastoma, Chest wall, Thoracic mass, Children

Increasing evidence suggests that elderly people with dementia are vulnerable to the development of severe coronavirus disease 2019 (COVID-19). In Alzheimer’s disease (AD), the major form of dementia, β-amyloid (Aβ) levels in the blood are increased; however, the impact of elevated Aβ levels on the progression of COVID-19 remains largely unknown. Here, our findings demonstrate that Aβ1-42, but not Aβ1-40, bound to various viral proteins with a preferentially high affinity for the spike protein S1 subunit (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the viral receptor, angiotensin-converting enzyme 2 (ACE2). These bindings were mainly through the C-terminal residues of Aβ1-42. Furthermore, Aβ1-42 strengthened the binding of the S1 of SARS-CoV-2 to ACE2 and increased the viral entry and production of IL-6 in a SARS-CoV-2 pseudovirus infection model. Intriguingly, data from a surrogate mouse model with intravenous inoculation of Aβ1-42 show that the clearance of Aβ1-42 in the blood was dampened in the presence of the extracellular domain of the spike protein trimers of SARS-CoV-2, whose effects can be prevented by a novel anti-Aβ antibody. In conclusion, these findings suggest that the binding of Aβ1-42 to the S1 of SARS-CoV-2 and ACE2 may have a negative impact on the course and severity of SARS-CoV-2 infection. Further investigations are warranted to elucidate the underlying mechanisms and examine whether reducing the level of Aβ1-42 in the blood is beneficial to the fight against COVID-19 and AD.

Background: The role of cardiopulmonary exercise testing (CPET) in the assessment of prognosis in CF (cystic fibrosis) is crucial. However, as the overall survival of the disease becomes better, the need for examinations that can predict pulmonary exacerbations (PEx) and subsequent deterioration becomes evident. Methods: Data from a 10-year follow up with CPET and spirometry of CF patients were used to evaluate whether CPET-derived parameters can be used as prognostic indexes for pulmonary exacerbations in patients with CF. Pulmonary exacerbations were recorded. We used a survival analysis through Cox Regression to assess the prognostic role of CPET parameters for PeX. CPET parameters and other variables such as sputum culture, age, and spirometry measurements were tested via multivariate cox models. Results: During a 10-year period (2009–2019), 78 CF patients underwent CPET. Cox regression analysis revealed that VO2peak% (peak Oxygen Uptake predicted %) predicted (hazard ratio (HR), 0.988 (0.975, 1.000) p = 0.042) and PetCO2 (end-tidal CO2 at peak exercise) (HR 0.948 (0.913, 0.984) p = 0.005), while VE/VO2 and (respiratory equivalent for oxygen at peak exercise) (HR 1.032 (1.003, 1.062) p = 0.033) were significant predictors of pulmonary exacerbations in the short term after the CPET. Additionally, patients with VO2peak% predicted 2peak

This work describes the Diels–Alder reaction of the naturally occurring substituted butadiene, myrcene, with a range of different naturally occurring and synthetic dienophiles. The synthesis of the Diels–Alder adduct from myrcene and acrylic acid, containing surfactant properties, was scaled-up in a plate-type continuous-flow reactor with a volume of 105 mL to a throughput of 2.79 kg of the final product per day. This continuous-flow approach provides a facile alternative scale-up route to conventional batch processing, and it helps to intensify the synthesis protocol by applying higher reaction temperatures and shorter reaction times.

In this data article, the potential role of p53 tumor suppressor gene (p53) on the attachment ability of MCF-7 breast cancer cells was investigated. In our main article, “IGF-I/ EGF and E2 signaling crosstalk through IGF-IR conduit point affect breast cancer cell adhesion” (K. Voudouri, D. Nikitovic, A. Berdiaki, D. Kletsas, N.K. Karamanos, G.N. Tzanakakis, 2016) [1], we describe the key role of IGF-IR in breast cancer cell adhesion onto fibronectin (FN). p53 tumor suppressor gene is a principal regulator of cancer cell proliferation. Various data have demonstrated an association between p53 and IGF-IR actions on cell growth through its’ putative regulation of IGF-IR expression. According to our performed experiments, p53 does not modify IGF-IR expression and does not affect basal MCF-7 cells adhesion onto FN. Moreover, technical details about the performance of adhesion assay onto the FN substrate were provided.

Introduction. Cardio-Pulmonary Exercise Testing (CPET) has been recognized as a valuable method in assessing disease burden and exercise capacity among CF patients. Aim. To evaluate whether Pseudomonas aeruginosa colonization status affects Exercise Capacity, LCI and High-Resolution Computed Tomography (HRCT) indices among patients with CF; to check if Pseudomonas colonization can predict exercise intolerance. Subjects. Seventy-eight (78) children and adults with CF (31 males) mean (range) age 17.08 (6.75; 24.25) performed spirometry, Multiple Breath Washout (MBW) and CPET along with HRCT on the same day during their admission or follow up visit. Results. 78 CF patients (mean FEV1: 83.3% mean LCI: 10.9 and mean VO2 peak: 79.1%) were evaluated: 33 were chronically colonized with Pseudomonas aeruginosa, 24 were intermittently colonized whereas 21 were Pseudomonas free. Statistically significant differences were observed among the three groups in: peak oxygen uptake % predicted (VO2 peak% (p

In this paper, a novel method to modify color images for the protanopia and deuteranopia color vision deficiencies is proposed. The method admits certain criteria, such as preserving image naturalness and color contrast enhancement. Four modules are employed in the process. First, fuzzy clustering-based color segmentation extracts key colors (which are the cluster centers) of the input image. Second, the key colors are mapped onto the CIE 1931 chromaticity diagram. Then, using the concept of confusion line (i.e., loci of colors confused by the color-blind), a sophisticated mechanism translates (i.e., removes) key colors lying on the same confusion line to different confusion lines so that they can be discriminated by the color-blind. In the third module, the key colors are further adapted by optimizing a regularized objective function that combines the aforementioned criteria. Fourth, the recolored image is obtained by color transfer that involves the adapted key colors and the associated fuzzy clusters. Three related methods are compared with the proposed one, using two performance indices, and evaluated by several experiments over 195 natural images and six digitized art paintings. The main outcomes of the comparative analysis are as follows. (a) Quantitative evaluation based on nonparametric statistical analysis is conducted by comparing the proposed method to each one of the other three methods for protanopia and deuteranopia, and for each index. In most of the comparisons, the Bonferroni adjusted p-values are

Obesity is defined as abnormal or excessive fat accumulation that presents a risk to health. The ability to exercise is affected by adiposity, and this mechanism involves low-grade chronic inflammation and homeostatic stress produced mainly in adipocytes, which can result in abnormal adipokine secretion. To date, the gold standard for cardiorespiratory fitness assessment is considered to be the maximum oxygen uptake (VO2max). The aim of the present study was to assess the prognostic value of hematological parameters of childhood obesity, as potential predictors of cardiorespiratory fitness (VO2max), using a sample of children and adolescents with obesity and risk for diabetes. A total of 84 clinically healthy children and adolescents were recruited, of which 21 were considered lean, 22 overweight and 41 obese, with a mean age of 12.0 ± 1.9, 11.4 ± 2.0, and 11.2 ± 2.1 years old, in each weight status category, respectively. Age and sex did not differ between groups. Hematologic testing was performed after 12 h of fasting including glucose, serum lipids, insulin, hc-CRP, adiponectin, leptin and fibrinogen levels. Cardiorespiratory capacity for exercise was assessed to determine VO2max, using a cycle ergometer. The VO2max was negatively correlated with progressive strength to the BMIz (−0.656, p ≤ 0.001), hs-CRP (r = −0.341, p ≤ 0.002), glucose (r = −0.404, p ≤ 0.001) and insulin levels (r = −0.348, p ≤ 0.001), the homeostasis model assessment of insulin resistance (HOMA-IR) (r = −0.345, p ≤ 0.002), as well as to the leptin (r = −0.639, p ≤ 0.001) and fibrinogen concentrations (r = −0.520, p ≤ 0.001). The multivariate analysis revealed that only leptin and fibrinogen concentrations could predict the VO2max adjusted for the BMIz of participants. The receiver operating characteristic (ROC) curve for the diagnostic accuracy of leptin, hs-CRP and fibrinogen concentrations for the prediction of VO2max revealed a good diagnostic ability for all parameters, with leptin being the most promising one (area under the curve (AUC): 99%). The results verify that in children with obesity, VO2max may be predicted from hematological parameters (leptin and fibrinogen), possibly bypassing more invasive methods.

The present work focuses on the in-silico investigation of the steady-state blood flow in straight microtubes, incorporating advanced constitutive modeling for human blood and blood plasma. The blood constitutive model accounts for the interplay between thixotropy and elasto-visco-plasticity via a scalar variable that describes the level of the local blood structure at any instance. The constitutive model is enhanced by the non-Newtonian modeling of the plasma phase, which features bulk viscoelasticity. Incorporating microcirculation phenomena such as the cell-free layer (CFL) formation or the Fåhraeus and the Fåhraeus-Lindqvist effects is an indispensable part of the blood flow investigation. The coupling between them and the momentum balance is achieved through correlations based on experimental observations. Notably, we propose a new simplified form for the dependence of the apparent viscosity on the hematocrit that predicts the CFL thickness correctly. Our investigation focuses on the impact of the microtube diameter and the pressure-gradient on velocity profiles, normal and shear viscoelastic stresses, and thixotropic properties. We demonstrate the microstructural configuration of blood in steady-state conditions, revealing that blood is highly aggregated in narrow tubes, promoting a flat velocity profile. Additionally, the proper accounting of the CFL thickness shows that for narrow microtubes, the reduction of discharged hematocrit is significant, which in some cases is up to 70%. At high pressure-gradients, the plasmatic proteins in both regions are extended in the flow direction, developing large axial normal stresses, which are more significant in the core region. We also provide normal stress predictions at both the blood/plasma interface (INS) and the tube wall (WNS), which are difficult to measure experimentally. Both decrease with the tube radius; however, they exhibit significant differences in magnitude and type of variation. INS varies linearly from 4.5 to 2 Pa, while WNS exhibits an exponential decrease taking values from 50 mPa to zero.

This work focuses on the advanced modeling of the thixotropic nature of blood, coupled with an elasto-visco-plastic formulation by invoking a consistent and validated model for TEVP materials. The proposed model has been verified for the adequate description of the rheological behavior of suspensions, introducing a scalar variable that describes dynamically the level of internal microstructure of rouleaux at any instance, capturing accurately the aggregation and disaggregation mechanisms of the RBCs. Also, a non-linear fitting is adopted for the definition of the model’s parameters on limited available experimental data of steady and transient rheometric flows of blood samples. We present the predictability of the new model in various steady and transient rheometric flows, including startup shear, rectangular shear steps, shear cessation, triangular shear steps and LAOS tests. Our model provides predictions for the elasto-thixotropic mechanism in startup shear flows, demonstrating a non-monotonic relationship of the thixotropic index on the shear-rate. The intermittent shear step test reveals the dynamics of the structural reconstruction, which in turn is associated with the aggregation process. Moreover, our model offers robust predictions for less examined tests such as uniaxial elongation, in which normal stress was found to have considerable contribution. Apart from the integrated modeling of blood rheological complexity, our implementation is adequate for multi-dimensional simulations due to its tensorial formalism accomplished with a single time scale for the thixotropic effects, resulting in a low computational cost compared to other TEVP models.

Novel targeted treatments for Cystic Fibrosis give rise to new hope for an ever-growing number of CF patients with various mutations. However, very little evidence and guidelines exist to steer clinical decisions regarding patients whose illness takes an unexpected course. In such cases, the benefits and risks of discontinuing these treatments must be carefully and individually weighed, since their long-term effects remain mainly uncharted territory. In this report we document the case of a homozygous F508del CF patient with severe lung disease who presented with a pulmonary exacerbation shortly after the beginning of treatment with lumacaftor/ivacaftor and the complicated initial phase of therapy, which was followed by significant improvements.

[This corrects the article DOI: 10.1371/journal.pone.0188564.].

The molecular techniques (C-PCR, RT-PCR) in the detection and quantification of allergic substances of hazelnut in various categories of food commodities, e.g. breakfast cereals, chocolates and biscuits, frequently involved in allergic outbreaks was implemented. For the detection of hazelnut a gene coding the major allergenic protein Cor a1 was selected. In some instances, the presence of hazelnuts is not declared on the label and the products may carry no warning for potentially allergenic substances, usually referred to as "traces". A total of 150 samples were collected from local supermarkets and analysed for the purpose of the study. From these, a total of 38 (25.3%) specimens contained hazelnut, 30 (20.0%) contained "traces" of hazelnut, 26 (17.3%) contained a label warning for the possible presence of "traces" of allergenic substances, and 56 (37.3%) specimens contained no food allergy labels. Among them, using the C-PCR, 36 (94.7%), 10 (33.3%), 5 (19.2%), and 5 (8.9%) specimens were detected as positive, respectively. Using the RT-PCR, 38 (100%), 15 (50%), 7 (26.9%) and 8 (14.3%) specimens were detected as positive, respectively. Finally, by combining both methods, 38 (100%), 17 (56.7%), 9 (34.6%), and 10 (17.9%) specimens were identified as positive, respectively.