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Abstract Cassava brown streak disease (CBSD) caused by Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV) is the most economically important viral disease of cassava. As cassava is a vegetatively propagated crop, the development of rapid and sensitive diagnostics would aid in the identification of virus-free planting material and development of effective management strategies. In this study, a rapid, specific and sensitive real-time reverse transcription recombinase polymerase amplification (RT-RPA) assay was developed for real-time detection of CBSV and UCBSV. The RT-RPA was able to detect as little as 2 pg/µl of purified RNA obtained from infected cassava leaves, a sensitivity equivalent to that obtained by quantitative real-time reverse transcription PCR (qRT-PCR), within 20 min at 37 °C. Further, the RT-RPA detected each target virus directly from crude leaf and stem extracts, avoiding the tedious and costly isolation of high-quality RNA. The developed RT-RPA assay provides a valuable diagnostic tool that can be adopted by cassava seed certification and virus resistance breeding programs to ensure distribution of virus-free cassava planting materials to farmers. This is the first report on the development and validation of crude sap-based RT-RPA assay for the detection of cassava brown streak viruses (UCBSV and CBSV) infection in cassava plants.

Abstract Phthorimaea absoluta is a global constraint to tomato production and can cause up to 100% yield loss. Farmers heavily rely on synthetic pesticides to manage this pest. However, these pesticides are detrimental to human, animal, and environmental health. Therefore, exploring eco-friendly, sustainable Integrated Pest Management approaches, including biopesticides as potential alternatives, is of paramount importance. In this context, the present study (i) evaluated the efficacy of 10 Bacillus thuringiensis isolates, neem, garlic, and fenugreek; (ii) assessed the interactions between the most potent plant extracts and B. thuringiensis isolates, and (iii) evaluated the gut microbial diversity due to the treatments for the development of novel formulations against P. absoluta. Neem recorded the highest mortality of 93.79 ± 3.12% with an LT50 value of 1.21 ± 0.24 days, Bt HD263 induced 91.3 ± 3.68% mortality with LT50 of 2.63 ± 0.11 days, compared to both Bt 43 and fenugreek that caused

Introduction and Objectives: Liver transplantation can be a curative treatment for patients with hepatocellular carcinoma (HCC); however, the morbidity and mortality associated with HCC varies by socioeconomic status and race and ethnicity. Policies like Share 35 were implemented to ensure equitable access to organ transplants; however, their impacts are unclear. We aimed to characterize differences in post-liver transplant (LT) survival among patients with HCC, when considering race and ethnicity, income, and insurance type, and understand if these associations were impacted by Share 35. Materials and Methods: We conducted a retrospective cohort study of 30,610 adult LT recipients with HCC. Data were obtained from the UNOS database. Survival analysis was carried out using Kaplan-Meier curves, and multivariate Cox regression analysis was used to calculate hazard ratios. Results: Men (HR: 0.90 (95% CI: 0.85-0.95)), private insurance (HR: 0.91 (95% CI: 0.87-0.92)), and income (HR: 0.87 (95% CI: 0.83-0.92)) corresponded with higher post-LT survival, when adjusted for over 20 demographic and clinical characteristics (Table 2). African American or Black individuals were associated with lower post-LT survival (HR: 1.20 (95% CI: 1.12-1.28)), whereas. Asian (HR: 0.79 (95% CI: 0.71-0.88)) or Hispanic (HR: 0.86 (95% CI: 0.81-0.92)) individuals were associated with higher survival as compared with White individuals (Table 2). Many of these patterns held in the pre-Share 35 and Share 35 periods. Conclusions: Racial, ethnic, and socioeconomic disparities at time of transplant, such as private insurance and income, influence post-LT survival in patients with HCC. These patterns persist despite the passage of equitable access policies, such as Share 35.

The ability to recognize and associate objects with prior experiences has been demonstrated in several avian taxa. Corvids, for example, recognize visual stimuli associated with negative previous experiences and will modify their behavioral responses according to the level of perceived threat. However, the extent to which similar memory-based behaviors exist in seabirds is poorly understood. Our study investigated object recognition by Herring Gulls ( Larus argentatus smithsonianus ) on their breeding grounds, the site of a long-term monitoring project. When handling gulls and conducting field research, researchers wear standard bicycle helmets as a protective measure against physical aggression by nesting gulls. We tested whether previously banded gulls vary their behavioral responses based on the headgear worn by human researchers. Herring Gulls were significantly more aggressive when approached by helmeted observers compared to those wearing neutral headwear or even holding a helmet, thus indicating a potential association between wearing bike helmets and the negative experience with researchers. Our study demonstrates that Herring Gulls are capable of object memory and object recognition within context, and display different behaviors toward different objects according to their levels of perceived threat. This information is key when designing studies with nesting gulls to ensure that behavioral biases are not unintentionally created due to gull prior experiences or researcher safety gear.

Naphthoquinones are important natural or synthetic compounds belonging to the general class of quinones. Many compounds in this class have become drugs that are on the pharmaceutical market for the treatment of various diseases. A special naphthoquinone derivative is menadione, a synthetic naphthoquinone belonging to the vitamin K group. This compound can be synthesized by different methods and it has a broad range of biological and synthetic applications, which will be highlighted in this review.

Commencing in December 2019 with the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), three years of the coronavirus disease 2019 (COVID-19) pandemic have transpired. The virus has consistently demonstrated a tendency for evolutionary adaptation, resulting in mutations that impact both immune evasion and transmissibility. This ongoing process has led to successive waves of infections. This study offers a comprehensive assessment spanning genetic, phylogenetic, phylodynamic, and phylogeographic dimensions, focused on the trajectory of the SARS-CoV-2 epidemic in Cyprus. Based on a dataset comprising 4700 viral genomic sequences obtained from affected individuals between October 2021 and October 2022, our analysis is presented. Over this timeframe, a total of 167 distinct lineages and sublineages emerged, including variants such as Delta and Omicron (1, 2, and 5). Notably, during the fifth wave of infections, Omicron subvariants 1 and 2 gained prominence, followed by the ascendancy of Omicron 5 in the subsequent sixth wave. Additionally, during the fifth wave (December 2021–January 2022), a unique set of Delta sequences with genetic mutations associated with Omicron variant 1, dubbed “Deltacron”, was identified. The emergence of this phenomenon initially evoked skepticism, characterized by concerns primarily centered around contamination or coinfection as plausible etiological contributors. These hypotheses were predominantly disseminated through unsubstantiated assertions within the realms of social and mass media, lacking concurrent scientific evidence to validate their claims. Nevertheless, the exhaustive molecular analyses presented in this study have demonstrated that such occurrences would likely lead to a frameshift mutation—a genetic aberration conspicuously absent in our provided sequences. This substantiates the accuracy of our initial assertion while refuting contamination or coinfection as potential etiologies. Comparable observations on a global scale dispelled doubt, eventually leading to the recognition of Delta-Omicron variants by the scientific community and their subsequent monitoring by the World Health Organization (WHO). As our investigation delved deeper into the intricate dynamics of the SARS-CoV-2 epidemic in Cyprus, a discernible pattern emerged, highlighting the major role of international connections in shaping the virus’s local trajectory. Notably, the United States and the United Kingdom were the central conduits governing the entry and exit of the virus to and from Cyprus. Moreover, notable migratory routes included nations such as Greece, South Korea, France, Germany, Brazil, Spain, Australia, Denmark, Sweden, and Italy. These empirical findings underscore that the spread of SARS-CoV-2 within Cyprus was markedly influenced by the influx of new, highly transmissible variants, triggering successive waves of infection. This investigation elucidates the emergence of new waves of infection subsequent to the advent of highly contagious and transmissible viral variants, notably characterized by an abundance of mutations localized within the spike protein. Notably, this discovery decisively contradicts the hitherto hypothesis of seasonal fluctuations in the virus’s epidemiological dynamics. This study emphasizes the importance of meticulously examining molecular genetics alongside virus migration patterns within a specific region. Past experiences also emphasize the substantial evolutionary potential of viruses such as SARS-CoV-2, underscoring the need for sustained vigilance. However, as the pandemic’s dynamics continue to evolve, a balanced approach between caution and resilience becomes paramount. This ethos encourages an approach founded on informed prudence and self-preservation, guided by public health authorities, rather than enduring apprehension. Such an approach empowers societies to adapt and progress, fostering a poised confidence rooted in well-founded adaptation.

Adaptable hydrogels have been used in the biomedical field to address several pathologies, especially those regarding tissue defects. Here, we describe unprecedented catechol-like functionalized polyrotaxane (PR) polymers able to form hydrogels. PR were functionalized with the incorporation of hydroxypyridinone (HOPO) moieties into the polymer backbone, with a degree of substitution from 4 to 22%, depending on the PR type. The hydrogels form through the functionalized supramolecular systems when in contact with a Fe(III) solution. Despite the hydrogel formation being at physiological pH (7.4), the HOPO derivatives are extremely resistant to oxidation, unlike common catechols; consequently, they prevent the formation of quinones, which can lead to irreversible bounds within the matrix. The resulting hydrogels demonstrated properties lead to unique hydrogels with improved mechanical behavior obtained by metallic coordination crosslinking, due to the synergies of the sliding-ring PR and the non-covalent (reversible) catechol analogues. Following this strategy, we successfully developed innovative, cytocompatible, oxidative-resistant, and reversible crosslinked hydrogels, with the potential of being used as structural self-materials for a variety of applications, including in the biomedical field.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in December 2019 resulted in the coronavirus disease 2019 (COVID-19) pandemic, which has had devastating repercussions for public health. Over the course of this pandemic, the virus has continuously been evolving, resulting in new, more infectious variants that have frequently led to surges of new SARS-CoV-2 infections. In the present study, we performed detailed genetic, phylogenetic, phylodynamic and phylogeographic analyses to examine the SARS-CoV-2 epidemic in Cyprus using 2352 SARS-CoV-2 sequences from infected individuals in Cyprus during November 2020 to October 2021. During this period, a total of 61 different lineages and sublineages were identified, with most falling into three groups: B.1.258 & sublineages, Alpha (B.1.1.7 & Q. sublineages), and Delta (B.1.617.2 & AY. sublineages), each encompassing a set of S gene mutations that primarily confer increased transmissibility as well as immune evasion. Specifically, these lineages were coupled with surges of new infections in Cyprus, resulting in the following: the second wave of SARS-CoV-2 infections in Cyprus, comprising B.1.258 & sublineages, during late autumn 2020/beginning of winter 2021; the third wave, comprising Alpha (B.1.1.7 & Q. sublineages), during spring 2021; and the fourth wave, comprising Delta (B.1.617.2 & AY. sublineages) during summer 2021. Additionally, it was identified that these lineages were primarily imported from and exported to the UK, Greece, and Sweden; many other migration links were also identified, including Switzerland, Denmark, Russia, and Germany. Taken together, the results of this study indicate that the SARS-CoV-2 epidemic in Cyprus was characterized by successive introduction of new lineages from a plethora of countries, resulting in the generation of waves of infection. Overall, this study highlights the importance of investigating the spatiotemporal evolution of the SARS-CoV-2 epidemic in the context of Cyprus, as well as the impact of protective measures placed to mitigate transmission of the virus, providing necessary information to safeguard public health.

Background: Survival following liver transplant (LT) is influenced by a variety of factors, including donor risk factors and recipient disease burden and co-morbidities. It is difficult to separate these effects from those of socioeconomic factors, such as income or insurance. The United Network for Organ Sharing (UNOS) created equitable access policies, such as Share 35, to ensure that organs are distributed to individuals with greatest medical need; however, the effect of Share 35 on disparities in post-LT survival is not clear. This study aimed to (1) characterize associations between post-transplant survival and race and ethnicity, income, insurance, and citizenship status, when adjusted for other clinical and demographic factors that may influence survival, and (2) determine if the direction of associations changed after Share 35. Methods: A retrospective, cohort study of adult LT recipients (n = 83,254) from the UNOS database from 2005 to 2019 was conducted. Kaplan-Meier survival graphs and stepwise multivariate cox-regression analyses were performed to characterize the effects of socioeconomic status on post-LT survival, adjusted for recipient and donor characteristics, across the time period and after Share 35. Findings: Male sex (HR: 0.93 (95% CI: 0.90–0.96)), private insurance (0.91 (0.88–0.94)), income (0.82 (0.79–0.85)), U.S. citizenship, and Asian (0.81 (0.75–0.88)) or Hispanic (0.82 (0.79–0.86)) race and ethnicity were associated with higher post-transplant survival, after adjustment for clinical and demographic factors (Table 3). These associations were found across the entire time period studied and many persisted after the implementation of Share 35 in 2013 (Table 3; male sex (0.84 (0.79–0.90)), private insurance (0.94 (0.89–1.00)), income (0.82 (0.77–0.89)), and Asian (0.87 (0.73–1.02)) or Hispanic (0.88 (0.81–0.96)) race and ethnicity). Interpretation: Recipients’ socioeconomic factors at time of transplant may impact long-term post-transplant survival, and a single policy may not significantly alter these structural health inequalities. Funding: None

Cassava roots, millet and cowpea leaves have short storage life thus the need for simple post-harvest handling and storage protocol to ensure prolonged availability to fully contribute toward food and nutrition security, a major challenge within Sub-Saharan Africa. The current study sought to investigate the effect of pre-treatment and processing on cyanide safety and nutrition composition of cassava roots, millet and cowpea leaves flours. The study used three popular cassava varieties grown along the Kenyan coast, cowpea leaves (M66) grown as vegetable and pearl millet. The study used analytical techniques as guided by AOAC standard methods, to determine the nutritional composition of the individual crops while subjecting them to pre-treatment processes (blanching, peeling, washing, drying, and fermentation) and optimizing for maximum nutrient composition. The cyanide content ranged 7.8–9.5, 3.4–5.0, and 2.2–2.8 ppb for raw, untreated, and fermented cassava flours, respectively. The carbohydrates content was in the range of 35–37, 81.73–83.49, and 70.28–71.20% for raw cowpea leaves, cassava roots, and millet, respectively; the carbohydrate content for untreated flours was in the range of 35.68–35.19, 66.07–83.49, and 66.07–68.89% for cowpea leaves, cassava roots, and millet, respectively; the carbohydrate content for the fermented flours was in the range of 29.06–28.01, 79.68–84.36, and 69.08–70.12% for cowpea leaves, cassava roots, and millet, respectively. The protein content was in the range of 25.69–26.01, 1.2–18, and 11.1–13.3% for untreated cowpea, cassava, and millet flours, respectively; fermented flours protein content was in the range of 25.7–29.3, 1.3–2.2, and 8.5–11.1% cowpea, cassava, and millet flours, respectively. Iron and zinc contents were in the range of 4.31–9.04, 1.0–1.3; 7.98–7.89, 1.21–1.25; 6.58–8.23, 0.99–1.22 (mg/100 g dwb) for raw, untreated, and fermented cowpea flours, respectively. Pre-treatment had significant effects (P ≤ 0.05) on cyanide content and nutritional composition of each of the flours. Farmers should be trained to utilize such simple processing techniques.

Background Despite wide usage across all areas of medicine, it is uncertain how useful standard reference ranges of laboratory values are for critically ill patients.Objectives The aim of this study is to assess the distributions of standard laboratory measurements in more than 330 selected intensive care units (ICUs) across the USA, Amsterdam, Beijing and Tarragona; compare differences and similarities across different geographical locations and evaluate how they may be associated with differences in length of stay (LOS) and mortality in the ICU.Methods A multi-centre, retrospective, cross-sectional study of data from five databases for adult patients first admitted to an ICU between 2001 and 2019 was conducted. The included databases contained patient-level data regarding demographics, interventions, clinical outcomes and laboratory results. Kernel density estimation functions were applied to the distributions of laboratory tests, and the overlapping coefficient and Cohen standardised mean difference were used to quantify differences in these distributions.Results The 259 382 patients studied across five databases in four countries showed a high degree of heterogeneity with regard to demographics, case mix, interventions and outcomes. A high level of divergence in the studied laboratory results (creatinine, haemoglobin, lactate, sodium) from the locally used reference ranges was observed, even when stratified by outcome.Conclusion Standardised reference ranges have limited relevance to ICU patients across a range of geographies. The development of context-specific reference ranges, especially as it relates to clinical outcomes like LOS and mortality, may be more useful to clinicians.

In East Africa, passion fruit woodiness disease is caused by potyviruses, among which are Cowpea Aphid-Borne Mosaic Virus (CABMV) and Uganda Passiflora Virus (UPV). Previous studies suggest that synergistic interaction of viruses causes mild or severe outcomes of the disease. However, mixed infections of these viruses have not been documented. The aim of this study was to determine the effects of the interaction between two CABMV isolates causing passion fruit woodiness disease in Kenya. Healthy plants were mechanically inoculated at six-leaf stage. Four treatments were used: CABMV isolate 1, CABMV isolate 2, mixture of the two isolates, and noninoculated control. The test plants were maintained in a screen house, and data on symptom severity and rate of disease development were recorded. ELISA test was conducted to confirm virus presence and distribution. The results indicate that the CABMV isolates used are systemic. There were various differences in disease progression, which was faster in the sweet passion variety than in the purple variety. However, the latter had a higher disease severity. Coinfected plants expressed severe symptoms compared to the singly infected ones, indicating synergistic interaction between the viral isolates. This implies that coinfection has adverse impact resulting in higher economic losses.

Neurodevelopmental disorders: Translating genomic advances into clinical practice The identification of genetic mutations associated with neurodevelopmental disorders (NDDs) along with routine diagnosis based on patients’ characteristics is aiding the delivery of personalized therapies. Dora Tarlungeanu and Gaia Novarino at the Institute of Science and Technology in Klosterneuburg, Austria, review recent advances in genetic technologies, such as whole exome sequencing, that can lead to early intervention, guide choice of treatment and prompt genetic counseling. Introducing the mutations associated with NDDs into model organisms or stem cells is revealing some of the mechanisms underlying NDDs and enabling the evaluation of novel therapeutic strategies that target core symptoms of the disorders. To accelerate the implementation of individualized treatments for NDD the authors highlight the need to adopt interdisciplinary research approaches and to keep clinical staff updated on the latest findings in NDD genetics.

Abstract Since HIV-1 treatment is increasingly considered an effective preventionstrategy, it is important to study local HIV-1 epidemics to formulate tailored preventionpolicies. The prevalence of HIV-1 in Cyprus was historically low until 2005. To investigatethe shift in epidemiological trends, we studied the transmission dynamics of HIV-1 in Cyprususing a densely sampled Cypriot HIV-1 transmission cohort that included 85 percent ofHIV-1-infected individuals linked to clinical care between 1986 and 2012 based on detailedclinical, epidemiological, behavioral and HIV-1 genetic information. Subtyping andtransmission cluster reconstruction were performed using maximum likelihood and Bayesianmethods, and the transmission chain network was linked to the clinical, epidemiological andbehavioral data. The results reveal that for the main HIV-1 subtype A1 and B sub-epidemics,young and drug-naïve HIV-1-infected individuals in Cyprus are driving the dynamics of thelocal HIV-1 epidemic. The results of this study provide a better understanding of thedynamics of the HIV-1 infection in Cyprus, which may impact the development of preventionstrategies. Furthermore, this methodology for analyzing densely sampled transmissiondynamics is applicable to other geographic regions to implement effective HIV-1 preventionstrategies in local settings.

Emerging infectious viruses have led to global advances in the development of specific and sensitive detection techniques. Viruses have an inherent potential to easily mutate, presenting major hurdles for diagnostics and requiring methods capable of detecting genetically diverse viral strains. One such infectious agent is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in December 2019 and has resulted in the global coronavirus disease 2019 (COVID-19) pandemic. This study presents a real-time reverse transcription PCR (RT-PCR) detection assay for SARS-CoV-2, taking into account its intrinsic polymorphic nature that arises due to genetic drift and recombination, as well as the possibility of continuous and multiple introductions of genetically nonidentical strains into the human population. This advance was achieved by using mismatch-tolerant molecular beacons designed to specifically detect the SARS-CoV-2 S, E, M, and N genes. These were applied to create a simple and reproducible real-time RT-PCR assay, which was validated using external quality control panels (QCMD: CVOP20, WHO: SARS-CoV-2-EQAP-01) and clinical samples. This assay was designed for high target detection accuracy and specificity and can also be readily adapted for the detection of other emerging and rapidly mutating pathogens.

The whitefly, Bemisia tabaci (Gennadium, Hemiptera) has been reported to transmit viruses that cause cassava mosaic disease (CMD) and cassava brown streak disease (CBSD) in many parts of sub-Saharan Africa (SSA). Currently, there is limited information on the distribution, species and haplotype composition of the whitefly populations colonizing cassava in Kenya. A study was conducted in the major cassava growing regions of Kenya to address this gap. Analyses of mitochondrial DNA cytochrome oxidase 1 (mtCO1) sequences revealed the presence of four distinct whitefly species: Bemisia tabaci, Bemisia afer, Aleurodicus dispersus and Paraleyrodes bondari in Kenya. The B. tabaci haplotypes were further resolved into SSA1, SSA2 and Indian Ocean (IO) putative species. The SSA1 population had three haplogroups of SSA1-SG1, SSA-SG2 and SSA1-SG3. Application of KASP genotyping grouped the Bemisia tabaci into two haplogroups namely sub-Saharan Africa East and Southern Africa (SSA-ESA) and sub-Saharan Africa East and Central Africa (SSA-ECA). The study presents the first report of P. bondari (Bondar’s nesting whitefly) on cassava in Kenya. Bemisia tabaci was widely distributed in all the major cassava growing regions in Kenya. The increased detection of different whitefly species on cassava and genetically diverse B. tabaci mitotypes indicates a significant influence on the dynamics of cassava virus epidemics in the field. The study highlights the need for continuous monitoring of invasive whitefly species population on cassava for timely application of management practices to reduce the impact of cassava viral diseases and prevent potential yield losses.

The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in an extraordinary global public health crisis. In early 2020, Cyprus, among other European countries, was affected by the SARS-CoV-2 epidemic and adopted lockdown measures in March 2020 to limit the initial outbreak on the island. In this study, we performed a comprehensive retrospective molecular epidemiological analysis (genetic, phylogenetic, phylodynamic and phylogeographic analyses) of SARS-CoV-2 isolates in Cyprus from April 2020 to January 2021, covering the first ten months of the SARS-CoV-2 infection epidemic on the island. The primary aim of this study was to assess the transmissibility of SARS-CoV-2 lineages in Cyprus. Whole SARS-CoV-2 genomic sequences were generated from 596 clinical samples (nasopharyngeal swabs) obtained from community-based diagnostic testing centers and hospitalized patients. The phylogenetic analyses revealed a total of 34 different lineages in Cyprus, with B.1.258, B.1.1.29, B.1.177, B.1.2, B.1 and B.1.1.7 (designated a Variant of Concern 202012/01, VOC) being the most prevalent lineages on the island during the study period. Phylodynamic analysis showed a highly dynamic epidemic of SARS-CoV-2 infection, with three consecutive surges characterized by specific lineages (B.1.1.29 from April to June 2020; B.1.258 from September 2020 to January 2021; and B.1.1.7 from December 2020 to January 2021). Genetic analysis of whole SARS-CoV-2 genomic sequences of the aforementioned lineages revealed the presence of mutations within the S protein (L18F, ΔH69/V70, S898F, ΔY144, S162G, A222V, N439K, N501Y, A570D, D614G, P681H, S982A and D1118H) that confer higher transmissibility and/or antibody escape (immune evasion) upon the virus. Phylogeographic analysis indicated that the majority of imports and exports were to and from the United Kingdom (UK), although many other regions/countries were identified (southeastern Asia, southern Europe, eastern Europe, Germany, Italy, Brazil, Chile, the USA, Denmark, the Czech Republic, Slovenia, Finland, Switzerland and Pakistan). Taken together, these findings demonstrate that the SARS-CoV-2 infection epidemic in Cyprus is being maintained by a continuous influx of lineages from many countries, resulting in the establishment of an ever-evolving and polyphyletic virus on the island.

Background and Purpose: Variability in transcranial Doppler (TCD) detection of embolic signals (ES) is important for risk stratification. We tested the effect of time of day on ES associated with 60–99% asymptomatic carotid stenosis.Materials and Methods: Subjects were from the Asymptomatic Carotid Stenosis Embolus Detection (ASED) Study such that half were previously ES-positive and half ES-negative with 6-monthly 60-min TCD monitoring. All underwent bilateral TCD monitoring for two 12-h sessions separated by 24 h. ES detection rates were calculated using 6 and 4-h intervals from midnight and effective TCD monitoring time.Results: Ten subjects (8 male, mean age 79.5 years) were monitored. Over 24 h, 5/10 study arteries with 60–99% asymptomatic carotid stenosis were ES-positive (range 1–28 ES/artery, 56 total ES from 177.9 total effective monitoring hours). The remaining five study arteries and all eight successfully monitored contralateral arteries were ES-negative. Using 6-h intervals the mean ES detection rate peaked at 0600-midday (0.64/h) and was lowest 1800-midnight (0.09/h) with an incidence rate ratio of 7.26 (95% CI 2.52–28.64, P ≤ 0.001). Using 4-h intervals the mean ES detection rate peaked at 0800-midday (0.64/h) and was lowest midnight-0400 (0.12/h) with an incidence rate ratio of 5.51 (95% CI 1.78–22.67, P = 0.001).Conclusions: Embolism associated with asymptomatic carotid stenosis shows circadian variation with highest rates 4–6 h before midday. This corresponds with peak circadian incidence of stroke and other vascular complications. These and ASED Study results show that monitoring frequency, duration, and time of day are important in ES detection.

A molecular epidemiology study of HIV-1 infection was conducted in one hundred diagnosed and untreated HIV-1-infected patients in Cyprus between 2010 and 2012, representing 65.4% of all the reported HIV-1 infections in Cyprus in this three-year period, using a previously defined enrolment strategy. Eighty-two patients were newly diagnosed (genotypic drug resistance testing within six months from diagnosis), and eighteen patients were HIV-1 diagnosed for a longer period or the diagnosis date was unknown. Phylogenetic trees of the pol sequences obtained in this study with reference sequences indicated that subtypes B and A1 were the most common subtypes present and accounted for 41.0 and 19.0% respectively, followed by subtype C (7.0%), F1 (8.0%), CRF02_AG (4.0%), A2 (2.0%), other circulating recombinant forms (CRFs) (7.0%) and unknown recombinant forms (URFs) (12%). Most of the newly-diagnosed study subjects were Cypriots (63%), males (78%) with median age 39 (Interquartile Range, IQR 33-48) reporting having sex with other men (MSM) (51%). A high rate of clustered transmission of subtype B drug-sensitive strains to reverse transcriptase and protease inhibitors was observed among MSM, twenty-eight out of forty-one MSM study subjects (68.0%) infected were implicated in five transmission clusters, two of which are sub-subtype A1 and three of which are subtype B strains. The two largest MSM subtype B clusters included nine and eight Cypriot men, respectively, living in all major cities in Cyprus. There were only three newly diagnosed patients with transmitted drug resistant HIV-1 strains, one study subject from the United Kingdom infected with subtype B strain and one from Romania with sub-subtype A2 strain, both with PI drug resistance mutation M46L and one from Greece with sub-subtype A1 with non-nucleoside reverse transcriptase inhibitors (NNRTI) drug resistance mutation K103N.

The effects of ultra-high-pressure homogenization (UHPH) at 200 MPa, in combination with different inlet temperatures (55 or 75 °C) during storage at 4 °C were studied and compared with pasteurized (90 °C, 90 s) almond beverage. Microbiological analysis of the physical (particle sedimentation and color) and volatile profile of the most relevant compound in almond beverages was performed at days 1, 7, 14, and 21 of cold storage. UHPH treatment 200 at 75 °C led to higher microbiological reduction after treatment and higher stability during cold storage in almond beverages than pasteurization or UHPH 200 at 55 °C. Physical characteristics of UHPH-treated samples exhibited a high stability during storage with a stable color. Volatile compounds extracted by solid-phase microextraction were identified by gas chromatography coupled with mass spectrometry. The effect of UHPH treatment significantly (p < 0.05) affected the volatile profile compared with pasteurized beverages, although UHPH conditions applied produced similar effects in almond beverages. Benzaldehyde was the most abundant compound detected in all treatments. Hexanal was more abundant in UHPH-treated samples, indicating a higher lipid oxidation compared to pasteurized almond beverages.

Inovirus-associated vectors (IAVs) are engineered, non-lytic, filamentous bacteriophages that are assembled primarily from thousands of copies of the major coat protein gp8 and just five copies of each of the four minor coat proteins gp3, gp6, gp7 and gp9. Inovirus display studies have shown that the architecture of inoviruses makes all coat proteins of the inoviral particle accessible to the outside. This particular feature of IAVs allows foreign antigenic peptides to be displayed on the outer surface of the virion fused to its coat proteins and for more than two decades has been exploited in many applications including antibody or peptide display libraries, drug design, and vaccine development against infectious and non-infectious diseases. As vaccine carriers, IAVs have been shown to elicit both a cellular and humoral response against various pathogens through the display of antibody epitopes on their coat proteins. Despite their high immunogenicity, the goal of developing an effective vaccine against HIV-1 has not yet materialized. One possible limitation of previous efforts was the use of broadly neutralizing antibodies, which exhibited autoreactivity properties. In the past five years, however, new, more potent broadly neutralizing antibodies that do not exhibit autoreactivity properties have been isolated from HIV-1 infected individuals, suggesting that vaccination strategies aimed at producing such broadly neutralizing antibodies may confer protection against infection. The utilization of these new, broadly neutralizing antibodies in combination with the architectural traits of IAVs have driven the current developments in the design of an inovirus-based vaccine against HIV-1. This article reviews the applications of IAVs in vaccine development, with particular emphasis on the design of inoviral-based vaccines against HIV-1.

Cervical cancer is the fourth most frequently occurring cancer in women around the world and can affect them during their reproductive years. Since the development of the Papanicolaou (Pap) test, screening has been essential in identifying cervical cancer at a treatable stage. With the identification of the human papillomavirus (HPV) as the causative agent of essentially all cervical cancer cases, HPV molecular screening tests and HPV vaccines for primary prevention against the virus have been developed. Accordingly, comparative studies were designed to assess the performance of cervical cancer screening methods in order to devise the best screening strategy possible. This review critically assesses the current cervical cancer screening methods as well as the implementation of HPV vaccination in Europe. The most recent European Guidelines and recommendations for organized population-based programs with HPV testing as the primary screening method are also presented. Lastly, the current landscape of cervical cancer screening programs is assessed for both European Union member states and some associated countries, in regard to the transition towards population-based screening programs with primary HPV testing.

Mycothiazole, a polyketide metabolite isolated from the marine sponge Cacospongia mycofijiensis, is a potent inhibitor of metabolic activity and mitochondrial electron transport chain complex I in sensitive cells, but other cells are relatively insensitive to the drug. Sensitive cell lines (IC50 0.36–13.8 nM) include HeLa, P815, RAW 264.7, MDCK, HeLa S3, 143B, 4T1, B16, and CD4/CD8 T cells. Insensitive cell lines (IC50 12.2–26.5 μM) include HL-60, LN18, and Jurkat. Thus, there is a 34,000-fold difference in sensitivity between HeLa and HL-60 cells. Some sensitive cell lines show a biphasic response, suggesting more than one mechanism of action. Mitochondrial genome-knockout ρ0 cell lines are insensitive to mycothiazole, supporting a conditional mitochondrial site of action. Mycothiazole is cytostatic rather than cytotoxic in sensitive cells, has a long lag period of about 12 h, and unlike the complex I inhibitor, rotenone, does not cause G2/M cell cycle arrest. Mycothiazole decreases, rather than increases the levels of reactive oxygen species after 24 h. It is concluded that the cytostatic inhibitory effects of mycothiazole on mitochondrial electron transport function in sensitive cell lines may depend on a pre-activation step that is absent in insensitive cell lines with intact mitochondria, and that a second lower-affinity cytotoxic target may also be involved in the metabolic and growth inhibition of cells.

Objective: Conduct a process evaluation of a health education resource (pamphlet)¸ Abre los Ojos, designed for street-involved youth in Medellín. The primary foci of the evaluation were the process of developing the resource and youth’s subsequent perception of the resource. Methodology: Drawing upon both qualitative and quantitative data, a process evaluation was undertaken. Ninety four street-involved youth between the ages of 14–24 years completed surveys about the resource. These semi-structured interviews were key for the information about youth perception of the resource. In addition to individual interviews, prior to resource creation, a series of focus groups were integral for the development of the resource. Results: The process of consulting with the target population through the focus groups was effective in obtaining their ideas and feedback about what type of content they would like to see in a health education resource, and how they wanted that content presented. After distribution, participants described that Abre los Ojos contained information that was valuable and relevant to their experiences. While not a primary focus of this evaluation, the individual interviews were also able to provide some preliminary insight into whether Abre los Ojos was an effective means for participants to increase their knowledge of content included in the resource. Conclusion: The collaborative process of jointly developing the resource content in partnership with the youth proved very worthwhile. While our research team chose to include information about HIV, through focus group dialogue, the youth themselves determined the additional content themes (piercings, use of solvents, and description of life on the street). The resulting resource was well-received by members of the street-involved population who had not been involved in its design.

In this study, we developed a methodology to improve the survival, vascular differentiation and regenerative potential of umbilical cord blood (UCB)-derived hematopoietic stem cells (CD34(+) cells), by co-culturing the stem cells in a 3D fibrin gel with CD34(+)-derived endothelial cells (ECs). ECs differentiated from CD34(+) cells appear to have superior angiogenic properties to fully differentiated ECs, such as human umbilical vein endothelial cells (HUVECs). Our results indicate that the pro-survival effect of CD34(+)-derived ECs on CD34(+) cells is mediated, at least in part, by bioactive factors released from ECs. This effect likely involves the secretion of novel cytokines, including interleukin-17 (IL-17) and interleukin-10 (IL-10), and the activation of the ERK 1/2 pathway in CD34(+) cells. We also show that the endothelial differentiation of CD34(+) cells in co-culture with CD34(+)-derived ECs is mediated by a combination of soluble and insoluble factors. The regenerative potential of this co-culture system was demonstrated in a chronic wound diabetic animal model. The co-transplantation of CD34(+) cells with CD34(+)-derived ECs improved the wound healing relatively to controls, by decreasing the inflammatory reaction and increasing the neovascularization of the wound.

La finalidad del proyecto fue determinar el tiempo estándar de las actividades del proceso para la obtención de leche pasteurizada y los movimientos innecesarios realizados por el operar io en una empresa procesadora de der ivados lácteos , mediante la ut i l ización de herramientas como el estudio de tiempos y movimientos, utilizando la observación directa y secuencial del proceso para la determinación de diagramas de flujo, tiempos, distancias, actividades, operaciones, tiempos muertos, esperas, almacenamientos y transportes que se registraron en cursogramas analíticos, formatos de tiempos y formatos de desplazamiento de operarios. Para poder alcanzar los objetivos, se formularon propuestas para mejorar los métodos de trabajo, debido a que la carencia de registros de esta naturaleza no permitió abordar una evaluación y corrección de las deficiencias existentes en la planta de procesamiento. Se utilizó un diseño estadístico completamente al azar (unifactorial) con dos niveles y una prueba de Dunnet para establecer las diferencias significativas con un α del 5%. Se encontraron diferencias significativas entre los tiempos de pasteurización y estándar del proceso.

Drawing on the identity literature and job crafting research, the present work investigates how occupational identity threat is positively related to individual job crafting (i.e., approach crafting and avoidance crafting) and how approach (or avoidance) crafting transforms occupational identity threat into increased job engagement and improved job performance. We also propose that the regulatory focus of individuals would moderate these relationships. After conducting two field studies, Study 1, which used data from 211 matched employee–supervisor pairs at an aluminium manufacturing company, found that occupational identity threat had a positive effect on approach and avoidance crafting. The results also showed further support for the moderating effect of prevention focus and a mediating effect of approach crafting in transferring the effect of occupational identity threat in a positive manner (i.e., higher job engagement and performance). In Study 2, we replicated the findings of Study 1 and found further evidence for the moderating effect of promotion focus and a moderated mediating effect of approach crafting on job engagement. Theoretical and practical implications of this research are discussed. [ABSTRACT FROM AUTHOR]