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Current guidelines limit pancreatic cancer screening to those BRCA1/2 patients who have a family history of pancreatic cancer. We aimed to assess the association between family history and risk of pancreatic neoplasms in BRCA1/2 patients.We reviewed medical records of BRCA1/2 patients followed at our institution between 1995 and 2020. Family history was defined as those with a first-degree relative with pancreatic cancer. We compared the incidence and prevalence of pancreatic neoplasms between patients with and without family history of pancreatic cancer.We identified 56 BRCA1/2 patients with family history and 238 without family history of pancreatic cancer. No difference between these groups was noted in age, race, or sex. Mean follow-up interval for BRCA1/2 patients was 4.6 years (range, 0-19.7 years). There was no significant difference in prevalence (19.6% vs 12.6; P = 0.3) or incidence (29% vs 14.1%; P = 0.08) of branch-duct intraductal papillary mucinous neoplasm between the 2 groups. No association between family history and pancreatic cancer risk was noted. Only 1 of 10 BRCA1/2 patients with pancreatic cancer had a family history.Our results do not support using family history to determine eligibility for pancreatic cancer screening.

Research has yielded accumulated insights that new venture team (NVT) compositional diversity is a driving force behind the NVT success. However, studies have largely examined diversity attributes in isolation and tended to focus on demographic diversity as the primary source of identification separation with a static approach. In this study, we adopted the team faultline perspective to examine the alignment effect of NVTs’ multiple diversity attributes on NVT performance. Meanwhile, we identified entrepreneurial passion as an alternative and affective source of identification, and investigated the joint influence of these two distinct sources of identification on NVT performance across four stages of competition. Our findings indicate that NVT faultline strength is negatively related to team performance; High team entrepreneurial passion (TEP) mean mitigates the negative effect, whereas high TEP focus variety exaggerates the same negative effect. Our study has important implications for the literature on NVT diversity and entrepreneurial passion.

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. ispartof: VIRUSES-BASEL vol:15 issue:1 ispartof: location:Switzerland status: published

Multilayered phosphate bonded CoFe2O4–BaTiO3–CoFe2O4 (CBC) and BaTiO3–CoFe2O4–BaTiO3 (BCB) multiferroic structures were formed by means of uniaxial pressing. The dielectric properties were studied in 20 Hz – 1 GHz frequency and 120–500 K temperature ranges. The complex dielectric permittivity is 15–0.17i for CBC and 22–0.04i for BCB, it is temperature- and frequency-independent below 250 K. At higher temperatures, strong dispersion appeared governed by the Maxwell–Wagner relaxation. Such behaviour is determined by the 2–2 connectivity of the sample. The highest direct magnetoelectric coupling coefficient was found for the BaTiO3–CoFe2O4–BaTiO3 structure of 0.2 mVOe–1cm–1.

Drawing on the identity asymmetry literature, transactional stress theory, and creativity literature, we investigate how a perceived discrepancy between an individual’s creative role identity and others’ views toward his/her creative role identity (i.e., creative identity asymmetry) influences individual’s creative performance via psychological strain. We also examine how perceived creativity requirement and self-monitoring alter the relationships between creative identity asymmetry, psychological strain, and creative performance. Based on two studies (an experimental study and a field study), we found that creative identity asymmetry was positively related to psychological strain and negatively and indirectly related to creative performance. We also found that the effects of negative asymmetry were stronger than positive asymmetry, while perceived creativity requirement and self-monitoring significantly strengthened most of these relationships. Hence, this study contributes to the literature on creativity, identity asymmetry, and stress.

Background Intraperitoneal local anaesthetic has shown benefit in operative laparoscopy; however, no randomised controlled trial has been reported with patients having diagnostic laparoscopy. Aims To determine the effect of intraperitoneal ropivacaine on post-operative analgesic requirements, pain, nausea scores and recovery following gynaecological diagnostic laparoscopy and hysteroscopy. Materials and methods Randomised double-blind placebo-controlled trial. Well women aged 18-50 years, undergoing day case hysteroscopy and diagnostic laparoscopy for gynaecological indications were randomised to 20 mL of 150 mg intraperitoneal ropivacaine diluted in saline, or 20 mL normal saline instillation (placebo) at the end of the procedure. Women were followed up until eight hours post-discharge. Results Slower than anticipated recruitment meant that the study was finished before the sample size of 100 patients was achieved. Fifty-nine patients were included for analysis. Thirty-one patients were randomised to ropivacaine and 28 patients to control. Sixty-one percent of patients in both arms required opioid medication in recovery. The total median equivalent morphine dose was significantly higher in the patients randomised to control (11.7 mg) vs ropivacaine (6.7 mg), P = 0.03. Time to discharge was 20 min faster in patients randomised to ropivacaine, but this finding did not reach significance. Overall pain and nausea scores in the first eight hours showed no significant differences. Conclusion There was significantly reduced opioid use in recovery when using intraperitoneal ropivacaine compared to placebo, in this randomised placebo-controlled trial on women undergoing day case diagnostic laparoscopy and hysteroscopy.

Drawing on the resource allocation theory, job crafting, and creativity literature, this paper examines a curvilinear (inverted U-shaped) relationship between job crafting and creative performance. Also investigated is how this curvilinear relationship is moderated by individuals’ cognitive ability and time scarcity. Two multi-wave multi-source survey studies conducted in mainland China provide convergent support. In Study 1, using data from 144 editors and their immediate supervisors, we confirmed our prediction that job crafting had an inverted U-shaped relationship with creative performance. In Study 2, the data from 198 matched employee-supervisor pairs replicated the findings in Study 1, while providing further support for the moderating effect of cognitive ability and time scarcity. Specifically, when individuals’ cognitive ability was lower (or time scarcity was higher), the inverted U-shaped relationship between job crafting and creative performance was stronger. We discuss the theoretical and practical implications of these studies.

A stereoselective, base-free Heck coupling between 1,4-naphthoquinone and 1H-1,2,3-triazole derivatives was reported for the first time. This study shows that depending on the 1,4-naphthoquinone, the use of an additional base is unnecessary to produce the naphthoquinone-triazole conjugates. This is also the first example of a Heck coupling of these two cores without using a base as an additive. In this work, sixteen new naphthoquinone-triazole hybrids were stereoselectively synthetized in good to excellent yields. The reaction mechanism was discussed based on DFT CAM−B3LYP calculations. The first step is the coordination of the arene to the palladium catalyst to form a palladacycle intermediate. After reorganization in this intermediate, the double bond in the arene is restored to proceed with the coupling step and formation of the C−C bond in the rate determining step. The Kozuchi-Shaik span model was employed to rationalize substituent effects.

Gut microbiota, a term that includes microorganisms present in the gastrointestinal tract, has become very attractive lately due to its propensity to act as a virtual organ with endocrine functions, generating various bio-active metabolites, while playing an important role in human health and diseases, including cardiovascular diseases (CVDs). Focusing on the latter field, gastrointestinal dysbiosis that is the imbalance in the gut microbiota composition has been linked to various pathologies such as hypertension, atherosclerosis, myocardial infarction and heart failure. Several pathways were demonstrated to play a role in the complex and intertwined association between the gut microbiota and host, including metabolic endotoxemia, alteration of pattern recognition receptors and short-chain fatty acids, uremic toxins, bile acids and trimethylamine-N-oxide levels, leading to CVDs. Understanding these pathways can allow the identification of metabolites that could be useful predictors for detecting incipient CVDs stages and potential therapeutic targets. In this review, we summarize the pathways associating the gut microbiota with CVDs.

Background There is no universally accepted age cut-off for defining young strokes. Aims We aimed to determine, based on the profile of young stroke patients in our regional centre, an appropriate age cut-off for young strokes. Methods A retrospective analysis of all ischaemic stroke patients admitted to our centre from 2015 to 2017. We identified 391 ischaemic stroke patients; 30 patients between the ages of ≤50, 40 between 51-60 inclusive and 321 ≥ 61 years of age. We collected data on demographic profiles, risk factors and stroke classification using the Trial of Org 10 172 in Acute Stroke Treatment criteria. Results We found significant differences between the ≤50 and ≥61 age groups for most of the risk factors and similarities between the 51-60 inclusive and ≥ 61 age groups. At least one of the six risk factors assessed in the study was present in 86.7% of the youngest group, 97.5% of the intermediate age group and 97.2% in the oldest group. In terms of the mechanisms of stroke, the youngest and oldest age groups in our study differed in the prevalence of cryptogenic, cardioembolic and other causes of stroke. The middle and older age groups had similar mechanisms of stroke. Conclusions The prevalence of vascular risk factors and mechanisms of stroke likewise differed significantly across age groups. This study suggests that 50 years is an appropriate age cut-off for defining young strokes and reinforces the importance of primary prevention in all age groups.

The natural history of branch-duct intraductal papillary neoplasm (BD-IPMN) in BRCA1/2 patients is unknown. Our goal was to estimate the incidence and prevalence of BD-IPMN and other pancreatic lesions in BRCA1/2 patients and compare it to that for average-risk individuals.We identified a cohort of BRCA1/2 patients followed at our institution between 1995 and 2020. Medical records and imaging results were reviewed to determine prevalence of pancreatic lesions. We then identified those who had undergone follow-up imaging and determined the incidence of new pancreatic lesions. We categorized pancreatic lesions as low, intermediate, or high-risk based on their malignant potential.During the study period, 359 eligible BRCA1/2 patients were identified. Average patient age was 56.8 years, 88.3% were women, and 51.5% had BRCA1. The prevalence of low-risk pancreatic lesions was 14.4%, intermediate-risk 13.9%, and high-risk 3.3%. The prevalence of BD-IPMN was 13.6% with mean cyst size 7.7 mm (range: 2 to 34 mm). The prevalence of pancreatic cancer was 3.1%. Subsequent imaging was performed in 169 patents with mean follow-up interval of 5.3 years (range: 0 to 19.7 y). The incidence of BD-IPMN was 20.1%, with median cyst size 5.5 mm (range: 2 to 30 mm). The incidence of pancreatic cancer was 2.9%. BRCA2 patients were almost 4-times more likely to develop pancreatic cancer than BRCA1 patients, however, there was no difference in incidence or prevalence of BD-IPMN.Incidence and prevalence of BD-IPMNs in BRCA1/2 patients was similar to that reported for average-risk individuals. BRCA2 patients were more likely than BRCA1 patients to develop pancreatic cancer but had similar rates of BD-IPMN.

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.

Acetylated compounds prepared from naphthoquinones have been reported as antitumoral prodrugs. Exploring the synthetic versatility of the naphthoquinone and triazolic nuclei, herein we report a simple and efficient synthetic route to prepare a series of sixteen prodrugs prototype of 1,2,3-triazoles-naphthoquinodoic acetyl derivatives. The compounds 10a-10h and 11a-11h were obtained by oxidative cycloaddition reaction between lawsone and 4-vinyl-1H-1,2,3-triazoles promoted by ceric ammonium nitrate (CAN) in alkaline medium followed by reductive acetylation of the quinones in excess of metallic zinc and acetic anhydride in yields up to > 98%. All derivatives revealed to be hemocompatible and the compound 11e exhibited the most promising profile against Caco-2 cells showing the higher selectivity index. Molecular docking suggests that these compounds could exert their cytotoxic activity through inhibition of one topoisomerase II isoform, at least.

Acetylated compounds prepared from naphthoquinones have been reported as antitumoral prodrugs. Exploring the synthetic versatility of the naphthoquinone and triazolic nuclei, herein we report a simple and efficient synthetic route to prepare a series of sixteen prodrugs prototype of 1,2,3-triazoles-naphthoquinodoic acetyl derivatives. The compounds 10a-10h and 11a-11h were obtained by oxidative cycloaddition reaction between lawsone and 4-vinyl-1H-1,2,3-triazoles promoted by ceric ammonium nitrate (CAN) in alkaline medium followed by reductive acetylation of the quinones in excess of metallic zinc and acetic anhydride in yields up to > 98%. All derivatives revealed to be hemocompatible and the compound 11e exhibited the most promising profile against Caco-2 cells showing the higher selectivity index. Molecular docking suggests that these compounds could exert their cytotoxic activity through inhibition of one topoisomerase II isoform, at least.

La necesidad del cambio en el comportamiento social en un contexto epidemiol��gico complejo, principalmente para el adulto mayor, nos convoca transformar los enfoques de g��nero y las din��micas con las que enfrentamos el trabajo con los mismos y asumir variantes para lograr su Resiliencia.. Teniendo en cuenta la importancia de este cambio fue necesario dise��ar desde la C��tedra de Adulto Mayor actividades a distancia para la continuidad del proyecto educativo desde una perspectiva de g��nero con los adultos mayores, en un ��mbito donde sus principales desaf��os es aprender a coexistir con la enfermedad y recuperarse del impacto psicol��gico y social que ha dejado el aislamiento, confinamiento y distanciamiento social, en el cual debemos mantener determinadas normas de convivencias con mucha responsabilidad contribuyendo a afrontar los retos y desaf��os durante la pandemia para mantener su calidad de vida.

BackgroundDespite wide usage across all areas of medicine, it is uncertain how useful standard reference ranges of laboratory values are for critically ill patients.ObjectivesThe 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.MethodsA 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.ResultsThe 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.ConclusionStandardised 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.

INTRODUCTION We describe a case in which femoroacetabular impingement (FAI) was identified as the cause of non-union of a femoral neck fracture and the subsequent treatment strategy. MATERIALS AND METHODS Retrospective review of a 35-year-old patient, without any risk factors for non-union, who sustained a femoral neck fracture. Pre-existing FAI was identified as the cause for the non-union of the femoral neck fracture, with successful treatment of the non-union according to established arthroscopic treatment of the hip. RESULTS After treatment of the FAI, the non-union healed uneventfully within 3 months. CONCLUSIONS FAI may be a less common but potential cause of delayed union or non-union in the setting of femoral neck fracture in the young.

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.

Platforms with liquid cores are extensively explored as cell delivery vehicles for cell-based therapies and tissue engineering. However, the recurrence of synthetic materials can impair its translation into the clinic. Inspired by the adhesive proteins secreted by mussels, liquefied capsule is developed using gelatin modified with hydroxypyridinones (Gel-HOPO), a catechol analogue with oxidant-resistant properties. The protein-based liquefied macrocapsule permitted the compartmentalization of living cells by an approachable and non-time-consuming methodology resorting to i) superhydrophobic surfaces as a processing platform of hydrogel beads, ii) gelation of gelatin at temperatures μPCL) is evaluated. Showing prevalence toward adhesion to the inner shell wall, hASC formed a monolayer evidencing the biocompatibility and adequate mechanical properties of these platforms for proliferation, diminishing the need forμPCL as a supporting substrate. This new protein-based liquefied platform can provide biofactories devices of both fundamental and practical importance for tissue engineering and regenerative medicine or in other biotechnology fields.

Leveraging 4D biofabrication for engineering biomimetic living constructs is rapidly emerging as a valuable strategy for recapitulating native tissue dynamics, via on-demand stimuli, or in a naturally evolving mode. Carefully selecting smart materials with suitable responsiveness and cell-supporting functionalities is crucial to take full operational advantage of this next-generation technology. Recent endeavors combining naturally available polymers or hybrid smart materials improve the potential to manufacture volumetrically defined, cell-rich constructs that may display stimuli–responsive properties, shape memory/shape morphing features, and/or dynamic motion in time. In this review, natural origin biomaterials and the stimuli that can be exploited for granting dynamic morphological features and functionalities post-printing are highlighted. A broad overview of recent reports focusing on 4D-bioprinted constructs for tissue engineering and regenerative medicine is also provided and critically discussed in light of current challenges, as well as foreseeable advances. It is envisioned that upon assurance of key regulatory demands, such technology will become translatable to numerous biomedical applications that require fabrication of constructs with dynamic functionality.

Introduction: Inovirus-associated vectors (IAVs) are derived from bacterial filamentous viruses (phages). As vaccine carriers, they have elicited both cellular and humoral responses against a variety of pathogens causing infectious diseases and other non-infectious diseases. By displaying specific antigen epitopes or proteins on their coat proteins, IAVs have merited much study, as their unique abilities are exploited for widespread vaccine development.Areas covered: The architectural traits of filamentous viruses and their derivatives, IAVs, facilitate the display of specific antigenic peptides which induce antibody production to prevent or curtail infection. Inoviruses provide a foundation for cost-efficient large-scale specific phage display. In this paper, the development of different applications of inovirus-based phage display vaccines across a broad range of pathogens and hosts is reviewed. The references cited in this review were selected from established databases based on the authors’ knowledge of the study subject.Expert commentary: The importance of phage-display technology has been recently highlighted by the Nobel Prize in Chemistry 2018 awarded to George P. Smith and Sir Gregory P. Winter. Furthermore, the symbiotic nature of filamentous viruses infecting intestinal F+ E. coli strains offers an attractive platform for the development of novel vaccines that stimulate mucosal immunity 18 9 913 920

Hepatitis C virus (HCV) genotype and subtype distribution differs according to geographic origin and transmission risk category. Previous molecular epidemiology studies suggest the presence of multiple subtypes among Cypriot subjects. To investigate HCV genotype- and subtype-specific dissemination patterns, origins, and transmission in Cyprus, we analyzed HCV sequences encoding partial Core-E1 and NS5B regions. Analyzed populations comprised the general population and high-risk cohorts in Cyprus and a globally sampled dataset. Maximum-likelihood phylogeny reconstruction with bootstrap evaluation, character reconstruction using parsimony, and bootstrap trees estimated by ML were performed to identify the geographic origin of HCV subtypes and statistically significant dispersal pathways among geographic regions. Phylogeographic analyses traced the origin of subtypes in the general population and among PWID in Cyprus to unique and overlapping globally distributed regions. Phylogenetic analysis in Core-E1 revealed that most sequences from incarcerated populations in Cyprus clustered with the general population and PWID. We estimate that HCV infections in Cyprus originate from multiple global sources while most HCV transmissions among incarcerated individuals occur locally. This analysis is one of a few studies tracing HCV dispersal patterns using global datasets, and these practices and findings should inform how HCV epidemics are targeted by future prevention policies.

Background:Resistance to antimicrobial agents is a major public health problem, being Staphylococcus aureus prevalent in infections in hospital and community environments and, admittedly, related to biofilm formation in biotic and abiotic surfaces. Biofilms form a complex and structured community of microorganisms surrounded by an extracellular matrix adhering to each other and to a surface that gives them even more protection from and resistance against the action of antimicrobial agents, as well as against host defenses.Methods:Aiming to control and solve these problems, our study sought to evaluate the action of 1,2,3- triazoles against a Staphylococcus aureus isolate in planktonic and in the biofilm form, evaluating the activity of this triazole through Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) tests. We have also performed cytotoxic evaluation and Scanning Electron Microscopy (SEM) of the biofilms under the treatment of the compound. The 1,2,3-triazole DAN 49 showed bacteriostatic and bactericidal activity (MIC and MBC 128 μg/mL). In addition, its presence interfered with the biofilm formation stage (1/2 MIC, p Results:Scanning Electron Microscopy images showed a reduction in the cell population and the appearance of deformations on the surface of some bacteria in the biofilm under treatment with the compound.Conclusion:Therefore, it was possible to conclude the promising anti-biofilm potential of 1,2,3-triazole, demonstrating the importance of the synthesis of new compounds with biological activity.

Background: Cancer is a major cause of death worldwide, despite many different drugs available to treat the disease. This high mortality rate is largely due to the complexity of the disease, which results from several genetic and epigenetic changes. Therefore, researchers are constantly searching for novel drugs that can target different and multiple aspects of cancer. Experimental: After a screening, we selected one novel molecule, out of ninety-four triazole derivatives, that strongly affects the viability and proliferation of the human breast cancer cell line MCF-7, with minimal effects on non-cancer cells. The drug, named DAN94, induced a dose-dependent decrease in MCF-7 cells viability, with an IC50 of 3.2 ± 0.2 µM. Additionally, DAN94 interfered with mitochondria metabolism promoting reactive oxygen species production, triggering apoptosis and arresting the cancer cells on G1/G0 phase of cell cycle, inhibiting cell proliferation. These effects are not observed when the drug was tested in the non-cancer cell line MCF10A. Using a mouse model with xenograft tumor implants, the drug preventing tumor growth presented no toxicity for the animal and without altering biochemical markers of hepatic function. Results and Conclusion: The novel drug DAN94 is selective for cancer cells, targeting the mitochondrial metabolism, which culminates in the cancer cell death. In the end, DAN94 has been shown to be a promising drug for controlling breast cancer with minimal undesirable effects.

Objectives To test a novel, low‐cost, home‐made model for needle aspiration of PTA. To ascertain whether simulation‐based teaching using this model was superior to lecture‐based teaching in increasing confidence and reducing anxiety relating to PTA aspiration. To assess whether there was an improvement in outcomes for PTA patients at one hospital following the delivery of a simulation‐based training session using our model. Methods We designed two teaching sessions for junior doctors starting work in ENT: a simulation‐based teaching session using a low‐cost home‐made simulation model and a lecture‐based teaching session covering the same content. We asked the participants to complete pre‐ and post‐session surveys regarding confidence and anxiety levels and analyzed this data. We also retrospectively collected data over 3 months for patients referred to ENT with suspected PTA and assessed their outcomes. We assessed patient outcomes before and after the delivery of a simulation‐based training course using our model. Results Simulation‐based teaching using our model was shown to be associated with a statistically significant increase in junior doctors' confidence levels. Reaccumulation and reattendance rates for PTA following aspiration were 16.67% and 22.7% respectively preintervention and 0% and 7.14% respectively postintervention. Conclusion A regular simulation‐based teaching session should be introduced using a PTA aspiration model for junior doctors as it leads to increased confidence levels, and reduced reaccumulation and recurrence rates of PTA. Level of evidence Level 4.

Comprehensive PCR assays for the genotypic drug resistance analysis of all HIV-1 antiretroviral agents (reverse transcriptase, protease and integrase inhibitors) are increasingly in demand due to introduction of integrase inhibitors in the first line regimens and the increasing presence of non-B HIV-1 clades around the world. This study focused on the development and evaluation of a new PCR-based assay for the amplification and sequencing of the entire HIV-1 pol region of major circulating group M HIV-1 strains in Europe for genotypic drug resistance analysis. The comprehensive touchdown PCR assay developed in this study utilized HIV-1 RNA extracted from the plasma of blood samples of consenting HIV-1 infected patients in Cyprus, collected from 2017 to 2019. The HIV-1 pol region was amplified by touchdown PCR for both the primary RT-PCR and the secondary PCR steps. Successful PCR amplicons were determined by population DNA sequencing, using the Sanger method and the genotypic drug resistance analysis was performed with the Stanford University HIV Drug Resistance Database Program. The newly developed assay successfully amplified the entire HIV-1 pol region (2844 nucleotides long) of 141 out of 144 samples of group M HIV-1 subtypes and recombinant strains of the Cyprus HIV-1 Transmission Cohort Study (CHICS) isolated from 2017 to 2019 and genotypic analyses were conducted for all currently available HIV-1 reverse transcriptase, protease and integrase inhibitors. The drug resistance, epidemiological and demographic data of these study subjects will be expanded upon in the CHICS (L.G. Kostrikis et al., manuscript in preparation for publication). The newly developed HIV-1 genotypic drug resistance assay would benefit clinical settings, and research focusing on the world-wide spread of HIV-1 drug-resistant strains, especially in geographic regions characterized by polyphyletic HIV-1 infections.

Antimicrobial Resistance (AMR) is a serious problem for the humans since it threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, parasites, viruses and fungi. One way around this problem is to act on the virulence factors, produced by bacteria, which increase their infection effectiveness. In view of these facts, new coumarin derivatives were synthesized and evaluated for their anti-virulence biological activity towards Pseudomonas aeruginosa. The results suggest that coumarin derivatives with a secondary carbon at C-3 position reduces P. aeruginosa growth whereas compounds with one additional substituent have a significant effect over pyocyanin production (10k EC50 7 ± 2 µM; 10l EC50 42 ± 13 µM). Moreover, 10k reduces P. aeruginosa motility and biofilm formation, what is compatible with a quorum sensing related mechanism of action.

Funder: European Regional Development Fund and the Republic of Cyprus through the Cyprus Research and Innovation Foundation and the Structural Funds 2021-2027; Grant(s): Project: CONCEPT-COVID_0420_0024, 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.

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.

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. 13 4

Drawing on the relevant identity literature, job crafting research, and work on sensemaking, this research investigates how occupational identity threat is positively related to individual job craf...

It is prevalent for individuals in organizations to define themselves according to simultaneous, multiple, salient identities. When individuals adopt multiple identities, they have several cognitiv...

Leveraging 4D biofabrication for engineering biomimetic living constructs is rapidly emerging as a valuable strategy for recapitulating native tissue dynamics, via on-demand stimuli, or in a naturally evolving mode. Carefully selecting smart materials with suitable responsiveness and cell-supporting functionalities is crucial to take full operational advantage of this next-generation technology. Recent endeavors combining naturally available polymers or hybrid smart materials improve the potential to manufacture volumetrically defined, cell-rich constructs that may display stimuli–responsive properties, shape memory/shape morphing features, and/or dynamic motion in time. In this review, natural origin biomaterials and the stimuli that can be exploited for granting dynamic morphological features and functionalities post-printing are highlighted. A broad overview of recent reports focusing on 4D-bioprinted constructs for tissue engineering and regenerative medicine is also provided and critically discussed in light of current challenges, as well as foreseeable advances. It is envisioned that upon assurance of key regulatory demands, such technology will become translatable to numerous biomedical applications that require fabrication of constructs with dynamic functionality. published

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 Seasonal peaks of influenza and cardiovascular disease tend to coincide. Many excess deaths may be triggered by influenza, and the severity of this effect may vary with the virulence of the circulating influenza strain and host susceptibility. We aimed to explore the association between hospital admissions for influenza and/or pneumonia (IP) and acute myocardial infarction (AMI) or ischaemic heart disease (IHD) in Queensland, Australia, taking into account temporal and spatial variation of influenza virus type and subtype in 2007, 2008 and 2009. Methods This ecological study at Statistical Subdivision level (SSD, n =38) used linked patient-level data. For each study year, Standardized Morbidity Ratios (SMRs) were calculated for hospital admissions with diagnoses of IP, AMI and IHD. We investigated the associations between IP and AMI or IHD using spatial autoregressive modelling, adjusting for socio-demographic factors. Results Spatial autocorrelation was detected in SMRs, possibly reflecting underlying social and behavioural risk factors, but consistent with infectious disease spread. SMRs for IP were consistently predictive of SMRs for AMI and IHD when adjusted for socioeconomic status, population density and per cent Indigenous population (coefficient: 0.707, 95% confidence interval (CI): 0.318 – 1.096; 0.553, 0.222 – 0.884; 0.598, 0.307 – 0.888 and 1.017, 0.711 – 1.323; 0.650, 0.342 – 0.958; 1.031, 0.827 – 1.236) in 2007, 2008 and 2009, respectively. Conclusions This ecological study provides further evidence that severe respiratory infections may trigger the onset of cardiovascular events, implicating the influenza virus as a contributing factor.

The default mode network (DMN) encompasses brain systems that exhibit coherent neural activity at rest. DMN brain systems have been implicated in diverse social, cognitive, and affective processes, as well as risk for forms of dementia and psychiatric disorders that associate with systemic inflammation. Areas of the anterior cingulate cortex (ACC) and surrounding medial prefrontal cortex (mPFC) within the DMN have been implicated specifically in regulating autonomic and neuroendocrine processes that relate to systemic inflammation via bidirectional signaling mechanisms. However, it is still unclear whether indicators of inflammation relate directly to coherent resting state activity of the ACC, mPFC, or other areas within the DMN. Accordingly, we tested whether plasma interleukin (IL)-6, an indicator of systemic inflammation, covaried with resting-state functional connectivity of the DMN among 98 adults aged 30–54 (39% male; 81% Caucasian). Independent component analyses were applied to resting state fMRI data to generate DMN connectivity maps. Voxel-wise regression analyses were then used to test for associations between IL-6 and DMN connectivity across individuals, controlling for age, sex, body mass index, and fMRI signal motion. Within the DMN, IL-6 covaried positively with connectivity of the sub-genual ACC and negatively with a region of the dorsal medial PFC at corrected statistical thresholds. These novel findings offer evidence for a unique association between a marker of systemic inflammation (IL-6) and ACC and mPFC functional connectivity within the DMN, a network that may be important for linking aspects of immune function to psychological and behavioral states in health and disease.