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Fetal hydrothorax (FH) or pleural effusion is a clinical entity, and refers to accumulation of fetal pleural fluid, which may presents a wide spectrum of severity ranging from small, harmless effusion, to life-threatening thoracic compression (1). The perinatal mortality associated with pleural effusion is at least 50 %. Cardiac and extra-cardiac abnormalities may accompany the hydrothorax and their presence also affects the prognosis (2). Division of the right atrium, first reported in 1868, also known as cor triatriatum dexter, is extremely a rare congenitally abnormality, in which persistence of right valve of the embryonic systemic venous sinus divides the right atrium into two chambers. The embryonic valvar structures, whose significance during fetal life is to direct the richly oxygenated inferior caval venous blood across to the left atrium and thence to the aorta, normal regress in late fetal life and early childhood. Cytomegalovirus (CMV) is a common human virus, member of herpes virus family, and the most common cause of intrauterine infection, occurring in 0.2 % to 2.2 % of life births (3,4). This report describes antenataly diagnosed a case of a divided right atrium, associated with severe form of hydrothorax and Cytomegalovirus infection. Here we present a fetus with sever hydrothorax associated with divided right atrium and cytomegalovirus infection.

Although seasonal variations in mortality have been recognized for millennia, the role of temperature remains unclear. We aimed to assess seasonal variation in mortality and to examine the contribution of temperature., This work was primarily supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI [Grant Number 19K19461]. Y.C. was supported by a Senior Research grant [2019R1A2C1086194] from the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT (Information and Communication Technologies). V.H. received support from the Spanish Ministry of Economy, Industry and Competitiveness [Grant ID: PCIN-2017-046]. J.K. and A.U. were supported by the Czech Science Foundation [project 18-22125S]. A.S. acknowledged funding from European Union’s Horizon 2020 research and innovation programme under grant agreement No 820655 (EXHAUSTION). A.G. was supported by the Medical Research Council-UK [Grant ID: MR/R013349/1], the Natural Environment Research Council UK [Grant ID: NE/R009384/1] and the European Union’s Horizon 2020 Project Exhaustion [Grant ID: 820655]. M.H. was supported by the Japan Science and Technology Agency (JST) as part of SICORP [Grant Number JPMJSC20E4].

Objective: It is important to put forward the characteristics of the COVID-19 cases to fight the disease effectively. The aim of this study is to determine the epidemiological characteristics of COVID-19 cases in Turkey. And also to determine the risk factors associated with intensive care unit (ICU) admission and death. Methods: In this cross-sectional study, the characteristics of the confirmed COVID-19 cases who applied to a University Hospital in Turkey between March 19th and June 11th, 2020, were analyzed. Variables such as epidemic trend, case fatality rate, need for hospitalization, ICU admission rate, and ICU mortality were calculated. In addition, risk factors affecting ICU admission and death were determined by logistic regression analysis. Results: 19.8% of 654 cases participating in the study were asymptomatic at admission. ICU admission rate was 7.6% and case fatality rate found to be 7.8%. Age, male gender, and cancer were associated with ICU admission. Each 1-unit increase in age increased ICU admissions by 8% (OR: 1.08; CI: 1.06-1.10). Men had a 2.71 times higher risk of ICU admission (OR: 2.71; CI: 1.37-5.39); and cancer patients showed 3.72 (OR: 3.72; CI: 1.35-10.20) times more ICU admissions (p

The petals of the saffron crocus (Crocus sativus L.) are considered a waste material in saffron production, but may be a sustainable source of natural biologically active substances of nutraceutical interest. The aim of this work was to study the cardiovascular effects of kaempferol and crocin extracted from saffron petals. The antiarrhythmic, inotropic, and chronotropic effects of saffron petal extract (SPE), kaempferol, and crocin were evaluated through in vitro biological assays. The antioxidant activity of kaempferol and crocin was investigated through the 2&prime, 7&prime, dichlorodihydrofluorescein diacetate (DCFH-DA) assay using rat cardiomyoblast cell line H9c2. The MTT assay was applied to assess the effects of kaempferol and crocin on cell viability. SPE showed weak negative inotropic and chronotropic intrinsic activities but a significant intrinsic activity on smooth muscle with a potency on the ileum greater than on the aorta: EC50 = 0.66 mg/mL versus EC50 = 1.45 mg/mL. Kaempferol and crocin showed a selective negative inotropic activity. In addition, kaempferol decreased the contraction induced by KCl (80 mM) in guinea pig aortic and ileal strips, while crocin had no effect. Furthermore, following oxidative stress, both crocin and kaempferol decreased intracellular ROS formation and increased cell viability in a concentration-dependent manner. The results indicate that SPE, a by-product of saffron cultivation, may represent a good source of phytochemicals with a potential application in the prevention of cardiovascular diseases.

Background Typhoid fever remains a major source of morbidity and mortality in low-income settings. Its most feared complication is intestinal perforation. However, due to the paucity of diagnostic facilities in typhoid-endemic settings, including microbiology, histopathology, and radiology, the etiology of intestinal perforation is frequently assumed but rarely confirmed. This poses a challenge for accurately estimating burden of disease. Methods We recruited a prospective cohort of patients with confirmed intestinal perforation in 2016 and performed enhanced microbiological investigations (blood and tissue culture, plus tissue polymerase chain reaction [PCR] for Salmonella Typhi). In addition, we used a Poisson generalized linear model to estimate excess perforations attributed to the typhoid epidemic, using temporal trends in S. Typhi bloodstream infection and perforated abdominal viscus at Queen Elizabeth Central Hospital from 2008–2017. Results We recruited 23 patients with intraoperative findings consistent with intestinal perforation. 50% (11/22) of patients recruited were culture or PCR positive for S. Typhi. Case fatality rate from typhoid-associated intestinal perforation was substantial at 18% (2/11). Our statistical model estimates that culture-confirmed cases of typhoid fever lead to an excess of 0.046 perforations per clinical typhoid fever case (95% CI, .03–.06). We therefore estimate that typhoid fever accounts for 43% of all bowel perforation during the period of enhanced surveillance. Conclusions The morbidity and mortality associated with typhoid abdominal perforations are high. By placing clinical outcome data from a cohort in the context of longitudinal surgical registers and bacteremia data, we describe a valuable approach to adjusting estimates of the burden of typhoid fever.

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991–2018. Across all study countries, we find that 37.0% (range 20.5–76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change., We thank the participants of the ISIMIP Health workshop in Barcelona in November 2018 where this work was discussed for the first time. This study was supported by the Medical Research Council UK (grant no. MR/M022625/1), the Natural Environment Research Council UK (grant no. NE/R009384/1) and the European Union’s Horizon 2020 Project Exhaustion (grant no. 820655). N.S. was supported by the NIEHS-funded HERCULES Center (P30ES019776). Y.H. was supported by the Environment Research and Technology Development Fund of the Environmental Restoration and Conservation Agency, Japan (JPMEERF15S11412). J.J.J.K.J. was supported by Academy of Finland (grant no. 310372). V.H. was supported by the Spanish Ministry of Economy, Industry and Competitiveness (grant no. PCIN-2017-046) and the German Federal Ministry of Education and Research (grant no. 01LS1201A2). J.K. and A.U. were supported by the Czech Science Foundation (grant no. 20-28560S). J.M. was supported by the Fundação para a Ciência e a Tecnologia (FCT) (SFRH/BPD/115112/2016). S.R. and F.d.R. were supported by European Union’s Horizon 2020 Project EXHAUSTION (grant no. 820655). M.H. was supported by the Japan Science and Technology Agency as part of SICORP, grant no. JPMJSC20E4. Y.G. was supported by the Career Development Fellowship of the Australian National Health and Medical Research Council (APP1163693). S.L. was support by the Early Career Fellowship of the Australian National Health and Medical Research Council (APP1109193). Y.L.L.G. was supported by the Taiwan Ministry of Science and Technology (MOST110-2918-I-002-007) as a visiting academic at the University of Sydney.

In the course of the COVID-19 pandemic, it has become clear that primary healthcare systems play a critical role in clinical care, such as patient screening, triage, physical and psychological support and also in promoting good community advice and awareness in coordination with secondary healthcare and preventive care. Because of the role of social and environmental factors in COVID-19 transmission and burden of disease, it is essential to ensure that there is adequate coordination of population-based health services and public health interventions. The COVID-19 pandemic has shown the primary and community healthcare (PCHC) system's weaknesses worldwide. In many instances, PCHC played only a minor role, the emphasis being on hospital and intensive care beds. This was compounded by political failures, in supporting local community resilience. Placing community building, social cohesion and resilience at the forefront of dealing with the COVID-19 crisis can help align solutions that provide a vision of a € planetary health'. This can be achieved by involving local well-being and participation in the face of any pervasive health and environmental crisis, including other epidemics and large-scale ecological crises. This paper proposes that PCHC should take on two critical roles: first, to support local problem-solving efforts and to serve as a partner in innovative approaches to safeguarding community well-being; and second, to understand the local environment and health risks in the context of the global health perspective. We see this as an opportunity of immediate value and broad consequence beyond the control of the COVID-19 pandemic., SCOPUS: ar.j, info:eu-repo/semantics/published

Summary Background Many regions of the world are now facing more frequent and unprecedentedly large wildfires. However, the association between wildfire-related PM2·5 and mortality has not been well characterised. We aimed to comprehensively assess the association between short-term exposure to wildfire-related PM2·5 and mortality across various regions of the world. Methods For this time series study, data on daily counts of deaths for all causes, cardiovascular causes, and respiratory causes were collected from 749 cities in 43 countries and regions during 2000–16. Daily concentrations of wildfire-related PM2·5 were estimated using the three-dimensional chemical transport model GEOS-Chem at a 0·25° × 0·25° resolution. The association between wildfire-related PM2·5 exposure and mortality was examined using a quasi-Poisson time series model in each city considering both the current-day and lag effects, and the effect estimates were then pooled using a random-effects meta-analysis. Based on these pooled effect estimates, the population attributable fraction and relative risk (RR) of annual mortality due to acute wildfire-related PM2·5 exposure was calculated. Findings 65·6 million all-cause deaths, 15·1 million cardiovascular deaths, and 6·8 million respiratory deaths were included in our analyses. The pooled RRs of mortality associated with each 10 μg/m3 increase in the 3-day moving average (lag 0–2 days) of wildfire-related PM2·5 exposure were 1·019 (95% CI 1·016–1·022) for all-cause mortality, 1·017 (1·012–1·021) for cardiovascular mortality, and 1·019 (1·013–1·025) for respiratory mortality. Overall, 0·62% (95% CI 0·48–0·75) of all-cause deaths, 0·55% (0·43–0·67) of cardiovascular deaths, and 0·64% (0·50–0·78) of respiratory deaths were annually attributable to the acute impacts of wildfire-related PM2·5 exposure during the study period., Australian Research Council, Australian National Health & Medical Research Council.

Testing for HIV is critical for early diagnosis of HIV infection, providing long-term good health for the individual and prevention of onward transmission if antiretroviral treatment is initiated early. The main purpose of the 2021 European Guideline on HIV Testing in Genito-Urinary Settings is to provide advice on testing for HIV infection in individuals aged 16 years and older who present to sexually transmitted infection, genito-urinary or dermato-venereology clinics across Europe. The guideline presents the details of best practice and offers practical guidance to clinicians and laboratories to identify and offer HIV testing to appropriate patient groups.

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INTRODUCTION Following the announcement of first coronavirus disease 2019 (COVID‐19) case on March 11, 2020, in Turkey we aimed to report the co‐infection rates, and the clinical, laboratory, radiological distinctive features of viral pneumonia caused by viruses other than severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). METHODS A cross‐sectional study was conducted between 18 and 31 March 2020. COVID‐19 suspected cases admitted to pandemic policlinic who had nasopharyngeal swab specimens tested for both SARS‐CoV‐2 and other respiratory viral pathogens were included. RESULTS Within 112 patients SARS‐CoV‐2 was detected in 34 (30%). Among the non‐SARS‐CoV‐2 viruses (n=25, 22%), metapneumovirus (n=10), was the most frequent agent. There were two co‐infections with SARS‐CoV‐2. Sputum was less in the SARS‐CoV‐2 group (p=0.003). The leukocyte, lymphocyte, and thrombocyte count and C‐reactive protein levels were lowest in the SARS‐CoV‐2 group (p

The IRONIC study group: Cuervo, Guillermo; Escrihuela-Vidal, Francesc; Tubau, Fe; Rodriguez Arias, Marisol; Merve Ayaz, Caglayan; Munita, Jose; Gasch, Oriol; Capilla, Silvia; Bochud, Pierre-Yves; Manuel, Oriol; Torre-Cisneros, Julian; Tabares, Salvador; Serrano Lopez, Josefina; Maschmeyer, Georg; Torres, Diego; Abdala, Edson; Bittencourt, Driele Peixoto; El Zein, Saeed; Jabbour, Jean-Francois; Bertz, Hartmut; Peyerl-Hoffmann, Gabriele; Lizasoain, Manuel; Maria Aguado, Jose; Clemencia Correa, Lina; Palop, Begona; Fortun, Jesus; Magnasco, Laura; Cespedes, Roberto; Lopez-Soria, Leire; Pablo Horcajada, Juan; Montaguti, Mia Hold; de Cueto, Marina; Rodriguez-Bano, Jesus; Greco, Raffaella; Cichero, Paola; Bassetti, Matteo; Castaldo, Nadia; Sangro del Alcazar, Paloma; Cardozo, Celia; Garcia-Vidal, Carolina; Aguilar-Company, Juan; Larrosa, Nieves; Uyan-Onal, Ayse; Nazli-Zeka, Arzu; Vasconcelos de Freitas, Wania; da Silva Machado, Amanda Aparecida, [Introduction]: Pseudomonas aeruginosa (PA) has historically been one of the major causes of severe sepsis and death among neutropenic cancer patients. There has been a recent increase of multidrug-resistant PA (MDRPA) isolates that may determine a worse prognosis, particularly in immunosuppressed patients. The aim of this study is to establish the impact of antibiotic resistance on the outcome of neutropenic onco-haematological patients with PA bacteraemia, and to identify the risk factors for MDRPA bacteraemia and mortality., [Methods and analysis]: This is a retrospective, observational, multicentre, international study. All episodes of PA bacteraemia occurring in neutropenic oncohaematological patients followed up at the participating centres from 1 January 2006 to 31 May 2018 will be retrospectively reviewed. The primary end point will be overall case-fatality rate within 30 days of onset of PA bacteraemia. The secondary end points will be to describe the following: the incidence and risk factors for multidrugresistant and extremely drug-resistant PA bacteraemia (by comparing the episodes due to susceptible PA with those produced by MDRPA), the efficacy of ceftolozane/tazobactam, the rates of persistent bacteraemia and bacteraemia relapse and the risk factors for very early (48 hours), early (7 days) and overall (30 days) case-fatality rates., [Ethics and dissemination]: The Clinical Research Ethics Committee of Bellvitge University Hospital approved the protocol of the study at the primary site. To protect personal privacy, identifying information of each patient in the electronic database will be encrypted. The processing of the patients’ personal data collected in the study will comply with the Spanish Data Protection Act of 1998 and with the European Directive on the privacy of data. All data collected, stored and processed will be anonymised. Results will be reported at conferences and in peerreviewed publications., This study was supported by Plan Nacional de I+D+i 2013‐2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0001) and co-financed by European Development Regional Fund “A way to achieve Europe”, Operative Programme Intelligent Growth 2014‐2020.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and associated COVID-19 have caused a global emergency that requires an engaged, integrated, interdisciplinary, and rapid response from the scientific community. Climate change, ecological change, and biodiversity loss might have played an important role in the occurrence of this zoonotic pandemic. Climatic and environmental factors, such as temperature, humidity, and air pollution, are potentially influencing the transmission, spread, and severity of SARS-CoV-2 infection. Strong scientific evidence about the contributions of these environmental determinants in the COVID-19 pandemic is needed, in combination with an understanding of the role of other important societal factors and public health interventions. This evidence will support the public health community in responding to the current crisis, and inform strategies to prevent the recurring effects of the COVID-19 pandemic and future emergencies.

The objective of this study was to investigate the effects of chronic environmental lead (Pb) exposure in blood lead level (BLL), δ-aminolevulinic acid dehydratase (ALAD) activity, hemoglobin (Hb) amount and hematocrit (Hct) value in primary schoolchildren and adults. Blood was obtained for BLL, ALAD, Hb and Hct measurements in 23 primary schoolchildren (girls and boys) and 117 adult residents (women and men) living in three villages (Kelmend, Boletin and Zhazhë) defined by concentric circles 2, 3 and 5 km in radius drawn around from the smelter-refinery complex "Trepça"in Zveçan and in Koliq village 40 km away. As expected, BLLs were substantially higher in the schoolchildren from smelter area compared with control (11 ± 4.2 µg/L and 6.9 ± 1.6 µg/L respectively) and in adult residents from Kelmend, Boletin and Zhazhë (24 ± 11.8, 12 ± 4.5, 11 ± 5.4 and 8.0 ± 2.8 µg/L respectively). Blood ALAD activity of children in Zhazhë is 16% inhibited compared to control and blood ALAD activity in adults in villages from smelter area is 32, 3%, 48, 4% and 17, 8% inhibited compared to control. There is no difference of Hb and Hct values in schoolchildren from Zhazhë and in adult residents from Kelmend and Zhazhë compared with control. Results of this study provide evidence of moderate inverse correlation between BLL and ALAD activity in both examined cohorts from smelter area. The inhibition of ALAD activity in primary schoolchildren and adults occurred at blood lead levels24 µg/L; consequently it can cause an increase of δ- Aminolevulinic acid.

Background and objectives Identification of the manifestations, assessment and follow up of children with hypertrophic cardiomyopathy (HCM) by transthoracic echocardiography may be important for clinical management and our understanding of pathogenesis. Methods We present a comprehensive analysis of 43 children seen in Kosovo, 23 were male, aged between 4 months and 9 years at first presentation (median of 2 years and 3 months). Results Cardiac failure, seen in almost half of them, was the most common presenting feature. At admission, the chest x-ray revealed an increased cardiothoracic ratio, to a mean of 72% in 6 infants and to 65% in 37 older children. Measured by transthoracic echocardiography, 28 children had asymmetric hypertrophy of left ventricle while 15 had concentric hypertrophy. Left ventricular ejection fraction was depressed in 21 children. Patients with cardiac failure received various combinations of diuretics, B-blockers, ACE inhibitors and anticoagulant therapy (aspirin). Death occurred in 8 children, in 4 of them shortly after admission, the other 4 left Kosovo and continued examination and treatment abroad Kosovo; their death has been confirmed by family members. The remaining 32 were followed- up for a mean 42 months, with a range from 5 to 115 months. Surgical intervention was not performed to any of them, despite the clinical and echocardiography indications due to a limitation of resources. Recovery was noted in 14 children but still requiring anti-heart failure medications. Slightly over two-fifths died. Of those with asymmetric form, 45% died, half of those presenting in infancy, and 89% of those who presented at admission with signs of cardiac failure. Conclusion The results of our study show that similar to many centers, the etiology of HCM is often uncertain. In the absence of etiology, treatment aimed at the cause is either impossible or, at best, empirical.

Global environmental change has degraded ecosystems. Challenges such as climate change, resource depletion (with its huge implications for human health and wellbeing), and persistent social inequalities in health have been identified as global public health issues with implications for both communicable and noncommunicable diseases. This contributes to pressure on healthcare systems, as well as societal systems that affect health. A novel strategy to tackle these multiple, interacting and interdependent drivers of change is required to protect the population’s health. Public health professionals have found that building strong, enduring interdisciplinary partnerships across disciplines can address environment and health complexities, and that developing Environmental and Public Health Tracking (EPHT) systems has been an effective tool. EPHT aims to merge, integrate, analyse and interpret environmental hazards, exposure and health data. In this article, we explain that public health decision-makers can use EPHT insights to drive public health actions, reduce exposure and prevent the occurrence of disease more precisely in efficient and cost-effective ways. An international network exists for practitioners and researchers to monitor and use environmental health intelligence, and to support countries and local areas toward sustainable and healthy development. A global network of EPHT programs and professionals has the potential to advance global health by implementing and sharing experience, to magnify the impact of local efforts and to pursue data knowledge improvement strategies, aiming to recognise and support best practices. EPHT can help increase the understanding of environmental public health and global health, improve comparability of risks between different areas of the world including Low and Middle-Income Countries (LMICs), enable transparency and trust among citizens, institutions and the private sector, and inform preventive decision making consistent with sustainable and healthy development. This shows how EPHT advances global health efforts by sharing recent global EPHT activities and resources with those working in this field. Experiences from the US, Europe, Asia and Australasia are outlined for operating successful tracking systems to advance global health.

Wild California condors (Gymnogyps californianus) are frequently exposed to lead via lead-based ammunition ingestion, and recent studies indicate significant exposure to organochlorines (e.g. dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyls (PCBs)) for condors feeding on beach-cast marine mammals. We investigated the influence of contaminant exposure on condor glucocorticoid response through comparisons between wild and captive populations and identification of modifiers of glucocorticoid release in wild condors. We assessed the glucocorticoid response to routine trapping and handling events through measurement of plasma corticosterone and urate glucocorticoid metabolites (GCM). Comparison of peak urate GCM levels showed wild condors exhibited higher responses to handling-associated stressors (2300 ± 1400 ng/g dry wt, average ± SD, n = 27) than captive condors (910 ± 490 ng/g dry wt., n = 6, U = 28, p = 0.003). Multiple linear regression models and an information theoretic approach (AICc) identified several extrinsic variables (e.g., time captive in flight pen before sample collection) that were negatively associated with plasma corticosterone and urate GCM levels in wild condors, which explained ~25% of glucocorticoid variation. When accounting for these extrinsic variables we found that behavioral variables associated with increased lead and organochlorine exposure risk were positively associated with GCM levels, explaining an additional 15% of glucocorticoid variation among wild condors. Days absent from management area, a variable associated with reduced survival attributed to increased lead exposure risk, had a positive influence on plasma corticosterone levels (β = 53 ± 20 SE) and peak urate GCM levels (β = 1090 ± 586 SE). Years observed feeding on marine mammals, a variable positively associated with DDE and PCB exposure, positively influenced peak urate GCM (β = 1100 ± 520 SE) and the magnitude of GCM response (peak GCM - 1st urate GCM) (β = 1050 ± 500 SE). Our findings suggest that individual propensities for contaminant-associated foraging behaviors predict higher stress-induced glucocorticoid levels in wild condors, and that accounting for variables associated with trapping and handling is essential for assessing the impact of environmental stressors such as contaminants on the condor stress response. As an abnormal glucocorticoid response to stress is associated with reduced reproduction and survival in vertebrates, this work indicates the need for further investigations into the physiological impacts of sub-lethal contaminant exposures in scavenging species worldwide.

BACKGROUND: About 70-80% of patients with colorectal liver metastases appear as ineligible for a curative treatment approach. Transarterial chemoembolisation (TACE) using irinotecan-eluting beads has emerged as a promising treatment option in cases with irresectable liver metastases. Despite being in clinical practice for years, little is known about the treatment characteristics and outcomes when used as per routine hospital practice. METHODS: Patients with hepatic metastases from colorectal cancer origin, admitted to contributing centres to receive TACE with drug-eluting LifePearl® Microspheres loaded with irinotecan, as part of their standard care, will be consecutively added to the registry. Data will be collected until the end of study, loss to follow-up or death. Primary endpoint is the characterisation of the treatment usage at the selected sites in Europe. Secondary endpoints include outcome parameters, safety and toxicity, as well as quality of life. CONCLUSION AND AIMS: This multicentre, international, prospective observational study conducted in European centres plans to collect real-life data. This data will form an evidence-base from which conclusions can be drawn on how to improve patient selection and optimise treatment protocols when treating with TACE using irinotecan-eluting microspheres. Trial registration NCT03086096. ispartof: DIGESTIVE AND LIVER DISEASE vol:52 issue:8 pages:857-861 ispartof: location:Netherlands status: published

Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with abnormal progenitor self-renewal and defective white blood cell differentiation. Its pathogenesis comprises subversion of transcriptional regulation, through mutation and by hijacking normal chromatin regulation. Kat2a is a histone acetyltransferase central to promoter activity, that we recently associated with stability of pluripotency networks, and identified as a genetic vulnerability in AML. Through combined chromatin profiling and single-cell transcriptomics of a conditional knockout mouse, we demonstrate that Kat2a contributes to leukemia propagation through preservation of leukemia stem-like cells. Kat2a loss impacts transcription factor binding and reduces transcriptional burst frequency in a subset of gene promoters, generating enhanced variability of transcript levels. Destabilization of target programs shifts leukemia cell fate out of self-renewal into differentiation. We propose that control of transcriptional variability is central to leukemia stem-like cell propagation, and establish a paradigm exploitable in different tumors and distinct stages of cancer evolution., eLife digest Less than 30% of patients with acute myeloid leukaemia – an aggressive cancer of the white blood cells – survive five years post-diagnosis. This disease disrupts the maturation of white blood cells, resulting in the accumulation of immature cells that multiply and survive but are incapable of completing their maturation process. Amongst these, a group of cancer cells known as leukemic stem cells is responsible for continually replenishing the leukaemia, thus perpetuating its growth. Cancers develop when cells in the body acquire changes or mutations to their genetic makeup. The mutations that lead to acute myeloid leukaemia often affect the activity of genes known as epigenetic regulators. These genes regulate which proteins and other molecules cells make by controlling the way in which cells ‘read’ their genetic instructions. The epigenetic regulator Kat2a is thought to ‘tune’ the frequency at which cells read their genetic instructions. This tuning mechanism decreases random fluctuations in the execution of the instructions cells receive to make proteins and other molecules. In turn, this helps to ensure that individual cells of the same type behave in a similar way, for example by keeping leukaemia cells in an immature state. Here, Domingues, Kulkarni et al. investigated whether interfering with Kat2a can make acute myeloid leukaemia less aggressive by allowing the immature white blood cells to mature. Domingues, Kulkarni et al. genetically engineered mice to remove Kat2a from blood cells on demand and then inserted a mutation that causes acute myeloid leukaemia. The experiments showed that the loss of Kat2a delayed the development of leukaemia in the mice and progressively depleted leukaemia stem cells, causing the disease to become less aggressive. The results also showed that loss of Kat2a caused more fluctuations in how the white blood cells read their genetic code, which resulted in more variability in the molecules they produced and increased the tendency of the cells to mature. These findings establish that loss of Kat2a causes leukaemia stem cells to mature and stop multiplying by untuning the frequency at which the cells read their genetic instructions. In the future, it may be possible to develop drugs that target human KAT2A to treat acute myeloid leukaemia.

Climate and ecological change impacts represent the greatest global health challenge but also the greatest opportunity of the 21st century. Interlinking climate and ecological change impacts, with societal change and human health, should form the scientific progress in public health for current and future generations of researchers. Ecological public health approach is proposed to address the challenges faced by public health today, by its aims to integrate complexity, multiple interactions and change of societal and environmental systems, and also as an adaptable approach which can assist in exploring and understanding complex public health questions in a way that are usable to all. The aim of this chapter is to outline why ecological public health approach is a useful framework when trying to understand and measure the public health impacts of complex ecological and climate change, and societal systems transitions. To achieve its aim the chapter highlights key issues within this framework, and also illustrates with a few examples, to make it more explicit on how this system's approach can assist any economic models of cost–benefits of environmental health interventions.

We aimed to assess the rate and predictive factors of bloodstream infection (BSI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa in neutropenic cancer patients. We performed a multicenter, retrospective cohort study including oncohematological neutropenic patients with BSI due to P. aeruginosa conducted across 34 centers in 12 countries from January 2006 to May 2018. A mixed logistic regression model was used to estimate a model to predict the multidrug resistance of the causative pathogens. of a total of 1,217 episodes of BSI due to P. aeruginosa, 309 episodes (25.4%) were caused by MDR strains. the rate of multidrug resistance increased significantly over the study period (P = 0.033). Predictors of MDR P. aeruginosa BSI were prior therapy with piperacillin-tazobactam (odds ratio [OR), 3.48; 95% confidence interval [CI], 2.29 to 5.30), prior antipseudomonal carbapenem use (OR, 2.53; 95% CI, 1.65 to 3.87), fluoroquinolone prophylaxis (OR, 2.99; 95% CI, 1.92 to 4.64), underlying hematological disease (OR, 2.09; 95% CI, 1.26 to 3.44), and the presence of a urinary catheter (OR, 2.54; 95% CI, 1.65 to 3.91), whereas older age (OR, 0.98; 95% CI, 0.97 to 0.99) was found to be protective. Our prediction model achieves good discrimination and calibration, thereby identifying neutropenic patients at higher risk of BSI due to MDR P. aeruginosa. the application of this model using a web-based calculator may be a simple strategy to identify high-risk patients who may benefit from the early administration of broad-spectrum antibiotic coverage against MDR strains according to the local susceptibility patterns, thus avoiding the use of broad-spectrum antibiotics in patients at a low risk of resistance development., ESGBIES study group; ESGICH study group; Spanish Plan Nacional de I+D+i 2013-2016; Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases [REIPI RD16/0016/0001]; European Development Regional Fund A Way To Achieve Europe, Operative Program Intelligent Growth 2014-2020; Promex Stiftung fur die Forschung (Carigest SA); GileadGilead Sciences; PfizerPfizer, We thank the ESGBIES and the ESGICH study groups for supporting the study.; This study was supported by the Spanish Plan Nacional de I+D+i 2013-2016 and the Instituto de Salud Carlos III, Subdireccion General de Redes y Centros de Investigacion Cooperativa, Ministerio de Economia, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (grant REIPI RD16/0016/0001), cofinanced by the European Development Regional Fund A Way To Achieve Europe, Operative Program Intelligent Growth 2014-2020.; A.-S.B. received a grant from Promex Stiftung fur die Forschung (via Carigest SA) and funding from Gilead to attend the ECCMID Congress (2018). O.R.S. received speaker honoraria from MSD, Astellas, Novartis, and Pfizer. S.S.K. received speaker honoraria from Pfizer, MSD, Astellas. F.H. received speaker honoraria from MSD, and Pfizer and a research and educational grant from Pfizer. the rest of the authors declare no conflicts of interest.

Most cases of neuromyelitis optica spectrum disorders (NMOSD) harbor pathogenic autoantibodies against the water channel aquaporin 4 (AQP4). Binding of these antibodies to AQP4 on astrocytes initiates damage to these cells, which culminates in the formation of large tissue destructive lesions in the central nervous system (CNS). Consequently, untreated patients may become permanently blind or paralyzed. Studies on the induction and breakage of tolerance to AQP4 could be of great benefit for NMOSD patients. So far, however, all attempts to create suitable animal models by active sensitization have failed. We addressed this challenge and identified peptides, which mimic the conformational AQP4 epitopes recognized by pathogenic antibodies of NMOSD patients. Here we show that these mimotopes can induce the production of AQP4-reactive antibodies in Lewis rats. Hence, our results provide a conceptual framework for the formation of such antibodies in NMOSD patients, and aid to improve immunization strategies for the creation of animal models suitable for tolerance studies in this devastating disease. Funding Agencies|Else Kroner-Fresenius-Stiftung [2013_A283]; Austrian Science FundAustrian Science Fund (FWF) [P28476-B30, P32699B]; Austrian Ministery of Science, Research and Economy (BIGWIG-MS); Ministry of Education, Culture, Sports, Science and Technology of JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)

Introduction: Management of carbapenem resistant Acinetobacter baumannii infections in intensive care units is challenging because of few treatment options and poor outcomes. In order to contribute to patients’ survival, the factors related to mortality in these infections were evaluated in this study. Materials and Methods: In the 6-month study period, we included 60 patients with carbapenem resistant A. baumannii infections (45 ventilator associated pneumonia and 15 bacteremia) in two intensive care units of our hospital. We collected data of the patients prospectively. We noted demographic features of patients, Acute Physiology and Chronic Health Evaluation (APACHE II) , Sequential Organ Failure Assessment (SOFA), Clinical Pulmonary Infection Score (CPIS), Acute Kidney Injury (AKIN) scores, antibiotic treatments, clinical and microbiological outputs, and mortality rates during treatment and on the 30th day. Results: We observed that infections appeared at mean 11th day of the patients’ stay in the intensive care unit. Carbapenem resistant A. baumannii isolates were highly resistant to antibiotics except colistin. Only 9% of the patients had proper empirical treatment. Twenty five percent of the patients were dead before having a specific antibiotic treatment. Crude mortality rate was 66.7%, and 30th day mortality was 71.7%. The patients who had colistin and tigecycline combination had higher survival rates, but it was statistically insignificant. In univariate analysis high SOFA score (p= 0.0001), high procalcitonin level (p= 0.01), septic shock (p= 0.005), renal insufficiency (p= 0.005), rheumatological disease (p= 0.03) were related to higher mortality. We detected high SOFA score on the first day of infection as the only mortality related factor in multivariate analysis (p= 0.012). The patients who had higher mortality were those with delayed (> 3 days) proper antimicrobial treatment (p= 0.03). Conclusion: In our study, the high SOFA score on the first day of infection in intensive care units was found as a risk factor for mortality. We suggest that prompt administration of the proper antibiotic treatment to the patients who have risk factors for carbapenem-resistant A. baumannii infection can contribute to survival.

Purpose Transarterial chemoembolisation (TACE) using irinotecan-eluting beads is an additional treatment option for colorectal cancer liver metastases (CRLM) patients that are not eligible for curative treatment approaches. This interim analysis focuses on feasibility of the planned statistical analysis regarding data distribution and completeness, treatment intention, safety and health-related quality of life (HRQOL) of the first 50 patients prospectively enrolled in the CIrse REgistry for LifePearl™ microspheres (CIREL), an observational multicentre study conducted across Europe. Methods In total, 50 patients ≥ 18 years diagnosed with CRLM and decided to be treated with irinotecan-eluting LifePearl™ microspheres TACE (LP-irinotecan TACE) by a multidisciplinary tumour board. There were no further inclusion or exclusion criteria. The primary endpoint is the categorisation of treatment intention, and secondary endpoints presented in this interim analysis are safety, treatment considerations and HRQOL. Results LP-irinotecan TACE was conducted in 42% of patients as salvage therapy, 20% as an intensification treatment, 16% as a first-line treatment, 14% a consolidation treatment and 8% combination treatment with ablation with curative intent. Grade 3 and 4 adverse events were reported by 4% of patients during procedure and by 10% within 30 days. While 38% reported a worse, 62% reported a stable or better global health score, and 54% of patients with worse global health score were treated as salvage therapy patients. Conclusion This interim analysis confirms in a prospective analysis the feasibility of the study, with an acceptable toxicity profile. More patients reported a stable or improved HRQOL than deterioration. Deterioration of HRQOL was seen especially in salvage therapy patients. Trial Registration NCT03086096.

There is strong experimental evidence that physiologic stress from high temperatures is greater if humidity is higher. However, heat indices developed to allow for this have not consistently predicted mortality better than dry-bulb temperature.We aimed to clarify the potential contribution of humidity an addition to temperature in predicting daily mortality in summer by using a large multicountry dataset.In 445 cities in 24 countries, we fit a time-series regression model for summer mortality with a distributed lag nonlinear model (DLNM) for temperature (up to lag 3) and supplemented this with a range of terms for relative humidity (RH) and its interaction with temperature. City-specific associations were summarized using meta-analytic techniques.Adding a linear term for RH to the temperature term improved fit slightly, with an increase of 23% in RH (the 99th percentile anomaly) associated with a 1.1% [95% confidence interval (CI): 0.8, 1.3] decrease in mortality. Allowing curvature in the RH term or adding terms for interaction of RH with temperature did not improve the model fit. The humidity-related decreased risk was made up of a positive coefficient at lag 0 outweighed by negative coefficients at lags of 1-3 d. Key results were broadly robust to small model changes and replacing RH with absolute measures of humidity. Replacing temperature with apparent temperature, a metric combining humidity and temperature, reduced goodness of fit slightly.The absence of a positive association of humidity with mortality in summer in this large multinational study is counter to expectations from physiologic studies, though consistent with previous epidemiologic studies finding little evidence for improved prediction by heat indices. The result that there was a small negative average association of humidity with mortality should be interpreted cautiously; the lag structure has unclear interpretation and suggests the need for future work to clarify. https://doi.org/10.1289/EHP5430.

Background and Objectives The aim of the present study is to report the early and mid-term clinical and haemodynamic results of the St Jude Medical Regent 19-mm aortic mechanical prothesis (SJMR-19). Materials and Methods Between January 2002 and January 2012, 265 patients with aortic valve disease underwent AVR (Aortic Valve Replacement) with a SJMR-19 (St Jude Medical Regent Nr.19). There were 51 males. Mean age was 67.5±12.72years and mean body surface area (BSA) was 1.67±0.14m2. Thirty-six patients required annulus enlargement. The mean follow-up was 34.5±18.8months (range 6–60 months). All patients underwent echocardiographic examination at discharge and within one year after surgery. Results There were 14 (5.3%) hospital deaths. Six of the hospital deaths were identified in patients undergoing reoperation, significantly higher than patients undergoing first time operation (p=0.0001). Also the postoperative mortality was significantly higher in patients undergoing annulus enlargement versus patients not requiring annulus enlargement (p=0.02). The mean transprosthesis gradient at discharge was 19±9mmHg. At six months follow-up the mean NYHA FC class was 1.6±0.5 significantly lower than preoperatively 2.4±0.75 (p i ) were significantly lower than preoperatively The actuarial survival and cumulative freedom from reoperation at one, two and three years follow-up were 99.5%, 97.5%, 96.7% and 99.2%, 96.5%, 94.5% respectively. The cumulative actuarial free-events survival at four years was 92%. The Cox model identified age (p=0.015), LVEF≤35% (p=0.043), reoperation (p=0.031), combined surgery (p=0.00002), and annulus enlargement (p=0.015) as strong predictors for poor actuarial free-major events survival. Conclusions The SJMR-19 offers excellent postoperative clinical, haemodynamic outcome and LVM i reduction in patients with small aortic annulus. These data demonstrate that the modern St Jude small mechanical protheses do not influence the intermediate free-reoperation survival.

Introduction and objective The left ventricular pseudoaneurysm (LVP) is rare, the surgical experience is limited and its surgical treatment remains still a challenge with an elevated mortality. Herein, it is presented a retrospective analysis of our experience with acquired post infarct LVP over a10-year period. Materials and methods Between January 2006 through August 2016, a total of 13 patients underwent operation for post infarct pseudoaneurysm of the left ventricle. There were 10 men and 3 women and the mean age was 61 ± 7.6 years. 4 patients presented acute LVP. Two patients had preoperative intraortic balloon pump implantation. Results Various surgical techniques were used to obliterate the pseudoaneurysm such as direct pledgeted sutures buttressed by polytetrafluoroethylene felt, a Gore-Tex or Dacron patch, transatrial closure of LVP neck in submitral pseudoaneurysm, or linear closure in cases presenting associated postinfarct ventricular septal defect. Concomitant coronary artery bypasses were performed for significant stenoses in 12 patients, ventricular septal defect closure in 4 patients, mitral valve replacement in 3 and aortic valve replacement in 1 patient. Operative mortality was 30.8% (4 patients). Three of them were acute LVP. Three patients required the continuous hemodyalisis and 8 patients required intra-aortic balloon pump. At follow-up two deaths occurred at 1 and 3 years after surgery. Conclusion In conclusion, this study revealed that surgical repair of post infarct left ventricular pseudoaneurysm was associated with an acceptable surgical mortality rate, that cardiac rupture did not occur in surgically treated patients., Highlights • Objective: Our experience with post-infarction left ventricular pseudoaneurysms (LVP) and surgical techniques in 13 patients. • Various techniques: 1) direct pledgeted sutures; 2) single patch; 3) double-patch; 4) pericardial patch through the left atrium. • Hospital mortality 4 (30.7%). Literature review: 306 patients with LVP undergoing surgery with 21.2% (65 deaths) mortality. • In conclusion, this study revealed that surgical repair of LVP was associated with an acceptable surgical mortality rate. • Cardiac rupture did not occur. Various techniques are available and should be considered according to the case presentation.

Book chapter, jointly written with authors from University of Cambridge, UK (Department of Haematology) and IBB University, Nigeria (Faculty of Natural Sciences) Metabolic syndrome is an umbrella term for a group of disorders related to imbalance of energy utilization and storage. It includes obesity, hypertension, increased triglyceride levels, aberrant cholesterol levels, and insulin resistance with resulting elevated fasting blood glucose levels that usually result in diabetes. Metabolic syndrome is associated with chronic low-grade local tissue inflammation and increased susceptibility to a variety of degenerative diseases. Lifestyle changes, e.g. more physical exercise, a diet rich in fruits and vegetables, etc. can help prevent or delay metabolic syndrome related problems. In addition, certain food supplements or herbal extracts are commonly believed to make an important contribution to a healthy life style, i.e glucomannan. Whereas there is a consensus that a vegetable-rich diet contributes to a lower occurrence of metabolic syndrome related disorders, the exact nature of the compounds in the diet that contribute to the prevention of degenerative diseases is still a matter of debate. This chapter book sets out to evaluate several natural products that are currently considered to play a role in the prevention or management of type 2 diabetes. Phytochemicals with antioxidant activity were long believed to be a major contributing factor in the suppression of chronic inflammation. However, not all antioxidant compounds have anti-inflammatory properties. Further, the peroxisome proliferator-activated receptor gamma (PPARγ)-activating potential of a wide range of natural products has been explored in great detail, and resulted in a credible model. A third model considers the potential role of phytoestrogens on human physiology. These compounds are known to interact with oestrogen receptors and can modulate a range of cell signalling pathways, either as agonists or as antagonists. The efficacy of several of the identified pharmaceutically active compounds and plant extracts, either as supplements, dietary factors or as part of a healthy life style, may be supported by laboratory results. However, caution is justified when considering food supplements in doses that greatly exceed the amounts that would be obtained through a regular diet.

Introduction: Wolcott–Rallison syndrome (WRS) is a rare, autosomal recessive disorder with infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, osteopenia, mental retardation or developmental delay, and hepatic and renal dysfunction as main clinical findings. Cardiovascular system is very rarely affected and there are a limited number of publications where WRS is associated with congenital heart disease. The aim of this interesting case is to report an infant with Wolcott – Rallison syndrome, type I diabetes mellitus, and complex congenital heart disease, diagnosed in a pre term neonate. Case report: A case of preterm neonate who presented immediately after delivery with hyperglycemia and heart murmur. Clinical and laboratory investigation showed diabetes mellitus type I and double outlet right ventricle. Genetic examination showed classic mutations in the EIF2AK3 gene - eukaryotic translation initiation factor 2α kinase 3. Conclusion: Diabetes in neonatal age raises doubts about the possibility of association with the syndrome and other diseases.

Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with abnormal progenitor self-renewal and defective myelo-monocytic differentiation. Its pathogenesis comprises subversion of transcriptional regulation, through mutation and by hijacking normal chromatin regulation. Kat2a is a histone acetyltransferase central to promoter activity that we recently associated with stability of pluripotency networks, and identified as a genetic vulnerability in AML. Through combined chromatin profiling and single-cell transcriptomics, we demonstrate that Kat2a contributes to leukemia propagation through homogeneity of transcriptional programs and preservation of leukemia stem-like cells. Kat2a loss reduces transcriptional bursting frequency in a subset of gene promoters, generating enhanced variability of transcript levels but minimal effects on mean gene expression. Destabilization of target programs shifts cellular equilibrium out of self-renewal towards differentiation. We propose that control of transcriptional variability is central to leukemia stem-like cell propagation, and establish a paradigm exploitable in different tumors and at distinct stages of cancer evolution. This work was funded by a Kay Kendall Leukaemia Fund Intermediate Fellowship (KKL888) and by a Leuka John Goldman Fellowship for Future Science (2017) to C.P.. S.P. is funded through a Cambridge-DBT Lectureship; R.K. was funded by an Isaac Newton Trust (INT) Research Grant and a Wellcome Trust ISSF/INT/University of Cambridge Joint Research Grant to C.P.; S.G. is funded by a Lady Tata Memorial Trust PhD Studentship, a Trinity Henry Barlow Trust Scholarship, and the Cambridge Trust; K.Z. received funding from AIRC (Italian Association for Cancer Research) and is the current recipient of a European Commission Horizon 2020 Marie Sklodowska Curie Post-Doctoral Fellowship.

Vertebrates respond to stressful stimuli with the secretion of glucocorticoid (GC) hormones, such as corticosterone (CORT), and measurements of these hormones in wild species can provide insight into physiological responses to environmental and human-induced stressors. California condors (Gymnogyps californianus) are a critically endangered and intensively managed avian species for which information on GC response to stress is lacking. Here we evaluated a commercially available I125 double antibody radioimmunoassay (RIA) and an enzyme-linked immunosorbent assay (ELISA) kit for measurement of CORT and GC metabolites (GCM) in California condor plasma, urate, and feather samples. The precision and accuracy of the RIA assay outperformed the ELISA for CORT and GCM measurements, and CORT and GCM values were not comparable between the two assays for any sample type. RIA measurements of total CORT in condor plasma collected from 41 condors within 15 minutes of a handling stressor were highly variable (median = 70 ng/mL, range = 1-189 ng/mL) and significantly different between wild and captive condors (p = 0.02, two-tailed t-test, n = 10 wild and 11 captive). Urate GCM levels (median = 620 ng/g dry wt., range = 0.74-7200 ng/g dry wt., n = 216) significantly increased within 2 hr of the acute handling stressor (p = 0.032, n = 11 condors, one-tailed paired t-test), while feather section CORT concentrations (median = 18 pg/mm, range = 6.3-68 ng/g, n = 37) also varied widely within and between feathers. Comparison of multiple regression linear models shows condor age as a significant predictors of plasma CORT levels, while age, sex, and plasma CORT levels predicted GCM levels in urates collected within 30 min of the start of handling. Our findings highlight the need for validation when selecting an immunoassay for use with a new species, and suggest that non-invasively collected urates and feathers hold promise for assessing condor responses to acute or chronic environmental and human-induced stressors.

Collaboration between Leicester School of Pharmacy, Faculty of Health and Life Sciences, De Montfort University, and Department of Pharmacy and Biotechnology, University of Bologna. open access article The occurrence of atherosclerosis and diabetes is expanding rapidly worldwide. These two metabolic disorders often co-occur, and are part of what is often referred to as the metabolic syndrome. In order to determine future therapies, we propose that molecular mechanisms should be investigated. Once the aetiology of the metabolic syndrome is clear, a nutritional intervention should be assessed. Here we focus on the protective effects of some dietary flavonoids, and their metabolites. Further studies may also pave the way for development of novel drug candidates.

We presented a sepsis outbreak caused by Serratia marcescens from contaminated propofol to raise awareness. Three patients had sepsis syndrome after chest surgery. Isolation of S marcescens from patients' respiratory and blood samples alerted us to a possible outbreak. Four syringes filled with propofol and 1 saline solution yielded S marcescens. Nine of 10 isolates from samples of patients and environment genotyped by pulsed-field gel electrophoresis were the same. Disobeying aseptic injection rules of propofol is still causing outbreaks. (C) 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

WOS: 000407294300013, Introduction: Hemophilia is a genetic disease presenting predominantly with joint hemorrhages in clinical course. Thus, its treatment requires transfusion of numerous blood and blood products. As a consequence, hemophilia patients are under high risk of many transfusion-borne infections, especially viral hepatitis and human immunodeficiency virus infection. Measures should be taken to prevent the transmission of blood-borne diseases in these patients. Vaccination against hepatitis A and B and patient education are especially crucial for prevention. The aim of this study was to evaluate hemophilia patients' knowledge on viral hepatitis and to test whether their knowledge could be improved by a two-hour training program. Materials and Methods: The study was conducted on June 6, 2015 during a full-day educational program on different topics for hemophilia patients being followed by the Department of Internal Medicine, Hematology Division at Ege University Faculty of Medicine. Twenty-four participating patients filled up pre-test questionnaires, followed by a training given by an expert. The same questionnaire was distributed as a post-test after the training session. There were 18 questions in the questionnaire, comprising six questions on socio-demographic characteristics, eight true/false questions on knowledge about hepatitis and four questions on their vaccination status. Pre-and post-tests were compared with the McNemar test. Results: The mean age of the participating 24 patients was 37.0 +/- 13.0 (20-67) years. The mean duration since the diagnosis of hemophilia was 32.7 +/- 12.8 (6-60) years. Among the participants, one had chronic hepatitis B, two had chronic hepatitis C and the rest were unaware of their viral hepatitis status. Before the training, 19 patients had heard of hepatitis B, 17 had heard of hepatitis A and C, four had heard of hepatitis D and two had heard of hepatitis E. Only two patients knew the routes of transmission of hepatitis A correctly. The patients had misconceptions on the transmission routes of hepatitis B and C. After the training, their information on the fact that hepatitis A is spread primarily through contaminated food or water, hepatitis C can be transmitted via sexual intercourse, there are vaccines to prevent hepatitis A and a vaccine against hepatitis C is not available yet, improved significantly. Conclusion: Patient education programs targeting special high-risk groups such as haemophilia patients could both increase their knowledge and render prevention of viral hepatitis possible.

open access journal Resveratrol is a well notorious compound that may play a role in the prevention of diabetes complications and different cancers. Along, resveratrol, a naturally occurring phytoalexin, is known to exert numerous beneficial effects in the organism. Isolation of resveratrol from plants, however, has been proved being difficult. Importantly, the bioavailability in the body is poor therefore capability is reduced and not enough resveratrol reaches the target organ. In this study we generated different methoxylated resveratrol analogues using Wittig reaction. Trans stilbene obtained was 0.08 g and the cis one was 0.01 g. Additionally with the Horner-Witting method a yield of 0.15 g trans stilbene was obtained. By substituting the hydroxyl group with methoxy group at different positions on the aromatic rings, we could increase the efficacy and bioavailability of the Trans form of resveratrol.

Telomerase has a critical role in cell proliferation, tumor maintaining, and therapy resistance, which act by modifying many signaling pathways. 2-[(E)-3-Naphtalen-2-yl-but-2-enoylamino]-benzoic acid (BIBR1532) is one of the most studied telomerase inhibitors, and it targets telomerase components TERC and TERT. In this novel study, we aimed to investigate the epigenetic effects of BIBR1532 on both hematologic malignancies and solid tumors. K-562 human chronic myeloid leukemia cell line and U87MG glioblastoma cell line were compared with control groups without BIBR1532 treatment. Cytotoxic effects of BIBR1532 were determined by using WST-1 assay. Apoptotic effects of BIBR1532 were detected by using annexin V method. To assess expression changes in the human epigenetic chromatin modification enzyme genes, total RNA was isolated from K-562 and U87MG cells treated with BIBR1532 and untreated control cells. BIBR1532 induced 2.41-fold apoptotic cell death in U87MG cell lines compared with control groups. Apoptosis was slightly induced in K-562 cells with BIBR1532 treatment compared with control cells. We observed that BIBR1532 also regulates similar genes in both cell lines, and it is useful on epigenetic mechanisms. As a result, telomerase inhibitor BIBR1532 has a significant effect on both hematological malignancies and solid tumors.

In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of non-invasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in two independent cohorts of 131 and 54 patients. Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis and overall survival, revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential expression analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 disease in both patient cohorts. Increasing levels of these miRNAs were also observed in serum from xenografted mice bearing human neuroblastoma tumors. Moreover, murine serum miRNA levels were strongly associated with tumor volume, suggesting this miRNA signature may be applied to monitor disease burden.

It is emphasized that cancer stem cells (CSCs) forming the subpopulation of tumour cells are responsible for tumour growth, metastasis, and cancer drug resistance. Inadequate response to conventional therapy in breast cancer leads researchers to find new treatment methods and literature surveys that support CSC studies. A selective anticancer agent BIBR1532 inhibits the telomerase enzyme. Many of the chemotherapeutic drugs used in clinical trials have harmful effects, but the advantage of telomerase-based inhibitors is that they are less toxic to healthy tissues. The phosphoinositide 3-kinase (PI3K)/serine/threonine kinase (Akt)/mammalian target of rapamycin (mTOR) pathway is common in breast cancer, and the interaction between the mTOR pathway and human telomerase reverse transcriptase (hTERT) is essential for the survival of cancer cells. In our study, we treated MCF-7, breast cancer stem cell (BCSC) and normal breast epithelial cell MCF10A with the BIBR1532 inhibitor. The IC 50 doses for the 48th hour of BIBR1532 treatment were detected as 34.59 μM in MCF-7, 29.91 μM in BCSCs, and 29.07 μM in MCF10A. It has been observed that this agent induces apoptosis in the BCSC and MCF-7 cell lines. According to the results of cell cycle analysis, G 2 /M phase accumulation was observed in BCSC and MCF-7 cell lines. It has also been shown that BIBR1532 suppresses telomerase activity in BCSC and MCF-7. The effect of BIBR1532 on the mTOR signalling pathway has been investigated for the first time in this study. It is thought that the telomerase inhibitor may bring a new approach to the treatment and it may be useful in the treatment of CSCs.

In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of noninvasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in 2 independent cohorts of 131 and 54 patients. Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis, and overall survival revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential abundance analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 disease in both patient cohorts. Increasing levels of these miRNAs were also observed in serum from xenografted mice bearing human neuroblastoma tumors. Moreover, murine serum miRNA levels were strongly associated with tumor volume. These findings were validated in longitudinal serum samples from metastatic neuroblastoma patients, where the 9 miRNAs were associated with disease burden and treatment response. CA extern