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The term liquid biopsy (LB) refers to the use of various biological fluids as a surrogate for neoplastic tissue to achieve information for diagnostic, prognostic and predictive purposes. In the current clinical practice, LB is used for the identification of driver mutations in circulating tumor DNA derived from both tumor tissue and circulating neoplastic cells. As suggested by a growing body of evidence, however, there are several clinical settings where biological samples other than tissue could be used in the routine practice to identify potentially predictive biomarkers of either response or resistance to targeted treatments. New applications are emerging as useful clinical tools, and other blood derivatives, such as circulating tumor cells, circulating tumor RNA, microRNAs, platelets, extracellular vesicles, as well as other biofluids such as urine and cerebrospinal fluid, may be adopted in the near future. Despite the evident advantages compared with tissue biopsy, LB still presents some limitations due to both biological and technological issues. In this context, the absence of harmonized procedures corresponds to an unmet clinical need, ultimately affecting the rapid implementation of LB in clinical practice. In this position paper, based on experts’ opinions, the AIOM–SIAPEC-IAP–SIBIOC–SIF Italian Scientific Societies critically discuss the most relevant technical issues of LB, the current and emerging evidences, with the aim to optimizing the applications of LB in the clinical setting., Highlights • In the current clinical practice LB is used for the identification of driver mutations in circulating tumor DNA (ctDNA). • New applications in tumors other than non-small-cell lung cancer (NSCLC) are emerging as useful clinical tools. • Other blood derivatives, together with other biofluids, are an active field of research and may be adopted in the near future. • Despite the evident advantages, liquid biopsy still presents limitations due to both biological and technological issues. • Standardization of the procedures needs to be addressed to ensure widespread implementation in clinical practice.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is emerging as a global pandemic outbreak. To date, approximately one million deaths and over 32 million cases have been reported. This ongoing pandemic urgently requires an accurate testing device that can be used in the field in a fast manner. Serological assays to detect antibodies have been proven to be a great complement to the standard method of reverse transcription-polymerase chain reaction (RT-PCR), particularly after the second week of infection. We have developed a specific and sensitive immunosensor for immunoglobulin detection produced against SARS-CoV-2. Unlike other lateral flow-based assays (LFAs) involving the utilization of multiple antibodies, we have reported a label-free paper-based electrochemical platform targeting SARS-CoV-2 antibodies without the specific requirement of an antibody. The presence of SARS-CoV-2 antibodies will interrupt the redox conversion of the redox indicator, resulting in a decreased current response. This electrochemical sensor was proven effective in real clinical sera from patients with satisfactory results. In addition, the proposed format was also extended to antigen detection (the spike protein of SARS-CoV-2), which presents new possibilities for diagnosing COVID-19., Highlights • Electrochemical sensor for COVID-19 diagnostic. • Serological assay for SARS-CoV-2 antibodies was demonstrated. • Sensitivity enhancement compared to the traditional LFA devices. • Applicable to real clinical sera with satisfactory results.

Pancreatic cancer (PC) is a common cause of cancer-related death, due to difficulties in detecting early-stage disease, to its aggressive behaviour, and to poor response to systemic therapy. Therefore, developing strategies for early diagnosis of resectable PC is critical for improving survival. Diabetes mellitus is another major public health problem worldwide. Furthermore, diabetes can represent both a risk factor and a consequence of PC: nowadays, the relationship between these two diseases is considered a high priority for research. New-onset diabetes can be an early manifestation of PC, especially in a thin adult without a family history of diabetes. However, even if targeted screening for patients at higher risk of PC could be a promising approach, this is not recommended in asymptomatic adults with new-onset diabetes, due to the much higher incidence of hyperglycaemia than PC and to the lack of a safe and affordable PC screening test. Prompted by a well-established and productive multidisciplinary cooperation, the Italian Association of Medical Oncology (AIOM), the Italian Medical Diabetologists Association (AMD), the Italian Society of Endocrinology (SIE), and the Italian Society of Pharmacology (SIF) here review available evidence on the mechanisms linking diabetes and PC, addressing the feasibility of screening for early PC in patients with diabetes, and sharing a set of update statements with the aim of providing a state-of-the-art overview and a decision aid tool for daily clinical practice., Highlights • The incidence of PC is increasing and its prognosis is very poor; therefore, early detection is fundamental. • New-onset diabetes may be an early manifestation of PC, often disappearing after its resection. • Screening for PC is not currently recommended among people with new-onset diabetes, due to its high incidence. • Thin subjects >50 years old at the time of diabetes onset, with sudden weight loss and severe hyperglycaemia are at higher risk. • Currently some clinical models are promising for stratifying cancer risk in people with new-onset diabetes.

Made available in DSpace on 2019-10-04T12:39:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-07-15 Japan Society for the Promotion of Science, Japan JSPS KAKENHI Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) This article presents results of a pulsed UV laser method for the simultaneous reduction of graphite oxide (GO) and patterning of reduced graphene oxide (rGO). This direct laser writing method was applied to the fabrication of graphene-based, in-plane interdigitated micro-supercapacitors (mu-SCs), prepared on free-standing GO paper (10 mu m thick). The electrochemical performance of mu-SCs was studied using two different electrolytes (KOH and NaCl). The results from cyclic voltammetry measurements exhibited typical electrical double layer behavior, with specific capacitances of 9.3 mu F/cm(2) and 13.8 mu F/cm(2) (at a scan rate of 10 mV/s) for KOH and NaCl electrolytes, respectively. The mu-SCs exhibited good performance, with retention of 95% of the original capacitance values after 3400 charge-discharge cycles. When compared to devices obtained by conventional lithographic techniques, the laser fabrication of planar mu-SCs is faster, cost-effective and scalable. We believe this one-step and environmentally friendly laser-assisted method to be a good alternative for the fabrication of flexible energy storage devices. (C) 2019 Elsevier Ltd. All rights reserved. Toyohashi Univ Technol, Dept Elect & Elect Informat Engn, 1-1 Hibarigaoka,Tempaku Cho, Toyohashi, Aichi 4418580, Japan Ctr Informat Technol Renato Archer CTI, BR-13069901 Campinas, SP, Brazil Univ Campinas UNICAMP, Ctr Semicond Components & Nanotechnol CCS Nano, BR-13083870 Campinas, SP, Brazil Sao Paulo State Univ, Dept Phys, Fac Sci & Technol, BR-19060900 Presidente Prudente, SP, Brazil CUHP, Sch Phys & Mat Sci, Dharamshala 176215, HP, India Univ Campinas UNICAMP, Inst Chem, Dept Analyt Chem, POB 6154, BR-13084974 Campinas, SP, Brazil Sao Paulo State Univ, Dept Phys, Fac Sci & Technol, BR-19060900 Presidente Prudente, SP, Brazil Japan Society for the Promotion of Science, Japan: P18063 JSPS KAKENHI: 18H03841 JSPS KAKENHI: 18F18063 FAPESP: 2017/22186-0 FAPESP: 2013/14262-7

Made available in DSpace on 2020-12-10T17:34:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-07-01 In the recent past, wildfires have received much attention both by science and by the media, especially in relation to deforestation, degradation and climate change and when affecting fire-sensitive ecosystems. On the other hand, fire is a natural process in many ecosystems, in particular those to be considered fire-dependent; here, maintaining natural fire regimes is important to maintain biodiversity and ecosystem services. In many regions of the world we are still in the need for a better understanding of fire effects on plant populations, communities and ecosystems. For instance, responses of individuals and populations to heat and fire can differ among distinct fire-prone ecosystems, and community level responses often vary depending on historical disturbance regimes or the fire regime as such. Effects on ecosystem processes, e.g. on carbon cycles, can vary greatly in scale and are even more difficult to predict. This adds up to uncertainties regarding appropriate fire management strategies, both in fire-prone and fire-sensitive ecosystems. Here, we introduce a set of opinion papers on fires in Brazil and a forthcoming Virtual Special Issue of Flora - Morphology, Distribution, Functional Ecology of Plants on Fire and vegetation, with contributions expected from a broad range of topics related to fire, plants, and vegetation. This special issue will contribute to the development not only of more knowledge on fire effects on plants and vegetation, but also to advances in fire management policies in different ecosystems around the world. The main issue, after all, is to go beyond simple classification of fires as 'good' or 'bad', but rather to develop strategies to deal with changing fire regimes and their effects in a dynamic world increasingly modified by human actions. Univ Fed Rio Grande do Sul, Dept Bot, Av Bento Goncalves 9500, BR-91501970 Porto Alegre, RS, Brazil Univ Fed Minas Gerais, Ctr Ecol Synth & Conservat, Dept Genet Ecol & Evolucao, Av Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG, Brazil Univ Estadual Paulista, Fac Ciencias Agr & Vet, Dept Biol, Via Acesso Prof Paulo Donato Castellane S-N, BR-14884000 Jaboticabal, Brazil TU Bergakad Freiberg, Inst Biosci, Leipziger Str 29, D-09599 Freiberg, Germany Univ Estadual Paulista, Fac Ciencias Agr & Vet, Dept Biol, Via Acesso Prof Paulo Donato Castellane S-N, BR-14884000 Jaboticabal, Brazil

A major application of microfluidic paper-based analytical devices (mu PADs) includes the field of point-of-care (POC) diagnostics. It is important for POC diagnostics to possess properties such as ease-of-use and low cost. However, mu PADs need multiple instruments and fabrication steps. In this study, two different chemicals (Hexamethyldisilazane and Tetra-ethylorthosilicate) were used, and three different methods (heating, plasma treatment, and microwave irradiation) were compared to develop mu PADs. Additionally, an inkjet-printing technique was used for generating a hydrophilic channel and printing certain chemical agents on different regions of a modified filter paper. A rapid and effective fabrication method to develop mu PADs within 10 min Was introduced using an inkjet-printing technique in conjunction with a microwave irradiation method. Environmental scanning electron microscope (ESEM) and x-ray photoelectron spectroscopy (XPS) were used for morphology characterization and determining the surface chemical compositions of the modified filter paper, respectively. Contact angle measurements were used to fulfill the hydrophobicity of the treated filter paper. The highest contact angle value (141 degrees +/- 1) was obtained using the microwave irradiation method over a period of 7 min, when the filter paper was modified by TEOS. Furthermore, by using this method, the XPS results of TEOS-modified filter paper revealed Si2p (23%) and Si-O bounds (81.55%) indicating the presence of Si-O-Si bridges and Si(OEt) groups, respectively. The ESEM results revealed changes in the porous structures of the papers and decreases in the pore sizes. Washburn assay measurements tested the efficiency of the generated hydrophilic channels in which similar water penetration rates were observed in the TEOS-modified filter paper and unmodified (plain) filter paper. The validation of the developed mu PADs was performed by utilizing the rapid urease test as a model test system. The detection limit of the developed mu PADs was measured as 1 unit ml(-1) urease enzyme in detection zones within a period of 3 min. The study findings suggested that a combination of microwave irradiation with inkjet-printing technique could improve the fabrication method of mu PADs, enabling faster production of mu PADs that are easy to use and cost-effective with long shelf lives. (C) 2016 Elsevier B.V. All rights reserved.

Gait analysis is recognized as a useful assessment tool in the field of human movement research. However, doubts remain on its real effectiveness as a clinical tool, i.e. on its capability to change the diagnostic-therapeutic practice. In particular, the conditions in which evidence of a favorable cost-benefit ratio is found and the methodology for properly conducting and interpreting the exam are not identified clearly. To provide guidelines for the use of Gait Analysis in the context of rehabilitation medicine, SIAMOC (the Italian Society of Clinical Movement Analysis) promoted a National Consensus Conference which was held in Bologna on September 14th, 2013. The resulting recommendations were the result of a three-stage process entailing i) the preparation of working documents on specific open issues, ii) the holding of the consensus meeting, and iii) the drafting of consensus statements by an external Jury. The statements were formulated based on scientific evidence or experts’ opinion, when the quality/quantity of the relevant literature was deemed insufficient. The aim of this work is to disseminate the consensus statements. These are divided into 13 questions grouped in three areas of interest: 1) General requirements and management, 2) Methodological and instrumental issues, and 3) Scientific evidence and clinical appropriateness. SIAMOC hopes that this document will contribute to improve clinical practice and help promoting further research in the field.

Scope Hepatitis B virus (HBV) infection reactivation is associated with high morbidity and mortality in patients with haematologic malignancy and/or haematopoietic stem cell transplantation (HSCT). However, information on this issue is limited. The scope of this position paper is to provide recommendations on HBV screening, monitoring, prophylaxis, treatment and vaccination in the patients described above. Methods These recommendations were developed from one meeting of experts attended by different Italian scientific societies as well as from a systematic literature review (of articles published through December 31, 2016) on HBV infection in haematologic patients and in patients who underwent haematopoietic stem cell transplantation published in the same issue of the journal. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess each recommendation's quality. Questions addressed These recommendations provide the answers to the following questions: (a) HBV screening and monitoring: Who should be screened before chemotherapy? Which screening tests should be used? Should HBV-DNA detection be used to monitor HBV reactivation before starting antivirals? What is the best timeline to monitor HBV reactivation? (b) Prophylaxis in HBsAg-positive patients: Which antiviral drugs should be used to treat HBsAg-positive patients? How long should antiviral prophylaxis be provided to HBsAg-positive patients? (c) Prophylaxis in patients with resolved HBV infection: Which patients with resolved HBV infection should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (d) HBV infection management strategy in autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT): Which HSCT recipients should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (e) Choice of antiviral drugs in the treatment of HBV reactivation: Should third-generation anti-HBV drugs be preferred to first- or second-generation antiviral drugs in the treatment of HBV reactivation with or without hepatitis flare in haematologic patients? (f) Immunization against HBV in patients with haematologic malignancies and/or patients who underwent HSCT: Should these patients be vaccinated? Which HBV vaccination schedule should be adopted? Recommendations Haematologic patients should be screened for hepatitis B surface antigen (HBsAg) plus anti-hepatitis B core protein (HBc), and HBV DNA before chemotherapy. HBV DNA levels should be monitored monthly in all HBV-positive patients who do not receive prophylaxis. HBsAg-positive haematologic patients and those undergoing HSCT should receive third-generation antiviral therapy as prophylaxis. Anti-HBc-positive lymphoma patients and those receiving HSCT should receive antiviral prophylaxis. All HBV-negative haematologic patients should be vaccinated for HBV. The acquisition of data from well-designed studies is desirable in the near future.

The use of human albumin is common in hepatology since international scientific societies support its administration to treat or prevent severe complications of cirrhosis, such as the prevention of post-paracentesis circulatory dysfunction after large-volume paracentesis and renal failure induced by spontaneous bacterial peritonitis, and the treatment of hepatorenal syndrome in association with vasoconstrictors. However, these indications are often disregarded, mainly because the high cost of human albumin leads health authorities and hospital administrations to restrict its use. On the other hand, physicians often prescribe human albumin in patients with advanced cirrhosis for indications that are not supported by solid scientific evidence and/or are still under investigation in clinical trials. In order to implement appropriate prescription of human albumin and to avoid its futile use, the Italian Association for the Study of the Liver (AISF) and the Italian Society of Transfusion Medicine and Immunohaematology (SIMTI) nominated a panel of experts, who reviewed the available clinical literature and produced practical clinical recommendations for the use of human albumin in patients with cirrhosis.

Aspect-Oriented Software Development (AOSD) and Model-Driven Development (MDD) are often said to be alike since both approaches are based on the selection of elements (i.e. join points in AOSD and model elements in MDD) and their subsequent adaptation (i.e. weaving in AOSD and transformation in MDD). But does this mean that AOSD and MDD are in fact two words for pretty much the same thing? In this position paper, we argue that there are essential differences between the aspect-oriented and the model-driven approach.

Background The COVID-19 pandemic has led to significant mental health consequences for frontline health care workers (FHCWs). However, no known study has examined the prevalence, determinants, or correlates of posttraumatic growth (PTG) in this population. Methods Data were analyzed from a prospective cohort of FHCWs at an urban tertiary care hospital in New York City (NYC). Assessments were conducted during the spring 2020 pandemic peak (Wave 1) and seven months later (Wave 2). Multivariable logistic regression analyses were conducted to identify Wave 1 sociodemographic, occupational, and psychosocial factors associated with PTG at Wave 2, and the association between aspects of PTG with burnout and pandemic-related PTSD symptoms at Wave 2. Results A total 76.8% of FHCWs endorsed moderate or greater PTG; the most prevalent domains were increased appreciation of life (67.0%), improved relationships (48.7%), and greater personal strength (44.1%). Non-White race/ethnicity, greater levels of positive emotions, pandemic-related PTSD symptoms, dispositional gratitude, and feelings of inspiration were independently associated with PTG. At Wave 2, endorsement of spiritual growth during the pandemic was associated with 52% and 44% lower odds of screening positive for pandemic-related PTSD symptoms and burnout, respectively; greater improvement in relationships was associated with 36% lower odds of screening positive for burnout. Limitations Single institution study and use of self-report instruments. Conclusions Nearly 4-of-5 FHCWs report pandemic-related PTG, driven largely by salutogenic factors assessed during the pandemic surge. Interventions to bolster these factors may help promote PTG and mitigate risk for burnout and pandemic-related PTSD symptoms in this population.

Background Unpaid caregivers of adults play critical roles in health care systems by providing care to older adults and those with chronic conditions. The COVID-19 pandemic has heightened caregiving needs, forcing some into caregiving roles and disrupting others. We sought to estimate the prevalence of and identify factors associated with adverse mental health symptoms, substance use, and suicidal ideation amongst unpaid caregivers of adults versus non-caregivers. Methods During June 24-30, 2020, surveys were administered to U.S. adults. Quota sampling and survey weighting were implemented to improve sample representativeness of age, gender, and race/ethnicity. Results Of 9,896 eligible invited adults, 5,412 (54.7%) completed surveys and 5,011 (92.6%) met screening criteria and were analyzed, including 1,362 (27.2%) caregivers. Caregivers had higher adverse mental health symptom prevalences than non-caregivers, including suicidal ideation (33.4% vs 3.7%, p

Background The mental health of racial/ethnic minority groups in the United States may be disproportionately impacted by the COVID-19 pandemic due to greater experience of peri-pandemic stressors. Yet, few studies have systematically examined racial/ethnic differences in mental health outcomes in this context. Methods Data came from the COVID-19 Southern Cities Study, a probability-based, cross-sectional study conducted in May/June 2020 among adults living in the metropolitan statistical areas of Atlanta, Austin, Dallas, Houston, and New Orleans. Unadjusted and adjusted associations between racial/ethnic identity and past-week depression and/or anxiety symptoms (Patient Health Questionnaire-2 score ≥ 3 or Generalized Anxiety Disorder-2 score ≥ 3), trouble sleeping, physical reactions when thinking about COVID-19, and self-rated worsened mental health due to the pandemic were estimated in separate logistic regression models. Results Over 30% of respondents reported depression and/or anxiety symptoms, 21% reported physical reactions, 25% had trouble sleeping, and 33% worsened mental health since the pandemic began. Adjusting for sociodemographic and health-related characteristics and pandemic-related stressors, odds of anxiety symptoms (odds ratio (OR) 0.53, 95% confidence interval (CI) 0.30–0.95) and worsened mental health (OR 0.58, 95% CI 0.36–0.94) were lower among non-Hispanic Black vs. non-Hispanic white respondents. Limitations No diagnostic assessments were used, and results may not be generalizable to later phases of the pandemic and the entire U.S. South. Conclusions Despite greater pandemic-related stressor experience, poor mental health outcomes were not more common among racial/ethnic minority individuals. However, interventions to reduce disparities in stressor experience and promote mental health are needed.

Background The potential benefits of the COVID-19 lockdown need to be carefully weighed versus the possible impact on people's daily life and negative mental health effects.We aimed to assess the prevalence of depression, anxiety, insomnia and quality of life before and during the COVID-19 lockdown,identifying subgroups at higher risk of mental distress as a consequence of COVID-19 associated restrictions. Methods Within the Lost in Italy project, a web-based cross-sectional study was conducted on a representative sample of 6003 Italian adults aged 18–74 recruited from April 27 to May 3, 2020, within the nation-wide stay-at-home order. Results The prevalence of depressive symptoms (PHQ-2 ≥ 3) increased from 14.3% before lockdown to 33.2% during lockdown, anxiety symptoms (GAD-2 ≥ 3) from 18.1% to 41.5%, insufficient sleep (≤6 h/day) from 33.7% to 41.1%, unsatisfactory sleep from 17.0% to 38.8% and unsatisfactory quality of life from 13.1% to 42.1%.Overall, 47.7% reported worsened depressive symptoms, 43.6% worsened anxiety symptoms, sleep quantity (31.5%) and quality (35.0%),and 64.1% worsened quality of life.A statistically significant relationship with all mental health outcomes considered was found for women vs. men (multivariate odds ratio,OR between 1.13 and 1.63), for current vs. never smokers (OR between 1.15 and 1.25), and with increasing physical activity (p for trend

Highlights • The prevalence of depression among Chinese pregnant women was 35.4%. • Drinking, morning sickness, and limited activity were risk factors for depression. • Less attention to fetal movement every day was also a risk factor for depression., Background The prevalence of depression increase with the outbreaks of epidemic disease. The prevalence of depression during the outbreak of Corona Virus Disease 2019 (COVID-19) in prenatal and postnatal women was examined in China. Methods 2201 prenatal and postnatal women in mainland China were recruited in this cross-sectional study from February 28th to April 26th, 2020. The Patient Health Questionnaire (PHQ-9) was used to assess depression in prenatal and postnatal women. Results The prevalence rate of depression was 35.4%. The risk factors for depression included drinking (p = 0.04; adjusted OR = 2.81, 95%CI: 1.26~6.24), nausea and vomiting during pregnancy (p

BACKGROUND: It is unclear how those with bipolar disorder (BD) have been affected by the coronavirus (COVID-19) pandemic. This study aimed to obtain a more detailed understanding of the current mental health needs of these individuals, which is important for both the development of intervention strategies to better manage patient distress and to better prepare for similar circumstances in future. METHODS: The sample comprised 43 individuals with a verified diagnosis of BD and 24 healthy controls. Data about pandemic-related mental health support use, socio-demographics, mood, lifestyle, social rhythm and subjective cognitive dysfunction data were collected and compared between groups. Inter-relationships between scores were also examined. RESULTS: No between-group differences were found in terms of age, sex, living situation, job loss or reduced work hours due to COVID-19. Most patients with BD reported a history of ongoing formal psychological support (68.3%), with most continuing this support throughout the pandemic (82.1%). A large, statistically significant pandemic-related increase in subjective cognitive dysfunction was evident in the BD group. Subjective cognitive dysfunction was significantly associated with negative symptomology, suicidal thoughts, and quality of life ratings. LIMITATIONS: Data was collected in self-report format in an online survey and objective symptom measures were not used at this time CONCLUSION: The absenceof substantial differences between patients and controls in terms of mood symptoms, COVID-19 fear or lifestyle factors and social rhythms suggests a degree of resilience in BD patients; despite large pandemic related increases in subjective cognitive dysfunction.

Highlights • A retrospective analysis was performed of all patients admitted to the Psychiatric Emergency Service 90 days before and after March 14th, 2020, the first day of lockdown in Spain due to COVID-19. • During the lockdown the number of admissions decreased by 37.9% while a significant increase in the percentage of patients requiring acute psychiatric hospitalization was observed. • Anxiety spectrum disorders accumulated the greatest decrease in admission rates compared to the three months before lockdown. • A statistically significant increase in admissions rates was found in patients with dementia-like cognitive impairments, autism spectrum, and substance use disorders during the lockdown., Background During the COVID-19 pandemic, a structural reorganization was imposed on public health systems. Psychiatry services were also affected with the imposed reduction of non-urgent consultations. We aim to explore the effect of these changes on a Psychiatry Emergency Service during COVID-19 lockdown in Spain. Methods A retrospective analysis was performed on all patients admitted to our Psychiatric Emergency Service 90 days before and after March 14th, 2020, the first day of lockdown in Spain. Extracted data were compared between the two periods. Poisson regression analysis was performed to analyze changes in admission rates. Results 1,958 psychiatric emergency admissions were analyzed. Although the number of admissions decreased by 37.9%, we observed a significant increase in the percentage of acute psychiatric hospitalization during the lockdown. Anxiety spectrum disorders accumulated the greatest significant decrease in admission rates during the lockdown. On the other hand, a significant increase in admissions rates was found in patients with dementia, autism spectrum disorders, and substance use disorders during the lockdown. Limitations This study was conducted in a single psychiatric emergency service, preventing a generalization of our results. The comparison time period might have biased our results due to the influence of external factors. Conclusion Mental health consequences of COVID-19 are becoming apparent. A reduction of admission rates for anxiety disorders might be related telepsychiatry implementation during the lockdown. Other conditions particularly vulnerable to the routine changes and lack of social support have suffered the most, and efforts should be placed to treat these situations.

Highlights • HCWs in Egypt and Saudi-Arabia experienced depression, anxiety, and stress during the COVID-19 pandemic. • Female sex, age ≤30 years, attending night shifts, and watching/reading COVID-19 news associated with worse psychological disturbances. • Providing psychological support to HCWs during the COVID-19 pandemic is an urgent need., Introduction As the Novel Corona Virus Disease (COVID-19) was declared by the world health organization a pandemic in March 2020, thousands of healthcare workers (HCWs) worldwide were on the frontlines fighting against the pandemic. Herein, we selected two Middle East countries; Egypt and Saudi Arabia to investigate the psychological impacts of the COVID-19 pandemic on their HCWs. Methods In this cross-sectional study, a Google survey was used to access HCWs in many hospitals in Egypt and Saudi Arabia between the 14th and 24th of April 2020. The survey assessed HCWs regarding their sociodemographic and occupational features, sleeping hours, and psychological impacts of the COVID-19 pandemic using the Depression Anxiety Stress Scale-21 (DASS-21). Results This study included 426 HCWs (48.4% physicians, 24.2% nurses, and 27.4% other HCWs). Of them, 69% had depression, 58.9% had anxiety, 55.9% had stress, and 37.3% had inadequate sleeping (

Background We aimed to estimate the population prevalence of people with changes in their usual patterns of alcohol use during the early stages of the novel coronavirus pandemic of 2020 (COVID-19) pandemic in Australia; assess the association between mental health status and changes in alcohol use during the pandemic; and examine if the associations were modified by gender and age. Methods This study was an anonymously-completed online self-report survey. Changes in alcohol use were assessed using a single fixed-choice study-specific question. Mental health was assessed using the Patient Health Questionnaire 9 and the Generalized Anxiety Disorder Scale. Results A total of 13,829 people contributed complete data and were included in the analysis. Overall, about one in five adults reported that they had been drinking more alcohol since the COVID-19 pandemic began than they used to. People were more likely to be drinking alcohol more than they used to if they had more severe symptoms of depression or anxiety. The associations between depressive and anxiety symptoms and increased alcohol use since the COVID-19 pandemic began were consistent between females and males. Limitations Online surveys are less accessible to some groups of people. The data are self-report and not diagnostic. Cross-sectional data can identify associations, not causal relationships. The study was limited to participants from Australia. Conclusions These data indicate that there is a need for public policies focused on alcohol use during the COVID-19 pandemic and the strategies should include specific consideration of the needs of people with mental health problems.

Highlights • The estimated self-reported rates of anxiety symptoms and depression symptoms among medical staff were 13.3% and 18.4% respectively under COVID-19 epidemic. • Up to 23.9% investigated medical staff reported having anxiety or depression symptoms. • Psychological interventions for medical staff should be integrated into the strategies for fighting COVID-19., Background It is well known that unexpected pandemic has led to an increase in mental health problems among a variety of populations. Methods In this study, an online non-probability sample survey was used to anonymously investigate the anxiety and depression symptoms among medical staff under the COVID-19 outbreak. The questionnaire included Perceived Stress Scale-10 (PSS-10), Generalized Anxiety Disorder 7-Item Scale (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). Factors associated with anxiety and depression symptoms were estimated by logistic regression analysis. Results A total of 1090 medical staff were investigated in this study. The estimated self-reported rates of anxiety symptoms, depression symptoms and both of the two were 13.3%, 18.4% and 23.9% respectively. Factors associated with self-reported anxiety symptoms include married status (OR=2.3, 95%CI: 1.2, 4.4), not living alone (OR=0.4, 95%CI: 0.2, 0.7), never confiding their troubles to others (OR=2.2, 95%CI: 1.4, 3.5) and higher stress (OR=14.4, 95%CI: 7.8, 26.4). Factors associated with self-reported depression symptoms include not living alone (OR=0.4, 95%CI: 0.3, 0.7), sometimes/often getting care from neighbours (OR=0.6, 95%CI: 0.4, 0.9), never confiding their troubles to others (OR=2.0, 95%CI: 1.3, 3.0) and higher stress (OR=9.7, 95%CI: 6.2, 15.2). Limitations The study was a non-probability sample survey. Besides, scales used in this study can only identify mental health states. Conclusions Under outbreak of COVID-19, self-reported rates of anxiety symptoms and depression symptoms were high in investigated medical staff. Psychological interventions for those at high risk with common mental problems should be integrated into the work plan to fight against the epidemic.

Highlights • Students report moderate-to-severe psychological impact of the COVID-19 pandemic. • Timely and adequate health information has protective psychological effect. • Health care workers are less likely to be psychologically affected. • Home quarantine is associated with depression, anxiety and stress symptoms., Background The 2019 coronavirus disease (COVID-19) pandemic poses a threat to societies’ mental health. This study examined the prevalence of psychiatric symptoms and identified the factors contributing to psychological impact in the Philippines. Methods A total of 1879 completed online surveys were gathered from March 28-April 12, 2020. Collected data included socio-demographics, health status, contact history, COVID-19 knowledge and concerns, precautionary measures, information needs, the Depression, Anxiety and Stress Scales (DASS-21) and the Impact of Events Scale-Revised (IES-R) ratings. Results The IES-R mean score was 19.57 (SD=13.12) while the DASS-21 mean score was 25.94 (SD=20.59). In total, 16.3% of respondents rated the psychological impact of the outbreak as moderate-to-severe; 16.9% reported moderate-to-severe depressive symptoms; 28.8% had moderate-to-severe anxiety levels; and 13.4% had moderate-to-severe stress levels. Female gender; youth age; single status; students; specific symptoms; recent imposed quarantine; prolonged home-stay; and reports of poor health status, unnecessary worry, concerns for family members, and discrimination were significantly associated with greater psychological impact of the pandemic and higher levels of stress, anxiety and depression (p

Aim:Prevention of medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis requires the cooperation of physicians and dentists. We investigated the knowledge, experience, and behaviour related to medical and dental cooperation for MRONJ prevention in patients with osteoporosis between physicians and dentists practising in the Shiga prefecture., Materials and methods:We conducted a cross-sectional study to investigate the cooperation between practising physicians and dentists for preventing osteonecrosis of the jaw (ONJ) in patients with osteoporosis using 2 separate questionnaires from July 28, 2018, to February 3, 2019, in Shiga prefecture, Japan., Results:Of 461 dentists who were sent the questionnaires at their dental clinics, 307 (67%) responded via fax. Of 846 physicians who were sent the questionnaire at their clinics, 378 (45%) responded via fax. Of these, 268 (32%) were finally analysed because 110 (13%) physicians had never treated patients with osteoporosis; 50% dentists and 24% physicians were familiar with the MRONJ position paper in Japan, and 39% dentists and 9% physicians had encountered MRONJ in their clinical practice. A total of 30% physicians had requested oral health care by a dentist before administering bone-modifying agents (BMA) therapy. The knowledge and experience of MRONJ differed between doctors and dentists., Conclusion:The behaviour of doctors and dentists was insufficient to enable medical and dental cooperation for the prevention of MRONJ in patients with osteoporosis. The lack of cooperation between physicians and dentists during osteoporosis treatment in the Shiga prefecture in Japan is documented in this study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA transmission route was thoroughly investigated in the hospital wastewater, sewage collection network, and wastewater treatment plants. Samples were taken on four occasions from December 2020 to April 2021. The performance of two different wastewater treatment processes of sequencing batch reactor (SBR) and conventional activated sludge (CAS) was studied for virus destruction. For this purpose, liquid phase, solid phase and bioaerosol samples were taken from different units of the investigated wastewater treatment plants (WWTPs). The results revealed that all untreated hospital wastewater samples were positive for SARS-CoV-2 RNA. The virus detection frequency increased when the number of hospitalized cases increased. Detection of viral RNA in the wastewater collection system exhibited higher load of virus in the generated wastewater in areas with poor socioeconomic conditions. Virus detection in the emitted bioaerosols in WWTPs showed that bioaerosols released from CAS with surface aeration contains SARS-CoV-2 RNA posing a potential threat to the working staff of the WWTPs. However, no viral RNA was detected in the bioaerosols of the SBR with diffused aeration system. Investigation of SARS-CoV-2 RNA in WWTPs showed high affinity of the virus to be accumulated in biosolids rather than transporting via liquid phase. Following the fate of virus in sludge revealed that it is completely destructed in anaerobic sludge treatment process. Therefore, based on the results of the present study, it can be concluded that receiving water resources could not be contaminated with virus, if the wastewater treatment processes work properly., Graphical abstract Unlabelled Image

Fascioliasis is a worldwide emerging snail-borne zoonotic trematodiasis with a great spreading capacity linked to animal and human movements, climate change, and anthropogenic modifications of freshwater environments. South America is the continent with more human endemic areas caused by Fasciola hepatica, mainly in high altitude areas of Andean regions. The Peruvian Cajamarca area presents the highest human prevalences reported, only lower than those in the Bolivian Altiplano. Sequencing of the complete rDNA ITS-2 allowed for the specific and haplotype classification of lymnaeid snails collected in seasonal field surveys along a transect including 2007–3473 m altitudes. The species Galba truncatula (one haplotype preferentially in higher altitudes) and Pseudosuccinea columella (one haplotype in an isolated population), and the non-transmitting species Lymnaea schirazensis (two haplotypes mainly in lower altitudes) were found. Climatic seasonality proved to influence G. truncatula populations in temporarily dried habitats, whereas L. schirazensis appeared to be more climatologically independent due to its extreme amphibious ecology. Along the southeastern transect from Cajamarca city, G. truncatula and L. schirazensis shared the same site in 7 localities (46.7% of the water collections studied). The detection of G. truncatula in 11 new foci (73.3%), predominantly in northern localities closer to the city, demonstrate that the Cajamarca transmission risk area is markedly wider than previously considered. Lymnaea schirazensis progressively increases its presence when moving away from the city. Results highlight the usefulness of lymnaeid surveys to assess borders of the endemic area and inner distribution of transmission foci. Similar lymnaeid surveys are still in need to be performed in the wide northern and western zones of the Cajamarca city. The coexistence of more than one lymnaeid transmitting species, together with a morphologically indistinguishable non-transmitting species and livestock movements inside the area, conform a complex scenario which poses difficulties for the needed One Health control intervention., Graphical abstract Unlabelled Image, Highlights • Lymnaeid surveys by rDNA ITS-2 in Cajamarca human fascioliasis hyperendemic area • New foci with Galba truncatula and Lymnaea schirazensis at 2007–3473 m altitudes • Only one Pseudosuccinae columella population found in a seasonal survey • Seasonal lymnaeid surveys useful to assess endemic area distribution and borders • Geographical distribution of Cajamarca endemic markedly wider than previously considered

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) levels by facilitating the degradation of the LDL receptor (LDLR) and is an attractive therapeutic target for hypercholesterolemia intervention. Herein, we generated a novel fully human antibody with favourable druggability by utilizing phage display-based strategy. Methods A potent single-chain variable fragment (scFv) named AP2M21 was obtained by screening a fully human scFv phage display library with hPCSK9, and performing two in vitro affinity maturation processes including CDR-targeted tailored mutagenesis and cross-cloning. Thereafter, it was transformed to a full-length Fc-silenced anti-PCSK9 antibody FAP2M21 by fusing to a modified human IgG1 Fc fragment with L234A/L235A/N297G mutations and C-terminal lysine deletion, thus eliminating its immune effector functions and mitigating mAb heterogeneity. Findings Our data showed that the generated full-length anti-PCSK9 antibody FAP2M21 binds to hPCSK9 with a KD as low as 1.42 nM, and a dramatically slow dissociation rate (koff, 4.68 × 10−6 s−1), which could be attributed to its lower binding energy (-47.51 kcal/mol) than its parent counterpart FAP2 (-30.39 kcal/mol). We verified that FAP2M21 potently inhibited PCSK9-induced reduction of LDL-C uptake in HepG2 cells, with an EC50 of 43.56 nM. Further, in hPCSK9 overexpressed C57BL/6 mice, a single tail i.v. injection of FAP2M21 at 1, 3 and 10 mg/kg, dose-dependently up-regulated hepatic LDLR levels, and concomitantly reduced serum LDL-C by 3.3% (P = 0.658, unpaired Student's t-test), 30.2% (P = 0.002, Mann-Whitney U-test) and 37.2% (P = 0.002, Mann-Whitney U-test), respectively. Interpretation FAP2M21 with potent inhibitory effect on PCSK9 may serve as a promising therapeutic agent for treating hypercholesterolemia and associated cardiovascular diseases.

Background The human gut microbiota has emerged as a key factor in the development of obesity. Certain probiotic strains have shown anti-obesity effects. The objective of this study was to investigate whether Bifidobacterium longum APC1472 has anti-obesity effects in high-fat diet (HFD)-induced obese mice and whether B. longum APC1472 supplementation reduces body-mass index (BMI) in healthy overweight/obese individuals as the primary outcome. B. longum APC1472 effects on waist-to-hip ratio (W/H ratio) and on obesity-associated plasma biomarkers were analysed as secondary outcomes. Methods B. longum APC1472 was administered to HFD-fed C57BL/6 mice in drinking water for 16 weeks. In the human intervention trial, participants received B. longum APC1472 or placebo supplementation for 12 weeks, during which primary and secondary outcomes were measured at the beginning and end of the intervention. Findings B. longum APC1472 supplementation was associated with decreased bodyweight, fat depots accumulation and increased glucose tolerance in HFD-fed mice. While, in healthy overweight/obese adults, the supplementation of B. longum APC1472 strain did not change primary outcomes of BMI (0.03, 95% CI [-0.4, 0.3]) or W/H ratio (0.003, 95% CI [-0.01, 0.01]), a positive effect on the secondary outcome of fasting blood glucose levels was found (-0.299, 95% CI [-0.44, -0.09]). Interpretation This study shows a positive translational effect of B. longum APC1472 on fasting blood glucose from a preclinical mouse model of obesity to a human intervention study in otherwise healthy overweight and obese individuals. This highlights the promising potential of B. longum APC1472 to be developed as a valuable supplement in reducing specific markers of obesity. Funding This research was funded in part by Science Foundation Ireland in the form of a Research Centre grant (SFI/12/RC/2273) to APC Microbiome Ireland and by a research grant from Cremo S.A.

Benefiting from emerging miniaturized and equipment-free nucleic acid testing (NAT) technologies, fully integrated NAT devices at point of care (POC) with the capability of “sample-in-answer-out” are proceeding at a break-neck speed to eliminate complex operations and reduce the risk of contamination. Like the development of PCR technology (standard technique for NAT), the detection signal of fully integrated NAT devices has evolved from qualitative to quantitative and recently to digital readout, aiming at expanding their extensive applications through gradually improving detection sensitivity and accuracy. This review firstly introduces the existing commercial products, and then illustrates recent fully integrated microfluidic devices for NAT at POC from the aspect of detection signals (i.e., qualitative, quantitative and digital). Importantly, the key issues of existing commercial products and the main challenges between scientific research and product development are discussed. On this basis, we envision that the MARCHED (miniaturized, automatic, reagent-preloaded, commercializable, high-throughput, environment-independent and disposable) NAT devices are expected to be realized in the near future., Highlights • The advances in fully integrated NAT devices from the aspect of detection signals (i.e., qualitative, quantitative and digital) were introduced. • Existing commercial products relevant to fully integrated POC NAT devices were summarized. • The MARCHED (miniaturized, automatic, reagent-preloaded, commercializable, high-throughput, environment-independent and disposable) NAT devices were proposed as prospective development tendency.

SARS-CoV-2 genetic material is detectable in the faeces of a considerable part of COVID-19 cases and hence, in municipal wastewater. This fact was confirmed early during the spread of the COVID-19 pandemic and prompted several studies that proposed monitoring its incidence by wastewater. This paper studies the fate of SARS-CoV-2 genetic material in wastewater treatment plants using RT-qPCR with a two-fold goal: i) to check its presence in the water effluent and in the produced sludge and ii) based on the understanding of the virus particles fate, to identify the most suitable spots for detecting the incidence of COVID-19 and monitor its evolution. On the grounds of the affinity of enveloped virus towards biosolids, we hypothesized that the sludge line acts as a concentrator of SARS-CoV-2 genetic material. Sampling several spots in primary, secondary and sludge treatment at the Ourense (Spain) WWTP in 5 different days showed that, in effect, most of SARS-CoV-2 particles cannot be detected in the water effluent as they are retained by the sludge line. We identified the sludge thickener as a suitable spot for detecting SARS-CoV-2 particles thanks to its higher solids concentration (more virus particles) and longer residence time (less sensitive to dilution caused by precipitation). These findings could be useful to develop a suitable strategy for early warning of COVID-19 incidence based on WWTP monitoring., Graphical abstract Unlabelled Image