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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.

Local food production systems of least developed countries (LDCs) are more vulnerable to environmental factors, such as climate change, with respect to those of developed ones. Hence, the development of low-tech processes to empower LDCs adaptive capacity through a circular economy approach is very promising. Here, we report on a straightforward process for potential application in LDCs contexts based on the thermal conversion of fishery by-products (fish bone) into calcium phosphate-based materials with application as fertilizers and biostimulants. Sardinella aurita bones collected from artisanal ports in Senegal were calcined in air at 300 °C, 600 °C and 900 °C. The sample obtained at 300 °C was a composite material made of an organic part, deriving from the uncomplete combustion of fish bone collagen and fatty acid, and an inorganic part made of very poorly crystalline hydroxyapatite. The other two samples obtained at 600 °C and 900 °C had a negligible content of organic matter, and consisted of hydroxyapatite and β-TCP. Materials phytotoxicity was tested against Lepidium sativum seed, and their bio-stimulation activity was assayed on Zea mais seedlings and coleoptiles. All the materials showed promising results in terms of seed germination, plant fertilization and corn coleoptile biostimulation. Finally, we briefly analyzed the environmental impacts and economic cost of the proposed low-tech thermal process to confirm its large-scale applicability in LDCs for the conversion of fish bones into valuable products.

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.

Antibiotic treatment; ESCMID; KPC; Klebsiella pneumoniae; position paper Background: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has become one of the most important contemporary pathogens, especially in endemic areas. Aims: To provide practical suggestion for physicians dealing with the management of KPC-KP infections in critically ill patients, based on expert opinions. Sources: PubMed search for relevant publications related to the management of KPC-KP infections. Contents: A panel of experts developed a list of 12 questions to be addressed. In view of the current lack of high-level evidence, they were asked to provide answers on the bases of their knowledge and experience in the field. The panel identified several key aspects to be addressed when dealing with KPC-KP in critically ill patients (preventing colonization in the patient, preventing infection in the colonized patient and colonization of his or her contacts, reducing mortality in the infected patient by rapidly diagnosing the causative agent and promptly adopting the best therapeutic strategy) and provided related suggestions that were based on the available observational literature and the experience of panel members. Implications: Diagnostic technologies could speed up the diagnosis of KPC-KP infections. Combination treatment should be preferred to monotherapy in cases of severe infections. For non–critically ill patients without severe infections, results from randomized clinical trials are needed for ultimately weighing benefits and costs of using combinations rather than monotherapy. Multifaceted infection control interventions are needed to decrease the rates of colonization and cross-transmission of KPC-KP.

Introduction Obesity and psychosocial stress (PS) co-exist in individuals of Western society. Nevertheless, how PS impacts cardiac and hippocampal phenotype in obese subjects is still unknown. Nor is it clear whether changes in local brain-derived neurotrophic factor (BDNF) account, at least in part, for myocardial and behavioral abnormalities in obese experiencing PS. Methods In adult male WT mice, obesity was induced via a high-fat diet (HFD). The resident-intruder paradigm was superimposed to trigger PS. In vivo left ventricular (LV) performance was evaluated by echocardiography and pressure-volume loops. Behaviour was indagated by elevated plus maze (EPM) and Y-maze. LV myocardium was assayed for apoptosis, fibrosis, vessel density and oxidative stress. Hippocampus was analyzed for volume, neurogenesis, GABAergic markers and astrogliosis. Cardiac and hippocampal BDNF and TrkB levels were measured by ELISA and WB. We investigated the pathogenetic role played by BDNF signaling in additional cardiac-selective TrkB (cTrkB) KO mice. Findings When combined, obesity and PS jeopardized LV performance, causing prominent apoptosis, fibrosis, oxidative stress and remodeling of the larger coronary branches, along with lower BDNF and TrkB levels. HFD/PS weakened LV function similarly in WT and cTrkB KO mice. The latter exhibited elevated LV ROS emission already at baseline. Obesity/PS augmented anxiety-like behaviour and impaired spatial memory. These changes were coupled to reduced hippocampal volume, neurogenesis, local BDNF and TrkB content and augmented astrogliosis. Interpretation PS and obesity synergistically deteriorate myocardial structure and function by depleting cardiac BDNF/TrkB content, leading to augmented oxidative stress. This comorbidity triggers behavioral deficits and induces hippocampal remodeling, potentially via lower BDNF and TrkB levels. Fund J.A. was in part supported by Rotary Foundation Global Study Scholarship. G.K. was supported by T32 National Institute of Health (NIH) training grant under award number 1T32AG058527. S.C. was funded by American Heart Association Career Development Award (19CDA34760185). G.A.R.C. was funded by NIH ( K01HL133368-01 ). APB was funded by a Grant from the Friuli Venezia Giulia Region entitled: “Heart failure as the Alzheimer disease of the heart; therapeutic and diagnostic opportunities”. M.C. was supported by PRONAT project ( CNR ). N.P. was funded by NIH ( R01 HL136918 ) and by the Magic-That-Matters fund (JHU) . V.L. was in part supported by institutional funds from Scuola Superiore Sant'Anna (Pisa, Italy) , by the TIM-Telecom Italia (WHITE Lab, Pisa, Italy) , by a research grant from Pastificio Attilio Mastromauro Granoro s.r.l. (Corato, Italy) and in part by ETHERNA project (Prog. n. 161/16, Fondazione Pisa, Italy). Funding source had no such involvement in study design, in the collection, analysis, interpretation of data, in the writing of the report; and in the decision to submit the paper for publication.

Background: In cystic fibrosis (CF), recurrent infections suggest impaired mucosal immunity but whether production of secretory immunoglobulin A (S-IgA) is impaired remains elusive. S-IgA is generated following polymeric immunoglobulin receptor (pIgR)-mediated transepithelial transport of dimeric (d-)IgA and represents a major defence through neutralisation of inhaled pathogens like Pseudomonas aeruginosa (Pa). Methods: Human lung tissue (n = 74), human sputum (n = 118), primary human bronchial epithelial cells (HBEC) (cultured in air-liquid interface) (n = 19) and mouse lung tissue and bronchoalveolar lavage were studied for pIgR expression, IgA secretion and regulation. Findings: Increased epithelial pIgR immunostaining was observed in CF lung explants, associated with more IgA-producing plasma cells, sputum and serum IgA, especially Pa-specific IgA. In contrast, pIgR and IgA transport were downregulated in F508del mice, CFTR-inhibited HBEC, and CF HBEC. Moreover, the unfolded protein response (UPR) due to F508del mutation, inhibited IgA transport in Calu-3 cells. Conversely, pIgR expression and IgA secretion were strongly upregulated following Pa lung infection in control and F508del mice, through an inflammatory host response involving interleukin-17. Interpretation: A complex regulation of IgA secretion occurs in the CF lung, UPR induced by CFTR mutation/dysfunction inhibiting d-IgA transcytosis, and Pa infection unexpectedly unleashing this secretory defence mechanism. Funding: This work was supported by the Forton's grant of the King Baudouin's Foundation, Belgium, the Fondazione Ricerca Fibrosi Cistica, Italy, and the Fonds National de la Recherche Scientifique, Belgium., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: The recently published COMPLETE trial has demonstrated that patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD), who underwent successful percutaneous coronary intervention (PCI) of both culprit and non-culprit (vs. culprit-only) lesions had a reduced risk of major adverse cardiac events (MACE), but not of cardiovascular or total mortality. The aim of this meta-analysis was to assess the efficacy of complete revascularization on cardiovascular or total mortality reduction using available randomized controlled trials (RCTs) including the COMPLETE trial, in hemodynamically stable STEMI patients with MVD. Methods: PubMed, MEDLINE, Embase, Scopus, Google Scholar, CENTRAL and ClinicalTrials.gov databases search identified 10 RCTs of 7033 patients with STEMI and MVD which compared complete (n = 3420) vs. only culprit lesion (n = 3613) PCI for a median 27.7 months follow-up. Random effect risk ratios were used to estimate for efficacy and safety outcomes. Results: Complete revascularization reduced the risk of MACE (10.4% vs.16.6%; RR = 0.59, 95% CI: 0.47 to 0.74, p < 0.0001), CV mortality (2.87% vs. 3.72%; RR = 0.73, 95% CI: 0.56 to 0.95, p = 0.02), reinfarction (5.1% vs. 7.1%; RR = 0.67, 95% CI: 0.52 to 0.86, p = 0.002), urgent revascularization (7.92% vs.17.4%; RR = 0.47, 95% CI: 0.30 to 0.73, p < 0.001), and CV hospitalization (8.68% vs.11.4%; RR = 0.65, 95% CI: 0.44to 0.96, p = 0.03) compared with culprit only revascularization. All-cause mortality, stroke, major bleeding events, or contrast induced nephropathy were not affected by the revascularization strategy. Conclusion: The findings of this meta-analysis suggest that in patients with STEMI and MVD, complete revascularization is superior to culprit-only PCI in reducing the risk of MACE outcomes, including cardiovascular mortality, without increasing the risk of adverse safety outcomes.

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