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The healthcare-associated infections (HAIs) and pandemics caused by multidrug-resistant (MDR) and new-generation pathogens threaten the whole world community. Cu and its alloys have been attracting widespread interest as anti-contamination materials due to the rapid inactivation of MDR-superbugs and viruses. Applying thin Cu-based foils on pre-existing surfaces in hygiene-sensitive areas represents a quick, simple, cost-effective self-sanitising practice. However, the influence of chemical composition and microstructure should be deeply investigated when evaluating the antimicrobial capability and durability of Cu-based materials. The effect of composition on micromechanical and antiviral properties was investigated by comparing Cu15Zn and Cu18Ni20Zn (foil thickness from 13 to 27 μm) with Phosphorous High-Conductivity (PHC) Cu. The influence of recrystallisation annealing of PHC Cu was also investigated. Microstructural characterisation was carried out by optical (OM) and scanning electron (FEG-SEM) microscopy, Energy-dispersive Spectroscopy (EDS) and Electron-Backscattered Diffraction (EBSD). The micromechanical behaviour was assessed by microhardness, microscale abrasion and scratch tests. Cu-based foils were exposed to SARS-CoV-2 for different time points in quasi-dry conditions (artificial sweat solution), evaluating their antiviral capability by quantitative Reverse-Transcriptase Polymerase Chain Reaction (qRT-PCR). Surface morphology, contact angle measurements and Cu release were measured. All Cu-based surfaces completely inactivated SARS-CoV-2 in 10 min: pure Cu was the best option regarding antiviral efficiency, while Cu15Zn showed the best trade-off between micromechanical and antiviral properties.

Abstract Precise, scalable, and quantitative evaluation of whole slide images is crucial in neuropathology. We release a deep learning model for rapid object detection and precise information on the identification, locality, and counts of cored plaques and cerebral amyloid angiopathy (CAA). We trained this object detector using a repurposed image-tile dataset without any human-drawn bounding boxes. We evaluated the detector on a new manually-annotated dataset of whole slide images (WSIs) from three institutions, four staining procedures, and four human experts. The detector matched the cohort of neuropathology experts, achieving 0.64 (model) vs. 0.64 (cohort) average precision (AP) for cored plaques and 0.75 vs. 0.51 AP for CAAs at a 0.5 IOU threshold. It provided count and locality predictions that approximately correlated with gold-standard human CERAD-like WSI scoring (p = 0.07 ± 0.10). The openly-available model can quickly score WSIs in minutes without a GPU on a standard workstation.

Women are disproportionately affected by Alzheimer's disease (AD), yet little is known about sex-specific effects on the development of AD in the Down syndrome (DS) population. DS is caused by a full or partial triplication of chromosome 21, which harbors the amyloid precursor protein (APP) gene, among others. The majority of people with DS in their early- to mid-40s will accumulate sufficient amyloid-beta (Aβ) in their brains along with neurofibrillary tangles (NFT) for a neuropathological diagnosis of AD, and the triplication of the APP gene is regarded as the main cause. Studies addressing sex differences with age and impact on dementia in people with DS are inconsistent. However, women with DS experience earlier age of onset of menopause, marked by a drop in estrogen, than women without DS. This review focuses on key sex differences observed with age and AD in people with DS and a discussion of possible underlying mechanisms that could be driving or protecting from AD development in DS. Understanding how biological sex influences the brain will lead to development of dedicated therapeutics and interventions to improve the quality of life for people with DS and AD.

Most instances of Alzheimer’s disease (AD) are sporadic or not associated with a particular mutation. Here, the authors develop knock-in mice that express wildtype human Aβ under control of the mouse App locus, which may have potential for modelling some aspects of sporadic late onset AD.

Summary: Microglia are strongly implicated in the development and progression of Alzheimer’s disease (AD), yet their impact on pathology and lifespan remains unclear. Here we utilize a CSF1R hypomorphic mouse to generate a model of AD that genetically lacks microglia. The resulting microglial-deficient mice exhibit a profound shift from parenchymal amyloid plaques to cerebral amyloid angiopathy (CAA), which is accompanied by numerous transcriptional changes, greatly increased brain calcification and hemorrhages, and premature lethality. Remarkably, a single injection of wild-type microglia into adult mice repopulates the microglial niche and prevents each of these pathological changes. Taken together, these results indicate the protective functions of microglia in reducing CAA, blood-brain barrier dysfunction, and brain calcification. To further understand the clinical implications of these findings, human AD tissue and iPSC-microglia were examined, providing evidence that microglia phagocytose calcium crystals, and this process is impaired by loss of the AD risk gene, TREM2.

Abstract This study aimed to evaluate whether skeletal development of the Pantanal Caiman (Caiman yacare) is similarly influenced by temperature variation and controlled increases in embryo motility. All eggs were incubated at 90% humidity and 29 °C for the first 45 days. Thereafter, the incubation temperature was either maintained at 29 °C and embryos were treated with 4-aminopyridine (4-AP) on days 46, 47, 48, and 49 (Group I, 29 °C 4-AP, n = 15); maintained at 29 °C (n = 14; Group II); or at 33 °C (n = 14, Group III). Embryonic movement was measured using an Egg Buddy® digital monitor on days 30, 35, 42, 49, 56, and 60, at which point embryos were euthanized and samples were collected for analysis. No differences were observed between groups with varying incubation temperatures. In contrast, embryonic motility was greater in embryos treated with 4-AP (P < 0.001) on day 49, and this was associated with higher proportions of snout-vent and hand lengths. This study demonstrates for the first time that pharmacologically induced increases in embryo motility result in phenotypic changes to the proportion of elements during prenatal ontogeny, thereby effectively altering the adaptation of the species to specific environments.

Abstract Background State and Territorial Health Departments (SHDs) have a unique role in protecting and promoting workers’ health. This mixed-methods study presents the first systematic investigation of SHDs’ activities and capacity in both Occupational Safety and Health (OSH) and Workplace Health Promotion (WHP) in the United States (US). Methods National survey of OSH and WHP practitioners from each of 56 SHDs, followed by in-depth interviews with a subset of survey respondents. We calculated descriptive statistics for survey variables and conducted conventional content analysis of interviews. Results Seventy percent (n = 39) of OSH and 71% (n = 40) of WHP contacts responded to the survey. Twenty-seven (n = 14 OSH, n = 13 WHP) participated in follow-up interviews. Despite limited funding, staffing, or organizational support, SHDs reported a wide array of activities. We assessed OSH and WHP surveillance activities, support that SHDs provided to employers to implement OSH and WHP interventions (implementation support), OSH and WHP services provided directly to workers, OSH follow-back investigations, and OSH standard and policy development. Each of the categories we asked about (excluding OSH standard and policy development) were performed by more than half of responding SHDs. Surveillance was the area of greatest OSH activity, while implementation support was the area of greatest WHP activity. Respondents characterized their overall capacity as low. Thirty percent (n = 9) of WHP and 19% (n = 6) of OSH respondents reported no funds at all for OSH/WHP work, and both groups reported a median 1.0 FTEs working on OSH/WHP at the SHD. Organizational support for OSH and WHP was characterized as “low” to “moderate”. To increase SHDs’ capacity for OSH and WHP, interview respondents recommended that OSH and WHP approaches be better integrated into other public health initiatives (e.g., infectious disease prevention), and that federal funding for OSH and WHP increase. They also discussed specific recommendations for improving the accessibility and utility of existing funding mechanisms, and the educational resources they desired from the CDC. Conclusions Results revealed current activities and specific strategies for increasing capacity of SHDs to promote the safety and health of workers and workplaces – an important public health setting for reducing acute injury and chronic disease.

Background: The importance of an efficient seal created by soft (connective) tissues around newly inserted dental implants has become increasingly clear. This study was aimed to compare the compatibility of fibroblasts – the main cell type in connective tissues – with three dental materials commonly employed for the manufacture of implant abutments, i.e. zirconia (ZrO2), titanium oxide (TiO2) and polyether-ether-ketone (PEEK), as well as the effects of UVC photofunctionalization of the materials prior to the contact with cells. Materials and methods: Human fibroblasts (MRC-5 cell line) were allowed to attach and grow up to 72 h on disks of each material, in absence or after UVC photofunctionalization. Cell viability as well as the expression of five genes related to extracellular matrix (ECM) homeostasis (fibronectin, collagen 1A1, vinculin, metalloproteases 2 and 9) were assessed at various times after cell seeding. Results: The viability of fibroblasts was higher when cultured on zirconia disks, in the order ZrO2 > TiO2 > PEEK. The lower viability observed with untreated PEEK could be however recovered after UVC photofunctionalization. Early upregulation was observed of genes involved in cell adhesion and migration (FN1, VCL) as well as in ECM remodeling (MMP9). UVC photofunctionalization significantly enhanced these effects with all three materials tested. At variance, the expression of Col1A1 gene – coding for collagen type I-alpha 1 – was precociously downregulated, but UVC photofunctionalization could largely reverse this phenomenon. Conclusions: Our observations suggest that fibroblasts cultured on UVC treated surfaces present an increased/accelerated activation of factors involved in the formation of new connective tissue. UVC photofunctionalization of dental implant abutments could thus enhance/accelerate the formation of soft tissue seals capable of preventing bacterial invasion.

Abstract The structural complexity of galls depends on species-specific interaction driven by the galling taxa. However, the host plant and environment stressors can impose limits on gall developmental patterns and impact the establishment of gall morphology. Herein, we employed qualitative and quantitative approaches in order to elucidate how cell divisions, elongation patterns, and tissue organization are determinant for the development of intralaminar gall morphology induced by Pseudophacopteron longicaudatum Malenovský, Burckhardt, Queiroz, Isaias & Oliveira (Hemiptera: Psylloidea: Phacopteronidae) on leaves of Aspidosperma tomentosum Mart. (Apocynaceae). In addition, we aimed to determine which anatomical process can discriminate the stages of gall development, plus, examine the histochemical and cytological profiles of the galls. The differentiated structures, mainly abaxial epidermis and spongy parenchyma, are associated with gall closure, with hyperplastic events concentrated in the young phase of the galls. Thus, epidermis and spongy parenchyma hypertrophy and are responsible for the determination of the nymphal chamber formation and gall shape. The mature galls do not differentiate into a typical nutritive cells and do not develop a histochemical gradient in their tissues. The cytological features of galls such as plastoglobules and multivesicular bodies are related to ROS scavenging mechanisms due the high oxidative stress.

Data from eight experiments were jointly analysed to characterize the ingestive behavior, displacement patterns, use of feeding stations and the dynamics of meals of beef heifers in different phenological stages of winter forages. The experiments included 360 heifers, with initial age of eight months and average body weight of 145.0 ± 17 kg. The grazing method was put-and-take stocking with variable number of animals. Grazing time, duration of meal and interval between meals were similar in the morning shift, regardless of the phenological stage. At the vegetative and pre-reproductive stages, in the afternoon, meals were longer. The average daily gain was greater at pre-reproductive being associated with the duration of the meal in the afternoon shift. Heifers change their ingestive behavior, bite rate, duration of meals, interval between meals, patterns of forage selection and number of steps per minute according to phenological stages and evaluation shifts in order to maintain a similar bite mass.

A pesar del frecuente empleo de los antiinflamatorios no esteroideos (AINEs), aún no se conocen los efectos secundarios de la inhibición crónica de las prostaglandinas. El objetivo del presente estudio fue evaluar los efectos del tratamiento crónico con dosis bajas/moderadas de AINEs sobre la función reproductiva de ratones. Ratones machos y hembras fueron inyectados (i.p. durante 60 ó 35 días respectivamente) con: dosis A, B o C de ibuprofeno (0.56, 1.12 ó 1.68mg/100g/día respectivamente) or dosis A, B o C de piroxicam (0.028, 0.056 ó 0.084mg/100g/día respectivamente). Los parámetros evaluados fueron: a) en hembras, ovulación espontánea e inducida, maduración ovocitaria y migración de espermatozoides a través del tracto genital, b) en machos y en espermatozoides epididimarios, concentración, motilidad, vitalidad, resistencia al shock hipoosmótico, estadío acrosomal y madurez de membrana y c) en ambos sexos, fertilización in vivo e in vitro, niveles plasmáticos de hormonas reproductivas e inhibición de ciclooxigenasa en tejido reproductivo. En las hembras, ibuprofeno (dosis A) disminuyó significativamente la ovulación espontánea e inducida y piroxicam (dosis A) disminuyó la concentración de espermatozoides en el tracto genital de la hembra luego de la cópula. Los espermatozoides obtenidos de machos tratados con ibuprofeno (dosis B) mostraron una disminución en su capacidad fertilizante in vitro. Nuestros datos revelan que la administración crónica de ibuprofeno o piroxicam pueden ejercer efectos deletéreos sobre la fisiología reproductiva, que dependen de la dosis y/o la droga empleada.

Melanoma is usually apparent on the skin and readily detected by trained medical providers using a routine total body skin examination, yet this malignancy is responsible for the majority of skin cancer-related deaths. Currently, there is no national consensus on skin cancer screening in the USA, but dermatologists and primary care providers are routinely confronted with making the decision about when to recommend total body skin examinations and at what interval. The objectives of this paper are: to propose rational, risk-based, data-driven guidelines commensurate with the US Preventive Services Task Force screening guidelines for other disorders; to compare our proposed guidelines to recommendations made by other national and international organizations; and to review the US Preventive Services Task Force's 2016 Draft Recommendation Statement on skin cancer screening.

Abstract Introduction Microglial cells play an important role in the development of Alzheimer's disease (AD). People with Down syndrome (DS) inevitably develop AD neuropathology (DSAD) by 40 years of age. We characterized the distribution of different microglial phenotypes in the brains of people with DS and DSAD. Methods Autopsy tissue from the posterior cingulate cortex (PCC) from people with DS, DSAD, and neurotypical controls was immunostained with the microglial marker Iba1 to assess five microglia morphological types. Results Individuals with DS have more hypertrophic microglial cells in their white matter. In the gray matter, individuals with DSAD had significantly fewer ramified microglia and more dystrophic microglia than controls and the younger individuals with DS. The DSAD group also exhibited more rod‐shaped and amoeboid cells than the AD group. Discussion Individuals with DS and DSAD show a microglial phenotype that distinguishes them from non‐DS controls.

Oxidative stress plays critical roles in the pathogenesis of diabetes, hypertension, and atherosclerosis; some authors reported that fat accumulation correlates to systemic oxidative stress in human and mice, but cellular redox environment effect on lipid accumulation is still unclear. In our laboratory we used mouse embryonic fibroblasts (undifferentiated cells: CC), which are capable of differentiating into mature adipocytes (differentiated cells: DC) and accumulate lipids, as obesity model. Here we analyzed the role of the well-known antioxidant and glutathione precursor N-acetylcysteine (NAC) in cellular MAPK modulation and lipid accumulation. We evaluated the effect of NAC on the adipogenic differentiation pathway using different doses: 0.01, 0.1, 1 and 5 mM; no toxic doses in these cells. A dose of 5 mM NAC [DCN-5] provoked a significant decrease in triglyceride accumulation (72±10 [DCN-5] vs 169±15 [DC], p

Land degradation affects 10–20 % of drylands globally. Intensive land use and management, large-scale disturbances such as extractive operations, and global climate change, have contributed to degradation of these systems worldwide. Restoring these damaged environments is critical to improving ecosystem services and functions, conserve biodiversity, and contribute to climate resilience, food security, and landscape sustainability. Here, we present a case study on plant species of the mining intensive semi-arid Pilbara region in Western Australia that examines the effects of climate and soil factors on the restoration of drylands. We analysed the effects of a range of rainfall and temperature scenarios and the use of alternative soil materials on seedling recruitment of key native plant species from this area. Experimental studies were conducted in controlled environment facilities where conditions simulated those found in the Pilbara. Soil from topsoil (T) stockpiles and waste materials (W) from an active mine site were mixed at different proportions (100 % T, 100 % W, and two mixes of topsoil and waste at 50 : 50 and 25 : 75 ratios) and used as growth media. Our results showed that seedling recruitment was highly dependent on soil moisture and emergence was generally higher in the topsoil, which had the highest available water content. In general, responses to the climate scenarios differed significantly among the native species which suggest that future climate scenarios of increasing drought might affect not only seedling recruitment but also diversity and structure of native plant communities. The use of waste materials from mining operations as growth media could be an alternative to the limited topsoil. However, in the early stages of plant establishment successful seedling recruitment can be challenging in the absence of water. These limitations could be overcome by using soil amendments but the cost associated to these solutions at large landscape scales needs to be assessed and proven to be economically feasible.

Tanto la obesidad como la infertilidad masculina han aumentado durante las últimas décadas por lo que se ha explorado una posible asociación entre estas patologías. Los estudios informan que la obesidad puede afectar la fertilidad del varón por diferentes mecanismos, los que en última instancia, pueden provocar disfunción eréctil y/o deteriorar la calidad espermática. Dichos mecanismos incluyen: 1) disrupción en la fisiología del eje hipotálamo-hipófiso-testicular (HHT): disminución en la concentración sérica de testosterona, gonadotrofinas, SHBG y/o inhibina B e hyperestrogenemia; 2) incremento en la liberación de hormonas derivadas del tejido adiposo, entre ellas leptina, que podrían alterar la fisiología del eje HHT y/o afectar directamente las células de Leydig y la espermatogénesis; 3) aumento de las adipoquinas (proinflamatorias), incremento de la temperatura escrotal y acumulación de disruptores endócrinos en los adipocitos; todos ellos responsables de un aumento en el estrés oxidativo testicular y 4) la apnea del sueño, frecuente en obesos, que suprime el pico nocturno de testosterona necesario para la espermatogénesis. Finalmente, si bien está discutido, estos mecanismos podrían alterar la espermatogénesis y/o la maduración epididimaria, disminuyendo así la concentración y la motilidad espermática y aumentando la fragmentación del ADN. En resumen, si bien la obesidad puede afectar la fertilidad masculina por algunos/todos los mecanismos mencionados, lo cierto es que sólo una pequeña proporción de obesos son infértiles; probablemente aquéllos con obesidad mórbida o genéticamente predispuestos. Sin embargo, ya que la incidencia de obesidad sigue aumentando, es de esperar que el número de hombres con sub/infertilidad también lo haga.

Objective: Work is considered one of the main forms of social organization; however, few individuals with schizophrenia find work opportunities. The purpose of this study was to evaluate the relationship between schizophrenia symptoms and job acquisition. Method: Fifty-three individuals diagnosed with schizophrenia from an outpatient treatment facility were included in an 18-month follow-up study. After enrollment, they participated in a prevocational training group. At the end of training (baseline) and 18 months later, sociodemographic, clinical data and occupational history were collected. Positive and negative symptoms (Positive and Negative Syndrome Scale – PANSS), depression (Calgary Depression Scale), disease severity (Clinical Global Impression – CGI), functionality (Global Assessment of Functioning – GAF), personal and social performance (Personal and Social Performance – PSP) and cognitive functions (Measurement and Treatment Research to Improve Cognition in Schizophrenia – MATRICS battery) were applied at baseline and at the end of the study. Results: Those with some previous work experience (n=19) presented lower scores on the PANSS, Calgary, GAF, CGI and PSP scales (p < 0.05) than those who did not work. Among those who worked, there was a slight worsening in positive symptoms (positive PANSS). Conclusions: Individuals with less severe symptoms were more able to find employment. Positive symptom changes do not seem to affect participation at work; however, this calls for discussion about the importance of employment support.

Ascribing mental states to non-human agents has been shown to increase their likeability and lead to better joint-task performance in human-robot interaction (HRI). However, it is currently unclear what physical features non-human agents need to possess in order to trigger mind attribution and whether different aspects of having a mind (e.g., feeling pain, being able to move) need different levels of human-likeness before they are readily ascribed to non-human agents. The current study addresses this issue by modeling how increasing the degree of human-like appearance (on a spectrum from mechanistic to humanoid to human) changes the likelihood by which mind is attributed towards non-human agents. We also test whether different internal states (e.g., being hungry, being alive) need different degrees of humanness before they are ascribed to non-human agents. The results suggest that the relationship between physical appearance and the degree to which mind is attributed to non-human agents is best described as a two-linear model with no change in mind attribution on the spectrum from mechanistic to humanoid robot, but a significant increase in mind attribution as soon as human features are included in the image. There seems to be a qualitative difference in the perception of mindful versus mindless agents given that increasing human-like appearance alone does not increase mind attribution until a certain threshold is reached, that is: agents need to be classified as having a mind first before the addition of more human-like features significantly increases the degree to which mind is attributed to that agent.

Our study demonstrates the repeated isolation of vaccine-derived Newcastle disease viruses from different species of wild birds across four continents from 1997 through 2014. The data indicate that at least 17 species from ten avian orders occupying different habitats excrete vaccine-derived Newcastle disease viruses. The most frequently reported isolates were detected among individuals in the order Columbiformes (n = 23), followed in frequency by the order Anseriformes (n = 13). Samples were isolated from both free-ranging (n = 47) and wild birds kept in captivity (n = 7). The number of recovered vaccine-derived viruses corresponded with the most widely utilized vaccines, LaSota (n = 28) and Hitchner B1 (n = 19). Other detected vaccine-derived viruses resembled the PHY-LMV2 and V4 vaccines, with five and two cases, respectively. These results and the ubiquitous and synanthropic nature of wild pigeons highlight their potential role as indicator species for the presence of Newcastle disease virus of low virulence in the environment. The reverse spillover of live agents from domestic animals to wildlife as a result of the expansion of livestock industries employing massive amounts of live virus vaccines represent an underappreciated and poorly studied effect of human activity on wildlife.