Systematic SARS-CoV-2 S-gene sequencing in wastewater samples enables early lineage detection and uncovers rare mutations in Portugal.

As the COVID-19 pandemic reached its peak, many countries implemented genomic surveillance systems to track the evolution and transmission of SARS-CoV-2. Transition from the pandemic to the endemic phase prioritized alternative testing strategies to maintain effective epidemic surveillance at the population level, with less intensive sequencing efforts. One such promising approach was Wastewater-Based Surveillance (WBS), which offers non-invasive, cost-effective means for analysing virus trends at the sewershed level. From 2020 onwards, wastewater has been recognized as an instrumental source of information for public health, with national and international authorities exploring options to implement national wastewater surveillance systems and increasingly relying on WBS as early warning of potential pathogen outbreaks. In Portugal, several pioneer projects joined the academia, water utilities and Public Administration around WBS. To validate WBS as an effective genomic surveillance strategy, it is crucial to collect long term performance data. In this work, we present one year of systematic SARS-CoV-2 wastewater surveillance in Portugal, representing 35 % of the mainland population. We employed two complementary methods for lineage determination - allelic discrimination by RT-PCR and S-gene sequencing. This combination allowed us to monitor variant evolution in near-real-time and identify low-frequency mutations. Over the course of this year-long study, spanning from May 2022 to April 2023, we successfully tracked the dominant Omicron sub-lineages, their progression and evolution, which aligned with concurrent clinical surveillance data. Our results underscore the effectiveness of WBS as a tracking system for virus variants, with the ability to unveil mutations undetected via massive sequencing of clinical samples from Portugal, demonstrating the ability of WBS to uncover new mutations and detect rare genetic variants. Our findings emphasize that knowledge of the genetic diversity of SARS-CoV-2 at the population level can be extended far beyond via the combination of routine clinical genomic surveillance with wastewater sequencing and genotyping.

Potential factors contributing to observed sex differences in virtual-reality-induced sickness.

Virtual reality (VR) technology has been widely adopted for several professional and recreational applications. Despite rapid innovation in hardware and software, one of the long prevailing issues for end users of VR is the experience of VR sickness. Females experience stronger VR sickness compared to males, and previous research has linked susceptibility to VR sickness to the menstrual cycle (Munafo et al., Exp Brain Res 235(3):889-901). Here we investigated the female versus male experience in VR sickness while playing an immersive VR game, comparing days of the menstrual cycle when hormones peak: day 15 (ovulation-peak estrogen) and day 22 (mid-luteal phase-peak progesterone). We found that immersion duration was greater in the second session than the first, and discomfort was lessened, suggesting a powerful adaptation with repeated exposure. Due to the estrogen levels changing along with the exposure, there was no clear independent impact of that; note, though, that there was a significant difference between self-report and physiological measures implying that GSR is potentially an unreliable measure of motion sickness. Although prior work found a delay over 2 days between session would not allow adaptation and habituation to reduce VR sickness susceptibility, we found that a week delay has potential success.

The Role of Sexual and Romantic Attraction in Human Mate Preferences.

Sex differences in mate preferences are ubiquitous, having been evidenced across generations and cultures. Their prevalence and persistence have compellingly placed them in the evolutionarily adaptive context of sexual selection. However, the psycho-biological mechanisms contributing to their generation and maintenance remain poorly understood. As such a mechanism, sexual attraction is assumed to guide interest, desire, and the affinity toward specific partner features. However, whether sexual attraction can indeed explain sex differences in partner preferences has not been explicitly tested. To better understand how sex and sexual attraction shape mate preferences in humans we assessed how partner preferences differed across the spectrum of sexual attraction in a sample of 479 individuals that identified as asexual, gray-sexual, demisexual or allosexual. We further tested whether romantic attraction predicted preference profiles better than sexual attraction. Our results show that sexual attraction accounts for highly replicable sex differences in mate preferences for high social status and financial prospects, conscientiousness, and intelligence; however, it does not account for the enhanced preference for physical attractiveness expressed by men, which persists even in individuals with low sexual attraction. Instead, sex differences in physical attractiveness preference are better explained by the degree of romantic attraction. Furthermore, effects of sexual attraction on sex differences in partner preferences were grounded in current rather than previous experiences of sexual attraction. Taken together, the results support the idea that contemporary sex differences in partner preferences are maintained by several psycho-biological mechanisms that evolved in conjunction, including not only sexual but also romantic attraction.

Malate production, sugar metabolism, and redox homeostasis in the leaf growth zone of Rye (Secale cereale) increase stress tolerance to aluminum stress: A biochemical and genome-wide transcriptional study.

Global soil acidification is increasing, enlarging aluminum (Al) availability in soils, leading to reductions in plant growth. This study investigates the effect of Al stress on the leaf growth zones of Rye (Secale cereale, cv Beira). Kinematic analysis showed that the effect of Al on leaf growth rates was mainly due to a reduced cell production rate in the meristem. Transcriptomic analysis identified 2272 significantly (log2fold > |0.5| FDR < 0.05) differentially expressed genes (DEGs) for Al stress. There was a downregulation in several DEGs associated with photosynthetic processes and an upregulation in genes for heat/light response, and H2O2 production in all leaf zones. DEGs associated with heavy metals and malate transport were increased, particularly, in the meristem. To determine the putative function of these processes in Al tolerance, we performed biochemical analyses comparing the tolerant Beira with an Al sensitive variant RioDeva. Beira showed improved sugar metabolism and redox homeostasis, specifically in the meristem compared to RioDeva. Similarly, a significant increase in malate and citrate production, which are known to aid in Al detoxification in plants, was found in Beira. This suggests that Al tolerance in Rye is linked to its ability for Al exclusion from the leaf meristem.

Cirrhotic cardiomyopathy: Pathogenesis, clinical features, diagnosis, treatment and prognosis.

Cardiac dysfunction among cirrhotic patients has long been recognized in the medical community. While it was originally believed to be a direct result of alcohol toxicity, in the last 30 years cirrhotic cardiomyopathy (CCM) has been described as a syndrome characterized by chronic cardiac dysfunction in cirrhotic patients in the absence of known cardiac disease, regardless of the etiology of cirrhosis. CCM occurs in about 60% of patients with cirrhosis and plays a critical role in disease progression and treatment outcomes. Due to its predominantly asymptomatic course, diagnosing CCM is challenging and requires a high index of suspicion and a multiparametric approach. Patients with CCM usually present with the following triad: impaired myocardial contractile response to exercise, inadequate ventricular relaxation, and electrophysiological abnormalities (notably prolonged QT interval). In recent years, research in this area has grown expeditiously and a new set of diagnostic criteria has been developed by the Cirrhotic Cardiomyopathy Consortium, to properly identify patients with CCM. Nevertheless, CCM is still largely unknown among clinicians, and a major part of its pathophysiology and treatment is yet to be understood. In the present work, we aim to compile and summarize the available data on the pathogenesis, clinical features, diagnosis, treatment, and prognosis of CCM.

Diversity and evolution of cerebellar folding in mammals.

The process of brain folding is thought to play an important role in the development and organisation of the cerebrum and the cerebellum. The study of cerebellar folding is challenging due to the small size and abundance of its folia. In consequence, little is known about its anatomical diversity and evolution. We constituted an open collection of histological data from 56 mammalian species and manually segmented the cerebrum and the cerebellum. We developed methods to measure the geometry of cerebellar folia and to estimate the thickness of the molecular layer. We used phylogenetic comparative methods to study the diversity and evolution of cerebellar folding and its relationship with the anatomy of the cerebrum. Our results show that the evolution of cerebellar and cerebral anatomy follows a stabilising selection process. We observed two groups of phenotypes changing concertedly through evolution: a group of 'diverse' phenotypes - varying over several orders of magnitude together with body size, and a group of 'stable' phenotypes varying over less than 1 order of magnitude across species. Our analyses confirmed the strong correlation between cerebral and cerebellar volumes across species, and showed in addition that large cerebella are disproportionately more folded than smaller ones. Compared with the extreme variations in cerebellar surface area, folial anatomy and molecular layer thickness varied only slightly, showing a much smaller increase in the larger cerebella. We discuss how these findings could provide new insights into the diversity and evolution of cerebellar folding, the mechanisms of cerebellar and cerebral folding, and their potential influence on the organisation of the brain across species.

Polymyxin B stabilized DNA micelles for sustained antibacterial and antibiofilm activity against P. aeruginosa.

Nucleic acid-based materials showcase an increasing potential for antimicrobial drug delivery. Although numerous reports on drug-loaded DNA nanoparticles outline their pivotal antibacterial activities, their potential as drug delivery systems against bacterial biofilms awaits further studies. Among different oligonucleotide structures, micellar nanocarriers derived from amphiphilic DNA strands are of particular interest due to their spontaneous self-assembly and high biocompatibility. However, their clinical use is hampered by structural instability upon cation depletion. In this work, we used a cationic amphiphilic antibiotic (polymyxin B) to stabilize DNA micelles destined to penetrate P. aeruginosa biofilms and exhibit antibacterial/antibiofilm properties. Our study highlights how the strong affinity of this antibiotic enhances the stability of the micelles and confirms that antibacterial activity of the novel micelles remains intact. Additionally, we show that PMB micelles can penetrate P. aeruginosa biofilms and impact their metabolic activity. Finally, PMB micelles were highly safe and biocompatible, highlighting their possible application against P. aeruginosa biofilm-colonized skin wounds.

Impact of emotional competence on physicians' clinical reasoning: a scoping review protocol.

INTRODUCTION: Clinical reasoning (CR) is a key competence for physicians and a major source of damaging medical errors. Many strategies have been explored to improve CR quality, most of them based on knowledge enhancement, cognitive debiasing and the use of analytical reasoning. If increasing knowledge and fostering analytical reasoning have shown some positive results, the impact of debiasing is however mixed. Debiasing and promoting analytical reasoning have also been criticised for their lack of pragmatism. Alternative means of increasing CR quality are therefore still needed. Because emotions are known to influence the quality of reasoning in general, we hypothesised that emotional competence (EC) could improve physicians' CR. EC refers to the ability to identify, understand, express, regulate and use emotions. The influence of EC on CR remains unclear. This article presents a scoping review protocol, the aim of which will be to describe the current state of knowledge concerning the influence of EC on physicians' CR, the type of available literature and finally the different methods used to examine the link between EC and CR. METHOD AND ANALYSIS: The population of interest is physicians and medical students. EC will be explored according to the model of Mikolajczak et al, describing five major components of EC (identify, understand, express, regulate and use emotions). The concept of CR will include terms related to its processes and outcomes. Context will include real or simulated clinical situations. The search for primary sources and reviews will be conducted in MEDLINE (via Ovid), Scopus and PsycINFO. The grey literature will be searched in the references of included articles and in OpenGrey. Study selection and data extraction will be conducted using the Covidence software. Search and inclusion results will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping review model (PRISMA-ScR). ETHICS AND DISSEMINATION: There are no ethical or safety concerns regarding this review. REGISTRATION DETAILS: OSF Registration DOI: https://doi.org/10.17605/OSF.IO/GM7YD.

Going beyond established model systems of Alzheimer's disease: companion animals provide novel insights into the neurobiology of aging.

Alzheimer's disease (AD) is characterized by brain plaques, tangles, and cognitive impairment. AD is one of the most common age-related dementias in humans. Progress in characterizing AD and other age-related disorders is hindered by a perceived dearth of animal models that naturally reproduce diseases observed in humans. Mice and nonhuman primates are model systems used to understand human diseases. Still, these model systems lack many of the biological characteristics of Alzheimer-like diseases (e.g., plaques, tangles) as they grow older. In contrast, companion animal models (cats and dogs) age in ways that resemble humans. Both companion animal models and humans show evidence of brain atrophy, plaques, and tangles, as well as cognitive decline with age. We embrace a One Health perspective, which recognizes that the health of humans is connected to those of animals, and we illustrate how such a perspective can work synergistically to enhance human and animal health. A comparative biology perspective is ideally suited to integrate insights across veterinary and human medical disciplines and solve long-standing problems in aging.

From fossils to mind.

Fossil endocasts record features of brains from the past: size, shape, vasculature, and gyrification. These data, alongside experimental and comparative evidence, are needed to resolve questions about brain energetics, cognitive specializations, and developmental plasticity. Through the application of interdisciplinary techniques to the fossil record, paleoneurology has been leading major innovations. Neuroimaging is shedding light on fossil brain organization and behaviors. Inferences about the development and physiology of the brains of extinct species can be experimentally investigated through brain organoids and transgenic models based on ancient DNA. Phylogenetic comparative methods integrate data across species and associate genotypes to phenotypes, and brains to behaviors. Meanwhile, fossil and archeological discoveries continuously contribute new knowledge. Through cooperation, the scientific community can accelerate knowledge acquisition. Sharing digitized museum collections improves the availability of rare fossils and artifacts. Comparative neuroanatomical data are available through online databases, along with tools for their measurement and analysis. In the context of these advances, the paleoneurological record provides ample opportunity for future research. Biomedical and ecological sciences can benefit from paleoneurology's approach to understanding the mind as well as its novel research pipelines that establish connections between neuroanatomy, genes and behavior.

Differences in office-based personal space perception between British and Korean populations.

We sought to understand how the perception of personal space is influenced by different levels of social density, spatial density, and type of window-view in South Korean and United Kingdom workplaces. We employed virtual reality to simulate shared and single occupancy offices. We obtained personal space estimations using a virtual disc around the participant which could be extended and retracted, inside the simulation, to indicate perceived amount of personal space, and compared this measure to questionnaire-based estimations. We found that in both cultures participants experienced greater perceived personal space (1) when in a sparse rather than dense office and (2) having a view of the city outside the office. However, British, but not Korean, participants had significantly higher personal space estimations in single occupancy offices than in shared offices. These results suggest subtle cross-cultural differences in workplace experience, that could only be investigated using virtual reality.

Myocardial infarction with non-obstructive coronary arteries: Etiology, diagnosis, treatment and prognosis.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is responsible for 10% of myocardial infarctions. Previously, patients were thought to have good prognosis, but evidence-based management and treatment strategies were scarce. Today, researchers and physicians recognize MINOCA as a condition with non-trivial mortality and morbidity. Therapeutic strategies are highly dependent on the underlying disease mechanism in each patient. However, to reach a diagnosis of MINOCA, a multimodal approach is required and, even with an optimal work-up, the cause remains unknown in 8-25% of patients. Research has been growing and position papers from the European Society of Cardiology (ESC) and the American Heart Association/American College of Cardiology have been published, and MINOCA has been included in the more recent ESC guidelines on myocardial infarction. Nonetheless, some clinicians still assume that the absence of coronary obstruction excludes the possibility of acute myocardial infarction. Therefore, in the present paper, we aim to compile and present the available data on the etiology, diagnosis, treatment, and prognosis of MINOCA.

Evolutionary and genomic perspectives of brain aging and neurodegenerative diseases.

This chapter utilizes genomic concepts and evolutionary perspectives to further understand the possible links between typical brain aging and neurodegenerative diseases, focusing on the two most prevalent of these: Alzheimer's disease and Parkinson's disease. Aging is the major risk factor for these neurodegenerative diseases. Researching the evolutionary and molecular underpinnings of aging helps to reveal elements of the typical aging process that leave individuals more vulnerable to neurodegenerative pathologies. Very little is known about the prevalence and susceptibility of neurodegenerative diseases in nonhuman species, as only a few individuals have been observed with these neuropathologies. However, several studies have investigated the evolution of lifespan, which is closely connected with brain size in mammals, and insights can be drawn from these to enrich our understanding of neurodegeneration. This chapter explores the relationship between the typical aging process and the events in neurodegeneration. First, we examined how age-related processes can increase susceptibility to neurodegenerative diseases. Second, we assessed to what extent neurodegeneration is an accelerated form of aging. We found that while at the phenotypic level both neurodegenerative diseases and the typical aging process share some characteristics, at the molecular level they show some distinctions in their profiles, such as variation in genes and gene expression. Furthermore, neurodegeneration of the brain is associated with an earlier onset of cellular, molecular, and structural age-related changes. In conclusion, a more integrative view of the aging process, both from a molecular and an evolutionary perspective, may increase our understanding of neurodegenerative diseases.

Evolutionary history of hominin brain size and phylogenetic comparative methods.

An absolutely and relatively large brain has traditionally been viewed as a distinctive characteristic of the Homo genus, with anatomically modern humans presented at the apex of a long line of progressive increases in encephalization. Many studies continue to focus attention on increasing brain size in the Homo genus, while excluding measures of absolute and relative brain size of more geologically recent, smaller brained, hominins such as Homo floresiensis, and Homo naledi and smaller brained Homo erectus specimens. This review discusses the benefits of using phylogenetic comparative methods to trace the diverse changes in hominin brain evolution and the drawbacks of not doing so.

Unveiling an Unusual Cause of Cardiac Tamponade.

This case presents a 48-year-old woman initially diagnosed with an ostium secundum atrial septal defect (ASD) at the age of 36. Twelve years post-intervention, she presented to the emergency department with cardiac tamponade. This case highlights the importance of maintaining prolonged follow-up for individuals undergoing percutaneous ASD closure, given the possibility of potentially fatal late complications of ASD occlusion devices.

Subcellular compartmentalization of aluminum reduced its hazardous impact on rye photosynthesis.

Aluminum (Al) toxicity limits crops growth and production in acidic soils. Compared to roots, less is known about the toxic effects of Al in leaves. Al subcellular compartmentalization is also largely unknown. Using rye (Secale cereale L.) Beira (more tolerant) and RioDeva (more sensitive to Al) genotypes, we evaluated the patterns of Al accumulation in leaf cell organelles and the photosynthetic and metabolic changes to cope with Al toxicity. The tolerant genotype accumulated less Al in all organelles, except the vacuoles. This suggests that Al compartmentalization plays a role in Al tolerance of Beira genotype. PSII efficiency, stomatal conductance, pigment biosynthesis, and photosynthesis metabolism were less affected in the tolerant genotype. In the Calvin cycle, carboxylation was compromised by Al exposure in the tolerant genotype. Other Calvin cycle-related enzymes, phoshoglycerate kinase (PGK), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), triose-phosphate isomerase (TPI), and fructose 1,6-bisphosphatase (FBPase) activities decreased in the sensitive line after 48 h of Al exposure. Consequentially, carbohydrate and organic acid metabolism were affected in a genotype-specific manner, where sugar levels increased only in the tolerant genotype. In conclusion, Al transport to the leaf and compartmentalization in the vacuoles tolerant genotype's leaf cells provide complementary mechanisms of Al tolerance, protecting the photosynthetic apparatus and thereby sustaining growth.

Hyperkalemia as a limiting factor of neurohormonal blockade/modulation in everyday clinical practice.

INTRODUCTION AND OBJECTIVES: Neurohormonal blockade (NB)/modulation is the combination of two renin-angiotensin-aldosterone system inhibitors (RAASi) with a beta blocker. It is the core therapy for heart failure with reduced ejection fraction (HFrEF). While improving long term prognosis, it also induces hyperkalemia (serum K+ >5.0 mEq/L) due to RAASi effects. This may cause lethal arrhythmias and increase mortality in the short term. Thus, hyperkalemia frequently leads to withholding or reducing the intensity of neurohormonal blockade/modulation, which is associated with worsening long term prognosis. We assessed the relevance of hyperkalemia as a limiting factor of neurohormonal blockade/modulation in real life clinical conditions. METHODS: We reviewed the medical records of HFrEF patients attending a HF clinic at a tertiary Portuguese hospital during 2018 (n=240). The number of patients not tolerating maximal neurohormonal blockade/modulation due to hyperkalemia was determined. The incidence and characteristics of hyperkalemia episodes were also assessed. RESULTS: Only six patients (3%) achieved maximal doses of neurohormonal blockade/modulation. Hyperkalemia was the limiting factor in 48 (20%) patients. A total of 185 hyperkalemia episodes occurred in 100 (42%) patients. Forty-five (24%) episodes were moderate or severe (serum K+ >5.5 mEq/L). In these HFrEF patients, the co-existence of hypertension, diabetes or renal failure was associated with the occurrence of hyperkalemia. CONCLUSIONS: In daily clinical practice, hyperkalemia is frequent and limits neurohormonal blockade/modulation by leading to the withholding or reducing of the intensity of RAAS inhibition. Considering the negative prognostic impact associated with sub-optimal neurohormonal blockade/modulation, addressing hyperkalemia is an important issue when treating HFrEF patients.

Do we enjoy what we sense and perceive? A dissociation between aesthetic appreciation and basic perception of environmental objects or events.

This integrative review rearticulates the notion of human aesthetics by critically appraising the conventional definitions, offerring a new, more comprehensive definition, and identifying the fundamental components associated with it. It intends to advance holistic understanding of the notion by differentiating aesthetic perception from basic perceptual recognition, and by characterizing these concepts from the perspective of information processing in both visual and nonvisual modalities. To this end, we analyze the dissociative nature of information processing in the brain, introducing a novel local-global integrative model that differentiates aesthetic processing from basic perceptual processing. This model builds on the current state of the art in visual aesthetics as well as newer propositions about nonvisual aesthetics. This model comprises two analytic channels: aesthetics-only channel and perception-to-aesthetics channel. The aesthetics-only channel primarily involves restricted local processing for quality or richness (e.g., attractiveness, beauty/prettiness, elegance, sublimeness, catchiness, hedonic value) analysis, whereas the perception-to-aesthetics channel involves global/extended local processing for basic feature analysis, followed by restricted local processing for quality or richness analysis. We contend that aesthetic processing operates independently of basic perceptual processing, but not independently of cognitive processing. We further conjecture that there might be a common faculty, labeled as aesthetic cognition faculty, in the human brain for all sensory aesthetics albeit other parts of the brain can also be activated because of basic sensory processing prior to aesthetic processing, particularly during the operation of the second channel. This generalized model can account not only for simple and pure aesthetic experiences but for partial and complex aesthetic experiences as well.