Based upon Maxwell's equations, it has long been established that oscillating electromagnetic (EM) fields incident upon a metal surface decay exponentially inside the conductor, leading to a virtual EM vacuum at sufficient depths. Magnetic resonance imaging (MRI) utilizes radiofrequency (r.f.) EM fields to produce images. Here we present the first visualization of a virtual EM vacuum inside a bulk metal strip by MRI, amongst several novel findings. We uncover unexpected MRI intensity patterns arising from two orthogonal pairs of faces of a metal strip, and derive formulae for their intensity ratios, revealing differing effective elemental volumes (voxels) underneath these faces. Further, we furnish chemical shift imaging (CSI) results that discriminate different faces (surfaces) of a metal block according to their distinct nuclear magnetic resonance (NMR) chemical shifts, which holds much promise for monitoring surface chemical reactions noninvasively. Bulk metals are ubiquitous, and MRI is a premier noninvasive diagnostic tool. Combining the two, the emerging field of bulk metal MRI can be expected to grow in importance. The fundamental nature of results presented here may impact bulk metal MRI and CSI across many fields.

This work aimed to elucidate how O3 pollution causes loss of regulation of the immune response in both the brain and the intestine. In this work, we studied the effect of exposing rats to low doses of O3 on the association between the antioxidant response of superoxide dismutase (SOD) levels and nuclear factor kappa light chains of activated B cells (NFκB) as a marker of inflammation. Method: 72 Wistar rats were used, divided into six groups that received the following treatments: Control, 7, 15, 30, 60, and 90 days at O3, respectively. After treatment, tissues were extracted and processed using Western blotting, biochemical, and immunohistochemical techniques. The results indicated an increase in 4-hydroxynonenal (4HNE) and Cu/Zn-SOD, a decrease in Mn-SOD, and SOD activity in the substantia nigra, jejunum, and colon decrease. Furthermore, the translocation of NFκB to the nucleus increased in the different organs studied. In conclusion, repeated exposure to ozone alters the regulation of the antioxidant and inflammatory response in the substantia nigra and the intestine. This suggests that these responses are critical in the loss of regulation of the inflammatory response, and they respond to ozone pollution, which could be occurring in the progression of chronic degenerative diseases.

Background: Data on the benefits of rapid microbiological testing on antimicrobial consumption (AC) and antimicrobial resistance patterns(ARP) are scarce. We evaluated the impact of a protocol based on rapid techniques on AC and ARP in intensive care (ICU) patients. Methods: Retrospective pre(2018) and post-intervention(2019-21) study in ICU patients. A rapid diagnostic algorithm was applied from 2019 in patients with lower respiratory tract infection. Incidence of nosocomial infection, ARP, and AC as DDD(defined daily dose) were monitored. Results: A total of 3635 patients were included, 987(pre-intervention) and 2648(post-intervention). A median age was 60 years, 64% male, with APACHE II of 19 points and SOFA of 3 points. Overall ICU mortality of 17.2% without differences between the periods. An increase in the number of infections was observed in the post-intervention period(44.5% vs 17.9%, p<0.01), especially due to an increase in ventilator-associated pneumonia(44.6% vs 25%,p<0.001). AC decreased from 128.7 DDD in 2018 to 66.0 DDD in 2021(Rate Ratio=0.51). A recovery of P.aeruginosa susceptibility of 23% for Piperacillin/tazobactam and 31% for Meropenem was observed. Conclusion: The implementation of an algorithm based on rapid microbiological diagnostic techniques allowed a significant reduction in AC and ARP without affecting the prognosis of critically ill patients.

Congenital heart disease (CHD) is among the 4 more common causes of infant mortality in Latin America. Pulse oximetry screening (POS) is useful for early diagnosis and improved outcomes of critical CHD. We describe POS implementation efforts in Latin American countries guided and/or coordinated by the Ibero American Society of Neonatology (SIBEN) as well as the unique challenges that are faced for universal implementation. SIBEN collaborates to improve neonatal quality of care and outcomes. A few years ago, a Clinical Consensus on POS was finalized. Since then, we participated in 12 Latin American countries to educate neonatal nurses and neonatologists on POS and to help with its implementation. The findings reveal that despite wide disparities in care that exist between and within countries, and the difficulties and challenges for implementing POS, significant progress was made. We conclude that universal POS is not easy to implement in Latin America but, when executed, not only it has been of significant value for babies with CHD but also for many with other hypoxemic conditions. The successful and universal implementation of POS in the future is essential to reduce the mortality associated with CHD and other hypoxemic conditions and will ultimately lead to the survival of many more Latin American babies. POS saves newborns’ lives in Latin America.

Introduction- The dynamics of SARS-CoV-2 shedding and replication in humans remain incompletely understood. Methods- We analyzed SARS-CoV-2 shedding from multiple sites in individuals with an acute COVID-19 infection by weekly sampling for five weeks in 98 immunocompetent and 25 immunosuppressed individuals. Samples and culture supernatants were tested by RT-PCR for SARS-CoV-2 to determine viral clearance rates and in vitro replication. Results- A total of 2447 clinical specimens were evaluated, including 557 nasopharyngeal swabs, 527 saliva samples, 464 urine specimens, 437 anal swabs and 462 blood samples. The SARS-CoV-2 genome sequences at each site were classified as belonging to the B.1.128 (ancestral strain) or Gamma lineage. SARS CoV-2 detection was highest in nasopharyngeal swabs regardless of the virus strain involved or the immune status of infected individuals. The duration of viral shedding varied between clinical specimens and individual patients. Prolonged shedding of potentially infectious virus varied from 10 days up to 191 days, and primarily occurred in immunosuppressed individuals. Virus was isolated in culture from 18 nasal swab or saliva samples collected 10 or more days after onset of disease. Conclusions-Our findings indicate that persistent SARS-CoV-2 shedding may occur in both competent or immunosuppressed individuals, at multiple clinical sites and in a minority of subjects is capable of in vitro replication.

The population’s mobility in urban areas is a necessary variable in the modeling of risk scenarios caused by atmospheric contamination. The inclusion of this concept makes static models more dynamic while considering people within a city to be an entity with complex mobility processes. We propose a conceptual and methodological tool to make the representation of the social, economic and territorial components, as well as the patterns in the population´s mobility to delimitate risk areas for human health by exposure of contaminants. In the volatile organic compounds (VOC), benzene, ethylbenzene, toluene and xylene (BTEX) are amongst the most dominant substances in fugitive vapor emissions in gas stations (GS). In urban areas, the exposure to BTEX by residential proximity and proximity to other facilities, which cause intra-urban agglomeration, can impact and affect human health. This model seeks to facilitate the focalization, identification and prioritization of risk areas by BTEX environmental contamination. This article goes beyond de conceptual framework. It suggests methodological and instrumental aspects to be applied in other cities. The government agencies must consider these results when establishing rules, permissions and procedures to reduce environmental pollution for managing the risk in a complex urban environment.

After the global challenges posed by COVID-19, researchers strived to identify risk factors for severe cases, which lead to various complications - including death. Lifestyle modifications, such as implementing a healthy diet and recommended physical activity, have shown to be protective against severe COVID-19 cases. Despite an association of a plant-based diet with reduced COVID-19 severity, specific dietary characteristics have not been identified. Also, the methodology for measuring physical activity is variable, with studies overlooking the intensity or the habit components of physical activity. To bridge this gap, our study designed, validated, and applied a retrospective questionnaire with aims of exploring the relationship between lifestyle factors, specifically diet and physical activity, and severe COVID-19. We considered the intensity and years of physical activity habit, which is a limitation of other questionnaires. Results reveal associations of age and BMI with severe COVID-19. An excessive sugar diet was found to be associated with severe COVID-19 and increased symptom duration. We also observed an inverse relationship pattern of moderate and vigorous intensity physical activity across case severity, which is absent in walking PA. This study lays a foundation for research aiming to identify lifestyle factors that prevent severe COVID-19 cases.

Background: Cutaneous malignant melanoma (CMM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice for the treatment of metastatic CMM. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CMM in several Italian centers which are part of the Clinical National Melanoma Registry (CNMR), and the oncological outcomes obtained. Methods: CNMR collects data of patients with a histologically confirmed diagnosis of primary CMM treated in one of the 38 Italian institutions (hospitals, research institutes, etc.) participating in the network. Melanoma-specific survival and Overall survival were calculated. Kaplan-Meier curves and medians of OS and 95% CI are presented overall and by immunotherapy and target treatments. The Log-rank test compared curves by treatments. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors. Results: The median follow-up time was 36 months (range 1.2-185.1). 787 CMM were included in the analysis with completed information about therapies.Global immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by nivolumab/pembrolizumab immunotherapy (anti-PD1 HR=0.25 95% CI 0.14-0.42), globally immunotherapy was significantly associated with improved survival, either for anti-CTL A4 monotherapy or combined with anti-PD1 (HR=0.47;95% CI 0.33-0.66 and HR=0.26; 95% CI 0.15-0.46, respectively). Conclusions: The nivolumab/pembrolizumab and the combination of ipilimumab can be considered the best therapy to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment.

We describe an interesting case report about a patient with hemophilia A with severe chronic elbow arthropathy who underwent multiple surgical because of his condition. We collected all the clinical and imaging findings, and we compared the decision-making flow chart and the surgery performed with the most recent indications, treatments and complications reported in the literature. The aim of this case report is to show how usually the hemophilic patient even if young usually comes to our attention from the beginning with complex and advance musculoskeletal disease. Elbow hemophilic arthropathy is a complex disease and the management in these patients could be more difficult than others because of the higher risk of complications rate after all surgical procedures, for this reason it’s very important to treat these patients in hub centers with expertise in well-coordinated multidisciplinary teams. The path from diagnosis to surgical treatment of hemophilic elbow arthropathy can be a risky one, as it happened in this case.

Alzheimer's disease (AD) is a neurodegenerative olfactory disorder affecting millions of people worldwide. Alterations in the hexosamine or glucose-related pathways have been described through AD progression. Specifically, an alteration in glucosamine 6 phosphate isomerase 2 (GNPDA2) protein levels has been observed in olfactory areas from AD subjects. However, the biological role of GNPDA2 in neurodegeneration remains unknown. Using mass-spectrometry, multiple GNPDA2 interactors were identified in human nasal epithelial cells (NECs) mainly involved in intraciliary transport. Moreover, GNPDA2 overexpression induced an increment in NEC proliferation rates, accompanied by transcriptomic alterations in Type II interferon signalling or cellular stress responses. In contrast, the presence of beta-amyloid or mutated Tau-P301L in GNPDA2-overexpressing NECs induced a slow-down in the proliferative capacity in parallel with a disruption in protein processing. The proteomic characterization of Tau-P301L transgenic zebrafish embryos demonstrated that GNPDA2 overexpression interfered with collagen biosynthesis and RNA/protein processing, without inducing additional changes in axonal outgrowth defects nor neuronal cell death. In humans, a significant increase in serum GNPDA2 levels was observed across multiple neurological proteinopathies (AD, Lewy body dementia, progressive supranuclear palsy, mixed-dementia, and amyotrophic lateral sclerosis) (n=187). These data shed new light on GNPDA2-dependent mechanisms associated to the neurodegenerative process beyond the hexosamine route.

Risk stratification for malignant ventricular arrhythmias and sudden cardiac death is a daunting task for physicians in daily practice. Multiparametric mapping sequences obtained via cardio-vascular magnetic resonance imaging can improve the risk for malignant ventricular arrhythmias by unveiling the presence of pathophysiological pro-arrhythmogenic processes. However, their employment in clinical practice is still restricted. The present review explores the current evidence supporting the association between mapping abnormalities and the risk of ventricular arrhyth-mias in several cardiovascular diseases. The key message is that further clinical studies are needed to test the additional value of mapping techniques beyond conventional cardiovascular magnetic resonance imaging for selecting patients eligible for an implantable cardioverter defibrillator.

Hepatocellular carcinoma (HCC) development is associated with altered modifications in DNA methylation, changing transcriptional regulation. Emerging evidence indicates that DNA methyltransferase 1 (DNMT1) plays a key role in carcinogenesis process. This study aimed to investigate how pirfenidone (PFD) modifies this pathway and the effect generated by the association between c-Myc expression and DNMT1 activation. Rats F344 were used for HCC development using 50 mg/kg of diethylnitrosamine (DEN) and 25 mg/kg of 2-aminofluorene (2-AAF). HCC/PFD group received simultaneous doses of 300 mg/kg of PFD. All treatments lasted 12 weeks. On the other hand, HepG2 cells were used to evaluate the effects of PFD in restoring DNA methylation in the presence of the inhibitor 5-Aza. Histopathological, biochemical, immunohistochemical, and western blot analysis were carried out and our findings showed that PFD treatment reduced the amount and size of tumors along with decreased Glipican-3, β-catenin, and c-Myc expression in nuclear fractions. Also, this treatment improved lipid metabolism by modulating PPARγ and SREBP1 signaling. Interestingly, PFD augmented DNMT1 and DNMT3a protein expression, which restores global methylation, both in our in vivo and in vitro models. In conclusion, our results suggest that PFD could slow down HCC development by controlling DNA methylation.

Within microeukaryotes, genetic and functional variation sometimes accumulate more quickly than morphological differences. To understand the evolutionary history and ecology of such lineages, it is key to examine diversity at multiple levels of organization. In the dinoflagellate family Symbiodiniaceae, which can form endosymbioses with cnidarians (e.g., corals, octocorals, sea anemones, jellies), other marine invertebrates (e.g., sponges, molluscs, flatworms), and protists (e.g., foraminifera), molecular data have been used extensively over the past three decades to describe phenotypes and to make evolutionary and ecological inferences. Despite advances in Symbiodiniaceae genomics, a lack of consensus among researchers with respect to interpreting genetic data has slowed progress in the field and acted as a barrier to reconciling observations. Here, we identify key challenges regarding the assessment and interpretation of Symbiodiniaceae genetic diversity across three levels: species, populations, and communities. We summarize areas of agreement and highlight techniques and approaches that are broadly accepted. In areas where debate remains, we identify unresolved issues and discuss technologies and approaches that can help to fill knowledge gaps related to genetic and phenotypic diversity. We also discuss ways to stimulate progress, in particular by fostering a more inclusive and collaborative research community. We hope that this perspective will inspire and accelerate coral reef science by serving as a resource to those designing experiments, publishing research, and applying for funding related to Symbiodiniaceae and their symbiotic partnerships.