Search

Abstract Introduction Sickle cell disease (SCD) is characterized by acute episodes called vaso‐occlusive crises (VOC). VOC is marked by severe pain due to blocked blood vessels by sickled cells. Ketamine has been reported to be effective and safe in managing VOC in SCD patients. Objectives/methods This review aims to determine ketamine's safety and efficacy through analysis of clinical trials and observational studies. Methods Adhering to PRISMA guidelines, this systematic review and meta‐analysis systematically searched seven databases on May 20, 2024 for randomized control trials (RCT), cohorts, and case–control studies. Results Five studies with 689 participants met the inclusion criteria. A meta‐analysis of two studies (518 observations) for the Numerical Rating Scale (NRS) pain score showed no significant difference, with a standardized mean difference (MD) of 0.23 (95% CI: −0.13 to 0.59, p = 0.21, I2 = 0%). For morphine milligram equivalent (MME), a meta‐analysis of two studies (344 observations) resulted in an MD of −0.03 (95% CI: −0.09 to 0.04, p = 0.45, I2 = 97%). However, the side effects analysis from four studies (608 observations) showed a significantly higher relative risk (RR) of 5.74 (95% CI: 2.80–11.79, p

Abstract The “Sign-tracker/Goal-tracker” (ST/GT) is an animal model of individual differences in learning and motivational processes attributable to distinctive conditioned responses to environmental cues. While GT rats value the reward-predictive cue as a mere predictor, ST rats attribute it with incentive salience, engaging in aberrant reward-seeking behaviors that mirror those of impulse control disorders. Given its potential clinical value, the present study aimed to map such model onto humans and investigated resting state functional magnetic resonance imaging correlates of individuals categorized as more disposed to sign-tracking or goal-tracking behavior. To do so, eye-tracking was used during a translationally informed Pavlovian paradigm to classify humans as STs (n = 36) GTs (n = 35) or as Intermediates (n = 33), depending on their eye-gaze towards the reward-predictive cue or the reward location. Using connectivity and network-based approach, measures of resting state functional connectivity and centrality (role of a node as a hub) replicated preclinical findings, suggesting a major involvement of subcortical areas in STs, and dominant cortical involvement in GTs. Overall, the study strengthens the translational value of the ST/GT model, with important implications for the early identification of vulnerable phenotypes for psychopathological conditions such as substance use disorder.

Abstract The lithium cycling in the supra-subduction mantle wedge is crucial for understanding the generation of Li-rich magmas that may potentially source ore deposition in continental arcs. Here, we look from the mantle source perspective at the geological processes controlling the Li mobility in convergent margins, by characterizing a set of sub-arc mantle xenoliths from the southern Andes (Coyhaique, western Patagonia). The mineral trace element signatures and oxygen fugacity estimates (FMQ > + 3) in some of these peridotite xenoliths record the interaction with arc magmas enriched in fluid-mobile elements originally scavenged by slab dehydration. This subduction-related metasomatism was poorly effective on enhancing the Li inventory of the sub-arc lithospheric mantle, underpinning the inefficiency of slab-derived fluids on mobilizing Li through the mantle wedge. However, major and trace element compositions of mantle minerals in other xenoliths also record transient thermal and chemical anomalies associated with the percolation of slab window-related magmas, which exhibit an “adakite”-type geochemical fingerprint inherited by slab-derived melts produced during ridge subduction and slab window opening event. As these melts percolated through the shallow (7.2–16.8 kbar) and hot (952–1054 °C) lithospheric mantle wedge, they promoted the crystallization of metasomatic clinopyroxene having exceptionally high Li abundances (6–15 ppm). Numerical modeling shows that low degrees (

ABSTRACT Objective: To develop and validate the content of checklists for safe admission and discharge in Neonatal Intensive Care Units. Methods: A methodological study conducted between 2018 and 2020 in four stages: 1) literature review; 2) checklist construction; 3) content validity by 32 neonatal nursing specialists from different Brazilian states, predominantly from the southeastern region; 4) development of the final version of the instruments. Validity was performed using a Likert-type scale. Items with a Content Validity Index of 0.90 or higher were accepted. Descriptive statistics were used for data analysis. Results: The contents of two checklists were constructed and validated: one for admission, with 18 items, and another for discharge, with seven items. For the admission checklist, 41.03% of items were validated in the first round, 33.33%, in the second, and 23.08%, in the third. One item was excluded for not achieving the minimum Content Validity Index (>0.90). For the discharge checklist, all items achieved a CVI ≥ 0.90, with 64.7% validated in the first round and 35.3% in the second round. No items were excluded. Conclusion: The content of patient safety checklists for admission and discharge in Neonatal Intensive Care Units was considered valid.

Problem considered: Chagas disease is a vector-borne parasitic infection considered of public health importance. For farmers and residents of endemic areas, vectors are part of their day to day life and they often lack awareness of their infectious potential, so the risk they pose is not a main concern in their lives. So far, existing measures set in place to eradicate the vector have not been effective long-term. Methods: In this study, a one-year program was designed and implemented to inform and assess the knowledge, attitudes, and perceptions of 81 parents or heads of household regarding the risk of transmission and prevention of Trypanosoma cruzi infection. The program aimed to raise awareness of the crucial role they play in the prevention and control of vectors associated with Chagas disease. Results: After educational interventions, a notable increase in the percentage of knowledge regarding the parasite, transmission factors, and Chagas disease was observed. Conclusion: This might suggest that properly implementing educational interventions within the population, with training from health professionals and through public programs, will allow for the reduction of infection risks. In the long term, it could significantly reduce the incidence of the disease in the region and state.

Abstract Termites of the genus Nasutitermes sp. (Blattodea: Termitidae), which feed on cellulose, may cause wood to become brittle and fragile. This study aimed to evaluate the natural resistance of three native wood species: Magonia pubescens (Sapindaceae), Dalbergia nigra and Machaerium amplum (Fabaceae) to attack by Nasutitermes sp. termites and to investigate the relationship between resistance, extractive content, and oven-dry density. Samples of each wood species were subjected to a forced feeding process with Nasutitermes sp. termites for 30 days. Following the exposure, the oven-dry density, extractive content, percentage of wood loss, and termite mortality were determined for each sample. Dalbergia nigra exhibited resistance to termite attack and had the highest extractive content at 13.14%. Conversely, M. amplum had the highest wood loss at 5.37% and the lowest extractive content at 1.94%. Both species showed a negative correlation between wood loss and extractive content, but no correlation with wood density. Magonia pubescens had the highest density at 0.90 g/cm3. Macherium amplum and M. pubescens caused 100% termite mortality, while D. nigra caused 40% mortality.

(1) Background: Parents’ awareness of malocclusion and their attitude towards early evaluation and interventions influence children’s orthodontic management. This cross-sectional study investigates factors that affect the perceived orthodontic needs and the attitude towards interceptive orthodontics among a sample of one-thousand eight-hundred and six (1806) parents of children aged between 6 and 11 years. (2) Methods: The investigation was carried out thought a 18-items online questionnaire divided as follows: characteristics of respondents; perceived child’s orthodontic needs; attitude toward early orthodontic evaluation and interventions. The associations between responses were assessed with a Chi-square test. (3) Results: Two-thirds of the respondents referred to having consulted an orthodontist for their child, and more than half of them initiated the required orthodontic treatment. In 44% of cases, the orthodontic consultation occurred after the age of 7 years. Parents’ higher education and history of orthodontic treatment were associated with a greater awareness of orthodontic needs. Parents’ perception of the impact of teeth on their child’s personality was significantly associated with the decision to start the orthodontic treatment (p < 0.001). (4) Conclusions: Although the parents’ level of awareness of their child’s orthodontic needs was generally satisfactory, the results of the present study pointed out the need for a better education regarding the importance of an early orthodontic assessment.

Abstract 5q-spinal muscular atrophy (SMA) is a neuromuscular disorder (NMD) that has become one of the first 5% treatable rare diseases. The efficacy of new SMA therapies is creating a dynamic SMA patient landscape, where disease progression and scoliosis development play a central role, however, remain difficult to anticipate. New approaches to anticipate disease progression and associated sequelae will be needed to continuously provide these patients the best standard of care. Here we developed an interpretable machine learning (ML) model that can function as an assistive tool in the anticipation of SMA-associated scoliosis based on disease progression markers. We collected longitudinal data from 86 genetically confirmed SMA patients. We selected six features routinely assessed over time to train a random forest classifier. The model achieved a mean accuracy of 0.77 (SD 0.2) and an average ROC AUC of 0.85 (SD 0.17). For class 1 ‘scoliosis’ the average precision was 0.84 (SD 0.11), recall 0.89 (SD 0.22), F1-score of 0.85 (SD 0.17), respectively. Our trained model could predict scoliosis using selected disease progression markers and was consistent with the radiological measurements. During post validation, the model could predict scoliosis in patients who were unseen during training. We also demonstrate that rare disease data sets can be wrangled to build predictive ML models. Interpretable ML models can function as assistive tools in a changing disease landscape and have the potential to democratize expertise that is otherwise clustered at specialized centers.

Stressors can initiate a cascade of central and peripheral changes that modulate mesocorticolimbic dopaminergic circuits and, ultimately, behavioral response to rewards. Driven by the absence of conclusive evidence on this topic and the Research Domain Criteria framework, random-effects meta-analyses were adopted to quantify the effects of acute stressors on reward responsiveness, valuation, and learning in rodent and human subjects.In rodents, acute stress reduced reward responsiveness (g = −1.43) and valuation (g = −0.32), while amplifying reward learning (g = 1.17). In humans, acute stress had marginal effects on valuation (g = 0.25), without affecting responsiveness and learning. Moderation analyses suggest that acute stress neither has unitary effects on reward processing in rodents nor in humans and that the duration of the stressor and specificity of reward experience (i.e., food vs drugs) may produce qualitatively and quantitatively different behavioral endpoints.Subgroup analyses failed to reduce heterogeneity, which, together with the presence of publication bias, pose caution on the conclusions that can be drawn and point to the need of guidelines for the conduction of future studies in the field.

This paper proposes a general analytical formulation for LCL filter design for grid-connected PWM-driven cascaded H-bridge inverters. The novelty of this work deals with providing some easy-of-use analytical expressions that allow for properly sizing the filter inductances and capacitance values considering the number of voltage levels, the DC-link voltage, the adopted multicarrier pulse width modulation strategy, and the switching frequency. Although multilevel inverters performance strongly depends on the adopted modulation strategy and switching frequency, a general mathematical formulation that allows for properly sizing the LCL filter by considering such parameters simultaneously is currently missing. The proposed approach is generalized for the most adopted multicarrier pulse width modulation strategies. To validate the proposed approach, an extended investigation analysis is performed by hardware-in-the-loop real-time tests. According to international standards EN50160 and IEEE Std 1547–2018, the voltage total harmonic distortion and current total rated distortion are adopted to evaluate the LCL filter performance. Tests are carried out in several working conditions, defined in terms of provided apparent power and power factor values. Finally, the proposed analytical formulation is adopted to formulate an optimized LCL filter design algorithm that allows for matching the standard requirements without oversizing the filter parameters.

O objetivo deste texto é apresentar uma proposta de atendimento psicossocial grupal realizada com adolescentes que cometeram ofensa sexual e caracterizada por uma perspectiva de serem atendidos em família (Grupo Multifamiliar). Além da demanda por atendimentos a adolescentes de 12 a 15 anos que cometeram ofensa sexual, tem sido observada a inclusão da faixa etária de 16 a 18 anos. Estas duas faixas etárias, 12-15 e 16-18 anos, apresentam distintas características com relação às violências sofridas em suas curtas histórias de vida, bem como à gravidade das violências cometidas. A proposta desenvolvida foi composta por sete sessões de três horas cada, com temas pré-definidos que têm processamentos dirigidos aos participantes em função de suas idades: crianças, adolescentes e adultos. Cada sessão se organizou em três momentos: aquecimento, discussão do tema e conclusão. O método do atendimento incluiu atividades lúdicas e utilização de recursos psicodramáticos adaptados aos adolescentes das duas faixas etárias e aos familiares. O presente texto é descritivo e relata a proposta de atendimento realizada adaptada para o contexto de adolescentes nessas faixas etárias e seus familiares, a partir de uma pesquisa-ação mais ampla. Discutem-se as possibilidades da proposta, a partir das observações dos profissionais que realizaram atendimento grupal, em conjunto com as informações presentes na literatura sobre ofensa sexual cometida por adolescentes. Ressalta-se a necessidade de estudos futuros que aprofundem sobre o tema de adolescentes que cometeram ofensa sexual, considerando as especificidades dessas faixas etárias. Indicam-se ainda os limites da proposta e impasses em sua aplicabilidade.

Background: Vestibulodynia (VBD) represents a summation and overlapping of trigger factors (infections, hormonal disturbances, allergies, genetic aspects, psychological vulnerability, and others) with broad individual variability. As there are no standard treatment options for VBD, the disease is still in need of appropriate therapeutic tools. Objectives: A prospective observational trial was performed to confirm the efficacy of a topical gel containing a spermidine–hyaluronate complex (UBIGEL donna™) as either a stand-alone or companion treatment through a multicenter study on a large sample population. Methods: For women with VBD (n = 154), the treatment consisted of approximately two months (4 + 4 weeks) of applications according to the posology of UBIGEL. Evaluation of symptoms was performed on relevant clinical endpoints: dyspareunia and vulvovaginal pain/burning by a visual scale (VAS); vestibular trophism by a vestibular trophic health (VeTH) score; vulvoscopy through a cotton swab test; and the level of hypertonic pelvic floor by a physical graded assessment of levator ani hypertonus. Results: A total of 154 patients treated with UBIGEL donna™ showed significant improvements across all five evaluated parameters, including pain, dyspareunia, swab test results, muscle hypertonicity, and vestibular trophism. Pain and dyspareunia scores decreased by 46.5% and 33.5%, respectively, while significant improvements were also observed in the other parameters (p < 0.0001). These improvements were consistent across various stratifications, including age and disease duration. Conclusions: The findings of the present study suggest that UBIGEL donna™ is effective in alleviating pain and dyspareunia, as well as reducing vestibular hypersensitivity in women with VBD. Although UBIGEL donna™ alone cannot serve as a comprehensive substitute for all recommended therapies, we suggest that multimodal therapy strategies may be crucial for attaining substantial improvement in any aspect of the condition.

L-arginine metabolism through arginases and inducible nitric oxide synthase (NOS2) constitutes a fundamental axis for the resolution or progression of Chagas disease. Infection with Trypanosoma cruzi can cause a wide spectrum of disease, ranging from acute forms contained by the host immune response to chronic ones, such as the chronic chagasic cardiomyopathy. Here, we analyzed, in an in vitro model, the ability of two T. cruzi isolates, with different degrees of virulence, to regulate the metabolism of L-arginine through arginase 1 (Arg-1) and NOS2 in macrophages and through arginase 2 (Arg-2) and NOS2 in cardiomyocytes. Stimulation of bone marrow-derived macrophages (BMMΦ), obtained from CD1 mice, with TNF-α + IFN-γ induced their polarization into classically activated macrophages (CAMΦ), which expressed functional NOS2, while stimulation with IL-4 induced their polarization into alternatively activated macrophages (AAMΦ), which expressed functional Arg-1. Interestingly, stimulation of cardiomyocytes, obtained from hearts of CD1 neonatal mice, with TNF-α + IFN-γ or IL-4 also resulted in functional NOS2 and arginase expression, as observed in CAMΦ and AAMΦ, but Arg-2 was the arginase isoform expressed instead of Arg-1. We observed that infection of BMMΦ with the more virulent T. cruzi isolate (QRO) importantly diminished NOS2 expression and nitric oxide (NO) production in CAMΦ, allowing parasite survival, while infection with the less virulent isolate (CI2) did not diminish NOS2 activity and NO production in CAMΦ to a great extent, which resulted in parasite killing. Regarding Arg-1, infection of BMMΦ with the QRO isolate significantly induced Arg-1 expression and activity in AAMΦ, which resulted in a higher parasite load than the one in the unstimulated BMMΦ. Even though infection with CI2 isolate did not increase Arg-1 expression and activity in AAMΦ, the parasite load was higher than the one in the unstimulated BMMΦ but at a lesser magnitude than that observed during infection with the QRO isolate. On the other hand, infection of cardiomyocytes with either QRO or CI2 isolates and further stimulation with TNF-α + IFN-γ inhibited NOS2 expression and NO production, leading to amelioration of infection. Surprisingly, infection of cardiomyocytes with either QRO or CI2 isolates and further stimulation with IL-4 strongly inhibited Arg-2 expression and function, which resulted in parasite loads similar to those observed in unstimulated cardiomyocytes. Our results suggest that T. cruzi isolates that exhibit variable virulence or pathogenicity degrees differentially regulate L-arginine metabolism through Arg-1/2 and NOS2 in macrophages and cardiomyocytes.

We present a technique for the detection of vertebrate skeletons buried at shallow depths through the use of a ground-penetrating radar (GPR). The technique is based on the acquisition of high-resolution data by medium-to-high frequency GPR antennas and the analysis of the radar profiles by a new forward modelling method that is applied on a set of representative traces. This approach allows us to obtain synthetic traces that can be used to build detailed reflectivity diagrams that plot spikes with a distinct amplitude and polarity for each reflector in the ground. The method was tested in a controlled experiment performed at the top of Cerro Los Quesos, one of the most fossiliferous localities in the Ica Desert of Peru. We acquired GPR data at the location of a partially buried fossil skeleton of a large whale and analyzed the reflections associated with the bones using the new technique, determining the possible signature of vertebrae, ribs, the cranium (including the rostrum), and mandibles. Our results show that the technique is effective in the mapping of buried structures, particularly in the detection of tiny features, even below the classical (Ricker and Rayleigh) estimates of the vertical resolution of the antenna in civil engineering and forensic applications.

The common bean (Phaseolus vulgaris L.) is one of the oldest food crops in the world. In this study, the ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-MS/MS) technique was used to characterize the polar lipid composition and polyphenolic fraction of five bean varieties commonly consumed in Italy: Cannellino (PVCA), Controne (PVCO), Borlotti (PVBO), Stregoni (PVST), and Vellutina (PVVE). Lipid content represents a minor fraction of the whole metabolome in dry beans, and little is known about their polar lipids, which could be potentially bioactive components. Thirty-three compounds were detected through UHPLC-MS/MS, including oxylipins, phospholipids, N-acyl glycerolipids, and several fatty acids. The dichloromethane extracts were subjected to principal component analysis (PCA), with the results showing greater differentiation for the Borlotti variety. Moreover, 27 components belonging to different polyphenol classes, such as phenolic acids, flavonoids, catechins, anthocyanins and their glycosides, and some saponins, were identified in the hydroalcoholic seed extracts. In addition, the mineral content of the beans was determined. Considering the high number of compounds in the five apolar seed extracts, all samples were examined to determine their in vitro inhibitory activity against the enzyme cyclooxygenase-2 (COX-2), which is inducible in inflammatory cells and mediates inflammatory responses. Only PVCO showed the best inhibition of the COX-2 enzyme with an IC50 = 31.15 ± 2.16 µg/mL. In light of these results, the potential anti-inflammatory properties of PVCO were evaluated in the LPS-stimulated murine macrophage cell line J774A.1. Herein, we demonstrate, for the first time, that PVCO at 30 µg/mL can significantly reduce the release of TNF-α, with a less significant anti-inflammatory effect being observed in terms of IL-6 release.

Good scientific practice (GSP) refers to both explicit and implicit rules, recommendations, and guidelines that help scientists to produce work that is of the highest quality at any given time, and to efficiently share that work with the community for further scrutiny or utilization. For experimental research using magneto- and electroencephalography (MEEG), GSP includes specific standards and guidelines for technical competence, which are periodically updated and adapted to new findings. However, GSP also needs to be regularly revisited in a broader light. At the LiveMEEG 2020 conference, a reflection on GSP was fostered that included explicitly documented guidelines and technical advances, but also emphasized intangible GSP: a general awareness of personal, organizational, and societal realities and how they can influence MEEG research. This article provides an extensive report on most of the LiveMEEG contributions and new literature, with the additional aim to synthesize ongoing cultural changes in GSP. It first covers GSP with respect to cognitive biases and logical fallacies, pre-registration as a tool to avoid those and other early pitfalls, and a number of resources to enable collaborative and reproducible research as a general approach to minimize misconceptions. Second, it covers GSP with respect to data acquisition, analysis, reporting, and sharing, including new tools and frameworks to support collaborative work. Finally, GSP is considered in light of ethical implications of MEEG research and the resulting responsibility that scientists have to engage with societal challenges. Considering among other things the benefits of peer review and open access at all stages, the need to coordinate larger international projects, the complexity of MEEG subject matter, and today's prioritization of fairness, privacy, and the environment, we find that current GSP tends to favor collective and cooperative work, for both scientific and for societal reasons.

ABSTRACT The knowledge deficit of health professionals has been a barrier to expanding and implementing of pulmonary rehabilitation (PR) services, despite the reported benefits of PR for individuals with Chronic Respiratory Disease (CRD). This study aims to assess the preparedness of health care professionals from two Brazilian cities to perform PR in the public health system. This is survey is part of a larger project to implement PR in the Brazilian public health system. A self-administered questionnaire was used to assess the knowledge (19 questions), training (7 questions), confidence (10 questions), and clinical experience (8 questions) of physical therapists (PT) and the multiprofessional team (MT) before a PR workshop. In total, 44 PT and 231 MT answered the questionnaire. The mean total knowledge score was 10±3 for PT and 6±3 for MT. Few physical therapist reported having “a lot” of experience (25%) and confidence (22.7%) to perform PR, as well as sufficient training to conduct the six-minute walk test (27.3%).Even fewer MT reported having “a lot” of experience (10%) and sufficient training (4.8%) to perform PR, as well as to plan the educational program for patients (10%) and the confidence to refer patients to PR (6.5%). This is the first study to evaluate the preparedness of professionals from the Brazilian public health network to provide PR. Notably, both PT and MT have low preparation to perform PR in the studied cities, reinforcing the need for continuing education.

An ever-growing body of evidence suggests that sex and gender influence the pathophysiology, incidence, prevalence, clinical manifestations, course, and response to therapy of diabetes. Sex and gender differences are particularly evident in type 1 diabetes, especially in patients using advanced technologies (CGM and AHCL), as they are factors that interact with each other and have an impact on adherence to therapy, which affects not only metabolic compensation, but also, therefore, the prevention of complications and quality of life.

The COVID-19 pandemic has exposed individuals to various risks, including job loss, income reduction, deteriorating well-being, and severe health complications and death. In Brazil and the U.S., as well as in other countries, the initial response to the pandemic was marked by governmental underestimation, leading to inadequate public health measures to curb the spread of the virus. Although progressively mitigated, this approach played a crucial role in the impacts on local populations. Therefore, the principal aim of this paper is to evaluate the impact of COVID-19 and, indirectly, of the policies adopted by the U.S. and the Brazilian governments to prevent pandemic diffusion on income distribution. Utilizing available microdata and employing novel econometric methods (RIF-regression for inequality measures) this study shows that growth in COVID-19 prevalence significantly exacerbates economic disparities. Furthermore, the impact of COVID-19 on inequality has increased over time, suggesting that this negative impact has been intensifying. In the U.S., results indicate that working from home, the inability to work, and barriers to job-seeking significantly increase inequalities. Although further data are necessary to validate the hypothesis, this preliminary evidence suggests that the pandemic has significantly contributed to increased inequality in these two countries already characterized by increasing polarization and significant social disparities.

Ancient manuscripts are precious and fragile objects, preserved in libraries, museums, and archives. Some of them are masterpieces, made with several materials and insights, but generally they are not accessible to wide communities of users. The purpose of this study is to present the preliminary results of the Codex4D project: a holographic showcase, conceived for museums, presenting the first 4D model of an ancient manuscript to the public at the Science Festival in Genoa in 2022. The manuscript, preserved in the Angelica Library in Rome, has been represented in a multidimensional digital model, documenting both its visible and invisible aspects, on the surface and in the stratigraphic layers. We analysed the visitor experience: informal learning, the meaning-making process, interactions between visitors, and gesture-based interaction with the showcase. The methodology used for evaluation is based on four different qualitative methods (grounded theory, narrative inquiry, case study, and digital ethnography). We collected notes from observation, narratives from interviews, and answers from structured interviews. The main findings are patterns of the visitors’ experiences with a digital interactive 4D model of an ancient manuscript, supported by storytelling, and a list of design issues and possible improvements for the next version of the Codex4D holographic showcase.

Abstract The transfer of chalcophile metals across the continental lithosphere has been traditionally modeled based on their chemical equilibrium partitioning in sulfide liquids and silicate magmas. Here, we report a suite of Ni-Fe-Cu sulfide droplets across a trans-lithospheric magmatic network linking the subcontinental lithospheric mantle to the overlying continental crust. Petrographic characteristics and numerical calculations both support that the sulfide droplets were mechanically scavenged from the mantle source during partial melting and transported upwards by alkaline magmas rising through the continental lithosphere. Nanoscale investigation by high-resolution transmission electron microscopy (HR-TEM) documents the presence of galena (PbS) nanoinclusions within the sulfide droplets that are involved in the mantle-to-crust magma route. The galena nanoinclusions show a range of microstructural features that are inconsistent with a derivation of PbS by exsolution from the solid products of the Ni-Fe-Cu sulfide liquid. It is argued that galena nanoinclusions crystallized from a precursor Pb(-Cu)-rich nanomelt, which was originally immiscible within the sulfide liquid even at Pb concentrations largely below those required for attaining galena saturation. We suggest that evidence of immiscibility between metal-rich nanomelts and sulfide liquids during magma transport would disrupt the classical way by which metal flux and ore genesis are interpreted, hinting for mechanical transfer of nanophases as a key mechanism for sourcing the amounts of mantle-derived metals that can be concentrated in the crust.

Erdheim–Chester disease (ECD) is a disease of non-Langerhans cell histiocyte multisystemic proliferation. The pathogenesis is related to accumulation of histiocytes across the body, leading to multiple organ failure, and thus necessitating an early diagnosis. In all ECD cases, BRAF and RAS mutations are critical. Clinical manifestations affect individuals between the fourth and seventh decades of life. The most common symptoms reported are central nervous system involvement with functional disability, and bone pain with osteosclerosis of long bones. Other reported symptoms are skin involvement with xanthelasma, diabetes insipidus, cardiovascular involvement with pericardial effusion and tamponade, perivascular thickening, and right atrial and atrioventricular grove infiltration, leading to heart failure. Females may develop galactorrhoea due to deposition in the pituitary gland, with or without menstrual irregularities. Only few publications address the cardiac MRI findings of ECD. The authors present a case of cardiac involvement of ECD and associated cardiac MRI findings. The patient presented with multisystemic disease with bone pain, diplopia, cardiac arrythmia, and dyspnoea.

BackgroundFlexible work arrangements have become increasingly popular, driven by the widespread adoption of digital technologies in the workplace because of the pandemic. However, there is a scarcity of studies concerning remote work, especially related to technical-administrative staff (TAS) in academia. Therefore, the current study, adopting the Job Demands-Resources model, aimed to investigate the relationships between remote working self-efficacy, organizational support, techno-complexity, mental well-being, and job performance among TAS during remote working.MethodsA total of 373 individuals from TAS of a large Italian university participated in this study by completing a self-report questionnaire.ResultsThe findings showed positive and significant relationships between remote self-efficacy and job satisfaction as well as between such a perceived efficacy and mental well-being. Perceived support from supervisors acted as a protective factor against techno-complexity. In contrast, perceived support from colleagues emerged as able to promote well-being and job satisfaction. In addition, the latter was positively associated with well-being. Finally, individual job performance was positively affected by job satisfaction and negatively by techno-complexity.ConclusionThis study highlights the need for interventions to support TAS in remote working environments by leveraging employees’ self-efficacy as a key factor in reducing stress related to new technologies as well as enhancing well-being, job satisfaction, and, in turn, their performance.

Background: Anti-melanoma differentiation-associated gene 5-positive (anti-MDA5) dermatomyositis (DM) is a rare autoimmune disease associated with rapidly-progressive interstitial lung disease (RP-ILD.) The reported morbidity and 6-month mortality remains high from 33 to 66 % with RP-ILD most often developing within three months of diagnosis. Most cases require aggressive immunosuppression with combination therapy. Asymptomatic or slowly progressive cases of anti-MDA5 ILD are not well described in the literature. We report three cases of Latino patients with asymptomatic or slowly progressive anti-MDA5 ILD.Case descriptions: Case 1: A 54-year-old woman from Honduras with known diagnosis of anti-MDA5 dermatomyositis presented for ILD. She denied respiratory symptoms. Computed tomography (CT) chest showed multifocal patchy areas of scattered groundglass opacities throughout all lobes of the lungs, predominately in a subpleural distribution within the lower lobes. Pulmonary function testing (PFTs) showed mild-to-moderate restriction. She was treated with mycophenolate mofetil monotherapy for her skin manifestations. At 18 months follow-up, she denied respiratory symptoms, and PFTs were normal. Case 2: An 80-year-old man from Cuba was seen in pulmonary clinic to establish care. He was diagnosed with pulmonary fibrosis 11 years earlier with positive anti-MDA5. He denied respiratory symptoms. PFTs showed moderate obstruction and mild to moderate restriction. CT chest showed reduced lung volumes and findings compatible with usual interstitial pneumonia. He was started on nintedanib. Fifteen months following the initial visit, his PFTs remained stable. Follow-up CT chest showed stable pulmonary fibrosis. At all subsequent visits, he reported mild to moderate, slowly progressive dyspnea on exertion and was maintained on nintedanib. Thirteen years after his initial ILD diagnosis, he was diagnosed with pancreatic adenocarcinoma. Case 3: A 70-year-old woman from Peru presented to pulmonary clinic with cough for two months. She also reported pain in several metacarpophalangeal joints. She denied dyspnea. Rheumatologic serologies revealed positive anti-MDA5. PFTs were normal. Her cough was treated with cough suppressants and resolved. At a subsequent visit 8 months after presentation, she denied respiratory symptoms, and her joint pain remained mild. Given her lack of respiratory symptoms and normal PFTs, she was not initiated on ILD-specific treatment. Conclusions: While anti-MDA5 ILD is certainly associated with RP-ILD, clinicians should maintain awareness that there may be cases of asymptomatic or slowly progressive ILD as well.

Background: Ureaplasma parvum (UP) is a causative agent of non-gonococcal urethritis, involved in the pathogenesis of prostatitis and epididymitis, and it could impair human fertility. Although UP infection is a frequent cause of male infertility the study evidence assessing their prevalence and the association in patients with infertility is still scarce. The molecular processes leading to defects in spermatozoa quality are not completely investigated. MicroRNAs (miRNAs) have been extensively reported as gene regulatory molecules on post-transcriptional levels involved in various biological processes such as gametogenesis, embryogenesis, and the quality of sperm, oocyte, and embryos. Methods: Therefore, the study design was to demonstrate that miRNAs in body fluids like sperm could be utilized as non-invasive diagnostic biomarkers for pathological and physiological conditions such as infertility. A post-hoc bioinformatics analysis was carried out to predict the pathways modulated by the miRNAs dysregulated in the differently motile spermatozoa. Results: Here it is shown that normospermic patients infected by UP had spermatozoa with increased quantity of superoxide anions, reduced expression of miR-122-5p, miR-34c-5, and increased miR-141-3p compared with non-infected normospermic patients. This corresponded to a reduction of sperm motility in normospermic infected patients compared with normospermic non-infected ones. A target gene prediction presumed that an essential role of these miRNAs resided in the regulation of lipid kinase activity, accounting for the changes in the constitution of spermatozoa membrane lipids caused by UP. Conclusions: Altogether, the data underline the influence of UP on epigenetic mechanisms regulating spermatozoa motility.

Chia (Salvia hispanica L.) seed (CS) and Pumpkin (Cucurbita moschata) seed (PS) are used in ruminant diets as energy sources. The current experiment studied the impact of dietary inclusion of CS and PS on nutrient intake and digestibility, milk yield, and milk composition of dairy sheep. Twelve primiparous Texel × Suffolk ewes [70 ± 5 days in milk (DIM); 0.320 ± 0.029 kg milk yield] were distributed in a 4 × 3 Latin square design and fed either a butter-based control diet [CON; 13 g/kg dry matter] or two diets with 61 g/kg DM of either CS or PS. Dietary inclusion of CS and PS did not alter live weight (p >0.1) and DM intake (p >0.1). However, compared to the CON, dietary inclusion of both CS and PS increased the digestibility of neutral detergent fiber (p 0.05) and C18:3n3 (p > 0.05). Overall short-term feeding of CS and/or PS (up to 6.1% DM of diet) not only maintains the production performance and digestibility of nutrients but also positively modifies the milk FA composition.

Key Clinical Message We report five case series of obese patients with severe left ventricular ejection fraction impairment undergoing Serratus Anterior Plane Block during S‐ICD Implantation. This anesthesia approach has a reduced impact on the patient's hemodynamics and adequately manages postprocedural pain. Abstract Subcutaneous implantable cardioverter‐defibrillator (S‐ICD) procedures are frequently performed under analgosedation or general anesthesia, leading to prolonged postoperative hospital stays and increased costs. This anesthetic technique may also have a greater hemodynamic impact, particularly in obese and cardiac patients. However, an alternative anesthetic technique can be employed: ultrasound‐guided serratus anterior plane block (US‐SAPB). We analyzed the anesthetic clinical course in 5 patients, 3 males and 2 females, who were obese (BMI ≥ 30) and underwent S‐ICD implantation for primary prevention using a two‐incision intermuscular technique and ultrasound‐guided serratus anterior plane block. All patients had a left ventricular ejection fraction less than or equal to 35%. It significantly facilitated pain control during the procedure and, especially, in the postoperative phase. However, the data available in the literature are mostly derived from case reports and small comparative studies. Therefore, further studies with a larger sample size and direct comparison with general anesthesia or deep sedation are needed.

Abstract Background Validated prognostic biomarkers for anti-angiogenic therapy using the anti-VEGF antibody Bevacizumab in ovarian cancer (OC) patients are still an unmet clinical need. The EGFR can contribute to cancer-associated biological mechanisms in OC cells including angiogenesis, but its targeting gave disappointing results with less than 10% of OC patients treated with anti-EGFR compounds showing a positive response, likely due to a non adequate selection and stratification of EGFR-expressing OC patients. Methods EGFR membrane expression was evaluated by immunohistochemistry in a cohort of 310 OC patients from the MITO-16A/MANGO-OV2A trial, designed to identify prognostic biomarkers of survival in patients treated with first line standard chemotherapy plus bevacizumab. Statistical analyses assessed the association between EGFR and clinical prognostic factors and survival outcomes. A single sample Gene Set Enrichment-like and Ingenuity Pathway Analyses were applied to the gene expression profile of 195 OC samples from the same cohort. In an OC in vitro model, biological experiments were performed to assess specific EGFR activation. Results Based on EGFR-membrane expression, three OC subgroups of patients were identified being the subgroup with strong and homogeneous EGFR membrane localization, indicative of possible EGFR out/in signalling activation, an independent negative prognostic factor for overall survival of patients treated with an anti-angiogenic agent. This OC subgroup resulted statistically enriched of tumors of histotypes different than high grade serous lacking angiogenic molecular characteristics. At molecular level, among the EGFR-related molecular traits identified to be activated only in this patients’ subgroup the crosstalk between EGFR with other RTKs also emerged. In vitro, we also showed a functional cross-talk between EGFR and AXL RTK; upon AXL silencing, the cells resulted more sensitive to EGFR targeting with erlotinib. Conclusions Strong and homogeneous cell membrane localization of EGFR, associated with specific transcriptional traits, can be considered a prognostic biomarker in OC patients and could be useful for a better OC patients’ stratification and the identification of alternative therapeutic target/s in a personalized therapeutic approach.

Non-invasive concealed object detection, identification, and discrimination have been of interest to the research community for decades due to the needs to preserve infrastructures and artifacts, guarantee safe conditions for the detection and location of landmines, etc. A modern approach is based on the use of an unmanned aerial vehicle equipped with ground-penetrating radar, which has the advantage of not requiring direct contact with the ground. Moreover, high-resolution underground images are obtained by coherently combining measurements by using a synthetic aperture radar algorithm. Due to the complexity of the real scenario, numerical analyses have always been welcomed to provide almost real-time information to make the best use of the potential of such kinds of techniques. This paper proposes an analysis of the scattering from a zero-thickness perfectly electrically conducting disk buried in a lossy half-space surrounded by air and illuminated by a field generated by a Hertzian dipole located in the air. It is carried out by means of a generalized form of the analytically regularizing Helmholtz–Galerkin technique, introduced and successfully applied by the authors to analyze the plane-wave scattering from a disk and a holed plane in a homogeneous medium. As clearly shown in the numerical results, the proposed method is very effective and drastically outperforms the commercial software CST Microwave Studio 2023.

Abstract Purpose This study aimed to determine the impact of uttering the word “quiet” on clinical workload during the overnight otolaryngology call shift and understand the factors contributing to resident busyness. Materials and Methods A multicenter, single‐blind, randomized‐controlled trial was conducted. A total of 80 overnight call shifts covered by a pool of 10 residents were randomized to the quiet or to the control group. At the start of shift, residents were asked to state aloud, “Today will be a quiet night” (quiet group) or “Today will be a good night” (control group). Clinical workload, as measured by number of consults, was the primary outcome. Secondary measures included number of sign‐out tasks, unplanned inpatient and operating room visits, number of phone calls and hours of sleep, and self‐perceived busyness. Results There was no difference in the number of total (P = 0.23), nonurgent (P = 0.18), and urgent (P = 0.18) consults. Tasks at signout, total phone calls, unplanned inpatient visits, and unplanned operating room visits did not differ between the control and quiet groups. While there were more unplanned operating room visits in the quiet group (29, 80.6%) compared to the control group (34, 94.4%), this was not found to be significant (P = 0.07). The majority of residents reported feeling “not busy” during control nights (18, 50.0%) compared to feeling “somewhat busy” during quiet nights (17, 47.2%; P = 0.42). Conclusion Contrary to popular belief, there is no clear evidence that uttering the word “quiet” significantly increases clinical workload.