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Horses revolutionized human history with fast mobility1. However, the timeline between their domestication and their widespread integration as a means of transport remains contentious2-4. Here we assemble a collection of 475 ancient horse genomes to assess the period when these animals were first reshaped by human agency in Eurasia. We find that reproductive control of the modern domestic lineage emerged around 2200 BCE, through close-kin mating and shortened generation times. Reproductive control emerged following a severe domestication bottleneck starting no earlier than approximately 2700 BCE, and coincided with a sudden expansion across Eurasia that ultimately resulted in the replacement of nearly every local horse lineage. This expansion marked the rise of widespread horse-based mobility in human history, which refutes the commonly held narrative of large horse herds accompanying the massive migration of steppe peoples across Europe around 3000 BCE and earlier3,5. Finally, we detect significantly shortened generation times at Botai around 3500 BCE, a settlement from central Asia associated with corrals and a subsistence economy centred on horses6,7. This supports local horse husbandry before the rise of modern domestic bloodlines.

Abstract To detect cellular activities deep within the body using magnetic resonance platforms, magnetosomes are the ideal model of genetically-encoded nanoparticles. These membrane-bound iron biominerals produced by magnetotactic bacteria are highly regulated by approximately 30 genes; however, the number of magnetosome genes that are essential and/or constitute the root structure upon which biominerals form is largely undefined. To examine the possibility that key magnetosome genes may interact in a foreign environment, we expressed mamI and mamL as fluorescent fusion proteins in mammalian cells. Localization and potential protein-protein interaction(s) were investigated using confocal microscopy and fluorescence correlation spectroscopy (FCS). Enhanced green fluorescent protein (EGFP)-MamI and the red fluorescent Tomato-MamL displayed distinct intracellular localization, with net-like and punctate fluorescence, respectively. Remarkably, co-expression revealed co-localization of both fluorescent fusion proteins in the same punctate pattern. An interaction between MamI and MamL was confirmed by co-immunoprecipitation. In addition, changes in EGFP-MamI distribution were accompanied by acquisition of intracellular mobility which all Tomato-MamL structures displayed. Analysis of extracts from these cells by FCS was consistent with an interaction between fluorescent fusion proteins, including an increase in particle radius. Co-localization and interaction of MamI and MamL demonstrate that select magnetosome proteins may associate in mammalian cells.

Abstract Interface engineering is the core of device optimization, and this is particularly true for perovskite photovoltaics (PVs). The steady improvement in their performance has been largely driven by careful manipulation of interface chemistry to reduce unwanted recombination. Despite that, PVs devices still suffer from unavoidable open circuit voltage (VOC) losses. Here, we propose a different approach by creating a photo-ferroelectric perovskite interface. By engineering an ultrathin ferroelectric two-dimensional perovskite (2D) which sandwiches a perovskite bulk, we exploit the electric field generated by external polarization in the 2D layer to enhance charge separation and minimize interfacial recombination. As a result, we observe a net gain in the device VOC reaching 1.21 V, the highest value reported to date for highly efficient perovskite PVs, leading to a champion efficiency of 24%. Modeling depicts a coherent matching of the crystal and electronic structure at the interface, robust to defect states and molecular reorientation. The interface physics is finely tuned by the photoferroelectric field, representing a new tool for advanced perovskite device design.

Abstract Aims To estimate the incidence of major adverse cardiovascular events (MACE), expanded MACE, and MACE or Death across Fibrosis- 4 score (FIB-4) categories in people with type 2 diabetes and to determine whether efpeglenatide’s effect varies with increasing FIB-4 severity. Materials and methods AMPLITUDE-O trial data were used to estimate the relationship of FIB-4 score categories to the hazard of MACE, expanded MACE, and MACE or death. Interactions on these outcomes between baseline FIB-4 score, and between FIB-4 score and efpeglenatide were also assessed. Results Baseline FIB-4 score was available for 4059 participants (99.6%) allowing subdivision of the population in tertiles. During a median follow-up of 1.8 years, numerical increases in the incidence of all 3 outcomes did not change significantly across tertiles of FIB-4 score (P for trend ≥ 0.25) with negligible relationship of the score to incident outcomes (MACE HR, per 1 SD higher score, 95% CI: 1.00, 0.89–1.13). Efpeglenatide’s effect on all MACE outcomes did not vary across FIB-4 tertiles (all interaction p values ≥ 0.64). Conclusions In high-risk people with type 2 diabetes, the degree of liver fibrosis, as estimated by FIB-4 score, was not related to incident cardiovascular outcomes. The beneficial effect of efpeglenatide on these outcomes is independent of FIB-4 category.

Abstract Bacteria constitute a significant part of the biomass of the human microbiota, but their interactions are complex and difficult to replicate outside the host. Exploiting the superior resolution of magnetic resonance imaging (MRI) to examine signal parameters of selected human isolates may allow tracking of their dispersion throughout the body. Here we investigate longitudinal and transverse MRI relaxation rates and found significant differences between several bacterial strains. Common commensal strains of lactobacilli display notably high MRI relaxation rates, partially explained by elevated cellular manganese content, while other species contain more iron than manganese. Lactobacillus crispatus show particularly high values, 4-fold greater than any other species; up to 60-fold greater signal than relevant tissue background; and a linear relationship between relaxation rate and fraction of live cells. Different bacterial strains have detectable, repeatable MRI relaxation rates that in the future may enable monitoring of their persistence in the human body for enhanced molecular imaging.

Sabrina Bimonte,1,* Piergiacomo Di Gennaro,2,* Anna Crispo,2 Sergio Coluccia,2 Assunta Luongo,2 Alfonso Amore,3,4 Egidio Celentano,2 Francesco Del Prato,1 Daniela Schiavo,1 Davide Nocerino,1 Marco Cascella,5 Arturo Cuomo1 1Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy; 2Epidemiology and Biostatistics Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy; 3Melanoma and Sarcoma Surgery Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy; 4PhD School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, Rome, Italy; 5Department of Medicine, University of Salerno, Salerno, Italy*These authors contributed equally to this workCorrespondence: Anna Crispo, Epidemiology and Biostatistics Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Via Mariano Semmola 53, Naples, Italy, Tel +39 081 17770298, Email a.crispo@istitutotumori.na.itPurpose: Breakthrough cancer pain (BTcP) is a temporary exacerbation of pain that “breaks through” a phase of adequate pain control by an opioid-based therapy. The non-predictable BTcP (NP-BTcP) subtype occurs in the absence of any specific activity. Evidence showed that gender differences exist in pain response sensitivity and clinical pain risk. This analysis aimed to signify the gender differences for the NP-BTcP phenomenon.Patients and Methods: This is a secondary analysis of the Italian Oncologic Pain multiSetting-Multicentric Survey (IOPS-MS), the largest study on BTcP. The subset of NP-BTcP cases for non-gender-specific cancer was considered. Univariable and multivariate analyses were conducted to identify gender differences for the NP-BTcP profile about its intensity, number of episodes per day, and type. A metastatic status-stratified analysis was performed to compare gender with the main clinical variables among the population with NP-BTcP.Results: Males exhibited a higher occurrence of BTcP in the thorax region compared to females (15% vs 11%, respectively, p = 0.03). Males also had a higher onset of BTcP, a higher BTcP therapy dosage (33% vs 28%, p = 0.04, mean: 201 vs 186, p = 0.02) and a lower Karnofsky score (mean: 46.9 vs 49.2, p = 0.03) compared to females. Similar gender differences were found for metastatic patients in the BTcP site (14% vs 8.5%, respectively; p = 0.01), peak onset (33% vs 27%, p = 0.02), BTcP therapy dosage (199 vs 185, p=0.04), and Karnofsky score (mean 47.5 vs 50.4, p = 0.009). Phenotype 2 was more characterized by non-metastatic males (41% vs 23%, p = 0.020) while non-metastatic females presence was predominant among others.Conclusion: In this study, gender differences according to site, onset and dosage of BTcP were found. The phenotype characterization of BTcP needs to be further investigated for a possible useful function in the management of cancer-related pain in non-metastatic patients.Keywords: non-predictable breakthrough cancer pain, gender cancer pain, cluster analysis

Abstract Introduction Persons with diabetes are at risk for developing a cardiomyopathy through several pathophysiological mechanisms independent of traditional risk factors for heart failure. Among those with diabetic cardiomyopathy (DbCM), the relationship between natriuretic peptides, cardiac structural abnormalities and functional capacity is largely unknown. Methods In this prespecified subgroup analysis of the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) trial, 685 participants with asymptomatic DbCM underwent baseline echocardiography data, laboratory investigations, and functional assessments. Participants were stratified by N-terminal pro-B type natriuretic peptide (NT-proBNP) quartiles, and correlation with echocardiographic and functional parameters were assessed using Spearman correlation test. Results The median NT-proBNP was 71 (Q1, Q3: 33, 135) ng/L. No association was observed between NT-proBNP concentrations and echocardiographic parameters of either diastolic or systolic dysfunction including global longitudinal strain, left ventricular ejection fraction, left ventricular mass index, left atrial volume index, E/E’, or right ventricular systolic pressure. In contrast, NT-proBNP was significantly correlated with overall Kansas City Cardiomyopathy Questionnaire score (rho = − 0.10; p = 0.007), the Physical Activity Scale in the Elderly (rho = − 0.12; p = 0.004), duration of cardiopulmonary exercise testing (rho = − 0.28; p 95 for females or > 115 for males or E/e’ >13 or left atrial volume index > 34. †Normal ECHO is defined as the absence of these abnormalities. Low NT-proBNP is defined as

Abstract Achieving stable and reliable 2D-2D van der Waals heterostructures remains challenging. The broadest strategy for synthesizing these heterostructures is growth or manually stacking one material on top of the other, yet it is inefficient. Here, we present a strategy for synthesizing covalently bonded MoS2-graphene heterostructures using organic linkers with two anchor sites at a low cost. Our covalent heterostructures exhibit a more homogeneously alternating structure than the corresponding randomly alternating structure of vdW heterostructures, as confirmed by surface-enhanced Raman spectroscopy (SERS) measurements. Moreover, different linkers can be used to adjust the interlayer distance between graphene and MoS2, leading to significant impacts on their optical and electrochemical properties, including Photoluminescence (PL), cyclic voltammetry (CV), Ultraviolet-visible spectroscopy (UV-Vis), and SERS. Our strategy offers opportunities to advance fundamental research and enable the practical application of 2D/2D van der Waals heterostructures in various fields, including optoelectronics, energy storage, and catalysis.

Background: This study compares dexmedetomidine and buprenorphine as potential adjuvants for spinal anesthesia. Dexmedetomidine enhances sensory block and minimizes the need for pain medication, while buprenorphine, a long-acting opioid, exhibits a favorable safety profile compared to traditional opioids. Methods: PubMed, Cochrane and EMBASE were systematically searched in December 2023. Eligibility criteria: RCTs with patients scheduled for lower abdominal, pelvic, or lower limb surgeries; undergoing spinal anesthesia with a local anesthetic and buprenorphine or dexmedetomidine. Results: Eight RCTs involving 604 patients were included. Compared with dexmedetomidine, buprenorphine significantly reduced time for sensory regression to S1 (Risk Ratio [RR = -131.28]; 95% CI -187.47 to -75.08; I2 = 99%) and motor block duration (RR = -118.58; 95% CI -170.08 to -67.09; I2 = 99%). Moreover, buprenorphine increased the onset time of sensory block (RR = 0.42; 95% CI 0.03 to 0.81; I2 = 93%) and increased the incidence of postoperative nausea and vomiting (RR = 4.06; 95% CI 1.80 to 9.18; I² = 0%). No significant differences were observed in the duration of analgesia, onset time of motor block, time to achieve the highest sensory level, shivering, hypotension, or bradycardia. Conclusions: The intrathecal administration of buprenorphine, when compared to dexmedetomidine, is linked to reduction in the duration of both sensory and motor blocks following spinal anesthesia. Conversely, buprenorphine was associated with an increased risk of postoperative nausea and vomiting and a longer onset time of sensory block. Further high-quality RCTs are essential for a comprehensive understanding of buprenorphine's effects compared with dexmedetomidine in spinal anesthesia.

Rice husk ash is an important waste of agricultural industry that, within the framework of the circular economy, has been easily converted into a sustainable sorbent material. This was tested in this work for the pre-concentration of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), representative perfluoroalkyl substances as probe environmental pollutants of waters, with HPLC-MS/MS quantification. The preparation involves a rapid microwave-assisted oxidation followed by a hydrothermal treatment, which was studied using a 22 design of experiments. The final material was thoroughly characterized and tested for its affinity to the target analytes by solid-phase extraction in environmental waters and wastewaters. Recoveries in the range 67–113 % (RSD < 11 %, n = 3) were achieved at environmentally relevant concentrations (10, 50, and 100 ng L-1) and the sorbent was reusable for at least ten consecutive extractions. Good linearity (R2 = 0.9997) was observed, with a method quantification limit in the water sample of 10 ng L-1 that allows the analysis of PFOA and PFOS below the established limits. The method was evaluated for greenness using AGREEprep and SPMS metrics, and it was then applied to the analysis of actual water samples from Northern Italy.

The magnetosome, a membrane-bound iron biomineral formed within magnetotactic bacteria, is a unique model for a magnetic resonance imaging (MRI) reporter gene contrast agent. We are translating this technology to mammalian cells by expressing essential magnetosome genes mamI, mamL, mamB, and mamE into MDA-MB-435 human melanoma cells. Currently, these genes are individually expressed in the cell although the future goal is to express all four genes together. We examined the influence of these genes on cellular MRI relaxation rates by culturing cells in the presence and absence of iron-supplemented medium and scanning them at 3 Tesla using a gelatin phantom. Total cellular iron was measured by inductively-coupled plasma mass spectrometry and correlated with relaxation rates obtained from phantom experiments. Apart from mamE , magnetosome genes that are individually expressed in mammalian cells grown in iron supplement significantly affected cellular transverse relaxation rates compared to cells grown without iron supplement. Interestingly, mamI, mamL, mamB, and mamE (even though the latter had no effect on relaxation rate) significantly affected cellular iron content. This developing gene-based contrast agent will equip MRI with improvement to imaging sensitivity and the technology to track cellular activities long term.

Introdução: As síndromes mielodisplásicas (SMD) são um grupo heterogêneo de doenças mieloides caracterizadas por hematopoiese clonal e insuficiência medular que causam citopenias periféricas, anormalidades citogenéticas recorrentes e um risco variável de progressão para leucemia mieloide aguda (LMA). Dada a heterogeneidade da doença e o comportamento clínico variável em termos de evolução para leucemia, muitas análises citogenéticas e molecular têm surgido como ferramentas para identificar pacientes com características biológicas, clínicas e prognósticas semelhantes. Nesse contexto, a alteração citogenética de del20q isolada denota um bom prognóstico, de acordo com a estratificação de risco vigente (IPSS-R e IPSS-M). Objetivo: Relatar um caso de SMD com del 20q isolada, em seguimento clínico há sete anos, sem progressão de doença. Relato de caso: Paciente masculino, 85 anos, evoluiu com bicitopenia – anemia leve com Hb 11,0 e plaquetopenia grave – 20.000, desde 2017. Na ocasião do diagnóstico, realizou estudo medular que mostrou displasia moderada nas três séries, associada a 20% de sideroblastos em anel e cariótipo com del 20q11.2 em 14 das 20 metáfases analisadas. Na ocasião, estratificado como risco baixo (IPSS-R: 2), no entanto, devido à plaquetopenia importante, optado por tratamento com hipometilante. Recebeu 3 ciclos de Azacitidina, com suspensão por sangramento com hemorragia subaracnóidea e infecções bacterianas graves de repetição. Desde então, manteve apenas seguimento clínico, sempre com plaquetopenia entre 20-30mil. Em Abril/24, quando teve piora da anemia – Hb 7,0, porém mantendo hemograma sem neutropenia e sem piora da plaquetopenia de base, optado por repetir estudo medular. Novo mielograma hipercelular, com displasia das três séries e 1,6% de blastos. Coloração para ferro mostrando 8% de sideroblastos em anel. Citogenética mantendo del 20q11.2 isolada em 19 das 20 metáfases analisadas. Não foi realizado estudo molecular por indisponibilidade pela operadora. Novo IPSS-R: 3 – baixo risco. Optado por iniciar tratamento com Alfapoetina 30.000 unidades semanais. Conclusão: Estudo retrospectivos demonstram que a entidade acima descrita é mais comum em homens, idosos, apresentando plaquetopenia como citopenia mais exuberante no diagnóstico e durante o acompanhamento. O caso do paciente acima vai de acordo ao encontrado na literatura disponível, e o tempo de seguimento do paciente está acima da média para a estratificação inicial, sem indícios atuais de evolução para LMA. Apesar de não termos estudo molecular disponível, a evolução do doente fala contra presença de mutação clonal de risco adicional em associação ao achado citogenético da del20q.

Introdução: A leucemia mieloide aguda (LMA) é a leucemia aguda mais comum, acometendo predominantemente um grupo de pessoas idosas, com uma idade mediana de 67 anos ao diagnóstico, sendo que esses pacientes frequentemente têm reposta insatisfatória ao tratamento quimioterápico convencional. A combinação de agente hipometilante com venetoclax, mostrou-se eficaz e segura neste cenário, sendo atualmente a terapia de escolha em pacientes maiores 60 anos e/ou com comorbidades limitantes. Efeitos adversos dessa terapia ainda estão sendo descobertos. Objetivo: Relatar dois casos de LMA em tratamento com o protocolo VIALE-A que tiveram surgimento de sidero blastos em anel ao curso do tratamento com Viale A. Relato de caso: Caso 1: LAB, sexo masculino, 63 anos, diagnóstico de LMA com TP53mutado, apresentava ao diagnóstico 60% de blastos à avaliação medular, foi submetido a tratamento com o protocolo VIALE-A e, após o 8° ciclo, foi observado medula óssea (MO)hipercelular, com displasia multilinhagem e presença de sidero blastos em anel (73%). Caso 2: AC, sexo masculino, 79 anos, LMA de risco intermediário, com displasia nas três séries analisadas e 18% de blastos no mielograma ao diagnóstico, após o 9° ciclo do protocolo VIALE-A, apresentava uma MO hipocelular, com displasia e presença desideroblastos em anel (59%) ao mielograma. Conclusão: Os pacientes relatados acima, alcançaram remissão morfológica com o protocolo de tratamento utilizado, evoluindo, após vários ciclos de tratamento, com displasia e presença de sidero blastos em anel. O caso 1 foi submetido a transplante de medula óssea após melhora do perfomance status e o segundo caso segue em tratamento com o protocolo VIALE-A. Relatos sobre o surgimento de tal displasia após tratamento nesse perfil de pacientes são escassos em literatura. É incerto se isso pode conferir fator prognóstico ou influenciar na resposta alcançada.

Objetivo: Descrever o perfil epidemiológico das internações pela Doença Hemolítica do Feto e Recém-nascido (DHRN) no SUS nos últimos dez anos. Métodos: Trata-se de um estudo populacional, descritivo, retrospectivo, de caráter transversal com coleta de dados no Sistema de Morbidade Hospitalar no banco de dados do DATASUS. A população foi composta pelos pacientes internados no Brasil entre maio de 2014 e maio de 2024 em decorrência da DHRN. Os dados foram estratificados de acordo com o número total e por ano de internações, valor total gasto, valor médio por internação do paciente, sexo, raça, número de óbitos e taxa de mortalidade. Por ser uma fonte de dados de acesso público, a aprovação pelo comitê de ética em pesquisa e humanos foi desnecessária. Resultados: No período analisado, foram registradas 30.335 internações por DHRN, com uma média de 3033 casos/ano. O ano 2018 teve maior número de hospitalizações com 3.490 seguido por 2017, com 3.411 e 2020 com 3.255. Até maio de 2024, foram registrados 979 casos. Por região, houve maior domínio no Sudeste com 45,83% (n = 13.912),seguido por Nordeste 27,61% (n = 8.383), Centro-Oeste 15,45% (n = 4.690), Norte 5,96% (n =1.812) e Sul com 5,06% (n = 1.538). Houve um predomínio do sexo masculino 50,83% (n = 15.430) sobre o feminino 49,10% (n = 14.905). A raça parda registrou o maior número de pacientes com 43,17% (n = 13.096) seguida pela branca com 21,87% (n = 6.635) e sem informação 32,66% (n = 9.914). O tempo médio de hospitalização foi de 5,2 dias conferindo R$ 20.811.446,60 gastos e uma média de 686,05 reais por internação. De todas as internações, 109 foram a óbito, cuja região SE obteve maior número, 72, em seguida o Nordeste, 16, e Norte com 10, expondo uma taxa de mortalidade total de 0,36%. Discussão: As internações por DHRN oscilaram, com época de aumento anual no intervalo de 2014 a 2018, com 1.718 e 3.490 registros, respectivamente. Houve um período de tendência a declínio de 2020 a 2023, com registros de 3.255 e 2.637 casos. Ademais, observou-se um maior número de internações e óbitos no sexo masculino. A região Sudeste, que concentra cerca de 42% da população do país, segundo dados do IBGE de 2022, foi responsável por 47,7% das internações e 53,1% dos óbitos pela DHRN. Em seguida, as regiões Nordeste, Centro-Oeste, Norte e, por último, Sul. Além disso, nota-se a importância do custo para as internações com cerca de R$ 603,31 para cada. No quesito sexo, houve um breve domínio masculino. Ademais, observou-se prevalência da raça parda e da branca. A categoria ‘’sem informação’’para raça/cor foi a segunda maior em número de registros, o que dificulta melhor análise dos dados. Embora a taxa de internação seja significativa, a taxa de mortalidade desses pacientes é menor que 1%. Conclusão: A DHRN persiste como um problema importante de saúde pública no país, indicando falha nos protocolos anti-RhD no diagnóstico pré-natal. Ainda que nos últimos quatro anos tenha ocorrido uma tendência de diminuição do número de casos, os dados descritos revelam a importância de estratégias de prevenção, diagnóstico e tratamento considerando a região de distribuição, sexo e raça do paciente acometido pela doença. Destarte, este estudo indica a importância do pré-natal priorizando a profilaxia dadas as desigualdades regionais e socioeconômicas do país. Proporcionando, desse modo, a redução no números de internações pela doença, maior disponibilidade de leitos no SUS e redução de gastos ao sistema.

Se reporta el caso de un felino doméstico que llega a consulta a la Policlínica Veterinaria de la Universidad del Zulia, por presentar historial de urolitiasis con posible futura programación a cirugía (Cistotomía). El paciente no presentaba sintomatología clínica asociativa a presencia de ácaros. El médico tratante al realizar la exploración física del paciente observa puntos blancos sobre las áreas de pelaje de color negro del felino, llamando su atención, por lo que procedió a realizar exámenes complementarios para poder llegar a un diagnóstico. Por medio de un tricograma y una citología de piel, mediante cinta adhesiva se encontraron huevos y ácaros de la especie Lynxacarus radovskyi en gran cantidad. Este ácaro de la piel en felinos es observado en varios países; presentándose su primera descripción en 1974, por Tenório, en el Hawái, y hay informes en algunos países, como: Australia, Brasil, India y Ecuador. Actualmente no existe un reporte del mismo en la ciudad de Maracaibo, estado Zulia.

Abstract 2D transition metal dichalcogenide materials have attracted increasing attention as active surface‐enhanced Raman spectroscopy (SERS) platforms. In this study, the influence of n‐ and p‐type doping of exfoliated MoS2 (exMoS2) hybrids on the SERS performance is investigated, employing Rhodamine 6G (R6G) as a probe molecule. It is demonstrated that n‐doped exMoS2 hybrids (exMoS2 mixed with C60, graphene, and sodium dodecyl sulfate) exhibit enhanced SERS intensities, while p‐doping (exMoS2 mixed with TCNQ) resulted in inhibited SERS enhancement. A key discovery is the linear relationship between Raman enhancement of MoS2/dopant hybrids and the difference in their LUMO energy levels, which dictate the degree and direction of charge transfer. Interestingly, MC60‐4, a C60‐doped hybrid, deviates from the linear relationship, displaying remarkable SERS enhancement owing to its chemical interaction and unique Raman scattering activity. The findings provide critical insights into the SERS enhancement behavior of doped MoS2, facilitating precise tuning of SERS intensities by manipulating the MoS2 doping state.

Abstract Etruria contained one of the great early urban civilisations in the Italian peninsula during the first millennium BC, much studied from a cultural, humanities-based, perspective, but relatively little with scientific data, and rarely in combination. We have addressed the unusual location of twenty inhumations found in the sacred heart of the Etruscan city of Tarquinia, focusing on six of these as illustrative, contrasting with the typical contemporary cremations found in cemeteries on the edge of the city. The cultural evidence suggests that the six skeletons were also distinctive in their ritualization and memorialisation. Focusing on the six, as a representative sample, the scientific evidence of osteoarchaeology, isotopic compositions, and ancient DNA has established that these appear to show mobility, diversity and violence through an integrated bioarchaeological approach. The combination of multiple lines of evidence makes major strides towards a deeper understanding of the role of these extraordinary individuals in the life of the early city of Etruria.

Some serology assays demonstrated useful for post-treatment monitoring of Strongyloides stercoralis infection. Serology frequently has low specificity, which might be improved by the use of recombinant antigens. The Strongy Detect ELISA is based on 2 recombinant antigens (SsIR and NIE) and proved good accuracy. Aim of this study was to evaluate the performance of this test for the post-treatment monitoring of strongyloidiasis. We tested 38 paired sera, with matched fecal tests results, stored in our biobank and originating from a randomized controlled trial. At baseline, all patients tested positive for at least 1 fecal assay among PCR, direct stool microscopy and agar plate culture. Patients were re-tested with both serology and fecal assays 12 months after treatment. Primary outcome was the relative reduction in optical density (OD) between baseline and follow up. We observed that about 95% samples showed a reduction between pre and post-treatment OD, with a median relative reduction of 93.9% (IQR 77.3%–98.1%). In conclusion, the test proved reliable for post-treatment monitoring. However, some technical issues, including that the threshold for positivity has not be predefined, and that a substantial number of samples showed overflow signals, need to be fixed to permit use in routine practice.

BackgroundMacrocephaly is described in almost 15% of children with Autism Spectrum Disorder (ASD). Relationships between head growth trajectories and clinical findings in ASD children show a high degree of variability, highlighting the complex heterogeneity of the disorder.ObjectivesThe aim of this study was to measure differences of the early growth trajectory of head circumference (HC) in children with ASD and macrocephaly compared to ASD normocephalic children, examining clinical correlates in the two groups of patients.MethodsHC data were collected from birth to 5 years of age in a sample of children with a confirmed diagnosis of ASD. Participants were classified into two groups: ASD macrocephaly (ASD-M, Z-scores ≥1.88 in at least two consecutive HC measurements), and ASD non-macrocephaly (ASD-N). Based on the distribution of HC measurements (Z-scores), five age groups were identified for the longitudinal study. Developmental and behavioral characteristics of the ASD-M children compared to the ASD-N group were compared by using standardized scores.Results20,8% of the children sample met criteria for macrocephaly. HC values became indicative of macrocephaly in the ASD-M group at the age range from 1 to 6 months, and persisted thereafter throughout the first five years of age. ASD-M children showed significantly higher developmental quotients of Griffiths III B and D subscales compared to ASD-N group. No significant differences in the severity of ASD symptoms assessed by ADOS-2 were observed between ASD-M and ASD-N groups.ConclusionIn this study HC size from birth to 5 years links to accelerated HC growth rate as early as the first 6 months of age in children with ASD and macrocephaly, preceding the onset and diagnosis of ASD. We found that in early childhood, children with ASD-M may exhibit some advantages in language and social communication and emotional skills without differences in autism severity, when compared with age-matched normocephalic ASD children. Longitudinal analyses are required to catch-up prospectively possible relationships between head size as proxy measure of brain development and neuro-developmental and behavioral features in children with ASD.

Abstract Heavy‐metal‐free III–V colloidal quantum dots (QDs) exhibit promising attributes for application in optoelectronics. Among them, InAs QDs are demonstrating excellent optical performance with respect to absorption and emission in the near‐infrared spectral domain. Recently, InAs QDs attained a substantial improvement in photoluminescence quantum yield, achieving 70% at a wavelength of 900 nm through the strategic overgrowth of a thick ZnSe shell atop the InAs core. In the present study, light‐emitting diodes (LEDs) based on this type of InAs/ZnSe QDs are fabricated, reaching an external quantum efficiency (EQE) of 13.3%, a turn‐on voltage of 1.5V, and a maximum radiance of 12 Wsr−1m−2. Importantly, the LEDs exhibit an extensive emission dynamic range, characterized by a nearly linear correlation between emission intensity and current density, which can be attributed to the efficient passivation provided by the thick ZnSe shell. The obtained results are comparable to state‐of‐the‐art PbS QD LEDs. Furthermore, it should be stressed not only that the fabricated LEDs are fully RoHS‐compliant but also that the emitting InAs QDs are prepared via a synthetic route based on a non‐pyrophoric, cheap, and commercially available as precursor, namely tris(dimethylamino)‐arsine.

BackgroundSleep is disturbed in Rett syndrome (RTT), a rare and progressive neurodevelopmental disorder primarily affecting female patients (prevalence 7.1/100,000 female patients) linked to pathogenic variations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene. Autonomic nervous system dysfunction with a predominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PSNS) is reported in RTT, along with exercise fatigue and increased sudden death risk. The aim of the present study was to test the feasibility of a continuous 24 h non-invasive home monitoring of the biological vitals (biovitals) by an innovative wearable sensor device in pediatric and adolescent/adult RTT patients.MethodsA total of 10 female patients (mean age 18.3 ± 9.4 years, range 4.7–35.5 years) with typical RTT and MECP2 pathogenic variations were enrolled. Clinical severity was assessed by validated scales. Heart rate (HR), respiratory rate (RR), and skin temperature (SkT) were monitored by the YouCare Wearable Medical Device (Accyourate Group SpA, L’Aquila, Italy). The average percentage of maximum HR (HRmax%) was calculated. Heart rate variability (HRV) was expressed by consolidated time-domain and frequency-domain parameters. The HR/LF (low frequency) ratio, indicating SNS activation under dynamic exercise, was calculated. Simultaneous continuous measurement of indoor air quality variables was performed and the patients’ contributions to the surrounding water vapor partial pressure [PH2O (pt)] and carbon dioxide [PCO2 (pt)] were indirectly estimated.ResultsOf the 6,559.79 h of biovital recordings, 5051.03 h (77%) were valid for data interpretation. Sleep and wake hours were 9.0 ± 1.1 h and 14.9 ± 1.1 h, respectively. HRmax % [median: 71.86% (interquartile range 61.03–82%)] and HR/LF [median: 3.75 (interquartile range 3.19–5.05)] were elevated, independent from the wake–sleep cycle. The majority of HRV time- and frequency-domain parameters were significantly higher in the pediatric patients (p ≤ 0.031). The HRV HR/LF ratio was associated with phenotype severity, disease progression, clinical sleep disorder, subclinical hypoxia, and electroencephalographic observations of multifocal epileptic activity and general background slowing.ConclusionOur findings indicate the feasibility of a continuous 24-h non-invasive home monitoring of biovital parameters in RTT. Moreover, for the first time, HRmax% and the HR/LF ratio were identified as potential objective markers of fatigue, illness severity, and disease progression.

Corporate social responsibility (CSR) has been seen as an opportunity to increase reputation, cost savings, business and financial opportunities, and create economic and sustainable value. The purpose of this review is twofold: first to draw attention to the complex relationship between common CSR practices used to deal with critical issues for our society and the impact they have on the trust and loyalty of stakeholders. Second, based on a study of 91 documents, to identify the advantages/weaknesses of implementing recognized standards (ISO 14001, ISO 26000, GRI, SA8000, AA1000) in different sectors of the economy. The standards provide a guideline for the elaboration, disclosure, and evaluation of the transparency reports of CSR. Some indicators used to measure CSR are more focused on environmental topics but recognizing social justice as a priority is critical to promoting the well-being of internal and external stakeholders. Furthermore, CSR standards play a crucial role in our world because they encourage ethical behaviors that reinforce the values and integrity of our society. The future research agenda should be oriented to monitor the impact of CSR initiatives in complex scenarios, consider the voices of non-specialized stakeholders, and integrate approaches that make visible the consequences of these practices.

Abstract Background Diabetic cardiomyopathy (DbCM) is a form of Stage B heart failure (HF) at high risk for progression to overt disease. Using baseline characteristics of study participants from the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) Trial we sought to characterize clinical characteristics of individuals with findings consistent with DbCM. Methods Among study participants meeting inclusion criteria, clinical characteristics, laboratory testing, imaging, Kansas City Cardiomyopathy Questionnaire (KCCQ), Physical Activity Scale of the Elderly (PASE) and cardiopulmonary exercise testing (CPET) results were tabulated. Cluster phenogroups were identified. Results Among 691 study participants (mean age 67.4 years; 50% were female), mean duration of type 2 diabetes mellitus (T2DM) was 14.5 years. The median (Q1, Q3) N-terminal pro-B type natriuretic peptide and high sensitivity cardiac troponin T were 71 (35, 135) ng/L and 9 [6, 12] ng/L. The most common echocardiographic abnormalities were reduced global longitudinal strain in 25.3% and impaired diastolic relaxation in 17.7%. Despite rather well-preserved KCCQ scores the average PASE score was markedly impaired at 155 accompanied by an average maximal oxygen consumption of 15.7 mL/Kg/minute on CPET. In K-means clustering, 4 phenogroups were identified including a higher-risk group with more advanced age, greater elevation of cardiac biomarkers, and more prevalent evidence for diastolic dysfunction and left ventricular hypertrophy. Conclusions Baseline data from the ARISE-HF Trial provide clinical characterization of individuals with T2DM and features of stage B HF, and may help clarify the diagnosis of DbCM. Trial Registration ARISE-HF, NCT04083339.

Abstract Background Non-alcoholic fatty liver disease (NAFLD), identified by the Fatty Liver Index (FLI), is associated with increased mortality and cardiovascular (CV) outcomes. Whether this also applies to type 1 diabetes (T1D) has not been yet reported. Methods We prospectively observed 774 subjects with type 1 diabetes (males 52%, 30.3 ± 11.1 years old, diabetes duration (DD) 18.5 ± 11.6 years, HbA1c 7.8 ± 1.2%) to assess the associations between FLI (based on BMI, waist circumference, gamma-glutamyl transferase and triglycerides) and all-cause death and first CV events. Results Over a median 11-year follow-up, 57 subjects died (7.4%) and 49 CV events (6.7%) occurred among 736 individuals with retrievable incidence data. At baseline, FLI was

Abstract This article addresses some critical aspects of the relationship between aesthetic medicine (AM) and ethics and proposes a possible deontological ethical line to pursue based on current practices. The role of AM has always been controversial and suffers from unclear practical and moral boundaries, even within academic settings, since it aims to improve the appearance of individuals, not to cure a disease. Today, it is essential and pertinent to discuss these issues, as AM specialists are dealing with a growing and increasingly demanding patient population that has undergone profound evolution in recent years. Current challenges within the field of AM include a lack of global uniformity concerning the education of AM specialists, an increasing number of physicians practicing AM with diverse training backgrounds, the spread of AM being practiced outside of medical practice or hospital settings, and the influence of social media where the success is modelled and dictated by the identification of a youthful appearance). By the field of action enriched by technologies that aim not only at enhancement per se but also at the preservation and regeneration of tissues, it is necessary to establish an active multidisciplinary discussion on the definition of shared ethical limits. This discussion would allow AM to fully reclaim its identity as a specialty that aims to improve patient well-being whilst maintaining respect for patient aesthetic harmony, the expertise of specialists who practice AM, the essential role of safety, and awareness of the importance of a confidential doctor−patient relationship.

Abstract Aim The aim of this qualitative study was to explore the barriers and facilitators to accessing and receiving mental health care for paid and unpaid carers of older adults. Methods Unpaid and paid carers for older adults in England were interviewed remotely between May and December 2022. Participants were asked about their experiences of mental health needs and support. Reflexive thematic analysis was used to analyse the data. Results Thirty‐seven carers participated (npaid = 9; nunpaid = 28), with the majority caring for a parent with dementia. Thematic analysis generated four themes: lack of healthcare support, social care system failing to enable time off, personal barriers and unsupportive work culture. Healthcare professionals failed to provide any link to mental health services, including when a dementia diagnosis was received. Structural and organisational barriers were evidenced by carers being unable to take time off from their unpaid caring duties or paid caring role, due to an absence of social care support for their relative. Conclusions This is the first study to have explored the barriers to mental health care and support for paid and unpaid carers for older adults and suggests that structural, organisational and personal barriers cause severe difficulties in accessing required support to care for older relatives, services users and residents. Public Involvement Two unpaid carers aided with the development of topic guides, data analysis, interpretation and dissemination. Both were supported and trained to code anonymised transcripts.

BackgroundTourette syndrome (TS) and autism spectrum disorder (ASD) are two neurodevelopmental disorders with an onset before the age of 18 years. TS patients frequently reported atypical sensory phenomena (SP). Sensory processing abnormalities are also particularly frequent in ASD individuals.ObjectivesConsidering the higher rate of atypical sensory behaviours in both neurodevelopmental disorders, in the present study we analysed sensory experiences in patients with ASD and in patients with TS.MethodsWe enrolled patients with a primary diagnosis of TS or ASD. All participants were assessed for primary diagnosis and associated comorbidities. The presence of sensory behaviours was investigated using the University of Sao Paulo’s Sensory Phenomena Scale (USP-SPS).ResultsSP were significantly more represented in the ASD-group versus TS-group, except for sound just-right perceptions and energy to released. ASD participants presented higher mean scores in all fields of USP-SPS severity scale respect on TS patients and healthy controls. The USP-SPS total score had significant positive correlations with the CYBOCS and MASC total scores in the TS cohort. In the ASD group, the USP-SPS total score was significantly negative correlated with the total IQ and marginally positive correlated with ADOS total score.ConclusionSP are a frequently reported characteristic both of ASD and TS. Future studies are needed to better evaluate the differences on their phenomenology in patients with TS and ASD.

Background The paper describes lead ion adsorption on variable charge oxidic calcined substrates with chemically modified surfaces. Amphoteric oxides of iron, aluminum, titanium, and manganese, change their surface electric charge after acid or alkaline treatment, letting cationic or anionic adsorption reactions from aqueous solutions. This property allows using them as adsorbing substrate for heavy metals retention in water treatment systems. Methods Substrate was prepared by extruding cylindrical strips from a saturate paste of the oxidic lithological material-OLM; dries it up and thermally treated by calcination. The study was performed by triplicated trial, on batch mode, using 2 grams samples of treated with NaOH 0.1N and non-treated substrate. Lead analysis was performed by AAS-GF. Freundlich and Langmuir models were used to fit results. Comparing differential behavior between treated and non-treated substrates showed the variable charge nature of the OLM. Results Results show L-type isotherms for the adsorption of Pb(II) ions on the activated substrate, suggesting good affinity between Pb(II) ions and OLM’s surface. Average value of adsorption capacity (K) for activated substrate (1791.73±13.06), is around four times greater than the non-activated substrate (491.54±31.97), during the adsorption reaction, 0.35 and 0.26 mmolH+ of proton are produced on the activated and non-activated substrate respectively using a 1 mM Pb(II) solution and 72.2 and 15.6 mmolH+ using a 10 mM Pb(II) solution. This acidification agrees with the theoretic model of transitional metals chemisorption on amphoteric oxides, present in lithological material used for the preparation of adsorbent substrates, confirming the information given by the L-type isotherms. Conclusions Results suggest that these variable charge oxidic adsorbent substrate show great potential as an alternative technique for water treatment at small and medium scale using granular filtration system. The easiness and low price make them suitable to apply in rural media where no treating water systems is available.

Background: Raw vegetables have been considered vehicles of enteroparasites. South American countries are among the most important exporters of fresh vegetables, including Ecuador, which has a tropical climate and soils rich in organic matter that allow it to harvest throughout the year for sale to different countries. The aim of the study was to assess the occurrence of the parasitic contamination of fruits, vegetables and leafy greens grown in an agricultural area of the Ecuadorian Andes. Methods: A cross-sectional field study was conducted with snowball sampling on 1,416 samples (516 fruits, 488 vegetables, and 412 leafy greens). Each sample were washed with water, and the resulting solution after removing the vegetables, was subjected to 24-hour sedimentation. The concentrated sediment underwent microscopic analysis. Results: The overall positivity for parasitic contamination was 63.4%, with leafy greens having the highest contamination rate (76.9%) (P

Non-alcoholic fatty liver disease (NAFLD), or hepatic steatosis, has become one of the most common pathologies among liver-related disorders. The rapid accumulation of fat in this organ, and the consequent increment in oxidative stress levels, have been recognized as one of the main factors involved in the pathological mechanism underlying hepatic steatosis, and progressive non-alcoholic steatohepatitis. Experimental and epidemiological data have shown how antioxidant compounds rich in phenolic groups, such as resveratrol and quercetin, are particular efficient in contrasting the onset of this pathology. In this work, an in vitro model of NAFLD was established based on oleic acid-treated HepG2 cells. Steatotic cells were treated with polydopamine nanoparticles (PDNPs), biocompatible polymeric nanostructures rich in phenolic groups with high antioxidant power. PDNP treatment has shown to be effective in counteracting the hallmarks characterizing hepatic steatosis, and a reduction in the accumulation of lipids has been observed. Further analyses showed a significant reduction in triglyceride and cholesterol levels, jointly to reduced levels of oxidative stress. All these data, corroborated by proteomics and gene ontology analysis, suggest PDNPs to be a promising pharmaceutical candidate for the prevention and treatment of hepatic steatosis.

Summary: Background: Despite the overall improvement in care, people with type 2 diabetes (T2D) experience an excess risk of end-stage kidney disease. We evaluated the long-term effectiveness of dapagliflozin on kidney function and albuminuria in patients with T2D. Methods: We included patients with T2D who initiated dapagliflozin or comparators from 2015 to 2020. Propensity score matching (PSM) was performed to balance the two groups. The primary endpoint was the change in estimated glomerular filtration rate (eGFR) from baseline to the end of observation. Secondary endpoints included changes in albuminuria and loss of kidney function. Findings: We analysed two matched groups of 6197 patients each. The comparator group included DPP-4 inhibitors (40%), GLP-1RA (22.3%), sulphonylureas (16.1%), pioglitazone (8%), metformin (5.8%), or acarbose (4%). Only 6.4% had baseline eGFR 30 mg/g. During a mean follow-up of 2.5 year, eGFR declined significantly less in the dapagliflozin vs comparator group by 1.81 ml/min/1.73 m2 (95% C.I. from 1.13 to 2.48; p