Search

Objetivo: As infecções relacionadas aos implantes ortopédicos (IRI), que abrange às infecções relacionadas às fraturas (IRF) e às infecções de próteses ortopédicas (IPO), persiste como uma complicação comum após procedimentos cirúrgicos ortopédicos para estabilização de fraturas. Mesmo durante a COVID-19, com a redução dos casos de traumatismo, as taxas de IRI permaneceram elevadas em nossa instituição. O presente estudo teve como objetivo investigar as características epidemiológicas e microbiológicas das IRI em um centro ortopédico terciário brasileiro entre 2020 e 2022. Método: Estudo de coorte retrospectivo em um único centro, envolvendo todos os pacientes submetidos a cirurgia ortopédica para estabilização de fraturas. O diagnóstico de IRF e IPO foi realizado de acordo com os critérios da EBJIS. Foram analisados 402 pacientes que passaram por algum tipo de correção cirúrgica de fratura, sendo incluídos na análise aqueles que desenvolveram IRF e IPO. Os patógenos foram isolados a partir de culturas de tecido peri-implante e fluido de sonicação, e identificados por meio de MALDI-TOF. Resultados: Um total de 65 pacientes com IRI foram incluídos, resultando em uma incidência de infecção de 16,1% (65/402). Os pacientes masculinos representaram 73,8% da amostra, com média de idade de 48,5 ± 18,6 anos. As fraturas fechadas corresponderam a 60% dos casos. Em relação ao mecanismo de trauma, quedas foram responsáveis por 43,1% dos casos, seguidas por acidentes automobilísticos (26,6%). Os sítios de infecção mais frequentemente afetados foram tíbia (26,2%) e quadril (12,3%). Observou-se que 86,2% dos casos correspondiam a IRF e 12,3% a IPO, enquanto infecções após instrumentação da coluna vertebral foram diagnosticadas em 1,5% dos casos. Entre os pacientes com culturas bacterianas positivas, 68,9% apresentaram bactérias gram-positivas e 31% bactérias gram-negativas, sendo o Staphylococcus aureus o patógeno mais prevalente em todos os sítios de infecção. Infecções polimicrobianas (24,1%), principalmente envolvendo bacilos gram-negativos, foram menos comuns do que infecções monomicrobianas (75,8%). Conclusão: Este estudo evidenciou que a incidência de IRI permaneceu alta durante a COVID-19, sendo as infecções monomicrobianas, incluindo espécies de Staphylococcus, as predominantes. A identificação da epidemiologia das vítimas de traumatismo ortopédico e da prevalência microbiológica constitui o primeiro passo em direção ao planejamento terapêutico bem-sucedido.

Introdução: A incidência da infecção relacionada à fratura (IRF) pode variar de 0,4 a 32%, sendo ainda maior em fraturas expostas. Os principais patógenos descritos são os cocos Gram-positivo (CGP), em especial o S. aureus. Entretanto, estudos que avaliam informações epidemiológicas e microbiológicas nas IRF são escassos no Brasil. Este estudo descreve a incidência de IRF e os patógenos associado em um hospital público terciário universitário brasileiro ao longo de 3 anos de coleta de dados. Métodos: Estudo transversal, unicêntrico, com dados coletados entre março de 2020 e março de 2023 de pacientes maiores de 18 anos com fraturas ósseas fechadas e expostas submetidas à fixação ortopédica, exceto próteses articulares. Para o diagnóstico de IRF foi utilizada a definição proposta por METSEMAKERS et al (2017). Resultados: Do total de 462 pacientes incluídos, 71,6% foram do sexo masculino com média de idade de 47,6 anos (DP±20,8). As principais comorbidades foram Hipertensão Arterial Sistêmica (19,3%), tabagismo (19,3%) e etilismo (17,3%). As fraturas expostas foram 25,1% dos casos, sendo a classificação de Gustilo-Anderson do tipo 3-A a mais frequente (69,8%). A incidência global de IRF, em fraturas fechadas, e em fraturas expostas foi de 19,7%, 16,5%, e 29,3% respectivamente. A principal profilaxia cirúrgica foi uma cefalosporina de 1a ou 2a geração (84,6%) associada a um aminoglicosídeo (44,6%) ou isolada (43,1%). Os principais patógenos identificados foram S. aureus (22,1%), K. pneumoniae (11,6%), S. epidermidis (10,5%), demais Staphylococcus coagulase-negativo (10,5%), E. coli (6,3%), P. aeruginosa (5,3%), Streptococcus spp beta-hemolítico (4,2%), outros CGP (9,5%) e outros bacilos Gram-negativo (BGN) (20,0%). A resistência à meticilina foi identificada em 60% das cepas do gênero Staphylococcus e a multidroga resistência (MDR) foi identificada em 53,7% dos BGN. Conclusão: A incidência de IRF global e em fraturas expostas foi elevada, assim como em fraturas fechadas nas quais menores valores são previstos devido à adoção sistemática da profilaxia antimicrobiana cirúrgica. A elevada frequência de BGN (43,2%) demonstrando perfil de MDR (53,7%) associada a uma alta resistência à meticilina do gênero Staphylococcus (60%) apontam para uma mudança no perfil epidemiológico de IRF e sugerem a revisão da profilaxia antimicrobiana em cirurgias ortopédicas com implantes no Brasil.

Introdução: O tratamento ideal da osteomielite ainda é um motivo importante de debate na literatura. Devido à dificuldade de erradicar o biofilme, um dos tratamentos preconizados envolve desbridamento e terapia local com a colocação de espaçadores de polimetilmetacrilato carregado de antibiótico (PMMA+ATB). Há ainda dúvidas se a permanência in situ prolongada do PMMA+ATB no paciente causaria eventos adversos. O objetivo deste estudo foi investigar se a permanência de culturas positivas de fluido de sonicação de PMMA+ATB in situ alteram o desfecho clínico de pacientes com osteomielite crônica. Metodologia: Realizamos estudo preliminar em uma série de casos de 13 pacientes que possuíam diagnóstico de osteomielite em um hospital universitário de São Paulo no período entre 2021 e 2022. Todos receberam tratamento antimicrobiano sistêmico e local com PMMA eluído de Vancomicina e/ou Gentamicina. As culturas de tecido infectado do paciente; o tempo de retenção do PMMA+ATB maior que 4 semanas; e as culturas do fluido de sonicação do PMMA+ATB foram comparados ao sucesso terapêutico destes pacientes avaliados após 6 meses e um ano do tratamento local. O desfecho clínico “sucesso terapêutico” foi definido como ausência de: necessidade de novas terapias antimicrobianas sistêmicas; necessidade de reabordagem cirúrgica; sinais clínicos de osteomielite ativa; e morte relacionada ao procedimento ortopédico. Resultados: As culturas do fluido de sonicação de PMMA+ATB foram positivas em 54% (7/13) dos pacientes. Destes, 100% tiveram sucesso terapêutico após 6 meses. Após um ano, foi possível avaliar o desfecho de 9 pacientes, e 44% (4/9) possuíam cultura de fluido de sonicação de PMMA+ATB positiva. Entretanto, o sucesso terapêutico foi atingido em 78% destes. O tempo de permanência in situ do PMMA+ATB variou de 1,5 a 37 semanas (média= 9 semanas; mediana= 5 semanas). Após 6 meses de seguimento, não houve diferença nas taxas de sucesso de tratamento nos pacientes que mantiveram PMMA+ATB in situ por mais (78%) ou menos (75%) de 4 semanas. Conclusão: A terapia com PMMA+ATB parece ser uma forma efetiva de tratamento de osteomielite crônica. A positividade das culturas em fluido de sonicação de PMMA+ATB após a retirada cirúrgica não parecem estar correlacionadas ao desfecho clínico de sucesso terapêutico após 6 meses e um ano.

Introdução: A infecção relacionada à fratura (IRF) pode ocorrer em taxas elevadas e a maioria causada por Staphylococcus aureus. Contudo, agentes etiológicos podem variar com a localização anatômica e geográfica, mecanismo de trauma e fatores do hospedeiro, sendo importante determinar os patógenos dominantes locais e suas implicações no desfecho do tratamento clínico e cirúrgico. O objetivo deste estudo foi caracterizar o perfil microbiológico nas IRF e associar a falha do tratamento aos patógenos encontrados. Métodos: Estudo observacional, do tipo coorte prospectiva, em pacientes maiores de 18 anos com IRF, conforme critérios de Metsemakers et al (2017), internados entre 2020 e 2023 em hospital terciário de São Paulo. Falha do tratamento de IRF foi definido como necessidade de reoperação ou reinício da terapia antibiótica para o mesmo patógeno, amputação ou óbito. Proporções das variáveis categóricas foram associadas utilizando o teste qui-quadrado ou exato de Fisher. Resultados: Foram avaliados 65 casos de IRF com diagnóstico microbiológico. A média de idade na população foi 44,41 (± 16,7) anos e 46 pacientes eram do sexo masculino (70,8%). Falha de tratamento ocorreu em 27 (41,5%) casos e 6 (9,2%) perderam seguimento após 6 meses de acompanhamento médio. O microrganismo mais frequente nos casos de falha foi o S. aureus (n = 9; 33,3%), K. pneumoniae (n = 6; 22,2%), S. epidermidis (n = 4; 14,8%), E. coli (n = 4; 14,8%) e P. aeruginosa (n = 4; 14,8%). Na análise por grupos houve risco maior de falha nas IRF por bacilos gram-negativo (BGN) não fermentadores [Incidência: 52,9% vs. 42,9%; RR: 1,24 (intervalo de confiança (IC)95% = 0,70-2,18)], S. aureus [Incidência: 50,0% vs. 43,9%; RR:1,14 (IC95% = 0,64-2,03)] e BGN fermentadores [Incidência: 50,0% vs. 45,5%; RR: 1,10 (IC95% = 0,40-3,06)]. Houve menor risco de falha no grupo de Staphylococcus coagulase-negativos [Incidência: 41,2% vs. 47,6%; RR: 0,86 (IC95% = 0,45-1,66)]. Em relação à resistência antimicrobiana, 60% dos Staphylococcus foram resistentes à meticilina (MRSA) e 53,7% dos BGN foram multidrogas resistentes (MDR). Conclusões: Este estudo evidencia altas taxas de falha de tratamento nas IRF, provavelmente associados a bactérias multirresistentes, incluindo o MRSA e BGN-MDR. S. aureus foi a etiologia mais prevalente, contudo, BGNs não fermentadores cursaram com maior risco de falha terapêutica, o que está de acordo a incidência crescente desses patógenos em infecções associadas à assistência à saúde no Brasil.

Introdução: O tratamento antimicrobiano sistêmico empírico ou dirigido por cultura para as infecções ósseas tem classicamente demonstrado altas taxas de falha. Por outro lado, a terapia antibiótica local associada a um biomaterial com o cimento ortopédico ou polimetilmetacrilato (PMMA), tem progressivamente mostrado altas taxas de resolutividade e poucos eventos adversos locais e sistêmicos. Este estudo avalia o desfecho de sobrevida livre de infecção após a terapia antibiótica local no tratamento das osteomielites crônicas e infecções associadas à fratura (IAF). Método: Estudo de série de casos com seguimento ambispectivo para avaliar a taxa de controle de infecção óssea em pacientes com osteomielite crônica cavitaria e IAF que foram tratados com terapia antibiótica local associado à PMMA, e acompanhados no Grupo de Infecções Musculoesqueléticas de um Hospital Universitário Terciário, de abril de 2020 a maio de 2023. Foram excluídos os pacientes com artroplastias infectadas. Resultados: No total, oito pacientes com osteomielite e 13 com IAF foram avaliados, sendo 15 (71%) homens, com média de idade de 42 anos (DP+- 18-72). A comorbidade mais comum foi o tabagismo (23%). Infecção em tíbia e fêmur foram predominantes (90%), seguido de coluna e úmero. Em 20 pacientes (95%) foi usado o PMMA como veículo para o antibiótico e em 1 (5%), biocerâmica. O cimento foi diluído apenas com vancomicina em 15 casos (71%) e em associação com gentamicina em 6 (28%). Dezesseis pacientes (76%) receberam tratamento sistêmico, enquanto 6 (28%) receberam apenas tratamento local. Foram identificados microrganismos em 95% dos casos, sendo metade infecção polimicrobiana. Trinta e sete patógenos foram isolados em culturas ósseas e de fluido de sonicação, 15 (41%) eram Staphylococcus coagulase negativos, 13 Staphylococcus aureus, 4 Bacilos Gram-negativos, 3 Streptococcus spp. e 2 Enterococcus faecalis. O tempo médio de seguimento foi de 9 meses (2 – 19 meses). Três pacientes (15%) tiveram recorrência de sintomas, enquanto 18 (85%) permanecem assintomáticos. Todos os 3 receberam também terapia antimicrobiana sistêmica. Conclusão: O tratamento para osteomielite com terapia antibiótica associado ao PMMA e outros biomateriais se mostrou eficiente como terapia adjuvante. Mais estudos são necessários para padronização de materiais e doses.

Merkel cell carcinoma is a rare and aggressive cutaneous neuroendocrine cancer that occurs in the photodamaged skin of white and elderly patients, usually presenting as a solitary plaque or nodule in the head and neck region. When located in the lower palpebral area, reconstructing the defect resulting from its excision can become challenging for the dermatological surgeon due to the local cosmetic and functional peculiarity. We report the use of a bilobed flap for lower eyelid reconstruction with a satisfactory result, both in terms of aesthetics and the resulting functionality.

AimThis prospective pilot study evaluated inflammatory and intestinal barrier biomarkers and the effects of a synbiotic in obese adolescents.MethodsEighteen obese and 20 eutrophic adolescents were evaluated for body composition using bioimpedance analysis (BIA), body mass index (BMI), IL-6 and lipopolysaccharide (LPS) serum levels, CD4 and FoxP3 Treg lymphocytes and monocytes. Synbiotic supplementation for 60 days was also evaluated for these parameters only in obese adolescents.ResultsWe observed an increase in CD4 lymphocyte (18.0 ± 12.4 vs. 8.9 ± 7.5; p

Introduction Older adults have high rates of primary care utilisation, and quality primary care has the potential to address their complex medical needs. Family physicians have different levels of knowledge and skills in caring for older patients, which may influence the quality of care delivery and resulting health outcomes. In this study, we aim to establish consensus on practice-based metrics that characterise quality of care for older primary care patients and can be examined using secondary, administrative data.Methods and analysis We describe a two-round RAND/UCLA Appropriateness Method (RAM) study to assess the consensus of a technical expert panel. We will recruit pan-Canadian experts who demonstrate excellence in clinical practice or scholarship related to the primary care of older adults. A literature review will generate a candidate list of practice-based quality indicators. The first round aims to evaluate the appropriateness and importance of candidate indicators through an online questionnaire. We will then develop technical definitions for each endorsed indicator using ICES data holdings. Panellists will offer feedback on the technical definitions in a virtual synchronous meeting and provide ratings on the same criteria in a second questionnaire.Ethics and dissemination Our study has been approved by the Hamilton Integrated Research Ethics Board (Project ID #15545). Findings will be disseminated via manuscripts, presentations and the lead author’s thesis.Trial registration number ISRCTN17074347

Kβ x-ray emission spectroscopy is a powerful probe for electronic structure analysis of 3d transition metal systems and their ultrafast dynamics. Selectively enhancing specific spectral regions would increase this sensitivity and provide fundamentally new insights. Recently we reported the observation and analysis of Kα amplified spontaneous x-ray emission from Mn solutions using an x-ray free-electron laser to create the 1s core-hole population inversion [Kroll et al., Phys. Rev. Lett. 120, 133203 (2018)PRLTAO0031-900710.1103/PhysRevLett.120.133203]. To apply this new approach to the chemically more sensitive but much weaker Kβ x-ray emission lines requires a mechanism to outcompete the dominant amplification of the Kα emission. Here we report the observation of seeded amplified Kβ x-ray emission from a NaMnO_{4} solution using two colors of x-ray free-electron laser pulses, one to create the 1s core-hole population inversion and the other to seed the amplified Kβ emission. Comparing the observed seeded amplified Kβ emission signal with that from conventional Kβ emission into the same solid angle, we obtain a signal enhancement of more than 10^{5}. Our findings are the first important step of enhancing and controlling the emission of selected final states of the Kβ spectrum with applications in chemical and materials science.

Innovative new crystallographic methods are facilitating structural studies from ever smaller crystals of biological macromolecules. In particular, serial X-ray crystallography and microcrystal electron diffraction (MicroED) have emerged as useful methods for obtaining structural information from crystals on the nanometre to micrometre scale. Despite the utility of these methods, their implementation can often be difficult, as they present many challenges that are not encountered in traditional macromolecular crystallography experiments. Here, XFEL serial crystallography experiments and MicroED experiments using batch-grown microcrystals of the enzyme cyclophilin A are described. The results provide a roadmap for researchers hoping to design macromolecular microcrystallography experiments, and they highlight the strengths and weaknesses of the two methods. Specifically, we focus on how the different physical conditions imposed by the sample-preparation and delivery methods required for each type of experiment affect the crystal structure of the enzyme.

Sleeping sickness is a fatal disease caused by the protozoan parasite Trypanosoma brucei (Tb). Inosine-5'-monophosphate dehydrogenase (IMPDH) has been proposed as a potential drug target, since it maintains the balance between guanylate deoxynucleotide and ribonucleotide levels that is pivotal for the parasite. Here we report the structure of TbIMPDH at room temperature utilizing free-electron laser radiation on crystals grown in living insect cells. The 2.80 Å resolution structure reveals the presence of ATP and GMP at the canonical sites of the Bateman domains, the latter in a so far unknown coordination mode. Consistent with previously reported IMPDH complexes harboring guanosine nucleotides at the second canonical site, TbIMPDH forms a compact oligomer structure, supporting a nucleotide-controlled conformational switch that allosterically modulates the catalytic activity. The oligomeric TbIMPDH structure we present here reveals the potential of in cellulo crystallization to identify genuine allosteric co-factors from a natural reservoir of specific compounds.

Single Particle Imaging (SPI) with intense coherent X-ray pulses from X-ray free-electron lasers (XFELs) has the potential to produce molecular structures without the need for crystallization or freezing. Here we present a dataset of 285,944 diffraction patterns from aerosolized Coliphage PR772 virus particles injected into the femtosecond X-ray pulses of the Linac Coherent Light Source (LCLS). Additional exposures with background information are also deposited. The diffraction data were collected at the Atomic, Molecular and Optical Science Instrument (AMO) of the LCLS in 4 experimental beam times during a period of four years. The photon energy was either 1.2 or 1.7 keV and the pulse energy was between 2 and 4 mJ in a focal spot of about 1.3 μm x 1.7 μm full width at half maximum (FWHM). The X-ray laser pulses captured the particles in random orientations. The data offer insight into aerosolised virus particles in the gas phase, contain information relevant to improving experimental parameters, and provide a basis for developing algorithms for image analysis and reconstruction.

Rape and sexual violence occur in all social classes and societies. In most cases, the sexual offenders are known to the victim and the majority of rapes happen in intimate relationships. Children are particularly vulnerable to sexual abuse, in particular, the female sex. The sexual abuse of minors is defined as “any sexual activities that an adult carries on or with a person under the age of consent.” Literature evidence that the prevalence of any type of violence among women with disabilities varies between 26.0% and 90.0%, compared to nondisabled women, showing that people with disabilities have an increased risk of suffering physical and sexual violence. Children with intellectual disabilities (ID) show a high risk of sexual victimization. The World Health Organization presently defines mental retardation as “a significantly reduced ability to understand new or complex information and to learn and apply new skills (impaired intelligence). This results in a reduced ability to cope independently (impaired social functioning), and begins before adulthood, with a lasting effect on development.” The aim of this study is to investigate the correct identification of sexual abuse and severe mental retardation through the collaboration of a team of experts (forensic pathologist, psychiatrist, psychologist, gynecologist, pediatrician, and social worker). We present a case of a 12-year-old female child, who suffers from severe mental retardation and was the victim of rape by a 79-year-old man. The study shows the difficulties in discovering episodes of sexual abuse among children affected by ID by evidencing the importance of adequate analysis through a multidisciplinary approach. The work focuses on the need to improve knowledge about medical and forensic investigations through proper protocols, for early recognition and appropriate management of these complicated cases.

Abstract The overall estimated risk of recurrence after an apparently complete thyroid cancer resection ranges from 5% CTCs (p = 0.09) and with >30% S‐phase cells at baseline (p = 0.0015), predicting ≤1 year relapsing lesion event. These results suggest a new intriguing frontier of precision oncology forefront cytology‐based liquid biopsy.

Metabolic reprogramming is an emerging hallmark of cancer, involving the overexpression of metabolism-related proteins, such as glucose and monocarboxylate transporters and intracellular glycolytic enzymes. The biology of testicular germ cell tumors (TGCTs) is very complex, and although their metabolic profile has been scantily explored, some authors have recently reported that the metabolic rewiring of cancer cells resulted in an association with aggressive clinicopathological characteristics. In this study we have investigated, by immunohistochemical analysis, the expression of key proteins sustaining the hyperglycolytic phenotype in pure seminoma (SE, nr. 35), pure embryonal carcinoma (EC, nr. 17) tissues samples, and normal testes (nr. 5). GLUT1, CD44, PFK-1, MCT1, MCT4, LDH-A, and PDH resulted in more expression in EC cells compared to SE cells. TOM20 was more expressed in SE than in EC. GLUT1, MCT1, and MCT4 expression showed a statistically significant association with SE histology, while for EC, the association resulted in being significant only for GLUT1 and MCT4. Finally, we observed that EC resulted as negative for p53, suggesting that the GLUT1 and MTC overexpression observed in EC could be also attributed to p53 downregulation. In conclusion, our findings evidenced that EC exhibits a higher expression of markers of active aerobic glycolysis compared to SE, suggesting that the aggressive phenotype is associated with a higher glycolytic rate. These data corroborate the emerging evidence on the involvement of metabolic reprogramming in testicular malignancies as well, highlighting that the metabolic players should be explored in the future as promising therapeutic targets.

Abstract Background AQUILA (NCT03470103) was a prospective, observational, 12-month cohort study evaluating treatment patterns, clinical effectiveness, and safety of intravitreal aflibercept (IVT-AFL) in patients from Latin America with neovascular age-related macular degeneration (nAMD). Methods Treatment-naïve and previously treated (switching to IVT-AFL) patients (aged ≥ 55 years) were enrolled from March 2018, with a primary completion date of September 2020, from Argentina, Colombia, Costa Rica, and Mexico. Patients received IVT-AFL in a routine clinical practice setting. Results Of 274 patients in the full analysis set, 201 were treatment-naïve and 73 had received previous treatment. The mean ± standard deviation number of IVT-AFL injections received by month 12 was 4.2 ± 1.9 (treatment-naïve) and 5.2 ± 2.7 (previously treated). The median duration from diagnosis to IVT-AFL treatment was 1.2 months (treatment-naïve) and 19.5 months (previously treated). Mean best-corrected visual acuity (BCVA) (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) improved from baseline to month 12 by + 5.2 ± 18.3 (treatment-naïve; baseline: 48.2 ± 23.5) and + 3.1 ± 15.3 letters (previously treated; baseline: 47.7 ± 21.4). Conclusion AQUILA is the first study to assess the use of IVT-AFL in routine clinical practice in Latin America. Mean BCVA and other visual acuity outcomes improved in both treatment groups, despite many patients not receiving the IVT-AFL label-recommended regimen of three initial monthly doses, or seven or more injections in 12 months. Patients who did receive the label-recommended number of injections had numerically greater improvements in visual acuity outcomes. Patients with nAMD treated regularly and more frequently with IVT-AFL, therefore, have the potential to achieve outcomes consistent with those observed in interventional studies. Trial registration: Clinicaltrials.gov, NCT03470103. Registered February 5, 2018, https://clinicaltrials.gov/ct2/show/NCT03470103

Abstract We have coupled the GEOS‐Chem tropospheric‐stratospheric chemistry mechanism and the Community Aerosol and Radiation Model for Atmospheres (CARMA), a sectional aerosol microphysics module, within the NASA Goddard Earth Observing System Chemistry‐Climate Model (GEOS CCM) in order to simulate the interactions between stratospheric chemistry and aerosol microphysics. We use observations of the 1991 Mount Pinatubo volcanic cloud to evaluate this new version of the GEOS CCM. The GEOS‐Chem chemistry module is used to simulate the oxidation of sulfur dioxide (SO2) more realistically than assuming hydroxyl radical (OH) fields are constant, as OH concentrations in the plume decrease dramatically in the weeks following the eruption. CARMA simulates sulfate aerosols with dynamic microphysical and optical properties. The CARMA‐calculated aerosol surface area is coupled to the chemistry module from GEOS‐Chem for the calculation of heterogeneous chemistry. We use a set of observational and theoretical constraints for Pinatubo to evaluate the performance of this new version of the GEOS CCM. These simulations are specifically compared with satellite and in‐situ observations and provide insights into the connections between the gas‐phase chemistry and the aerosol microphysics of the early plume and how they impact the climatic and chemical changes following a large volcanic eruption. A second, smaller eruption is also included in these simulations, the 15 August 1991, eruption of Cerro Hudson in Chile, which we find essential in explaining the aerosol optical depth in the Southern Hemisphere in 1991.

ABSTRACT Adaptive antibiotic resistance is a transient metabolic adaptation of bacteria limiting their sensitivity to low, progressively increased, concentrations of antibiotics. Unlike innate and acquired resistance, adaptive resistance is dependent on the presence of antibiotics, and it disappears when the triggering factor is removed. Low concentrations of antibiotics are largely diffused in natural environments, in the food industry or in certain body compartments of humans when used therapeutically, or in animals when used for growth promotion. However, molecular mechanisms underlying this phenomenon are still poorly characterized. Here, we present experiments suggesting that epigenetic modifications, triggered by low concentrations of ampicillin, gentamicin, and ciprofloxacin, may modulate the sensitivity of bacteria to antibiotics. The epigenetic modifications we observed were paralleled by modifications of the expression pattern of many genes, including some of those that have been found mutated in strains with permanent antibiotic resistance. As the use of low concentrations of antibiotics is spreading in different contexts, our findings may suggest new targets and strategies to avoid adaptive antibiotic resistance. This might be very important as, in the long run, this transient adaptation may increase the chance, allowing the survival and the flourishing of bacteria populations, of the onset of mutations leading to stable resistance. IMPORTANCE In this study, we characterized the modifications of epigenetic marks and of the whole transcriptome in the adaptive response of Escherichia coli cells to low concentrations of ampicillin, gentamicin, and ciprofloxacin. As the transient adaptation does increase the chance of permanent resistance, possibly allowing the survival and flourishing of bacteria populations where casual mutations providing resistance may give an immediate advantage, the importance of this study is not only in the identification of possible molecular mechanisms underlying adaptive resistance to antibiotics, but also in suggesting new strategies to avoid adaptation.

Dynamic digital radiography (DDR) is a high-resolution radiographic imaging technique using pulsed X-ray emission to acquire a multiframe cine-loop of the target anatomical area. The first DDR technology was orthostatic chest acquisitions, but new portable equipment that can be positioned at the patient’s bedside was recently released, significantly expanding its potential applications, particularly in chest examination. It provides anatomical and functional information on the motion of different anatomical structures, such as the lungs, pleura, rib cage, and trachea. Native images can be further analyzed with dedicated post-processing software to extract quantitative parameters, including diaphragm motility, automatically projected lung area and area changing rate, a colorimetric map of the signal value change related to respiration and motility, and lung perfusion. The dynamic diagnostic information along with the significant advantages of this technique in terms of portability, versatility, and cost-effectiveness represents a potential game changer for radiological diagnosis and monitoring at the patient’s bedside. DDR has several applications in daily clinical practice, and in this narrative review, we will focus on chest imaging, which is the main application explored to date in the literature. However, studies are still needed to understand deeply the clinical impact of this method.

Background: Healthcare systems represent complex organizations within which multiple factors (physical environment, human factor, technological devices, quality of care) interconnect to form a dense network whose imbalance is potentially able to compromise patient safety. In this scenario, the need for hospitals to expand reactive and proactive clinical risk management programs is easily understood, and artificial intelligence fits well in this context. This systematic review aims to investigate the state of the art regarding the impact of AI on clinical risk management processes. To simplify the analysis of the review outcomes and to motivate future standardized comparisons with any subsequent studies, the findings of the present review will be grouped according to the possibility of applying AI in the prevention of the different incident type groups as defined by the ICPS. Materials and Methods: On 3 November 2023, a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was carried out using the SCOPUS and Medline (via PubMed) databases. A total of 297 articles were identified. After the selection process, 36 articles were included in the present systematic review. Results and Discussion: The studies included in this review allowed for the identification of three main “incident type” domains: clinical process, healthcare-associated infection, and medication. Another relevant application of AI in clinical risk management concerns the topic of incident reporting. Conclusions: This review highlighted that AI can be applied transversely in various clinical contexts to enhance patient safety and facilitate the identification of errors. It appears to be a promising tool to improve clinical risk management, although its use requires human supervision and cannot completely replace human skills. To facilitate the analysis of the present review outcome and to enable comparison with future systematic reviews, it was deemed useful to refer to a pre-existing taxonomy for the identification of adverse events. However, the results of the present study highlighted the usefulness of AI not only for risk prevention in clinical practice, but also in improving the use of an essential risk identification tool, which is incident reporting. For this reason, the taxonomy of the areas of application of AI to clinical risk processes should include an additional class relating to risk identification and analysis tools. For this purpose, it was considered convenient to use ICPS classification.

Tamoxifen-resistant breast cancer cells (TamR-BCCs) are characterized by an enhanced metabolic phenotype compared to tamoxifen-sensitive cells. FoxO3a is an important modulator of cell metabolism, and its deregulation has been involved in the acquisition of tamoxifen resistance. Therefore, tetracycline-inducible FoxO3a was overexpressed in TamR-BCCs (TamR/TetOn-AAA), which, together with their control cell line (TamR/TetOn-V), were subjected to seahorse metabolic assays and proteomic analysis. FoxO3a was able to counteract the increased oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) observed in TamR by reducing their energetic activity and glycolytic rate. FoxO3a caused glucose accumulation, very likely by reducing LDH activity and mitigated TamR biosynthetic needs by reducing G6PDH activity and hindering NADPH production via the pentose phosphate pathway (PPP). Proteomic analysis revealed a FoxO3a-dependent marked decrease in the expression of LDH as well as of several enzymes involved in carbohydrate metabolism (e.g., Aldolase A, LDHA and phosphofructokinase) and the analysis of cBioPortal datasets of BC patients evidenced a significant inverse correlation of these proteins and FoxO3a. Interestingly, FoxO3a also increased mitochondrial biogenesis despite reducing mitochondrial functionality by triggering ROS production. Based on these findings, FoxO3a inducing/activating drugs could represent promising tools to be exploited in the management of patients who are refractory to antiestrogen therapy.

Over the past 80 years, research on dopamine has undergone significant evolution, reshaping our understanding of its roles in the brain and the body [...]

Abstract Background AQUILA (NCT03470103) was a prospective, observational, 12-month cohort study to understand treatment patterns and to evaluate the clinical effectiveness and safety of intravitreal aflibercept (IVT-AFL) in patients from Latin America with diabetic macular edema (DME). Methods Treatment-naïve and previously treated (switching to IVT-AFL) patients (aged ≥ 18 years) were enrolled from March 2018, with a primary completion date of September 2020, from Argentina, Colombia, Costa Rica and Mexico. Patients received IVT-AFL in a routine clinical practice setting. Results Of 258 patients in the full analysis set, 181 were treatment-naïve and 77 had received previous treatment. The mean ± standard deviation number of IVT-AFL injections by Month 12 was 3.7 ± 1.8 (treatment-naïve) and 4.0 ± 2.2 (previously treated). The median duration from diagnosis to IVT-AFL treatment was 1.8 months (treatment-naïve) and 16.0 months (previously treated). Mean best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letters) improved from baseline to Month 12 by + 8.1 ± 17.7 (treatment-naïve; baseline: 54.5 ± 19.4) and + 4.6 ± 15.4 letters (previously treated; baseline: 52.9 ± 18.6). Conclusion AQUILA is the first study to assess the use of IVT-AFL in routine clinical practice in Latin America. Despite few patients being treated with the label-recommended regimen of 5 initial monthly doses or receiving ≥ 8 injections in 12 months, functional and anatomic visual outcomes improved during 12 months of treatment with IVT-AFL. Patients receiving the label-recommended number of injections had numerically greater improvements in visual acuity outcomes. Patients with DME treated regularly and more frequently with IVT-AFL therefore have the potential to achieve outcomes consistent with those observed in interventional studies. Trial registration Clinicaltrials.gov, NCT03470103. Registered February 5, 2018, https://clinicaltrials.gov/ct2/show/NCT03470103

mTOR limits the activation of an inflammatory gene response in monocytes. Inhibitors of mTOR enhance NF-κB-driven transcription in LPS-stimulated monocytes while depleting NAD+ through effects on the salvage pathway.

The Pacific Northwest Pyrocumulonimbus Event (PNE) took place in British Columbia during the evening and nighttime hours between 12 and 13 August 2017. Several pyroconvective clouds erupted on this occasion, and released in the upper troposphere and lower stratosphere unprecedented amounts of carbonaceous aerosols (300 ktn). Only a few years later, an even larger pyrocumulonimbus (pyroCb) injection took place over Australia. This event, named “the Australian New Year (ANY) event”, injected up to 1100 ktn of aerosol between 29 December 2019 and 4 January 2020. Such large injections of carbonaceous aerosol modify the stratospheric radiative budgets, locally perturbing stratospheric temperatures and winds. In this study, we use the Goddard Earth Observing System Chemistry Climate Model (GEOS CCM) to study the perturbations on the stratospheric meteorology induced by an aerosol injection of the magnitude of the PNE. Our simulations include the radiative interactions of aerosols, so that their impact on temperatures and winds are explicitly simulated. We show how the presence of the carbonaceous aerosols from the pyroCb causes the formation and maintenance of a synoptic-scale stratospheric anticyclone. We follow this disturbance considering the potential vorticity anomaly and the brown carbon aerosol loading and we describe its dynamical and thermodynamical structure and its evolution in time. The analysis presented here shows that the simulated anticyclone undergoes daily expansion–compression cycles governed by the radiative heating, which are directly related to the vertical motion of the plume, and that the aerosol radiative heating is essential in maintaining the anticyclone itself.

Abstract Serological testing for SARS-CoV-2 IgG antibodies is used to assess their presence in blood samples from exposed individuals and provides a measure of the magnitude of immune response to infection. The measurement of neutralizing antibodies (NAbs) in particular provides information about the severity of prior infection and level of protective immunity against re-infection. Much of the work investigating the association between prior infection severity and NAb levels has been conducted among clinical populations, and less is known about this relationship in the general population. Accordingly, we utilize data from a large (n = 790) community-based cohort of unvaccinated, seropositive participants. We analyzed the association between NAb response, measured via surrogate virus neutralization assay, with patterns of symptoms and household exposure. Our results indicate no detectable NAb activity in 63.8% of the seropositive participants (n = 504). Those with detectable NAb levels demonstrated a positive relationship between NAb activity and both self-reported previous symptom severity and household exposure. These findings are significant in light of recent concerns about degree of protective immunity conferred by prior infection or vaccination, and we highlight the value of community-based research for investigating variation in immune response.

Abstract Stratospheric injections of sulfur dioxide from major volcanic eruptions perturb the Earth's global radiative balance and dominate variability in stratospheric sulfur loading. The atmospheric component of the GFDL Earth System Model (ESM4.1) uses a bulk aerosol scheme and previously prescribed the distribution of aerosol optical properties in the stratosphere. To quantify volcanic contributions to the stratospheric sulfur cycle and the resulting climate impact, we modified ESM4.1 to simulate stratospheric sulfate aerosols prognostically. Driven by explicit volcanic emissions of aerosol precursors and non‐volcanic sources, we conduct ESM4.1 simulations from 1989 to 2014, with a focus on the Mt. Pinatubo eruption. We evaluate our interactive representation of the stratospheric sulfur cycle against data from Moderate Resolution Imaging Spectroradiometer, Multi‐angle Imaging SpectroRadiometer, Advanced Very High Resolution Radiometer, High Resolution Infrared Radiation Sounder, and Stratospheric Aerosol and Gas Experiment II. To assess the key processes associated with volcanic aerosols, we performed a sensitivity analysis of sulfate burden from the Mt. Pinatubo eruption by varying injection heights, emission amount, and stratospheric sulfate's dry effective radius. We find that the simulated stratospheric sulfate mass burden and aerosol optical depth in the model are sensitive to these parameters, especially volcanic SO2 injection height, and the optimal combination of parameters depends on the metric we evaluate.

Introduction Homicide-suicide is a rarer phenomenon than homicides or suicides alone. However, this event shows a devastating psychological impact on relatives with effects on the mental health of survivors. The possibility of early intervention through the identification of psychopathological risk factors in offenders remains a challenge of current forensic psychiatry, also for the geographic heterogeneity of the phenomenon. Objectives The purpose of the work is to offer a homogeneous review of the state of the art on the homicide-suicide phenomenon, focusing attention on the psychopathological characteristics of the offenders and related prevention. Methods A literature review was carried out through the PubMed NCBI search engine by entering the keywords “homicide-suicide” and psychiatry. A screening of the titles was carried out, with reading of the abstracts and full texts only in the selected papers that respected the research objectives. Results The search evidenced 71 papers and only 20 met the inclusion criteria. The review revealed in the vast majority of offenders, most often male, the presence of mental disorders such as major depression and schizophrenia, especially in the context of relationship problems, with triggers such as the fear of separation or partner unfaithfulness. In these cases, the relationship between victim and killer shows pathological dependence or extreme possession. The event can involve children or relatives (filicide/familicide suicides). The review showed the frequent association with psychiatric depressive disorders, and obsessive-compulsive, paranoid, or narcissistic traits, with a lack of specialist consultations and very poor adherence to psychiatric treatment. Firearms were the most widely used means. In the history of perpetrators there were frequent episodes of domestic violence, previous suicide attempts and substance abuse. In rarer cases, the event takes place in the context of mass murder-suicides in which the offender assumes positions of responsibility (eg. Airplane pilot) or acts in extremist religious contexts. Conclusions The review showed an association with mental health disorders and the need for early identification of risk signals. Appropriate psychiatric prevention programs, through the close collaboration of the family, social community and the mass media, are necessary in the management of the phenomenon, especially through the reporting of episodes of domestic violence or self-harming attempts. Disclosure of Interest None Declared

Introduction Suicide is one of the main cause of death in the world. It’s an important public health problem that is growning on new generations. Objectives The manners used to die have always been studied from psychiatry to understand which mental illness induced victim to various ways of suicide. They are multiples and are influenced by different factors. This study includes suicides cases defined “atypical”. Methods The cases were examined at the Insitute of legal Medicine Institute of Magna Graecia University of Catanzaro. Methods used were autopsies, and psycological autopsies. The study of the three cases also included the first level toxicological tests.. Results In the first case, the victim died for cut injuries by using a kitchen knife on the lateral-cervical region of neck; the inspection revealed superficial lesions (test cuts) which, with progressive depth, reached the vascular-nervous bundle. In the second case, in a family contest of apparent welfare, the victim decided to go out home in the middle of the night, to reach an isolated place: there, when he still was in his car, he spilled on his head flammable liquid to accelerate fire effects. In the case number 3, the victim was found at the bottom of a cliff with earplugs; maybe she was hearing voices in her mind that induced her to death. At home, police found a message on paper about her autopsy will. Conclusions The autopsy findings on the cases described are atypical. In every three cases of atypical suicide, the victim was not being treated with therapy, and all victims, probably, were very able to hide their socio-relational malaise. Forensic investigations for the study of suicides must not be limited to the study of fatal injuries. Forensic study about the modalities used to commit suicide wants to be a help to improve knowledge on certain psychiatric pathologies at high risk of suicide. Disclosure of Interest None Declared

Introduction Nearly 300 million people worldwide are affected by depression. According to the DSM-5, the depressive episode is characterized by a depressed mood, a marked decrease in interest or pleasure in all activities, insomnia, agitation or psychomotor slowdown. It occurs mainly in the female sex. Traumatic life events are associated with a depressive onset. Objectives It is well known that interpersonal relationships are foundations for human beings, especially emotional ones and that they have an important effect on mental health. Specifically, 60% of divorced people with a previous history of depression will develop a new depressive episode; this will develop in 10% of subjects without a previous history of depression. The recurring thought of death and suicide is also frequent, as well as the abuse of drugs and ethanol in cases of depression. The forensic pathologist often finds himself having to carry out complex inspections in order to trace the cause of death in these types of deaths. Methods We report the case of a lady, found dead at her home, in her bed. Results A medical prescription for benzodiazepines was found on the cabinet next to her bed with five bottles of benzodiazepines, one of which was empty, two semi-empty packs of antidepressants. Under the bed there was a photo album containing 58 pages to which the photographs of the lady’s wedding were attached. In all the photographs the groom’s face appeared torn. The hygienic-sanitary conditions of the house were precarious. The analysis of the medical record showed that the lady was being treated for major depressive disorder with psychotic manifestations, severe chronic insomnia disorder and abuse of ethyl alcohol and anxiolytics, which arose after separation from her husband five years before her. The toxicological examination performed on blood and urine confirmed the presence of massive doses of benzodiazepines and ethanol, causing death from respiratory depression. Conclusions In similar cases, the clinical and family history as well as the toxicological examination help the forensic pathologist in defining the cause of death. Depression leads to family and social isolation, affecting all aspects of a person’s life. Divorce is not only a painful and expensive experience but also harmful to health. The subject is not only in a condition of marital and economic abandonment but also health because the resources currently used in this field are few. Together with the legal process, there should also be a health process with prevention strategies such as questionnaires, interviews, exercises in order to identify those at risk and treat them appropriately. Disclosure of Interest None Declared

Introduction There are about 10 million inmates in the world, of which 6 million are held in American prisons. While in Europe there was a 6.6% reduction in the detention rate, in Italy the number of prisoners is constantly growing. Due to the worldwide importance of the phenomenon in the field of public health, it is necessary to analyze the relationship between detention and prisoner health, as well as the change in the psychophysical state of a subject after a period of incarceration. Objectives The analysis of the results deriving from the completion of forensic examinations was carried with the aim of assessing the compatibility of the health conditions of prisoners with imprisonment. Methods We report the results of a preliminary study on a sample of fifty prisoners held in Southern and Central Italy prisons. Results The average age of the prisoners was 41. The prevalence of psychiatric disorders in the sample examined was about 39 %. 45 % of subjects with mental disorders made one suicide attempt in prison at least. We emphasize the pathogenic role of prison in the development or aggravation of psychiatric disorders. This happens particularly in subjects coming from degraded socio-family backgrounds. Conclusions In order to reduce the prevalence of psychiatric disorders and the risk of suicide, it is necessary to carry out careful medical and psychological evaluation at each new entry, so as to be able to frame the inmate’s state of health and plan periodic monitoring of diagnosed diseases. This evaluation should include a psychiatrist, so as to be able to set up an adequate drug treatment when it’s necessary. The correct management of psychiatric disorders is essential in order to improve the inmate’s mental health and prevent medico-legal consequences for health workers. Disclosure of Interest None Declared

Serial crystallography of membrane proteins often employs high-viscosity injectors (HVIs) to deliver micrometre-sized crystals to the X-ray beam. Typically, the carrier medium is a lipidic cubic phase (LCP) media, which can also be used to nucleate and grow the crystals. However, despite the fact that the LCP is widely used with HVIs, the potential impact of the injection process on the LCP structure has not been reported and hence is not yet well understood. The self-assembled structure of the LCP can be affected by pressure, dehydration and temperature changes, all of which occur during continuous flow injection. These changes to the LCP structure may in turn impact the results of X-ray diffraction measurements from membrane protein crystals. To investigate the influence of HVIs on the structure of the LCP we conducted a study of the phase changes in monoolein/water and monoolein/buffer mixtures during continuous flow injection, at both atmospheric pressure and under vacuum. The reservoir pressure in the HVI was tracked to determine if there is any correlation with the phase behaviour of the LCP. The results indicated that, even though the reservoir pressure underwent (at times) significant variation, this did not appear to correlate with observed phase changes in the sample stream or correspond to shifts in the LCP lattice parameter. During vacuum injection, there was a three-way coexistence of the gyroid cubic phase, diamond cubic phase and lamellar phase. During injection at atmospheric pressure, the coexistence of a cubic phase and lamellar phase in the monoolein/water mixtures was also observed. The degree to which the lamellar phase is formed was found to be strongly dependent on the co-flowing gas conditions used to stabilize the LCP stream. A combination of laboratory-based optical polarization microscopy and simulation studies was used to investigate these observations.

Khanolkar et al. compare the immune response in perinatally-infected HIV+ patients with differing patterns of virological control on treatment with antiretroviral therapy. Patients with sub-optimally suppressed HIV displayed no deficits in lymphocyte functional fitness.

To improve current and future use of existing (oral, injectable) and potential future (implants, douches) pre-exposure prophylaxis (PrEP) products, we must understand product preferences relative to one another, among gay and bisexual men (GBM), and physicians who prescribe PrEP. We completed an online discrete choice experiment (DCE) with separate groups of GBM and/or physicians from the United States, South Africa, Spain, and Thailand. Participants were presented information on PrEP products, including daily pills, event-driven pills (2-1-1 regimen), injections, subdermal implants (dissolvable, removable), and rectal douches. Next, they completed a choice exercise in which they were shown 10 screens, each presenting 3 of the aforementioned products at a time with 11 attributes for physicians and 10 attributes for GBM. For the attributes that were not constant, one level was shown per screen for each product. Participants selected the product they preferred most and rated their likelihood to select (GBM) or recommend (physicians) that product. Data were modeled using hierarchical Bayes estimation; resulting model coefficients were used to develop attribute importance measures and product preferences. For GBM across all countries, if all aforementioned PrEP products were on the market at the same time, over 90% of GBM would use some form of PrEP; 100% of physicians would recommend at least one of the PrEP products. There were variations in product preference by country. GBM in the United States and Thailand preferred the injection (21.7%, 22.9%, respectively), while the dissolvable implant was preferred in South Africa and Spain (19.9%, 19.8%, respectively). In the United States, South Africa, and Spain (where physician data were available), physicians were most likely to recommend the dissolvable implant (37.2%, 40.6%, 38.3%, respectively). [ABSTRACT FROM AUTHOR]

The advent of smart grid technologies has facilitated the integration of new and intermittent renewable forms of electricity generation in power systems. Advancements are driving transformations in the context of energy planning and operations in many countries around the world, particularly impacting short-term horizons. Therefore, one of the primary challenges in this environment is to accurately provide forecasting of the short-term load demand. This is a critical task for creating supply strategies, system reliability decisions, and price formation in electricity power markets. In this context, nonlinear models, such as Neural Networks and Support Vector Machines, have gained popularity over the years due to advancements in mathematical techniques as well as improved computational capacity. The academic literature highlights various approaches to improve the accuracy of these machine learning models, including data segmentation by similar patterns, input variable selection, forecasting from hierarchical data, and net load forecasts. In Brazil, the national independent system operator improved the operation planning in the short term through the DESSEM model, which uses short-term load forecast models for planning the day-ahead operation of the system. Consequently, this study provides a comprehensive review of various methods used for short-term load forecasting, with a particular focus on those based on machine learning strategies, and discusses the Brazilian Experience.

(1) Background: Waning of neutralizing and cell-mediated immune response after the primary vaccine cycle (PVC) and the first booster dose (BD) is of concern, especially for PLWH with a CD4 count ≤200 cells/mm3. (2) Methods: Neutralizing antibodies (nAbs) titers by microneutralization assay against WD614G/Omicron BA.1 and IFNγ production by ELISA assay were measured in samples of PLWH at four time points [2 and 4 months post-PVC (T1 and T2), 2 weeks and 5 months after the BD (T3 and T4)]. Participants were stratified by CD4 count after PVC (LCD4, ≤200/mm3; ICD4, 201–500/mm3, and HCD4, >500/mm3). Mixed models were used to compare mean responses over T1–T4 across CD4 groups. (3) Results: 314 PLWH on ART (LCD4 = 56; ICD4 = 120; HCD4 = 138) were enrolled. At T2, levels of nAbs were significantly lower in LCD4 vs. ICD4/HCD4 (p = 0.04). The BD was crucial for increasing nAbs titers above 1:40 at T3 and up to T4 for WD614G. A positive T cell response after PVC was observed in all groups, regardless of CD4 (p = 0.31). (4) Conclusions: Waning of nAbs after PVC was more important in LCD4 group. The BD managed to re-establish higher levels of nAbs against WD614G, which were retained for 5 months, but for shorter time for Omicron BA.1. The T cellular response in the LCD4 group was lower than that seen in participants with higher CD4 count, but, importantly, it remained above detectable levels over the entire study period.