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Background: Identification of high-impact chronic pain (HICP) among patients receiving total shoulder arthroplasty (TSA) may allow for the design and implementation of tailored pain interventions to address the negative impact on postoperative outcomes and quality of life. This analysis sought to determine if Patient-Reported Outcome Measurement Information System (PROMIS) measures could be used to estimate HICP status following TSA. Methods: This was a secondary analysis of a cohort of patients (n = 227) who received a TSA at a single, academic medical center, of whom 25 (11.5%) met HICP status postoperatively. Generalized linear models estimated HICP from each PROMIS measure of physical function, pain interference, sleep disturbance, anxiety, and dyspnea individually, then in a combined model. Area under the curve (AUC) was calculated using receiver operator characteristic curves to assess accuracy of each PROMIS measure to estimate HICP status for patients receiving TSA. Results: Bivariate generalized linear models and mean difference analyses revealed individuals with HICP had worse PROMIS scores in every included domain (all P values < .01). Only pain interference (AUC = 0.964) and physical function (AUC = 0.907) PROMIS measures met criteria (AUC > 0.850) to accurately predict HICP. A pain interference score ≥58.3 and/or a physical function score ≤41.2 could be used to estimate HICP from PROMIS measures in this cohort. Conclusion: Two PROMIS measures commonly administered in orthopedic surgery settings, physical function and pain interference, can be used to estimate HICP for patients receiving TSA. Further application and evaluation of these cutoff scores can be used to assist in refining assessment of outcomes for patients receiving TSA.

The aim of this case report was to present an alternative therapeutic combination involving lip repositioning (LR) in the correction of gummy smile (GS). This treatment is less invasive than orthognathic surgery and is highly acceptable to patients, using a modified technique that combines myotomy with the insertion of polyester threads as a physical barrier against relapse.

Objetivos: O linfoma de Burkitt (LB) é uma neoplasia hematológica das células B, localizada no centro germinativo dos linfonodos. A resistência aos quimioterápicos e a alta toxicidade das terapias atuais são um desafio, especialmente em pacientes idosos e imunocomprometidos. Este estudo visa avaliar a atividade citotóxica de compostos de coordenação em linhagens celulares de LB. Materiais e métodos: Para a avaliação da citotoxicidade dos compostos de coordenação de cobre (II) (compostos 6 e 8) e platina (II) (composto 3) foram realizadas curvas de concentração e tempo resposta em células de linhagem de LB (Daudi) pelo método do MTT. Para isso, as células foram incubadas em diferentes concentrações e tempos, e a concentração inibitória 50% (CI50) foi determinada por meio de regressão linear. A fim de avaliar o mecanismo de morte celular causada pelos compostos 3, 6 e 8, foram empregadas duas metodologias: avaliação da morfologia das células coradas com brometo de etídio (BE) e a laranja de acridina (LA) por microscopia de fluorescência e avaliação da exposição dos resíduos de fosfatidilserina pelo método da Anexina V por citometria de fluxo (CF). A avaliação das proteínas Bax, Bcl-2, AIF, FasR, Caspase-3 ativada, Ki-67, survivina e do potencial de membrana mitocondrial (Δψm) na morte celular causada pelos compostos foi realizada por CF. Resultados: Inicialmente, foi avaliado o efeito citotóxico dos três compostos de coordenação sobre células Daudi para a obtenção da CI50. Nos tempos de 24, 48 e 72h foi observada a CI50 de 3,72 ± 0,17 μM, 3,26 ± 0,27 μM, 6,42 ± 0,48 μM para o composto 3. O composto 6 apresentou CI50 de 74,05 ± 2,70 μM (24h), 10,46 ± 0,40 μM (48h) e 5,15 ± 0,46 μM (72h). Por fim, o composto 8 apresentou CI50 de 6,90 ± 0,39 μM (24h), 32,14 ± 1,42 μM (48h) e 15,37 ± 0,50 μM (72h). Após a incubação com os compostos, foi observado por microscopia perda do volume celular e condensação da cromatina, além de perda da integridade da membrana celular, sinais de apoptose inicial e tardia. Os três compostos também causaram a externalização de resíduos de fosfatidilserina, o que confirma a morte celular por apoptose. Os resultados apresentados para os compostos 3, 6 e 8 mostram que a morte celular causada pelos compostos, envolve a apoptose intrínseca, pois houve aumento da relação Bax/Bcl-2, bem como, aumento da expressão de AIF, após tratamento com os compostos 6 e 8, e perda do Δψm após tratamento com o composto 6 e ativação de caspase-3 após o tratamento com os compostos 3, 6 e 7. Os compostos 6 e 8 também participam da ativação da via extrínseca da apoptose, pois aumentaram a expressão de FasR. A incubação com os compostos também diminuiu a expressão do Ki-67 e da proteína survivina. Discussão: Os compostos avaliados desencadearam morte celular por apoptose intrinseca, evidenciada pela perda do Δψm, aumento da razão Bax/Bcl-2 e da expressão de AIF, e apoptose extrinseca, confirmada pelo aumento de FasR. O aumento da caspase-3, uma caspase efetora, confirma a execução da apoptose. Além disso, os compostos diminuíram a expressão da proteína survivina, que quando aumentada, contribui para resistência celular aos quimioterápicos. Conclusão: A partir do conjunto de resultados apresentados, sugere-se que os compostos são bons candidatos para o desenvolvimento de novos fármacos para o tratamento do LB.

Introdução: A Leucemia Linfoblástica Aguda de precursores B (LLA-pB) é uma das neoplasias mais comuns na infância, representando cerca de 25% dos casos em crianças abaixo de 15 anos, com pico de incidência entre 2 e 3 anos. Mecanismos de reparo de DNA, como a Reparação por Excisão de Base (BER), a Reparação por Excisão de Nucleotídeo (NER) e a Recombinação Homóloga (HRR), são cruciais para manter a estabilidade do genoma. Alterações nesses mecanismos podem afetar negativamente a resposta ao tratamento e a sobrevivência. Objetivo: Relatar um caso de resistência à quimioterapia em um paciente pediátrico com LLA-pB, com foco nas alterações genéticas e moleculares, especialmente nos mecanismos de reparo de DNA. Relato de caso: Menino de 11 anos com astenia, palidez e dor abdominal, apresentando HB 4,5 g/dL, leucometria 4.500/mm3 e plaquetas 258.000/mm3. A imunofenotipagem da medula óssea revelou LLA-pB com 40% de células precursoras B leucêmicas, e a citogenética mostrou 46XY. Foi tratado com o protocolo BFM AEIOP 2013. A medula óssea permaneceu infiltrada no D15 (18% de blastos) e D33/TP1 (21% de blastos), e entrou em remissão morfológica no D78/TP2 (4% de blastos), detectados por citometria de fluxo (CF). Alcançou a primeira Doença Residual Mensurável (MRD) negativa (< 0,001%) após o bloco HR-II. Na avaliação pré-protocolo III, foi observada progressão com 3,2% de DRM, evoluindo rapidamente para 55% de blastos. O protocolo de recaída Flag-Ida foi realizado sem resposta. O tratamento com anti-CD19 (Blinatumomab) por 28 dias também foi ineficaz, impossibilitando o transplante haploidêntico, previamente agendado. O paciente faleceu em maio de 2020, 11 meses após o diagnóstico. Em análise genética retrospectiva, realizada a partir de material genético criopreservado, a técnica de MLPA revelou deleções nos genes IKZF1, CDKN2A, CDKN2B e PAX5, classificando o paciente como IKZF1plus devido à ausência de deleção no gene ERG1. O sequenciamento dos genes de reparo de DNA APEX1, XRCC1, XPD, XPA, RAD51 e XRCC3 revelou 54 variantes, das quais 19 eram mutações raras com frequência populacional menor que 0,01. Polimorfismos de único nucleotídeo (SNPs) de reconhecida relevância clínica foram identificados nos genes APEX1 (Asp148Glu) e XRCC1 (Arg399Gln e Arg194Trp). Discussão: A presença de múltiplas variantes raras é considerado um indicativo de mutagênese elevada. Os genes APEX1 e XRCC1 estão envolvidos na via BER, e os SNPs são encontrados associados como fatores de pior prognóstico em diversas neoplasias. A via BER é fundamental na proteção do tecido hematopoiético, e defeitos nesta via podem afetar negativamente a resposta ao tratamento e a evolução da doença. A mutagênese aumentada pode ter contribuído para o surgimento de alterações secundárias, como o perfil IKZF1plus. Estudos sobre o papel do reparo de DNA em neoplasias hematológicas são escassos, sem dados suficientes para uma correlação estatística conclusiva. Conclusão: Integrar análises genéticas com achados clínicos é essencial para otimizar o tratamento em pacientes com perfis genéticos complexos. Identificamos defeitos na via BER como potenciais moduladores da resposta terapêutica. Avaliar individualmente o reparo de DNA pode ajudar a entender como variações genéticas individuais influenciam a resposta clínica e assim melhorar a precisão do prognóstico.

For dosimetry of radiopharmaceutical therapies, it is essential to determine the volume of relevant structures exposed to therapeutic radiation. For many radiopharmaceuticals, the kidneys represent an important organ-at-risk. To reduce the time required for kidney segmentation, which is often still performed manually, numerous approaches have been presented in recent years to apply deep learning-based methods for CT-based automated segmentation. While the automatic segmentation methods presented so far have been based solely on CT information, the aim of this work is to examine the added value of incorporating PSMA-PET data in the automatic kidney segmentation. Methods: A total of 108 PET/CT examinations (53 [68Ga]Ga-PSMA-I&T and 55 [18F]F-PSMA-1007 examinations) were grouped to create a reference data set of manual segmentations of the kidney. These segmentations were performed by a human examiner. For each subject, two segmentations were carried out: one CT-based (detailed) segmentation and one PET-based (coarser) segmentation. Five different u-net based approaches were applied to the data set to perform an automated segmentation of the kidney: CT images only, PET images only (coarse segmentation), a combination of CT and PET images, a combination of CT images and a PET-based coarse mask, and a CT image, which had been pre-segmented using a PET-based coarse mask. A quantitative assessment of these approaches was performed based on a test data set of 20 patients, including Dice score, volume deviation and average Hausdorff distance between automated and manual segmentations. Additionally, a visual evaluation of automated segmentations for 100 additional (i.e., exclusively automatically segmented) patients was performed by a nuclear physician. Results: Out of all approaches, the best results were achieved by using CT images which had been pre-segmented using a PET-based coarse mask as input. In addition, this method performed significantly better than the segmentation based solely on CT, which was supported by the visual examination of the additional segmentations. In 80% of the cases, the segmentations created by exploiting the PET-based pre-segmentation were preferred by the nuclear physician. Conclusion: This study shows that deep-learning based kidney segmentation can be significantly improved through the addition of a PET-based pre-segmentation. The presented method was shown to be especially beneficial for kidneys with cysts or kidneys that are closely adjacent to other organs such as the spleen, liver or pancreas. In the future, this could lead to a considerable reduction in the time required for dosimetry calculations as well as an improvement in the results.

Background: Both conservative and surgical treatment options for tendinopathies often have less than ideal outcomes. Platelet-rich plasma (PRP) has become an increasingly popular treatment option with only limited evidence for effectiveness. Methods: A retrospective review was performed of all consecutive patients undergoing PRP for hip tendinopathies during a three-year period in a single outpatient spine and musculoskeletal clinic. Each procedure was performed under ultrasound guidance with a concurrent needle tenotomy. Categorical data analysis was performed to determine percent of patients achieving at least 30 %, 50 %, and 80 % relief of pain as measured by NRS. Results: A total of 48 patients were included with an average follow period of 14 weeks. Seventy-seven percent of patient achieved at least 30 % improvement in pain by NRS (95 % CI: 63%–88 %), 65 % achieved at least 50 % improvement in pain (95 % CI: 49%–78 %), and 27 % achieved at least 80 % pain improvement (95 % CI: 15%–42 %). Conclusion: This retrospective study demonstrates relatively good outcomes for this novel treatment. The results of this single practice audit are similar to previously published retrospective and prospective trials.

Background: Pediatric surgery is a highly specialised field, with minimally invasive surgery (MIS) posing greater technical challenges than conventional open surgery. Proficiency requires both in and out-of-operating-room training, with simulation playing a crucial role. The purpose of this study was to explore MIS perceptions, training experiences, and preferences regarding laparoscopic simulation training. Furthermore, we aimed to validate two synthetic EA/TEF models. Method: A questionnaire focused on the degree of adoption of MIS among paediatric surgeons was proposed online to participants at the 68th Czech and Slovak Pediatric Surgery Congress in Slovakia in 2024. All participants also had scheduled sessions to practice advanced laparoscopic skills on two synthetic EA/TEF models. The purpose of this study was to analyse experiences with paediatric MIS, the implementation of simulation training, and personal stances on integrating simulation training into training curricula. EA/TEF models were validated with a 5-point Likert scale. Results: Thirty-three paediatric surgeons from 14 centres in two countries completed the questionnaire. Six (18 %) were novices, 12 (36 %) intermediate trainees, and 15 (45 %) specialists with over 11 years of practice. Eight participants (18 %) declared weekly access to simulation training, while 49 % had none. Additionally, 15 individuals (45.5 %) strongly agree and 48.5 % agree that regular training on simulators enhances surgical skills in MIS procedures in the operating room. Twenty-six respondents (76 %) believe that simulator training should be part of the requirements for pediatric surgical trainees, with no significant difference according to the surgeons' experience (p = 0.290). Thirty surgeons validated the EA/TEF models. Highest ratings were for overall impression and tool usefulness in experienced surgeons' training (mean scores: 4.5 and 4.6). The working space received the lowest score (mean: 3.6 ± 0.8), with experienced surgeons rating it significantly lower (3.4) than the inexperienced group (4.1, p = 0.030). No significant differences were observed between models in Likert scale parameters. Conclusion: Simulation training is essential for teaching MIS in paediatric surgery, improving skills, and should be part of specialisation preparation. Synthetic EA/TEF models received high ratings as effective training tools for thoracoscopic EA/TEF training. Further studies are needed to prove construct validity.

Background: Addressing perinatal psychological distress in Sierra Leone faces challenges due to the lack of culturally appropriate assessment tools, despite recent WHO recommendations for screening during the pre- and postpartum periods. While high-income countries use tools like the Edinburgh Postnatal Depression Scale or Patient Health Questionnaire-9 (PHQ-9), their cross-cultural validity and efficacy in developing countries are uncertain. The aim of this study was to address this gap by developing a functional assessment tool, culturally appropriate screening tool for perinatal psychological distress, and validate it with the PHQ-9. Method: Following scale development guidelines, the study encompassed three phases: Item Development, Scale Development, and Scale Evaluation. Data from free listing interviews (n = 96), FGDs (n = 24), and cognitive interviews (n = 8) informed the development of the Sierra Leone Perinatal Psychological Distress Scale (SLPPDS) and a Function scale. Item reduction via exploratory factor analysis (n = 120) and validation (n = 140) were conducted in subsequent phases. Result: Two screening instruments were developed: the 10-item SLPPDS and a 5-item Function scale assessing perinatal women's ability to perform daily tasks. Sensitivity/specificity values for the SLPPDS and PHQ-9 were 80.0/85.7 and 73.8/76.2 respectively. Internal consistency reliability was 0.88 for the SLPPDS and 0.81 for the PHQ-9. Confirmatory factor analysis supported a one-factor model with 54.9 % variance explained. ROC/cut-off points for SLPPDS and PHQ-9 were 0.90/0.81 and 8.0/7.0 respectively. Conclusion: The PHQ-9 shows validity and reliability as a screening instrument, but the SLPPDS emerges as a potentially more salient alternative for assessing perinatal psychological distress in Sierra Leone. This implies the SLPDDS is particularly relevant, meaningful, and applicable to the specific cultural or community context it was designed for. It suggests that the tool effectively addresses the unique needs, perspectives, and experiences of the perinatal women, making it more likely to resonate with users and stakeholders. This relevance may enhance the tool's acceptance, usability, and overall impact in identifying and addressing perinatal mental health issues in Sierra Leone. These instruments could enable effective evaluation of perinatal mental health initiatives by government agencies, locals, and international NGOs.

A 63-year-old male developed a mycotic pseudoaneurysm (MPA) two months after a renal transplant at the anastomotic site. He presented with uncontrolled hypertension and elevated creatinine. The pseudoaneurysm occurred at the anastomosis between the two donor renal arteries and the left external iliac artery. We describe a unique surgical reconstruction where the MPA was resected and the vasculature was reconstructed using deceased donor vessels. A deceased donor common iliac artery including superior gluteal and inferior gluteal branches were used as a jump graft from the contralateral common iliac artery to the two transplanted renal arteries. The external iliac artery was repaired with an interposition bypass using deceased donor iliac vein. The patient received 8 weeks of antifungal therapy after the specimen grew candida albicans. Post-operatively, the patient had an acute kidney injury requiring dialysis, but after two months of dialysis, his renal function returned to normal and he remains dialysis-free.

Privacy Impact Assessments (PIAs) offer a process for assessing the privacy impacts of a project or system. As a privacy engineering strategy, they are one of the main approaches to privacy by design, supporting the early identification of threats and controls. However, there is still a shortage of empirical evidence on their use and proven effectiveness in practice. To better understand the current literature and research, this paper provides a comprehensive Scoping Review (ScR) on the topic of PIAs “in the wild,” following the well-established Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. This ScR includes 45 studies, providing an extensive synthesis of the existing body of knowledge, classifying types of research and publications, appraising the methodological quality of primary research, and summarising the positive and negative aspects of PIAs in practice, as reported by those studies. This ScR also identifies significant research gaps (e.g., evidence gaps from contradictory results and methodological gaps from research design deficiencies), future research pathways, and implications for researchers, practitioners, and policymakers developing and using PIA frameworks. As we conclude, there is still a significant need for more primary research on the topic, both qualitative and quantitative. A critical appraisal of qualitative studies revealed deficiencies in the methodological quality, and only four quantitative studies were identified, suggesting that current primary research remains incipient. Nonetheless, PIAs can be regarded as a prominent sub-area in the broader field of empirical privacy engineering, in which further scientific research to support existing practices is needed.

Anthelmintic resistance in sheep parasitic gastrointestinal nematodes is widespread and a severe health and economic issue but prevalence of resistance and involved parasite species are unknown in Germany. Here, the faecal egg count reduction test (FECRT) was performed on eight farms using fenbendazole, ivermectin and moxidectin and on four farms using only moxidectin. A questionnaire was used to obtain data on management practices to potentially identify risk factors for presence of resistance. All requirements of the recently revised WAAVP guideline for diagnosing anthelmintic resistance using the FECRT were applied. Nematode species composition in pre- and post-treatment samples was analysed with the nemabiome approach. Using the eggCounts statistic package, resistance against fenbendazole, ivermectin and moxidectin was found on 7/8, 8/8 and 8/12 farms, respectively. No formal risk factor analysis was conducted since resistance was present on most farms. Comparison with the bayescount R package results revealed substantial agreement between methods (Cohen's κ = 0.774). In contrast, interpretation of data comparing revised and original WAAVP guidelines resulted in moderate agreement (Cohen's κ = 0.444). The FECR for moxidectin was significantly higher than for ivermectin and fenbendazole. Nemabiome data identified 4 to 12 species in pre-treatment samples and treatments caused a small but significant decrease in species diversity (inverse Simpson index). Non-metric multidimensional scaling and k-means clustering were used to identify common patterns in pre- and post-treatment samples. However, post-treatment samples were scattered among the pre-treatment samples. Resistant parasite species differed between farms. In conclusion, the revised FECRT guideline allows robust detection of anthelmintic resistance. Resistance was widespread and involved multiple parasite species. Resistance against both drug classes on the same farm was common. Further studies including additional drugs (levamisole, monepantel, closantel) should combine sensitive FECRTs with nemabiome data to comprehensively characterise the anthelmintic susceptibility status of sheep nematodes in Germany.

Neuroendocrine analyses of posttraumatic stress disorder (PTSD) have generally focused on hypothalamic-pituitary-adrenal (HPA) axis alterations. In the present analyses, we examine two additional neuroendocrine factors that have been previously implicated in biological stress responses: oxytocin (OT) and arginine vasopressin (AVP). Here we examined basal neuropeptide status in military veterans clinically diagnosed with PTSD (n = 29) and in two non-traumatized comparison groups with previous stress exposure (n = 11 SWAT trainees and n = 21 ultramarathon runners). PTSD patients showed low levels of plasma OT and high levels of AVP. The ratio of AVP/OT robustly related to PTSD status, and emerged as a statistically plausible mediator of relationships between the number of personal traumatic experiences and subsequent PTSD symptom burden. Over the course of behavioral therapy for PTSD, measures of OT showed a significant but modest normalization. Plasma cortisol levels were not statistically different among the three groups. This study suggests that AVP/OT ratios may represent a neuroendocrine predictor of severe PTSD, as well as a potential treatment response biomarker.

Summary: Human genetic studies of critical COVID-19 pneumonia have revealed the essential role of type I interferon-dependent innate immunity to SARS-CoV-2 infection. Conversely, an association between the HLA-B∗15:01 allele and asymptomatic SARS-CoV-2 infection in unvaccinated individuals was recently reported, suggesting a contribution of pre-existing T cell-dependent adaptive immunity. We report a lack of association of classical HLA alleles, including HLA-B∗15:01, with pre-omicron asymptomatic SARS-CoV-2 infection in unvaccinated participants in a prospective population-based study in the United States (191 asymptomatic vs. 945 symptomatic COVID-19 cases). Moreover, we found no such association in the international COVID Human Genetic Effort cohort (206 asymptomatic vs. 574 mild or moderate COVID-19 cases and 1,625 severe or critical COVID-19 cases). Finally, in the Human Challenge Characterisation study, the three HLA-B∗15:01 individuals infected with SARS-CoV-2 developed symptoms. As with other acute primary infections studied, no classical HLA alleles favoring an asymptomatic course of SARS-CoV-2 infection were identified.

Objective: Time spent among the 24-h movement behaviors (physical activity [PA], sleep, sedentary behavior [SB]) in the perinatal period is important for maternal and child health. We described changes to 24-h movement behaviors and behavior guideline attainment during pregnancy and postpartum and identified correlates of behavior changes. Methods: This secondary data analysis included the standard of care group (n = 439) from the U.S.-based Lifestyle Interventions For Expectant Moms (LIFE-Moms) consortium, including persons with overweight and obesity. Wrist-worn accelerometry was used to measure movement behaviors early (9–15 weeks) and late (35–36 weeks) pregnancy, and ∼ 1-year postpartum. Sleep and moderate-to-vigorous PA (MVPA) were compared to adult and pregnancy-specific guidelines, respectively. SB was classified into quartiles. PA and SB context were quantified using questionnaires. Mixed models were used to examine changes in behaviors and guidelines and identify correlates. Results: Participants were 31.3 ± 3.5 years, 53.5 % were Black or Hispanic, and 45.1 % had overweight. Sleep duration decreased across time, but participants consistently met the guideline (range: 85.0–93.6 %). SB increased during pregnancy and decreased postpartum, while light PA and MVPA followed the inverse pattern. Participants met slightly fewer guidelines late pregnancy (1.2 ± 0.7 guidelines) but more postpartum (1.7 ± 0.8 guidelines) than early pregnancy (1.4 ± 0.8 guidelines). Black or Hispanic race/ethnicity, higher pregravid body mass index, and non-day work-shift (e.g., night-shift) were identified correlates of lower guideline adherence and varying PA and SB context. Conclusion: Perinatal interventions should consider strategies to prevent SB increase and sustain MVPA to promote guideline adherence.

Tungsten targets produced by the additive manufacturing (AM) method of electron-beam powder-bed fusion, or 3-D metal printing, are exposed to high flux D plasma in the Pisces-RF linear plasma device with the plasma-exposed surface normal to the AM build direction. D retention was measured by thermal desorption mass spectrometry following exposure to D plasma with an associated ∼50eV D+ ion flux. D+ fluence, and operational temperature, in the ranges 5×1024–5×1026 m−2 and 400–1000 K, are explored. D retention values for the AM W are compared to identically plasma exposed ’conventional’ sintered W and it is found that total D retention is similar. However, the D thermal release is notably different. Desorption from the AM W shows reduced D retention in traps typical of sintered W, and moderately increased trapping in defect types of higher trap release energy. The dependence of D retention on fluence is also different for the AM W, revealing an uptake slower than expected from Fickian diffusion, while that for sintered W is consistent and in agreement with previous poly-crystalline W results from Pisces-B. Hydrogen transport modeling of the fluence dependence suggests that interconnected pathways for D release back to the surface during plasma-exposure can account for the slower D uptake in the AM W.

Exposure to xenobiotics can increase the production of reactive oxygen species (ROS). When detoxification organs such as the intestines and liver cannot neutralise these xenobiotics, it can induce oxidative stress and cause damage to tissues. Therefore, cell-based bioassays that indicate intracellular ROS production are a useful screening tool to evaluate the effect of these chemicals. Although flow cytometry is commonly used to measure ROS in cells, many research laboratories in the Global South do not always have access to such specialised instrumentation. Therefore, we describe a sensitive but low-cost method that can easily be used to determine ROS production in vitro. This method employs the fluorogenic dye, 2′,7′-dichlorodihydrofluorescein diacetate (H2DCF-DA), which emits fluorescence after being oxidised to a fluorescent derivative. Since the H2DCF-DA bioassay indicates non-specific ROS production it can be used as a marker of overall oxidative stress. This method was validated by exposing human duodenum epithelial adenocarcinoma (HuTu-80) and rat liver epithelial hepatoma (H4IIE-luc) cells to agricultural soil samples. • Production of ROS can be determined in vitro in intestinal and liver cells. • This method is inexpensive and can be easily performed in standard laboratories. • The method provides a tool for the high-throughput screening of environmental samples.

Background: Infectious diseases can contribute to substance abuse. Here, a fatal case of borreliosis and substance abuse is reported. This patient had a history of multiple tick bites and increasing multisystem symptoms, yet diagnosis and treatment were delayed. He experimented with multiple substances including phencyclidine (PCP), an N-methyl-d-aspartate (NMDA) receptor antagonist that opposes NMDA agonism caused by Borrelia infection. During PCP withdrawal, he committed one homicide, two assaults, and suicide. Methods: Brain tissue was obtained from autopsy and stained for microglial activation and quinolinic acid (QA). Immunoflouresence (IFA) and fluorescence in situ hybridization (FISH) were used to identify the presence of pathogens in autopsy tissue. Results: Autopsy tissue evaluation demonstrated Borrelia in the pancreas by IFA and heart by IFA and FISH. Activated microglia and QA were found in the brain, indicating neuroinflammation. It is postulated that PCP withdrawal may exacerbate symptoms produced by Borrelia-induced biochemical imbalances in the brain. This combination may have greatly increased his acute homicidal and suicidal risk. Patient databases also demonstrated the risk of homicide or suicide in patients diagnosed with borreliosis and confirmed multiple symptoms in these patients, including chronic pain, anxiety, and anhedonia. Conclusions: Late-stage borreliosis is associated with multiple symptoms that may contribute to an increased risk of substance abuse and addictive disorders. More effective diagnosis and treatment of borreliosis, and attention to substance abuse potential may help reduce associated morbidity and mortality in patients with borreliosis, particularly in endemic areas.

Investigation of neural mechanisms of real-time functional MRI neurofeedback (rtfMRI-nf) training requires an efficient study control approach. A common rtfMRI-nf study design involves an experimental group, receiving active rtfMRI-nf, and a control group, provided with sham rtfMRI-nf. We report the first study in which rtfMRI-nf procedure is controlled through counterbalancing training runs with active and sham rtfMRI-nf for each participant. Healthy volunteers (n = 18) used rtfMRI-nf to upregulate fMRI activity of an individually defined target region in the left dorsolateral prefrontal cortex (DLPFC) while performing tasks that involved mental generation of a random numerical sequence and serial summation of numbers in the sequence. Sham rtfMRI-nf was provided based on fMRI activity of a different brain region, not involved in these tasks. The experimental procedure included two training runs with the active rtfMRI-nf and two runs with the sham rtfMRI-nf, in a randomized order. The participants achieved significantly higher fMRI activation of the left DLPFC target region during the active rtfMRI-nf conditions compared to the sham rtfMRI-nf conditions. fMRI functional connectivity of the left DLPFC target region with the nodes of the central executive network was significantly enhanced during the active rtfMRI-nf conditions relative to the sham conditions. fMRI connectivity of the target region with the nodes of the default mode network was similarly enhanced. fMRI connectivity changes between the active and sham conditions exhibited meaningful associations with individual performance measures on the Working Memory Multimodal Attention Task, the Approach-Avoidance Task, and the Trail Making Test. Our results demonstrate that the counterbalanced active-sham study design can be efficiently used to investigate mechanisms of active rtfMRI-nf in direct comparison to those of sham rtfMRI-nf. Further studies with larger group sizes are needed to confirm the reported findings and evaluate clinical utility of this study control approach.

ABSTRACT: Iron is routinely supplemented in broiler feeds aiming to prevent dietary deficiencies. Limestone and phosphates are very rich in Fe; however, its contribution from these sources have not been thoroughly investigated with chickens. The present research was conducted to evaluate live performance and blood parameters of broilers when using limestone and dicalcium phosphate as sources of Fe. A total of 576 one-day-old male Cobb x Cobb 500 were allocated into a total of 72 battery cages, 6 treatments with 12 replication cages of 8 chicks at placement. Chicks were fed diets formulated with corn, soybean meal (SBM) with laboratory grade calcium carbonate and phosphoric acid (having traces of Fe). All chicks were fed a common prestarter without Fe supplementation (analyzed total 58.2 ± 2.4 mg/kg Fe) from placement to 7 d. Allocation of birds to dietary treatments was completely randomized on day 8. Treatments had increasing Fe derived from commercial limestone and dicalcium phosphate (analyzed Fe 7,218 and 4,783 mg/kg, respectively) progressively replacing calcium carbonate and phosphoric acid to provide graded increases in total Fe (analyzed Fe in the feeds were 57.6 ± 2.1, 92.0 ± 2.3, 124.1 ± 2.7, 159.3 ± 3.1, 187.2 ± 3.2, 223.7 ± 3.6 mg/kg, respectively). There were no effects of dietary Fe on live performance, hematocrit, and hemoglobin the end of the study on day 28 (P > 0.05). Increasing dietary Fe from commercial limestone and dicalcium phosphate led to a linear reduction in the percent ileal digestible Fe. However, linear increments in Fe retention, serum ferritin and liver Fe occurred when compared to feeds without Fe derived from limestone and phosphate dicalcium. It is concluded that Fe from limestone and dicalcium phosphate can be partially utilized by broiler chickens. It was estimated that the Fe retained from limestone and dicalcium phosphate is of 1.9%. Broilers fed corn-soy feeds (58.2 mg/kg Fe) do not require supplemental Fe.

Cancer survivorship was recently identified as a prostate cancer (PCa) research priority by PIONEER, a European network of excellence for big data in PCa. Despite being a research priority, cancer survivorship lacks a clear and agreed definition, and there is a distinct paucity of patient-reported outcome (PRO) data available on the subject. Data collection on cancer survivorship depends on the availability and implementation of (validated) routinely collected patient-reported outcome measures (PROMs). There have been recent advances in the availability of such PROMs. For instance, the European Organisation for Research and Treatment of Cancer Quality of Life Group (EORTC QLG) is developing survivorship questionnaires. This provides an excellent first step in improving the data available on cancer survivorship. However, we propose that an agreed, standardised definition of (prostate) cancer survivorship must first be established. Only then can real-world data on survivorship be collected to strengthen our knowledge base. With more men than ever surviving PCa, this type of research is imperative to ensure that the quality of life of these men is considered as much as their quantity of life. Patient summary: As there are more prostate cancer survivors than ever before, research into cancer survivorship is crucial. We highlight the importance of such research and provide recommendations on how to carry it out. The first step should be establishing agreement on a standardised definition of survivorship. From this, patient-reported outcome measures can then be used to collect important survivorship data.

Introduction: Participant characteristics are known to affect group discourse and discussion outcomes. In medicine, many decisions are made by group consensus, therefore an understanding of these factors is highly relevant. We aimed to measure the effects of participant characteristics on tumor board discussions. Methods: We performed a prospective, multi-institution, quantitative study of multi-disciplinary virtual tumor board meetings. Participant characteristics included age, gender, and clinical discipline. Outcomes of interest were speech events, duration, and discourse style. Participant impressions was assessed by a post-hoc survey. Results: A total of 361 cases were discussed across 32 virtual meetings. Of the 283 attendees, 66.4 % were women, and all moderators were men. Women comprised 43 % of the 54 speakers, thus speaking less than male attendees (p

Objective: To determine associations between post-emergency department (ED) management pathways and downstream opioid prescriptions in patients seeking care for incident neck and/or back pain. Patients and Methods: We identified patients seeking first-time ED care for neck and/or back pain from January 1, 2013, through November 6, 2017. We reported demographic characteristics and opioid prescriptions across management pathways using descriptive statistics and assessed the relative risk of any opioid prescription 12 months post-ED visit among 5 different post-ED management pathways using Poisson regression adjusted for patient demographic characteristics. Results: Within 12 months after the index ED visit, 58.0% (n=10,949) were prescribed an opioid, with most patients prescribed an opioid within the first week (average daily morphine milligram equivalents of 6.8 mg (SD 9.6 mg). The morphine milligram equivalents decreased to 0.7 mg (SD 8.2 mg) by week 4 and remained consistently less than 1 mg between week 4 and 12 months. Compared with the ED to primary care provider pathway, the relative risk of opioid prescription between 7 days and 12 months after the index ED visit was similar for the ED to physical therapy pathway, higher for both the ED to hospital admission or repeat ED visit pathway (30% increase; relative risk (RR), 1.3; 95% CI, 1.17-1.44) and the ED to specialist pathway (19% increase; RR, 1.19; 95% CI, 1.07-1.33), and lower in the ED with no follow-up visits pathway (41% decrease; RR, 0.59; 95% CI, 0.54-0.65). Conclusion: In general, more conservative care was associated with lower opioid prescription rates, and escalated care was associated with higher opioid prescription rates.

Background: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is an effective treatment for refractory epilepsy; however, seizure outcome varies among individuals. Identifying a reliable noninvasive biomarker to predict good responders would be helpful. Objectives: To test whether the functional connectivity between the ANT-DBS sites and the seizure foci correlates with effective seizure control in refractory epilepsy. Methods: We performed a proof-of-concept pilot study of patients with focal refractory epilepsy receiving ANT-DBS. Using normative human connectome data derived from 1000 healthy participants, we investigated whether intrinsic functional connectivity between the seizure foci and the DBS site was associated with seizure outcome. We repeated this analysis controlling for the extent of seizure foci, distance between the seizure foci and DBS site, and using functional connectivity of the ANT instead of the DBS site to test the contribution of variance in DBS sites. Results: Eighteen patients with two or more seizure foci were included. Greater functional connectivity between the seizure foci and the DBS site correlated with more favorable outcome. The degree of functional connectivity accounted for significant variance in clinical outcomes (DBS site: |r| = 0.773, p

The driving style of an automated vehicle (AV) needs to be comfortable to encourage the broad acceptance and use of this newly emerging transport mode. However, current research provides limited knowledge about what influences comfort, how this concept is described, and how it is measured. This knowledge is especially lacking when comfort is linked to the AV’s driving styles. This paper presents results from an online workshop with nine experts, all with hands-on experience of AVs and a long track record of research in this context. Using online tools, experts were invited to introduce concepts they considered relevant to comfort/discomfort in currently available modes of transport which offer a ride (taxi/bus/train) to users and compare these to the concepts used to define comfort and discomfort in AVs. Results showed that a wide range of terms were used to describe user comfort and discomfort for both modes. Although all terms used for existing vehicles were found to apply to AVs, additional terms were proposed for determining comfort/discomfort of AVs. For example, to enhance comfort in AVs, designers should consider good communication channels, as well as ensuring that the AV’s capabilities match users’ expectations. Results also revealed that more terms were used, overall, to define discomfort, and that a comfortable ride in AVs is not just about mitigating discomfort. New concepts specific to AVs were also revealed when considering what increases their discomfort, such as whether riders’ safety and privacy are affected, or if they feel in control. Experts’ input from the workshop was used to enhance and expand a simple conceptual framework, explaining how AV driving styles, as well as other, non-driving-related factors, affect user comfort. It is hoped that this framework provides a more comprehensive list of the concepts affecting user comfort, also allowing more accurate measurement of the concept. As well as allowing for a more accurate comparison between empirical studies measuring comfort in AVs, this study will facilitate the design of more comfortable and acceptable automated driving for future vehicles.

This position paper elaborates on the significance and implications of the world's soil systems as climate regulators in their still unexploited potential to fight climate change and in the aspiration of modern society aiming at sustainable use of resources and safeguarding of life on the planet.The paper stresses the importance of Soil Management and Land Conservation as essential tools for the longevity of civilizations.Under the current climate change, there is a close relationship between climate factors and soil performance, but soil influences climate parameters, making it an important climate regulator.The text calls for a vision that recognizes soil as a natural system with socio-economic benefits and ecological functions and mentions the European Green Deal and United Nations Sustainable Development Goals as initiatives addressing soil and land issues.The text emphasizes the need for a profound and intelligent radical change in environmental, social, and economic approaches to address climate change. It highlights the responsibility of the current generation to make the right choices for the planet and future generations.

Environmental oligotrophic bacteria are suspected to be highly relevant carriers of antimicrobial resistance (AMR). However, there is a lack of validated methods for monitoring in the aquatic environment. Since extended-spectrum β-lactamases (ESBLs) play a particularly important role in the clinical sector, a culturing method based on R2A-medium spiked with different combinations of β-lactams was applied to quantify β-lactamase-producing environmental bacteria from surface waters. In German surface water samples (n = 28), oligotrophic bacteria ranging from 4.0 × 103 to 1.7 × 104 CFU per 100 mL were detected on the nutrient-poor medium spiked with 3rd generation cephalosporins and carbapenems. These numbers were 3 log10 higher compared to ESBL-producing Enterobacteriales of clinical relevance from the same water samples. A MALDI-TOF MS identification of the isolates demonstrated, that the method leads to the isolation of environmentally relevant strains with Pseudomonas, Flavobacterium, and Janthinobacterium being predominant β-lactam resistant genera. Subsequent micro-dilution antibiotic susceptibility tests (Micronaut-S test) confirmed the expression of β-lactamases. The qPCR analysis of surface waters DNA extracts showed the presence of β-lactamase genes (blaTEM, blaCMY-2, blaOXA-48, blaVIM-2, blaSHV, and blaNDM-1) at concentrations of 3.7 (±1.2) to 1.0 (±1.9) log10 gene copies per 100 mL. Overall, the results demonstrate a widespread distribution of cephalosporinase and carbapenemase enzymes in oligotrophic environmental bacteria that have to be considered as a reservoir of ARGs and contribute to the spread of antibiotic resistance.

Summary: Background: Despite the high prevalence and major disability associated with fatigue and cognitive deficits after SARS-CoV-2 infection, little is known about long-term trajectories of these sequelae. We aimed to assess long-term trajectories of these conditions and to identify risk factors for non-recovery. Methods: We analyzed longitudinal data from the population-based COVIDOM/NAPKON-POP cohort in Germany. Participants with confirmed SARS-CoV-2 infection were assessed at least 6 months (baseline) and again at least 18 months (follow-up) after infection using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Scale (cutoff ≤ 30) and the Montreal Cognitive Assessment (MoCA, cutoff ≤ 25). Predictors of recovery from fatigue or cognitive deficits between assessments were identified through univariate and multivariable logistic regression models. The COVIDOM study is registered at the German registry for clinical studies (DRKS00023742) and at ClinicalTrials.gov (NCT04679584). Findings: Between 15 November 2020 and 9 May 2023, a total of 3038 participants were assessed at baseline (median 9 months after infection) and 83% responded to invitations for follow-up (median 26 months after infection). At baseline, 21% (95% confidence interval (CI) [20%, 23%]) had fatigue and 23% (95% CI [22%, 25%]) had cognitive deficits according to cutoff scores on the FACIT-Fatigue or MoCA. Participants with clinically relevant fatigue (at baseline) showed significant improvement in fatigue scores at follow-up (Hedges’ g [95% CI] = 0.73 [0.60, 0.87]) and 46% (95% CI [41%, 50%]) had recovered from fatigue. Participants with cognitive deficits showed a significant improvement in cognitive scores (g [95% CI] = 1.12 [0.90, 1.33]) and 57% (95% CI [50%, 64%]) had recovered from cognitive deficits. Patients with fatigue exhibiting a higher depressive symptom burden and/or headache at baseline were significantly less likely to recover. Significant risk factors for cognitive non-recovery were male sex, older age and

Introduction: Targeting the tumor microenvironment may enhance response to immunotherapy (immune checkpoint inhibitors) and improve outcomes for patients. This study tested the safety and efficacy of vorolanib, a novel tyrosine kinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and c-KIT, in combination with programmed cell death protein 1 blockade using nivolumab for refractory thoracic malignancies. Methods: This single-arm multicenter study enrolled patients with extensive-stage SCLC, thymic carcinoma, and NSCLC, either naive or had progressed on previous chemotherapy or immune checkpoint inhibitors (either primary or acquired resistance). The primary objective of phase 1 was to determine the maximum tolerated dose, and the primary end point for each dose-expansion cohort was the objective response rate. Results: A total of 88 patients were enrolled in phase 1 (n = 11) and dose expansion (n = 77) cohorts. Transaminitis was dose-limiting and expansion proceeded with oral vorolanib 200 mg daily combined with intravenous nivolumab 240 mg every 2 weeks. The objective response rate per cohort were as follows: NSCLC naive 33% (five of 15, 95% confidence interval [CI]: 13%–60%), NSCLC primary refractory 5.9% (one of 17, 95% CI: 0%–17.6%), NSCLC acquired resistance 11.1% (two of 18, 95% CI: 0%–27.8%); SCLC 0% (zero of 18), and thymic carcinoma 11% (one of nine, 95% CI: 0%–33%). Disease control rate ranged from 11.1% in SCLC (two of 18, 0%–27.8%) to 66.7 % in thymic carcinoma (six of nine, 95% CI: 33.3%–100%). The most common adverse events were fatigue (32%), aspartate transaminase (27%) and alanine transaminase elevation (25%), and diarrhea (19%). Transaminitis was more common in patients with thymic carcinoma than other tumors. Conclusions: Vorolanib plus nivolumab had a manageable safety profile and may have clinical benefits in various thoracic malignancies. The disease control rate in thymic malignancies warrants further assessment.

Summary: Background: Lyme disease is caused by the bacteria Borreliella burgdorferi sensu lato (Bb) transmitted to humans from the bite of an infected Ixodes tick. Current diagnostics for Lyme disease are insensitive at the early disease stage and they cannot differentiate between active infections and people with a recent history of antibiotic-treated Lyme disease. Methods: Machine learning technology was utilized to improve the prediction of acute Lyme disease and identify sialic acid and galactose sugar structures (N-glycans) on immunoglobulins associated specifically at time points during acute Lyme disease time. A plate-based approach was developed to analyze sialylated N-glycans associated with anti-Bb immunoglobulins. This multiplexed approach quantitates the abundance of Bb-specific IgG and the associated sialic acid, yielding an accuracy of 90% in a powered study. Findings: It was demonstrated that immunoglobulin sialic acid levels increase during acute Lyme disease and following antibiotic therapy and a 3-month convalescence, the sialic acid level returned to that found in healthy control subjects (p

The Institutional Review Board (IRB) is fundamental to conducting ethical research involving human subjects. IRB applications require detailed descriptions of the research and specific indications of how the research will be implemented. This can be difficult for inexperienced researchers. Preparing the application is a significant time commitment, even for experienced researchers. In order to lighten the administrative burden on busy clinical professionals, this software application will automatically generate a draft human subject research protocol (the most laborious element of an IRB application) based on responses to a short form. This technology uses generative AI and a custom literature search plug-in to draft the protocol from succinct, user-provided details. User inputs include a brief description of the research, including the hypothesis, inclusion/exclusion criteria, and the study design type (e.g., randomized clinical trial). This tool can expedite the IRB application creation process, provide additional consistency for reviewers, and may reduce clinician researcher burnout through a reduction in clerical work thereby facilitating participation in meaningful research.

Background: In untreated ALK-positive non-small cell lung cancer no randomized controlled trials (RCTs) are available directly comparing next-generation ALK-inhibitors. We conducted a sensitivity analysis using the likelihood of being helped or harmed (LHH). Methods: Phase III trials comparing ALK-inhibitors to crizotinib were included. Efficacy outcomes were progression-free survival (PFS), objective response rate (ORR), PFS in patients with brain metastases and intracranial ORR. Safety outcomes were grade 3–4 adverse events (AEs), dose reductions and discontinuations. Results: Six RCTs (1524 patients) were included. Lorlatinib and brigatinib had the lowest NNT for intracranial outcomes. Alectinib demonstrated favourable LHHs for grade 3–4 AEs, dose reductions and discontinuations. Brigatinib LHHs were low for common AEs, mainly laboratory anomalies and hypertension. Ensartinib showed mainly skin toxicity. Lorlatinib LHHs were low for specific grade 3–4 AEs, mainly metabolic alterations. Conclusions: The four ALK-inhibitors exhibited favourable risk-benefit ratios. Lorlatinib showed the lowest NNT for systemic efficacy and, alongside with Brigatinib, lower NNTs for intracranial efficacy. Alectinib exhibited higher LHHs for AEs. Registration: PROSPERO registration number: CRD42023389101.

Objective: Aneurysmal subarachnoid hemorrhage (aSAH) and angiographically negative subarachnoid hemorrhage (anSAH) cause an abrupt rise in intracranial pressure, resulting in shearing forces, causing damage to the white matter tracts. This study aims to investigate whole-brain white matter abnormalities with diffusion kurtosis imaging (DKI) after both aSAH and anSAH and explores whether these abnormalities are associated with impaired cognitive functioning. Methods: Five months post-ictus, 34 patients with aSAH, 24 patients with anSAH and 17 healthy controls (HC) underwent DKI MRI scanning and neuropsychological assessment (measuring verbal memory, psychomotor speed, executive control, and social cognition). Differences in DKI measures (fractional anisotropy, mean diffusivity, axial diffusivity [AD], radial diffusivity, and mean kurtosis) were examined using tract-based spatial statistics. Significant voxel masks were then correlated with neuropsychological scores. Results: All DKI measures differed significantly between patients with aSAH and HC, but no significant differences were found between patients with anSAH and HC. Although the two SAH groups did not differ significantly on all DKI parameters, effect sizes indicated that the anSAH group might be more similar to HC. Cognitive impairments were found for both SAH groups relative to HC. No significant associations were found between these impairments and white matter abnormalities in the aSAH group, but lower psychomotor speed scores were associated with higher AD values (r = -0.41, p = 0.04) in patients with anSAH. Conclusions: Patients with aSAH showed significant white matter diffusion abnormalities, while the anSAH group, despite cognitive deficits, did not. However, there were no significant differences between the SAH groups, and no correlations between DKI metrics and cognitive measures, except for one test on psychomotor speed in the anSAH group. Overall, this study suggests that while anSAH may not be as severe as aSAH, it is still not a benign condition. Further research with larger anSAH cohorts is necessary to gain a more precise understanding of white matter injuries, particularly regarding their prevalence.

Patients who receive allogeneic hematopoietic stem cell transplantation (alloHSCT) are at risk for developing persistent thrombocytopenia. Here, we describe treatment with avatrombopag, a thrombopoietin receptor agonist, in a pediatric patient with chronic, severe, transfusion-dependent thrombocytopenia (100 × 103/µL. No adverse events or medication toxicities have been reported, and he has resumed his pre-alloHSCT activities.

The purpose of the European Green Deal and the regulation associated with the so-called EU Taxonomy for Sustainable Activities is to lead capital flows towards sustainable investments. According to the European Commission this is necessary to finance solutions for the immense challenges ahead, such as climate change, social inequality, and loss of biodiversity. However, academic research raises concerns that sustainable investments may earn lower risk-adjusted returns in the long run. The European Supervisory Authorities identify greenwashing risks and pronounce the limited ability of retail investors to make informed investment decisions. The aim of this perspective article is to provide suggestions for a regulation on relevant information on sustainable investments provided by financial service providers to retail investors. Therefore, the existing regulations are put in relation with recent research on investments considering ESG issues. To enable retail investors' self-determined decision-making, financial service providers such as banks, mutual funds, and financial advisors must provide easily accessible, clear, and easily understandable information regarding the ESG-conformity of the offered financial products. In addition, financial service providers must inform retail investors about some specific risks that can arise from a narrow focus on ESG assets such as under-diversification, an overweight of large stocks, and returns that can be lower than the market return.

Resting-state fMRI can be used to identify recurrent oscillatory patterns of functional connectivity within the human brain, also known as dynamic brain states. Alterations in dynamic brain states are highly likely to occur following pediatric mild traumatic brain injury (pmTBI) due to the active developmental changes. The current study used resting-state fMRI to investigate dynamic brain states in 200 patients with pmTBI (ages 8-18 years, median = 14 years) at the subacute (∼1-week post-injury) and early chronic (∼ 4 months post-injury) stages, and in 179 age- and sex-matched healthy controls (HC). A k-means clustering analysis was applied to the dominant time-varying phase coherence patterns to obtain dynamic brain states. In addition, correlations between brain signals were computed as measures of static functional connectivity. Dynamic connectivity analyses showed that patients with pmTBI spend less time in a frontotemporal default mode/limbic brain state, with no evidence of change as a function of recovery post-injury. Consistent with models showing traumatic strain convergence in deep grey matter and midline regions, static interhemispheric connectivity was affected between the left and right precuneus and thalamus, and between the right supplementary motor area and contralateral cerebellum. Changes in static or dynamic connectivity were not related to symptom burden or injury severity measures, such as loss of consciousness and post-traumatic amnesia. In aggregate, our study shows that brain dynamics are altered up to 4 months after pmTBI, in brain areas that are known to be vulnerable to TBI. Future longitudinal studies are warranted to examine the significance of our findings in terms of long-term neurodevelopment.

A novel distraction technique is described for total hip arthroplasty in symptomatic high hip dislocation (Crowe IV) combining an intramedullary motorized lengthening nail with a pelvic support plate to gradually stretch hip soft tissues (distalization) and performing total hip arthroplasty with the cup in the primary acetabulum. Twelve patients (15 hips) were identified in a retrospective study via chart review. Medical records and radiographs were reviewed for details of the initial case parameters, surgical details, magnitude of distalization, duration of treatment, outcomes, and complications. Followed by an average of 67.4 mm of distalization, nearly anatomical cup placement, and equal leg length were achieved in all patients. During distalization, pain level was low with acceptable range of motion. One unplanned surgery and no complications with long-term sequelae occurred.

Assessing root sources of three uncertainties – parameterization of soil hydraulic characteristics, boundary conditions, and estimation of source/sink terms – is a significant challenge in soil water transport modeling. This study aims to evaluate the uncertainty of three each widely-used parameter estimation methods affecting plot-scale water dynamics. The study employs HYDRUS, a process-based hydrologic model, to incorporate these uncertainties and compare model predictions to measured values in a semiarid Inner Mongolia steppe, China. Soil hydraulic parameters are determined using two direct methods (laboratory-derived approach and evaporation method) and one indirect method (neural network). While each hydraulic parameter method generally simulates soil moisture dynamics, the evaporation method performed better, especially under dry conditions. This suggests that measuring the intensity properties, such as unsaturated hydraulic conductivity, with the evaporation method is crucial for reasonable soil moisture simulation. The study also demonstrates the impact of different applied boundary conditions on simulated soil moisture, specifically the partitioning of reference FAO evapotranspiration via one direct method (soil fraction cover) and two indirect methods (leaf area index and crop height). The partitioning via soil fraction cover reflected a better simulation. Additionally, the study compares the uncertainties of root water uptake function with root growth parameters and constant root depth referenced to grass and pasture, and finds no significant difference among them. Comparing three sources of uncertainty in predicting soil moisture, the study concludes that the input soil hydraulic parameter is more sensitive than evapotranspiration partitioning or representation of root water uptake function. Our study highlights that measuring soil intensity properties can better reflect the effects of land use change, such as compaction, on field water transports.

Traditional methods for determining superoxide dismutase (SOD) content and catalase (CAT) activity rely on measuring the absorbance of individual tissue (biological) samples using a cuvette and spectrophotometer, rather than cell cultures. Although there are kits available for SOD and CAT assays, these allow for high-throughput analysis of samples and might be too expensive for research laboratories in countries from the Global South, such as South Africa. This paper describes a simple and cost-effective method to determine SOD content and CAT activity in mammalian cell cultures following exposure to environmental chemical mixtures by measuring absorbance in 96-well microplates. Moreover, the equipment used for this method is considered standard for cell culture laboratories, while the reagents and consumables are easily obtainable. • Antioxidant enzyme levels can be measured in vitro in cell cultures. • The supernatant obtained can be used to determine protein concentration, SOD content, and CAT activity. • This method is simple and affordable, allowing for the analysis of multiple samples (up to 32 samples per microplate).

The state-of-the-art magnesia-based dry vibrateable tundish linings are predominantly bonded by resin. However, besides high energy consumption, the pyrolysis of the resin-containing lining during the tundish heat-up process generates hazardous gases and carbon residues, resulting in an unwanted carbon pick by the molten steel after the finished ladle treatment.Hence, the aim of this study was to develop novel carbon free binder system, therefore combine acid-based with thermally activated binder systems. Their influence on the physical and mechanical properties were investigated. Additionally, utilizing a unique steel casting simulator, the influence of newly developed lining compositions on the steel quality compared to a reference binder system was tested and analyzed. The influence on the inclusion population in the molten steel and the steel quality was evaluated.Newly developed compositions showed no significant influence on the steel cleanliness, only a minor change in the population could be detected.

Background: Emotion dysregulation is a characteristic central to borderline personality disorder (BPD). Valuably, verbal behaviour can provide a unique perspective for studying emotion dysregulation in BPD, with recent research suggesting that the varieties of emotion words one actively uses (i.e., active emotion vocabularies [EVs]) reflect habitual experience and potential dysregulation therein. Accordingly, the present research examined associations between BPD and active EVs across two studies. Methods: Study 1 (N = 530) comprised a large non-clinical sample recruited from online forums, whereby BPD traits were measured via self-report. Study 2 (N = 64 couples) consisted of mixed-gender romantic couples in which the woman had a BPD diagnosis, as well as a control group of couples. In both studies, participants’ verbal behaviours were analysed to calculate their active EVs. Results: Results from both studies revealed BPD to be associated with larger negative EV (i.e., using a broad variation of unique negative emotion words), which remained robust when controlling for general vocabulary size and negative affect word frequency in Study 2. The association between BPD and negative EV was insensitive to context. Limitations: Limitations of this research include: 1) the absence of a clinical control group; 2) typical constraints surrounding word-counting approaches; and 3) the cross-sectional design (causality cannot be inferred). Conclusions: Our findings contribute to BPD theory as well as the broader language and emotion literature. Importantly, these findings provide new insight into how individuals manifesting BPD attend to and represent their emotional experiences, which could be used to inform clinical practice.

Objective: Fragile X Syndrome (FXS) is the leading monogenic cause of intellectual disability and autism spectrum disorder. Currently, there are no established biomarkers for predicting and monitoring drug effects in FXS, and no approved therapies are available. Previous studies have shown electrophysiological changes in the brain using electroencephalography (EEG) in individuals with FXS and animal models. These changes may be influenced by drug therapies. In this study, we aimed to assess the reliability of resting-state EEG measures in individuals with FXS, which could potentially serve as a biomarker for drug discovery. Methods: We collected resting-state EEG data from 35 individuals with FXS participating in placebo-controlled clinical trials (23 males, 12 females; visit age mean+/-std 25.6 +/−8.3). The data were analyzed for various spectral features using intraclass correlation analysis to evaluate test-retest reliability. The intervals between EEG recordings ranged from same-day measurements to up to six weeks apart. Results: Our results showed high reliability for most spectral features, with same-day reliability exceeding 0.8. Features of interest demonstrated ICC values of 0.60 or above at longer intervals. Among the features, alpha band relative power exhibited the highest reliability. Conclusion: These findings indicate that resting-state EEG can provide consistent and reproducible measures of brain activity in individuals with FXS. This supports the potential use of EEG as an objective biomarker for evaluating the effects of new drugs in FXS. Significance: The reliable measurements obtained from power spectrum-based resting-state EEG make it a promising tool for assessing the impact of small molecule drugs in FXS.

Chemically-induced models of intestinal inflammation are a useful tool for the study of immune responses and inflammation. Although well established in mammals, application of these models is currently limited in teleosts. Based on a variety of factors, including genetic diversity, known toxicological sensitivity, and economic importance, we propose salmonids as a model family of fishes for studying intestinal inflammation. We present a rainbow trout model of chemically-induced intestinal inflammation using 2,4,6-trinitrobenzene sulfonic acid (TNBS), assessed through histological analysis of primary and secondary intestinal folding, enterocyte morphology, goblet cell size and frequency, tissue layer thickness, and immune cell infiltration. Twenty-four hours after treatment with one of three concentrations of TNBS, trout developed classic signs of intestinal inflammation, including notably increased thickness of primary and secondary folds, and increased immune cell infiltration as compared to controls. This study provides a simple, reproducible model of rapid TNBS-induction of moderate intestinal inflammation.

Summary: IGHV3-33-encoded antibodies are prevalent in the human humoral response against the Plasmodium falciparum circumsporozoite protein (PfCSP). Among VH3-33 antibodies, cross-reactivity between PfCSP major repeat (NANP), minor (NVDP), and junctional (NPDP) motifs is associated with high affinity and potent parasite inhibition. However, the molecular basis of antibody cross-reactivity and the relationship with efficacy remain unresolved. Here, we perform an extensive structure-function characterization of 12 VH3-33 anti-PfCSP monoclonal antibodies (mAbs) with varying degrees of cross-reactivity induced by immunization of mice expressing a human immunoglobulin gene repertoire. We identify residues in the antibody paratope that mediate cross-reactive binding and delineate four distinct epitope conformations induced by antibody binding, with one consistently associated with high protective efficacy and another that confers comparably potent inhibition of parasite liver invasion. Our data show a link between molecular features of cross-reactive VH3-33 mAb binding to PfCSP and mAb potency, relevant for the development of antibody-based interventions against malaria.

The policy report published by the European Academies Science Advisory Council (EASAC) introduces a new concept, ‘Regenerative Agriculture’, but but does not provide an exact definition for the term. The roots of the ideological concept lie in the French Enlightenment period, when food supplies of local communities were not a real concern. Nowadays, agriculture struggles to keep up with the population explosion. The EASAC position paper sets ecological farming and large-scale agriculture against each other despite the fact that their common aim is to supply the world population with high quality food and industrial raw materials. The comments in the present paper aim to provide a more nuanced approach to some of the ideas discussed in the EASAC report, with special emphasis on the fact that, although the report formulates noble aims, it does not present concrete suggestions on how they could be achieved economically.

Introdução/Objetivo: A endocardite infecciosa é uma inflamação do endocárdio e das válvulas cardíacas comumente causada por microrganismos. Entre os fatores de risco estão o uso de dispositivos cardíacos, doença valvar e diabetes mellitus. A incidência, considerada rara, é de 3 a 10 casos a cada 100.000 pessoas; entretanto, é potencialmente fatal e de difícil diagnóstico. A mortalidade intra-hospitalar é de cerca de 18% e a mortalidade em um ano chega a 40%, atingindo principalmente idosos. Para o diagnóstico laboratorial, a hemocultura é o padrão ouro, porém, em grande parte dos casos, as infecções são causadas por bactérias fastidiosas, resultando em uma hemocultura negativa mesmo na presença do patógeno. O objetivo deste estudo foi avaliar a taxa de positividade e os patógenos identificados em amostras de hemocultura de pacientes com suspeita de endocardite internados no Hospital de Clínicas de Porto Alegre. Métodos: Foi realizado um estudo transversal descritivo retrospectivo utilizando os dados do sistema de informática laboratorial do período 2018 a 2022. Hemoculturas provenientes de pacientes internados com suspeita de endocardite foram incubadas no sistema Bact/Alert (bioMérieux, França) e a identificação bacteriana foi realizada pelo Vitek©MS (bioMérieux, França). Resultados: No período analisado, foram encaminhadas amostras de 691 pacientes para pesquisa de endocardite com uma taxa de positividade de 6,8% (n = 47). As bactérias mais prevalentes foram as espécies de Staphylococcus coagulase negativa 47% (n = 22), dentre elas Staphylococcus epidermidis (n = 8), Staphylococcus hominis (n = 8) foram as mais frequentes, seguido de Staphylococcus capitis (n = 3), Staphylococcus haemolyticus (n = 2) e Staphylococcus lugdunensis (n = 1). Staphylococcus aureus foi detectado em 36% (n = 17) dos pacientes. Os demais patógenos identificados foram: Klebsiella pneumoniae (n = 3), Pseudomonas aeruginosa (n = 2), Serratia marcescens (n = 1), Enterobacter spp. (n = 1) e Acinetobacter lwoffii (n = 1). Um total de 70% dos pacientes (n = 33) tiveram duas amostras de hemocultura positivas para o mesmo microrganismo. Conclusão: Este estudo indicou um predomínio de Staphylococcus em pacientes com suspeita de endocardite infecciosa. No entanto, não é possível definir a doença apenas com os dados microbiológicos pois, conforme Duke-ISCVID IE Criteria (2023), a avaliação dos dados clínicos e exames de imagem são necessários para complementar o diagnóstico.

Introdução/Objetivo: Clostridioides Difficile (CDI) é um bacilo gram-positivo produtor de esporos e toxinas relacionado com desordens do trato gastrointestinal. Diarreia e colite pseudomembranosa são as principais manifestações clínicas que ocorrem pela produção das toxinas A, B e binária, e das enzimas hialuronidase e colagenase, que danificam o citoesqueleto da célula epitelial, causando a secreção de fluido e inflamação. CDI é uma grande ameaça à saúde. Em 2017, foram estimados 223.900 casos em pacientes hospitalizados e 12.800 mortes nos Estados Unidos. O objetivo do estudo foi avaliar a prevalência de CDI produtor de toxina e a prevalência da cepa hipervirulenta, relacionando com o local de internação e idade dos pacientes no Hospital de Clínicas de Porto Alegre (HCPA). Materiais e métodos: Estudo retrospectivo para análise da prevalência de CDI produtor de toxina. Foram utilizados os dados do sistema de informática laboratorial do período de janeiro a 30 de abril de 2023. O diagnóstico de CDI foi realizado através de uma testagem em duas etapas: primeiramente, as amostras foram submetidas a um imunoensaio fluorescente (ECO F GDH, ECO Diagnóstica) para a detecção da enzima Glutamato Desidrogenase (GDH). Amostras GDH positivas foram submetidas à técnica de qPCR (Xpert® C. difficile BT, Cepheid) para detecção dos genes que codificam as toxinas B (tcdB) e binária (cdt), assim como a deleção em tcdC que identifica a cepa hipervirulenta pertencente ao ribotipo 027 e resistente às fluoroquinolonas. Resultados: Foram investigadas 473 amostras de fezes de pacientes com diarreia clínica. Encontrou-se uma prevalência de CDI toxigênico em 12,4% (59/473), dos quais 5 pacientes testaram positivo para a cepa hipervirulenta. Apesar de ser relatada a idade avançada como fator de risco, 33% dos pacientes com CDI toxigênico estavam na faixa etária de 0 a 10 anos, enquanto que 27% tinham idade acima de 60 anos. 16,9% dos pacientes tinham de 18 a 30 anos e 22% tinham entre 31 e 59 anos. Quanto ao local da solicitação, observa-se uma predominância de testes da internação pediátrica (23,7%) e internação clínica (22%). Conclusão: A prevalência de CDI toxigênico foi de 12,4% nas amostras analisadas. Esses resultados mostram a importância da epidemiologia local para melhorar o tratamento e as medidas de controle de infecção. CDI é uma importante infecção nosocomial e incorre em tratamentos caros, isolamento do paciente e maior tempo de internação.

Introdução: Os vírus Influenza A e B (FLU A e B) são responsáveis por epidemias sazonais, sendo considerados os agentes etiológicos mais comumente relacionados às síndromes respiratórias agudas. Segundo a atualização mais recente do Sistema Global de Vigilância e Resposta à Influenza, 63,7% dos casos globais de influenza foram devido a um dos subtipos de FLU A e 36,3% são casos de FLU B. Este estudo procurou relatar os casos de FLU A e B no contexto de um hospital terciário do Sul do país. Métodos: Foi realizado um estudo transversal descritivo no período de fevereiro de 2022 a maio de 2023 para identificar a positividade dos vírus FLU A e B. Foram avaliados os resultados dos exames encaminhados para o Laboratório de Biologia Molecular do Hospital de Clínicas de Porto Alegre para pesquisa de vírus respiratório (Resp-4-Plex, Abbott Molecular Inc., EUA). Resultados: Foram realizados 7.556 exames para a pesquisa de vírus respiratórios na instituição no período de fevereiro de 2022 a maio de 2023. Desse total, 5,1% (386/7.556) apresentaram positividade para FLU A e 1,37% (104/7.556) apresentaram positividade para FLU B. No ano de 2022, o período de maior positividade foi entre fevereiro e maio, em que foram realizados 1.569 testes, com uma taxa de 5,22% (82/1.569) de positivos para FLU A e 0,38% (6/1.569) positivos para FLU B. No mesmo período no ano de 2023 foram realizados 1.616 testes, sendo 9,28% (150/1.616) casos positivos para FLU A e 5,07% (82/1.616) casos positivos para FLU B. Essa taxa de positividade entre os períodos analisados reflete um aumento na circulação do FLU B quando comparado a 2022 que correspondia a 6,8% do total de casos de influenza e em 2023 está representando 35,3% dos casos. Conclusões: Nos últimos anos os vírus respiratórios apresentaram uma alteração no perfil de transmissão, principalmente devido à pandemia de COVID-19. Essa mudança de comportamento deve-se tanto à predominância do SARS-CoV-2 quanto à adoção de medidas de prevenção como uso de máscaras e isolamento social. Entretanto, a falta crônica da exposição natural ao vírus, sustentada a outros subtipos do vírus influenza pode ter impactado no aumento da circulação do FLU B após esse período de medidas de restrição. Essa mudança de comportamento ressalta a importância da vigilância genômica e do conhecimento do perfil epidemiológico desses vírus e esses dados reforçam a importância de uma cobertura vacinal adequada para reduzir os impactos no sistema público de saúde.

Introdução/objetivo: O poliomavírus BK (BKV) é um vírus de dupla fita de DNA pertencente à família Polyomaviridae. Estima-se que 80-90% da população adulta seja soropositiva para BKV, ficando em fase latente no organismo após infecção primária que, em sua maioria, é assintomática. Este vírus possui tropismo pelo aparelho urinário e pode persistir nele por um longo período de tempo, o que o torna um importante agente infeccioso oportunista para pacientes receptores de transplante renal. Situações como disfunção renal e nefropatia causadas pelo vírus BK em pacientes transplantados causam preocupação devido ao dano e, consequentemente, o risco da perda do enxerto ao reduzir a imunossupressão do aloenxerto. Diante disto, o objetivo do estudo foi realizar um levantamento dos casos positivos de BKV, com quantificação da carga viral no plasma, em um hospital terciário de Porto Alegre. Métodos: Foi realizado um estudo transversal descritivo do período de janeiro a junho de 2022 para análise da prevalência de BKV em amostras de plasma. Foram avaliados os resultados obtidos pela pesquisa quantitativa do BKV (kit Xgen Master BKV, Mobius), através da técnica de PCR em tempo real (limite de detecção de 200 cópias/mL), realizada pelo Laboratório de Biologia Molecular do Hospital de Clínicas de Porto Alegre. Resultados: No período observado foram realizadas 323 análises de BKV quantitativo em plasma de pacientes transplantados. Os pacientes eram majoritariamente do gênero masculino (64%), com mediana de idade de 49 anos (IIQ: 36-61), 234 (72%) transplantados renais. Foram positivos para BKV 18% (n = 59) das amostras, com log abaixo de 4 e log ≥ 4 em 34 (41%) e 25 (59%) amostras, respectivamente. Conclusão: A prevenção aos danos causados pela infecção por BK é essencial para o sucesso dos transplantes renais. Com a quantificação do BKV, é possível monitorar o aumento da sua carga viral e, dessa forma, avaliar precocemente a reativação da infecção possibilitando uma ágil intervenção.