Identifying potential drug targets in the kinomes of two monogenean species.

Protein kinases are enzymes involved in essential biological processes such as signal transduction, transcription, metabolism, and the cell cycle. Human kinases are targets for several drugs approved by the US Food and Drug Administration. Therefore, the identification and classification of kinases in other organisms, including pathogenic parasites, is an interesting subject of study. Monogeneans are platyhelminths, mainly ectoparasites, capable of causing health problems in farmed fish. Although some genomes and transcriptomes are available for monogenean species, their full repertoire of kinases is unknown. The aim of this study was to identify and classify the putative kinases in the transcriptomes of two monogeneans, Rhabdosynochus viridisi and Scutogyrus longicornis, and then to predict potential monogenean drug targets (MDTs) and selective inhibitor drugs using computational approaches. Monogenean kinases having orthologs in the lethal phenotype of C. elegans but not in fish or humans were considered MDTs. A total of 160 and 193 kinases were identified in R. viridisi and S. longicornis, respectively. Of these, 22 kinases, belonging mainly to the major groups CAMK, AGC, and TK, were classified as MDTs, five of which were evaluated further. Molecular docking analysis indicated that dihydroergotamine, ergotamine, and lomitapide have the highest affinity for the kinases BRSK and MEKK1. These well-known drugs could be evaluated in future studies for potential repurposing as anti-monogenean agents. The present study contributes valuable data for the development of new antiparasitic candidates for finfish aquaculture.

Interprofessional interventions and factors that improve end-of-life care in intensive care units: An integratory review.

INTRODUCTION: The changes in health dynamics, caused by the SARS-COVD-2 pandemic and its consequences, generated a greater need to integrate palliative care in the ICU to promote a dignified death. OBJECTIVE: Identify interprofessional interventions and factors that improve the care of patients at the end of life. METHODOLOGY: Integrative review, including experimental, quasi-experimental, observational, analytical, and descriptive studies with correlation of variables, published from 2010 to 2021, identified in COCHRANE, CINAHL, CUIDEN, LILACS, SCIELO, Dialnet, PsychInfo, PubMed, PROQUES, PSYCHOLOGY, JOURNALS, SCIENCEDIRECT, with MeSH/DECS terms: "Critical Care", "IntensiveCare" "Life support care", "Palliative care", "Life Quality", "Right to die". 36,271 were identified, after excluding duplicate title, abstract, year of publication, design, theme, methodological quality, objectives, and content, 31 studies were found. RESULTS: It included 31 articles, 16.7% experimental, 3.3% quasi-experimental, 80% observational, analytical, and descriptive with correlation of variables, 38% published in the United States, 38%, and 19% in Brazil. The pooled sample was 24,779 participants. 32.2% of the studies had level of evidence 1 recommendation (c), and 25.8% level of evidence 2 recommendation (c). This paper synthesises evidence to promote Interprofessional Collaborative Practice in the ICU, improve end-of-life care, and interventions to achieve established therapeutic goals, implement effective care policies, plans, and programmes for critically ill patients and their families; factors that affect palliative care and improve with training and continuing education for health personnel. CONCLUSION: There are interventions to manage physical and emotional symptoms, training strategies and emotional support aimed at health personnel and family members to improve the quality of death and reduce stays in the ICU. The interdisciplinary team requires training on palliative and end-of-life care to improve care.

Comparison of two serological diagnosis tests for bovine paratuberculosis.

Mycobacterium avium subsp. paratuberculosis (MAP) is the causal agent of paratuberculosis (PTBC), a chronic infectious granulomatous enteritis of ruminants. The PTBC diagnosis with commercial ELISA has limitations in sensitivity and specificity, and its results depend on the state of progress of the disease. This research aimed to evaluate two different ELISAs: (a) an "in-house" ELISA with a sonicated antigen obtained from a MAP I47 strain, and (b) a commercial ELISA. In total, the evaluated sample consisted of 394 bovine serum samples from 12 farms in Argentina with high (5-9%) and low (≤ 0.05%) prevalence of PTBC. The evaluation of the new antigen (2.5 µg/mL) was against a 1:50 dilution of the M. phlei faced sera. The cut-off point, sensitivity, and specificity determinations of both techniques were by ROC curve analysis. The area under the curve for the I47 ELISA was 0.9 (CI 95%, 0.93-0.97). With a cut-off point of 8.8%, the sensitivity was 84.3% and the specificity 96.6%. The agreement between both techniques was 0.7 (CI 95%, 0.6-0.8). These results indicate a high discriminative capacity to differentiate positive and negative bovine sera of MAP infection with the I47 ELISA. This result would represent an advantage to dispense with the imported kit.

Evaluation of the incorporation of an IOTA-ADNEX model in the discrimination of adnexal masses in our third-level hospital centre, taking into account the menopausal status of patients. Five years of experience / Evaluación de la incorporación del IOTA-ADNEX model en la discriminación de las masas anexiales en nuestro centro hospitalario de tercer nivel teniendo en cuenta el estado menopáusico en la predicción de malignidad. Cinco años de experiencia

Objective: The objectives were to estimate the performance of the IOTA-ADNEX model test after its incorporation into the ultrasound tests of our third-grade hospital gynecology service, as well as to assess whether its capacity of accuracy is modified when taking into account the patient's menopausal status. Methods: A cross-sectional study was conducted to clinically evaluate the diagnostic performance of the IOTA-ADNEX model test, which was performed between January 2016 and December 2021. The study included 573 women with an adnexal injury who underwent surgical excision within 180 days after ultrasound diagnosis and histological confirmation (gold standard). After the ultrasound exam, the injuries were classified using the ADNEX model. The study estimated the area under the receiver-operating-characteristics curve (AUC) of the ADNEX model for classifying between benign and malignant adnexal masses and compared the performance by menopausal state. Sensitivity and specificity were determined for different cut-off points. Results: Out of the 573 women, 183 (31.9%) had a malignant tumor. The AUC of the ADNEX model for differentiating between benign and malignant adnexal masses at the time of ultrasound examination was 0.92 and the best malignancy threshold, detected by Youden index, was 22.5%. At this cut-off, the sensitivity of the ADNEX model was 91.8% and the specificity was 76.4%. However, it varies according to menopausal status: in the group of pre-menopausal patient, sensitivity was 86.1% (95% CI, 85.4%–86.8%) and specificity was 81.3% (95% CI, 85.4%–86.8%). In the postmenopausal group, sensitivity was 96.1% (95% CI, 95.6%–96.7%) and specificity was 68.5% (95% CI, 68.1%–68.8%)...(AU)

Objetivo: Los objetivos eran estimar el rendimiento del test IOTA ADNEX model después de su incorporación en el estudio ecográfico en nuestro servicio de ginecología, en un hospital de tercer nivel, así como evaluar si su capacidad de precisión se modifica al tener en cuenta el estado menopáusico de la paciente. Método: Se llevó a cabo un estudio transversal para evaluar clínicamente el rendimiento diagnóstico del test IOTA ADNEX model, el cual se realizó entre enero de 2016 y diciembre de 2021. El estudio incluyó a 573 mujeres con una lesión anexial que se sometieron a tratamiento quirúrgico en un plazo de 180 días después del diagnóstico por ecografía y confirmación histológica (gold standard). Después de realizar la ecografía, las lesiones fueron clasificadas utilizando el modelo ADNEX. El estudio estimó el área bajo la curva (AUC) del modelo ADNEX para diferenciar entre masas anexiales benignas y malignas, y se comparó el rendimiento según el estado menopáusico. Se determinó la sensibilidad y la especificidad para diferentes puntos de corte. Resultados: De las 573 mujeres, 183 (31,9%) tenían un tumor maligno. El AUC del modelo ADNEX para diferenciar entre masas anexiales benignas y malignas en el momento del examen ecográfico fue de 0,92 y el umbral de malignidad óptimo, detectado por el índice de Youden, fue del 22,5%. Con este punto de corte, la sensibilidad (SE) del modelo ADNEX fue del 91,8% y la especificidad (SP) fue del 76,4%. Sin embargo, esto varía según el estado menopáusico: en el grupo de pacientes premenopáusicas, la sensibilidad fue del 86,1% (IC del 95%: 85,4-86,8%) y la especificidad fue del 813% (IC del 95%: 85,4-86,8%). En el grupo de pacientes posmenopáusicas, la sensibilidad fue del 96,1% (IC del 95%: 95,6-96,7%) y la especificidad fue del 68,5% (IC del 95%: 68,1-68,8%)...(AU)

Inflammatory lesions of the brainstem: Keys for the diagnosis by MRI.

OBJECTIVE: To describe the magnetic resonance imaging (MRI) findings for the most common inflammatory and immune-mediated diseases that involve the brainstem. CONCLUSION: Inflammatory lesions involving the brainstem are associated with a wide range of autoimmune, infectious, and paraneoplastic syndromes, making the differential diagnosis complex. Being familiar with these entities, their clinical characteristics, and their manifestations on MRI, especially the number of lesions, their shape and extension, and their appearance in different sequences, is useful for orienting the radiological diagnosis.

Lesiones inflamatorias del troncoencéfalo: claves diagnósticas en RM / Inflammatory lesions of the brainstem: Keys for the diagnosis by MRI

Objetivo: Describir los hallazgos en resonancia magnética (RM) de las principales enfermedades inflamatorias e inmunomediadas que afectan al troncoencéfalo. Conclusión: El diagnóstico diferencial de las lesiones inflamatorias localizadas en el troncoencéfalo es complicado debido al amplio espectro de enfermedades autoinmunes, infecciosas y síndromes paraneoplásicos que pueden causarlas. Conocer estas entidades, sus características clínicas y sus manifestaciones en RM, sobre todo en cuanto a número, morfología, extensión y apariencia en las diferentes secuencias, es útil a la hora de orientar el diagnóstico radiológico.(AU)

Objective: To describe the magnetic resonance imaging (MRI) findings for the most common inflammatory and immune-mediated diseases that involve the brainstem. Conclusion: Inflammatory lesions involving the brainstem are associated with a wide range of autoimmune, infectious, and paraneoplastic syndromes, making the differential diagnosis complex. Being familiar with these entities, their clinical characteristics, and their manifestations on MRI, particularly the number of lesions, their shape and extension, and their appearance in different sequences, is useful for orienting the radiological diagnosis.(AU)

Brachytherapy for high grade prostate cancer induces distinct changes in circulating CD4 and CD8 T cells - Implications for systemic control.

This exploratory study is a follow up to our previous investigation of immune response in the circulation of high-grade Gleason 9 prostate cancer patients treated with EBRT + BT compared to EBRT alone. Notably, EBRT + BT demonstrates the potential to elicit an effect on CD4/CD8 ratio which may have attributed to improved clinical response to therapy. Our findings show promise for leveraging circulating immune cells as predictive biomarkers for radiotherapy response.

["Rheuma (be-)greifen"- A multimodal teaching concept to improve rheumatology education for medical students]. / "Rheuma (be-)greifen" ­ ein multimodales Lehrkonzept zur Verbesserung der rheumatologischen Lehre für Studierende der Humanmedizin.

BACKGROUND: The German Society for Rheumatology, through its campaign Rheuma2025, aims to improve student teaching in order to ensure patient care for rheumatological patients in the future. OBJECTIVE: To assess whether a combination of traditional and innovative educational methods provide both an improvement in the quality of teaching and an increase in the attractiveness of rheumatology as a discipline. MATERIAL AND METHODS: Establishment of the teaching concept "Rheuma (be-)greifen" consisting of five modules on patient history taking with acting patients, musculoskeletal ultrasound, arthrocentesis, 3D printing of pathological joints and virtual reality applications based on real patient cases in the curricular teaching of medical students. RESULTS: The evaluation of the teaching concept with 93 students of medicine showed a consistently high acceptance of all modules, which were rated as very effective or rather effective. Direct patient-related modules, such as history taking with acting patients, musculoskeletal ultrasound and arthrocentesis, received even higher acceptance than the visualization methods utilizing 3D printing and virtual reality. CONCLUSION: Innovative teaching methods can help to improve the acceptance of teaching in the field of rheumatology, especially when combined with classical teaching contents.

Adaptive controller based on barrier Lyapunov function for a composite Cartesian-delta robotic device for precise time-varying position tracking.

This study presents the design of an adaptive event-driven controller for solving the trajectory tracking problem of a composite robotic device made up of a three-dimensional Cartesian and a parallel Delta robot. The proposed composite device has a mathematical model satisfying a standard Lagrangian structure affected by modeling uncertainties and external perturbations. The adaptive gain of the controller is considered to enforce the convergence of the tracking error while the state bounds are satisfied. The barrier Lyapunov function addresses the preconceived state constraints for both robotic devices by designing a time-varying gain that guarantees the ultimate boundedness of the tracking error under the effect of external perturbations. The event-driven approach considers that the Cartesian robot is moving into a predefined invariant zone near to the origin. In contrast, the delta robot can complete the tracking problem once the end-effector is inside the given zone. The suggested controller was evaluated using a virtual representation of the composite robotic device showing better tracking performance (while the restrictions are satisfied) than the performances obtained with the traditional linear state feedback controllers. Analyzing the mean square error and its integral led to confirming the benefits of using the adaptive barrier control.

Prolonged fixation and post-mortem delay impede the study of adult neurogenesis in mice.

Adult hippocampal neurogenesis (AHN) gives rise to new neurons throughout life. This phenomenon takes place in more than 120 mammalian species, including humans, yet its occurrence in the latter was questioned after one study proposed the putative absence of neurogenesis markers in the adult human hippocampus. In this regard, we showed that prolonged fixation impedes the visualization of Doublecortin+ immature neurons in this structure, whereas other authors have suggested that a dilated post-mortem delay (PMD) underlies these discrepancies. Nevertheless, the individual and/or additive contribution of fixation and the PMD to the detection (or lack thereof) of other AHN markers has not been studied to date. To address this pivotal question, we used a tightly controlled experimental design in mice, which allowed the dissection of the relative contribution of the aforementioned factors to the visualization of markers of individual AHN stages. Fixation time emerged as the most prominent factor globally impeding the study of this process in mice. Moreover, the visualization of other particularly sensitive epitopes was further prevented by prolonged PMD. These results are crucial to disambiguate current controversies related to the occurrence of AHN not only in humans but also in other mammalian species.

Healthcare utilization and unmet needs of patients with antisynthetase syndrome: An international patient survey.

Antisynthease syndrome (ASSD) is a rare, complex and understudied autoimmune disease. Internet-based studies can overcome barriers of traditional on-site research and are therefore very appealing for rare diseases. The aim of this study was to investigate patient-reported symptoms, diagnostic delay, symptoms, medical care, health status, working status, disease knowledge and willingness to participate in research of ASSD patients by conducting an international web-based survey. The multilingual questionnaire was created by an international group of rheumatologists and patients and distributed online. 236 participants from 22 countries completed the survey. 184/236 (78.0%) were female, mean age (SD) was 49.6 years (11.3) and most common antisynthetase antibody was Jo-1 (169/236, 71.6%). 79/236 (33.5%) reported to work full-time. Median diagnostic delay was one year. The most common symptom at disease onset was fatigue 159/236 (67.4%), followed by myalgia 130/236 (55.1%). The complete triad of myositis, arthritis and lung involvement verified by a clinician was present in 42/236 (17.8%) at disease onset and in 88/236 (37.3%) during the disease course. 36/236 (15.3%) reported to have been diagnosed with fibromyalgia and 40/236 (16.3%) with depression. The most reported immunosuppressive treatments were oral corticosteroids 179/236 (75.9%), followed by rituximab 85/236 (36.0%). 73/236 (30.9%) had received physiotherapy treatment. 71/236 (30.1%) reported to know useful online information sources related to ASSD. 223/236 (94.5%) were willing to share health data for research purposes once a year. Our results reiterate that internet-based research is invaluable for cooperating with patients to foster knowledge in rare diseases.

ASSESSMENT OF OVERRANGING AS A FUNCTION OF PITCH, COLLIMATION AND ROTATION TIME FOR THREE OF THE MOST RECENT AND WIDESPREAD CT SCANS IN FRANCE.

PURPOSE: to assess overranging (OR) as a function of pitch, collimation and rotation time for three commonly used CT models in France. METHODS: OR was measured using XR-SP2 Gafchromic films (Ashland, USA) and computed from exposure data for three widely used CT models in France. The impact of collimation, pitch and rotation time on OR was analyzed while comparing the three CT models. RESULTS: for a typical head protocol, measured OR was found to be equal to 1.64 cm for CT scan A, 0.5 cm for CT scan B and 3.44 cm for CT scan C. OR values were respectively of 4.47, 3.24 and 7.81 cm for the typical chest protocol and the 3 CT models. OR was lowest at pitch values <1 for CT scan A, while it linearly increased with pitch for CT scan B and was lowest for high pitch values for CT scan C. Additionally, OR increase with collimation (24 mm to 38.4 mm) was most pronounced for CT scan B (factor of 2.2 for low pitch (0.5) and 2.8 for high pitch (1.2)) while it increased linearly regardless of the pitch for CT scans A and C. Rotation time also proved to slightly affect OR mainly for CT scan B (up to 2.2 mm). CONCLUSION: the present study shows that overranging remains an issue in modern CT scanners with large disparities across the vendors.

CT findings for dental disease.

Traumatic and especially inflammatory-infectious dental lesions are very prevalent in our context. Inflammatory-infectious disease is usually discovered incidentally on imaging studies that include the orofacial region. Moreover, these conditions can result in potentially severe complications, so early diagnosis and treatment are important. Multidetector computed tomography offers good diagnostic performance for dental lesions, although the radiological findings can be subtle and can go undetected if the radiologist is not familiar with them. Likewise, invasive dental procedures are becoming increasingly common, and these can also result in complications. On the other hand, in daily practice a variety of radiolucent mandibular lesions or developmental anomalies can lead to erroneous interpretations. For these reasons, radiologists should be familiar with possible findings related with dental conditions.

Hallazgos por imagen de patología dentaria en tomografía computarizada / CT findings for dental disease

La patología dentaria traumática y en especial la inflamatorio-infecciosa son muy prevalentes en nuestro medio. Esta última suele encontrarse de forma incidental en muchos de los estudios radiológicos que incluyen la región orofacial. Además, es una potencial causa de complicaciones graves, lo que hace que su diagnóstico y tratamiento precoz sean importantes. La tomografía computarizada multidetector ofrece un buen rendimiento diagnóstico en la patología dentaria, aunque sus manifestaciones radiológicas pueden ser sutiles y si no se conocen, pasar desapercibidas. Asimismo, son cada vez más frecuentes los procedimientos dentales invasivos, no exentos de complicaciones. Por otra parte, en la práctica diaria pueden encontrarse variedad de lesiones mandibulares radiolucentes o anomalías del desarrollo que pueden llevar a interpretaciones erróneas. Por todo ello, es recomendable que el radiólogo esté familiarizado con los posibles hallazgos en la patología dentaria.(AU)

Traumatic and especially inflammatory-infectious dental lesions are very prevalent in our context. Inflammatory-infectious disease is usually discovered incidentally on imaging studies that include the orofacial region. Moreover, these conditions can result in potentially severe complications, so early diagnosis and treatment are important. Multidetector computed tomography offers good diagnostic performance for dental lesions, although the radiological findings can be subtle and can go undetected if the radiologist is not familiar with them. Likewise, invasive dental procedures are becoming increasingly common, and these can also result in complications. On the other hand, in daily practice a variety of radiolucent mandibular lesions or developmental anomalies can lead to erroneous interpretations. For these reasons, radiologists should be familiar with possible findings related with dental conditions.(AU)

Lead Sequestration from Halide Perovskite Solar Cells with a Low-Cost Thiol-Containing Encapsulant.

Perovskite solar cells (PSCs) are being studied and developed because of the outstanding properties of halide perovskites as photovoltaic materials and high conversion efficiencies achieved with the best PSCs. However, leaching out of lead (Pb) ions into the environment presents potential public health risks. We show that thiol-functionalized nanoparticles provide an economic way of minimizing Pb leaching in the case of PSC module damage and subsequent water exposure (at most, ∼2.5% of today's crystal silicon solar panel production cost per square meter). Using commercial materials and methods, we retain ∼90% of Pb without degrading the photovoltaic performance of the cells, compared with nonencapsulated devices, yielding a worst-case scenario of top-soil pollution below natural Pb levels and well below the U.S. Environmental Protection Agency limits.

Measurement of Lepton-Jet Correlation in Deep-Inelastic Scattering with the H1 Detector Using Machine Learning for Unfolding.

The first measurement of lepton-jet momentum imbalance and azimuthal correlation in lepton-proton scattering at high momentum transfer is presented. These data, taken with the H1 detector at HERA, are corrected for detector effects using an unbinned machine learning algorithm (multifold), which considers eight observables simultaneously in this first application. The unfolded cross sections are compared with calculations performed within the context of collinear or transverse-momentum-dependent factorization in quantum chromodynamics as well as Monte Carlo event generators.

CT findings for dental disease. / Hallazgos por imagen de patología dentaria en tomografía computarizada.

Traumatic and especially inflammatory-infectious dental lesions are very prevalent in our context. Inflammatory-infectious disease is usually discovered incidentally on imaging studies that include the orofacial region. Moreover, these conditions can result in potentially severe complications, so early diagnosis and treatment are important. Multidetector computed tomography offers good diagnostic performance for dental lesions, although the radiological findings can be subtle and can go undetected if the radiologist is not familiar with them. Likewise, invasive dental procedures are becoming increasingly common, and these can also result in complications. On the other hand, in daily practice a variety of radiolucent mandibular lesions or developmental anomalies can lead to erroneous interpretations. For these reasons, radiologists should be familiar with possible findings related with dental conditions.

Prediction of response to Certolizumab-Pegol in rheumatoid arthritis (PreCePRA) by functional MRI of the brain - Study protocol for a randomized double-blind controlled study.

BACKGROUND: Tumor necrosis factor inhibitors (TNFi) signify a major advance in the treatment of rheumatoid arthritis (RA). However, treatment success initially remains uncertain as approximately half of the patients do not respond adequately to TNFi. Thus, an unmet need exists to better predict therapeutic outcome of biologicals. OBJECTIVES: We investigated whether brain activity associated with arthritis measured by functional magnetic resonance imaging (fMRI) of the brain can serve as a predictor of response to TNFi in RA patients. METHODS: PreCePRA is a multi-center, randomized, double-blind, placebo-controlled fMRI trial on patients with RA [1] [2]. Active RA patients failing csDMARDs therapy with a DAS28 > 3.2 and at least three tender and/or swollen joints underwent a brain BOLD (blood-oxygen-level dependent) fMRI scan upon joint compression at screening. Patients were then randomized into a 12-week double-blinded treatment phase with 200 mg Certolizumab Pegol (CZP) every two weeks (arm 1: fMRI BOLD signal activated volume > 2000 voxel, i.e. 2 cm3; arm 2: fMRI BOLD signal activated volume <2000 voxel) or placebo (arm 3). DAS28 low disease activity at 12 weeks was assigned as primary endpoint. A 12-week follow-up phase in which patients were switched from the placebo to the treatment arm followed the blinded phase. fMRI was carried out at screening as well as after 12 and 24 weeks of receiving CZP or placebo. CONCLUSION: We hypothesize that high-level central nervous representation of pain in patients with rheumatoid arthritis predicts response to the TNFi CZP which we further investigate in the PreCePRA trial.