["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.

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.

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.

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.

Bilateral facial nerve palsy associated with COVID-19 and Epstein-Barr virus co-infection.

COVID-19 can occasionally be associated with cranial nerve involvement, but facial palsy, particularly if bilateral, is exceptional. We here report a patient who presented with severe bilateral facial palsy and evidence of SARS-CoV-2 infection preceded by upper respiratory symptoms. He also had serological evidence of coinfection with Epstein-Barr virus, which could have also played a role in his neurological manifestations. PCR in the cerebrospinal fluid was negative for both EBV and SARS-CoV-2, which suggests an indirect, immune-mediated mechanism rather than direct, viral-induced damage. The patient was treated with prednisone 60 mg/24h with a tapering schedule and had a favorable outcome, with an almost complete recovery in 3 weeks. SARS-CoV-2 adds to the list of infectious agents causative of bilateral facial palsy. Coinfection with SARS-CoV-2 is not rare and should be considered in the differential diagnosis.

Hemocyte cell types of the Cortes Geoduck, Panopea globosa (Dall 1898), from the Gulf of California, Mexico.

The geoduck Panopea globosa is an endemic and economic valuable species from the Mexican Northwest coast whose biology has been little studied. No information exists about their hemocytes to date, which is highly important to assess the welfare of wild and cultured organisms. In this study, hemocytes of adult P. globosa were characterized at the morphological, ultrastructural and functional level. The mean number of hemocytes in the hemolymph of P. globosa was 6 × 105 ± 2 × 105 cells mL-1. The cells were identified as granulocytes (Gr) and hyalinocytes (H). The former accounted for 28% of adhered cells in the hemolymph, measured 6-18 µm, showed numerous basophilic granules in the cytoplasm, with round and eccentric nuclei, and a nucleus:cytoplasm ratio of 0.44 ± 0.01. Hyalinocytes were the most abundant cells in the hemolymph of P. globosa (72% adhered cells) and were subdivided, according to their size, in small (Hs) 4-12 µm and large (HL) 6-18 µm. Hyalinocytes were eosinophilic round or ovoid cells with a central or eccentric nucleus, few or no granules in the cytoplasm and similar nucleus:cytoplasm ratio (Hs: 0.63 and HL: 061). Lysosomes and lipids were observed in Gr, while carbohydrates were the most abundant energy substrate in H. Both hemocytic cell types, mainly Gr, were capable to ingest particles and yield superoxide (P > 0.05). The present study shows for the first time the cell types, abundance and immune activities of hemocytes present in the hemolymph of P. globosa. This information provides a useful baseline to carry out further research on the cellular immune response of the clam to potential pathogens or changes in environmental factors.

A classical and semiclassical study of collisions between Xq+ ions and water molecules.

Collisions of He2+, Li3+ and C3+ ions with water molecules are studied at energies ranging between 20 keV u-1 and 500 keV u-1. Three methods are employed: the classical trajectory Monte Carlo (CTMC), the expansion of the scattering wave function in terms of asymptotic frozen molecular orbitals (AFMO) and a lattice method to numerically solve the time-dependent Schrödinger equation (GridTDSE). Total cross sections for single ionization, single electron capture, transfer ionization and electron production are calculated and compared with previous close-coupling calculations and experiments. The fragmentation branching ratios are discussed.

Nonadiabatic fragmentation of H2O+ and isotopomers. Wave packet propagation using ab initio wavefunctions.

The fragmentation of the water cation from its B[combining tilde] 2B2 electronic state, allowing the participation of the X[combining tilde] 2B1, Ã 2A1 and C[combining tilde] 2B1 states in the process, is simulated using the extended capabilities of the collocation GridTDSE code to account for the nonadiabatic propagation of wave packets in several potential energy surfaces connected by nonadiabatic couplings. Molecular data are calculated ab initio. Two initial wave packets are considered to reproduce two different experiments. The isotopic effect in the fragmentation of D2O+ and HDO+ is also studied and the results show very good agreement with the experimental cleavage preference in the fragmentation of HDO+.

Ionization and Single and Double Electron Capture in Proton-Ar Collisions.

Total cross sections for formation of H and H-, and electron production, in H+ + Ar collisions have been calculated at energies between 100 eV and 200 keV by employing two methods: for E < 10 keV, a semiclassical treatment with an expansion in a basis of electronic wave functions of the ArH+ quasimolecule and, for E > 10 keV, the switching-classical-trajectory-Monte Carlo method (s-CTMC). The semiclassical calculation involves transitions to molecular autoionizing states, calculated by applying a block-diagonalization technique. The s-CTMC method is adept to treat two-electron processes and yields total cross sections for H- formation in reasonably good agreement with the experimental data. Cross sections for electron- and H-production processes, which are dominated by one-electron transitions, are in good agreement with the experimental data.

A comparative study of two cooling protocols on stallion sperm cryosurvival.

There are many protocols for horse sperm cryopreservation, but results are inconsistent; sperm survival after freeze-thawing is usually poor; in consequence, fertility is low. The objective of this work was to see whether slow cooling before freezing to minus 3 °C instead of +5 °C, the traditional target temperature, could improve horse sperm cryosurvival, capability to carry out capacitation and the acrosome reaction induced by progesterone. Spermatozoa from five stallions were packaged in straws and slowly cooled to +5 °C. Half of the straws were frozen directly and the other half was further cooled to -3 °C before freezing. Progressive motility, viability, plasma membrane integrity, acrosome integrity and capacitation status were assessed. After thawing, there were no differences between cooling treatments on motility, viability, acrosome integrity and capacitation status; however, there was difference (P < 0.05) regarding plasma membrane integrity. Acrosome integrity decreased as incubation, without or with progesterone (2 µg ml(-1) ), progressed, but there were no differences between cooling treatments regardless of progesterone. Both capacitated and acrosome-reacted spermatozoa increased as incubation progressed, but there were no differences between cooling treatments regardless of progesterone. Slow cooling to -3 °C before freezing did not improve horse sperm cryosurvival or capability to undergo the acrosome reaction.

[Long term results of mitral balloon valvuloplasty]. / Resultados a largo plazo de la valvuloplastía mitral con balón.

BACKGROUND: Mitral balloon valvuloplasty (MBV) is the therapy of choice for the treatment of symptomatic mitral stenosis with suitable anatomy. Although its short and mid-term results are favorable, there is a paucity of information about long-term follow-up. AIM: To assess the late results of MBV. MATERIAL AND METHODS: A cohort of 225 patients aged 8 to 20 years who were subjected to a MBV from 1989 to 2001, was studied. All variables at the time of the procedure, short and long-term results and major events during follow-up (new mitral intervention and mortality) were recorded. Uni and multivariate analysis were used to assess prognosis. RESULTS: The mean follow-up lapse was 13.5 years (range 8 to 20 years). During this period, 88 patients (39.1%) remained event-free and in acceptable functional capacity. Eight percent died, 8% required a second MBV and 43.5% required a surgical mitral valve replacement. A post-procedural area equal or greater to 1.9 cm² was associated with a greater likelihood of free-event survival (log rank test: p = 0.02/Cox proportional regression model: coefficient 0.54, p = 0.04). CONCLUSIONS: MBV is effective, although there is a high chance of new interventions in the long-term follow-up. A larger post-procedure mitral area is associated with a better prognosis.

[Transrectal biopsy scheme can predict incorrect histological grading in prostate cancer]. / El esquema de biopsia transrectal puede predecir la gradación histológica incorrecta del cáncer de próstata.

OBJECTIVE: To identify factors that might explain why a prostate with a Gleason score (GS) <7 in the biopsy specimen can turn out to have a GS ≥7 in the surgical specimen. MATERIAL AND METHODS: We compared the GS of biopsy specimens with the GS of surgical specimens in 185 patients who underwent surgery for prostate cancer. We calculated the sensitivity, specificity, and predictive values for the GS of the biopsy specimens. We used Cohen's kappa to determine the degree of concordance between a GS of <7 and ≥7 for the biopsy specimen and the surgical specimen. Age, a family history of prostate cancer, total prostate-specific antigen (tPSA), digital rectal examination, prostate structure and volume, and the number of biopsy cores (biopsy scheme) were analyzed using multivariable logistic regression. RESULTS: Histological study of biopsy specimens yielded high sensitivity (98%) but low specificity (49%) for GS ≤6 and low sensitivity (35, 26%) and high specificity (93, 99%) for GS=7 and GS ≥7, respectively. Cohen's kappa for the GS from the biopsy and surgical specimens was 0.43 (95% CI=30-56%). The biopsy scheme was the only predictor of discordance in the GS between the two techniques. Among the other variables included in the model, only tPSA showed a slightly significant association. Taking a scheme with less than 7 cores as a reference, we found no difference with 8 to 9 cores but we did find a difference with 10 to 11 cores and with 12 or more cores, with a prevalence ratio of 0.138 (95% CI=0.030-0.513) and 0.277 (95% CI=0.091-0.806), respectively. CONCLUSION: The GS of the biopsy depends on the scheme. This factor must be taken into account when choosing a treatment option in patients with low tumor grade in biopsy specimens.

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.

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.

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.

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.

New light shed on charge transfer in fundamental H+ + H2 collisions.

There is no consensus on the magnitude and shape of the charge transfer cross section in low-energy H+ + H2 collisions, in spite of the fundamental importance of these collisions. Experiments have thus been carried out in the energy range 15≤E≤5000 eV. The measurements invalidate previous recommended data for E≤200 eV and confirm the existence of a local maximum around 45 eV, which was predicted theoretically. Additionally, vibrationally resolved cross sections allow us to investigate the evolution of the underlying charge transfer mechanism as a function of E.

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.

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.

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.