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This research aims at exploring in an irregular orthographic system like French, if spelling is related to written composition. French spelling is particularly interesting because it includes phonographic irregularities (i.e., inconsistencies), lexical difficulties and numerous morphological silent marks (e.g., plural noun, adjective, and verb agreement). In a longitudinal study from the beginning of Grade 3 to the end of Grade 4, pupils (N = 173) were asked twice in every grade to compose narrative texts from strips. Text length, text completeness and three categories of spelling errors were coded and analyzed through multilevel growth curve models. Results show (1) a growing relationship between text production and orthographic performance, (2) that this relationship varied according to whether it related to text length or to text completeness, and (3) its strength and evolution depended on the type of errors (phonographic, lexical, or morphological).

Abstract Background The Brief Educational Workshops in Secondary Schools Trial (BESST) is an England-wide school-based cluster randomised controlled trial assessing the clinical and cost-effectiveness of an open-access psychological workshop programme (DISCOVER) for 16–18-year-olds. This baseline paper describes the self-referral and other recruitment processes used in this study and the baseline characteristics of the enrolled schools and participants. Method We enrolled 900 participants from 57 Secondary schools across England from 4th October 2021 to 10th November 2022. Schools were randomised to receive either the DISCOVER day-long Stress workshop or treatment as usual which included signposting information. Participants will be followed up for 6 months with outcome data collection at baseline, 3-month, and 6-month post randomisation. Results Schools were recruited from a geographically and ethnically diverse sample across England. To reduce stigma, students were invited to self-refer into the study if they wanted help for stress. Their mean age was 17.2 (SD = 0.6), 641 (71%) were female and 411 (45.6%) were from ethnic minority groups. The general wellbeing of our sample measured using the Mood and Feelings Questionnaire (MFQ) found 314 (35%) of students exhibited symptoms of depression at baseline. Eighty percent of students reported low wellbeing on the Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) suggesting that although the overall sample mean is below the cut-off for depression, the self-referral approach used in this study supports distressed students in coming forward. Conclusion The BESST study will continue to follow up participants to collect outcome data and results will be analysed once all the data have been collected. Trial registration ISRCTN registry ISRCTN90912799. Registered on 28 May 2020.

The technological capability of artificial intelligence (AI) continues to advance with great strength. Recently, the release of large language models has taken the world by storm with concurrent excitement and concern. As a consequence of their impressive ability and versatility, their provide a potential opportunity for implementation in oncology. Areas of possible application include supporting clinical decision making, education, and contributing to cancer research. Despite the promises that these novel systems can offer, several limitations and barriers challenge their implementation. It is imperative that concerns, such as accountability, data inaccuracy, and data protection, are addressed prior to their integration in oncology. As the progression of artificial intelligence systems continues, new ethical and practical dilemmas will also be approached; thus, the evaluation of these limitations and concerns will be dynamic in nature. This review offers a comprehensive overview of the potential application of large language models in oncology, as well as concerns surrounding their implementation in cancer care.

Rituximab (RTX) plus chemotherapy (R-CHOP) applied as a first-line therapy for lymphoma leads to a relapse in approximately 40% of the patients. Therefore, novel approaches to treat aggressive lymphomas are being intensively investigated. Several RTX-resistant (RR) cell lines have been established as surrogate models to study resistance to R-CHOP. Our study reveals that RR cells are characterized by a major downregulation of CD37, a molecule currently explored as a target for immunotherapy. Using CD20 knockout (KO) cell lines, we demonstrate that CD20 and CD37 form a complex, and hypothesize that the presence of CD20 stabilizes CD37 in the cell membrane. Consequently, we observe a diminished cytotoxicity of anti-CD37 monoclonal antibody (mAb) in complement-dependent cytotoxicity in both RR and CD20 KO cells that can be partially restored upon lysosome inhibition. On the other hand, the internalization rate of anti-CD37 mAb in CD20 KO cells is increased when compared to controls, suggesting unhampered efficacy of antibody drug conjugates (ADCs). Importantly, even a major downregulation in CD37 levels does not hamper the efficacy of CD37-directed chimeric antigen receptor (CAR) T cells. In summary, we present here a novel mechanism of CD37 regulation with further implications for the use of anti-CD37 immunotherapies.

This paper discusses the interactional construction of personal trajectories of migrant children with a focus on its implications for the enhancement of children's agency. The discussion is supported by the analysis of three extracts transcripts of audio or video-recorded classroom activities that illustrate the main forms of facilitation of migrant children's agency as authorship of narratives of personal trajectories of migration, also showing that facilitation is influenced by children's language proficiency. The construction of narratives can be context for the negotiation of hybrid integration, at the intersection between forms of facilitation, social and cultural contexts and personal trajectories and experiences.

IntroductionSeroma development is a known complication following extremity and trunk soft-tissue sarcoma (STS) resection. The purpose of this study is to evaluate and characterize seroma outcomes and the development of associated complications.MethodsA retrospective review of 123 patients who developed postoperative seromas following STS resection at a single institution was performed. Various patient and surgical factors were analyzed to determine their effect on overall seroma outcomes.Results77/123 seromas (62.6%) were uncomplicated, 30/123 (24.4%) developed infection, and 16/123 (13.0%) were symptomatic and required aspiration or drainage for symptom relief at an average of 12.2 months postoperatively. 65/123 (52.8%) seromas resolved spontaneously at an average time of 12.41 months. Seromas in the lower extremity (p=0.028), surgical resection volume >864 cm3, (p=42 cm3 (p=864 cm3 and a large seroma volume >42 cm3 are risk factors for complications.

Abstract Background Access to long‐term ambulatory recording to detect atrial fibrillation (AF) is limited for economical and practical reasons. We aimed to determine whether 24 h ECG (24hECG) data can predict AF detection on extended cardiac monitoring. Methods We included all US patients from 2020, aged 17–100 years, who were monitored for 2–30 days using the PocketECG device (MEDICALgorithmics), without AF ≥30 s on the first day (n = 18,220, mean age 64.4 years, 42.4% male). The population was randomly split into equal training and testing datasets. A Lasso model was used to predict AF episodes ≥30 s occurring on days 2–30. Results The final model included maximum heart rate, number of premature atrial complexes (PACs), fastest rate during PAC couplets and triplets, fastest rate during premature ventricular couplets and number of ventricular tachycardia runs ≥4 beats, and had good discrimination (ROC statistic 0.7497, 95% CI 0.7336–0.7659) in the testing dataset. Inclusion of age and sex did not improve discrimination. A model based only on age and sex had substantially poorer discrimination, ROC statistic 0.6542 (95% CI 0.6364–0.6720). The prevalence of observed AF in the testing dataset increased by quintile of predicted risk: 0.4% in Q1, 2.7% in Q2, 6.2% in Q3, 11.4% in Q4, and 15.9% in Q5. In Q1, the negative predictive value for AF was 99.6%. Conclusion By using 24hECG data, long‐term monitoring for AF can safely be avoided in 20% of an unselected patient population whereas an overall risk of 9% in the remaining 80% of the population warrants repeated or extended monitoring.

Creative thinking is sometimes neglected by schools. Introducing philosophy in schools represents a commitment to balancing the development of logical and creative thinking, currently exercised only orally. In the present study, the focus is on writing. Firstly, the value of authentic pupil writings is underscored. The pupils and students studied wrote texts for "Adolescence et Société," a magazine produced by researchers. 100 students' works, written by philosophizing students in fourth-year college in France, culled from the "PreCPhi/Philosophemes" Corpus (1,300 texts collected from 43 classrooms) were studied in order to measure the progress of philosophizing students between a pre-test and a post-test following the introduction of a pedagogical tool that unites Art with Philosophy, "Philo & Carto." Their writing skills were measured according to the following five dimensions: linguistic, philosophical, cognitive, reflective and creative. Performance measures, calculated on group averages and applied to the group's variance between the pre- and the post-tests, were related to each dimension. Linguistic performance (presence of an introduction and conclusion) did not progress, remaining subject to pupils' academic level. Philosophical, cognitive, creative and reflective performance increased significantly, or at least confirmed the trend. Reasoning, metaphors, conceptual differences and discourse ownership increased, while anecdotal examples decreased. These increases were accompanied by an increase in the post-test variance: gaps between the strongest and the weakest performances widened, except in the case of questioning, personal examples and generation of doubt, which were at the core of the effect produced. The study validates the fact that the Art and Philosophy link promises unprecedented educational prospects with regard to the production of early quality philosophical writings. This will require validation with other samplings.

Background: Palpitations are a frequent reason for referral to pediatric cardiology providers and diagnostic workup includes ambulatory cardiac monitoring. While common practice, the diagnostic yield is unknown in the pediatric population. The objective is to evaluate the diagnostic yield of 24-h Holter and extended ambulatory cardiac monitoring in pediatric patients with palpitations. Methods and Results: All pediatric patients aged 10–18 years who had ambulatory cardiac monitoring (1–30 days) through the Pocket Electrocardiogram (PocketECG™) system (Medi-Lynx) between January 2016 and July 2020 were included. Patients with an International Classification of Diseases-10 diagnosis code of palpitations (R00.2) during enrollment were evaluated separately. Tachyarrhythmia diagnoses included atrial fibrillation (AF), nonsustained supraventricular tachycardia (nSVT), supraventricular tachycardia (SVT), nonsustained ventricular tachycardia (nVT), and ventricular tachycardia (VT). Age, heart rates, arrhythmia type, and symptomatic transmission data were collected and analyzed. A total of 2388 patients (mean age 11.6 years, 58% F) with the R00.2 code had ambulatory cardiac monitoring (28% 24-h Holter, 72% extended) performed during the study period and there were 6287 total patients (mean age 13.9 years, 54% F) that underwent ambulatory cardiac monitoring (42% 24-h Holter, 58% extended) during that time. Of 2388 patients, 321 (13%) were diagnosed with tachyarrhythmia: AF (9), nSVT (192), SVT (59), and nVT (61). In the overall cohort, 764 (12%) patients were diagnosed with tachyarrhythmia: AF (22), nSVT (478), SVT (85), nVT (177), and VT (2). Symptomatic transmissions with normal cardiac rhythm were common in the R00.2 (n = 1697, 71%) and overall (n = 3848, 61%) groups. No episodes of nSVT, SVT, nVT, or VT were associated with symptomatic transmissions. Conclusion: Ambulatory cardiac monitors are an integral part of the diagnostic workup for pediatric palpitations patients and have demonstrated a high yield of combined positive arrhythmia diagnoses and symptomatic normal transmissions. Further prospective study of this population with the integration of clinical information is warranted.

Philosophy for Children (P4C) is a collective (teaching) practice which has been shown to foster language abilities, logic and creativity in children. While these benefits obtained with the P4C "oral" practice have been well documented, philosophical writing received little attention. The aim of this paper is to examine which conditions better promote the quality of philosophical writing. Six writing conditions were proposed to a total of 317 students between the age of 12 and 13 from various socioeconomic backgrounds. These conditions varied according to the media (image, dialogue, key words) and the topic (dichotomous, not dichotomous). The quality of philosophical writing was assessed according to several indicators reflecting linguistic, logical and creative performances. Results show that the quality of philosophical writing depended on the media and the topic which were proposed, indicating different types of language planning across conditions. Interestingly, the image (vs. dialogue or key words) encouraged creativity, detected by a more frequent use of metaphors, while distinctions between concepts were more frequently made from a dichotomous (vs. not dichotomous) topic. The functions of metaphors and examples are discussed in parallel with gender and school effects obtained in this study.

The primary objective of this investigative work was to determine among the ISICs analyzed – the furniture removal services (H4923.04) and construction of bridges and viaducts (F4210.32), both of which maintain good operation and management – the ISIC that has better economic operation than the other. Bibliographic materials and calculations were studied, and a quantitative approach based on a deductive scheme was applied. Data were analyzed using the Microsoft Excel sheet. It was found that Ciiu 1: H4923.04 – FURNITURE MOVING SERVICES – has had a better economic standing in its operation compared to Ciiu 2 F4210.32 – CONSTRUCTION OF BRIDGES AND VIADUCTS – that presents values at 0 in its financial ratios, that is to say, its financial performance is not positive. The means obtained from each financial ratio were analyzed together with the coefficient of variation which showed that the data tend to be more dispersed in Ciiu 1: H4923.04 – FURNITURE MOVING SERVICES – since Ciiu 2 did not present data. Therefore, to conclude, it was possible to obtain the means of each of the ISICs in question in order to obtain a comparison between the two and to know the benefits they have obtained in the years 2018 and 2019.

The article studies the verbal manifestation of critical thought in a school context. Four modes of thought--logical, creative, responsible, and metacognitive--accompanied by six epistemological perspectives, are studied from 1,730 pupils turns to speak analyzed in eight class groups. The pupils dialog about freedom. Quantitatively and gradually the collective thought gives the lion's share to the manifestation of logical, followed by creative and then responsible thought, and very little to that of metacognitive thought. The study reveals a significant developmental effect for logical and responsible thought--to the advantage of the girls. While each mode of thought evolves following its own developmental path, the epistemological congruence that emerges between the logical and responsible modes of thought on the one hand and responsible and creative on the other seems perhaps debatable. The results lead to a pedagogic proposal which consists in proposing to introduce a cognitive activity of doubt, not spontaneously adopted by the pupils, to favor the advent of a form of critical thinking more balanced as concerns the modes of thoughts of which it composed.

The superior colliculus (SC) is a critical hub for the generation of visually-evoked orienting and defensive behaviors. Among the SC’s myriad downstream targets is the parabigeminal nucleus (PBG), the mammalian homolog of the nucleus isthmi, which has been implicated in motion processing and the production of defensive behaviors. The inputs to the PBG are thought to arise exclusively from the SC but little is known regarding the precise synaptic relationships linking the SC to the PBG. In the current study, we use optogenetics as well as viral tracing and electron microscopy in mice to better characterize the anatomical and functional properties of the SC-PBG circuit, as well as the morphological and ultrastructural characteristics of neurons residing in the PBG. We characterized GABAergic SC-PBG projections (that do not contain parvalbumin) and glutamatergic SC-PBG projections (which include neurons that contain parvalbumin). These two terminal populations were found to converge on different morphological populations of PBG neurons and elicit opposing postsynaptic effects. Additionally, we identified a population of non-tectal GABAergic terminals in the PBG that partially arise from neurons in the surrounding tegmentum, as well as several organizing principles that divide the nucleus into anatomically distinct regions and preserve a coarse retinotopy inherited from its SC-derived inputs. These studies provide an essential first step toward understanding how PBG circuits contribute to the initiation of behavior in response to visual signals.

Aging affects iron homeostasis, as evidenced by tissue iron loading and anemia in the elderly. Iron needs in mammals are met primarily by iron recycling from senescent red blood cells (RBCs), a task chiefly accomplished by splenic red pulp macrophages (RPMs) via erythrophagocytosis. Given that RPMs continuously process iron, their cellular functions might be susceptible to age-dependent decline, a possibility that has been unexplored to date. Here, we found that 10- to 11-month-old female mice exhibit iron loading in RPMs, largely attributable to a drop in iron exporter ferroportin, which diminishes their erythrophagocytosis capacity and lysosomal activity. Furthermore, we identified a loss of RPMs during aging, underlain by the combination of proteotoxic stress and iron-dependent cell death resembling ferroptosis. These impairments lead to the retention of senescent hemolytic RBCs in the spleen, and the formation of undegradable iron- and heme-rich extracellular protein aggregates, likely derived from ferroptotic RPMs. We further found that feeding mice an iron-reduced diet alleviates iron accumulation in RPMs, enhances their ability to clear erythrocytes, and reduces damage. Consequently, this diet ameliorates hemolysis of splenic RBCs and reduces the burden of protein aggregates, mildly increasing serum iron availability in aging mice. Taken together, we identified RPM collapse as an early hallmark of aging and demonstrated that dietary iron reduction improves iron turnover efficacy.

Background: Women are less likely to receive oral anticoagulation or ablation for treatment of atrial fibrillation (AF). Identification of sex differences in arrhythmia characteristics and symptoms may lead to a better understanding of potential reasons for these differences. Objectives: To determine sex differences in AF with respect to heart rate, duration, burden, and symptoms in patients undergoing mobile cardiac telemetry (MCT) monitoring. Methods: All patients who registered for ≤30-day MCT using PocketECG (MediLynx) in the USA in 2017 were included (n = 27,512, 58 % women). PocketECG records and transmits a three-lead ambulatory electrocardiogram (ECG) with real-time beat-to-beat analysis. Sex-related differences were analyzed with Chi2 and Spearmans rho. Results: Fewer women than men were diagnosed with AF lasting ≥30s (13.7 % versus [vs] 19.0 %, p

Polygonum maritimum L. (sea knotgrass) belongs to a genus commonly used in folk medicine to treat inflammation-related disorders. In vitro pharmacological studies have confirmed these properties that were ascribed to bioactive flavonoids, such as myricetin and quercetin glycosides. Therefore, this study aimed at establishing a micropropagation procedure for sea knotgrass for obtaining standardized materials for its potential commercial cultivation. For that, a complete plant regeneration protocol was developed by improving shoot multiplication from nodal explants, rooting and acclimatization procedures, followed by the assessment of the phenolic profile of the in vitro-produced plants. The combination of 3 mg/L 6-benzylaminopurine (BA) + 0.1 mg/L indole-3-acetic acid (IAA) induced the maximum shoot formation (10.3), which was significantly increased from the first to the second cycle (18.3). The best rooting capacity was observed on shoots derived from the control medium (100%), followed by 2 mg/L kinetin (KIN) (97%) and 3 mg/L BA + 0.1 mg/L IAA (90%); however, the shoot number at the end of the rooting phase was higher on shoots derived from 3 mg/L BA + 0.1 mg/L IAA (6.16). The plant growth regulators used in the multiplication phase influenced survival in the acclimatization process, and plants derived from the control medium had the highest survival percentage (63.1%). Acetone extracts made from aerial organs of micropropagated sea knotgrass showed a predominance of the flavonoid myricetin-3-O-rhamnoside (8.135 mg/g). Overall, the halophyte sea knotgrass was successfully micropropagated showing its potential as a medicinal crop for the extraction of bioactive molecules.

Children's emotion understanding has emerged as one of the best predictors of their psychological well-being, pro-social competences and school achievement. The main goal of this study was to evaluate for the first time the impact of an easy-to-use and not time-consuming classroom dialogue-based intervention (a) on preschool children's understanding of both simple and complex components of emotions and (b) on the range of individual differences in children's understanding of emotions. Participants were 112 typical 5-year-old children attending 10 different preschools in Canada and France. They were divided into an intervention group (N = 55, 7 classrooms) and a control group (N = 57, 7 classrooms). The intervention, "The Tales of Audrey-Anne," lasted over 8-9 months (15 h in total) and was conducted in the classroom by the children's habitual teachers without previous training in using the intervention. Children were assessed before and after the intervention for their emotion understanding with the Test of Emotion Comprehension (TEC). Four results were found. First, the intervention had a positive impact on children's both overall and specific levels of emotion understanding. Second, it did not change the hierarchical order of the specific levels (i.e. external, mental and reflective). Third, it did not have an impact on the range of individual differences (considerable both before and after the intervention). Fourth, it had a positive impact on the longitudinal stability of these differences (much smaller for the children in the experimental group after the intervention). These findings are discussed in terms of the theoretical and applied implications.

Elective shoulder arthroplasty is commonly performed in elderly patients with end-stage arthritis. However, a significant number of young patients also undergo this procedure. The surgical outcomes for young patients are not extensively studied compared to older patients. This study aimed to assess the short-term outcomes of anatomic total shoulder arthroplasty (aTSA) in patients aged 18-50 years with primary glenohumeral arthritis and compare them to patients aged 65-75 years. A retrospective review was conducted on aTSA procedures performed for glenohumeral arthritis at a single hospital system between January 1st, 2005, to September 15th, 2023. Patients aged 18-50 years with a minimum 2-years of follow-up were compared to a cohort of patients aged 65-75 years. Data included range of motion and patient-reported outcome measures (Disabilities of the Arm, Shoulder, and Hand [DASH], American Shoulder and Elbow Surgeons, Simple Shoulder [SS], and Visual Analog Scale pain scores), which were compared between the two groups preoperatively and at final follow-up. The younger group included 19 shoulders with a mean age of 44.2 ± 6.4 years at the time of surgery and a mean follow-up of 3.9 ± 1.9 years. The older group included 27 shoulders with a mean age of 70.3 ± 3.0 years at the time of surgery and a mean follow-up of 2.5 ± 0.8 years. The younger group failed to show improvements in all range of motion parameters at final follow-up, while the older group demonstrated improvement in range of motion for all measures. The older group had superior forward elevation and abduction at final follow-up. Both groups exhibited improvements in pain and shoulder function at final follow-up. The younger group did not show significant improvement in DASH scores at final follow-up. Preoperatively, the older group had significantly better DASH and SS scores compared to the younger group. The older group had significantly better DASH, American Shoulder and Elbow Surgeons, SS, and pain scores at final follow-up compared to the younger group. Both groups experienced significant improvement in pain and subjective outcome measures after a 2-year follow-up. Despite this, the younger cohort had worse shoulder range of motion outcomes and lower function and higher pain scores than the older cohort. Nonetheless, aTSA remains a valuable treatment option for young patients in the short-term. However, it is crucial to consider that younger patients may experience dissatisfaction and receive less pain relief compared to older patients, and these factors should be considered when determining the suitability of this treatment approach. [ABSTRACT FROM AUTHOR]

Noninvasive detection of molecular targets in living subjects could provide valuable insights into healthy function and disease. Here, the authors develop vasoactive imaging probes which allow wide-field in vivo mapping of nanomolar-level molecular species in rat brain.

Molecular imaging could have great utility for detecting, classifying, and guiding treatment of brain disorders, but existing probes offer limited capability for assessing relevant physiological parameters. Here, we describe a potent approach for noninvasive mapping of cancer-associated enzyme activity using a molecular sensor that acts on the vasculature, providing a diagnostic readout via local changes in hemodynamic image contrast. The sensor is targeted at the fibroblast activation protein (FAP), an extracellular dipeptidase and clinically relevant biomarker of brain tumor biology. Optimal FAP sensor variants were identified by screening a series of prototypes for responsiveness in a cell-based bioassay. The best variant was then applied for quantitative neuroimaging of FAP activity in rats, where it reveals nanomolar-scale FAP expression by xenografted cells. The activated probe also induces robust hemodynamic contrast in nonhuman primate brain. This work thus demonstrates a potentially translatable strategy for ultrasensitive functional imaging of molecular targets in neuromedicine.

L’étude porte sur les emplois du marqueur de cohérence discursive mais étudié en contexte de soin. Dans le cadre d’un projet, DECLICS, nous nous sommes focalisés sur la distribution fonctionnelle de mais en fonction du rôle du locuteur (médecins vs thérapeutes). En appui sur la littérature scientifique, trois macro-fonctions de mais (interlocutive-interactionnelle, logico-argumentative et logico-sémantique) sont décomposées en 17 types dont 16 sont présents dans le corpus DECLICS2016. Le relevé systématique des 122 occurrences de mais présentes dans le corpus a permis d’étudier la fréquence d’emplois comparatifs entre médecins et thérapeutes. Les résultats quantitatifs indiquent que les médecins emploient davantage mais que les thérapeutes, ce, indépendamment de leur service hospitalier. Grâce à une analyse qualitative, nous éclairons ensuite les mécanismes interactionnels en jeu lors des entretiens thérapeutiques médicaux vs cliniques, en déterminant les fonctions prépondérantes, secondaires et tertiaires assignables à chacune des 122 occurrences de mais. Sur ces 122 occurrences d’emplois, 32 occurrences sont le fait d’une fonction prépondérante unique, 80 emplois correspondent à une bi-fonctionnalité du marqueur et 10 d’une tri-fonctionnalité. Les résultats montrent que les macro-catégories interactionnelles et sémantiques permettent la distinction des rôles des soignants, et on constate un lien entre l’utilisation de la fonction prépondérante argumentative et la fonction secondaire logico-sémantique de type circonstanciel. Les résultats ont permis d’extraire deux patterns d’emplois de la tri-fonctionnalité de mais, utilisée presque exclusivement par les thérapeutes. Cette étude montre que les médecins utilisent mais pour activer des opérations logico-argumentatives, les thérapeutes activant préférentiellement un but interactionnel.

Spinal cord injury (SCI) causes disturbances of motor skills. Free radicals have been shown to be essential for the development of spinal cord trauma. Despite some progress, until now no effective pharmacological therapies against SCI have been verified. The purpose of our experiment was to investigate the neuroprotective effects of ebselen on experimental SCI. Twenty-two rats subjected to SCI were randomly subjected to SCI with no further treatment (n = 10) or intragastric administration of ebselen (10 mg/kg) immediately and 24 hours after SCI. Behavioral changes were assessed using the Basso, Beattie, and Bresnahan locomotor scale and footprint test during 12 weeks after SCI. Histopathological and immunohistochemical analyses of spinal cords and brains were performed at 12 weeks after SCI. Magnetic resonance imaging analysis of spinal cords was also performed at 12 weeks after SCI. Rats treated with ebselen presented only limited neurobehavioral progress as well as reduced spinal cord injuries compared with the control group, namely length of lesions (cysts/scars) visualized histopathologically in the spinal cord sections was less but cavity area was very similar. The same pattern was found in T2-weighted magnetic resonance images (cavities) and diffusion-weighted images (scars). The number of FluoroGold retrogradely labeled neurons in brain stem and motor cortex was several-fold higher in ebselen-treated rats than in the control group. The findings suggest that ebselen has only limited neuroprotective effects on injured spinal cord. All exprimental procedures were approved by the Local Animal Ethics Committee for Experiments on Animals in Katowice (Katowice, Poland) (approval No. 19/2009).

We investigated the effect of diets containing organic zinc and a mixture of medicinal herbs on ruminal microbial fermentation and histopathology in lambs. Twenty-eight lambs were divided into four groups: unsupplemented animals (Control), animals supplemented with organic zinc (Zn, 70 mg Zn/kg diet), animals supplemented with a mixture of dry medicinal herbs (Herbs, 100 g dry matter (DM)/d) and animals supplemented with both zinc and herbs (Zn+Herbs). Each lamb was fed a basal diet composed of meadow hay (700 g DM/d) and barley (300 g DM/d). The herbs Fumaria officinalis L. (FO), Malva sylvestris L. (MS), Artemisia absinthium L. (AA) and Matricaria chamomilla L. (MC) were mixed in equal proportions. The lambs were slaughtered after 70 d. The ruminal contents were used to determine the parameters of fermentation in vitro and in vivo and to quantify the microbes by molecular and microscopic methods. Samples of fresh ruminal tissue were used for histopathological evaluation. Quantitative analyses of the bioactive compounds in FO, MS, AA, and MC identified 3.961, 0.654, 6.482, and 12.084 g/kg DM phenolic acids and 12.211, 6.479, 0.349, and 2.442 g/kg DM flavonoids, respectively. The alkaloid content in FO was 6.015 g/kg DM. The diets affected the levels of total gas, methane and n-butyrate in vitro (P < 0.046, < 0.001, and < 0.001, respectively). Relative quantification by real-time PCR indicated a lower total ruminal bacterial population in the lambs in the Zn and Zn+Herbs groups than the Control group (P < 0.05). The relative abundances of Ruminococcus albus, R. flavefaciens, Streptococcus bovis, and Butyrivibrio proteoclasticus shifted in the Zn group. Morphological observation found a focally mixed infiltration of inflammatory cells in the lamina propria of the rumen in the Zn+Herbs group. The effect of the organic zinc and the herbal mixture on the parameters of ruminal fermentation in vitro was not confirmed in vivo, perhaps because the ruminal microbiota of the lambs adapted to the zinc-supplemented diets. Long-term supplementation of a diet combining zinc and medicinal herbs, however, may negatively affect the health of the ruminal epithelium of lambs.

Surface protein CD20 serves as the critical target of immunotherapy in various B-cell malignancies for decades, however its biological function and regulation remain largely elusive. Better understanding of CD20 function may help to design improved rational therapies to prevent development of resistance. Using CRISPR/Cas9 technique, we have abrogated CD20 expression in five different malignant B-cell lines. We show that CD20 deletion has no effect upon B-cell receptor signaling or calcium flux. Also B-cell survival and proliferation is unaffected in the absence of CD20. On the contrary, we found a strong defect in actin cytoskeleton polymerization and, consequently, defective cell adhesion and migration in response to homeostatic chemokines SDF1α, CCL19 and CCL21. Mechanistically, we could identify a reduction in chemokine-triggered PYK2 activation, a calcium-activated signaling protein involved in activation of MAP kinases and cytoskeleton regulation. These cellular defects in consequence result in a severely disturbed homing of B cells in vivo.

Despite the unquestionable success achieved by rituximab-based regimens in the management of diffuse large B-cell lymphoma (DLBCL), the high incidence of relapsed/refractory disease still remains a challenge. The widespread clinical use of chemo-immunotherapy demonstrated that it invariably leads to the induction of resistance; however, the molecular mechanisms underlying this phenomenon remain unclear. Rituximab-mediated therapeutic effect primarily relies on complement-dependent cytotoxicity and antibody-dependent cell cytotoxicity, and their outcome is often compromised following the development of resistance. Factors involved include inherent genetic characteristics and rituximab-induced changes in effectors cells, the role of ligand/receptor interactions between target and effector cells, and the tumor microenvironment. This review focuses on summarizing the emerging advances in the understanding of the molecular basis responsible for the resistance induced by various forms of immunotherapy used in DLBCL. We outline available models of resistance and delineate solutions that may improve the efficacy of standard therapeutic protocols, which might be essential for the rational design of novel therapeutic regimens.