Daily quetiapine after severe TBI improves learning and memory.

BACKGROUND: Traumatic brain injury (TBI) induces cognitive deficits driven by neuroinflammation and cerebral edema. The commonly used atypical antipsychotic, quetiapine (QTP), has been recently shown to improve post-TBI outcomes. We hypothesized that QTP would thereby improve animal learning and memory 2 weeks after severe TBI. METHODS: CD1 male mice (n = 35) underwent severe TBI (controlled cortical impact, injury, I) or sham craniotomy (S), followed by BID saline (P, placebo) or QTP (10 or 20 mg/kg, IP) for 2 weeks. Animals underwent Morris Water Maze (MWM) exercises to gauge spatial learning and memory. The distance and time required for swimming animals to reach the platform area (Zone 5, Z5) located in quadrant 1 (Zone 1, Z1) was calculated from digital video recordings analyzed using Ethovision software. Animal bodyweights were recorded daily and on day 14, injured cerebral hemispheres were procured for edema determination (wet-to-dry ratio). Intergroup differences were evaluated with ANOVA/Bonferroni correction (p < 0.05). RESULTS: On day 14, animal weight loss recovery was lowest in I + P compared to I + QTP20 and I + QTP10 (p ≤ 0.01 for either). Cerebral edema was greatest in I + P, and only significantly decreased in I + QTP20 (p < 0.05). Both QTP doses similarly improved spatial learning by significantly reducing latency time and travel distance to target zones (p < 0.05). In probe memory trials, only I + QTP20 and not I + QTP10 significantly favored animal reaching or crossing into target zones (p < 0.05). CONCLUSION: Post-TBI QTP reduces brain edema and improves spatial learning and memory with a potential dose dependence impact benefiting memory up to 14 days. These data suggest an unanticipated QTP benefit following brain injury that should be specifically explored.

Is vitamin D receptor (VDR) polymorphism associated with head and neck cancer risk? A systematic review and meta-analysis.

BACKGROUND: Head and neck cancer encompasses neoplasms affecting the oral cavity, pharynx, larynx, and thyroid. Identifying factors that modulate the carcinogenesis process can aid in identifying subgroups at higher risk of developing the disease, enabling implementation of prevention programs. Vitamin D receptor polymorphisms can affect the carcinogenesis of various tumors by altering vitamin D metabolism and cellular response. METHODS: To elucidate the role of vitamin D receptor polymorphisms in head and neck cancer, a systematic review was performed, searching the Embase, PubMed, Scopus, and Lilacs databases. A total of 19 articles met the inclusion criteria. The frequency of vitamin D receptors polymorphism alleles (FokI, ApaI, BsmI, TaqI, Cdx2, rs2107301, rs2238135) was recorded and pooled to calculate the odds ratio in a meta-analysis using the Review Manager software. RESULTS: Subgroup analysis demonstrated significant associations in the anatomical site of cancer (oral cancer in ApaI and BsmI, and unspecified subsites of head and neck cancer in TaqI), genotyping method (FokI and BsmI), and continent of the study (ApaI, FokI, and BsmI). CONCLUSION: Our findings were heterogeneous, as with other evidence available in the literature. Therefore, more clinical studies with larger sample sizes are needed to obtain more accurate results on the relationship between vitamin D receptor polymorphism and head and neck cancer.

Multivariate analysis applied to X-ray fluorescence to assess soil contamination pathways: case studies of mass magnetic susceptibility in soils near abandoned coal and W/Sn mines.

Determining the origin and pathways of contaminants in the natural environment is key to informing any mitigation process. The mass magnetic susceptibility of soils allows a rapid method to measure the concentration of magnetic minerals, derived from anthropogenic activities such as mining or industrial processes, i.e., smelting metals (technogenic origin), or from the local bedrock (of geogenic origin). This is especially effective when combined with rapid geochemical analyses of soils. The use of multivariate analysis (MVA) elucidates complex multiple-component relationships between soil geochemistry and magnetic susceptibility. In the case of soil mining sites, X-ray fluorescence (XRF) spectroscopic data of soils contaminated by mine waste shows statistically significant relationships between magnetic susceptibility and some base metal species (e.g., Fe, Pb, Zn, etc.). Here, we show how qualitative and quantitative MVA methodologies can be used to assess soil contamination pathways using mass magnetic susceptibility and XRF spectra of soils near abandoned coal and W/Sn mines (NW Portugal). Principal component analysis (PCA) showed how the first two primary components (PC-1 + PC-2) explained 94% of the sample variability, grouped them according to their geochemistry and magnetic susceptibility in to geogenic and technogenic groups. Regression analyses showed a strong positive correlation (R2 > 0.95) between soil geochemistry and magnetic properties at the local scale. These parameters provided an insight into the multi-element variables that control magnetic susceptibility and indicated the possibility of efficient assessment of potentially contaminated sites through mass-specific soil magnetism.

Profiling of Tumor-Infiltrating Immune Cells and Their Impact on Survival in Glioblastoma Patients Undergoing Immunotherapy with Dendritic Cells.

Glioblastomas (GBM) are the most common primary malignant brain tumors, comprising 2% of all cancers in adults. Their location and cellular and molecular heterogeneity, along with their highly infiltrative nature, make their treatment challenging. Recently, our research group reported promising results from a prospective phase II clinical trial involving allogeneic vaccination with dendritic cells (DCs). To date, six out of the thirty-seven reported cases remain alive without tumor recurrence. In this study, we focused on the characterization of infiltrating immune cells observed at the time of surgical resection. An analytical model employing a neural network-based predictive algorithm was used to ascertain the potential prognostic implications of immunological variables on patients' overall survival. Counterintuitively, immune phenotyping of tumor-associated macrophages (TAMs) has revealed the extracellular marker PD-L1 to be a positive predictor of overall survival. In contrast, the elevated expression of CD86 within this cellular subset emerged as a negative prognostic indicator. Fundamentally, the neural network algorithm outlined here allows a prediction of the responsiveness of patients undergoing dendritic cell vaccination in terms of overall survival based on clinical parameters and the profile of infiltrated TAMs observed at the time of tumor excision.

Implementation Strategies to Promote Short-Course Radiation for Bone Metastases.

Importance: For patients with nonspine bone metastases, short-course radiotherapy (RT) can reduce patient burden without sacrificing clinical benefit. However, there is great variation in uptake of short-course RT across practice settings. Objective: To evaluate whether a set of 3 implementation strategies facilitates increased adoption of a consensus recommendation to treat nonspine bone metastases with short-course RT (ie, ≤5 fractions). Design, Setting, and Participants: This prospective, stepped-wedge, cluster randomized quality improvement study was conducted at 3 community-based cancer centers within an existing academic-community partnership. Rollout was initiated in 3-month increments between October 2021 and May 2022. Participants included treating physicians and patients receiving RT for nonspine bone metastases. Data analysis was performed from October 2022 to May 2023. Exposures: Three implementation strategies-(1) dissemination of published consensus guidelines, (2) personalized audit-and-feedback reports, and (3) an email-based electronic consultation platform (eConsult)-were rolled out to physicians. Main Outcomes and Measures: The primary outcome was adherence to the consensus recommendation of short-course RT for nonspine bone metastases. Mixed-effects logistic regression at the bone metastasis level was used to model associations between the exposure of physicians to the set of strategies (preimplementation vs postimplementation) and short-course RT, while accounting for patient and physician characteristics and calendar time, with a random effect for physician. Physician surveys were administered before implementation and after implementation to assess feasibility, acceptability, and appropriateness of each strategy. Results: Forty-five physicians treated 714 patients (median [IQR] age at treatment start, 67 [59-75] years; 343 women [48%]) with 838 unique nonspine bone metastases during the study period. Implementing the set of strategies was not associated with use of short-course RT (odds ratio, 0.78; 95% CI, 0.45-1.34; P = .40), with unadjusted adherence rates of 53% (444 lesions) preimplementation vs 56% (469 lesions) postimplementation; however, the adjusted odds of adherence increased with calendar time (odds ratio, 1.68; 95% CI, 1.20-2.36; P = .003). All 3 implementation strategies were perceived as being feasible, acceptable, and appropriate; only the perception of audit-and-feedback appropriateness changed before vs after implementation (19 of 29 physicians [66%] vs 27 of 30 physicians [90%]; P = .03, Fisher exact test), with 20 physicians (67%) preferring reports quarterly. Conclusions and Relevance: In this quality improvement study, a multicomponent set of implementation strategies was not associated with increased use of short-course RT within an academic-community partnership. However, practice improved with time, perhaps owing to secular trends or physician awareness of the study. Audit-and-feedback was more appropriate than anticipated. Findings support the need to investigate optimal approaches for promoting evidence-based radiation practice across settings.

Automated Capillary Electrophoresis Immunoblot for the Detection of Alpha-Synuclein in Mouse Tissue.

Background: Alpha-synuclein (aSyn) is a key player in neurodegenerative diseases such as Parkinson's disease (PD), dementia with Lewy bodies, or multiple system atrophy. aSyn is expressed throughout the brain, and can also be detected in various peripheral tissues. In fact, initial symptoms of PD are non-motoric and include autonomic dysfunction, suggesting that the periphery might play an important role in early development of the disease. aSyn is expressed at relatively low levels in non-central tissues, which brings challenges for its detection and quantification in different tissues. Objective: Our goal was to assess the sensitivity of aSyn detection in central and peripheral mouse tissues through capillary electrophoresis (CE) immunoblot, considering the traditional SDS-PAGE immunoblot as the current standard. Methods: Tissues from central and non-central origin from wild type mice were extracted, and included midbrain, inner ear, and esophagus/stomach. aSyn detection was assessed through immunoblotting using Simple Western size-based CE and SDS-PAGE. Results: CE immunoblots show a consistent detection of aSyn in central and peripheral tissues. Through SDS-PAGE, immunoblots revealed a reliable signal corresponding to aSyn, particularly following membrane fixation. Conclusion: Our results suggest a reliable detection of aSyn in central and peripheral tissues using the CE Simple Western immunoblot system. These observations can serve as preliminary datasets when aiming to formally compare CE with SDS-PAGE, as well as for further characterization of aSyn using this technique.

Dose-Dependent Tranexamic Acid Blunting of Penumbral Leukocyte Mobilization and Blood-Brain Barrier Permeability Following Traumatic Brain Injury: An In Vivo Murine Study.

BACKGROUND: Early posttraumatic brain injury (TBI) tranexamic acid (TXA) may reduce blood-brain barrier (BBB) permeability, but it is unclear if this effect is fixed regardless of dose. We hypothesized that post-TBI TXA demonstrates a dose-dependent reduction of in vivo penumbral leukocyte mobilization, BBB microvascular permeability, and enhancement of neuroclinical recovery. METHODS: CD1 male mice (n = 40) were randomly assigned to TBI by controlled cortical impact (injury [I]) or sham TBI (S), followed by intravenous bolus of either saline (placebo [P]) or TXA (15, 30, or 60 mg/kg). At 48 h, in vivo pial intravital microscopy visualized live penumbral BBB microvascular leukocytes and albumin leakage. Neuroclinical recovery was assessed by Garcia Neurological Test scores and animal weight changes at 24 h and 48 h after injury. RESULTS: I + TXA60 reduced live penumbral leukocyte rolling compared with I + P (p < 0.001) and both lower TXA doses (p = 0.017 vs. I + TXA15, p = 0.012 vs. I + TXA30). Leukocyte adhesion was infrequent and similar across groups. Only I + TXA60 significantly reduced BBB permeability compared with that in the I + P (p = 0.004) group. All TXA doses improved Garcia Test scores relative to I + P at both 24 h and 48 h (p < 0.001 vs. I + P for all at both time points). Mean 24-h body weight loss was greatest in the I + P (- 8.7 ± 1.3%) group and lowest in the I + TXA15 (- 4.4 ± 1.0%, p = 0.051 vs. I + P) group. CONCLUSIONS: Only higher TXA dosing definitively abrogates penumbral leukocyte mobilization, preserving BBB integrity post TBI. Some neuroclinical recovery is observed, even with lower TXA dosing. Better outcomes with higher dose TXA after TBI may occur secondary to blunting of leukocyte-mediated penumbral cerebrovascular inflammation.

Alternate routes to mnm5s2U synthesis in Gram-positive bacteria.

The wobble bases of tRNAs that decode split codons are often heavily modified. In bacteria, tRNAGlu, Gln, Asp contains a variety of xnm5s2U derivatives. The synthesis pathway for these modifications is complex and fully elucidated only in a handful of organisms, including the Gram-negative Escherichia coli K12 model. Despite the ubiquitous presence of mnm5s2U modification, genomic analysis shows the absence of mnmC orthologous genes, suggesting the occurrence of alternate biosynthetic schemes for the conversion of cmnm5s2U to mnm5s2U. Using a combination of comparative genomics and genetic studies, a member of the YtqA subgroup of the radical Sam superfamily was found to be involved in the synthesis of mnm5s2U in both Bacillus subtilis and Streptococcus mutans. This protein, renamed MnmL, is encoded in an operon with the recently discovered MnmM methylase involved in the methylation of the pathway intermediate nm5s2U into mnm5s2U in B. subtilis. Analysis of tRNA modifications of both S. mutans and Streptococcus pneumoniae shows that growth conditions and genetic backgrounds influence the ratios of pathway intermediates owing to regulatory loops that are not yet understood. The MnmLM pathway is widespread along the bacterial tree, with some phyla, such as Bacilli, relying exclusively on these two enzymes. Although mechanistic details of these newly discovered components are not fully resolved, the occurrence of fusion proteins, alternate arrangements of biosynthetic components, and loss of biosynthetic branches provide examples of biosynthetic diversity to retain a conserved tRNA modification in Nature.IMPORTANCEThe xnm5s2U modifications found in several tRNAs at the wobble base position are widespread in bacteria where they have an important role in decoding efficiency and accuracy. This work identifies a novel enzyme (MnmL) that is a member of a subgroup of the very versatile radical SAM superfamily and is involved in the synthesis of mnm5s2U in several Gram-positive bacteria, including human pathogens. This is another novel example of a non-orthologous displacement in the field of tRNA modification synthesis, showing how different solutions evolve to retain U34 tRNA modifications.

Effects of foam roller on pain intensity in individuals with chronic and acute musculoskeletal pain: a systematic review of randomized trials.

OBJECTIVE: To analyze the effects of using foam roller on pain intensity in individuals with chronic and acute musculoskeletal pain. METHODS: This systematic review was registered in the National Institute for Health Research's prospective online registry of systematic reviews (PROSPERO) under CRD42023456841. The databases Pubmed, Medline (via Ovid), Embase, BVS, and PEDro (Physiotherapy Evidence Database) were consulted to carry out this systematic review. Notably, the records of clinical trials characterized as eligible were manually searched. The search terms were: (foam rolling OR foam rolling vibration) AND (acute musculoskeletal pain) AND (chronic musculoskeletal pain). The search was performed until August 22, 2023. For the analysis of the methodological quality, the PEDro scale was used for each of the manuscripts included in the systematic review. Due to the heterogeneity in the studies included in this systematic review, performing a meta-analysis of the analyzed variables was impossible. RESULTS: Only six manuscripts were eligible for data analysis. The type of FR used was non-vibrational, being applied by a therapist in only one of the manuscripts. With an application time ranging from at least 45 s to 15 min, the non-vibrational FR was applied within a day up to six weeks. Using the PEDro scale, scores were assigned that varied between 4 and 8 points, with an average of 6 ± 1.29 points. Only two randomized clinical trials found a significant benefit in pain intensity of adding FR associated with a therapeutic exercise protocol in individuals with patellofemoral pain syndrome and chronic neck pain. CONCLUSION: The results of this systematic review do not elucidate or reinforce the clinical use of FR in pain intensity in individuals with chronic and acute musculoskeletal pain.

A Survey on Environmental Sustainability Among Anesthesiologists: An Opportunity for Changing Behaviors.

Introduction  Environmental sustainability (ES) is a current issue related to natural resource scarcity, pollution and climate change. Although operating rooms (ORs) comprise a small proportion of the entire hospital infrastructure, they significantly impact the environment. Anesthesiologists are ideally positioned to assume leadership, mitigating this negative impact regarding OR waste in the environment. We created a Green Team, comprising multidisciplinary professionals from different areas of a tertiary Portuguese medical center, and conducted a survey that was sent to all the institution's anesthesiologists to assess the current state of ES. Results  From the sample of 133 participants, 101 responses were obtained. Concerning knowledge and training on ES, a significant portion of the respondents (66.7%) seem to attribute "great importance" to the subject. As to the greatest barrier to waste separation in the OR, several respondents highlighted the issues of "inadequate information/education/training" (62.6%) and "lack of support from hospital/OR in-chief/administration" (26.3%). Finally, among seven methods to raise awareness of ES, "training during residency" was the top choice for these professionals, with 52.5% of the votes. Discussion  Most anesthesiologists who responded to the survey recognize the utmost importance of ES and have perceived the environmental impact of their anesthetic practices in the OR. Overall, this tendency is consistent with other international studies. Moreover, most of those surveyed separate waste at home and want to extend this practice -in a more structured approach- to their workplace, with an effective separation of anesthetic and general waste in the OR. Conclusion Professionals perceive barriers to performing green practices, whether the lack of environmental education and awareness, the absence of recycling containers or waste separation bags, or the lack of protocols and guidelines implementing these circuits. With the publication of this work, we aim to encourage other institutions to implement ES projects in their hospitals and ORs.

Getting pastoral systems productivity right.

Beef production in pasture-based systems is increasingly contested due to related biophysical and environmental challenges. Addressing these requires rigorous science-based evidence to inform private decisions and public policies. Increasing yields and simultaneously reducing the negative environmental impacts of agricultural and livestock production are central to sustainable intensification approaches. Yet, stocking rate, the commonly used metric for animal productivity in pastures, or more broadly, of sustainable intensification in pastoral production systems, warrants scrutiny to signpost successful transformative change of food systems and to avoid provision of misleading policy advice. Here we discuss why future studies would benefit of considering the two constituent elements of productivity in pastoral systems - animal performance (kg of animal product/head) and stocking rates (heads/ha) -, rather than stocking rates alone.

Cardiorespiratory coupling is associated with exercise capacity in athletes: A cross-sectional study.

PURPOSE: To determine the association between exercise capacity based on peak oxygen uptake (VO2peak) and resting cardiorespiratory coupling (CRC) levels in athletes and non-athletes' subjects. METHODS: A cross-sectional study was carried out in 42 apparently healthy male subjects, aged between 20 and 40 years old. The participants were allocated into athletes (n = 21) and non-athletes (n = 21) groups. Resting electrocardiogram and respiratory movement (RESP) were simultaneously acquired during 15 min in supine position and quiet breathing. The beat-to-beat heart period (HP) and RESP series were determined from the recorded signals. Traditional analysis of HP based on frequency domain indexes was performed considering the high-frequency (0.15 - 0.45 Hz) components. To compute the CRC, the linear association between HP and RESP series was determined via squared coherence function and directionality of interaction was investigated through the causal extension of this approach. The exercise capacity was assessed through incremental cardiopulmonary exercise testing in order to determine the VO2peak. RESULTS: Traditional analysis of HP based on high-frequency index was not correlated with exercise capacity in the athletes (r = -0.1, p = 0.5) and non-athletes (r = -0.1, p = 0.3) cohorts. However, resting CRC values was associated with exercise capacity in athletes (r = 0.4, p = 0.03), but not in the non-athletes group (r = -0.2, p = 0.3). CONCLUSION: These results suggest that improved resting values of CRC is associated with higher exercise capacity (VO2peak) in endurance athletes. Moreover, frequency domain of HP was not sensitive to identifying this relationship, probably because effects of training on parasympathetic modulation might be affected by respiratory dynamics, and this influence has a directionality (i.e., from RESP to HP).

Heart rate variability in adults with chronic musculoskeletal pain: A systematic review.

PURPOSE: The aim of this review was to compare the heart rate variability (HRV) responses at rest of adults with chronic musculoskeletal pain against healthy controls. METHODS: The PubMed, Scopus, Web of Science (Science and Social Science Citation Index), and CINAHL databases were searched, with no date restrictions. Two independent reviewers selected observational studies that characterized the HRV responses at rest in adults with chronic musculoskeletal pain compared with those of healthy controls. Methodological quality was assessed using the Downs and Black checklist. RESULTS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. HRV in adults with chronic musculoskeletal pain was evaluated systematically. Of the 4893 studies screened, 20 of poor-to-moderate quality met the inclusion criteria. Most studies used electrocardiography and at least one time and/or frequency domain index. Studies were found that investigated HRV in adults with temporomandibular disorders, neck pain, whiplash, low back pain, and fibromyalgia. The heterogeneity of the studies in relation to painful conditions, parameters or position for HRV analysis precluded a meta-analysis. In general, these studies seem to show increased sympathetic and decreased parasympathetic modulation in adults with musculoskeletal pain when compared to controls. CONCLUSIONS: Adults with musculoskeletal pain exhibited a decline in HRV compared to controls. However, definitive conclusions cannot be drawn since the evidence is heterogeneous and of moderate quality. Further high-quality research with standardized measurements is needed.

Disparities in Access to Radiotherapy Among Hispanic/Latinx Populations in the United States: How Far Have We Left to Go?

OBJECTIVES: The Hispanic/Latinx population has consistently faced disparities in oncology access and outcomes with cancer being the leading cause of death in this population. We evaluate recent research in radiation therapy disparities among the Hispanic/Latinx population in the United States since our seminal analysis from 2017. METHODS: A PubMed literature search was conducted for articles published from January 2017 through March 2023. Four term combinations were utilized, including: (1) "Hispanic" and "Radiotherapy" and "Disparities", (2) "Latino" and "Radiotherapy" and "Hispanic", (3) "Hispanic" and "Radiation" and "Disparities", and (4) "Latino" and "Radiation" and "Disparities." Included studies were those taking place in the United States, examined radiation oncology care, and examined health disparities. RESULTS: Fifty-eight of 245 articles returned met inclusion criteria and spanned 6 disparity-types: (1) Stage at Presentation, (2) Time to Treatment Initiation & Completion, (3) Receipt of Treatment and Guideline-Concordant Care, (4) Geography, (5) Clinical Trial Access and (6) Insurance Barriers and Treatment Center Type. The most common disparity was receipt of treatment and guideline-concordant care (n=39 studies), demonstrating that the Hispanic/Latinx population was less likely to receive guideline-concordant treatment or treatment at all. In additon, studies identified disparities in time to treatment and completion (n=12), geography (n=5), clinical trial access (n=3), and insurance and treatment center access (n=5). CONCLUSIONS: Disparities in radiotherapy access remain prominent for the Hispanic/Latinx population through a multitude of barriers, despite increasing interest in disparities research. Continued health care disparities research with tangible interventions are needed in radiation oncology to properly understand and address this problem.

Development and validation of method for the simultaneous determination of sulfamethazine, trimethoprim and doxycycline in veterinary formulation using high performance liquid chromatography.

Sulfamethazine (SMZ), trimethoprim (TMP) and doxycycline (DOXY) are drugs of choice used in the treatment of intestinal and respiratory infections that affect poultry and swine. The aim of this study was develop and validate a simple, sensitive and fast method for the simultaneous determination of SMZ, TMP and DOXY in veterinary formulations by high-performance liquid chromatography. The separation was performed on a Macherey-Nagel C8 analytical column (4 × 125 mm, 5 µm), with a flow rate of 0.5 ml min-1 and detection at 268, 270 and 350 nm, for SMZ, TMP and DOXY, respectively. All measurements were performed in acetonitrile-water (45:55 v/v; pH 3.0). The analytical curves were linear (r > 0.9997) in the concentration range of 5.0-35.0 µg ml-1 for SMZ, 1.0-7.0 µg ml-1 for TMP and 7.0-13.0 µg ml-1 for DOXY. The method proved to be precise, robust, accurate and selective. In accelerated stability, the sample was analyzed for 6 months, with no major variations observed in organoleptic analysis and pH. Therefore, the developed method was proved to be suitable for routine quality control analyses for the simultaneous determination of SMZ, TMP and DOXY in pharmaceutical formulations.

Delayed tranexamic acid after traumatic brain injury impedes learning and memory: Early tranexamic acid is favorable but not in sham animals.

BACKGROUND: Early but not late tranexamic acid (TXA) after TBI preserves blood-brain-barrier integrity, but it is unclear if and how dose timing affects cognitive recovery beyond hours postinjury. We hypothesized that early (1 hour post-TBI) but not late (24 hours post-TBI) TXA administration improves cognitive recovery for 14 days. METHODS: CD1 male mice (n = 25) were randomized to severe TBI (injury [I], by controlled cortical impact) or sham craniotomy (S) followed by intravenous saline at 1 hour (placebo [P1]) or 30 mg/kg TXA at 1 hour (TXA1) or 24 hours (TXA24). Daily body weights, Garcia Neurological Test scores, brain/lung water content, and Morris water maze exercises quantifying swimming traffic in the platform quadrant (zone [Z] 1) and platform area (Z5) were recorded for up to 14 days. RESULTS: Among injured groups, I-TXA1 demonstrated fastest weight gain for 14 days and only I-TXA1 showed rapid (day 1) normalization of Garcia Neurological Test ( p = 0.01 vs. I-P1, I-TXA24). In cumulative spatial trials, compared with I-TXA1, I-TXA24 hindered learning (distance to Z5 and % time in Z1, p < 0.05). Compared with I-TXA1, I-TXA24 showed poorer memory with less Z5 time (0.51 vs. 0.16 seconds, p < 0.01) and Z5 crossing frequency. Unexpectedly, TXA in uninjured animals (S-TXA1) displayed faster weight gain but inferior learning and memory. CONCLUSION: Early TXA appears beneficial for cognitive and behavioral outcomes following TBI, although administration 24 hours postinjury consistently impairs cognitive recovery. Tranexamic acid in sham animals may lead to adverse effects on cognition.

Anemia hemolítica autoimune induzida pelo uso de imatinibe em paciente com leucemia mieloide crônica / Autoimmune hemolytic anemia induced by the use of imatinib in a patient with chronic myeloid leukemia

A leucemia mieloide crônica é uma neoplasia mieloproliferativa clonal ocasionado, em 95% dos casos, pela translocação recíproca do cromossomo 9 e 22 (cromossomo Philadelphia), gerando um gene de fusão (BCR-ABL', que promove aumento da atividade da enzima tirosina kinase, levando assim, ao aumento da produção de granulócitos maduros e em maturação. O principal tratar-ento desta comorbidade é uso de drogas que inibem a atividade dessa enzima :mpedindo a proliferação celular, chamados inibidores de tirosina kinase, sendo o mes"ato de imatinibe uma dessas drogas. Efeitos colaterais leves devido ao uso do mesilato de imatinibe foram relatados em literatura, como citopenias, edemas e efeitos gastrointestinais, sendo a anemia hemolítica autoimune um evento raro com poucos relatos em literatura. A anemia hemolítica autoimune é uma patologia que surge quando anticorpos se contra as hemácias do indivíduo, e podem ser induzidas pelo uso de alguns medicamentos (anemia hemolítica autoimune induzida por drogas), dentre eles, o nesilato de imatinibe. O principal tratamento da anemia hemolítica autoimune Induzida por drogas é a suspensão da medicação. O presente estudo visa relatar um caso raro de anemia hemolítica autoimune induzida pelo uso de imatinibe no "atamento de leucemia mieloide crônica. Como conclusão, oferece evidênc:as c:rnicas dessa associação

Chronic myeloid leukemia is a clonal myeloproliferative neoplasm caused, in 95% of cases, by the reciprocal translocation of chromosomes 9 and 22 (Philadelphia chromosome), generating a fusion gene (BCR-ABL) that promotes increased activity of the tyrosine kinase enzyme, thus leading to increased production of mature and maturing granulocytes. The main treatment for this comorbidity is the use of drugs that Inhibit the activity of this enzyme, preventing cellular control, called tyrosine kinase inhibitors, with imatinib mesylate being one of these drugs. Mild side effects due to the use of imatinib mesylate have been reported in the literature, such as cytopenias, edema and gastrointestinal effects, with autoimmune hemolytic anemia being a rare event with few reports In the literature. Autoimmune hemolytic anemia is a pathology that arises when antibodies are directed against the individual's red blood cells, and can be caused by the use of some medications (autoimmune hemolytic anemia caused by drugs), including imatinib mesylate. The main treatment for autoimmune hemolytic anemia caused by drugs is stopping the medication. The present study aims to report a rare case of autoimmune hemolytic anemia caused by the use of imatinib in the treatment of chronic myeloid leukemia. In conclusion, it offers clinical evidence of this association

Why orthodontists need to know about molar incisor hypomineralization.

Molar incisor hypomineralization (MIH) is a systemic developmental qualitative defect of the enamel that affects 1-4 first permanent molars with or without incisor involvement. Enamel hypomineralization is identified visually as a demarcated opacity with a clear border with varying extensions and can be white, yellow, or brown. This opacity is characterized by a reduced quality of enamel that is of normal thickness but not fully mineralized. It is very common for the affected teeth to present with posteruptive breakdown, making them susceptible to caries, leading to their subsequent loss. Thus, MIH is a significant dental problem with clinical, economic, and psychosocial implications. The planned extraction of compromised teeth is a valid alternative to complex restorative treatment. Orthodontists' involvement is essential in developing effective treatment strategies for children affected by MIH, contributing to their oral health and well-being.