Bacterial Tracheitis: A New Presentation of a Well-Known Disease.

Bacterial tracheitis (BT) is an uncommon life-threatening condition that results in acute upper airway obstruction. Classical signs include a toxic appearance, stridor, tachypnoea, and fever, often leading to rapid clinical deterioration. Recent studies have shown a shift in BT epidemiology and presentation, where stridor and respiratory distress are now predominant. A poor response to corticosteroids or nebulized epinephrine is also commonly described, along with a need for mechanical ventilation. We present the case of a five-year-old boy admitted to the emergency department with cough, stridor, and dyspnea that had significantly worsened over the previous hours. He presented reasonable general condition, marked retractions, poor air entry, stridor, and wheezing. Investigation revealed a slight elevation of C-reactive protein and leukocytosis with neutrophilia. Anteroposterior x-ray showed narrowing of subglottic airways (steeple sign). There was no response to oral/nebulized corticoids, nebulized adrenaline, or bag-valve-mask oxygenation. Antibiotic therapy with ceftriaxone was initiated. Due to deteriorating clinical conditions with severe respiratory acidosis, orotracheal intubation was required. Later Streptococcus pyogenes was isolated in the bronchial secretions and a targeted antibiotic regimen was administered. Progressive clinical and analytical improvement was observed with no complications. Although uncommon, BT remains a severe infectious condition affecting otherwise healthy children. Our case underscores the severity of the disease and the imperative for invasive interventions to achieve favorable outcomes. It also supports recent findings indicating a shift in predominant symptoms and prognosis. Clinicians must be vigilant and knowledgeable, recognizing that worsening stridor and respiratory distress unresponsive to conservative treatment are key indicators for diagnosing BT.

Selective Synthesis of 3-(1H-Tetrazol-5-yl)-indoles from 2H-Azirines and Arynes.

A new selective synthetic approach to indole derivatives bearing a tetrazole moiety has been developed. Arynes, generated in situ from o-(trimethylsilyl)aryl triflates and KF, reacted smoothly with 2-(2-benzyl-2H-tetrazol-5-yl)-2H-azirines to give 3-(2-benzyl-2H-tetrazol-5-yl)-indole derivatives with high selectivity. Deprotection of the tetrazole moiety gave 3-(1H-tetrazol-5-yl)-indole derivatives.

Identification of Predictive Biomarkers of Lameness in Transition Dairy Cows.

The aim of this study was to identify with a high level of confidence metabolites previously identified as predictors of lameness and understand their biological relevance by carrying out pathway analyses. For the dairy cattle sector, lameness is a major challenge with a large impact on animal welfare and farm economics. Understanding metabolic alterations during the transition period associated with lameness before the appearance of clinical signs may allow its early detection and risk prevention. The annotation with high confidence of metabolite predictors of lameness and the understanding of interactions between metabolism and immunity are crucial for a better understanding of this condition. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with authentic standards to increase confidence in the putative annotations of metabolites previously determined as predictive for lameness in transition dairy cows, it was possible to identify cresol, valproic acid, and gluconolactone as L1, L2, and L1, respectively which are the highest levels of confidence in identification. The metabolite set enrichment analysis of biological pathways in which predictors of lameness are involved identified six significant pathways (p < 0.05). In comparison, over-representation analysis and topology analysis identified two significant pathways (p < 0.05). Overall, our LC-MS/MS analysis proved to be adequate to confidently identify metabolites in urine samples previously found to be predictive of lameness, and understand their potential biological relevance, despite the challenges of metabolite identification and pathway analysis when performing untargeted metabolomics. This approach shows potential as a reliable method to identify biomarkers that can be used in the future to predict the risk of lameness before calving. Validation with a larger cohort is required to assess the generalization of these findings.

Protocols for breaking bad news in health care: a scoping review protocol.

OBJECTIVE: This scoping review will map the available evidence on communication protocols for breaking bad news to adult patients and their families in health care. INTRODUCTION: Breaking bad news to adult patients and their families is a challenging task for health care professionals. To address these challenges, communication protocols have been developed to support health care professionals in breaking bad news in a compassionate and effective manner while respecting each patient's individuality. INCLUSION CRITERIA: This scoping review will consider all studies that focus on communication protocols (original or adapted versions) to break bad news to adult patients and/or their families (adults) in any health care context, regardless of the approach (face-to-face, telephone, video, or other). Quantitative, qualitative, and mixed methods studies, systematic reviews, and text and opinion papers will be considered for inclusion in this review. METHODS: This review will be conducted in accordance with the JBI methodology for scoping reviews. The search strategy will aim to locate both published and unpublished evidence in English, Spanish, and Portuguese. The databases to be searched include CINAHL Plus Complete (EBSCOhost), MEDLINE (PubMed), Academic Search Complete, Psychology and Behavioral Sciences Collection, Scopus, and Web of Science Core Collection. Gray literature will also be searched for. Two independent reviewers will independently perform study selection and data extraction. Data will be extracted using a data extraction tool developed by the reviewers. Any disagreements that arise between the reviewers will be resolved through discussion or with an additional reviewer. Data will be presented in tabular and narrative format. DETAILS OF THE REVIEW CAN BE FOUND IN OPEN SCIENCE FRAMEWORK: https://osf.io/s6ru7/.

Barriers and facilitators of evidence-based practice in the Portuguese context: perceptions of formal nursing leaders.

INTRODUCTION: Formal nursing leaders play an important role in promoting and sustaining evidence-based practice (EBP) in the clinical context, particularly by creating a conducive environment for change and increasing clinicians' awareness of the positive results of EBP. However, nursing leaders encounter both barriers and facilitators in their work; therefore, it is important to understand their perceptions on this topic. OBJECTIVE: The objective of this study was to understand the perceptions of formal nursing leaders about barriers and facilitators for EBP. METHODS: A descriptive exploratory study with a qualitative approach was conducted. A convenience sample was obtained, consisting of formal nursing leaders from three Portuguese health care institutions. Data were collected through semi-structured interviews. Content analysis was conducted using MAXQDA Analytic Pro 2022 software. RESULTS: Seventeen formal nursing leaders were interviewed. Five categories of EBP barriers were identified: (1) scarce resources and inefficient resource management; (2) non-conducive organizational culture; (3) distance between academia and the clinical context; (4) demotivation; and (5) resistance to change. Seven categories of EBP facilitators were identified: (1) availability of resources and efficient resource management; (2) conducive organizational culture; (3) partnerships between academia and the clinical context; (4) motivation and commitment; (5) leadership; (6) organization that regulates professional practice; and (7) multidisciplinary meetings. CONCLUSIONS: This study identified barriers and facilitators for EBP through the perceptions of formal nursing leaders. Collaborative multidisciplinary efforts by leaders, direct care professionals, academics, and researchers should be conducted to overcome barriers and strengthen facilitators for EBP. SPANISH ABSTRACT: http://links.lww.com/IJEBH/A242.

eHealth early intervention programs to support premature parents transitioning from NICU to home on parental and infant outcomes: a systematic review protocol.

OBJECTIVE: This review aims to assess the effectiveness of eHealth early intervention programs in supporting premature infants and their parents transition from neonatal intensive care units (NICUs) to home and the impact of such programs on parental and infant outcomes. INTRODUCTION: The literature has shown the benefits of eHealth early intervention programs to support premature infants and their parents after discharge from NICUs. Parents have reported benefits such as enhanced user-friendliness, increased confidence in infant care, satisfaction, and knowledge acquisition. However, the effectiveness of these programs on parental and infant outcomes remains unclear. INCLUSION CRITERIA: This review will consider studies that assess any early intervention program using eHealth to support premature infants and their parents after discharge from NICU. The programs may be initiated during hospitalization or within the first month of discharge. The programs will include interventions that use eHealth components (eg, teleconsultation), either alone or in combination with face-to-face interventions (eg, home visits). This review will consider parental outcomes, including stress, anxiety, competence, and satisfaction, as well as infant outcomes, including health service utilization and cognitive, motor, and social development. METHODS: This review will follow the JBI methodology for systematic reviews of effectiveness. The search strategy will aim to find both published and unpublished quantitative studies in English, Spanish, and Portuguese, without any geographical or cultural limitations. Two reviewers will independently perform study selection, critical appraisal, and data extraction. The results will be accompanied by a narrative synthesis. If possible, a meta-analysis will be conducted and the Summary of Findings will be presented using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO: CRD42023444721.

Metabolic syndrome induces benefits in mice experiencing severe sepsis, comparable to the effects of low-dose aspirin pretreatment in septic mice lacking metabolic syndrome.

BACKGROUND: Sepsis is a complex condition characterized by systemic host inflammation caused by an infection. Experimental and observational studies indicate that obesity, one of the components of metabolic syndrome (MetS), or aspirin (ASA) treatment could be associated with sepsis survival. However, the effects of ASA on septic mice with MetS-induced conditions have not been explored. METHODS: Swiss mice were administered monosodium glutamate (MSG) (4 mg/kg) during their first 5 days of life for MetS induction, while the control mice received an equimolar saline solution. MetS was validated in male mice on their 60th day of life. ASA treatment was administered for 15 days prior to sepsis (40 mg/kg). On the 75th day, sepsis was induced in MetS and control mice through cecal ligation and puncture (CLP). The effects of ASA on septic mice with MSG-induced MetS were assessed by determining survival rates, quantification of nitric oxide (NO), and cytokine levels in the plasma, while correlating these data with hematological, blood glucose and cardiovascular parameters. RESULTS: MetS was validated by Lee-Index (3 body weight/naso-anal length×1000), hypertension, and hyperglycemia in animals receiving MSG as neonates. In control animals, severe sepsis promoted hypoglycemia, which was associated with mortality, as well as increased plasma NO levels, hypotension, hematological alterations, and elevation of proinflammatory cytokines. In contrast, MetS and pre-treatment with ASA were able to prevent sepsis-related alterations. CONCLUSIONS: MetS and ASA pre-treatment provided protection against severe sepsis. However, ASA was ineffective in mice with MetS undergoing severe sepsis.

Knowledge, Use, and Perception of Brazilian Women about Contraceptive Methods: An Observational Study.

Background: In Brazil, where approximately 48.7 million women are of reproductive age, understanding contraceptive practices is essential for addressing public health challenges. This study evaluated into the knowledge, usage, and perceptions of contraceptive methods among Brazilian women, highlighting the influence of socioeconomic and demographic factors on their choices. Methods: We conducted a cross-sectional survey with a representative sample of 2000 Brazilian women aged 18-49 years. The questionnaire collected detailed information on their awareness, preferences, and utilization of various contraceptive methods, alongside demographic and socioeconomic data. Results: Oral contraceptives, condoms, injectables, and intrauterine devices (IUDs) were the most recognized methods. Younger women demonstrated greater awareness of modern methods. Socioeconomic disparities were evident, with lower-income women displaying limited knowledge about condoms and IUDs but a higher usage for injectable contraceptives. Oral contraceptives were the most used method, with higher use in the South, and lower in the Central-West and Northeast regions. Satisfaction with current contraceptive methods was high (87.5%), closely associated with personal responsibility in method choice. Although the majority self-financed their contraceptives (63.1%), a significant portion of lower-income women (27.7%) relied on public health care. Physicians' recommendations predominantly influenced contraceptive choice (53.9%), with younger women also guided by other influences. Conclusions: Persistent disparities in contraceptive awareness and access highlight the need for educational initiatives and policy interventions. Health care providers play a vital role in facilitating informed contraceptive choices, enhancing the chances of satisfaction with the method.

Real-World Study of Adjuvant Biosimilar Trastuzumab-dkst for HER2-Positive Breast Cancer Treatment in a Brazilian Population.

INTRODUCTION: Biological monoclonal antibodies play a pivotal role in cancer treatment, with biosimilars significantly enhancing their accessibility. In Brazil's ethnically diverse setting, real-world evidence is crucial for assessing the effectiveness and applicability of these therapies in routine clinical practice. METHODS: We performed a multicentric, observational, prospective real-world study on biosimilar trastuzumab-dkst for adjuvant treatment of early HER2-positive breast cancer in Brazilian patients. Data were collected using a case-report form. RESULTS: Of the 176 recruited, we present data from the first 59 patients (mean age 51.7 ± 12.9 years) who had completed treatment with trastuzumab-dkst. The mean time from diagnosis to the first adjuvant treatment with trastuzumab-dkst was 5.5 ± 2.7 months. Of the patients, 59% of patients achieved at least a 30-month follow-up. The 31.7-month invasive disease-free survival rate (IDFS) was 94.5% (95% CI 83.9-98.2%) and median IDFS was not achieved, since only three patients had invasive disease recurrence. The overall survival rate was 100% until the last assessment. The observed adverse events were similar to those presented by other studies using biosimilar or reference trastuzumab. Four serious adverse events (8.5%) were observed. A reduction in left ventricular ejection fraction of at least 10% was observed in 16.9% of participants. There was no treatment interruption, and three participants (5.1%) had their trastuzumab-dkst dose reduced. CONCLUSION: Our study reinforces the existing pivotal data, underscoring the real-world efficacy and safety of biosimilar trastuzumab-dkst in the adjuvant treatment for early HER2-positive breast cancer. The preliminary long-term effectiveness and safety data we present further validate trastuzumab-dkst's role as a cost-saving alternative in oncological care. These findings have important implications for improving patient access to crucial treatments and for the more efficient use of healthcare resources. GOV REGISTRATION: NCT03892655.

Long-Term Safety and Effectiveness of Rituximab Biosimilar RTXM83: A Retrospective Extension Study in Brazilian Patients with Diffuse Large B-Cell Lymphoma.

INTRODUCTION: RTXM83, a biosimilar of rituximab, was approved after physicochemical, functional, non-clinical, and clinical studies demonstrated their similarity; these studies included RTXM83-AC-01-11, a multicentric double-blind international prospective pivotal study. Long-term data on biosimilars can potentially elucidate their clinical robustness and facilitate their broader adoption. METHODS: In this retrospective observational study, we analyzed a dataset from a Brazilian cohort previously randomized in the RTXM83-AC-01-11 study followed by the assessment of long-term outcomes in an observational extension phase from randomization in the RTXM83-AC-01-11 study to the last recorded evaluation. Patients with diffuse large B cell lymphoma (DLBCL) received either reference rituximab (R) or RTXM83 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) as adjuvant treatment. RESULTS: The median follow-up period was 77.0 months. Patients with initial DLBCL stages III and IV comprised 50% of the R-CHOP group and 40% of the biosimilar group. Five (18.5%) patients, including two RTXM83-CHOP-treated and three R-CHOP-treated individuals, experienced late adverse events (AEs) of interest. No new safety signs were established. At the final assessment, the progression-free survival (PFS) rates were 93.3% and 50.0% in the RTXM83-CHOP and R-CHOP groups, respectively. Median PFS was not achieved in the RTXM83-CHOP group, which was 40.5 months in the R-CHOP group. The overall survival (OS) rates were 100% and 66.7% in the RTXM83-CHOP and R-CHOP groups, respectively. The median OS was not reached in any group. CONCLUSION: This study demonstrated the long-term safety and effectiveness of RTXM83 in treating DLBCL; outcomes comparable to those of the reference product and potentially improved access to treatment have been indicated. However, further research with more diverse patient groups can validate these findings and advocate the broader adoption of biosimilars in cancer care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04928573. June 16, 2021, "retrospectively registered".

Functional and structural basis of human parainfluenza virus type 3 neutralization with human monoclonal antibodies.

Human parainfluenza virus type 3 (hPIV3) is a respiratory pathogen that can cause severe disease in older people and infants. Currently, vaccines against hPIV3 are in clinical trials but none have been approved yet. The haemagglutinin-neuraminidase (HN) and fusion (F) surface glycoproteins of hPIV3 are major antigenic determinants. Here we describe naturally occurring potently neutralizing human antibodies directed against both surface glycoproteins of hPIV3. We isolated seven neutralizing HN-reactive antibodies and a pre-fusion conformation F-reactive antibody from human memory B cells. One HN-binding monoclonal antibody (mAb), designated PIV3-23, exhibited functional attributes including haemagglutination and neuraminidase inhibition. We also delineated the structural basis of neutralization for two HN and one F mAbs. MAbs that neutralized hPIV3 in vitro protected against infection and disease in vivo in a cotton rat model of hPIV3 infection, suggesting correlates of protection for hPIV3 and the potential clinical utility of these mAbs.

WFUMB Guideline/Guidance on Liver Multiparametric Ultrasound: Part 1. Update to 2018 Guidelines on Liver Ultrasound Elastography.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) endorsed the development of this document on multiparametric ultrasound. Part 1 is an update to the WFUMB Liver Elastography Guidelines Update released in 2018 and provides new evidence on the role of ultrasound elastography in chronic liver disease. The recommendations in this update were made and graded using the Oxford classification, including level of evidence (LoE), grade of recommendation (GoR) and proportion of agreement (Oxford Centre for Evidence-Based Medicine [OCEBM] 2009). The guidelines are clinically oriented, and the role of shear wave elastography in both fibrosis staging and prognostication in different etiologies of liver disease is discussed, highlighting advantages and limitations. A comprehensive section is devoted to the assessment of portal hypertension, with specific recommendations for the interpretation of liver and spleen stiffness measurements in this setting.

Rediscovering Portuguese White Crowberries (Corema album): Cultural Insights and Nutritional Significance.

White crowberries (Corema album) are a fruit from an endemic shrub found in Southern European Atlantic costal dunes. Although this shrub and its fruits never became a formal commercial crop for a number of reasons, it has a long-lasting relevance and tradition, much associated with summer, beach and holidays. The main goal of this study was to conduct a thematic analysis of the words and small expressions people associate with white crowberries. For that, a questionnaire was used, and the participants were asked to indicate in an open-ended question which top-of-mind words/small expressions they associate with white crowberries. A total of 501 people participated in this study, of which only 394 knew about white crowberries, and from those, only 229 answered the open-ended question of interest to this purpose. The results showed that the words/small expressions given by the participants were distributed between five categories (1-Memories of places, people and times, 2-Emotions and experiences, 3-Sensorial perception, 4-Properties and uses, and 5-Natural resources' valuation). Additionally, 18 subcategories were also identified. The most representative of the categories was sensorial perception and the most relevant of the subcategories was habitats (a subcategory from category 1). The most frequent words mentioned by the participants were beach, berry and summer. In addition, the effect of sociodemographic groups was investigated and some variations were observed in the categories of the words mentioned by the participants according to sex, living environment or region. This work allowed for the identification of a high variability in the words or expressions that account for a rich patrimony of tacit knowledge, memories, emotions and perceptions of the population towards white crowberries, thus confirming their social as well as nutritional relevance.

WFUMB Guidelines/Guidance on Liver Multiparametric Ultrasound. Part 2: Guidance on Liver Fat Quantification.

The World Federation for Ultrasound in Medicine and Biology (WFUMB) has promoted the development of this document on multiparametric ultrasound. Part 2 is a guidance on the use of the available tools for the quantification of liver fat content with ultrasound. These are attenuation coefficient, backscatter coefficient, and speed of sound. All of them use the raw data of the ultrasound beam to estimate liver fat content. This guidance has the aim of helping the reader in understanding how they work and interpret the results. Confounding factors are discussed and a standardized protocol for measurement acquisition is suggested to mitigate them. The recommendations were based on published studies and experts' opinion but were not formally graded because the body of evidence remained low at the time of drafting this document.

Vitamin D regulates microbiome-dependent cancer immunity.

A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of Bacteroides fragilis, which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.

Advanced renal cell carcinoma management: the Latin American Cooperative Oncology Group (LACOG) and the Latin American Renal Cancer Group (LARCG) consensus update.

PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.

Anti-Acanthamoeba metallopharmaceuticals: Amoebicidal activity and synergistic effect of copper(II) coordination compound.

Acanthamoeba spp. emerged as a clinically important pathogen related to amoebic keratitis. It is among the main causes of corneal transplantation and vision loss in ophthalmology. The treatment protocols have a low cure rate, high toxicity, and need for drug combination. Transition metal compounds have shown promising antiprotozoal effects. This study evaluates the amoebicidal activity of copper(II) coordination compounds in combination with chlorhexidine and the cytotoxicity to topical ocular application. These copper(II) coordination compounds were screened against Acanthamoeba castellanii trophozoites (ATCC 50492). The cytotoxicity on rabbit corneal cell line (ATCC-CCL 60) was performed. The compounds showed high amoebicidal potential, with inhibition of trophozoite viability above 80%. The Cp12 and Cp13 compounds showed Minimal Inhibitory Amoebicidal Concentration (MIAC) at 200 µM and mean inhibitory concentration (IC50) values lower than 10 µM. Against the cysts, Cp12 showed a reduction in viability (48%) in the longest incubation period. A synergistic effect for Cp12 with chlorhexidine was observed. The compounds have a dose-dependent effect against rabbit corneal cells. Compound Cp12 has potential for future application in developing ophthalmic formulations against Acanthamoeba keratitis and its use in multipurpose solutions is highlighted.

Fertilization with follicular fluid reduces HSP70 and BAX expression on bovine in vitro embryos.

The in vivo fertilization process occurs in the presence of follicular fluid (FF). The aim of this study was to evaluate the effect of in vitro fertilization medium supplementation with 5% or 10% bovine follicular fluid (BFF) on the production of in vitro bovine embryos. FF was collected from ovarian follicles with a diameter of 8-10 mm, and cumulus-oocyte complexes (COCs) were co-incubated with sperm for 24 h in the commercial medium BotuFIV® (BotuPharma©), being distributed among the experimental groups: oocytes fertilized in a control medium; oocytes fertilized in a medium supplemented with 5% BFF; and oocytes fertilized in a medium supplemented with 10% BFF. After fertilization, the zygotes were cultured in vitro for 8 days. Embryo development was assessed through cleavage rates (day 2) and blastocyst formation rates (day 8). The relative expression of the genes OCT4, IFNT2, BAX, HSP70 and SOD2 was measured using the real-time polymerase chain reaction method. There was no difference (p > .05) among the different experimental groups in terms of cleavage rates and blastocyst formation rates. Regarding the gene expression results, only the blastocysts from oocytes fertilized with 10% BFF showed significantly lower expression of IFNT2 (p = .003) and SOD2 (p = .01) genes compared to blastocysts from oocytes fertilized in control medium alone, while there was no difference between blastocyst from oocytes fertilized in control medium and the ones from oocytes fertilized with 5% BFF. In addition to this, the blastocysts from oocytes fertilized with 5% BFF showed significantly reduced levels of expression of the heat shock protein HSP70 (p < .001) and the pro-apoptotic protein BAX (p = .015) compared to blastocysts from oocytes fertilized with control medium. This may indicate that lower supplementation of BFF to the IVF medium creates a more suitable environment for fertilization and is less stressful for the zygote.

Early Intensive Neurorehabilitation in Traumatic Peripheral Nerve Injury-State of the Art.

Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration through animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, from a One Health perspective. This review offers a hands-on vision of the non-invasive and conservative approaches to peripheral nerve injury, focusing on the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation of BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities (low-level laser therapy, ultrasounds, pulsed electromagnetic fields, electroacupuncture and others). In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoid situations of permanent monoplegic limbs that could lead to amputation.

Safety and possible anti-inflammatory effect of paclitaxel associated with LDL-like nanoparticles (LDE) in patients with chronic coronary artery disease: a double-blind, placebo-controlled pilot study.

Introduction: Studies in cholesterol-fed rabbits showed that anti-proliferative chemotherapeutic agents such as paclitaxel associated with solid lipid nanoparticles (LDE) have marked anti-atherosclerotic effects. In addition, association with LDE nearly abolishes paclitaxel toxicity. We investigated whether treatment with LDE-paclitaxel changes plaque progression by coronary CT angiography and is safe in patients with chronic coronary artery disease. Methods: We conducted a prospective, randomized, double-blind, placebo-controlled pilot study in patients with multi-vessel chronic coronary artery disease. Patients were randomized to receive IV infusions of LDE-paclitaxel (paclitaxel dose: 175 mg/m2 body surface) or LDE alone (placebo group), administered every 3 weeks for 18 weeks. All participants received guideline-directed medical therapy. Clinical and laboratory safety evaluations were made at baseline and every 3 weeks until the end of the study. Analysis of inflammatory biomarkers and coronary CTA was also performed at baseline and 4 weeks after treatment. Results: Forty patients aged 65.6 ± 8 years, 20 in LDE-paclitaxel and 20 in placebo group were enrolled. Among those, 58% had diabetes, 50% had myocardial infarction, and 91% were in use of statin and aspirin. Baseline demographics, risk factors, and laboratory results were not different between groups. In all patients, no clinical or laboratory toxicities were observed. From the baseline to the end of follow-up, there was a non-significant trend toward a decrease in IL-6 levels and hsCRP in the LDE-paclitaxel group (-16% and -28%, respectively), not observed in placebo. Regarding plaque progression analysis, variation in plaque parameter values was wide, and no difference between groups was observed. Conclusion: In patients with multivessel chronic coronary artery disease and optimized medical therapy, LDE-paclitaxel was safe and showed clues of potential benefits in reducing inflammatory biomarkers. Clinical Trial Registration: https://clinicaltrials.gov/study/NCT04148833, identifier (NCT04148833).