Strength of activation and temporal dynamics of bioluminescent-optogenetics in response to systemic injections of the luciferin.

BioLuminescent OptoGenetics ("BL-OG") is a chemogenetic method that can evoke optogenetic reactions in the brain non-invasively. In BL-OG, an enzyme that catalyzes a light producing reaction (i.e., a luciferase) is tethered to an optogenetic element that is activated in response to bioluminescent light. Bioluminescence is generated by injecting a chemical substrate (luciferin, e.g., h-Coelenterazine; h-CTZ) that is catalyzed by the luciferase. By directly injecting the luciferin into the brain, we show that bioluminescent light is proportional to spiking activity, and this relationship scales as a function of luciferin dosage. Here, we build on these previous observations by characterizing the temporal dynamics and dose response curves of bioluminescence generated by luminopsins (LMOs), a proxy of BL-OG effects, to intravenous (IV) injections of the luciferin. We imaged bioluminescence through a thinned skull of mice running on a wheel, while delivering h-CTZ via the tail vein with different dosage concentrations and injection rates. The data reveal a systematic relationship between strength of bioluminescence and h-CTZ dosage, with higher concentration generating stronger bioluminescence. We also found that bioluminescent activity occurs rapidly (< 60 s after IV injection) regardless of concentration dosage. However, as expected, the onset time of bioluminescence is delayed as the injection rate decreases. Notably, the strength and time decay of bioluminescence is invariant to the injection rate of h-CTZ. Taken together, these data show that BL-OG effects are highly consistent across injection parameters of h-CTZ, highlighting the reliability of BL-OG as a minimally invasive neuromodulation method.

Safety and outcome of children, adolescents and young adults participating in phase I/II clinical oncology trials: a 9-year center experience.

Introduction: Enrolling children with cancer in early phase trials is crucial to access innovative treatments, contributing to advancing pediatric oncology research and providing tailored therapeutic options. Our objective is to analyze the impact of these trials on patient outcomes and safety, and to examine the evolution and feasibility of trials in pediatric cancer over the past decade. Methods: All patients recruited in pediatric anticancer phase I/II clinical trials from January 2014 to December 2022 were included. Clinical records and trial protocols were analyzed. Results: A total of 215 patients (median age 11.2 years, range 1-29.5) were included in 52 trials (258 inclusions). Patients with extracranial solid tumors (67%), central nervous system (CNS) tumors (24%), and leukemia (9%) were included. The most common investigational drugs were small molecules (28.3%) and antibodies (20.5%). Serious adverse events were experienced by 41% of patients, 4.4% discontinued treatment because of toxicity and two had toxic deaths. Median event-free survival was 3.7 months (95%CI: 2.8-4.5), longer in phase II trials than in phase I (2 vs. 6.3 months; p ≤ 0.001). Median overall survival was 12 months (95%CI: 9-15), higher in target-specific vs. non-target-specific trials (14 vs. 6 months; p ≤ 0.001). Discussion: A significant and increasing number of patients have been included in early clinical trials, suggesting that both oncologists and families consider it valuable to be referred to specialized Units to access new therapies. Moreover, our data suggests that participation in early clinical trials, although not without potential toxicities, might have a positive impact on individual outcomes.

Clinical presentation and microbiological characteristics of community-acquired Staphylococcus aureus bacteraemia at a tertiary hospital in Costa Rica.

Introduction. Staphylococcus aureus is a leading agent in community-acquired bacteraemia (CAB) and has been linked to elevated mortality rates and methicillin resistance in Costa Rica.Gap statement and aim. To update and enhance previous data obtained in this country, we analysed the clinical manifestations of 54 S. aureus CAB cases in a tertiary hospital and delineated the sequence types (STs), virulome, and resistome of the implicated isolates.Methodology. Clinical information was retrieved from patient files. Antibiotic susceptibility profiles were obtained with disc diffusion and automated phenotypic tests. Genomic data were exploited to type the isolates and for detection of resistance and virulence genes.Results. Primary infections predominantly manifested as bone and joint infections, followed by skin and soft tissue infections. Alarmingly, 70% of patients continued to exhibit positive haemocultures beyond 48 h of treatment modification, with nearly a quarter requiring mechanical ventilation or developing septic shock. The 30-day mortality rate reached an alarming 40%. More than 60% of the patients were found to have received suboptimal or inappropriate antibiotic treatment, and there was an alarming tendency towards the overuse of third-generation cephalosporins as empirical treatment. Laboratory tests indicated elevated creatinine levels, leukocytosis, and bandaemia within the first 24 h of hospitalization. However, most showed improvement after 48 h. The isolates were categorized into 13 STs, with a predominance of representatives from the clonal complexes CC72 (ST72), CC8 (ST8), CC5 (ST5, ST6), and CC1 (ST188). Twenty-four isolates tested positive for mecA, with ST72 strains accounting for 20. In addition, we detected genes conferring acquired resistance to aminoglycosides, MLSB antibiotics, trimethoprim/sulfamethoxazole, and mutations for fluoroquinolone resistance in the isolate collection. Genes associated with biofilm formation, capsule synthesis, and exotoxin production were prevalent, in contrast to the infrequent detection of enterotoxins or exfoliative toxin genes.Conclusions. Our findings broaden our understanding of S. aureus infections in a largely understudied region and can enhance patient management and treatment strategies.

Use of Neuroendoscopy in Combination Treatment of a Three-Year-Old Patient With Primary Disseminated Medulloblastoma: A Case Report.

A three-year-four-month-old boy with primary disseminated medulloblastoma M3 stage and secondary occlusive hydrocephalus underwent an endoscopic triventriculocisternostomy (ETVC) and tumor biopsy, followed by ventriculoperitoneal shunt (VPS) placement due to ETVC failure. The treatment regimen, which included intensive induction chemotherapy, proton beam therapy (PBT), and maintenance chemotherapy, led to significant clinical improvement and a complete radiological response. Four years post-treatment, the child remains in remission, illustrating the effectiveness of a multimodal approach in managing complex cases of medulloblastoma in pediatric patients.

Exercise and tumor proteome: Insights from a neuroblastoma model.

BACKGROUND/AIM: The impact of exercise on pediatric tumor biology is essentially unknown. We investigated the effects of regular exercise on tumor proteome profile (as assessed with liquid chromatography with tandem mass spectrometry) in a mouse model of one of the most aggressive childhood malignancies, high-risk neuroblastoma (HR-NB). METHODS: Tumor samples of 14 male mice (aged 6-8 weeks) that were randomly allocated into an exercise (5-week combined aerobic and resistance training) or nonexercise control group (6 and 8 mice per group, respectively) were analyzed. The Search Tool for the Retrieval of Interacting Genes/Proteins database was used to generate a protein-protein interaction (PPI) network and enrichment analyses. The Systems Biology Triangle (SBT) algorithm was applied for analyses at the functional category level. RESULTS: Tumors of exercised mice showed a higher and lower abundance of 101 and 150 proteins, respectively, compared to controls [false discovery rate (FDR)<0.05], which were enriched in metabolic pathways, aminoacid metabolism, regulation of hormone levels, and peroxisome proliferator-activated receptor signaling pathway (FDR<0.05). The SBT algorithm indicated that 184 and 126 categories showed a lower and higher abundance, respectively, in the tumors of exercised mice (FDR<0.01). Categories with lower abundance were involved in energy production while those with higher abundance were related to transcription/translation, apoptosis, and tumor suppression. CONCLUSION: Regular exercise altered the abundance of hundreds of intratumoral proteins and molecular pathways, particularly those involved in energy metabolism, apoptosis, and tumor suppression. These findings provide preliminary evidence of the molecular mechanisms underlying potential effects of exercise in HR-NB.

Dual-pore protocells with multitasking capacities for simultaneous delivery of therapeutic enzymes and drugs in macrophage depletion therapy.

Macrophages are usually present in solid tumors where they participate in tumor progression, angiogenesis, immunosuppression and metastasis. The design of nanocarriers capable of delivering therapeutic agents to specific cell populations has received considerable attention in the last decades. However, the capacity of many of these nanosystems to deliver multiple therapeutic agents with very different chemical properties is more limited. Herein, a novel multitasking nanoplatform capable of delivering large macromolecules and cytotoxic drugs to macrophages is presented. This novel nanosystem has exhibited excellent skills in performing simultaneous tasks, macrophage depletion and glucose starvation, maintaining the oxygen levels in the tissue. This nanodevice is composed of a dual-pore mesoporous silica core with the capacity to house small cytotoxic drugs, such as doxorubicin or zoledronic acid, and large macromolecules, such as glucose oxidase. The external surface of the silica core was coated with a lipid bilayer to avoid the premature release of the housed drugs. Finally, polymeric nanocapsules loaded with catalase were covalently anchored on the outer lipid bilayer, and carboxy-mannose was attached to the exposed side of the nanocapsules to provide selectivity to the macrophages. These nanoassemblies were able to transport enzymes (Gox and CAT), maintaining their catalytic activity. Therefore, they could induce glucose starvation, keeping the oxygen levels in the tissue, owing to the tandem enzymatic reaction. The capacity of these nanoassemblies to deliver therapeutic agents to macrophages was evaluated both in static and under flow conditions, showing a rapid capture of the nanoparticles by the macrophages. Once there, the nanoassemblies also exhibited excellent capacity to induce potent macrophage depletion. This strategy can be directly adapted for the treatment of different malignancies due to the modular nature of the nanoplatform, which can be loaded with different therapeutic agent combinations and pave the way for the development of personalized nanomedicines for diverse types of tumors.

Ase1 selectively increases the lifetime of antiparallel microtubule overlaps.

Microtubules (MTs) are dynamically unstable polar biopolymers switching between periods of polymerization and depolymerization, with the switch from the polymerization to the depolymerization phase termed catastrophe and the reverse transition termed rescue.1 In presence of MT-crosslinking proteins, MTs form parallel or anti-parallel overlaps and self-assemble reversibly into complex networks, such as the mitotic spindle. Differential regulation of MT dynamics in parallel and anti-parallel overlaps is critical for the self-assembly of these networks.2,3 Diffusible MT crosslinkers of the Ase1/MAP65/PRC1 family associate with different affinities to parallel and antiparallel MT overlaps, providing a basis for this differential regulation.4,5,6,7,8,9,10,11 Ase1/MAP65/PRC1 family proteins directly affect MT dynamics12 and recruit other proteins that locally alter MT dynamics, such as CLASP or kinesin-4.7,13,14,15,16 However, how Ase1 differentially regulates MT stability in parallel and antiparallel bundles is unknown. Here, we show that Ase1 selectively promotes antiparallel MT overlap longevity by slowing down the depolymerization velocity and by increasing the rescue frequency, specifically in antiparallelly crosslinked MTs. At the retracting ends of depolymerizing MTs, concomitant with slower depolymerization, we observe retention and accumulation of Ase1 between crosslinked MTs and on isolated MTs. We hypothesize that the ability of Ase1 to reduce the dissociation of tubulin subunits is sufficient to promote its enrichment at MT ends. A mathematical model built on this idea shows good agreement with the experiments. We propose that differential regulation of MT dynamics by Ase1 contributes to mitotic spindle assembly by specifically stabilizing antiparallel overlaps, compared to parallel overlaps or isolated MTs.

Storage Optimization of Transmission Holographic Gratings in Photohydrogels.

The development and optimization of holographic materials represent a great challenge today. These materials must be synthesized according to the characteristics that are desirable in photonic devices whose application is the object of investigation. In certain holographic sensors and biosensors, it is essential that the recording material be stable in liquid media. Furthermore, the holographic gratings stored in them must have temporal and structural stability, so that they can act as transducers of the analytical signal. Therefore, it is essential to optimize its storage in terms of the chemical composition of the material and the optical parameters of recording. This work focuses on the study of the storage optimization of unslanted transmission volume phase holograms in photohydrogels based on acrylamide and N,N'-methylenebis(acrylamide). Hydrogel matrices, also composed of acrylamide and N,N'-methylenebis(acrylamide), with different degrees of cross-linking were used and analyzed by scanning electron microscopy and UV-visible spectroscopy. The best results in terms of diffraction efficiency were reached for hydrogel matrices with an acrylamide/N,N'-methylenebis(acrylamide) molar ratio between 19.9 and 26. This relationship was also optimized in the incubator solution used to incorporate the components necessary for the formation of the holograms in the hydrogel matrices. The maximum diffraction efficiency, about 35%, was achieved when using an incubation solution with an acrylamide/N,N'-methylenebis(acrylamide) molar ratio of 4.35. The influence of the physical thickness of the hydrogel layers, the intensity, and the exposure time on the diffraction efficiency was also investigated and optimized. In addition, the behavior of the hologram was analyzed after a washing stage with PBST. A simple model that considered the effects of bending and attenuation of holographic gratings was proposed and used to obtain the optical parameters of the holograms.

Clinical Outcome After Epidural Spinal Cord Stimulation in Patients With Severe Traumatic Brain Injury.

INTRODUCTION:  Epidural spinal cord stimulation is a minimally invasive procedure with a growing list of indications. It has a good safety profile and analgesic effect, reduces the severity of spasticity, and activates various brain regions. The purpose of this study is to evaluate the clinical outcome of epidural spinal cord stimulation in patients with spastic syndrome and chronic disorders of consciousness resulting from severe traumatic brain injury (sTBI). METHODS: Between 2021 and 2023, an epidural spinal cord stimulation test was performed in 34 patients with central paresis, severe hypertonia, and chronically altered consciousness following sTBI. The severity of spastic syndrome was assessed using a modified Ashworth scale. All patients underwent implantation of a cylindrical eight-contact test epidural electrode at C3-C5 cervical level, followed by neurostimulation and selection of individual modes. Tonic stimulation at a frequency of 60 Hz, "burst" mode, or a combination of the two was used. RESULTS:  Epidural spinal cord stimulation was administered for an average of 4 ± 1.5 days, with tonic stimulation mode applied in 15 (44.1%) patients, "burst" mode in 10 (29.4%), and a combination of two in nine (26.5%) patients. A reduction in spasticity with clinical improvement was observed in 21 patients (61.8%). The Ashworth scale scores for distal and proximal upper extremities decreased from 3 points to 2.5 points and from 3 points to 2 points, respectively. This was significant in the right upper limbs (p = 0.0152 distally and p = 0.0164 proximally). Significant improvements were also seen in the lower extremities. Active movements in paretic limbs increased or appeared in 12 patients (35.3%), while a heightened level of consciousness was observed in six patients (17.6%). Permanent neurostimulator implantation was performed in 12 patients (35.3%), with no reported surgical complications. CONCLUSION:  Epidural spinal cord stimulation shows promise as an invasive rehabilitation method for patients with sTBI sequelae. Its use reduced the severity of spastic syndrome in over half of patients and increased active movements in paretic limbs in over a third. Notably, neuromodulation at the cervical level yielded pronounced effects on the upper extremities, both proximally and distally. Findings regarding consciousness level improvement are particularly intriguing but warrant further validation through randomized trials.

Role of the mesenchymal stromal cells in bone marrow failure of Fanconi Anemia patients.

Introduction: Fanconi anemia (FA) is an inherited disorder characterized by bone marrow failure, congenital malformations, and predisposition to malignancies. Alterations in hematopoietic stem cells (HSC) have been reported, but little is known regarding the bone marrow (BM) stroma. Thus, the characterization of Mesenchymal Stromal Cells (MSC) would help to elucidate their involvement in the BM failure. Methods: We characterized MSCs of 28 FA patients (FA-MSC) before and after treatment (hematopoietic stem cell transplantation, HSCT; or gene therapy, GT). Phenotypic and functional properties were analyzed and compared with MSCs expanded from 26 healthy donors (HD-MSCs). FA-MSCs were genetically characterized through, mitomycin C-test and chimerism analysis. Furthermore, RNA-seq profiling was used to identify dysregulated metabolic pathways. Results: Overall, FA-MSC had the same phenotypic and functional characteristics as HD-MSC. Of note, MSC-GT had a lower clonogenic efficiency. These findings were not confirmed in the whole FA patients' cohort. Transcriptomic profiling identified dysregulation in HSC self-maintenance pathways in FA-MSC (HOX), and was confirmed by real-time quantitative polymerase chain reaction (RT-qPCR). Discussion: Our study provides a comprehensive characterization of FA-MSCs, including for the first time MSC-GT and constitutes the largest series published to date. Interestingly, transcript profiling revealed dysregulation of metabolic pathways related to HSC self-maintenance. Taken together, our results or findings provide new insights into the pathophysiology of the disease, although whether these niche defects are involved in the hematopoietic defects seen of FA deserves further investigation.

Investigating the Link between Intermediate Metabolism, Sexual Dimorphism, and Cardiac Autonomic Dysfunction in Patients with Type 1 Diabetes.

Sexual dimorphism influences cardiovascular outcomes in type 1 diabetes (T1D), with women facing a higher relative risk of macrovascular events compared to men, especially after menopause. This study hypothesizes that abnormalities in intermediate metabolism may be associated with cardiac autonomic neuropathy (CAN) in T1D. We aim to assess low molecular weight metabolites (LMWM) as markers of CAN in T1D, considering the effects of sexual dimorphism and age. In this cross-sectional study, we included 323 subjects with T1D (147 women and 176 men), with a mean age of 41 ± 13 years. A total of 44 women and 41 men were over 50 years old. CAN was assessed using Ewing's tests, and serum metabolites were analyzed by proton nuclear magnetic resonance spectroscopy (1H-NMR). Patients with CAN had lower levels of valine, isoleucine, and threonine, and higher levels of lactate, compared to those without CAN. These differences persisted after adjusting for BMI and estimated glucose disposal rate (eGDR). In a logistic regression model (R² = 0.178, p < 0.001), the main determinants of CAN included isoleucine [Exp(ß) = 0.972 (95% CI 0.952; 0.003)], age [Exp(ß) = 1.031 (95% CI 1.010; 1.053)], A1c [Exp(ß) = 1.361 (95% CI 1.058; 1.752)], and microangiopathy [Exp(ß) = 2.560 (95% CI 1.372; 4.778)]. Sex influenced LMWM profiles, with over half of the metabolites differing between men and women. However, no interactions were found between CAN and sex, or between sex, age, and CAN, on metabolomics profiles. Our findings suggest an association between CAN and LMWM levels in T1D. The sexual dimorphism observed in amino acid metabolites was unaffected by the presence of CAN.

Exploring Pathways for Pain Relief in Treatment and Management of Lumbar Foraminal Stenosis: A Review of the Literature.

BACKGROUND: Lumbar foraminal stenosis (LFS) involves the narrowing of neural foramina, leading to nerve compression, significant lower back pain and radiculopathy, particularly in the aging population. Management includes physical therapy, medications and potentially invasive surgeries such as foraminotomy. Advances in diagnostic and treatment strategies are essential due to LFS's complexity and prevalence, which underscores the importance of a multidisciplinary approach in optimizing patient outcomes. METHOD: This literature review on LFS employed a systematic methodology to gather and synthesize recent scientific data. A comprehensive search was conducted across PubMed, Scopus and Cochrane Library databases using specific keywords related to LFS. The search, restricted to English language articles from 1 January 2000 to 31 December 2023, focused on peer-reviewed articles, clinical trials and reviews. Due to the heterogeneity among the studies, data were qualitatively synthesized into themes related to diagnosis, treatment and pathophysiology. RESULTS: This literature review on LFS analyzed 972 articles initially identified, from which 540 remained after removing duplicates. Following a rigorous screening process, 20 peer-reviewed articles met the inclusion criteria and were reviewed. These studies primarily focused on evaluating the diagnostic accuracy, treatment efficacy and pathophysiological insights into LFS. CONCLUSION: The comprehensive review underscores the necessity for precise diagnostic and management strategies for LFS, highlighting the role of a multidisciplinary approach and the utility of a unified classification system in enhancing patient outcomes in the face of this condition's increasing prevalence.

Improving wine fermentation efficiency of Torulaspora delbrueckii by increasing the ploidy of yeast inocula.

The life cycle of most non-conventional yeasts, such as Torulaspora delbrueckii (Td), is not as well-understood as that of Saccharomyces cerevisiae (Sc). Td is generally assumed to be haploid, which detracts from some biotechnological properties compared to diploid Sc strains. We analyzed the life cycle of several Td wine strains and found that they were mainly diploid during exponential growth in rich medium. However, most cells became haploid in stationary phase, as observed for Sc haploid heterothallic strains. When transferred and incubated in nutrient-deficient media, these haploid cells became polymorphic, enlarged, and transitioned to diploid or polyploid states. The increased ploidy, that mainly results from supernumerary mitosis without cytokinesis, was followed by sporulation. A similar response was observed in yeasts that remained alive during the second fermentation of base wine for sparkling wine making, or during growth in ethanol-supplemented medium. This response was not observed in the Sc yeast populations under any of the experimental conditions assayed, which suggests that it is a specific adaptation of Td to the stressful fermentation conditions. This response allows Td yeasts to remain alive and metabolically active longer during wine fermentation. Consequently, we designed procedures to increase the cell size and ploidy of haploid Td strains. Td inocula with increased ploidy showed enhanced fermentation efficiency compared to haploid inocula of the same strains.

Integrating Augmented Reality in Spine Surgery: Redefining Precision with New Technologies.

INTRODUCTION: The integration of augmented reality (AR) in spine surgery marks a significant advancement, enhancing surgical precision and patient outcomes. AR provides immersive, three-dimensional visualizations of anatomical structures, facilitating meticulous planning and execution of spine surgeries. This technology not only improves spatial understanding and real-time navigation during procedures but also aims to reduce surgical invasiveness and operative times. Despite its potential, challenges such as model accuracy, user interface design, and the learning curve for new technology must be addressed. AR's application extends beyond the operating room, offering valuable tools for medical education and improving patient communication and satisfaction. MATERIAL AND METHODS: A literature review was conducted by searching PubMed and Scopus databases using keywords related to augmented reality in spine surgery, covering publications from January 2020 to January 2024. RESULTS: In total, 319 articles were identified through the initial search of the databases. After screening titles and abstracts, 11 articles in total were included in the qualitative synthesis. CONCLUSION: Augmented reality (AR) is becoming a transformative force in spine surgery, enhancing precision, education, and outcomes despite hurdles like technical limitations and integration challenges. AR's immersive visualizations and educational innovations, coupled with its potential synergy with AI and machine learning, indicate a bright future for surgical care. Despite the existing obstacles, AR's impact on improving surgical accuracy and safety marks a significant leap forward in patient treatment and care.

Mexican Multicenter Experience of Metastatic Spinal Disease.

Background Spinal metastatic disease is a silent progressive cancer complication with an increasing prevalence worldwide. The spine is the third most common site where solid tumors metastasize. Complications involved in spinal metastasis include root or spinal cord compression, progressing to a declining quality of life as patient autonomy reduces and pain increases. The main objective of this study is to report the incidence of patients and typology of spinal metastases in three reference centers in Mexico. Methodology Retrospective cohorts of patients diagnosed with spinal metastases from January 2010 to February 2017 at the National Cancer Institute, National Rehabilitation Institute, and the Traumatology and Orthopedics Hospital "Lomas Verdes" in Mexico City were analyzed. Results A total of 326 patients (56% males) with spinal metastases were reported. The mean age was 58.06 ± 14.05 years. The main sources of spinal metastases were tumors of unknown origin in 53 (16.25%) cases, breast cancer in 67 (20.5%) cases, prostate cancer in 59 (18%) cases, myeloma in 24 (7.4%) cases, and lung cancer in 23 (7.1%) cases. Conclusions The data obtained in this analysis delivers an updated standpoint on Mexico, providing the opportunity to distinguish the current data from global references. Collecting more epidemiological information for better recording of cancer and its associated complications, as well as further studies on them, is necessary.

A randomized controlled trial of ivabradine in patients with acute myocardial infarction related cardiogenic shock.

Objective: . Acute myocardial infarction-related cardiogenic shock (AMI-CS) is often accompanied by tachycardia, which, in turn, increases myocardial oxygen consumption and hinders the use of ventricular assist devices, such as intra-aortic balloon pump. Evidence suggests that ivabradine may reduce heart rate (HR) without affecting other hemodynamic parameters. The aim of the present study was to determine the effect of ivabradine on reducing HR and changes in other hemodynamic parameters such as cardiac index (CI), in patients with AMI-CS and tachycardia. Materials and methods: . A single-center, open label, randomized clinical trial included patients diagnosed with AMI-CS and tachycardia with >100 beats per minute (BPM). Heart rate, cardiac index, and other hemodynamic parameters measured by pulmonary flotation catheter were compared at 0, 6, 12, 24, and 48 hours after randomization. Results: . A total of 12 patients were randomized; 6 received standard therapy, and 6 received ivabradine in addition to standard therapy. Baseline clinical characteristics were similar at randomization. A statistically significant lower heart rate was found at 12 hours (p=0.003) and 48 hours (p=0.029) after randomization, with differences of -23.3 (-8.2 to -38.4) BPM and -12.6 (-0.5 to -25.9) BPM, respectively. No differences in cardiac index, or any other evaluated hemodynamic parameters, length of hospital stay, nor mortality rate were noted between both groups. Conclusions: . The use of ivabradine in patients with AMI-CS was associated with a significant reduction in heart rate at 12 and 48 h, without affecting other hemodynamic parameters.

Objetivo: . El choque cardiogénico relacionado con el infarto agudo de miocardio (AMI-CS, por sus siglas en inglés) suele ir acompañado de taquicardia, lo que, a su vez, aumenta el consumo de oxígeno miocárdico y dificulta el uso de dispositivos de asistencia ventricular, como la bomba de balón intraaórtico. La evidencia sugiere que la ivabradina puede reducir la frecuencia cardíaca (FC) sin afectar otros parámetros hemodinámicos. El objetivo del presente estudio fue determinar el efecto de la ivabradina en la reducción de la FC y los cambios en otros parámetros hemodinámicos como el índice cardíaco (CI) en pacientes con AMI-CS y taquicardia. Materiales y métodos: Se incluyeron pacientes diagnosticados con AMI-CS y taquicardia con >100 latidos por minuto (LPM) en un ensayo clínico aleatorizado de un solo centro. La frecuencia cardíaca, el índice cardíaco y otros parámetros hemodinámicos medidos mediante catéter de flotación pulmonar se compararon a las 0, 6, 12, 24 y 48 h después de la aleatorización. Resultados: Se aleatorizaron un total de 12 pacientes; 6 recibieron terapia estándar y 6 recibieron ivabradina además de la terapia estándar. Las características clínicas basales fueron similares en la aleatorización. Se encontró una frecuencia cardíaca significativamente más baja a las 12 h (p=0,003) y a las 48 h (p=0,029) después de la aleatorización, con diferencias de -23,3 (-8,2 a -38,4) LPM y -12,6 (-0,5 a -25,9) LPM, respectivamente. No se observaron diferencias en el índice cardíaco, en ningún otro parámetro hemodinámico evaluado; tampoco en la duración de la estancia hospitalaria, ni en la tasa de mortalidad entre ambos grupos. Conclusiones: El uso de ivabradina en pacientes con AMI-CS se asoció con una reducción significativa en la frecuencia cardíaca a las 12 y 48 h, sin afectar otros parámetros hemodinámicos.

Intraoperative Ultrasound: An Old but Ever New Technology for a More Personalized Approach to Brain Tumor Surgery.

BACKGROUND: Although the use of transcranial ultrasound dates to the mid-20th century, the main purpose of this research work is to standardize its use in the resection of brain tumors. This is due to its wide availability, low cost, lack of contraindications, and absence of harmful effects for the patient and medical staff, along with the possibility of real-time verification of the complete resection of tumor lesions and minimization of vascular injuries or damage to adjacent structures. METHODS: A retrospective study was conducted from June to December 2022. The study included eight patients (three men and five women) aged between 32 and 76 years. Histological examination revealed two high-grade gliomas, one low-grade glioma, and five metastatic lesions. RESULTS: The low-grade glioma appeared as a homogeneously echogenic structure and easily distinguishable from brain parenchyma, whereas metastases and high-grade gliomas showed higher echogenicity, being identified as malignant lesions due to areas of low echogenicity necrosis and peritumoral edema identified as a hyperechogenic structure. CONCLUSIONS: The use of intraoperative transcranial ultrasound constitutes an important tool for neurosurgeons during tumor resection. Although it is easy to use, intraoperative ultrasound requires a relatively short learning curve and a good understanding of the fundamentals of ultrasound. Its main advantage over neuronavigation is that it is not affected by the "brain shift" phenomenon that commonly occurs during tumor resection, since the ultrasound images are updated during surgery.

Challenging assumptions: "unveiling meritocracy's reality in neurosurgery".

Introduction: Meritocracy, a concept revered as the cornerstone of fairness and equal opportunity, is critically examined in the context of neurosurgery. This article challenges the notion that success in this demanding field is solely determined by individual abilities and effort. It reveals that factors such as background, gender, and socioeconomic status significantly influence one's career trajectory. By investigating how these systemic barriers impact admissions to neurosurgical training programs and professional advancement, the paper underscores the complexity of meritocracy in neurosurgery, suggesting that the meritocratic ideal is more nuanced and influenced by external variables than commonly believed. Results: Certain universities deemed elite offer a curriculum divergent from that of their counterparts in low and middle-income countries. Students at these "elite" institutions gain exposure to new technologies and research incentives, which brings us to the realm of research. Remarkably, 75% of articles originating from developed nations account for just 25% of traumatic brain injury cases. This disparity highlights a significant research imbalance, and the common refrain underscores the need to bolster research capabilities in low-income countries. For neurosurgeons in the developing world, engaging in research often becomes a luxury due to multifaceted challenges. Financial barriers, including publication costs and paywalls for accessing articles, pose significant hurdles. Comparing salaries between countries underscores the glaring divide according to "Neurosurgeon Salary" in 2024. Neurosurgeons in the United States receive a median salary of $412,000 dollars per year, compared to $13,200 dollars in Latin America, as of June 2023. Given such incongruities, the prospect of even attending conferences or workshops abroad remains difficult for neurosurgeons from developing nations. Research isn't cast aside due to a lack of interest but due to resource limitations. The present landscape demands reconsideration. Conclusion: We underscore the journey towards a more inclusive and equitable future in neurosurgery as not just a goal, but a dynamic process fuelled by resilience, collaboration, and a commitment to diversity. The narrative promotes a collective endeavour to dismantle barriers and embrace innovation, emphasizing the importance of mentorship, cross-institutional collaboration, and the amplification of underrepresented voices.

Alternative molecular mechanisms for force transmission at adherens junctions via ß-catenin-vinculin interaction.

Force transmission through adherens junctions (AJs) is crucial for multicellular organization, wound healing and tissue regeneration. Recent studies shed light on the molecular mechanisms of mechanotransduction at the AJs. However, the canonical model fails to explain force transmission when essential proteins of the mechanotransduction module are mutated or missing. Here, we demonstrate that, in absence of α-catenin, ß-catenin can directly and functionally interact with vinculin in its open conformation, bearing physiological forces. Furthermore, we found that ß-catenin can prevent vinculin autoinhibition in the presence of α-catenin by occupying vinculin´s head-tail interaction site, thus preserving force transmission capability. Taken together, our findings suggest a multi-step force transmission process at AJs, where α-catenin and ß-catenin can alternatively and cooperatively interact with vinculin. This can explain the graded responses needed to maintain tissue mechanical homeostasis and, importantly, unveils a force-bearing mechanism involving ß-catenin and extended vinculin that can potentially explain the underlying process enabling collective invasion of metastatic cells lacking α-catenin.