Toward a brighter constellation: multiorgan neuroimaging of neural and vascular dynamics in the spinal cord and brain.

Significance: Pain comprises a complex interaction between motor action and somatosensation that is dependent on dynamic interactions between the brain and spinal cord. This makes understanding pain particularly challenging as it involves rich interactions between many circuits (e.g., neural and vascular) and signaling cascades throughout the body. As such, experimentation on a single region may lead to an incomplete and potentially incorrect understanding of crucial underlying mechanisms. Aim: We aimed to develop and validate tools to enable detailed and extended observation of neural and vascular activity in the brain and spinal cord. The first key set of innovations was targeted to developing novel imaging hardware that addresses the many challenges of multisite imaging. The second key set of innovations was targeted to enabling bioluminescent (BL) imaging, as this approach can address limitations of fluorescent microscopy including photobleaching, phototoxicity, and decreased resolution due to scattering of excitation signals. Approach: We designed 3D-printed brain and spinal cord implants to enable effective surgical implantations and optical access with wearable miniscopes or an open window (e.g., for one- or two-photon microscopy or optogenetic stimulation). We also tested the viability for BL imaging and developed a novel modified miniscope optimized for these signals (BLmini). Results: We describe "universal" implants for acute and chronic simultaneous brain-spinal cord imaging and optical stimulation. We further describe successful imaging of BL signals in both foci and a new miniscope, the "BLmini," which has reduced weight, cost, and form-factor relative to standard wearable miniscopes. Conclusions: The combination of 3D-printed implants, advanced imaging tools, and bioluminescence imaging techniques offers a coalition of methods for understanding spinal cord-brain interactions. Our work has the potential for use in future research into neuropathic pain and other sensory disorders and motor behavior.

Obesity and polycystic ovary syndrome influence on intestinal permeability at fasting, and modify the effect of diverse macronutrients on the gut barrier.

Women with the extremely prevalent polycystic ovary syndromegather multiple cardiovascular risk factors and chronic subclinical inflammation. Interactions between diet, adiposity, and gut microbiota modulate intestinal permeabilityand bacterial product translocation, and may contribute to the chronic inflammation process associated with the polycystic ovary syndrome. In the present study, we aimed to address the effects of obesity, functional hyperandrogenism, and diverse oral macronutrients on intestinal permeabilityby measuring circulating markers of gut barrier dysfunction and endotoxemia. Participants included 17 non-hyperandrogenic control women, 17 women with polycystic ovary syndrome, and 19 men that were submitted to glucose, lipid, and protein oral loads. Lipopolysaccharide-binding protein, plasma soluble CD14, succinate, zonulin family peptide, and glucagon-like peptide-2 were determined at fasting and after oral challenges. Macronutrient challenges induced diverse changes on circulating intestinal permeabilitybiomarkers in the acute postprancial period, with lipids and proteins showing the most unfavorable and favorable effects, respectively. Particularly, lipopolysaccharide-binding protein, zonulin family peptide, and glucagon-like peptide-2 responses were deregulated by the presence of obesity after glucose and lipid challenges. Obese subjects showed higher fasting intestinal permeabilitybiomarkers levels than non-obese individuals, except for plasma soluble CD14. The polycystic ovary syndromeexacerbated the effect of obesity further increasing fasting glucagon-like peptide-2, lipopolysaccharide-binding protein, and succinate concentrations. We observed specific interactions of the polycystic ovary syndromewith obesity in the postprandial response of succinate, zonulin family peptide, and glucagon-like peptide-2. In summary, obesity and polycystic ovary syndromemodify the effect of diverse macronutrients on the gut barrier, and alsoinfluence intestinal permeabilityat fasting,contributing to the morbidity of functional hyperandrogenism by inducing endotoxemia and subclinical chronic inflammation.

Surgical treatment of orbital tumors in a single center: Analysis and results.

Background: Orbital tumors, arising within the bony orbit and its contents, present diverse challenges due to their varied origins and complex anatomical context. These tumors, classified as primary, secondary, or metastatic, are further subdivided into intraconal and extraconal based on their relationship with the muscle cone. This classification significantly influences surgical approach and management. This study highlights surgical experiences with orbital tumors, underscoring the importance of tailored surgical approaches based on the lesion's site and its proximity to the optic nerve. Methods: This retrospective study at the National Institute of Cancer's Head and Neck Department (2005-2014) analyzed 29 patients with orbital tumors treated with surgery, radiotherapy, chemotherapy, or combinations of them. Patient demographics, tumor characteristics, and treatment responses were evaluated using computed tomography (CT), magnetic resonance imaging, and positron emission tomography-CT imaging. Malignant tumors often required orbital exenteration and reconstruction, highlighting the study's commitment to advancing orbital tumor treatment. Results: 29 patients (18 females and 11 males, age 18-88 years, mean 53.5 years) with orbital tumors exhibited symptoms such as decreased vision and exophthalmos. Tumors included primary lesions like choroidal melanoma and secondary types like epidermoid carcinoma. Treatments varied, involving a multidisciplinary team for surgical approaches like exenteration, with follow-up from 1 to 9 years. Radiotherapy and chemotherapy were used for specific cases. Conclusion: Our study underscores the need for a multidisciplinary approach in treating orbital tumors, involving various surgical specialists and advanced technologies like neuronavigation for tailored treatment. The integration of surgery with radiotherapy and chemotherapy highlights the effectiveness of multidimensional treatment strategies.

On the balance beam: facing the challenges of neurosurgical education in the third millennium.

Background: Neurosurgery is one of the most complex and challenging areas of medicine, and it requires an ongoing commitment to education and expertise. Preparing young neurosurgeons with comprehensive education that can allow them to achieve high professional standards is a pivotal aspect of our profession. Methods: This paper aims to analyze the current scenario in neurosurgical training identifying innovative methods that can guarantee the highest level of proficiency in our specialty. Results: Given the inherent high-stakes nature of neurosurgical procedures, there is a significant burden of responsibility in ensuring that neurosurgical training is of the highest caliber, capable of producing practitioners who possess not just theoretical knowledge but also practical skills and well-tuned judgment. Conclusion: Providing high-quality training is one of the major challenges that the neurosurgical community has to face nowadays, especially in low- and middle-income countries; one of the main issues to implementing neurosurgery worldwide is that the majority of African countries and many areas in Southeast Asia still have few neurosurgeons who encounter enormous daily difficulties to guarantee the appropriate neurosurgical care to their population.

Choosing T-cell sources determines CAR-T cell activity in neuroblastoma.

Introduction: The clinical success of chimeric antigen receptor-modified T cells (CAR-T cells) for hematological malignancies has not been reproduced for solid tumors, partly due to the lack of cancer-type specific antigens. In this work, we used a novel combinatorial approach consisting of a versatile anti-FITC CAR-T effector cells plus an FITC-conjugated neuroblastoma (NB)-targeting linker, an FITC-conjugated monoclonal antibody (Dinutuximab) that recognizes GD2. Methods: We compared cord blood (CB), and CD45RA-enriched peripheral blood leukapheresis product (45RA) as allogeneic sources of T cells, using peripheral blood (PB) as a control to choose the best condition for anti-FITC CAR-T production. Cells were manufactured under two cytokine conditions (IL-2 versus IL-7+IL-15+IL-21) with or without CD3/CD28 stimulation. Immune phenotype, vector copy number, and genomic integrity of the final products were determined for cell characterization and quality control assessment. Functionality and antitumor capacity of CB/45RA-derived anti-FITC CAR-T cells were analyzed in co-culture with different anti-GD2-FITC labeled NB cell lines. Results: The IL-7+IL-15+IL-21 cocktail, in addition to co-stimulation signals, resulted in a favorable cell proliferation rate and maintained less differentiated immune phenotypes in both CB and 45RA T cells. Therefore, it was used for CAR-T cell manufacturing and further characterization. CB and CD45RA-derived anti-FITC CAR-T cells cultured with IL-7+IL-15+IL-21 retained a predominantly naïve phenotype compared with controls. In the presence of the NB-FITC targeting, CD4+ CB-derived anti-FITC CAR-T cells showed the highest values of co-stimulatory receptors OX40 and 4-1BB, and CD8+ CAR-T cells exhibited high levels of PD-1 and 4-1BB and low levels of TIM3 and OX40, compared with CAR-T cells form the other sources studied. CB-derived anti-FITC CAR-T cells released the highest amounts of cytokines (IFN-γ and TNF-α) into co-culture supernatants. The viability of NB target cells decreased to 30% when co-cultured with CB-derived CAR-T cells during 48h. Conclusion: CB and 45RA-derived T cells may be used as allogeneic sources of T cells to produce CAR-T cells. Moreover, ex vivo culture with IL-7+IL-15+IL-21 could favor CAR-T products with a longer persistence in the host. Our strategy may complement the current use of Dinutuximab in treating NB through its combination with a targeted CAR-T cell approach.

Advancing insights into recurrent lumbar disc herniation: A comparative analysis of surgical approaches and a new classification.

Background: The management of recurrent lumbar disc herniation (rLDH) lacks a consensus. Consequently, the choice between repeat microdiscectomy (MD) without fusion, discectomy with fusion, or endoscopic discectomy without fusion typically hinges on the surgeon's expertise. This study conducts a comparative analysis of postoperative outcomes among these three techniques and proposes a straightforward classification system for rLDH aimed at optimizing management. Patients and Methods: We examined the patients treated for rLDH at our institution. Based on the presence of facet resection, Modic-2 changes, and segmental instability, they patients were categorized into three groups: Types I, II, and III rLDH managed by repeat MD without fusion, MD with transforaminal lumbar interbody fusion (TLIF) (MD + TLIF), and transforaminal endoscopic discectomy (TFED), respectively. Results: A total of 127 patients were included: 52 underwent MD + TLIF, 50 underwent MD alone, and 25 underwent TFED. Recurrence rates were 20%, 12%, and 0% for MD alone, TFED, and MD + TLIF, respectively. A facetectomy exceeding 75% correlated with an 84.6% recurrence risk, while segmental instability correlated with a 100% recurrence rate. Modic-2 changes were identified in 86.7% and 100% of patients experiencing recurrence following MD and TFED, respectively. TFED exhibited the lowest risk of durotomy (4%), the shortest operative time (70.80 ± 16.5), the least blood loss (33.60 ± 8.1), and the most favorable Visual Analog Scale score, and Oswestry Disability Index quality of life assessment at 2 years. No statistically significant differences were observed in these parameters between MD alone and MD + TLIF. Based on this analysis, a novel classification system for recurrent disc herniation was proposed. Conclusion: In young patients without segmental instability, prior facetectomy, and Modic-2 changes, TFED was available should take precedence over repeat MD alone. However, for patients with segmental instability, MD + TLIF is recommended. The suggested classification system has the potential to enhance patient selection and overall outcomes.

The importance of social networks in neurosurgery training in low/middle income countries.

Introduction: Neurosurgery is evolving with new techniques and technologies, relies heavily on high-quality education and training. Social networks like Twitter, Facebook, Instagram and LinkedIn have become integral to this training. These platforms enable sharing of surgical experiences, fostering global knowledge-sharing and collaboration among neurosurgeons. Virtual conferences and courses are accessible, enhancing learning regardless of location. While these networks offer real-time communication and collaborative opportunities, they also pose challenges like the spread of misinformation and potential distractions. According to the PICO format, the target population (P) for the purpose of this paper are medical students, neurosurgical residents and consultants on the role of social media (I) in neurosurgery among Low-Middle income countries (C) with the main outcome to understand the collaborative domain of learning. Material and method: This cross-sectional survey, conducted in June-July 2023, involved 210 medical students, neurosurgery residents, fellows, and practicing neurosurgeons from low and middle-income countries. A structured questionnaire assessed social network usage for neurosurgery training, covering demographic details, usage frequency, and purposes like education, collaboration, and communication. Participants rated these platforms' effectiveness in training on a 1-5 scale. Data collection employed emails, social media groups, and direct messaging, assuring respondent anonymity. The survey aimed to understand and improve social networks' use in neurosurgery, focusing on professional development, challenges, and future potential in training. Results: In a survey of 210 participants from low and middle-income countries, 85.5% were male, 14.5% female, with diverse roles: 42.9% neurosurgery residents, 40% practicing neurosurgeons, 14.6% medical students, and 2.4% other healthcare professionals. Experience ranged from 0 to 35 years, with Mexico, Nigeria, and Kenya being the top participating countries. Most respondents rated neurosurgery training resources in their countries as poor or very poor. 88.7% used social media professionally, predominantly WhatsApp and YouTube. Content focused on surgical videos, research papers, and webinars. Concerns included information quality and data privacy. Interactive case discussions, webinars, and lectures were preferred resources, and most see a future role for social media in neurosurgery training. Conclusions: Our study underscores the crucial role of social media in neurosurgery training and practice in low and middle-income countries (LMICs). Key resources include surgical videos, research papers, and webinars. While social media offers a cost-effective, global knowledge-sharing platform, challenges like limited internet access, digital literacy, and misinformation risks remain significant in these regions.

Latex vascular injection as method for enhanced neurosurgical training and skills.

Background: Tridimensional medical knowledge of human anatomy is a key step in the undergraduate and postgraduate medical education, especially in surgical fields. Training simulation before real surgical procedures is necessary to develop clinical competences and to minimize surgical complications. Methods: Latex injection of vascular system in brain and in head-neck segment is made after washing out of the vascular system and fixation of the specimen before and after latex injection. Results: Using this latex injection technique, the vascular system of 90% of brains and 80% of head-neck segments are well-perfused. Latex-injected vessels maintain real appearance compared to silicone, and more flexible vessels compared to resins. Besides, latex makes possible a better perfusion of small vessels. Conclusions: Latex vascular injection technique of the brain and head-neck segment is a simulation model for neurosurgical training based on real experiencing to improve surgical skills and surgical results.

Clivus-Cervical Stabilization through Transoral Approach in Patients with Craniocervical Tumor: Three Cases and Surgical Technical Note.

Craniocervical tumors lead to cervical pain, instability, and neurological symptoms, reducing the quality of life. Effective surgical intervention at the craniocervical junction (CCJ) is critical and complex, involving comprehensive approaches and advanced reconstructive techniques. This study, conducted at Mexico City's National Institute of Cancerology, focused on three surgical cases that occurred in 2023 involving tumors at the CCJ: two chordomas and one prostate adenocarcinoma. We utilized a specialized technique: clivus-cervical stabilization reinforced with a polymethylmethacrylate (PMMA)-filled cervical mesh. Postoperatively, patients showed marked neurological recovery and reduced cervical pain, with enhanced Karnofsky and Eastern Cooperative Oncology Group (ECOG) scores indicating improved life quality. The surgical technique provided excellent exposure and effective tumor resection, utilizing PMMA-filled cervical mesh for stability. Tumoral lesions at the CCJ causing instability can be surgically treated through a transoral approach. This type of approach should be performed with precise indications to avoid complications associated with the procedure.

The Vertebrobasilar Trunk and Its Anatomical Variants: A Microsurgical Anatomical Study.

BACKGROUND: The trunk of the basilar artery has not been included in microanatomy studies. Anatomical variants of the perforant branches of the vertebrobasilar trunk and their relationship with neural structures are very important in surgical approaches. Surgical dissection for the treatment of vascular lesions requires a perfect knowledge of the microsurgical anatomy. METHODS: We conducted a descriptive analysis of 50 brains, which were fixed with formalin at 10% for 2 weeks, and the arterial system was injected with colored latex. After microsurgical dissection, it was divided into three segments: the lower portion went from the anterior spinal artery to the anteroinferior cerebellar artery, the middle segment was raised from the upper limit of the lower portion to the origin of the superior cerebellar artery, and the upper segment ranged from the previous portion until the origin of the posterior cerebral artery. RESULTS: The basilar artery had an average length of 30 mm. The average diameter at its junction with the vertebral arteries was 4.05 mm. The average middle segment was 3.4 mm in diameter and 15.2 mm in length. The diameter of the upper segment was 4.2 mm, and its average length was 3.6 mm. The average number of bulbar arteries was three, and their average diameter was 0. 66 mm. The number of caudal perforator arteries were five on average, with a diameter of 0.32 mm. We found three rare cases of anatomical variants in the vertebra-basilar junction. CONCLUSIONS: The basilar artery emits penetrating branches in its lower, middle, and upper portions. The origin of penetrating branches was single or divided after forming a trunk. However, we observed long branches from perforant arteries.

PomBase: a Global Core Biodata Resource-growth, collaboration, and sustainability.

PomBase (https://www.pombase.org), the model organism database (MOD) for fission yeast, was recently awarded Global Core Biodata Resource (GCBR) status by the Global Biodata Coalition (GBC; https://globalbiodata.org/) after a rigorous selection process. In this MOD review, we present PomBase's continuing growth and improvement over the last 2 years. We describe these improvements in the context of the qualitative GCBR indicators related to scientific quality, comprehensivity, accelerating science, user stories, and collaborations with other biodata resources. This review also showcases the depth of existing connections both within the biocuration ecosystem and between PomBase and its user community.

What exercise programme is the most appropriate to mitigate anterior cruciate ligament injury risk in football (soccer) players? A systematic review and network meta-analysis.

OBJECTIVES: To examine the effectiveness of different exercise-based interventions to mitigate the risk of anterior cruciate ligament injury in football players, and to determine which is the most appropriate for them, specifically for female football players. DESIGN: Four databases were accessed in July 2023 using the keywords football, soccer, athletic injuries, anterior cruciate ligament, knee injuries, injury prevention, exercise-based programme, and risk factor. METHODS: Randomised controlled trials that evaluated any exercise-based injury prevention intervention compared with a control group on the prevention of anterior cruciate ligament injury in football players were included. RESULTS: Eleven studies were included. Data were presented as logarithm hazard ratio, credible intervals and standard deviation. FIFA 11+ was the most effective in reducing anterior cruciate ligament injury risk in football players (logarithm hazard ratio = -1.23 [95% credible intervals: -2.20, -0.35]; SD = 0.47), followed by the Knäkontroll programme (logarithm hazard ratio = -0.76 [95% credible intervals: -1.60, -0.03]; standard deviation = 0.42). For females, only Knäkontroll had a significant impact on reducing the risk of anterior cruciate ligament injury (logarithm hazard ratio = -0.62 [95% credible intervals: -1.71, 0.62]; standard deviation = 0.58). CONCLUSIONS: Our results support the use of FIFA 11+ and Knäkontroll to mitigate injury incidence at overall level. However, the effectiveness of these interventions changed when adjusting for females. Knäkontroll is postulated as the programme with the greatest preventive nature, although these results should be interpreted with caution due to the lack of the sample.

Analyzing the Clinical Potential of Stromal Vascular Fraction: A Comprehensive Literature Review.

Background: Regenerative medicine is evolving with discoveries like the stromal vascular fraction (SVF), a diverse cell group from adipose tissue with therapeutic promise. Originating from fat cell metabolism studies in the 1960s, SVF's versatility was recognized after demonstrating multipotency. Comprising of cells like pericytes, smooth muscle cells, and, notably, adipose-derived stem cells (ADSCs), SVF offers tissue regeneration and repair through the differentiation and secretion of growth factors. Its therapeutic efficacy is due to these cells' synergistic action, prompting extensive research. Methods: This review analyzed the relevant literature on SVF, covering its composition, action mechanisms, clinical applications, and future directions. An extensive literature search from January 2018 to June 2023 was conducted across databases like PubMed, Embase, etc., using specific keywords. Results: The systematic literature search yielded a total of 473 articles. Sixteen articles met the inclusion criteria and were included in the review. This rigorous methodology provides a framework for a thorough and systematic analysis of the existing literature on SVF, offering robust insights into the potential of this important cell population in regenerative medicine. Conclusions: Our review reveals the potential of SVF, a heterogeneous cell mixture, as a powerful tool in regenerative medicine. SVF has demonstrated therapeutic efficacy and safety across disciplines, improving pain, tissue regeneration, graft survival, and wound healing while exhibiting immunomodulatory and anti-inflammatory properties.

Comparative Analysis of Stromal Vascular Fraction and Alternative Mechanisms in Bone Fracture Stimulation to Bridge the Gap between Nature and Technological Advancement: A Systematic Review.

BACKGROUND: Various stimulation methods, including electrical, ultrasound, mechanical, and biological interventions, are explored, each leveraging intricate cellular and molecular dynamics to expedite healing. The advent of stromal vascular fraction (SVF) marks a significant stride, offering multifarious benefits in bone healing, from enhanced bone formation to optimal vascular integration, drawing a harmonious balance between innate mechanisms and scientific advancements. METHODS: This systematic review was conducted focusing on literature from 2016 to 2023 and encompassing various bone healing stimulation mechanisms like SVF, electrical, ultrasound, and mechanical stimulation. The extracted data underwent meticulous synthesis and analysis, emphasizing comparative evaluations of mechanisms, applications, and outcomes of each intervention. RESULTS: The reviewed studies reveal the potential of SVF in bone fracture healing, with its regenerative and anti-inflammatory effects. The purification of SVF is crucial for safe therapeutic use. Characterization involves flow cytometry and microscopy. Studies show SVF's efficacy in bone regeneration, versatility in various contexts, and potential for clinical use. SVF appears superior to electrical, ultrasound, and mechanical stimulation, with low complications. CONCLUSIONS: This review compares bone healing methods, including SVF. It provides valuable insights into SVF's potential for bone regeneration. However, due to limited human studies and potential bias, cautious interpretation is necessary. Further research is essential to validate these findings and determine the optimal SVF applications in bone healing.

Familial ApoB-specific familial hypobetalipoproteinemia in a patient with non-classical congenital adrenal hyperplasia. / Hipobetalipoproteinemia familiar ApoB específica en una paciente con hiperplasia suprarrenal congénita no clásica.

Familial hypobetalipoproteinaemia is a disorder of lipid metabolism characterized by low levels of total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B. ApoB-related familial hypolipoproteinemia is an autosomal condition with a codominance inheritance pattern. Non-classical congenital adrenal hyperplasia is an autosomal recessive disorder due to mutations in the CYP21A2, a gene encoding for the enzyme 21-hydroxylase, which results in an androgen excess production from adrenal source. We here present the case of a 25-year-old woman with NCAH showing decreased levels of total-cholesterol, low-density lipoprotein cholesterol and triglycerides. Her parent had digestive symptoms and severe hepatic steatosis with elevated liver enzymes, as well as decreased levels of total and low-density lipoprotein cholesterol. A genetic-molecular study of the proband identified a mutation in the APOB gene, which allowed a diagnosis of heterozygous ApoB-related hypolipoproteinaemia to be made.

Bipolar, high-voltage, long-duration pulsed radiofrequency ablation of the Gasserian ganglion for the treatment of trigeminal neuralgia in a patient with a cardiac implantable electronic device: illustrative case.

BACKGROUND: One of the common methods of treating trigeminal neuralgia (TN) nowadays is radiofrequency therapy. However, it has serious limitations in patients with a cardiac pacemaker because of electromagnetic interference. Therefore, it is crucial to select optimal radiofrequency ablation parameters to make this procedure safe with favorable outcomes for such patients. OBSERVATIONS: In this study, the authors present a case of a 70-year-old man with a history of cardiac pacemaker dependency and previous microvascular decompression with complaints of severe, constant facial pain. After reprogramming the cardiac implantable electronic device (CIED), the authors performed bipolar, high-voltage, long-duration pulsed radiofrequency therapy (PRFT) of the Gasserian ganglion under electrocardiography and pulse rate control in the pre-, intra-, and postoperative periods. There were no cardiovascular or neurological complications after PRFT. The patient reported relief of pain after the procedure, and at the 9-month follow-up, he was pain-free. LESSONS: This clinical case demonstrates that the use of bipolar, high-voltage PRFT for TN treatment in patients with a CIED can be safe and effective, provided that the rules and pacemaker instructions are followed. It is necessary to use ablative treatment with caution and to guide the patient in collaboration with a cardiac surgeon and an anesthesiologist resuscitator.

The effect of physical exercise on anticancer immunity.

Regular physical activity is associated with lower cancer incidence and mortality, as well as with a lower rate of tumour recurrence. The epidemiological evidence is supported by preclinical studies in animal models showing that regular exercise delays the progression of cancer, including highly aggressive malignancies. Although the mechanisms underlying the antitumorigenic effects of exercise remain to be defined, an improvement in cancer immunosurveillance is likely important, with different immune cell subtypes stimulated by exercise to infiltrate tumours. There is also evidence that immune cells from blood collected after an exercise bout could be used as adoptive cell therapy for cancer. In this Perspective, we address the importance of muscular activity for maintaining a healthy immune system and discuss the effects of a single bout of exercise (that is, 'acute' exercise) and those of 'regular' exercise (that is, repeated bouts) on anticancer immunity, including tumour infiltrates. We also address the postulated mechanisms and the clinical implications of this emerging area of research.