Clinical Investigation Research Articles

Rapamycin suppresses rheumatoid arthritis fibroblast synovial cell proliferation and induces apoptosis via the AKT/mTORC1 pathway

AbstractBackgroundRheumatoid arthritis (RA) is an autoimmune disease characterized by the overproliferation of synovial fibroblast‐like synoviocytes (FLSs) in the lining, leading to chronic inflammation and progressive joint damage. RA pathogenesis involves lymphocyte infiltration, increased synovial cell proliferation, and impaired cell death. This study investigated the effects of rapamycin on RA‐FLSs and explored the underlying molecular mechanisms.MethodsThe optimal drug concentration and time for rapamycin administration were determined using a cell counting kit‐8 assay. The concentration of rapamycin varied from 1 to 25 nmol/L. The mRNA expression levels of protein kinase B (AKT), mammalian target of rapamycin (mTOR), B cell lymphoma 2 (Bcl‐2), and Bcl‐2‐associated X protein (Bax) were quantified by real‐time polymerase chain reaction. Protein expression (p‐AKT, AKT, p‐mTOR, mTOR, pS6 kinase [S6K], S6K, p‐4E‐binding protein 1 [4EBP1], 4EBP1, Bcl‐2, Bax, caspase 3, caspase 9, cyclin‐dependent kinase 2 [CDK2], and CD1) were detected by Western blotting analysis.ResultsRapamycin suppresses RA‐FLS proliferation and induces apoptosis in a dose‐dependent manner. Rapamycin significantly elevated the protein expression of Bax (p < 0.01), caspase 3 (p < 0.05), and caspase 9 (p < 0.001), and downregulated Bcl‐2 expression (p < 0.01). Rapamycin increased Bax mRNA expression (p < 0.01) and decreased Bcl‐2 (p < 0.05), AKT (p < 0.05), and mTOR (p < 0.05) expression. Additionally, there was a marked reduction in the expression levels of p‐AKT(Ser473) (p < 0.01), p‐mTOR (Ser2448) (p < 0.01), p‐S6K1 (p < 0.01), and p‐4EBP1, CDK2, and CD1 (p < 0.01).ConclusionsRapamycin effectively inhibited proliferation and induced apoptosis of RA‐FLSs by targeting the AKT/mTORC1 pathway. These findings underscore the potential of rapamycin as a therapeutic candidate for addressing the dysregulated proliferation and inflammatory characteristics of RA. Further clinical investigations are required to validate its application in the management of RA.

A Roadmap of CAR-T-Cell Therapy in Glioblastoma: Challenges and Future Perspectives.

Glioblastoma (GBM) is the most common primary malignant brain tumor, with a median overall survival of less than 2 years and a nearly 100% mortality rate under standard therapy that consists of surgery followed by combined radiochemotherapy. Therefore, new therapeutic strategies are urgently needed. The success of chimeric antigen receptor (CAR) T cells in hematological cancers has prompted preclinical and clinical investigations into CAR-T-cell treatment for GBM. However, recent trials have not demonstrated any major success. Here, we delineate existing challenges impeding the effectiveness of CAR-T-cell therapy for GBM, encompassing the cold (immunosuppressive) microenvironment, tumor heterogeneity, T-cell exhaustion, local and systemic immunosuppression, and the immune privilege inherent to the central nervous system (CNS) parenchyma. Additionally, we deliberate on the progress made in developing next-generation CAR-T cells and novel innovative approaches, such as low-intensity pulsed focused ultrasound, aimed at surmounting current roadblocks in GBM CAR-T-cell therapy.

Fatty acid-binding protein 5 is a functional biomarker and indicator of ferroptosis in cerebral hypoxia

The progression of human degenerative and hypoxic/ischemic diseases is accompanied by widespread cell death. One death process linking iron-catalyzed reactive species with lipid peroxidation is ferroptosis, which shows hallmarks of both programmed and necrotic death in vitro. While evidence of ferroptosis in neurodegenerative disease is indicated by iron accumulation and involvement of lipids, a stable marker for ferroptosis has not been identified. Its prevalence is thus undetermined in human pathophysiology, impeding recognition of disease areas and clinical investigations with candidate drugs. Here, we identified ferroptosis marker antigens by analyzing surface protein dynamics and discovered a single protein, Fatty Acid-Binding Protein 5 (FABP5), which was stabilized at the cell surface and specifically elevated in ferroptotic cell death. Ectopic expression and lipidomics assays demonstrated that FABP5 drives redistribution of redox-sensitive lipids and ferroptosis sensitivity in a positive-feedback loop, indicating a role as a functional biomarker. Notably, immunodetection of FABP5 in mouse stroke penumbra and in hypoxic postmortem patients was distinctly associated with hypoxically damaged neurons. Retrospective cell death characterized here by the novel ferroptosis biomarker FABP5 thus provides first evidence for a long-hypothesized intrinsic ferroptosis in hypoxia and inaugurates a means for pathological detection of ferroptosis in tissue.

A correlational study to determine the correlation of clinical, ultrasonographic and biochemical markers with histopathological findings of various ovarian masses in rural hospitals

Background Ovarian masses are a significant health concern among women, and their accurate diagnosis and characterization are paramount for effective management. This study protocol outlines a correlational investigation into the relationship between clinical, ultrasonographic, and biochemical markers and histopathological findings of ovarian masses in rural hospitals. Methods The study employs a correlational research design and will be conducted within the Department of Obstetrics and Gynecology at a rural hospital affiliated with Datta Meghe Institute of Higher Education and Research. The study population will comprise women of all ages diagnosed with ovarian masses. Clinical evaluations, ultrasonography, biochemical investigations, preoperative workup, and histopathological examinations will be conducted to gather data. The sample size will be determined based on statistical and practical considerations, yielding approximately 60 participants. Expected outcome The study expects to yield valuable insights into the diagnostic and prognostic indicators for ovarian masses. The data collected will enable the correlation of clinical symptoms, ultrasonographic findings, CA 125 levels, and histopathological characteristics, contributing to enhanced diagnostic accuracy, improved patient care, and potentially reduced healthcare costs in rural healthcare settings.

Magnetite nanoparticles: an emerging adjunctive tool for the improvement of cancer immunotherapy.

Cancer immunotherapy has emerged as a groundbreaking field, offering promising and transformative tools for oncological research and treatment. However, it faces several limitations, including variations in cancer types, dependence on the tumor microenvironments (TMEs), immune cell exhaustion, and adverse reactions. Magnetic nanoparticles, particularly magnetite nanoparticles (MNPs), with established pharmacodynamics and pharmacokinetics for clinical use, hold great promise in this context and are now being explored for therapeutic aims. Numerous preclinical studies have illustrated their efficacy in enhancing immunotherapy through various strategies, such as modulating leukocyte functions, creating favorable TMEs for cytotoxic T lymphocytes, combining with monoclonal antibodies, and stimulating the immune response via magnetic hyperthermia (MHT) treatment (Front Immunol. 2021;12:701485. doi: 10.3389/fimmu.2021.701485). However, the current clinical trials of MNPs are mostly for diagnostic aims and as a tool for generating hyperthermia for tumor ablation. With concerns about the adverse effects of MNPs in the in vivo systems, clinical translation and clinical study of MNP-boosted immunotherapy remains limited. The lack of extensive clinical investigations poses a current barrier to patient application. Urgent efforts are needed to ascertain both the efficacy of MNP-enhanced immunotherapy and its safety profile in combination therapy. This article reviews the roles, potential, and challenges of using MNPs in advancing cancer immunotherapy. The application of MNPs in boosting immunotherapy, and its perspective role in research and development is also discussed.

Revision of Failed Short Stems in Total Hip Arthroplasty.

Background: The current literature lacks studies which evaluate the failure of short stems in total hip arthroplasty (THA). Therefore, the present clinical investigation reported our experience with the failure of short stems in THA, evaluating the causes of failure, survivorship, and the clinical outcomes of revision arthroplasty. Methods: The present study was performed according to the STROBE guidelines. This study was conducted at the Department of Orthopaedic Surgery of the Humanitas Clinical Institute, Milan, Italy, between 2017 and 2022. All patients who underwent revision surgery of a previously implanted THA using a short stem were prospectively included in the present study. Surgeries were performed with patients in lateral position, using a minimally invasive posterolateral approach. The outcomes of interest were to report information on the type and survivorship of implants used for the revision surgery and evaluate the clinical outcomes and the rate of complications. The following patient-reported outcome measures (PROMs) used for the clinical assessment were the Western Ontario McMaster Osteo-Arthritis Index (WOMAC) and related subscales of pain, stiffness, and function, and the visual analogue scale (VAS). Results: Data from 45 patients were retrieved. Of them, 31% (14 of 45 patients) were women. The mean age was 63.7 ± 13.9 years. The mean length of the implant survivorship was 6.2 ± 5.7 years. In total, 58% (26 of 45 patients) underwent revision of all components, 36% (16 of 45 patients) revised only the stem, and 1% (3 of 45 patients) received a two-stage revision. The mean length of the follow-up was 4.4 ± 1.5 years. The cup was revised in 58% (26 of 45) of patients. At 4.4 ± 1.5 years of follow-up, the WOMAC score was 3.5 ± 1.3 and the VAS was 1.2 ± 1.3. In total, 9% (4 of 45) of patients experienced minor complications. One patient used a walking aid because of reduced function. One patient evidenced muscular hypotrophy. Two patients experienced hip dislocations. All two dislocations were managed conservatively with repositioning in the emergency room under fluoroscopy. No patient needed additional revision surgery or experienced further dislocations. Conclusions: Revision surgery is effective and safe when a short stem THA fails. At approximately four years of follow-up, all patients were highly satisfied with their clinical outcomes. Despite the relatively high number (9%), complications were of a minor entity and were successfully managed conservatively.

Preparation and Performance Evaluation of a Zinc Oxide-Graphene Oxideloaded Chitosan-Based Thermosensitive Gel.

This study aimed to develop and assess a chitosan biomedical antibacterial gel ZincOxideGrapheneOxide/Chitosan/β-Glycerophosphate (ZnO-GO/CS/β-GP) loaded with nano-zinc oxide (ZnO) and graphene oxide (GO), known for its potent antibacterial properties, biocompatibility, and sustained drug release. ZnO nanoparticles (ZnO-NPs) were modified and integrated with GO sheets to create 1% and 3% ZnO-GO/CS/β-GP thermo-sensitive hydrogels based on ZnO-GO to Chitosan (CS) mass ratio. Gelation time, pH, structural changes, and microscopic morphology were evaluated. The hydrogel's antibacterial efficacy against Porphyromonas gingivalis, biofilm biomass, and metabolic activity was examined alongside its impact (MC3T3-e1). The findings of this study revealed that both hydrogel formulations exhibited temperature sensitivity, maintaining a neutral pH. The ZnO-GO/CS/β-GP formulation effectively inhibited P. gingivalis bacterial activity and biofilm formation, with a 3% ZnO-GO/CS/β-GP antibacterial rate approaching 100%. MC3T3-e1 cells displayed good biocompatibility when cultured in the hydrogel extract.The ZnO-GO/CS/β-GP thermo-sensitive hydrogel demonstrates favorable physical and chemical properties, effectively preventing P. gingivalis biofilm formation. It exhibits promising biocompatibility, suggesting its potential as an adjuvant therapy for managing and preventing peri-implantitis, subject to further clinical investigations.

Targeted genetic analysis in a cohort of sporadic death from spontaneous rupture of thoracic aortic dissection in Han Chinese population

PurposeThoracic aortic dissection (TAD) is a life-threatening cardiovascular disease that often results in sudden cardiac death (SCD). However, the genetic characteristics of individuals with TAD confirmed at autopsy have been rarely studied. Our objective was to determine the prevalence of pathogenic variants in TAD-associated genes in a cohort of sporadic deaths resulting from spontaneous rupture of TAD and identify relevant genotype-phenotype relationships in Han Chinese population. MethodsWe included sixty-one consecutive sporadic decedents whose primary cause of death was spontaneous rupture of TAD, and performed a whole exome sequencing based strategy comprising 26 known TAD-associated genes. ResultsWe identified 7 pathogenic or likely pathogenic (P/LP) variants in 7 cases (11.48 %) and 22 variants of uncertain significance (VUS) in 22 cases (36.07 %). The FBN1 gene was found to be the major disease-causing gene. Notably, TAD decedents with P/LP variant exhibited significantly earlier mortality. Moreover, we reported for the first time that TAD decedents with P/LP variant had a shorter diagnosis and treatment time. ConclusionOur study investigated the genetic characteristics of TAD individuals confirmed until autopsy in Han Chinese population. The findings enhanced the understanding of the genetic underpinnings of TAD and have significant implications for clinical management and forensic investigations.

Mechanical thrombectomy for middle cerebral artery M2 occlusions.

The safety and efficacy of mechanical thrombectomy (MT) for proximal large vessel occlusion after acute ischemic stroke (AIS) have been demonstrated. Clinical investigations of endovascular approaches for treating AIS due to M2 occlusions have been ongoing. To assess the outcomes of M2 occlusions according to treatment modality and anatomical division. A total of 113 consecutive M2 occlusions treated with endovascular treatment (EVT) at our tertiary stroke center between January 2019 and December 2022 were retrospectively analyzed. Patients were divided into three groups: mechanical thrombectomy (MT); intravenous thrombolysis plus MT (IVT + MT); and IVT alone. The primary outcomes were good prognosis (mRS = 0-2) and mortality (mRS = 6) on day 90. The secondary outcome was to determine the differences in outcomes between lesions in the superior and inferior branches of M2. In total, 55 (48.7%) patients underwent MT. In 42 (37.2%) patients, bridging IVT was performed with MT, and IVT alone was applied in 16 (14.2%) patients. Neither the prognosis at 90 days nor the mortality rate significantly differed among the groups. The outcomes did not significantly differ between occlusions in the superior and inferior branches of M2. MT was found to be safe and effective for treating M2 occlusions in this series.

Efficacy of Wearable low-intensity pulsed Ultrasound treatment in the Movement disorder in Parkinson’s disease (the SWUMP trial): protocol for a single-site, double-blind, randomized controlled trial

BackgroundParkinson’s disease (PD) is a progressive, neurodegenerative illness marked by the loss of dopaminergic neurons, causing motor symptoms. Oral levodopa replacement therapy remains the gold standard in the treatment of PD. It is, nevertheless, a symptomatic treatment. There is currently no effective treatment for PD. Therefore, new therapies for PD are highly desirable. Low-intensity pulsed ultrasound (LIPUS) has been shown to improve behavioral functions in PD animal models. It is a new type of neuromodulation approach that combines noninvasiveness with high spatial precision. The purpose of this study is to establish a new clinical protocol for LIPUS in the treatment of movement disorders in patients with PD.MethodsThis protocol is a single-site, prospective, double-blind, randomized controlled trial (RCT). Forty-eight participants with clinically confirmed PD will be randomly allocated to one of two groups: LIPUS group or sham group. All of the participants continue to use pharmacological therapy as a fundamental treatment. The primary outcome is the difference between groups from baseline to 4 months in the change in the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score (part III). The secondary outcomes include the rating scales such as the Mini-Mental State Examination (MMSE), and other three rating scales, and medical examinations including high-density electroencephalography (hdEEG) and functional magnetic resonance imaging (fMRI). The primary safety outcome will be assessed at 4 months, and adverse events will be recorded.DiscussionThis study represents the clinical investigation into the efficacy of therapeutic LIPUS in the treatment of PD for the first time. If LIPUS is determined to be effective, it could offer a practical and innovative means of expanding the accessibility of ultrasound therapy by using a wearable LIPUS device within a home setting.Trial registrationChinese Clinical Trial Registry ChiCTR2100052093. Registered on 17 October 2021.

Vitamin A - discovery, metabolism, receptor signaling and effects on bone mass and fracture susceptibility.

The first evidence of the existence of vitamin A was the observation 1881 that a substance present in small amounts in milk was necessary for normal development and life. It was not until more than 100 years later that it was understood that vitamin A acts as a hormone through nuclear receptors. Unlike classical hormones, vitamin A cannot be synthesized by the body but needs to be supplied by the food as retinyl esters in animal products and ß-carotene in vegetables and fruits. Globally, vitamin A deficiency is a huge health problem, but in the industrialized world excess of vitamin A has been suggested to be a risk factor for secondary osteoporosis and enhanced susceptibility to fractures. Preclinical studies unequivocally have shown that increased amounts of vitamin A cause decreased cortical bone mass and weaker bones due to enhanced periosteal bone resorption. Initial clinical studies demonstrated a negative association between intake of vitamin A, as well as serum levels of vitamin A, and bone mass and fracture susceptibility. In some studies, these observations have been confirmed, but in other studies no such associations have been observed. One meta-analysis found that both low and high serum levels of vitamin A were associated with increased relative risk of hip fractures. Another meta-analysis also found that low levels of serum vitamin A increased the risk for hip fracture but could not find any association with high serum levels of vitamin A and hip fracture. It is apparent that more clinical studies, including large numbers of incident fractures, are needed to determine which levels of vitamin A that are harmful or beneficial for bone mass and fracture. It is the aim of the present review to describe how vitamin A was discovered and how vitamin A is absorbed, metabolized and is acting as a ligand for nuclear receptors. The effects by vitamin A in preclinical studies are summarized and the clinical investigations studying the effect by vitamin A on bone mass and fracture susceptibility are discussed in detail.

Assessing input parameter hyperspace and parameter identifiability in a cardiovascular system model via sensitivity analysis

We aim to clarify our understanding of the process of state-space model input parameter identification, known, within the clinical context, as model personalisation. To do so, we apply reference sensitivity and identifiability techniques to a lumped parameter, single ventricle representation of the systemic circulation, chosen in view of its relative simplicity and prior art. We attempt to quantify the reliability of input parameter identifiability through the lens of 4 clinically relevant measurements and the attendant difficulty in personalising the model. In turn, this that we extend existing methods which combine both parameter influence and orthogonality, to global sensitivities. By examining different parameter sensitivity evaluation methodologies, we investigate the stability of optimal parameter subsets which are commonly used to aid clinical investigations. In order to perform the personalisation process, one must understand the complexity of the high dimensional input parameter hyperspace associated with this class of model. By utilising Sobol indices, we propose a domain-agnostic and intuitive approach. This involves varying the bounds of the input parameter space relative to the model’s base state. These investigations yield a pseudo-mapping of the input hyperspace, cementing our understanding of the role of identifiable input parameters in the state-space model. Our findings suggest a novel global methodology for input parameter identifiability and input hyperspace mapping, providing valuable insights into solving the personalisation process.

Mechanistic correlation of molecular pathways in obesity-mediated stroke pathogenesis.

Obesity, a prominent risk factor for the development of heart attacks and several cardiovascular ailments. Obesity ranks as the second most significant avoidable contributor to mortality, whereas stroke stands as the second leading cause of death on a global scale. While changes in lifestyle have been demonstrated to have significant impacts on weight management, the long-term weight loss remains challenging, and the global prevalence of obesity continues to rise. The pathophysiology of obesity has been extensively studied during the last few decades, and an increasing number of signal transduction pathways have been linked to obesity preclinically. This review is focused on signaling pathways, and their respective functions in regulating the consumption of fatty food as well as accumulation of adipose tissue, and the resulting morphological and cognitive changes in the brain of individuals with obesity. We have also emphasized the recent progress in the mechanisms behind the emergence of obesity, as elucidated by both experimental and clinical investigations. The mounting understanding of signaling transduction may shed light on the future course of obesity research as we move into a new era of precision medicine.

Management of Polycystic Ovarian Syndrome: A Qualitative Inquiry among Complementary and Alternative Medicine Practitioners in South Africa.

Polycystic ovarian syndrome (PCOS) is a complex reproductive endocrinopathy affecting 4-20% of females of reproductive age. PCOS and its consequent complications such as infertility, diabetes mellitus and cardiovascular disease significantly impact clinical management. Complementary and alternative medicine (CAM), including homeopathy, is gaining recognition in PCOS management. There remains a paucity of formal protocols for managing PCOS within homeopathy and other CAM systems. This study aimed to explore and document existing therapeutic practices in the management of PCOS from diagnosis to treatment used by practitioners within various disciplines of CAM: viz., homeopathy, ayurveda, unani tibb, traditional Chinese medicine (TCM) and naturopathy, in the context of their unique philosophical background. In this explorative, descriptive study, data were collected from CAM practitioners in eThekwini Municipality, KwaZulu Natal, South Africa, using semi-structured interviews and analysed using Tesch's and Creswell's methods for qualitative analysis. Four themes emerged from the data, namely: CAM philosophical perspectives on PCOS, contributing factors, diagnosis of PCOS, and management of PCOS. Five sub-themes emerged: clinical diagnosis of PCOS, CAM-specific characterisation of PCOS, CAM-specific treatment of PCOS, adjunctive therapies, and lifestyle interventions. Homeopathic management comprised several prescribing methods, the most common ones being miasmatic/constitutional, keynote and clinical, alongside adjunctive therapies and lifestyle interventions. Other CAM modalities adopted similar holistic approaches. This paper offers a comprehensive exploration of the perceptions, clinical investigations and management practices in PCOS by homeopaths and four other CAM modalities - ayurveda, unani tibb, TCM and naturopathy - as documented in the study. Homeopaths and other CAM practitioners employed CAM-specific therapies, along with adjunctive therapies and lifestyle interventions, adopting holistic approaches. Enhancing the quality of life through emotional counselling, stress reduction and lifestyle improvements emerged as shared objectives across modalities. Our findings underscore the need to further explore inter-disciplinary collaboration in PCOS management among registered CAM practitioners, with the potential to expand the scope of comprehensive care for PCOS patients.

Effect of inflammatory response on joint function after hip fracture in elderly patients: A clinical study

BACKGROUND Excellent hip joint function facilitates limb recovery and improves the quality of survival. This study aimed to investigate the potential risk factors affecting postoperative joint functional activity and outcomes in elderly hip fractures patients and to provide evidence for patient rehabilitation and clinical management. AIM To explore the relationship between inflammatory factors and hip function and the interaction between inflammation and health after hip fracture in elderly patients. METHODS The elderly patients who had hip fracture surgery at our hospital between January 1, 2021, and December 31, 2022 were chosen for this retrospective clinical investigation. Patients with excellent and fair postoperative hip function had their clinical information and characteristics gathered and compared. Age, gender, fracture site, surgical technique, laboratory indices, and other variables that could have an impact on postoperative joint function were all included in a univariate study. To further identify independent risk factors affecting postoperative joint function in hip fractures, risk factors that showed statistical significance in the univariate analysis were then included in a multiple logistic regression analysis. In addition to this, we also compared other outcome variables such as visual analogue scale and length of hospital stay between the two groups. RESULTS A total of 119 elderly patients with hip fractures were included in this study, of whom 37 were male and 82 were female. The results of univariate logistic regression analysis after excluding the interaction of various factors showed that there was a statistically significant difference in interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP), and complement C1q (C1q) between the fair and excellent joint function groups (P < 0.05). The results of multiple logistic regression analysis showed that IL-6 > 20 pg/mL [(Odds ratio (OR) 3.070, 95%CI: 1.243-7.579], IL-8 > 21.4 pg/ mL (OR 3.827, 95%CI: 1.498-9.773), CRP > 10 mg/L (OR 2.142, 95%CI: 1.020-4.498) and C1q > 233 mg/L (OR 2.339, 95%CI: 1.094-5.004) were independent risk factors for poor joint function after hip fracture surgery (all P < 0.05). CONCLUSION After hip fractures in older patients, inflammatory variables are risk factors for fair joint function; therefore, early intervention to address these markers is essential to enhance joint function and avoid consequences.

Therapeutic efficacy of cinnamein, a component of balsam of Tolu/Peru, in controlled cortical impact mouse model of TBI

Traumatic brain injury (TBI) remains a major health concern which causes long-term neurological disability particularly in war veterans, athletes and young adults. In spite of intense clinical and research investigations, there is no effective therapy to cease the pathogenesis of the disease. It is believed that axonal injury during TBI is potentiated by neuroinflammation and demyelination and/or failure to remyelination. This study highlights the use of naturally available cinnamein, also chemically known as benzyl cinnamate, in inhibiting neuroinflammation, promoting remyelination and combating the disease process of controlled cortical impact (CCI)-induced TBI in mice. Oral delivery of cinnamein through gavage brought down the activation of microglia and astrocytes to decrease the expression of inducible nitric oxide synthase (iNOS), glial fibrillary acidic protein (GFAP) and ionized calcium binding adaptor molecule 1 (Iba1) in hippocampus and cortex of TBI mice. Cinnamein treatment also stimulated remyelination in TBI mice as revealed by PLP and A2B5 double-labeling, luxol fast blue (LFB) staining and axonal double-labeling for neurofilament and MBP. Furthermore, oral cinnamein reduced the size of lesion cavity in the brain, improved locomotor functions and restored memory and learning in TBI mice. These results suggest a new neuroprotective property of cinnamein that may be valuable in the treatment of TBI.

The power of integrative medicine: A summary of the 58th annual scientific meeting of the European Society of Clinical Investigation, Barcelona June 5-7, 2024.

The power of integrative medicine: A summary of the 58th annual scientific meeting of the European Society of Clinical Investigation, Barcelona June 5-7, 2024.

SYNE1 gene mutation: A recessive ataxic syndrome presenting with weakness and muscle atrophy. A case report

BackgroundAutosomal recessive spinocerebellar ataxia type 8 (SCAR8) is a rare neurodegenerative disease that can be manifest in a wide spectrum from ataxias and motoneuron syndromes. ObjectiveTo report a case of mutation in the SYNE1 gene with predominant motoneuron disease signs. MethodsIndex case medical report and literature review. ResultsA 32-year-old woman onset with pyramidal and lower motoneuron signs and symptoms during the second decade of life, with marked dysarthria showing associated cerebellar pattern. Clinical investigation with electroneuromyography showed chronic preganglionic disease and brain MRI showed cerebellar atrophy. Genetic testing confirmed pathogenic mutation in homozygosity in the SYNE1 gene. ConclusionsRare neurological condition that may be associated with signs of impairment of the pyramidal pathway and second motoneuron (amyotrophic lateral sclerosis-like syndrome), in addition to cerebellar ataxia in insidious course.

The causal relationship between thoracic aortic aneurysm and immune cells: a mendelian randomization study

One of the pathogenic causes of thoracic aortic aneurysm (TAA), a dangerous vascular condition that can cause aortic rupture, is autoimmune disorders. Currently, immune cell clustering is becoming more and more refined, and the specific immune cell phenotypes involved are yet unknown. Here, we want to clarify the causal link between TAA risk and 731 immune cell traits. There was a Mendelian randomization analysis (MR). We discovered that the presence of TAA led to an increase in CD45 on CD33− HLA-DR− myeloid cells, an increase in CD45 on natural killer cells, and a decrease in FSC-A on granulocytes after applying FDR correction. Our research also revealed a strong correlation between the incidence of TAA and an increase in immune cells with CD3 on CD39+ CD4+, and CD25 on IgD− CD27− phenotypes. Through genetic techniques, our research has shown the intimate relationship between immune cells and TAA, offering direction for future clinical investigations.

Computational Retinal Microvascular Biomarkers from an OCTA Image in Clinical Investigation.

Retinal structural and functional changes in humans can be manifestations of different physiological or pathological conditions. Retinal imaging is the only way to directly inspect blood vessels and their pathological changes throughout the whole body non-invasively. Various quantitative analysis metrics have been used to measure the abnormalities of retinal microvasculature in the context of different retinal, cerebral and systemic disorders. Recently developed optical coherence tomography angiography (OCTA) is a non-invasive imaging tool that allows high-resolution three-dimensional mapping of the retinal microvasculature. The identification of retinal biomarkers from OCTA images could facilitate clinical investigation in various scenarios. We provide a framework for extracting computational retinal microvasculature biomarkers (CRMBs) from OCTA images through a knowledge-driven computerized automatic analytical system. Our method allows for improved identification of the foveal avascular zone (FAZ) and introduces a novel definition of vessel dispersion in the macular region. Furthermore, retinal large vessels and capillaries of the superficial and deep plexus can be differentiated, correlating with retinal pathology. The diagnostic value of OCTA CRMBs was demonstrated by a cross-sectional study with 30 healthy subjects and 43 retinal vein occlusion (RVO) patients, which identified strong correlations between OCTA CRMBs and retinal function in RVO patients. These OCTA CRMBs generated through this "all-in-one" pipeline may provide clinicians with insights about disease severity, treatment response and prognosis, aiding in the management and early detection of various disorders.