Hypofractionated stereotactic radiotherapy in Spetzler Martin grades 4 and 5 arteriovenous malformations in the pediatric population: Is it a viable alternative?

OBJECTIVE: To analyze the outcomes of hypofractionated stereotactic radiotherapy (HFSRT) for Spetzler Martin grades 4 and 5 arteriovenous malformations (AVMs) in a pediatric population. METHODS: Fourteen patients with Spetzler Martin (SM) grades IV and V large AVMs who underwent HFSRT between January 2013 and July 2019 were retrospectively reviewed. All patients received HFSRT at a dose of 30-36 Gy in 5 to 6 fractions. They were followed up annually with clinical and imaging assessments to evaluate obliteration rates. RESULTS: The median age at presentation was 15 years (range 8-21 years). Ten (71%) were SM grade 4 AVMs and the rest were SM grade 5 AVMs. The majority presented with headache (8 [57%]), and 3 (21%) presented with bleeding. The median nidus volume was 39.4 cc (IQR, 31.4-52.4). Two (14%) patients had infratentorial AVMs. All of them had deep venous drainage. The median clinical follow-up duration was 75 months (range 31-107 months). There was complete obliteration of the nidus in 3 (21%) patients with a median time to obliteration of 39 months. HFSRT resulted in a reduction of the AVM volume to 12 cc or less in nearly 70% of patients. None of the patients experienced re-bleeding. 79% reported an improvement in their symptoms. CONCLUSION: HFSRT is a highly effective treatment for high-grade AVMs in children, which can result in either complete elimination or significant reduction of the nidus volume or make it suitable for additional treatment, such as single-session stereotactic radiosurgery (SRS).

Neurobrucellosis presenting as an infected cerebellopontine cistern epidermoid cyst.

Neurobrucellosis is a rare complication of brucella infection which presents as meningitis, meningoencephalitis, subdural empyema, brain abscess, myelitis, and radiculo- neuritis. We report the first case of neurobrucellosis presenting as an infected cerebellopontine cistern epidermoid cyst in a young immunocompetent male who presented with fever and acute raised intracranial pressure. MRI brain showed an extra-axial mass in the right cerebellopontine angle cistern with peripheral rim enhancement and diffusion restriction. Emergency surgery unveiled a well-encapsulated lesion containing thick pus and keratinous material, confirming an infected epidermoid cyst. Intriguingly, the culture revealed Brucella infection, but the source of the infection remained unclear.

"Undercutting of the corresponding rib": a novel technique of increasing the length of donor in intercostal to musculocutaneous nerve transfer in brachial plexus injury.

Intercostal nerves (ICN) are often utilized as donors for various neurotization procedures in brachial plexus injuries. ICN to musculocutaneous nerve (MCN) transfer is usually a standard in pan brachial plexus injuries, in order to restore flexion at the elbow. A tensionless co-aptation of the donor-recipient nerves often necessitates either a distal dissection of the ICNs where the number of fascicles is rather low or a proximal dissection, often at the cost of dissection of the serratus anterior digitation with a risk of later fibrosis and adhesion. We report two cases of pan brachial plexus injuries where ICN-MCN transfer was performed to restore elbow function. These patients underwent clinical and electrodiagnostic evaluation before surgery. We used the standard technique of harvesting ICNs 3-5, with our technical modification of "undercutting of rib" for increasing the donor length. The procedure was applied in two patients with pan brachial plexus injury (mean age = 23). Mean duration since the injury to surgery was ten months. Both patients underwent tensionless anastomosis with a combination of suture and fibrin glue co-aptation. While one patient had some improvement in elbow flexion, another one was under active rehabilitation protocol during follow-up. We found that undercutting of the ribs near serratus digitations can allow mobilization of the ICN from its groove, which in turn lengthens the donor nerve length without violating the serratus anterior digitations and without too anterior dissection of the nerve. It can be a viable option when a tensionless co-aptation at the axilla is otherwise not feasible intraoperatively.

Surgical excision of large-to-giant petroclival meningiomas focusing on the middle fossa approaches: The lessons learnt.

INTRODUCTION: Petroclival meningiomas are based on or arising from the petro-clival junction in upper two-thirds of clivus, medial to the fifth cranial nerve. This study focuses on the surgical experience in resecting large-giant tumors >3.5 in size predominantly utilizing middle fossa approaches. MATERIAL AND METHODS: 33 patients with a large or a giant petroclival meningioma (size >3.5 cm) were included. Clinical features, preoperative radiological details, operative findings, and postoperative clinical course at the follow-up visit were reviewed. Group A tumors (n = 17,51.5%) were sized 3.5cm-5cm, and Group B (n = 16,48.48%) tumors were of size >5 cm. Extent of resection was described as 'gross total' (no residual tumor), 'near total' (<10% residual tumor) and 'subtotal resection' (>10% residual tumor). Glasgow outcome scale (GOS) quantitatively scored postoperative neurological outcome (mean follow up: 35.77months; range 1-106 months). RESULTS: 25 (75.8%) patients had tumour extension into both supratentorial and infratentorial compartments. Extension into Meckel's cave (n = 25,75.8%), cavernous sinus (n = 17,48.4%], sphenoid sinus (n = 12,38.7%] and suprasellar area [12,38.7%] was often seen. In 31 (93.9%) patients, the tumor crossed the midline in the premedullary, prepontine, and interpeduncular cisterns. In 20 (60.6%) patients, the tumour extended below and posterior to the internal auditory meatus (IAM), while in 13 (39.4%) patients, the tumor was located above and anterior to the IAM. Kawase's approach was the most commonly used approach in 16 (48.48%) patients and resulted in maximum tumor resection. Other approaches included half-and-half (trans-Sylvian with subtemporal) [n = 6, 18.18%]; frontotemporal craniotomy with orbitozygomatic osteotomy [n = 1, 3%] and retromastoid suboccipital craniectomy (RMSO) [n = 7, 21.21%]. In 2 (6.06%) patients, staged anterior petrosectomy with RMSO; and, in 1, staged presigmoid with half-and-half approach was used. Gross total excision was achieved in 12 (36.36%), near-total excision in 15 (45.45%) and subtotal excision in 6 (18.18%) patients. 20 (60.6%) patients had a good functional outcome; 6 patients succumbed due to meningitis, pneumonitis, perforator injury or a large tumor recurrence. CONCLUSIONS: Half-and-half approach was used in tumors with middle and posterior cranial fossae components often extending to the suprasellar region. Kawase's anterior petrosectomy was utilized in resecting tumors with predominant posterior fossa component (along with a small middle fossa component) that was crossing the midline anterior to the brain stem, and mainly situated superomedial to the IAM. Tumors confined to the posterior fossa, that extended laterally and below the IAM were resected utilizing the RMSO approach. Occasionally, a combination of these approaches was used. Middle fossa approaches help in significantly avoiding morbidity by an early devascularisation and decompression of the tumor. In tumors lacking a plane of cleavage, a thin rim of capsule of tumor may be left to avoid brain stem signs.

Brain-stem hemangioblastomas: The seemingly innocuous lesion in a perilous location.

INTRODUCTION: Hemangioblastomas [75% sporadic, 25% with Von Hippel Lindau (VHL) disease] are highly vascular, benign lesions. The surgical nuances, management, and complication avoidance in brain-stem hemangioblastomas (BHs) have been studied. MATERIAL AND METHODS: Over 18 years, 27(mean age: 29 years; range 15-60 years) consecutive cases of BH underwent microsurgical excision. All patients were assessed clinico-radiologically for neurological deficits and screened for VHL disease. Outcome of the patients was based on Karnofsky Performance Status scale (KPS). RESULTS: 12 out of 19 (70.4%) patients with hydrocephalus underwent a cerebrospinal fluid (CSF) diversion procedure. Lower cranial nerve palsy was present in 10 (37%) patients and motor weakness in 13 (48%). The tumours [mean size 3.34 ± 1.06 cm, range: 1.4-5.5 cm; 11 solid, rest solid-cystic; 18 (66.7%) subpial and 9 (33.33%) intramedullary] were divided into four categories based on size: A: <2 cm (n = 5,18.5%); B: 2-3 cm (n = 10,37%); C: 3-4 cm (n = 6,22.2%); D: >4 cm (n = 6,22.2%). Their location was at posterior cervicomedullary junction (n = 12); pontomedullary junction (n = 7); pons (n = 3), medulla (n = 3) and ponto-mesencephalic region (n = 2). Multiple flow voids were seen in >50% patients with tumour >2 cm. 5 patients had syringomyelia; and, 8 had diffuse cervical cord expansion. Two patients with a large vascular tumour underwent preoperative embolization. Six patients had VHL disease; one underwent bilateral adrenalectomy for refractory hypertension; and, the another, nephrectomy for renal cell carcinoma. Twenty-six patients underwent a midline suboccipital craniectomy; and, 1 with a cerebellopontine angle tumour, a retromastoid craniectomy. 15 patients underwent total excision; 10 patients, near-total (<10% remaining) excision, and 2 patients, a subtotal (>10% remaining)) excision. Three patients (2 with VHL disease) expired due to exsanguinating hemorrhage, spreading venous thrombosis and aspiration pneumonitis, respectively. At follow-up visit (median: 25 ± interquartile range 2-56months), 17 patients had improved KPS, 4 remained in same status and 3 (recently operated, on tracheostomy) had worsened KPS. CONCLUSIONS: Significant improvement is achievable in neurological status in patients following successful extirpation of a brain-stem hemangioblastoma, despite a turbulent perioperative period. Leaving tumour capsule adherent to the brain-stem often helps in preserving brain-stem function. Postoperatively, the patients should be monitored for their respiratory and lower cranial nerve status to prevent aspiration pneumonitis.

An HLA-DRB1-coded signal transduction ligand facilitates inflammatory arthritis: a new mechanism of autoimmunity.

Particular alleles of HLA contribute to disease susceptibility and severity in many autoimmune conditions, but the mechanisms underlying these associations are often unknown. In this study, we demonstrate that the shared epitope (SE), an HLA-DRB1-coded sequence motif that is the single most significant genetic risk factor for erosive rheumatoid arthritis, acts as a signal transduction ligand that potently activates osteoclastogenesis, both in vitro and in vivo. The SE enhanced the production of several pro-osteoclastogenic factors and facilitated osteoclast (OC) differentiation in mouse and human cells in vitro. Transgenic mice expressing a human HLA-DRB1 allele that code the SE motif demonstrated markedly higher propensity for osteoclastogenesis and enhanced bone degradation capacity ex vivo. In addition, the SE enhanced the differentiation of Th17 cells expressing the receptor activator for NF-κB ligand. When the two agents were combined, IL-17 and the SE enhanced OC differentiation synergistically. When administered in vivo to mice with collagen-induced arthritis, the SE ligand significantly increased arthritis severity, synovial tissue OC abundance, and bone erosion. Thus, the SE contributes to arthritis severity by activating an OC-mediated bone-destructive pathway. These findings suggest that besides determining the target specificity of autoimmune responses, HLA molecules may influence disease outcomes by shaping the pathogenic consequences of such responses.

A high-throughput image-based screen for the identification of Bax/Bak-independent caspase activators against drug-resistant cancer cells.

Despite the use of new generation target specific drugs or combination treatments, drug-resistance caused by defective apoptosis signaling remains a major challenge in cancer treatment. A common apoptotic defect in drug-resistant tumor is the failure of cancer cells to undergo Bax/Bak-dependent mitochondrial permeabilization due to impaired signaling of Bcl-2 family proteins. Therefore, Bax and Bak-independent caspase-activating compounds appear to be effective in killing such tumor cells. An image-based cellular platform of caspase sensors in Bax and Bak deficient background allowed us to identify several potential Bax/Bak-independent caspase-activating compounds from a limited high-throughput compound screening. FRET-based caspase sensor probe targeted at the nucleus enabled accurate and automated segmentation, yielding a Z-value of 0.72. Some of the positive hits showed promising activity against drug-resistant human cancer cells expressing high levels of Bcl-2 or Bcl-xL. Using this approach, we describe thiolutin, CD437 and TPEN as the most potentially valuable drug candidates for addressing drug-resistance caused by aberrant expression of Bcl-2 family proteins in tumor cells. The screen also enables the quantification of multiparameter apoptotic events along with caspase activation in HTS manner in live mode, allowing characterization of non-classical apoptosis signaling.

Annexin II interactions with the annexin II receptor enhance multiple myeloma cell adhesion and growth in the bone marrow microenvironment.

Multiple myeloma (MM) is an incurable B-cell malignancy in which the marrow microenvironment plays a critical role in our inability to cure MM. Marrow stromal cells in the microenvironment support homing, lodging, and growth of MM cells through activation of multiple signaling pathways in both MM and stromal cells. Recently, we identified annexin II (AXII) as a previously unknown factor produced by stromal cells and osteoclasts (OCL) that is involved in OCL formation, HSC and prostate cancer (PCa) homing to the BM as well as mobilization of HSC and PCa cells. AXII expressed on stromal cells supports PCa cell lodgment via the AXII receptor (AXIIR) on PCa cells, but the role of AXII and AXIIR in MM is unknown. In this study, we show that MM cells express AXIIR, that stromal/osteoblast-derived AXII facilitates adhesion of MM cells to stromal cells via AXIIR, and OCL-derived AXII enhances MM cell growth. Finally, we demonstrate that AXII activates the ERK1/2 and AKT pathways in MM cells to enhance MM cell growth. These results demonstrate that AXII and AXIIR play important roles in MM and that targeting the AXII/AXIIR axis may be a novel therapeutic approach for MM.

Bibliometric Analysis and Visualization of Scientific Literature on Heart Disease Classification Using a Logistic Regression Model.

With the advancement in artificial intelligence, the use of machine learning algorithms for clinical prediction has increased tremendously. Logistic regression is one of the powerful machine learning algorithms that can be used to predict the probability of a variable. Logistic regression is very popular among medical researchers owing to its simplicity, interpretability, and solid statistical foundation. This study aims to investigate the research productivity of heart disease classification using a logistic regression model to analyze the current patterns and potential future trends through bibliometric analysis. Additionally, it aims to highlight the impact and quality of research in the area, identify prominent research groups, the countries actively contributing to the field, which will help the researchers and healthcare professionals to pinpoint research gaps, influential authors, and make informed decisions and invest resources accordingly. The data is collected from a database of Scopus spanning from 2019 to 2023. We have used two bibliometric software, Biblioshiny (Aria and Cuccurullo, 2017) and VOSviewer (Centre for Science and Technology Studies (CWTS), Leiden University, the Netherlands), to analyze the bibliographic data regarding the citation count, contribution of authors, publication count, the contribution of institutions, etc. There are 2331 documents under study which were fed into both software to analyze the data. With 700 documents, China topped the list of most productive countries indicating the vast contribution of the country followed by India and the United States. Contributions of the Harvard Medical School, Boston, MA, United States are found to be the greatest with six papers. The most productive author is Wang Y with 73 documents. Analysis of trending topics reveals that the field progressing towards using support vector machines (SVM), k-nearest neighbours (KNN), and naïve Bayes algorithms. The article has only considered data from Scopus excluding literature indexed in other databases which limits the potential coverage of the data. Also, the work focuses on recent developments excluding older literature from 2019 which could be a limitation. Furthermore, since the study is a bibliometric analysis targeting the use of logistic regression for heart disease prediction, powerful techniques such as SVM, decision trees, random forests, neural networks and deep learning have not been included, which could be another limitation.

The Rise of Digital Twins in Healthcare: A Mapping of the Research Landscape.

The place of digital twin technology in any healthcare system is a truly disruptive innovation that has profound consequences all across medical research and practice. Digital twins represent the virtual replicas that correspond to some physical entity by pulling real-time data streams from different sources to model biological systems for health monitoring and personalization of treatment strategies. This paper presents a detailed review of the current research landscape into digital twins for healthcare. Through bibliometric analysis, we obtained 1,663 publications from 2012 to 2024, basically sourced from the Scopus database, establishing a portion of the trends, productive authors, influential sources, and collaboration networks in this fast-evolving field. Descriptively, our results indicate that although research into this area started way back, the bulk of research began to be realized from 2018 onwards, with appreciable contributions coming in from interdisciplinary fields of artificial intelligence, machine learning, and data analytics. Even with challenges to data interoperability and other privacy concerns, this change brought on by digital twin technology is undoubtedly a considerable promise for chronic disease management, predictive analytics, drug discovery, and surgical planning. This work brings immense insight into this new domain of digital twins in health, which shall set up a strong foundation for future research and innovation in this area.

Mapping Research Trends and Collaborative Networks in Swarm Intelligence for Healthcare Through Visualization.

Swarm intelligence, evolved from the self-organized behavior of social insects, has become an essential method under artificial intelligence for handling complex and dynamic issues. This study visualizes and analyzes the use of swarm intelligence in healthcare, focusing on its role in managing rising medical data complexity, optimizing diagnostic and therapeutic solutions, and supporting personalized healthcare. The analysis, based on literature from Scopus (2003-2024) using Biblioshiny and VOSviewer, reveals a strong increase in publications since 2017, with central themes around disease diagnosis, treatment optimization, medical image analysis, and real-time patient monitoring through frameworks like the Internet of Medical Things (IoMT) and swarm learning. Key findings include the identification of prolific authors, influential journals, and significant collaborative networks, with China and India emerging as major contributors. These insights underscore the multidisciplinary nature of swarm intelligence in healthcare, positioning it as a potential game-changer in medical diagnostics and patient care through collaborative and innovative research.

Primary CNS Melanoma of Meckel's Cave: A Rare Case with Literature Review.

Meckel's cave is a dural recess in the posteromedial portion of the middle cranial fossa, serving as a conduit for the trigeminal nerve and hosting various pathologies. The radiological diagnosis of Meckel's cave pathologies is often challenging, especially when they are atypical and rarely encountered. Here, we discuss the case of a 41-year-old woman who presented with right hemifacial pain, numbness, and binocular diplopia. Imaging features suggested a T2 hypointense, T1 hyperintense, and nonenhancing mass in the right Meckel's cave. Intraoperatively, an extra-axial black mass was observed, suggestive of melanoma, which was radically excised. Further postoperative workup and biopsy revealed it was a primary central nervous system (CNS) malignant melanoma, an exceedingly rare condition. Due to the rarity of the disease, a consensus regarding treatment regimens is lacking. This case report underscores the significance of considering uncommon diagnoses when faced with unusual radiological findings and emphasizes the importance of aggressive surgical resection and the evolving landscape of adjuvant treatments for primary CNS melanomas.

En bloc resection followed by gluteal advancement flap for sacral Ewing's sarcoma: A novel technique.

Ewing's sarcoma is a rare and highly aggressive bone tumor primarily affecting children and adolescents. It commonly presents in the pelvic and axial skeleton, with sacral involvement posing unique challenges due to its intricate anatomical location. This report details the case of an 18-year-old male with sacral Ewing's sarcoma, emphasizing the diagnostic, surgical, and reconstructive aspects of management. The patient presented with lower back pain, lower limb weakness, and urinary incontinence, which prompted an extensive diagnostic evaluation. Magnetic resonance imaging and computed tomography scans revealed a large lytic mass extending from the S2 vertebra to the coccyx invading the presacral space. Biopsy confirmed the diagnosis of Ewing's sarcoma, characterized by the EWS-FLI1 type 1 translocation. A multidisciplinary team comprising neurosurgeons, colorectal surgeons, and plastic surgeons was formulated. En bloc resection of the tumor, lumbopelvic fixation, and soft-tissue reconstruction using bilateral gluteus maximus advancement flaps were successfully performed. The procedure aimed to address both the oncological and functional aspects of the patient's condition. Chemotherapy and radiotherapy were administered as adjuvant therapies. At 2-year follow-up, the patient was ambulating independently with no residual tumor on imaging. This case highlights the complex nature of sacral Ewing's sarcoma and underscores the importance of a multidisciplinary approach. The described surgical technique, including the innovative use of gluteus maximus advancement flaps for soft-tissue reconstruction, contributes to reducing wound complications and promoting successful patient outcomes. The presented approach serves as a valuable addition to the armamentarium of treatment options for this challenging malignancy.

Mapping the Landscape of Electronic Health Records and Health Information Exchange Through Bibliometric Analysis and Visualization.

The adoption of Electronic Health Records (EHRs) and the establishment of Health Information Exchange (HIE) systems have significantly transformed healthcare delivery and management. This study presents a comprehensive bibliometric analysis and visualization of the landscape surrounding EHRs and HIE to provide insights into the current state and emerging trends in this field. Leveraging advanced bibliometric methodologies, including co-citation analysis, keyword co-occurrence analysis, and network visualization techniques, we systematically map the scholarly literature spanning several decades. Our analysis reveals key thematic clusters, influential publications, prolific authors, and collaborative networks within the domain of EHRs and HIE. Furthermore, we identify significant research gaps and areas for future exploration, including interoperability challenges, privacy concerns, and the integration of emerging technologies such as artificial intelligence and blockchain. The findings of this study offer valuable insights for researchers, policymakers, and healthcare practitioners seeking to navigate and contribute to the ongoing evolution of EHRs and HIE systems, ultimately enhancing the quality, efficiency, and accessibility of healthcare services.

Recurrent post-operative extradural and subdural collections due to intracranial hypotension following a lumbar subarachnoid drain.

Intracranial hypotension (IH) represents a syndrome secondary to low cerebrospinal fluid pressure. This case of IH following a lumbar drain inserted before the excision of a left intraconal lesion, leading to recurrent post-operative unilateral subdural and extradural collections, was treated successfully with the evacuation of the collection and simultaneous epidural blood patch (EBP) injection. Our report provides an important perspective on the management of IH with recurrent intracranial collections and reiterates that IH should be considered when dealing with recurrent unilateral intracranial collections in the post-operative period. Evacuation with a simultaneous EBP is an effective strategy for managing IH.

Visualizing Scholarly Trends in Stochastic Models for Disease Prediction.

Stochastic models play a pivotal role in disease prediction by accounting for randomness and uncertainty in biological systems. This study offers a visualization of trends in the application of stochastic models for disease prediction from 1990 to 2024, based on a bibliometric analysis of Scopus data. Key findings reveal a significant growth in research post-2014, largely driven by global health challenges like COVID-19. Despite these advancements, gaps remain in applying these models to non-communicable diseases and low-resource settings. By integrating computational techniques like machine learning, stochastic models hold promise for improving predictive accuracy. This study highlights the need for further international collaboration and interdisciplinary research, offering practical insights for researchers and public health professionals aiming to enhance disease prediction and intervention strategies.

Challenges of anaesthetising a child with Bow Hunter's syndrome and dilated cardiomyopathy for occipitocervical fusion.

Paediatric Bow Hunter's syndrome (BHS), or rotational vertebral artery syndrome, is a rare cause of posterior circulation insufficiency in children. It results from mechanical obstruction of the vertebral artery by the transverse process of cervical vertebrae resulting in vertebrobasilar insufficiency during the neck rotation to the sides. Paediatric dilated cardiomyopathy (DCM) is a rare myocardial disease that presents with ventricular dilatation and cardiac dysfunction. This case report describes the successful anaesthetic management of an boy with BHS due to atlantoaxial dislocation and DCM. The child was anaesthetised by keeping the following anaesthetic goals in mind such as maintenance of the heart rate, rhythm, preload, afterload and contractility close to the baseline for both DCM and BHS. Haemodynamic management with optimal fluids, inotrope and a vasopressor and titrating its volume and doses using multimodal haemodynamic monitoring while keeping both cardio and neuroprotective strategies, and the multimodal analgesia techniques helped the child for faster recovery.

Spinal Arachnoid Cyst Analysis of Surgical Experience in a Single Tertiary Care Centre and Review of Literature.

OBJECTIVE: To study patients with spinal arachnoid cysts, who underwent cyst excision with dural defect repair or marsupialization, and their outcomes. METHODS: The retrospective analysis involved reviewing the records of 38 patients who underwent surgical treatment for spinal arachnoid cysts in the Department of Neurosurgery at Christian Medical College, Vellore, between August 2004 and December 2022. The study examined the demographics, clinical presentation, imaging, surgical intervention, and outcomes of these patients. RESULTS: The majority of patients in the study were male (29/38, with 76.3%) and the thoracic region was the most common location for the cyst (17, with 44.7%). Weakness was the primary complaint and 94.7% of patients had myelopathy. The bladder was affected in 13 patients (34.2%). Of the 38 patients, 26 (71%) had cysts in extradural locations, while the rest were intradural. In total, 45.5% of intradural cysts were located in the ventral region. Seventeen (65.4%) had dural defects along the root sleeve and 29 (76.3%) underwent complete excision. All extradural cysts underwent complete excision and repair of the dural defect. Thirty patients (78.9%) experienced improved outcomes with reduced spasticity and improved weakness. One patient developed new-onset weakness postoperatively due to epidural hematoma. The mean follow-up period was 41 months and one patient experienced a recurrence. CONCLUSIONS: Spinal arachnoid cyst is a rare benign spinal condition that is typically treated with surgery in symptomatic patients. Surgical intervention may involve either the excision of the cyst or marsupialization.

Erythropoietin mediated bone formation is regulated by mTOR signaling.

The role of erythropoietin (Epo) and Epo/Epo receptor (EpoR) signaling pathways for production of red blood cells are well established. However, little is known about Epo/EpoR signaling in non-hematopoietic cells. Recently, we demonstrated that Epo activates JAK/STAT signaling in hematopoietic stem cells (HSCs), leading to the production of bone morphogenetic protein 2 (BMP2) and bone formation and that Epo also directly activates mesenchymal cells to form osteoblasts in vitro. In this study, we investigated the effects of mTOR signaling on Epo-mediated osteoblastogenesis and osteoclastogenesis. We found that mTOR inhibition by rapamycin blocks Epo-dependent and -independent osteoblastic phenotypes in human bone marrow stromal cells (hBMSCs) and ST2 cells, respectively. Furthermore, we found that rapamycin inhibits Epo-dependent and -independent osteoclastogenesis in mouse bone marrow mononuclear cells and Raw264.7 cells. Finally, we demonstrated that Epo increases NFATc1 expression and decreases cathepsin K expression in an mTOR-independent manner, resulting in an increase of osteoclast numbers and a decrease in resorption activity. Taken together, these results strongly indicate that mTOR signaling plays an important role in Epo-mediated bone homeostasis.

Correction: Calpain and Reactive Oxygen Species Targets Bax for Mitochondrial Permeabilisation and Caspase Activation in Zerumbone Induced Apoptosis.

[This corrects the article DOI: 10.1371/journal.pone.0059350.].