Brain cancer remains among the most lethal malignancies worldwide, with approximately 321,476 new cases and 248,305 deaths reported globally in 2022. The treatment of malignant brain tumors presents substantial clinical challenges, primarily due to their resistance to standard therapeutic approaches. Despite decades of intensive research, effective treatment strategies for brain cancer are still lacking. Nuclear receptors (NRs), a superfamily of ligand-activated transcription factors, regulate a broad range of physiological processes including metabolism, immunity, stress response, reproduction, and cellular differentiation. Increasing evidence highlights the involvement of NRs in oncogenesis, with several members demonstrating altered expression and function in brain tumors. Aberrations in NR signaling, encompassing receptors such as androgen receptors, estrogen receptors, estrogen-related receptors, glucocorticoid receptors, NR subfamily 4 group A, NR subfamily 1 group D member 2, NR subfamily 5 group A member 2, NR subfamily 2 group C member 2, liver X receptors, peroxisome-proliferator activated receptors, progesterone receptors, retinoic acid receptors, NR subfamily 2 group E member 1, thyroid hormone receptors, vitamin D receptors, and retinoid X receptors, have been implicated in promoting hallmark malignant phenotypes, including enhanced survival, proliferation, invasion, migration, metastasis, and resistance to therapy. This review aims to explore the roles of key NRs in brain cancer, with an emphasis on their prognostic significance, and to evaluate the therapeutic potential of targeting these receptors using selective agonists or antagonists.
Humans ; Brain Neoplasms/drug therapy* ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Animals ; Signal Transduction/physiology*

Methods: Four FE models of multilevel posterior cervical fixation were created and tested by FEA in various permutations and combinations. Generic differences in fixation were determined, and the following parameters were assessed: (1) maximum moment at failure, (2) maximum angulation at failure, (3) maximum stress at failure, (4) point of failure, (5) intervertebral disc stress, and (6) influence of adding a C2 pars screw to the multilevel construct. Results: The maximum moment at failure was higher in the LMS fixation group than in the TPS group. The maximum angulation in flexion allowed by LMS was higher than that by TPS. The maximum strain at failure was higher in the LMS group than in the TPS group. The maximum stress endured before failure was higher in the TPS group than in the LMS group. Intervertebral stress levels at C6–C7 and C7–T1 intervertebral discs were higher in the LMS group than in the TPS group. For both models where C2 fixation was performed, lower von Mises stress was recorded at the C2–C3 intervertebral disc level. Conclusions Ending a multilevel posterior cervical fixation construct with TPS fixation rather than LMS fixation at the C7 vertebra provides a stiff and more constrained construct system, with higher stress endurance to compressive force. The constraint and durability of the construct can be further enhanced by adding a C2 pars screw in the fixation system.

Background: High-grade gliomas (HGG) are highly fatal tumors despite advanced multimodalitymanagement. They are also associated with neurocognitive impairment, both due to disease pathology and treatment. We aimed to assess various risk factors responsible for neurocognitive decline in HGG patients undergoing adjuvant chemoradiation. Methods: Newly diagnosed HGG patients who underwent maximal safe resection were includ-ed. Patients received volumetric modulated arc therapy to a dose of 60 Gy in 30 fractions, along with concurrent temozolomide (TMZ) at a dose of 75 mg/m2 /day orally; thereafter adjuvant TMZ (150–200 mg/m 2 for 5 days), given every 28 days for 6 to 8 cycles. The Mini-Mental State Examination questionnaire was used to measure cognitive impairment of each study patient at various time points. Cox regression model was used for univariate and multivariable analysis of data to establish possible risk factors. Results: Fifty-three patients were enrolled and analyzed. At a median follow-up of 15 months,30 patients (56.6%) developed cognitive impairment, and 23 patients (43.4%) did not. On univariate analysis, HGG with WHO grade 4, glioblastoma and diffuse midline glioma histology, IDH-wild type, recursive partitioning analysis class IV/V, and only biopsy of primary tumor were significantly associated with neurocognitive impairment, but none of them were independent risk factors on multivariable analysis. Planning target volume and dose received by ipsilateral hippocampus were also significantly correlated with cognitive decline in HGG patients. Conclusion Decline in neurocognitive functions in HGG patients is multifactorial and can be attrib-uted to an amalgam of various tumor, patient, and treatment-related factors.

Objective: In previous research, we found that Sestrin2 has a strong association with plasma atherogenicity and combats the progression of atherogenesis by regulating the AMPK-mTOR pathway. Metformin, an activator of AMPK, is widely used as a first-line therapy for diabetes, but its role in preventing atherosclerosis and cardiac outcomes is unclear. Hence, we aimed to assess the effect of metformin on preventing atherosclerosis and its regulatory role in the Sestrin2-AMPK -mTOR pathway in obese/diabetic rats. Methods: Animals were fed a high-fat diet to induce obesity, administered streptozotocin to induce diabetes, and then treated with metformin (150 mg/kg body weight) for 14 weeks. Aorta and heart tissues were analyzed for Sestrin2 status by western blotting and immunohistochemistry, AMPK and mTOR activities were investigated using western blotting, and atherogenicity-related events were evaluated using reverse transcription quantitative polymerase chain reaction and histology. Results: Obese and diabetic rats showed significant decrease in Sestrin2 levels and AMPK activity, accompanied by increased mTOR activity in the heart and aorta tissues. Metformin treatment significantly restored Sestrin2 and AMPK levels, reduced mTOR activity, and restored the altered expression of inflammatory markers and adhesion molecules in obese and diabetic rats to normal levels. A histological analysis of samples from obese and diabetic rats showed atherosclerotic lesions both in aorta and heart tissues. The metformin-treated rats showed a decrease in atherosclerotic lesions, cardiac hypertrophy, and cardiomyocyte degeneration. Conclusion This study presents further insights into the beneficial effects of metformin and its protective role against atherosclerosis through regulation of the Sestrin2-AMPK-mTOR pathway.

Background: Epidural analgesia failure episodes can be reduced by catheter fixation techniques with a lower incidence of catheter migration. In this clinical study, we compared the roles of two epidural catheter tunneling techniques for the prevention of epidural catheter migration. Methods: Patients undergoing major abdominal surgery were randomized into three groups of 50 patients each based on the method used to secure the epidural catheter. In the control group (CG), the epidural catheter was secured without tunneling. Tunneling groups 1 and 2 (TG1 and TG2) were defined as tunneling with and without a catheter loop, respectively. The primary outcome measure was the migration of the epidural catheter, while the secondary outcome measures were the adequacy of analgesia and signs of inflammation. All patients were followed up by the acute pain service team twice daily in the postoperative period until the epidural catheter was removed. The results were analyzed by the one-way analysis of variance (ANOVA), chi-square test, and Fisher’s exact test. P values <0.050 were considered significant. Results: The three groups were similar with respect to patient characteristics. Catheter migration was significantly reduced in TG2 (two patients) compared to those in the other two groups, i.e., TG1 (eight patients) (P = 0.045) and CG (17 patients) (P = 0.001). No differences were found amongst the three groups in analgesia adequacy and catheter site inflammation (P > 0.050). Conclusions Catheter migration was significantly reduced by tunneling without a catheter loop in TG2 as compared to the other two groups. Therefore, we suggest routine use of tunneling without a catheter loop technique in anesthesia practice and look forward to future studies with larger sample sizes.

Objective: With the development of endovascular technique and devices, large and giant intracranial aneurysms are increasingly being managed by this less invasive method. Here we discuss our experience on managing such aneurysms via endovascular technique. Methods: Retrospective data on 42 patients with large and giant intracranial aneurysms managed by endovascular techniques between September 2015 to December 2017 at our neurosurgery institute were included in this analysis. Results: There were a total 42 patients with 9 giant and 33 large aneurysms in this study. Eight aneurysms were treated by parent vessel occlusion, 22 aneurysms with coils and rest 12 aneurysms were treated with stent assisted coiling. Following the procedure, Raymond class I occlusion was accomplished in 31 (73.8%) patients while class Ⅱ in 9 (21.4%) and class Ⅲ in 2 (4.8%) patients. Overall morbidity and mortality were 9.5% and 14.3% respectively and favorable outcome was seen in 80.9% patients. Significant correlation was observed with clinical outcome and initial neurological status. Conclusions The study indicates that endovascular intervention is a safe and effective method in managing large and giant intracranial aneurysms with lesser morbidity and mortality.

Angioleiomyoma is a benign soft tissue tumor originating from vascular smooth muscle. We report a case of a 20-year-old student who presented with pain in the right shoulder of 4 years duration. Shoulder movements were pain-free throughout the range of motion except resisted external rotation. Magnetic resonance imaging visualized a well-circumscribed lesion over the infraspinatus tendon. The lesion was surgically removed and sent for histopathological analysis. Morphology and immunohistochemistry results were suggestive of angioleiomyoma. The most common location for such a lesion is the lower limb, with less than 1% being reported in the upper arm, of which an angioleiomyoma of the shoulder is extremely rare.

Objective: With the development of endovascular technique and devices, large and giant intracranial aneurysms are increasingly being managed by this less invasive method. Here we discuss our experience on managing such aneurysms via endovascular technique. Methods: Retrospective data on 42 patients with large and giant intracranial aneurysms managed by endovascular techniques between September 2015 to December 2017 at our neurosurgery institute were included in this analysis. Results: There were a total 42 patients with 9 giant and 33 large aneurysms in this study. Eight aneurysms were treated by parent vessel occlusion, 22 aneurysms with coils and rest 12 aneurysms were treated with stent assisted coiling. Following the procedure, Raymond class I occlusion was accomplished in 31 (73.8%) patients while class Ⅱ in 9 (21.4%) and class Ⅲ in 2 (4.8%) patients. Overall morbidity and mortality were 9.5% and 14.3% respectively and favorable outcome was seen in 80.9% patients. Significant correlation was observed with clinical outcome and initial neurological status. Conclusions The study indicates that endovascular intervention is a safe and effective method in managing large and giant intracranial aneurysms with lesser morbidity and mortality.