The way in which Aquaporin-4 (AQP4) is localized on the astrocytes’ surface—i.e., with AQP4 channels predominantly located on the endfeet of astrocytes near the blood vessels—represents an important structural element for maintaining brain fluid homeostasis. In addition to this structural function, AQP4 polarity also facilitates glymphatic transport, the maintenance of the blood–brain barrier (BBB) functions, ion buffering, and neurotransmitter removal, and helps regulate neurovascular communications. The growing body of literature suggests that the loss of AQP4 polarity—a loss in the organization of AQP4 channels to the perivascular membrane—is associated with increased vascular, inflammatory, and metabolic disturbances in the context of many neurological diseases. As a result, this review attempts to synthesize both experimental and clinical studies to highlight that AQP4 depolarization often occurs in conjunction with early signs of neurodegeneration and neuroinflammation; however, we are aware that the loss of AQP4 polarity is only one factor in a complex pathophysiological environment. This review examines the molecular structure responsible for maintaining the polarity of AQP4—such as dystrophin–syntrophin complexes, orthogonal particle arrays, lipid microdomains, trafficking pathways, and transcriptional regulators—and describes how the vulnerability of these systems to various types of vascular stress, inflammatory signals, energy deficits, and mechanical injury can lead to a loss of AQP4 polarity. Furthermore, we will explore how a loss of AQP4 polarity can lead to the disruption of perivascular fluid movement, changes in blood–brain barrier morphology, enhanced neuroimmune activity, changes in ionic and metabolic balance, and disruptions in the global neural network synchronization. Importantly, we recognize that each of these disruptions will likely occur in concert with other disease-specific mechanisms. Alterations in AQP4 polarity have been observed in a variety of neurological disorders including Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, traumatic brain injury, and glioma; however, we also observe that the same alterations in fluid regulation occur across all of these different diseases, but that no single upstream event accounts for the alteration in polarity. Ultimately, we will outline emerging therapeutic avenues to restore perivascular fluid transport, and will include molecular-based therapeutic agents designed to modify the anchoring of AQP4, methods designed to modulate the state of astrocytes, biomaterials-based drug delivery systems, and therapeutic methods that leverage dynamic modulation of the neurovascular interface. Future advances in multi-omic profiling, spatial proteomics, glymphatic imaging, and artificial intelligence will allow for earlier identification of AQP4 polarity disturbances and potentially allow for the development of more personalized treatment plans. Ultimately, by linking these concepts together, this review aims to frame AQP4 polarity as a modifiable aspect of the “fluidic connectome”, and highlight its importance in maintaining overall brain health across disease states.

Myxomas are the most common cardiac tumors. This study aimed to analyze the possible risk factors associated with late mortality in this group of patients and assess long-term survival. A retrospective study was conducted among patients who underwent myxomas resection between January 2008 and July 2019 in our service. The patients' preoperative, intraoperative, and postoperative data were analyzed. Multivariate logistic regression was performed to identify predictors of mortality at five years. The Kaplan-Meier curve and Cox proportion-adjusted survival curves were used to assess mortality at five and 10 years. A total of 108 patients with cardiac myxomas were identified. All cardiac tumors resected were confirmed as myxomas on histopathological examination. Ninety-six patients presented with left-side myxomas (94 left-atria and two left-ventricle) and 12 with right-side myxomas (11 right-atria, one right-ventricle); 78 of the tumors were capsulated, and 30 were sessile-papillary. The mean dimensions were 37 ±6.1 mm on the left side and 41 ±6.7 mm on the right side. Surgical excision was successful in all cases, with 25% requiring interatrial septum patch repair. Recurrence occurred in 2.77% of the patients. Multivariate logistic regression showed chronic kidney disease (CKD) (OR: 7.96, 95% CI: 1.469-43.125, p=0,016) to be an independent predictor for five-year mortality. The mean follow-up period was 7.13 ±2.965 years, and the Kaplan-Meier curve cumulative proportion survival of patients at five years and 10 years were 100% and 88.8%, respectively. There was no statistically significant difference in late-term survival between patients with and without CKD in the Cox proportion-adjusted survival curve (p=0.275). Patients with myxomas have a good long-term prognosis following surgical resection. The multivariate logistic regression showed CKD to be an independent predictor of five-year mortality.

The development of the optic nerve and its surrounding tissues during the early fetal period is a convoluted period because it spans both the organogenesis period and the fetal period. This study details the microscopic anatomy and histoembryology of the optic nerve in embryos during the early fetal period, including the second half of the first trimester of pregnancy. Serial sections through the orbit of variously aged embryos allowed us to analyze the nerve in both longitudinal and transverse aspects. A histological assessment and description of the structures surrounding and inside the nerve were performed, highlighting the cellular subtypes involved. By employing immunohistochemical techniques, we could characterize the presence and distribution of astrocytes within the optic nerve. Our findings suggest that by the 8th gestational week (WG) the structures are homologs to all the adult ones but with an early appearance so that maturation processes take place afterward. By this age, the axons forming the nerve are definitive adult axons. The glial cells do not yet exhibit adult phenotype, but their aspect becomes adult toward the 13th week. During its development the optic nerve increases in size then, at 14 weeks, it shrinks considerably, possibly through its neural maturation process. The morphological primordium of the blood–nerve barrier can be first noted at 10 WG and at 13 WG the morphological blood–nerve barrier is definitive. The meningeal primordium can be first noted as a layer of agglomerated fibroblasts, later toward 13 WG splitting in pachymeninx and leptomeninges and leaving space for intrinsic blood vessels.

The primary treatment of breast cancer in sentinel -positive ganglia includes axillary lymphatic nodal dissection. The LAD (lymphatic axillary dissection) has decreased in overall numbers but due to the increasing incidence of breast cancer, it is practised on a daily basis, even though there is a myriad of complications such as numbness of the upper limb and chest wall, movement restriction of the upper limb, and chronic pain which appear due to trauma to the nerves which pass through the axilla. However, the utility in the overall survival or DFS (disease -free survival) of the patient is unquestionable. In our study, through the dissection of cadavers, we exposed the vital structures and the anatomical relations of this region. We aimed to offer a map or technique for the surgeon to follow to decrease the overall morbidity of this procedure.

Background: First described by Carl Toldt in the late 19th century, the mesorectum has since been a topic of anatomical and surgical debate. Its clinical importance was redefined by Heald’s introduction of Total Mesorectal Excision (TME), nowadays the golden standard in oncologic rectal surgery. This study aims to elucidate the embryological development and adult anatomy of the mesorectum and the mesorectal fascia, with a focus on clinically significant relations, particularly the peritoneum, and components of the hypogastric plexuses. Methods: We performed anatomical dissections on four 12–15-week-old human fetuses and eight formalin-fixed adult cadavers. In addition, a transverse pelvic section was examined to assess the spatial organization of mesorectal and fascial structures. Results: Our findings confirm the presence of a dorsal mesentery at the rectal level during fetal development, illustrating its transformation into the adult mesorectum. We identified the mesorectal contents in the fetus and examined the course and relations of the superior rectal vessels, hypogastric nerves, and pelvic splanchnic nerves, in both fetal and adult specimens. Conclusions: The observed fetal and adult configurations provide a continuous morphological description of the mesorectum and its compartmental organization within the pelvis. This study enhances the understanding of the mesorectum’s embryology, structure, and vital surgical landmarks. By delineating the so-called ‘Holy plane’ of Heald (the natural avascular plane between the mesorectal and presacral fasciae used during total mesorectal excision) and the delicate connective fibers known surgically as ‘angel’s hair’, which become visible when this plane is correctly entered, rectal and presacral fasciae, and neurovascular elements, provides a comprehensive anatomical framework that may inform surgical plane identification and support future clinical investigations into nerve-sparing rectal surgery.

Next-generation sequencing (NGS) is a fast and relatively inexpensive method to sequence a large number of genes with crucial importance in cancer medicine. Nowadays, NGS is frequently used in diagnostic and therapeutic decisions in oncology; however, recently, it was demonstrated that only a few cancer sites actually benefit from this assessment. Moreover, the association of a mutant gene with a targeted drug is not always as predicted during in-vitro trials and is often not associated with tumor response. To predict the efficacy of such an association several classification systems have been developed. The present review aims to analyze the most important tumor agnostic treatment trials and assess how they shape selecting cancer patients for NGS. Moreover, it aims to determine how mutation-drug associations can be classified by their targetability and level of evidence of efficacy in non-small-cell lung cancer.