Molecular Basis of Cerebral Vasospasm: What Can We Learn from Transcriptome and Temporal Gene Expression Profiling in Intracranial Aneurysm?

Cerebral vasospasm (CV) is a significant complication following aneurysmal subarachnoid hemorrhage (aSAH), and lacks a comprehensive molecular understanding. Given the temporal trajectory of intracranial aneurysm (IA) formation, its rupture, and development of CV, altered gene expression might be a molecular substrate that runs through these clinical events, influencing both disease inception and progression. Utilizing RNA-Seq, we analyzed tissue samples from ruptured IAs with and without vasospasm to identify the dysregulated genes. In addition, temporal gene expression analysis was conducted. We identified seven dysregulated genes in patients with ruptured IA with vasospasm when compared with those without vasospasm. We found 192 common genes when the samples of each clinical subset of patients with IA, that is, unruptured aneurysm, ruptured aneurysm without vasospasm, and ruptured aneurysm with vasospasm, were compared with control samples. Among these common genes, TNFSF13B, PLAUR, OSM, and LAMB3 displayed temporal expression (progressive increase) with the pathological progression of disease that is formation of aneurysm, its rupture, and consequently the development of vasospasm. We validated the temporal gene expression pattern of OSM at both the transcript and protein levels and OSM emerges as a crucial gene implicated in the pathological progression of disease. In addition, RSAD2 and ATP1A2 appear to be pivotal genes for CV development. To the best of our knowledge, this is the first study to compare the transcriptome of aneurysmal tissue samples of aSAH patients with and without CV. The findings collectively provide new insights on the molecular basis of IA and CV and new leads for translational research.

Mapping ACE2 and TMPRSS2 co-expression in human brain tissue: implications for SARS-CoV-2 neurological manifestations.

The Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily targets respiratory cells, but emerging evidence shows neurological involvement, with the virus directly affecting neurons and glia. SARS-CoV-2 entry into a target cell requires co-expression of ACE2 (Angiotensin-converting enzyme-2) and TMPRSS2 (Trans membrane serine protease-2). Relevant literature on human neurological tissue is sparse and mostly focused on the olfactory areas. This prompted our study to map brain-wide expression of these entry proteins and assess age-related changes. The normal brain tissue samples were collected from cerebral cortex, hippocampus, basal ganglia, thalamus, hypothalamus, brain stem and cerebellum; and were divided into two groups - up to 40 years (n = 10) and above 40 years (n = 10). ACE2 and TMPRSS2 gene expression analysis was done using qRT-PCR and protein co-expression was seen by immunofluorescence. The ACE2 and TMPRSS2 gene expression was observed to be highest in hypothalamus and thalamus regions, respectively. Immunoreactivity for both ACE-2 and TMPRSS2 was observed in all examined brain regions, confirming the presence of these viral entry receptors. Co-localisation was maximum in hypothalamus. Our study did not find any trend related to different age groups. The expression of both these viral entry receptors suggests that normal human brain is susceptibility to SARS-CoV-2, perhaps which could be related to the cognitive and neurological impairment that occur in patients.

The Role of Serum Matrix Metalloproteinase-9 as a Predictor of Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage.

Delayed cerebral ischemia (DCI) is one of the major causes of a poor neurological outcome following aneurysmal subarachnoid hemorrhage (aSAH). Several biomarkers, including matrix metalloproteinase-9 (MMP-9), have been evaluated to predict the development of DCI for timely management. This prospective cohort study was done on 98 patients with aSAH presenting within 72 h of the ictus. Serum samples were collected preoperatively, 7 days after ictus, 10 days after ictus, or when the patient developed DCI, whichever was earlier. The primary objective was to correlate the serum MMP-9 levels with the development of DCI. The secondary objectives were to correlate the serum MMP-9 levels with sonographic vasospasm and the neurological outcome. There was no correlation between the serum MMP-9 levels and the development of DCI (p = 0.37). Similarly, there was no correlation between the serum MMP-9 levels and the sonographic vasospasm (0.05) nor with the modified Rankin Scale (mRS) at discharge (p = 0.27), mRS at 3 months (p = 0.22), and Glasgow Outcome Scale Extended (GOSE) at 3 months (p = 0.15). Serum MMP-9 levels do not predict the development of DCI following aSAH.

Surgical anatomy of the cerebellar tonsils: A cadaveric study.

BACKGROUND: Knowledge of the normal anatomy of the cerebellar tonsils is a prerequisite in various surgeries of the posterior cranial fossa Clinical conditions, as the Chiari I malformations (CIM) alter the normal position of the cerebellar tonsils. OBJECTIVE: Therefore, we aim to better elucidate the surgical anatomy of and around the cerebellar tonsils in regard to the CIM. METHODS: Fifty formalin-fixed adult cadavers injected with colored latex through vertebral arteries underwent craniotomy and durotomy to expose the cerebellar tonsils and related structures. The tonsils and their surrounding anatomy were then studied. RESULTS: Forty cerebellar tonsils were at or above the foramen magnum. Five specimens presented with CIM with the tonsils below (3-5 mm) the FM with a mean tonsillar decent of 7.9 ± 2.3 mm. Of the cadavers without CIM, in forty-two cases, the thickness of the dura mater was within ±3SD ranges. In three cases, the dura mater was thinner at the CVJ and one case; the dura adhered tightly to the inner aspect of the occipital squama. In five CIM cadavers, the dura mater was markedly thicker at the CVJ. The PICA caudal loop was 5.9 ± 1.6 mm long. In CIM cases, the PICA loop was longer, nearer the dura, 1 mm below the superior border of the C1 posterior arch. The distances from the PICA loop were markedly reduced by 3 mm from the spinal accessory nerve and 2 mm from the first spinal nerve. The DN was significantly closer to the tonsillar peduncle in CIM cases. CONCLUSION: These data are important for better understanding the intrinsic and extrinsic anatomy of the cerebellar tonsils in patients with and without CIM. Importantly, tonsillectomy/tonsillar coagulation must consider the close relationship of the dentate nucleus to the base of the cerebellar tonsil to avoid iatrogenic injury.

Investigating the Glucagon-like Peptide-1 and Its Receptor in Human Brain: Distribution of Expression, Functional Implications, Age-related Changes and Species Specific Characteristics.

Introduction: Emerging evidence has shown that the glucagon-like peptide-1 (GLP-1) agonist can be used to treat Alzheimer disease; however, knowledge of its neural targets is limited. To understand the neural substrates of GLP-1, we have done whole brain mapping for GLP-1 and its receptor (GLP-1R), in 30 human brains. Methods: GLP-1 expression was studied by immuno-histochemistry and confirmed by the western blot method. The GLP-1R gene expression was studied by reverse transcription polymerase chain reaction. Results: GLP-1 expression was observed in most of the cortical areas (maximum in frontal, prefrontal and parietal cortex), diencephalon, and brainstem, but not in the cerebellum. Protein expression studies validated these results. The highest expression of GLP-1R was found in the frontal cortex. The orbitofrontal cortex and cerebellum had negligible expression. Hippocampus demonstrated a significant presence of GLP-1R but patchy immunoreactivity to GLP-1. GLP-1R presence in most of the human cortical regions and absence in the cerebellum is the major deviation from the animal brain. Sites that might be of interest in Alzheimer have been identified. GLP-1 demonstrated an age-related decline in most of the areas after the fifth decade. At 60 years, GLP-1 was not found in any of the cortical areas except in the prefrontal cortex; however, it was present in the sub-cortical areas. Conclusion: Age-related profiling of GLP-1 in various brain areas has been analyzed, which can have an important bearing on understanding Alzheimer disease. This study provides a detailed description of GLP-1 and an brain mapping for the first time and may lead to novel treatment options targeting the GLP-1 receptors. Highlights: Glucagon like peptide-1 (GLP-1) agonist can be used for treating Alzheime'rs disease.GLP-1 gene expression was seen in cortical areas, diencephalon and brainstem, but not in cerebellum.Hippocampus demonstrated significant presence of GLP-1R but patchy immunoreactivity to GLP-1.GLP-1 demonstrated age related decline in most of the areas after fifth decade.A detailed description of GLP-1 and amp; GLP-1R locations was given which may lead to novel treatment options. Plain Language Summary: Emerging evidence has shown that the glucagon like peptide-1 (GLP1-1) agonist can be used for treating Alzheimer's disease but knowledge of its neural targets is limited. To understand the neural substrates of GLP-1, we have done whole brain mapping for GLP-1 and its receptor (GLP-1R), in 30 human brains. GLP-1 expression was studied by immuno-histochemistry and confirmed by western blot method. GLP-1R gene expression was studied by RT-PCR. GLP-1 expression was seen in most of the cortical areas (maximum in frontal, prefrontal & amp; parietal cortex), diencephalon and brainstem, but not in cerebellum. Protein expression studies validated these results. Highest expression of GLP-1R was found in the frontal cortex. The orbito-frontal cortex and cerebellum had negligible expression. Hippocampus demonstrated significant presence of GLP-1R but patchy immunoreactivity to GLP-1. GLP-1R presence in most of the human cortical regions and absence in cerebellum is the major deviation from the animal brain. Sites which might be of interest in Alzheimer's have been identified. GLP-1 demonstrated age related decline in most of the areas after 5 th decade. At 60 years GLP-1 was not found in any of the cortical areas except in the prefrontal cortex but it was present in the sub-cortical areas. Age related profiling of GLP-1 in various brain areas has been analysed, which can have important bearing on understanding the Alzheimer's. This study provides detailed description of GLP-1 and ations by complete human brain mapping for the first time and may lead to novel treatment options targeting the GLP-1 receptors.

Analysis of distribution and localization of proteins of the reelin signalling pathway in mesial temporal lobe epilepsy.

INTRODUCTION: Granule cell dispersion (GCD) is pathognomonic of hippocampal sclerosis seen in the mesial temporal lobe epilepsy (MTLE). Current animal studies indicate deficiency of Reelin is associated with abnormal granule cell migration leading to GCD. The present study aimed to evaluate complete Reelin signalling pathway to assess whether Reelin deficiency is related to MTLE. MATERIALS AND METHODS: Hippocampal sclerosis was confirmed by H and E stain. To explore the amount and cellular location of the Reelin cascade molecules, the hippocampal tissues from MTLE surgery and controls (n = 15 each) were studied using Immuno-histochemistry (IHC). Additionally, confocal imaging was used to validate the IHC findings by co-localization of different proteins. Quantification of IHC images was performed using histo-score and confocal images by Image J software. RESULTS: Immune expression of active Reelin was significantly reduced in patients. Reelin receptors were deranged, apolipoprotein E receptor 2 was increased while very low-density lipoprotein receptor was reduced. Disabled-1, a downstream molecule was significantly reduced in MTLE. Its ultimate target, cofilin was thus disinhibited and expressed more in MTLE. Reelin cleaving protease, matrix metalloprotease-9 (MMP-9) and MMP-9 inhibitor, tissue inhibitor of matrix protease-1, showed reduced expression in extracellular matrix. Semi-quantification of immunohistochemistry was done using Histo (H) score. H score of Reelin in diseased patients was 15 against 125 for control patients. These results were validated by confocal fluorescence microscopy. CONCLUSIONS: Reelin signalling cascade was deranged in chronic MTLE. Pharmacological manipulation of Reelin cascade can be done at various levels and it may provide novel treatment options for MTLE.

Dysregulated Genes and Signaling Pathways in the Formation and Rupture of Intracranial Aneurysm.

Intracranial aneurysm (IA) has the potential to rupture. Despite scientific advances, we are still not in a position to screen patients for IA and identify those at risk of rupture. It is critical to comprehend the molecular basis of disease to facilitate the development of novel diagnostic strategies. We used transcriptomics to identify the dysregulated genes and understand their role in the disease biology. In particular, RNA-Seq was performed in tissue samples of controls, unruptured IA, and ruptured IA. Dysregulated genes (DGs) were identified and analyzed to understand the functional aspects of molecules. Subsequently, candidate genes were validated at both transcript and protein level. There were 314 DGs in patients with unruptured IA when compared to control samples. Out of these, SPARC and OSM were validated as candidate molecules in unruptured IA. PI3K-AKT signaling pathway was found to be an important pathway for the formation of IA. Similarly, 301 DGs were identified in the samples of ruptured IA when compared with unruptured IAs. CTSL was found to be a key candidate molecule which along with Hippo signaling pathway may be involved in the rupture of IA. We conclude that activation of PI3K-AKT signaling pathway by OSM along with up-regulation of SPARC is important for the formation of IA. Further, regulation of Hippo pathway through PI3K-AKT signaling results in the down-regulation of YAP1 gene. This along with up-regulation of CTSL leads to further weakening of aneurysm wall and its subsequent rupture.

Central myelin-peripheral myelin junction in trigeminal, facial, and vestibulocochlear nerve: A histo-morphometric study.

BACKGROUND: The study aimed to locate the central myelin and peripheral myelin junction (CNS PNS Junction, CPJ) in trigeminal, facial and vestibulocochlear nerves. METHODS: The cisternal segments of the nerves were cut from the brainstem to the proximal margin of trigeminal ganglia (trigeminal nerve) and internal acoustic meatus (facial and vestibulocochlear nerve) from cadavers. Horizontal sections of H&E stained slides were analysed and histo morphometry was performed. The CPJ was confirmed by immunohistochemistry using monoclonal myelin basic protein antibody. RESULTS: The mean length of the trigeminal, facial and vestibulocochlear nerves were 13.6 ± 3.1 mm, 12.4 ± 1.9 mm and 11.5 ± 2.0 mm respectively; mean length of the centrally myelinated segment at the point of maximum convexity was 4.1 ± 1.5 mm, 3.7 ± 1.6 mm, 3.6 ± 1.4 mm respectively. Six different patterns were observed fortheCPJ.Utilizing the derived values, the CPJwas located at a distance of 18 - 48% and 17 - 61% of the total length of the nerve in all the cases in trigeminal and facial nerve respectively. In vestibulocochlear nerve, it was located at a distance of about 13 - 54% of the total length of the nerve. CONCLUSIONS: The location of the CPJ in the vestibulocochlear nerve was midway between the brainstem and internal acoustic meatus which is a novel observation.For all the nerves, the CPJ was located either at or before the half way along the length of the nerve in huge majority (97%); never crossing the 60% of the nerve length.

Reelin Signaling Pathway and Mesial Temporal Lobe Epilepsy: A Causative Link.

Introduction: Mesial temporal lobe epilepsy (MTLE) is the most frequent form of partial epilepsy. Granule cell dispersion, resulting from aberrant neuronal migration in the hippocampus, is pathognomonic of MTLE. Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons. Several animal studies have implicated Reelin in the MTLE pathogenesis Mesial temporal lobe epilepsy (MTLE) is the most frequent form of partial epilepsy. Granule cell dispersion, resulting from aberrant neuronal migration in the hippocampus, is pathognomonic of MTLE. Reelin, a secreted neurodevelopmental glycoprotein has a crucial role in controlling the radial migration of neurons. Several animal studies have implicated Reelin in the MTLE pathogenesis. Methods: The aim of this study was to investigate the Reelin signalling pathway in the MTLE patients. Therefore, we studied each step in the Reelin signalling pathway for the gene and protein expressions, in the hippocampal tissue obtained from patients undergoing surgery for MTLE and compared it with age matched normal autopsy cases. Results: We found statistically significant decrease (P<0.001) in the Reelin mRNA expression in MTLE patients. Among the two reelin receptors, apolipoprotein E receptor 2 (ApoER2) was significantly increased whereas very low density lipoprotein receptor (VLDLR) was decreased among the patients. Disabled 1 (Dab1), the downstream target of reelin, was found to be decreased. Dab1 in turn inhibits Cofilin, which is responsible for cytoskeletal reorganization, thus limiting aberrant neuronal migration. Statistically significant over expression of Cofilin protein was found in the patient group. Matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteases-1 (TIMP-1), both of which are involved in processing of Reelin, were down regulated in 70-85% of cases. Conclusion: The whole pathway was found to be deranged in MTLE. These results indicate that Reelin signalling pathway is disturbed at various points in the MTLE patients and might be involved in the pathogenesis & progression of MTLE. Our results extend the existing information regarding the components of the Reelin pathway and further, establish a link between pathway disturbance and MTLE.

Morphometry and anatomical variations of the inferior oblique muscle as relevant to the strabismus surgeries.

Effective outcome of inferior oblique (IO) corrective surgeries demands a detailed knowledge of morphometry and variations of IO. Our aim was to study and morphometrically define the surgical anatomy of the IO muscle and its variations. Also to provide easily identifiable surgical coordinates to locate, the IO origin and the oculomotor nerve entry point into the IO. Dissection was performed on 16 cadaveric orbits. IO anatomy, variations, morphometry and relevant surgical distances were measured using digital caliper. IO with multiple bellies was found in five specimens. The IO mean length was 33.1 ± 3.3 mm, width at origin was 3.1 ± 0.6 mm, and width at insertion was 8.8 ± 1.5 mm. For easy localization of origin, its distance from the palpable landmarks, Zygomatico-maxillary suture and fronto-maxillary suture was measured. The mean distance between IO and the optic nerve was 10 mm. Distance of the nerve to inferior oblique entry point to the origin and insertion of the inferior oblique was measured. The nerve to IO was 28 mm long. The mean distance of the nerve entry point to IO origin was 15.5 ± 2.3 mm and distance to IO insertion was 15.2 ± 2.8 mm. A muscular bridge between the Inferior rectus (IR) & IO was found in one case, affecting ~» of the IO length; the distal end of the bridge was 5 mm from the IO insertion. Origin of the IO can be localized on the orbital surface of maxilla, 1-2 cm from the point where zygomatico-maxillary suture cuts the inferior orbital margin and 1-2 cm from the fronto-maxillary suture. In 19% of the orbits, the IO length was less than 30 mm, which may cause traction injury in muscle transposition procedures. The width at insertion is useful as most corrective surgeries are performed at the insertion site. The nerve to IO consistently entered at the center of medial border. The nerve entry point is important surgically as myectomy is performed between it and the insertion point. The safe distance available from the optic nerve was 7 mm. Detailed morphometry of IO may aid surgeons in better surgical planning and execution.

A Novel Pedicle Screw Design with Variable Thread Geometry: Biomechanical Cadaveric Study with Finite Element Analysis.

BACKGROUND: Pedicle screw fixation provides one of the most stable spinal constructs. Their designs together with osseous characteristics have been known to influence the screw-bone interplay during surgical maneuvers and thereafter the fusion process. Various technical modifications to enhance screw performance have been suggested. This study evaluated the pull-out strength and axial stiffness of a novel pedicle screw design with variable thread geometry and pitch. METHODS: The newly designed triple threaded pedicle screw is tapered, and has unique out-turned flanges to hold the cancellous bone and a finer pitch at its distal and proximal end to engage the cortical bone. Five lumbar and 4 lower thoracic cadaveric vertebrae were divided into hemivertebrae. A standard cancellous pedicle screw and the newly designed pedicle screw were inserted into each hemivertebra. Axial stiffness and peak pull-out force between the screw types were compared; a finite element analysis was also performed to additionally compare the pull out under toggle forces. RESULTS: In cadaveric study, the axial stiffness of the new screw was significantly better than that of the standard screw. However, the peak load between the screws was not statistically different. Finite element analyses suggested lesser stress at bone-implant interface for the new screw along with better axial stiffness under both co-axial and toggle forces. CONCLUSIONS: Our novel pedicle screw design with variable thread geometry demonstrates greater axial stiffness compared with the standard screws, and therefore is likely to withstand a greater surgical manipulation.

Expressional Study of Permeability Glycoprotein and Multidrug Resistance Protein 1 in Drug-resistant Mesial Temporal Lobe Epilepsy.

Introduction: About 30% of patients with epilepsy do not respond to anti-epileptic drugs, leading to refractory seizures. The pathogenesis of drug-resistance in mesial temporal lobe epilepsy (MTLE) is not completely understood. Increased activity of drug-efflux transporters might be involved, resulting in subclinical concentrations of the drug at the target site. The major drug-efflux transporters are permeability glycoprotein (P-gp) and multidrug-resistance associated protein-1 (MRP-1). The major drawback so far is the expressional analysis of transporters in equal numbers of drug-resistant epileptic tissue and age-matched non-epileptic tissue. Methods: We have studied P-gp and MRP-1 drug-efflux transporters in the sclerotic hippocampal tissues resected from the epilepsy surgery patients (n=15) and compared their expression profile with the tissues resected from non-epileptic autopsy cases (n=15). Results: Statistically significant over expression of both P-gp (P<0.0001) and MRP-1 (P=0.01) at gene and protein levels were found in the MTLE cases. The fold change of P-gp was more pronounced than MRP-1. Immunohistochemistry of the patient group showed increased immunoreactivity of P-gp at blood-brain barrier and increased reactivity of MRP-1 in the parenchyma. The results were confirmed by confocal immunofluorescence microscopy. Conclusion: Our results suggested that P-gp in association with MRP-1 might be responsible for the multi-drug resistance in epilepsy. P-gp and MRP-1 could be important determinants of bio availability and tissue distribution of anti-epileptic drugs in the brain which can pharmacologically inhibited to achieve optimal drug penetration to target site.

Interplay between anisotropy and magnetic exchange to modulate the magnetic relaxation behaviours of phenoxo bridged Dy2 dimers with axial ß-diketonate co-ligands.

A series of Schiff base LH ((E)-2-((pyridin-2-ylmethylene)amino)phenol) supported phenoxo bridged symmetric [Dy2(L)2(hfac)4] (1), [Dy2(L)2(tfac)4] (2) and asymmetric [Dy2(L)2(thd)3(NO3)]·1.5H2O (3) binuclear complexes were isolated using differently substituted ß-diketonate co-ligands (Hhfac = hexafluoroacetylacetonate, Htfac = trifluoroacetylacetonate, and Hthd = 2,2,6,6-tetramethyl-3,5-heptanedione). In all the three complexes 1-3, the two LH ligands provide phenoxo bridging and N-donor atoms. The {Dy2(µ2-O)2} magnetic core structures with LH ligands are found to be the same in 1-3 while the dissimilar functionalities of the axially coordinated different ß-diketonate co-ligands play a crucial role in modulating the magnetic anisotropy of individual DyIII sites and magnetic exchange between them. The experimental static magnetic behaviour suggests the presence of intramolecular antiferromagnetic interactions in all the three complexes 1-3. The strength of the magnetic exchange coupling decreases with increasing magnetic anisotropy of individual DyIII ions from complex 1 to complex 3 and simultaneously their zero-field slow magnetic relaxation behaviors were found to increase with effective energy barriers (ΔE/kB) of 9.04 K, 24.06 K and 25.65 K, respectively. Furthermore, the DFT and ab initio theoretical calculations performed on the X-ray structures of complexes 1-3 support our experimental findings.

Cadaver dissection for oculoplastic procedures: A beginner's guide.

The purpose of this article is to form a basic guide for beginning the cadaver dissection training programs focused on oculoplastic surgical procedures. Ours was a collaborative study between the departments of Ophthalmology and Anatomy in a tertiary care teaching institute. We formed a step-wise approach to begin the cadaver dissection focused on the oculoplastic surgical procedures. The basics of cadaver procurement, processing, and preparation for dissections were described. The operative requirements of trainees, surgical handling of cadavers, and basic oculoplastic surgical steps were discussed. The types of embalming (cadaver preservation process) and steps have been described in detail. We have emphasized the preoperative discussion about the proposed dissections using standard teachings and skull models for easier understanding. Additional helping tools like soft embalming and injectable substances for better intra-dissection understanding (intra-arterial, intravenous and orbital injections) have been described. Post-dissection cadaver handing and soft-tissue disposal protocols have also been described. Overall, the cadaver dissections provide holistic surgical learning for the residents, specialty trainees, and practitioners. This article may act as a basic step-wise guide for starting the cadaver-based oculoplastics lab dissection in various institutes and workshops.

Setting up a Neurosurgical Skills Laboratory and Designing Simulation Courses to Augment Resident Training Program.

Background: The surgical skill practice in neurosurgery is being compromised in the recent past owing to the duty time constraint, patient safety concerns, and medico-legal issues. Surgical practice outside the operating room is essential to enhance a resident's operative skills and to gain confidence. Objective: To discuss the experience of establishing an 'in-house neurosurgery skills laboratory' and various training sessions conducted with cadaveric and non-cadaveric simulation modules. Methods: A skills laboratory was set up in the existing resident teaching hall with nine workstations. Each station has been equipped with an operating table, surgeon's chair, basic microscope, endoscope, high-speed drill system, and a suction machine. Vascular anastomosis, high-speed drilling, and basic neuroendoscopy were planned on low-cost non-cadaveric modules. Craniotomy and various surgical approaches were designed on cadaveric modules obtained from the anatomy department. Result: A total of 18 residents in divided groups during their initial three semesters had participated in the non-cadaveric simulation courses. Twenty-six residents had participated and 12 sessions were conducted on the cadaveric modules. Three workshops were conducted and 20 residents and faculty members from five other institutions had participated in the cadaveric hands-on training session. Conclusion: A well-equipped skills laboratory provides an opportunity for the residents to acquire operative expertise in a similar atmosphere to that of the operating theater. A structured program comprising various operative practice sessions should be incorporated into the resident training program.

Revisiting the surgical anatomy of the triangle of doom and the triangle of pain.

Better understanding of the surgical anatomy of the triangle of doom and the triangle of pain with fixed bony landmarks like the anterior superior iliac spine (ASIS) and the pubic symphysis (PS) can help in defining a safe location for trocar placement during laparoscopic surgeries and minimize neurovascular complications. Ten cadavers were dissected bilaterally to explore the surgical anatomy of both the triangles. ASIS and PS were evaluated in relation to the deep inguinal ring, external iliac artery, femoral nerve, and inferior epigastric artery. The deep inguinal ring was located at a depth of ~3 cm, about 4.9 ± 0.56 cm along the y-axis and 6.2 ± 0.94 cm along the x-axis, from the ASIS. The external iliac artery was located ~4.33 ± 0.6 cm along the y-axis and 7.29 ± 0.76 along the x-axis from the ASIS. The inferior epigastric artery was at ~4.31 ± 0.38 cm from the midline at the level of ASIS. This knowledge can help in the surface localization of both the triangles and prevent injury to the various neurovascular structures in relation to these triangles. In the current study, cranial to the ASIS lying at a distance of >5 cm from the midline was observed to be a safe zone for accessory trocar placement. The umbilical port has been observed to be safe for trocar placement. The mean angle between ductus deferens and testicular vessels was observed to be 43.5° ± 4.79°, which could help in determining their relative locations during various surgical procedures.

Osseous deficiencies, pockets, superfluous lateral border thickening in scapula: a rare occurrence.

BACKGROUND: Beyond the nutrient and suprascapular foramen, the other foramina, holes or osseous deficiencies, pockets has rarely been reported in scapula. If present, the bony holes or deficiencies may lead to radiolucent areas and may be mistaken for sites of osteolytic destruction related to skeletal metastases, multiple myeloma or others. CASE REPORT: In the present case of left scapula, unusual osseous deficiencies of different size and shape along with pockets were observed in the body of scapula. The maximum height and width of largest bony deficiency was 35.8 mm and 12.6 mm. There was abnormal osseous thickening beside the lateral border of scapula along with the presence of some spines. Five nutrient foramina, three on the costal and two on the dorsal surface were noticed. CONCLUSIONS: The present case reports the osseous deficiencies, pockets and extra osseous growth along the lateral border, multiple nutrient foramina altogether in one specimen. Thorough anatomical knowledge of these unusual osseous variations can provide the clinicians, radiologists and forensic experts with better clinical judgement and may add insight to the surgical planning by orthopaedic surgeons.

Digastric musculus sternalis.

PURPOSE: To report a rare variant muscle. METHODS: Aberrant muscle was observed in the anterior chest wall musculature during routine cadaver prosection. RESULTS: Musculus sternalis consisting of two muscular bellies united at an angle by an intermediate tendon was observed anterior to the pectoral major of the left side. The muscle did not have any bony attachment. CONCLUSIONS: The present case represents a hybrid muscle with superior belly derived from the prepectoral mass and inferior belly from ventral longitudinal muscle column. Clinically, the musculus sternalis may be misinterpreted as a pathological mass or lesion thus its accurate knowledge is significant to radiologists, angiologists and surgeons for better interpretation of mammographic images, safer interventions and for reconstructive surgeries.

Identification of novel pulmonary vein nodes as generators of ectopic arrhythmic foci for atrial fibrillation: an immunohistochemical proof.

PURPOSE: The atrial muscle sleeve (AMS) of the pulmonary vein is the most common source of the arrhythmogenic triggers in atrial fibrillation (AF). Anatomical substrate generating these ectopic currents is still elusive. The present study was designed to study the AMS of pulmonary veins with an emphasis on the structural basis which might govern AF initiation and perpetuation. METHODS: The study was conducted on a longitudinal tissue section of pulmonary vein, taken from 15 human cadaveric nondiseased hearts. Tissue was studied histologically using H&E and Gömöri trichrome stain. The pacemaker channels were identified by immunohistochemistry using monoclonal HCN4 and HCN1 antibodies. RESULTS: The AMS was identified in each pulmonary vein, located between the tunica adventitia and tunica media. A node-like arrangement of myocytes was seen within the AMS in 30% of veins. It had a compact zone limited by a fibrous capsule and contained much smaller, paler and interconnected myocytes. Outside the capsule, there was a zone of dispersed, singly placed myocytes separating the compact zone from the working myocytes of the AMS. HCN4 and HCN1 antibodies were expressed on the cell membrane of nodal myocytes, while the working myocytes demonstrated none to minimal staining. CONCLUSION: Pulmonary veins nodes are similar to the specialized cardiac conductive tissue in the histological arrangement of compact and transitional zones, cellular characteristics and the presence of pacemaker channels. They might be the anatomical basis of ectopic arrhythmogenic foci. To our knowledge, these nodes are being described for the first time in human.

Basilar Artery Bands: Anatomic and Histologic Study with Application to Coiling and Stenting Procedures.

BACKGROUND: Internal bands of the basilar artery (BA) have been rarely studied. Because bands could have obvious consequences in patient diagnosis and care, the present multiinstitutional cadaveric study was performed. METHODS: The intraluminal bands of BAs were studied in 80 cadaveric specimens derived from India (Group 1) and the United States (Group 2). Their orientation within the vessel was recorded. Measurements included the length of the BA, diameter of the BA, intraluminal band length and thickness, and distance of the band to the vertebrobasilar junction. Selected bands were submitted for histologic analysis. RESULTS: In Group 1, an intraluminal band (all vertically oriented) was identified in 16.6%. The mean length and thickness of the bands were 2.04 mm and 1.33 mm, respectively. These bands were located at a mean distance of 1.74 mm superior to the vertebrobasilar junction. In Group 2, an intraluminal band was identified in 6%. One band was vertically positioned, and 2 were horizontally positioned. The mean length and thickness of the bands were 2.5 mm and 0.9 mm, respectively. These latter bands were located at a mean distance of 2.23 mm superior to the vertebrobasilar junction. Histologically, the bands were essentially extensions of the tunica media and interna of the artery. CONCLUSIONS: To our knowledge, this study is the first multiethnic study of the prevalence and morphometry of the BA bands. A better understanding of these bands may help reveal their relationship to thrombus and aneurysmal formation and their impact on endovascular procedures.