Effects of Aging and Nerve Growth Factor on Neuropeptide Expression and Cholinergic Innervation of the Rat Basolateral Amygdala.

The basolateral amygdala (BLA) contains interneurons that express neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP), both of which are involved in the regulation of functions and behaviors that undergo deterioration with aging. There is considerable evidence that, in some brain areas, the expression of NPY and VIP might be modulated by acetylcholine. Importantly, the BLA is one of the brain regions that has one of the densest cholinergic innervations, which arise mainly from the basal forebrain cholinergic neurons. These cholinergic neurons depend on nerve growth factor (NGF) for their survival, connectivity, and function. Thus, in this study, we sought to determine if aging alters the densities of NPY- and VIP-positive neurons and cholinergic varicosities in the BLA and, in the affirmative, if those changes might rely on insufficient trophic support provided by NGF. The number of NPY-positive neurons was significantly reduced in aged rats, whereas the number of VIP-immunoreactive neurons was unaltered. The decreased NPY expression was fully reversed by the infusion of NGF in the lateral ventricle. The density of cholinergic varicosities was similar in adult and old rats. On the other hand, the density of cholinergic varicosities is significantly higher in old rats treated with NGF than in adult and old rats. Our results indicate a dissimilar resistance of different populations of BLA interneurons to aging. Furthermore, the present data also show that the BLA cholinergic innervation is particularly resistant to aging effects. Finally, our results also show that the reduced NPY expression in the BLA of aged rats can be related to changes in the NGF neurotrophic support.

Functional anatomy of the orbit in strabismus surgery: Connective tissues, pulleys, and the modern surgical implications of the "arc of contact" paradigm.

Oculomotricity is a multidimensional domain characterised by a delicate interplay of anatomical structures and physiological processes. This manuscript meticulously dissects the nuances of this interplay, bringing to the fore the integral role of the extraocular muscles (EOMs) and their intricate relationship with the myriad orbital connective tissues as it harmoniously orchestrates binocular movements, ensuring synchronised and fluid visual tracking. Historically, the peripheral oculomotor apparatus was conceptualised as a rudimentary system predominantly driven by neural directives. While widely accepted, this perspective offered a limited view of the complexities inherent in ocular movement mechanics. The twentieth century heralded a paradigm shift in this understanding. With advances in anatomical research and imaging techniques, a much clearer picture of the gross anatomy of the EOMs emerged. This clarity challenged traditional viewpoints, suggesting that the inherent biomechanical properties of the EOMs, coupled with their associated tissue pulleys, play a pivotal role in dictating eye movement dynamics. Central to this revised understanding is the "arc of contact" paradigm. This concept delves deep into the mechanics of eye rotation, elucidating the significance of the point of contact between the EOMs and the eyeball. The arc of contact is not just a static anatomical feature; its length and orientation play a crucial role in determining the effective torque generated by a muscle, thereby influencing the amplitude and direction of eye rotation. The dynamic nature of this arc, influenced by the position and tension of the muscle pulleys, offers a more comprehensive model for understanding ocular kinematics. Previously overlooked in traditional models, muscle pulleys have now emerged as central players in the biomechanics of eye movement. These anatomical structures, formed by dense connective tissues, guide the paths of the EOMs, ensuring that their pulling angles remain optimal across a range of gaze directions. The non-linear paths resulting from these pulleys provide a more dynamic and intricate understanding of eye movement, challenging two-dimensional, linear models of orbital anatomy. The implications of these revelations extend beyond mere theoretical knowledge. The insights garnered from this research promise transformative potential in the realm of strabismus surgery. Recognising the pivotal role of muscle pulleys and the "arc of contact" paradigm allows for more precise surgical interventions, ensuring better post-operative outcomes and minimising the risk of complications. Surgical procedures that previously relied on basic mechanical principles now stand to benefit from a more nuanced understanding of the underlying anatomical and physiological dynamics. In conclusion, this manuscript serves as a testament to the ever-evolving nature of scientific knowledge. Challenging established norms and introducing fresh perspectives pave the way for more effective and informed clinical interventions in strabismus surgery.

An anatomical approach to the tarsal tunnel syndrome: what can ankle's medial side anatomy reveal to us?

BACKGROUND: The heel is a complex anatomical region and is very often the source of pain complaints. The medial heel contains a number of structures, capable of compressing the main nerves of the region and knowing its anatomical topography is mandatory. The purpose of this work is to evaluate if tibial nerve (TN) and its main branches relate to the main anatomical landmarks of the ankle's medial side and if so, do they have a regular path after emerging from TN. METHODS: The distal part of the legs, ankles and feet of 12 Thiel embalmed cadavers were dissected. The pattern of the branches of the TN was registered and the measurements were performed according to the Dellon-McKinnon malleolar-calcaneal line (DML) and the Heimkes Triangle (HT). RESULTS: The TN divided proximal to DML in 87.5%, on top of the DML in 12,5% and distal in none of the feet. The Baxter's nerve (BN) originated proximally in 50%, on top of the DML in 12,5% and distally in 37.5% of the cases. There was a strong and significant correlation between the length of DML and the distance from the center of the medial malleolus (MM) to the lateral plantar nerve (LPN), medial plantar (MPN) nerve, BN and Medial Calcaneal Nerve (MCN) (ρ: 0.910, 0.866, 0.970 and 0.762 respectively, p <  0.001). CONCLUSIONS: In our sample the TN divides distal to DML in none of the cases. We also report a strong association between ankle size and the distribution of the MPN, LPN, BN and MCN. We hypothesize that location of these branches on the medial side of the ankle could be more predictable if we take into consideration the distance between the MM and the medial process of the calcaneal tuberosity.

Superior Gluteal Nerve Anatomy and Its Injuries: Aiming for a More Secure Surgical Approach of the Pelvic Region.

Because most of the recognized causes of superior gluteal nerve (SGN) injury are iatrogenic, detailed knowledge of the anatomy of the SGN is crucial to prevent its injury associated with surgical procedures. This study aims to describe the precise location of SGN or its branches at the greater sciatic foramen, measure the distances of these neural structures to palpable bony landmarks, and evaluate the possible correlation between these parameters and pelvis size. Twenty human cadaveric hemipelvises were studied. After dissection to expose the SGN or its branches at the greater sciatic foramen, the distances from these neural structures to the greater trochanter (GT), to the anterior superior iliac spine (ASIS), to the posterior superior iliac spine (PSIS), to the ischial tuberosity (IT), and to the greater sciatic notch apex were measured. We found that at the greater sciatic foramen, the SGN emerges as a common trunk in 75% of hemipelvises, and already divided in its superior and inferior branches in 25% of hemipelvises. When the SGN exits the pelvis as a common trunk, it does so, in most cases, in contact with the bone at the apex of the greater sciatic notch or superior to the level of the apex. The median distance from the SGN at the greater sciatic notch to the PSIS, ASIS, GT and IT is 7.6 cm, 10.9 cm, 7.5 cm and 10.8 cm, respectively. We found a positive correlation between some of the analyzed parameters and the size of the pelvis. The anatomical data of this study may serve as pivotal guides during orthopedic pelvic surgery, contributing to minimize SNG iatrogenic lesions with significant implications in the patient's quality of life.

Repurposed Edaravone, Metformin, and Perampanel as a Potential Treatment for Hypoxia-Ischemia Encephalopathy: An In Vitro Study.

Hypoxia-ischemia encephalopathy results from the interruption of oxygen delivery and blood flow to the brain. In the developing brain, it can lead to a brain injury, which is associated with high mortality rates and comorbidities. The hippocampus is one of the brain regions that may be affected by hypoxia-ischemia with consequences on cognition. Unfortunately, clinically approved therapeutics are still scarce and limited. Therefore, in this study, we aimed to test three repurposed drugs with good pharmacological properties to evaluate if they can revert, or at least attenuate, the deleterious effects of hypoxia-ischemia in an in vitro model. Edaravone, perampanel, and metformin are used for the treatment of stroke and amyotrophic lateral sclerosis, some forms of epileptic status, and diabetes type 2, respectively. Through cell viability assays, morphology analysis, and detection of reactive oxygen species (ROS) production, in two different cell lines (HT-22 and SH-SY5Y), we found that edaravone and low concentrations of perampanel are able to attenuate cell damage induced by hypoxia and oxygen-glucose deprivation. Metformin did not attenuate hypoxic-induced events, at least in the initial phase. Among these repurposed drugs, edaravone emerged as the most efficient in the attenuation of events induced by hypoxia-ischemia, and the safest, since it did not exhibit significant cytotoxicity, even in high concentrations, and induced a decrease in ROS. Our results also reinforce the view that ROS and overexcitation play an important role in the pathophysiology of hypoxia-ischemia brain injury.

Increased choroidal thickness is not a disease progression marker in keratoconus.

The recent findings of increased Choroidal Thickness (CT) in Keratoconus (KC) patients raised the question of whether CT could be an indicator of progressive KC. To test this hypothesis, we evaluated and compared the choroidal profile in progressive and non-progressive KC. We ran a cross-sectional observational study in 76 patients diagnosed with KC, age 14-30, to assess KC progression. Progression was defined as when at least two of the studied variables confirmed progression (Kmax, Km, PachyMin, D-Index, Astig, K2, 3 mm PCR). Included patients performed a Spectralis Optical Coherence Tomography (OCT) with enhanced depth image (EDI) technology to evaluate choroidal profile. Choroidal measurements were taken subfoveally and at 500 µm intervals from the fovea, in 7 different locations, and compared between groups. Multivariate linear regression analyses were also performed to assess the influence of CT in KC progression. Thirty-six eyes (47.4%) were classified as KC progressors. The mean subfoveal CT observed in the total sample was 382.0 (± 97.0) µm. The comparison between groups (progressive and non-progressive KC) showed no differences in the locations evaluated (mean subfoveal CT difference between groups was 2.4 µm, p = 0.915). In the multivariate analysis CT seems not be influenced by KC progression (B = 6.72 µm, 95% CI - 40.09 to 53.53, p = 0.775). Assessment of choroidal profile does not appear to be a useful tool to differentiate progressive and non-progressive KC. Further research is needed in order to better understand the role of choroid in KC.

Increased Choroidal Thickness in Keratoconus Patients: Perspectives in the Disease Pathophysiology.

PURPOSE: To analyze and compare choroidal thickness between keratoconus (KC) patients and age-matched non-KC subjects. METHODS: A cross-sectional, case-control study. One hundred and thirty-four keratoconic eyes and 78 control eyes, from individuals aged from 12 to 30 years old, were studied. Patients with KC followed in Corneal Department of Centro Hospitalar São João, Porto, Portugal, were identified and consecutively included between December 2017 and February 2018. A spectral-domain optical coherence tomography (OCT) using depth enhanced imaging was performed, and choroidal thickness in the center of the fovea and at 500 µm intervals along a horizontal section was measured and compared. RESULTS: The statistical analysis showed that keratoconic eyes present a thicker choroid in every measured location (p < 0.05). Mean subfoveal choroidal thickness (SFCT) values obtained were 375.86 ± 89.29 and 322.91 ± 85.14 in keratoconus and control groups, respectively (p < 0.001). In a multivariate analysis, SFCT was significantly associated with spherical equivalent (p=0.004) and the presence of keratoconus (p < 0.001), but not with age (p=0.167), gender (p=0.579), or best-corrected visual acuity (p=0.178). In a "fixed model," keratoconus patients were found to have a 67.55 µm (95% CI 36.61-98.49) thicker subfoveal choroid compared to controls. CONCLUSION: Keratoconus patients seem to have a thicker choroid than healthy individuals. The exact pathophysiological mechanism resulting in a thicker choroid in KC patients is not known, but it could possibly be associated with inflammatory choroidal mechanisms.

Performance equivalency between computer-based and traditional pen-and-paper assessment: A case study in clinical anatomy.

The time, material, and staff-consuming nature of anatomy's traditional pen-and-paper assessment system, the increase in the number of students enrolling in medical schools and the ever-escalating workload of academic staff have made the use of computer-based assessment (CBA) an attractive proposition. To understand the impact of such shift in the assessment method, an experimental study evaluating its effect on students' performance was designed. Additionally, students' opinions toward CBA were gathered. Second-year medical students attending a Clinical Anatomy course were randomized by clusters in two groups. The pen-and-paper group attended two sessions, each consisting of a traditional sectional anatomy steeplechase followed by a theoretical examination, while the computer group was involved in two similar sessions conducted in a computerized environment. At the end of each of the computer sessions, students in this group filled an anonymous questionnaire. In the first session, pen-and-paper group students scored significantly better than computer-group students in both the steeplechase (mean ± standard deviation: 66.00 ± 14.15% vs. 43.50 ± 19.10%; P < 0.001) and the theoretical examination (52.50 ± 12.70% vs. 39.00 ± 21.10%; P < 0.001). In the second session, no statistically significant differences were found for both the steeplechase (59.50 ± 17.30% vs. 54.50 ± 17.00%; P = 0.085) and the theoretical examination (57.50 ± 13.70% vs. 54.00 ± 14.30%; P = 0.161). Besides, an intersession improvement in students' perceptions toward CBA was registered. These results suggest that, after a familiarization period, CBA might be a performance equivalent and student accepted alternative to clinical anatomy pen-and-paper theoretical and practical examinations. Anat Sci Educ 11: 124-136. © 2017 American Association of Anatomists.

Rethinking Anatomy: How to Overcome Challenges of Medical Education's Evolution.

INTRODUCTION: Due to scientific and technological development, Medical Education has been readjusting its focus and strategies. Medical curriculum has been adopting a vertical integration model, in which basic and clinical sciences coexist during medical instruction. This context favours the introduction of new complementary technology-based pedagogical approaches. Thus, even traditional core sciences of medical curriculum, like Anatomy, are refocusing their teaching/learning paradigm. MATERIAL AND METHODS: We performed a bibliographic review aiming to reflect on Medical Education's current pedagogical trend, by analysing the advantages of the introduction and diversification of pedagogical approaches in Anatomy Education. RESULTS: Anatomy Education's status quo is characterized by: less available teaching time, increasing demands from radiology and endoscopy imaging and other invasive and non-invasive medical techniques, increasing number of medical students and other logistical restrains exposed by the current Medical Education scenario. The traditional learning approach, mainly based on cadaveric dissection, is drifting to complementary newer technologies - such as 3D models or 2D/3D digital imaging - to examine the anatomy of the human body. Also, knowledge transfer is taking different channels, as learning management systems, social networks and computer-assisted learning and assessment are assuming relevant roles. DISCUSSION: The future holds promising approaches for education models. The development of Artificial Intelligence, Virtual Reality and Learning Analytics could provide analytic tools towards a real-time and personalized learning process. CONCLUSION: A reflection on Anatomy Education, as a comprehensive model, allows us to understand Medical Education's complexity. Therefore, the present Medical Education context favours a blended learning approach, in which multi-modality pedagogical strategies may become the landmark.

Introdução: A Educação Médica, face ao desenvolvimento científico e tecnológico, reajustou o enfoque. Progressivamente, o programa curricular em Medicina tem adotado o modelo vertical. Neste modelo, ciências básicas e clínicas coexistem ao longo da formação médica. Este contexto favorece a introdução de novas abordagens pedagógicas de base tecnológica. De facto, áreas de conhecimento tradicionais, como Anatomia, igualmente refocalizaram o seu paradigma de ensino. Material e Métodos: Nesse sentido, realizamos uma revisão bibliográfica com objetivo de refletir a tendência pedagógica atual da Educação Médica, analisando as vantagens da introdução/diversificação de abordagens pedagógicas em Anatomia. Resultados: O status quo da Anatomia é caracterizado por menor tempo disponível para o ensino, pela expansão da imagiologia radiológica e endoscópica, bem como, de outras técnicas médicas invasivas/não-invasivas, pelo aumento do número de estudantes e por restrições logísticas inerentes ao presente contexto da Educação Médica. A abordagem pedagógica tradicional, alicerçada na disseção cadavérica, vem sendo complementada por novas tecnologias auxiliares (modelos 3D ou imagiologia digital 2D/3D) ao estudo anatómico. Também, a transmissão de conhecimento vem adotando diferentes vias. Assim, os Sistemas Gestores de Aprendizagem, redes sociais ou plataformas de aprendizagem/avaliação virtuais assumem papéis relevantes. Discussão: O futuro reserva metodologias educativas promissoras. O desenvolvimento de Inteligência Artificial, da Realidade Virtual e a aplicação dos princípios de Learning Analytics favorece a disponibilização de ferramentas analíticas ao processo de aprendizagem em tempo-real, personalizando-o. Conclusão: A reflexão sobre a Educação em Anatomia, como modelo compreensivo, permite perceber a complexidade da Educação Médica. Assim, o presente contexto favorece a perspectiva de blended learning, sustentada em estratégias pedagógicas multimodais.

Dendritic right/left asymmetries in the neurons of the human hippocampal formation: a quantitative Golgi study

OBJECTIVE: To search for right/left asymmetries in the dendritic trees of the neuronal populations and in the cell-free layer volumes of the human hipoccampal formation. METHOD: In necropsic material obtained from six male individuals we performed a quantitative Golgi study of the dendritic trees of dentate granules, CA3 and CA1 pyramidal neurons and a volumetric analysis of dentate gyrus molecular layer, strata oriens plus alveus and strata lacunosum-moleculare plus radiatum of CA3 and CA1 fields. RESULTS: We found inter-hemispheric asymmetries in the dendrites trees of all neurons, reaching the significant level in the number of granule cells dendritic segments (higher in the left than in the right hemisphere), dendritic branching density of CA3 pyramidal cells and mean dendritic length of CA1 apical terminal segments (higher in the right than in the opposite side). No volumetric differences were observed. CONCLUSION: This study points to different anatomical patterns of connectivity in the hippocampal formations of both hemispheres which may underlie functional asymmetries.

OBJETIVO: Pesquisar a existência de assimetrias direita/esquerda nas arborizações dendríticas neuronais e nos volumes das camadas não celulares da formação do hipocampo humano. MÉTODO: Efectuamos estudo quantitativo Golgi das arborizações dendríticas dos grânulos da fascia denteada e das células piramidais de CA3 e CA1, e uma análise estereológica dos volumes da camada molecular da fascia denteada, do strata oriens + alveus e do strata lacunosum-moleculare + radiatum de CA3 e de CA1 em material necrópsico colhido em 6 indivíduos do sexo masculino. RESULTADOS: Encontrámos assimetrias inter-hemisféricas nas arborizações dendríticas de todos os neurónios, significativas no número de segmentos dendríticos das células granulares (maior à esquerda do que à direita) na densidade de ramificação dendrítica das pirâmides de CA3 e no comprimento dendrítico médio dos segmentos apicais terminais das pirâmides de CA1 (maiores à direita do que à esquerda). Não encontramos diferenças volumétricas. CONCLUSÃO: Estes resultados alertam para diferentes padrões anatómicos de conectividade nas formações do hipocampo de ambos os hemisférios que podem fundamentar assimetrias funcionais.

Dendritic right/left asymmetries in the neurons of the human hippocampal formation: a quantitative Golgi study.

OBJECTIVE: To search for right/left asymmetries in the dendritic trees of the neuronal populations and in the cell-free layer volumes of the human hipoccampal formation. METHOD: In necropsic material obtained from six male individuals we performed a quantitative Golgi study of the dendritic trees of dentate granules, CA3 and CA1 pyramidal neurons and a volumetric analysis of dentate gyrus molecular layer, strata oriens plus alveus and strata lacunosum-moleculare plus radiatum of CA3 and CA1 fields. RESULTS: We found inter-hemispheric asymmetries in the dendrites trees of all neurons, reaching the significant level in the number of granule cells dendritic segments (higher in the left than in the right hemisphere), dendritic branching density of CA3 pyramidal cells and mean dendritic length of CA1 apical terminal segments (higher in the right than in the opposite side). No volumetric differences were observed. CONCLUSION: This study points to different anatomical patterns of connectivity in the hippocampal formations of both hemispheres which may underlie functional asymmetries.