The effects of age, genotype and diet on hippocampal subfield iron dysregulation and Alzheimer's disease biomarkers in an ApoE mouse model.

Current theories regarding accumulation of Alzheimer's disease-related deposits of abnormal intra- and extracellular proteins include reactions to inflammation and mitochondrial dysfunction. In this study, we explored whether age, genotype and inflammation via diet have a greater effect on dysregulatory protein accumulation in any particular subfield of the hippocampus. We stained for ferritin, ferroportin, hyperphosphorylated tau and ß-amyloid proteins in the hippocampal region of Apolipoprotein E2 (ApoE2), ApoE3 or ApoE4 mice fed a control diet or a hypothesized inflammation-inducing methionine diet and euthanized at 3, 6, 9 or 12 months. We analysed stains based on hippocampal subfield and compared the protein accumulation levels within each group. We found significantly decreased ferritin expression in ApoE4 mice in the CA1 and Hi regions and decreased ferroportin expression in ApoE4 mice in the Hi region. There was also a significant effect on hyperphosphorylated tau protein levels based upon a given mouse genotype and diet interaction. Additionally, there were nonsignificant trends in each hippocampal subfield of increasing ferroportin and hyperphosphorylated tau after 6 months of age and decreasing ß-amyloid and ferritin with age. This study identified that there are changes in iron regulatory molecules based on genotype in the Hi and CA1 regions. Our findings also suggest a diet-genotype interaction, which affects levels of specific Alzheimer's disease biomarkers in the hippocampus. Additionally, we identified a trend toward increased ability to clear ß-amyloid and decreased ability to clear hyperphosphorylated tau with age in all subfields, in addition to evidence of increasing iron load with time.

Rural versus Urban Residence in Adulthood and Incident Cognitive Impairment.

INTRODUCTION: Rural versus urban living is a social determinant of cognitive health. We estimated the association of rural versus urban residence in the USA with incident cognitive impairment (ICI) and assessed effect heterogeneity by sociodemographic, behavioral, and clinical factors. METHODS: The Reasons for Geographic and Racial Differences in Stroke Study (REGARDS) is a population-based prospective observational cohort of 30,239 adults, 57% female, 36% Black, aged 45+ years, sampled from 48 contiguous states in the USA in 2003-2007. We analyzed 20,878 participants who at baseline were cognitively intact with no history of stroke and had ICI assessed on average 9.4 years later. We classified participants' home addresses at baseline as urban (population ≥50,000), large rural (10,000-49,999), or small rural (≤9,999) by Rural-Urban Commuting Area codes. We defined ICI as ≥1.5 SD below the mean on at least 2 of the following tests: word list learning, word list delayed recall, and animal naming. RESULTS: Participants' home addresses were 79.8% urban, 11.7% large rural, and 8.5% small rural. ICI occurred in 1,658 participants (7.9%). Small rural residents had higher odds of ICI than urban residents, adjusted for age, sex, race, region, and education (OR = 1.34 [95% CI: 1.10, 1.64]), and after further adjustment for income, health behaviors, and clinical characteristics (OR = 1.24 [95% CI: 1.02, 1.53]). Former smoking versus never, nondrinking versus light alcohol drinking, no exercise versus ≥4 times/week, CES-D depressive symptom score of 2 versus 0, and fair versus excellent self-rated health had stronger associations with ICI in small rural areas than in urban areas. For example, in urban areas, lack of exercise was not associated with ICI (OR = 0.90 [95% CI: 0.77, 1.06]); however, lack of exercise combined with small rural residence was associated with 1.45 times the odds of ICI compared with ≥4 bouts of exercise/week in urban areas (95% CI: 1.03, 2.03). Overall, large rural residence was not associated with ICI; however, black race, hypertension, and depressive symptoms had somewhat weaker associations with ICI, and heavy alcohol drinking a stronger association with ICI, in large rural areas than in urban areas. CONCLUSION: Small rural residence was associated with ICI among USA adults. Further research to better understand why rural residents are at higher risk for developing ICI and mechanisms to ameliorate that risk will support efforts to advance rural public health.

A novel scale for the evaluation of physician drawn medical illustrations.

Effective communication is a crucial component of patient-centered care and individuals with low health literacy face significant challenges in managing their health, leading to longer hospital stays and worse outcomes. Visual aids, such as medical illustrations and pictograms, can enhance patient understanding and memory retention; however, there is a lack in the medical field of tools for evaluating and improving a physician's ability to draw clinical illustrations for their patient. This article explores an aesthetic scale created in collaboration between Boston University Medical School and the Boston University Fine-Arts department. The scale scores basic design elements that could reasonably be improved in a clinical setting. A pilot study demonstrated interrater reliability between trained artists scoring images of varying concepts and visual quality with a Cronbach's alpha of 0.95. This scale has potential use in medical visual education and clinical evaluation.

Novel forms of prostate cancer chemoresistance to successful androgen deprivation therapy demand new approaches: Rationale for targeting BET proteins.

In patients with prostate cancer, the duration of remission after treatment with androgen deprivation therapies (ADTs) varies dramatically. Clinical experience has demonstrated difficulties in predicting individual risk for progression due to chemoresistance. Drug combinations that inhibit androgen biosynthesis (e.g., abiraterone acetate) and androgen signaling (e.g., enzalutamide or apalutamide) have proven so effective that new forms of ADT resistance are emerging. In particular, prostate cancers with a neuroendocrine transcriptional signature, which demonstrate greater plasticity, and potentially, increased predisposition to metastasize, are becoming more prevalent. Notably, these subtypes had in fact been relatively rare before the widespread success of novel ADT regimens. Therefore, better understanding of these resistance mechanisms and potential alternative treatments are necessary to improve progression-free survival for patients treated with ADT. Targeting the bromodomain and extra-terminal (BET) protein family, specifically BRD4, with newer investigational agents may represent one such option. Several families of chromatin modifiers appear to be involved in ADT resistance and targeting these pathways could also offer novel approaches. However, the limited transcriptional and genomic information on ADT resistance mechanisms, and a serious lack of patient diversity in clinical trials, demand profiling of a much broader clinical and demographic range of patients, before robust conclusions can be drawn and a clear direction established.

A case of abnormally dilated and tortuous arc of Buhler and pancreaticoduodenal arteries in the absence of celiac trunk stenosis.

INTRODUCTION: The Arc of Buhler is a rare vascular variant describing a persistent remnant of the embryologic ventral anastomosis between the celiac trunk (CT) and superior mesenteric artery (SMA), invariably reported in the context of CT stenosis. PURPOSE: To report a case of (1) a large and tortuous pancreaticoduodenal arcade and (2) a large and tortuous Arc of Buhler in the absence of celiac axis stenosis. METHODS: The variant was discovered during routine cadaver dissection. We acquired transverse biopsies of variant vessels and evaluated their wall thickness. RESULTS: The donor's anterior PDA, posterior PDA, and Arc of Buhler had larger diameters, and the common hepatic artery had a smaller diameter than the literature-reported values of a standard human body. The posterior PDA had significantly increased wall thickness compared to the other investigated vessels. CONCLUSIONS: The Arc of Buhler is a rare remnant of the embryologic ventral anastomosis that is estimated to be hemodynamically active in only half of cases. Previous reports have documented hemodynamically active Arcs of Buhler only in cases of CT stenosis. To the best of the authors' knowledge, this is a unique case of a persistent and hemodynamically active Arc of Buhler in the absence of CT stenosis. Clinicians should be aware of this variant as its abnormal position may increase risk of herniation and surgical complications, and its tortuosity may increase risk of clot formation.

Unusual bilateral variation of the flexor digitorum accessorius longus muscle and its relation on tarsal tunnel syndrome.

PURPOSE: During standard anatomical dissection for a medical anatomy course, we encountered an unusual bilateral variant of a unipennate flexor digitorum accessorius longus (FDAL) muscle, a supernumery muscle of the deep posterior leg and medial ankle. METHODS: We documented the muscles course and measured the diameter and length of the FDAL muscle belly, as well as the full length of its tendinous attachments. RESULTS: On both right and left legs, the FDAL originated from the proximal posterior fibula and distal one-third of the flexor hallucis longus muscle. The tendon had a distal attachment on the flexor digitorum longus (FDL) tendon and traveled with the FDL tendon as it inserted on the third distal phalanx. The left FDAL full length was 42.54 cm; the length of the muscle belly was 16.26 cm; and the circumference of the muscle belly was 4.44 cm. The right FDAL full length was 44.20 cm; the length of muscle belly was 12.06; and the circumference (belly) was 4.44 cm. Surrounding musculature and neurovasculature follow standard anatomical courses. CONCLUSION: This anatomical documentation provides opportunities for clinicians to consider mechanical influences of the FDAL on plantar foot function and further consider the accessory ankle muscles that have the potential to cause compressive neuropathies such as tarsal tunnel syndrome.

The components of the adolescent brain and its unique sensitivity to sexually explicit material.

INTRODUCTION: The focus of this brief literature review is to explore whether there is a relationship between the unique anatomical and physiological paradigms of the adolescent brain and an increased sensitivity to sexually explicit material. METHODS: The EBSCO Research Data bases were searched using the following key terms: adolescence, adolescent brain development, neuroplasticity, sexually explicit material, sexualization, and pornography. RESULTS: The literature highlighted several components of the adolescent brain that are different than the mature brain. These include: an immature prefrontal cortex and over-responsive limbic and striatal circuits, heightened period for neuroplasticity, overactive dopamine system, a pronounced HPA axis, augmented levels of testosterone, and the unique impact of steroid hormones. The physiological response to sexually explicit material is delineated. The overlap of key areas associated with the unique adolescent brain development and sexually explicit material is noteworthy. A working model summary that compares the response of the adult and adolescent brain to the same sexually explicit stimulus is outlined. CONCLUSIONS: The literature suggests that the adolescent brain may indeed be more sensitive to sexually explicit material, but due to a lack of empirical studies this question cannot be answered definitively. Suggestions for future research are given to further advance the work in this applicable field of today.

Weave pattern of accessory heads to the anterior digastric muscle.

During routine anatomical dissection, we discovered bilateral superficial and deep heads of the anterior belly of the digastric muscle with concomitant accessory heads arranged in a weave pattern in the submental triangle. In addition, the left stylohyoid muscle coursed deep into the intermediate tendon of the digastric muscle bellies.

A Near-Peer Interprofessional Educational Fellowship Program for Training Pre-Clinical Medical Students in the Best Practices of Teaching and Learning.

Medical school often has opportunities for students to engage in peer or near-peer teaching, however structured teacher training is rarely conducted. We present an Educational Fellowship for rising M2 students as teaching assistants for first year Physician Assistant students. In this near-peer interprofessional teaching model, the M2 students learn pedagogical theory and best practices for teaching and learning. The curriculum and experience may be used by any healthcare profession. Since many healthcare professions have classes during the summer, we present our program as a conceptual model for other institutions.

Evidence for the functional compartmentalization of the temporalis muscle: a 3-dimensional study of innervation.

PURPOSE: The temporalis muscle is commonly used for functional transfer. It is architecturally complex, but few studies have examined its intramuscular innervation and none has used 3-dimensional modeling techniques. Understanding neuromuscular compartmentalization may allow the design of local muscle transfers to minimize donor-site morbidity. The purpose of the present study was to document the intramuscular innervation patterns throughout the volume of the temporalis muscle and define functional units within the muscle. MATERIALS AND METHODS: In 10 formalin-embalmed cadaveric specimens, the foramen ovale was exposed and the branches of the mandibular nerve were identified. Each branch was digitized in short segments extramuscularly and intramuscularly. Three-dimensional models were reconstructed from the digitized data using Maya software, and the innervation patterns were documented. RESULTS: The temporalis muscle was found to have superior and inferior parts that were further grouped by innervation into regions, with each receiving its innervation from 1 primary nerve. The nerves originated directly from the mandibular nerve, except in 3 specimens, where the posterior deep temporal nerve arose from the masseteric nerve. CONCLUSION: These results provide a detailed mapping of innervation patterns and suggest there are at least 5 functional compartments. Each of these has the capacity for selective activation, 3 of which have clinical value. These findings may allow for decreased donor-site morbidity and more functionally sophisticated designs in clinical practice.

The Prevention of Inflammation and the Maintenance of Iron and Hepcidin Homeostasis in the Gut, Liver, and Brain Pathologies.

The human gut microbiome consists of a variety of microorganisms that inhabit the intestinal tract. This flora has recently been shown to play an important role in human disease. The crosstalk between the gut and brain axis has been investigated through hepcidin, derived from both hepatocytes and dendritic cells. Hepcidin could potentially play an anti-inflammatory role in the process of gut dysbiosis through a means of either a localized approach of nutritional immunity, or a systemic approach. Like hepcidin, mBDNF and IL-6 are part of the gut-brain axis: gut microbiota affects their levels of expression, and this relationship is thought to play a role in cognitive function and decline, which could ultimately lead to a number of neurodegenerative diseases such as Alzheimer's disease. This review will focus on the interplay between gut dysbiosis and the crosstalk between the gut, liver, and brain and how this is mediated by hepcidin through different mechanisms including the vagus nerve and several different biomolecules. This overview will also focus on the gut microbiota-induced dysbiotic state on a systemic level, and how gut dysbiosis can contribute to beginnings and the progression of Alzheimer's disease and neuroinflammation.

Comparing the emotional experiences of students in similar dissection- and prosection-based medical gross anatomy courses: A mixed-methods study.

The anatomy laboratory can incite strong emotional reactions in students, which can in turn facilitate growth in empathy, care for vulnerable others, and professionalism. Despite this, little is known about the relative emotional impacts of different laboratory modalities. The response to the COVID-19 pandemic created an opportunity to compare the emotional experiences of students in similar courses in which one group of students dissected donors and the other group learned from prosected donors. The courses were otherwise the same in content, length, instructional design, and assessment. Students in the dissection-based (Fall 2019) and prosection-based (Fall 2020) courses completed a previously validated survey that used quantitative and qualitative questions to assess their feelings about the donors and the anatomy laboratory experience. Students in both cohorts reported overall appreciation for having had the experience. Negative themes experienced by both groups included feeling anxiety, worries about depersonalizing donors, and physical discomfort in the laboratory. Students in the dissection course reported stronger connections with the donors and the donors' families but also more frequently felt negative feelings such as disgust, anxiety, and feeling alone. Students in the prosection course reported more consistently positive responses but worried about not using the donors to the fullest extent possible. Regardless of pedagogical design, students have complex emotional experiences in the anatomy laboratory and our results indicate that these feelings may be more intense in the context of dissection. Anatomists should foster educational settings that enable students to learn to process complex or challenging emotions.

A Call to Action for Improving LGBTQIA2S+ Inclusive Policies and Practices in Educating Science and Medical Professionals.

Based on Nature's novel sex and gender guidelines, we share a call to action to enact policy changes in medical and scientific education. We conducted a literature search of current policies and practices affecting sex and gender minorities. Our work indicated a scarcity of guidelines and curricula dedicated to standardizing LGBTQIA2S+ topics. Educational policies must be enacted to ensure that sex and gender guidelines are implemented across all institutions as it impacts the future of healthcare and science. It is essential that sex and gender considerations be mandated topics in both medical and scientific education.

A heat map of superior cervical ganglion location relative to the common carotid artery bifurcation.

BACKGROUND: Determining the superior cervical ganglion's precise anatomical location for local anesthetic block, when stellate block is not feasible or is contraindicated, is difficult. METHODS: We dissected the superior cervical ganglion in 60 embalmed cadaveric specimens. Multiple regressions determined whether subject characteristics predicted the distance between the superior cervical ganglion and common carotid artery bifurcation and the superior cervical ganglion dimensional width and area. Based on these regressions, we mapped the ganglion and common carotid artery bifurcation using a pseudocolor statistical heat map. RESULTS: The statistical model significantly predicted the superior cervical ganglion-common carotid artery bifurcation distance (P = 0.01), and the superior cervical ganglion dimensional width (P = 0.02). CONCLUSION: This study determined that the common carotid artery bifurcation is a good landmark for localizing the superior cervical ganglion for anesthetic block.

Revision of hip flexor anatomy and function in modern humans, and implications for the evolution of hominin bipedalism.

Hip flexor musculature was instrumental in the evolution of hominin bipedal gait and in endurance running for hunting in the genus Homo. The iliacus and psoas major muscles were historically considered to have separate tendons with different insertions on the lesser trochanter. However, in the early 20th century, it became "common knowledge" that the two muscles insert together on the lesser trochanter as the "iliopsoas" tendon. We revisited the findings of early anatomists and tested the more recent paradigm of a common "iliopsoas" tendon based on dissections of hips and their associated musculature (n = 17). We rediscovered that the tendon of the psoas muscle inserts only into a crest running from the superior to anterior aspect of the lesser trochanter, separate from the iliacus. The iliacus inserts fleshly into the anterior portion of the lesser trochanter and into an inferior crest extending from it. We developed 3D multibody dynamics biomechanical models for: (a) the conjoint "iliopsoas" tendon hypothesis and (b) the separate insertion hypothesis. We show that the conjoint model underestimates the iliacus' capacity to generate hip flexion relative to the separate insertion model. Further work reevaluating the primate lower limb (including human) through dissection, needs to be performed to develop those datasets for reconstructing anatomy in fossil hominins using the extant phylogenetic bracket approach, which is frequently used for tetrapods clades outside of paleoanthropology.

Effectiveness of Pedagogical Tools for Teaching Medical Gross Anatomy During the COVID-19 Pandemic.

Medical institutions have been forced to modify gross anatomy pedagogy to comply with the health restrictions imposed by the novel coronavirus (COVID-19). Boston University School of Medicine (BUSM) is one such institution that temporarily restructured its course. We replaced cadaveric dissection activities with prosections and placed a greater emphasis on a flipped classroom model. This study investigates the effectiveness of new course materials developed to aid these curriculum changes. Course materials were developed for three purposes: (1) preparation before laboratory sessions (orientation videos and Complete Anatomy (3D4Medical, Elsevier) screens); (2) guidance during laboratory sessions (laboratory guides); and (3) review after laboratory sessions (Zoom recitation sessions). We performed a grounded theory thematic analysis of students' responses (80/160, 50% response) to qualitative survey questions and to focus group questions (16 students who self-selected between 4 different sessions). Data from both the survey and focus groups demonstrated that the vast majority of students agreed that the materials helped them navigate through learning gross anatomy. However, laboratory guides were used mostly for post-lab review as opposed to the intended direction during laboratory sessions. Students within all focus groups overwhelmingly touted the value of Zoom recitation sessions, with many stating that they were imperative to course success. When comparing performance data between 2019 (pre-COVID) and 2020 students, we found that the students who took the anatomy course during the onset of COVID had a slightly higher overall average score in all three modules of the course than compared to the 2019 students. We propose that the utilization of course materials that students perceived as time saving and pertinent to their exam performance, when combined with cadaveric prosection, emphasized the benefits of flipped-classroom learning to help students learn gross anatomy effectively and efficiently during the pandemic and beyond. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-022-01524-x.

Integration of Clinical Skills into Preclinical Medical Curriculum Via a Low-Cost Femoral Triangle Ultrasound Model.

We created a low-cost femoral triangle model that allows first year medical students to practice ultrasound-guided procedures while reinforcing their knowledge of femoral triangle anatomy. Use of this model also increased opportunities for informal near-peer teaching and student involvement in the creation of instructional materials.

The anatomy of nasopharyngeal carcinoma spread through the pharyngobasilar fascia to the trigeminal mandibular nerve on 1.5 T MRI.

PURPOSE: To analyze, from 1.5 Tesla (T) MRI clinical cases, anatomical accessibility of nasopharyngeal tumors through the pharyngobasilar fascia (PBF) to the mandibular nerve for potential perineural spread. METHODS: A 6-year retrospective review of 1.5 T MR images were rated for tumor involvement of fascial planes and perineural spread in 15 consecutive patients (10 female, 5 male; mean age 45.8 years, range 19-86) with histopathologically proven tumors of the nasopharynx and referrals for radiotherapy due to intracranial extension. RESULTS: Nasopharyngeal tumors were best appreciated on T1 fat-saturated, post-gadolinium MRI. Tumors extended through the sinus of Morgagni in all cases. This sinus is a defect in the PBF through which the Eustachian tube and levator veli palatini muscle gain access to the nasopharynx. In six patients, the PBF and tensor veli palatini fascia were breached anteriorly with tumor infiltration of the tensor veli palatini and medial pterygoid muscles. In 13 cases, tumor breached the posterolateral PBF with extension into the poststyloid parapharyngeal space. In three subjects, 3 T images were also acquired and exhibited superior delineation of the anatomy and perineural tumor spread. CONCLUSIONS: At 1.5 T, images showed nasopharyngeal tumors extending through the PBF into the masticator and parapharyngeal spaces, with access to the mandibular nerve and potential for perineural spread. At 3 T, soft tissue resolution appeared superior to 1.5 T. This may reflect not only the increased field strength, but an improved technique and matrix, and future studies are necessary to confirm this observation. Awareness of this anatomy for radiation and surgical planning is essential and may improve the ability for obtaining negative margins, and increasing overall survival.

The human temporalis muscle: superficial, deep, and zygomatic parts comprise one structural unit.

The structure of the temporalis muscle was examined in detail from cadaveric specimens (32 specimens from 16 subjects: 5 males, average age 80.6 years; 11 females, average age 88.6 years) and Computerized Tomography (CT) and T1-weighted Magnetic Resonance (MR) images from normal clinical patients (10 females: average age 45.0 years). Three parts of the muscle were clearly delineated in all cadaveric specimens: (1) the classically recognized superficial part, (2) a zygomatic part, and (3) a complex deep part. In one female specimen, the superficial temporalis demonstrated extensive insertions into the zygomatic process and temporomandibular joint. The zygomatic temporalis originates from the zygomatic arch to insert into the superficial part of the temporalis as it inserts into the lateral surface of the coronoid process. In all specimens, the deep temporalis contained muscle bundles that originated from various crests along the anterior surface of the temporal fossa and inserted into the internal aspect of the coronoid process and retromolar triangle, interdigitating with the buccinator, mylohyoid, and superior constrictor muscles. The confluence of muscle fibers into the buccinator muscle was confirmed in all CT/MRI images. The deep and zygomatic parts described were regarded as accessory muscle bellies previously, but are demonstrably part of the temporalis muscle as a whole.