Cerebral cavernous malformation proteins, CCM1, CCM2 and CCM3, are decreased in metastatic lesions in a murine breast carcinoma model.

Three genes are associated with cerebral cavernous malformations (CCMs): CCM1, CCM2 and CCM3. These genes participate in microvascular angiogenesis, cell-to-cell junctions, migration and apoptosis. We evaluated the expression in vivo of CCM genes in primary tumors and metastastases in a murine model of metastatic breast carcinoma. We used cell lines obtained from metastasis of 4T1, 4TLM and 4THM breast cancer to liver and heart. These cells were injected into the mammary ridge of Balb/C female mice. After 27 days, the primary tumors, liver and lung were removed and CCM proteins were assessed using immunohistochemistry and western blot analysis. CCM proteins were expressed in primary tumor tissues of all tumor-injected animals; however, no CCM protein was expressed in metastatic tumor cells that migrated into other tissues. CCM proteins still were observed in the lung and liver tissue cells. Our findings suggest that CCM proteins are present during primary tumor formation, but when these cells develop metastatic potential, they lose CCM protein expression. CCM protein expression was lost or reduced in metastatic tissues compared to the primary tumor, which indicates that CCM proteins might participate in tumorigenesis and metastasis.

A comparison of pre- and post-clinical education learning preferences among medical students who elected to dissect compared to those who did not during the COVID-19 pandemic.

Anatomy instructional methods varied widely during the COVID-19 pandemic and programs are assessing innovations for retention. Learning preferences were assessed among medical students dichotomized as elective dissectors (ED) or non-dissectors (ND) during the COVID-19 partial re-opening in 2020 (preclinical) and again in 2022 after clinical exposure (post-clinical) to assess the viability of elective dissection post-pandemic. A mixed-method approach was used for the assessment of test scores, learning preference surveys, learning activities rankings, and thematic analyses. No significant differences occurred in anatomy examination scores. Dissection was considered useful by both preclinical groups but significantly more so by ED, while the presence of an instructor was significantly preferred by ED although a majority of ND agreed. Elective dissection was significantly preferred by ND but also by a large minority of ED students. Pre- and post-clinical ND believed that elective dissection offered more academic flexibility, did not hinder clinical learning, and did not negatively impact medical education. The corresponding ED stated that confidence improved, clinical experiences were enhanced, and dissection was irreplaceable. Preclinical ND preferred self-learning, while ED students preferred online learning, but these differences largely disappeared post-clinically. Learning activity rankings were not significantly different among all groups (ND, ED, preclinical, and post-clinical). A hybrid laboratory with a virtual learning environment ranked highest across groups and preferences increased over time suggesting that students benefited from this instructional method during clinical exposure. The absence of laboratory experience ranked lowest, and preference decreased over time suggesting that anatomy dissection is valued.

Ethical analysis of cadaver supply and usage processes for research within the scope of the Helsinki Declaration.

Recent technological developments have considerably transformed the supply, storage, and transportation processes of cadavers, creating new and previously unforeseen ethical challenges regarding cadaver usage. In this study, we analyzed two aspects of the cadaver processing system-cadaver supply and its use in research. Thereafter, we highlighted the major ethical concerns underlying these stages and correlated our search results with the ethical principles outlined in the Declaration of Helsinki (DoH), or Helsinki Declaration. To ensure the reliability and continuity of medical progress, human-especially cadaver-research depends on the ethical priorities as outlined in the DoH: respect for autonomy, privacy/confidentiality, risks/burdens/benefits, and the protection of vulnerable groups. According to our ethics analysis, which also corresponds with the ethics guidelines of the Consensus Panel on Research with the Recently Dead, the most ignored values were respect for autonomy and privacy/confidentiality issues. Based on these ethical concerns, we provide recommendations to address these challenges in anatomy research.

Extended reality veterinary medicine case studies for diagnostic veterinary imaging instruction: Assessing student perceptions and examination performance.

Educational technologies in veterinary medicine aim to train veterinarians faster and improve clinical outcomes. COVID-19 pandemic, shifted face-to-face teaching to online, thus, the need to provide effective education remotely was exacerbated. Among recent technology advances for veterinary medical education, extended reality (XR) is a promising teaching tool. This study aimed to develop a case resolution approach for radiographic anatomy studies using XR technology and assess students' achievement of differential diagnostic skills. Learning objectives based on Bloom's taxonomy keywords were used to develop four clinical cases (3 dogs/1 cat) of spinal injuries utilizing CT scans and XR models and presented to 22 third-year veterinary medicine students. Quantitative assessment (ASMT) of 7 questions probing 'memorization', 'understanding and application', 'analysis' and 'evaluation' was given before and after contact with XR technology as well as qualitative feedback via a survey. Mean ASMT scores increased during case resolution (pre 51.6% (±37%)/post 60.1% (± 34%); p < 0.01), but without significant difference between cases (Kruskal-Wallis H = 2.18, NS). Learning objectives were examined for six questions (Q1-Q6) across cases (C1-4): Memorization improved sequentially (Q1, 2 8/8), while Understanding and Application (Q3,4) showed the greatest improvement (26.7%-76.9%). Evaluation and Analysis (Q5,6) was somewhat mixed, improving (5/8), no change (3/8) and declining (1/8).Positive student perceptions suggest that case studies' online delivery was well received stimulating learning in diagnostic imaging and anatomy while developing visual-spatial skills that aid understanding cross-sectional images. Therefore, XR technology could be a useful approach to complement radiological instruction in veterinary medicine.

Effects of Melatonin and Doxorubicin on Primary Tumor And Metastasis in Breast Cancer Model.

BACKGROUND: Melatonin exerts oncostatic effects on breast cancer via immunomodulation and antioxidation. Doxorubicin is an effective chemotherapeutic agent, but parallel studies also provide ample evidence of an off-target effect of Doxorubicin in breast cancer patients. OBJECTIVE: Combinatorial use of doxorubicin and melatonin has not been comprehensively analyzed in breast cancer models. We hypothesized that the anti-oxidative, anti-proliferative and anti-inflammatory effects of melatonin could ameliorate the off-target effects of doxorubicin in breast cancer patients and enhance the anti-tumoral effects of doxorubicin. The goal of the study is to test this hypothesis in cancer cell lines and xenografted mice. METHODS: The effects of Melatonin and doxorubicin on the cell viability were evaluated in 4T1-Brain Metastatic Tumor (4TBM). Furthermore, the effects of melatonin and doxorubicin on the primary tumors and systemic metastasis were evaluated in the xenografted mice. Lung and liver tissues were removed and metastasis analyses were performed. The levels of p65, phospho-STAT3, CD11b+, GR1+, Ki67, and cleaved caspase-3 proteins were determined with immunohistochemistry and western blot analysis. We examined the effects of melatonin and Melatonin+Doxorubicin combination therapy on 4TBM cells. RESULTS: Our results showed that doxorubicin inhibited the proliferation of metastatic breast cancer cells while melatonin did not affect cells. Tumor growth and metastasis were markedly suppressed in melatonin alone and in combination with doxorubicin. The expression of CD11b+ and GR1+ proteins, which are indicators of myeloid-derived suppressor cells (MDSCs), were noted to be reduced in both primary tumor and metastatic tissues in melatonin and doxorubicin groups. CONCLUSION: The combination of melatonin with doxorubicin reduced primary tumor growth and distant metastasis. Based on these results, melatonin is a promising candidate for combinatory use with conventional chemotherapeutics for breast cancer treatment.

Role of melatonin in TLR4-mediated inflammatory pathway in the MTPT-induced mouse model.

Neuroinflammation has an essential role in various neurodegenerative diseases including Parkinson's disease (PD). Microglial activation as a result of neuroinflammation exacerbates the pathological consequences of the disease. The toxic effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes alpha-synuclein (α-synuclein) accumulation, which leads to dopaminergic neuron death in the MPTP-induced mouse model. Toll-like receptor 4 (TLR4) stimulates release of cytokine through NF-kB by activating glial cells, thus resulting in the death of dopaminergic neurons. Melatonin has the ability to cross the blood-brain barrier and protect neurons through anti-inflammatory properties. We hypothesized that melatonin could suppress TLR4-mediated neuroinflammation, decrease cytokine release due to the inflammatory response, and reduce dopaminergic neuron loss in the MPTP-induced mouse model. In the MPTP-induced mouse model, we aimed to assess the neuroinflammatory responses caused by TLR4 activation as well as the effect of melatonin on these responses. Three-month-old male C57BL/6 mice were randomly divided into five groups; Control (Group-C), Sham (Group-S), Melatonin-treated (Group-M), MPTP-injected (Group-P), and MPTP + melatonin-injected (Group-P + M). MPTP toxin (20 mg/kg) was dissolved in saline and intraperitoneally (i.p.) injected to mice for two days with 12 h intervals. The total dose per mouse was 80 mg/kg. Melatonin was administered (20 mg/kg) intraperitoneally to Group-M and Group-P + M twice a day for five days. Eight days after starting the experiment, the motor activities of mice were evaluated by locomotor activity tests. The effects on dopamine neurons in the SNPc was determined by tyrosine hydroxylase (TH) immunohistochemistry. TLR4, α-synuclein, and p65 expression was evaluated by immunostaining as well. The amount of TNF-alpha in the total brain was evaluated by western blot analysis. In our results seen that locomotor activity was lower in Group-P compared to Group-C. However, melatonin administration was improved this impairment. MPTPcaused decrease in TH immuno-expression in dopaminergic neurons in Group-P. TLR4 (p < 0.001), α-synuclein (p < 0.001), and p65 (p < 0.01) immuno-expressions were also decreased in Group-P+M compared to Group-P (using MPTP). TNF-α expression was lower in Group-C, Group-S, Group-M, and Group-P+M, when compared to Group-P (p < 0.0001) due to the absence of inflammatory response. In conclusion, our study revealed that melatonin administration reduced α-synuclein aggregation and TLR4-mediated inflammatory response in the MPTP-induced mouse model.

Case-based radiological anatomy instruction using cadaveric MRI imaging and delivered with extended reality web technology.

PURPOSE: Extended reality (XR) technology enhances learning in medical education. The purpose of this study was to develop and apply a case-based approach for teaching radiological anatomy utilizing XR technology for improved student exploration and engagement. METHODS: The workflow consisted of MRI scanning cadavers followed by radiological, pathological, and anatomical assessment, and finally case presentation based on XR visualizations and student interaction. Case information (Subject, History, and Physical Exam) was presented to student groups who generated and recorded hypotheses using Google Forms. RESULTS: Use of all components of the system was voluntary and a total of 74 students responded to the survey request (response rate = 95%). Assessment of the experience was conducted through a qualitative survey comprising four Likert scale questions (1-5, 1 lowest), three binary questions, and open-ended comments. Mean, standard deviation, and overall agreement (mean ± SD, OA) showed that students found MRI scans of cadavers to be helpful for dissections (4.14 ± 1.1, 74.3%) and provided an understanding of relevant anatomy (4.32 ± 0.9, 79.7%), while 78.4% of students used the DICOM viewer to visualize scans of cadavers. The difficulty of use was found to be average (2.90 ± 1.0, 23%). zSpace visualizations were used by 40.5% of students, generally agreeing that an understanding of spatial relationships improved as a result (3.60 ± 1.0, 43.2%). More case-based sessions were favored by 97.3% of students. CONCLUSIONS: Results suggest that cadaveric MRI radiological visualization and XR technology enhance understanding of case-based anatomical dissections and encourage student exploration and engagement.

Evaluation of manubriosternal joint fusion and second costal cartilage calcification: Are they useful for estimating advanced age groups?

The objectives of this study were to evaluate the manubriosternal joint (MSJ) to estimate the minimum chronological age of complete fusion, and how changes in this joint influence age estimation. The study also focused on investigating the calcification patterns of the second costal cartilage (SCC), as they may be related to age. Between January and September 2020, individuals between 30 and 80 years of age, who underwent chest tomography at our institution, were listed by sex and divided into five groups according to age with intervals of 10 years. Twenty patients from each age group and sex were randomly selected, and 200 patients were evaluated. The relationship between age and changes in MSJ and SCC was evaluated. The incidence of complete fusion did not differ significantly between the 30 and 80 age groups. A significant difference was found between the age groups and MSJ degeneration (p < 0.001). The degree of MSJ degeneration and calcification in SCC significantly increased with age, but the range was wide. These values might be used to support traditionally accepted age-estimation methods but not as independent indicators of specific age ranges.

The role of lateralisation and sex on insular cortex: 3D volumetric analysis

Background/aim: The insula has attracted the attention of many neuroimaging studies because of its key role between brain structures. However, the number of studies investigating the effect of sex and laterality on insular volume is insufficient. The aim of this study was to investigate the differences in insular volume between sexes and hemispheres. Materials and methods: A total of 47 healthy participants [24 males (20.08 ± 1.44 years) and 23 females (19.57 ± 0.90 years)] underwent magnetic resonance imaging (MRI). Imaging was performed using the 3T MRI scanner. The insular volume was measured using the Individual Brain Atlases using Statistical Parametric Mapping (IBASPM); total intracranial, cerebral, grey and white matter volumes were measured using volBrain. Results: The right insular volume was significantly higher than the left insular volume in the participants, and the left cerebral volume was significantly higher than the right cerebral volume (p < 0.05). The total brain, total cerebral, left and right insular, and cerebral volumes were significantly larger in males than in females (p < 0.001). Also, the ratios of the insular volume to total brain and cerebral volume were significantly higher in males than in females (p < 0.05). Conclusion: This study shows that insular volume differs with laterality and sex. This outcome may be explained by the anatomical relationship between the insula and behavioural functions and emotional reactions and the fact that the right side of the brain is best at expressive and creative tasks.

Melatonin decreases metastasis, primary tumor growth and angiogenesis in a mice model of breast cancer.

The goal of this study was to mechanistically analyze the effects of pre-treatment or post-treatment melatonin on the metastatic spread in a mice model. Consequently, the effects on the tumor growth, angiogenesis and metastasis were evaluated with immunohistochemical and western blot analysis. 8-10 weeks-old female BALB/c mice (n = 60, 10/group) were used. Liver metastatic cells (4TLM) from 4T1 murine breast carcinoma were previously isolated. Melatonin was administrated either before or after the injection of 4TLM cells into the mammary pad. Tumor and vehicle (%6 ethanol) injections were given to vehicle groups. Tumor group consisted of the mice injected with only 4TLM cells injected to tumor group and no intervention to control group. Necropsies were performed 27 days after injection of 4TLM. Primary tumors and metastatic tissues were removed. Furthermore, changes in lung and liver metastasis and primary tumor growth and angiogenesis were evaluated. In our study neutrophil levels were noted to be increased in peripheral blood of the tumor-bearing mice. Melatonin exerted inhibitory effects on the 4TLM-induced leukocytosis. Melatonin significantly decreased lung and liver metastasis, primary tumor growth and angiogenesis. The results demonstrated that melatonin might have a therapeutic role through reducing systemic inflammatory responses, metastasis, tumor growth and angiogenesis.

Comparison of various tendon repair techniques in extansor zone 3 injuries: an experimental biomechanical cadaver study.

PURPOSE: To compare five different repair techniques for extensor tendon zone III modified Kessler (MK), double-modified Kessler (DMK), modified Kessler epitendinous (MKE), double-modified Kessler epitendinous (DMKE), and running-interlocking horizontal mattress (RIHM) in terms of shortening, stiffness, gap formation, and ultimate load to failure. METHODS: A total of 35 human cadaver fingers were randomly assigned to five suture techniques with 7 fingers each and were tested under dynamic and static loading conditions. RESULTS: DMK was found to be superior over MK in terms of ultimate load to failure (36 N vs. 24 N, respectively), shortening (1.75 vs. 2.20 mm, respectively) and gap formation. However, these two methods had similar characteristics in terms of stiffness. The addition of epitendinous sutures to the repair methods resulted in approximately 40% increase in ultimate load to failure, whereas epitendinous sutures had no effect on shortening. DMKE was found to be superior over MKE in terms of shortening (1.77 vs. 2.22 mm, respectively). However, these two methods had similar characteristics in terms of mean ultimate load to failure and stiffness. RIHM was found to be superior over the other four methods in terms of ultimate load to failure (89 N), stiffness, and shortening (0.75 mm). CONCLUSION: RIHM was found to be stronger and more durable for extensor tendon zone III than the other techniques in terms of ultimate load to failure and stiffness.

Mutualistic Effects of the Myeloid-Derived Suppressor Cells and Cancer Stem Cells in the Tumor Microenvironment.

Myeloid-derived suppressor cells (MDSCs) are derived from myeloid progenitor cells present in the bone marrow. When the differentiation of the myeloid progenitor cells is impaired, MDSCs arise. The immunosuppressive functions of the MDSCs are significantly upregulated in the tumor microenvironment. MDSCs are promoted by many inflammatory molecules. Likewise, chemokines, cytokines, and enzymes that are secreted by MDSCs mediate tumor cell invasion, proliferation, survival, and adhesion. Cancer stem cells (CSCs) are known as malignant cancer cells with characteristics such as self-regeneration and differentiation. Cancer stem cells have been the focus of many cancer studies for many years. Recently, MDSCs have also become the focus of cancer researchers. According to a hypothesis, both CSCs and MDSCs have mutual effects on the development of cancer. Therefore, the aims of this review are to summarize the link between CSCs and MDSCs and to describe the immunosuppressor metastatic properties of the MDSCs.

Diabetes mellitus accelerates fatty degeneration of the supraspinatus muscle after tendon tear: An experimental study in rats.

OBJECTIVES: This study aims to evaluate the effect of diabetes mellitus (DM) on intramuscular fatty degeneration after a full-thickness supraspinatus (SS) tendon tear in rats. MATERIALS AND METHODS: The study included 24 adult male Wistar Albino rats (age, 18 to 24 weeks; weighing, 320-380 g) randomized into a sham group (n=6), control group (n=6) and experimental group (n=12). Rats with fasting blood glucose levels ≥250 mg/dL at each measurement after an injection of streptozotocin were accepted to have DM. On the seventh day of the study, the SS muscles of the rats in the experimental and control groups were cut from the insertion. All animals were performed euthanasia four weeks after the surgical procedure and SS muscles were excised completely. Fatty degeneration in the SS muscle was assessed histologically and immunohistochemically with oil red O and peroxisome proliferator-activated receptor gamma (PPAR-γ) staining using histological score (H-score) and quantitative methods. RESULTS: More intense oil red O and PPAR-γ staining was observed in all regions of the SS muscles of the experimental group compared to control and sham groups (p<0.05). CONCLUSION: The results of this study showed that DM accelerates intramuscular fatty degeneration after SS tendon tears. Fatty degeneration should be monitored closely in diabetic patients with rotator cuff tear who were selected for conservative treatment and early surgical treatment should be considered as an option.

Occipital artery arising from the internal carotid artery: a case report.

Variations of the branches of the external carotid artery have been well documented in the available literature. However, variation of the occipital artery arising from the internal carotid artery is extremely rare case. A 42-year-old man patient who suffered from subarachnoid hemorrhage with suspicious vascular anomalies was found to have this variation on the right side by angiography during selective catheterisation of main carotid artery for vascular mapping. Our literature searches revealed that there was rare case such variations. We think that this variation should contribute to literature and should be kept in mind during surgical, radiological and diagnostic procedures.

Accessory Ossicles of the Foot and Ankle: Disorders and a Review of the Literature.

Accessory ossicles of the foot and ankle are normal variants of bone development that usually remain asymptomatic. However, they may be involved in various disorders and become a source of pain such as in fractures, dislocations, degenerative changes, osteonecrosis, osteoarthritis, osteochondral lesions, avascular necrosis, and irritation or impingement of adjacent soft tissues. Hence, during the assessment of the situations above, knowledge about these little-known ossicles could be very important to reach the correct diagnosis. Recent studies in the literature have mostly focused on the most frequent 9-12 accessory bones. In this review, 24 types of accessory ossicle are described. These ossicles are accessory navicular bone, os peroneum, os trigonum, os intermetatarseum, os vesalianum. os subfibulare, os subtibiale, os calcaneus secundarius, os calcanei accessorium, os supratalare, os sustentaculi, os talotibiale, os tali accessorium, talus secundarius, os subcalcis, os cuboideum secundarium, os supranaviculare, os infranaviculare, os paracuneiforme, os intercuneiforme, os cuneometatarsale I tibiale, os cuneometatarsale plantare, os cuneo-I metatarsale-II dorsale, and os aponeurosis plantaris. The clinical importance of these bones should be known thoroughly to reduce unnecessary orthopedic consultations and misdiagnosis. This article describes the clinical importance of the accessory ossicles and their possible pathological conditions. Understanding the possible disorders of the accessory ossicles of the foot and ankle can provide a more accurate diagnostic process.

Evaluation of the origin and branching patterns of the iliolumbar artery and its implications on pelvic and vertebral surgery.

OBJECTIVES: To evaluate the origin, distribution pattern, branches, and neighboring structures of the iliolumbar artery (ILA) concerning the anterolateral surgical approaches to the spine. METHODS: This study was performed in the Anatomy Department of Medical School, Mersin University, Mersin, Turkey between 2014 and 2015. Pelvises of 11 male formalin-fixed human cadavers were dissected by anterior and posterior approaches under surgical microscope. The origins, distribution patterns, calibers, and distances to certain structures were measured. RESULTS: The ILA was found as a single trunk on 17 sides arising either from the IIA (12 sides, 70.6%) or the PT (5 sides, 29.4%). The average caliber of those originated from the posterior trunk was significantly larger (p=0.010). The ILA started as a single trunk in 17 sides, while its lumbar and iliac branches separately originating from different arteries in 4 sides. The close relation of the posterior rami of both the lumbar and iliac branches with transverse process and spinal nerve were noted. CONCLUSION: Findings suggest that the ILA and its branches may have different and significant patterns, which may be crucial to consider during certain surgical procedures, such as far lateral disc herniation and posterior pelvic fixations.