bluuebunny/crossref_metadata_2025 huggingface dataset:
miR‐195 and RNA‐binding protein CELF1 jointly regulate translation of IGF2 receptor in intestinal epithelium
Authors: Zhang Yuan , Chung Hee Kyoung , Xiao Lan , Wu Jing , Turner Douglas J. , Jaladanki Rao N. , Wang Jian‐Ying
Published: November 2023

Insulin‐like growth factor‐2 receptor (IGF2R) specifically binds to the IGF‐2 and its activation is crucial for stimulation of mucosal regeneration after small bowel resection, but the exact mechanism underlying the control of cellular IGF2R abundance remains largely unknown. microRNAs and RNA‐binding proteins (RBP) regulate the stability and translation of target mRNAs and are involved in many aspects of cellular functions. This study tested the hypothesis that miR‐195 and RBP CELF1 (also named as CUG‐binding protein 1) modulate IGF2R expression posttranscriptionally.

Methods

Studies were conducted in intestinal epithelial cells (IECs) and mice.

Results

miR‐195 directly interacted with the Igf2R mRNA via its 3′‐untranslated region (3′‐UTR) rather than its 5′‐UTR and coding region, and ectopically expressed miR‐195 repressed IGF2R translation without effect on its mRNA stability in cultured IECs. In contrast, intestinal epithelial tissue‐specific miR‐195 knockout in mice increased levels of IGF2R expression in the small intestinal mucosa, which was associated with an increase in mucosal growth. Moreover, CELF1 also associated with the Igf2R 3′‐UTR and inhibited IGF2R translation. Further studies showed that miR‐195 and CELF1 repressed IGF2R translation synergistically. Functionally, decreased IGF2R by miR‐195 altered the structure and homeostasis of Golgi apparatus, since there were significant redistribution of syntaxin 6 (Golgi structural protein) at Golgi network and endosomal compartments following reduction in IGF2R by miR‐195.

Conclusion

miR‐195 and CELF1 repress IGF2R translation synergistically, thus down‐regulating intestinal epithelial renewal by altering Golgi stability and functions.

Support or Funding Information

Department of Veterans Affairs (RNJ, DJT, JYW) and NIH (JYW)
Expression and localization of the major receptor of vasoactive intestinal peptide (VPAC1) along the length of the intestine
Authors: Jayawardena Dulari , Guzman Grace , Gill Ravinder , Alrefai Waddah , Onyuksel Hayat , Dudeja Pradeep
Published: November 2023

Vasoactive intestinal peptide (VIP) is an endogenous neuropeptide with a broad array of physiological functions in the nervous system and peripheral organs including the intestine. This peptide exerts its action via binding to VPAC1, VPAC2 and PAC1, which are G‐protein coupled receptors (GPCR). VPAC1 is the major receptor constitutively expressed in many cell types and is responsible for majority of VIP's biological activity. However, the distribution of VPAC1 along the length of the gastrointestinal tract and its sub cellular localization in intestinal epithelial cells has not been fully defined. Therefore, the current studies were undertaken to determine VPAC1 distribution and localization so that VIP based therapies can be targeted to specific regions of the intestine.

Methods

Real time PCR, immunoblotting and immuno‐fluorescence staining were used to determine the mRNA, protein and cellular localization of VPAC1 respectively. Intestinal tissues from male C57Bl/6 mice (6–8 weeks) and human tissues as well as colonic adenocarcinoma cell lines were used. The results indicated that the mRNA levels of VPAC1 in mouse intestine were highest in colon followed by jejunum and ileum. In parallel, the VPAC1 protein levels were higher in the mouse colon (proximal > distal) followed by the jejunum and ileum. Immuno‐fluorescence studies in mouse colonic tissue sections demonstrated that the receptor was specifically localized to the luminal surface as evident by co‐localization of the VPAC1 protein with the apical marker villin but not with the basolateral marker sodium potassium ATPase. In the human intestine, VPAC1 mRNA expression exhibited an expression pattern similar to mouse intestine (colon > jejunum> ileum). Furthermore, in human colon, VPAC1 predominantly showed apical localization as observed by immuno fluorescence staining. Western analysis demonstrated almost equal protein levels of VPAC1 in human adenocarcinoma cell lines e.g. Caco2, T84, HT‐29 and SKC015 cells. The luminal localization was further confirmed by relatively high apical staining for VPAC1 in differentiated Caco2 monolayers. Our current data showed differential expression of VPAC1 along the length of intestine and demonstrated its localization on the luminal membrane of colonocytes. The physiological relevance of this expression and apical localization of VPAC1 remains elusive. We speculate that apical localization of VPAC1 in intestinal epithelial cells has physiological relevance in recognizing secreted peptides in the intestinal lumen and supports the potential therapeutic use of VIP nanomedicine via oral route to target gut inflammation.

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Support or Funding Information

Supported by NIDDK and VA Merit
Gene Expression of the GIP and GLP‐1 Receptors in the Horse
Authors: Kheder Murad H. , Dudley Kevin , Sillence Martin N. , de Laat Melody A.
Published: November 2023

Introduction

The Glucagon‐like peptide‐1 (GLP‐1R) and gastric insulinotropic polypeptide (GIPR) receptors are members of the secretin family of G‐protein coupled receptors that regulate insulin secretion from pancreatic beta cells. Both receptors are well studied in rodents and humans, but there are limited data available for horses. In horses, GIP and GLP‐1 contribute to hyperinsulinaemia, which causes a painful foot disease called laminitis.

Aim

This study aimed to determine whether the GIPR and GLP‐1R genes are expressed in equine tissues.

Methods

Archived tissue samples (pancreas, skeletal muscle, heart, liver, kidney, digital lamellae (which is the organ affected by laminitis), tongue and small intestine) from healthy horses were subject to mRNA extraction and cDNA synthesis prior to primers design and PCR. Sequencing of the PCR product was undertaken to confirm amplification of the target gene.

Results

Both the GIPR and GLP‐1R were expressed in the pancreas as expected, and this tissue was used as a positive control for tissue distribution studies. The GIPR was expressed in the heart, liver, kidney and small intestine. The GLP‐1R gene was expressed in all tissues except the tongue and small intestine. Sequence identity to the Equus caballus mRNA sequence available from GenBank was 98% for GIPR and 100% for GLP‐1R.

Discussion

These data indicate that GIPR and GLP‐Rs may be potential therapeutic targets for the treatment/prevention of hyperinsulinaemia and laminitis in horses. The expression of both receptors in tissues other than the pancreas suggests that they may have other physiological functions and this requires investigation.

Support or Funding Information

Australian Research Council (ARC)
FFA2‐mediated 5‐HT release increases HCO3− secretion, but induces mucosal injury in rat duodenum
Authors: Maruta Koji , Akiba Yasutada , Kaji Izumi , Kaunitz Jonathan D
Published: November 2023

Although serotonin (5‐HT) is an important mediator of ion secretion and propulsive motility, excessive 5‐HT release induces emesis and diarrhea, treatable with 5‐HT3 antagonists. The short‐chain fatty acid receptor FFA2 is expressed on 5‐HT synthesizing enterochromaffin (EC) cells. The selective FFA2 agonist phenylacetamide‐1 (PA1) increases the rate of duodenal HCO3− secretion (DBS) via 5‐HT4 receptor activation. We hypothesized that EC cell FFA2 activation increases 5‐HT release, affecting duodenal mucosal defenses under physiological and pathological conditions. We measured DBS in vivo in a PA1‐perfused duodenal loop, measuring 5‐HT released into the portal vein (PV) with or without the selective FFA2 antagonist GLPG0974 (0.1 – 10 μM). Intestinal injury was induced by indomethacin (IND) with or without PA1 (0.1 – 1 mg/kg, ig), GLPG0974, the 5‐HT3 receptor antagonist ondansetron (Ond), the 5‐HT4 receptor antagonist RS23597. Luminal perfusion with PA1 (1 μM and 0.1 mM) similarly augmented DBS, whereas 5‐HT release into the PV was 8‐fold higher in response to 0.1 mM PA1 compared with 1 μM. GLPG0974 dose‐dependently inhibited PA1‐induced DBS increase with corresponding reductions of 5‐HT release. IND alone induced small intestinal ulcers with duodenal sparing, whereas PA1 + IND dose‐dependently induced duodenal lesions. PA1 + IND‐induced duodenal lesions were inhibited by GLPG0974 and Ond, but not affected by RS23597. These results suggest that physiological 5‐HT concentrations released into the PV in response to FFA2 activation enhance duodenal mucosal defenses, whereas excessive 5‐HT release induced by FFA2 overactivation disrupts defenses via 5‐HT3 activation, injuring the duodenal mucosa during COX inhibition. FFA2 overactivation may be implicated in the genesis of symptoms such as emesis, bloating, and diarrhea.

Support or Funding Information

Supported by VA Merit Review, NIH R01 DK54221
GLP‐2 enhances duodenal SGLT1‐mediated glucose absorption via EGF signaling
Authors: Kaji Izumi , Akiba Yasutada , Kaunitz Jonathan D.
Published: November 2023

Glucagon‐like peptide 2 (GLP‐2) released from enteroendocrine cells has trophic, barrier strengthening, and anti‐inflammatory effects on the gut mucosa. Chronic administration of GLP‐2 accelerates the rate of jejunal glucose absorption through upregulation of sodium‐dependent glucose transporter (SGLT)1 expression. Nevertheless, glucose absorption by duodenal epithelial cells in response to the acute administration of GLP‐2 has not been investigated. We assessed SGLT1‐mediated electrogenic glucose absorption by measuring short‐circuit current (Isc) in Ussing chambers in mucosa‐submucosal preparations of rat distal duodenum and in full‐thickness preparations of mouse duodenum. GLP‐2 receptor (GLP‐2R) localization was confirmed by immunohistochemistry in frozen duodenal sections. Mucosal application of glucose (10 mM) increased Isc in muscle‐stripped mucosa‐submucosal preparations of duodena from overnight‐fasted rats, but had no effect after feeding. This glucose‐evoked Isc was completely reversed by the SGLT inhibitor phloridzin, consistent with electrogenic SGLT1‐mediated absorption. Full‐thickness duodenum from fed mice responded to mucosal glucose, accelerated by 4‐h fasting. Pretreatment with GLP‐2 (20 – 100 nM) for 15 min significantly enhanced the glucose‐induced increase in Isc. GLP‐2 did not alter electrogenic Cl− secretion evoked by serosal nicotine (0.1 mM), bethanechol (1 mM), or forskolin (1 μM) in rat and mouse duodenum. The enhancement of the glucose absorptive Isc was mimicked by mucosal incubation with epidermal growth factor (EGF, 50 ng/ml) for 15 min, abrogated by the tyrosine kinase inhibitor AG18 (0.1 mM). Since GLP‐2R is not expressed on duodenal epithelial cells, GLP‐2‐mediated EGF release from interstitial cells with consequent activation of epithelial ErbB (EGF receptor) may underlie the acute alteration of SGLT1 activity. GLP‐2R immunoreactivity was detected in vasoactive intestinal peptide (VIP)‐containing myenteric neurons in the duodenum, whereas a selective antagonist for VIP receptors (VPAC1) (1 μM) had no effect on GLP‐2‐induced enhancement of glucose absorptive Isc. In full‐thickness preparations with myenteric neurons from mouse duodenum, the nitric oxide synthase inhibitor L‐NAME (0.1 mM) or tetrodotoxin (1 μM) had no effect on GLP‐2‐enhanced glucose‐induced Isc, inconsistent with mediation of GLP‐2‐related acute acceleration of glucose absorption via SGLT1 by a neural pathway. These findings suggest that the GLP2R‐EGF pathway in duodenal epithelial cells acutely affects nutrient absorption, another important and novel effect of GLP‐2.

Support or Funding Information

Supported by VA Merit Review, NIH R01 DK54221
Utilizing Shared Virtual Microscopy Slides to Create Innovative Anatomical Science Resources in an Integrated Curriculum
Authors: Goldman Haviva M.
Published: November 2023

The shift towards integrated medical education curricula and digital imaging has transformed the teaching of histology, leading to new challenges and opportunities for the discipline (Drake et al, Anat Sci Educ 7:321–5, 2014). Educators face limited curricular time and support for histology laboratories, and a demand for integrated, interactive and clinically applied learning activities. Virtual microscope technology has already transformed the histology laboratory, providing a high quality and flexible alternative to microscopes. A shared virtual microscopy database provides a resource for educators that can be used to create customized content that can readily be adapted towards an integrated and applied curriculum.

Drexel University College of Medicine is moving towards an integrated curriculum where much of the course content is delivered electronically. We utilize our University's virtual microscopy collection within our customized online independent‐learning modules. Slides have been annotated to demonstrate important structures so that students can learn on their own using independent learning modules. These are then supplemented with images from shared virtual microscope collections (for example University of Michigan and University of Iowa collections, and now numerous others via the Virtual Microscopy Database) as mystery slides in live sessions. Several examples of teaching modules and in‐class exercises that utilize shared microscopy resources will be demonstrated during this presentation. These include tutorials, review exercises and clinical application exercises integrating histology with gross anatomy, radiology, neuroscience and embryology, as well as pathology. Through the creation and use of these innovative resources we are able to ensure that histology remains the important bridge it always has been, providing a linkage between gross morphology, physiological function and the biochemical and molecular basis of disease.
Intestinal Dysbiosis During Neonatal Development Alters the Microbiota‐Gut‐Brain Axis in Adulthood
Authors: Hennessey Carly H , Sladek Jessica , Miller Elaine , Kim Janis , Kaur Manvir , Gareau Melanie G
Published: November 2023

The neonatal period of life is critical for bacterial colonization of the gastrointestinal (GI) tract, formation of GI mucosal barrier function, and neural development. Previous studies from our group have shown that infection of adult mice with a bacterial pathogen causes changes in the microbiota‐gut‐brain (MGB) axis, including intestinal dysbiosis and behavioral deficits. However, the relationship between intestinal dysbiosis during the early stages of development and cognitive and behavioral function in adulthood have not been investigated. We hypothesized that dysbiosis due to bacterial infection in early life would lead to a dysregulated MGB axis with lasting deficits into adulthood. A mouse model (C57BL/6) of neonatal bacterial infection with enteropathogenic Escherichia coli (EPEC; strain e2348/69) was used to study effects of intestinal dysbiosis on the MGB axis. Behavior was assessed using the light/dark box (anxiety‐like behavior) and the novel object recognition (NOR) task (cognitive function). The microbiota was characterized by qPCR, and Ussing chambers were used to study intestinal physiology. Mice infected with EPEC as neonates showed impaired memory as adults (p<0.05), without evidence of anxiety‐like behavior compared to sham‐infected controls. This was accompanied with down‐regulation of innate immune pattern recognition receptors (Nod1 and Nod2) and regulatory cytokines (IL10), coupled with up‐regulation of pro‐inflammatory cytokines (TNF‐α) and the serotonin biosynthesis pathway (Tph) in the hippocampus (p<0.05). Neonatal infection resulted in long‐lasting intestinal dysbiosis (decreased Lactobacillus, increased Enterobacteriaceae) and intestinal pathophysiology characterized by increased secretory state (short circuit current; Isc) and permeability (conductance; G) (p<0.05). Transcriptional analysis of the colon showed down‐regulation of protective gut factors (RegIIIγ) and increased NF‐κB activation in adulthood (p<0.05). In conclusion, our data demonstrates that neonatal bacterial infection leads to alterations of the development of the MGB axis that extend through to adulthood. These findings may have important clinical implications for pediatric patients exposed to bacterial enteric pathogens during early development.

Support or Funding Information

This work was funded by an APS undergraduate summer research fellowship (JK); NIH 5R21MH108154‐01 (MGG), U54 HD079125 (MGG).
Effects of Exercise Before and During Pregnancy on Microbiomes in High‐Fat Fed Pregnant Mice
Authors: Chung Eunhee , Grue Katherine A , Kottapalli Kameswara Rao , Kaur Gurvinder , Dufour Jannette , Shen Chwan‐Li
Published: November 2023

Gut microbiota profile changes from first to third trimester and is associated with mild insulin resistance that typically occurs in late pregnancy. It has been shown that diet‐induced obesity negatively changes gut microbiota profiles, while exercise normalizes the gut microbiota in high‐fat diet‐induced obesity. However, the beneficial effects of exercise on gut microbiota during pregnancy have not been investigated. Thus, the objective of this study was to determine the effects of exercise on gut microbiota in high‐fat fed pregnant mice. Female C57BL/6 mice were fed either a high fat diet (HFD) or a low fat diet (LFD) for twelve weeks. Four weeks prior to pregnancy initiation, the HFD group was split into sedentary (HFD) or exercised (HFD+Ex) Mice in HFD+Ex continued to exercise throughout the pregnancy. All mice were sacrificed at gestation day 19, and fecal samples were collected. 16S ribosomal RNA gene sequencing was performed from DNA extracted from cecum. Voluntary exercise did not alter HFD induced body weight gain. Both HFD and HFD+Ex had impaired glucose tolerance compared to LFD at 15 days of gestation. However, serum insulin levels were significantly reduced in HFD+Ex compared to the HFD. HFD decreased Bacteroidetes as well as the ratio of Bacteroidetes/Firmicutes. Exercise (HFD+Ex) further decreased BacteroidetesCe and the ratio of Bacteroidetes /Firmicutes. In addition, increase in Verrucomicrobia phylla induced by HFD was suppressed by exercise during pregnancy. Our findings suggest that alteration of gut microbiota may facilitate fuel needed for exercise and prevent the hyperinsulinemia that is associated with a HFD.
Apolipoprotein (apo)AV deficiency aggravates ethanol‐induced liver injury, promoting progression from simple steatosis to alcoholic steatohepatitis and then to liver fibrosis in mice
Authors: Wang David Q , Gao Bin , Wang Helen H , de Bari Ornella , Tso Patrick
Published: November 2023

Background

Alcoholic liver disease (ALD) includes a broad spectrum of disorders, ranging from simple steatosis to severe forms of liver injury such as alcoholic steatohepatitis (ASH), fibrosis, and hepatocellular carcinoma. Almost all heavy drinkers suffer from fatty liver, but only 20–40% of them develop more severe forms of ALD, and the underlying mechanisms contributing to disease progression remain elusive. Although there are an increasing number of animal models of ALD, none of them depicts the complex metabolic profile and the histological patterns typical of ALD patients. Because apoAV is synthesized exclusively in the liver, we hypothesizethat it plays a critical role in regulating hepatic lipid metabolism, and ethanol interacts with apoAV to severely disrupt hepatic lipid homeostasis, leading to lipotoxic hepatocellular injury.

Methods

Male apoAV KO, transgenic (Tg) and WT mice were given chronic (5%, v/v) and binge (5g/kg once per wk) ethanol feeding (a modified NIAAA model) for 4 wk. Liver histopathology was examined by H&E and Sirius Red staining. The murine primary hepatocytes and hepatic stellate cells were treated with lysophosphatidylcholine (lysoPC). mRNA and protein levels were studied by qRT‐PCR and Western blots. Lipidomic analysis of liver was performed by ESI‐MS/MS.

Results

Ethanol caused a dose‐dependent inhibitory effect on mRNA and protein expression of apoAV in WT hepatocytes. This induced the accumulation of excess triglyceride and the formation of numerous lipid droplets in apoAV KO, but not Tg hepatocytes vs. WT controls. After ethanol feeding, apoAV KO mice displayed rapid development of liver steatosis, subsequently evolving from simple steatosis to ASH and then to liver fibrosis. WT mice developed only liver steatosis. Ethanol increased hepatic lysoPC levels, a known lipotoxic fatty acid metabolite, by enhancing its synthesis in KO mice compared to WT mice. Increased lysoPC induced hepatic lipo‐apoptosis through TNFα by stimulating both caspase‐induced apoptosis and reactive oxygen species (ROS)‐mediated mitochondrial dysfunction in KO, but not WT mice. These alterations triggered ASH with a key histological feature of hepatocellular ballooning, and increased collagen secretion by hepatic stellate cells through activating profibrogenic genes and heat shock protein 47, leading to liver fibrosis in KO mice.

Conclusions

The apoAV KO mouse model closely recapitulates many characteristics of the pathogenic processes and histological patterns of ALD in patients. LysoPC may be a key trigger for ASH, similar to its proposed role in NASH. These innovative studies elucidate a critical role of apoAV in the pathogenesis of ALD.

Support or Funding Information

This work was supported in part by research grants DK101793 and DK106249, both from the National Institutes of Health (US Public Health Service).
The anterior jugular veins: preliminary study
Authors: Hojaij Flávio , Santos Lesley , Souza Bruna , Pacheco Juliana , Andrade Mauro , Akamatsu Flávia Emi , Jacomo Alfredo Luiz
Published: November 2023

The jugular venous system is responsible for the head and neck drainage. The anterior jugular vein has the smallest caliber when compared with the other jugular veins. Near to the superior thoracic opening, the anterior jugular veins run sideways, deep to the sterno bone. Above the sterno bone, the anterior jugular veins run side by side lateral to the midline and they can communicate to each other through an arch – the jugular venous arch. There are many relevant anatomical variations among the anterior jugular veins. Therefore, an anatomical pattern study about these veins have a relevant clinical importance for the enhancement of the surgical technique and improvement of post‐operative cares for procedures done in the anterior region of the neck like thiroidectomies and trachoestomies

Objective

Describing the anterior jugular veins relations in the infrahyoid area and comparing possible variations with anthropometric characteristics.

Method

To study the anterior jugular veins positions, Using a form, previously elaborated, the anterior jugular veins are observed according to the following characteristics: the number of veins, caliber, position, path, distance between the middle line, presence and anastomoses location, presence and jugular venous arch location. The cadavers' anthropometric characteristics. had been collected.

Results

These are the preliminary results : 5 cases with 2 anterior jugular veins;4 cases with only one anterior jugular vein e one case with 3 anterior jugular veins. Fifty per cent of the cases showed the anterior jugular veins near to the midline plan (1cm or less). The veins' caliber were 5 mm or less in 60% of the cases. There are many variantions talking about the arch.

Conclusions

as a preliminary study we are able to state that there are many relevant anatomical variations in number of veins and their caliber
Comparison of 3D laser‐based photonic scans and manual anthropometric measurements of body size and shape in a Swiss validation study
Authors: Ruhli Frank , Bender Nicole , Staub Kaspar
Published: November 2023

Manual anthropometric measurements are time‐consuming and challenging to perform within acceptable intra‐ and inter‐individual error margins in large studies. Three‐dimensional (3D) laser body scanners provide a fast and precise alternative: Within a few seconds the system produces a 3D image of the body topography and calculates some 150 standardized body size measurements.

The aim was to enhance the small number of existing validation studies and compare scan and manual techniques based on five selected measurements. We assessed the agreement between two repeated measurements within the two methods, analyzed the direct agreement between the two methods, and explored the differences between the techniques when used in regressions assessing the effect of health related determinants on body shape indices.

We performed two repeated body scans on 123 volunteering young men using a Vitus Smart XXL body scanner. We manually measured height, waist, hip, buttock, and chest circumferences twice for each participant according to the WHO guidelines. The participants also filled in a basic questionnaire.

Mean differences between the two scan measurements were smaller than between the two manual measurements, and precision and intra‐class correlation coefficients were higher. Both techniques were strongly correlated. When comparing means between both techniques we found significant differences: Height was systematically shorter by 2.1cm, whereas waist, hip and bust circumference measurements were larger in the scans by 1.17–4.37cm. In consequence, body shape indices also became larger and the prevalence of overweight was greater when calculated from the scans. Between 4.1% and 7.3% of the probands changed risk category from normal to overweight when classified based on the scans. However, when employing regression analyses the two measurement techniques resulted in very similar coefficients, confidence intervals, and p‐values.

For performing a large number of measurements in a large group of probands in a short time, body scans generally showed good feasibility, reliability, and validity in comparison to manual measurements. The systematic differences between the methods may result from their technical nature (contact vs. non‐contact).

Support or Funding Information

Mäxi Foundation
Patterns of Thyrocervical Trunk Variation
Authors: Ballas Elissa R , Inouye Sandra
Published: November 2023

This study reports the classification of thyrocervical trunk branching patterns from 64 subclavian arteries in 33 adult cadavers. Of the 64 subclavian arteries, 28 (43.8%) were from male cadavers and 36 (56.3%) were from female cadavers. Branching patterns were classified based on a scheme described by Lippert and Pabst.1 A thyrocervical trunk was observed 63 times in the sample and was absent on one side in one cadaver; two cadavers had one side that was unusable due to previous dissections. In all cadavers that had a thyrocervical trunk, branching occurred at the subclavian artery distal to the vertebral artery and medial to the anterior scalene muscle. The incidence of the traditional thyrocervical trunk branching pattern described in textbooks (type a), in which the thyrocervical trunk is formed by the inferior thyroid, suprascapular, and transverse cervical arteries, was 64.1% (36.6% male, 63.4% female). The incidence of the next most common pattern (type c), in which the inferior thyroid and suprascapular arteries branched from a common trunk and the transverse cervical artery had a separate origin, was 21.9% (71.4% male, 28.6% female). The incidence of the third most common pattern (type b), in which the internal thoracic artery originated from the thyrocervical trunk in addition to the inferior thyroid, suprascapular, and transverse cervical arteries, was 6.3% (20.0% male, 80.0% female). Four other subclavian arteries had different branching patterns, including one that had no thyrocervical trunk. The cadaver with no thyrocervical trunk exhibited the inferior thyroid, suprascapular, and transverse cervical arteries arising separately from the subclavian artery.

Chi‐square analyses comparing male and female distribution samples, as well as comparing right and left sides, yielded no significant differences for either. However, comparisons between the frequency of branching patterns in this study with those reported by Lippert and Pabst revealed a significant difference between the two samples (p<.05). While Lippert and Pabst reported the incidence of types a and c at 30% each, this study reports the incidence of those types at 64.1% and 21.9%, respectively. The cadaver with no thyrocervical trunk and separate arteries arising from the subclavian artery was not described in the extensive study by Lippert and Pabst, and perhaps may be a rare variant.

This region of the body is a common site of invasive procedures; therefore, it is critical to be aware of common and variable arterial branching patterns.

Support or Funding Information

This study was made possible with the support of the Chicago College of Osteopathic Medicine and Midwestern University.
Anatomical Investigation of the Tensor Vastus Intermedius in the Quadriceps Muscle Group
Authors: Collins Christopher T. , Figge Lauren , Reeves Rustin , Lovely Rehana
Published: November 2023

Study Objectives

The aim of this study is to further investigate the presence of the tensor vastus intermedius (TVI) in a larger sample size of 80 thighs and also attempt to bring novel imaging techniques to the discussion.

Background

Until this year, the quadriceps muscle group has been described as containing four muscles, with few studies describing its deviation from this definition. Most recently, a study reported finding this additional muscle belly in all 26 cadaver dissections performed, which was then named TVI for its similarities to the tensor fascia lata (TFL) and its anatomical relationship to the vastus intermedius (VI) (Grob et al 2016).

Methods

In the preliminary dissections performed on 49 donor thighs we focused specifically on TVI presence, tendinous properties and nerve innervation. This current study includes 80 donor thighs and will include the previously stated focuses as well as the vascular supply of the TVI. Biostatistical analysis will also be used to find any correlation of TVI bilaterally or with known factors of the donor such as gender.

Results

Along with the TVI muscle belly presence, there is variation among its tendinous contribution to the quadriceps tendon, which is classified based on the muscle it fuses with, vastus lateralus (VL), VI or both, or whether it is completely independent.

Conclusion

Our preliminary investigation showed TVI presence in 38% of cadaver thighs, which is also what we expect to find in the additional 80 thighs analyzed of the present study.
Incidence of Right Lung Fissuring and Lobation in Human Cadavers
Authors: Ettarh Raj , Reynolds Amberly , Hassan Sherif S , Govero Austin
Published: November 2023

Lobes in the human lung possess relative functional independence. The delineating fissures between lobes provide a physical barrier to help confine disease processes; therefore, knowledge of lobation patterns for the lungs has significant implications for clinical management of pulmonary pathologies. Traditionally, the right lung is believed to be commonly divided into 3 lobes and the left lung into 2 lobes. However, there is no data in the published literature to support this conventional knowledge. This study addressed this gap in the literature by examining the lungs bilaterally in 68 cadavers. Fissures in each lung were inspected for complete or incomplete formation by determining presence of full or partial depth. Fissures were photographed, and proper (true) lobes were defined as completely delineated if they were bordered by full‐depth fissures that extend from costal surface of lung to hilum of lung. There were 3 distinct patterns of lobe formation in both lungs: no lobes (lobeless), two lobes (bi‐lobed) and three lobes (tri‐lobed). Three percent of right lungs were lobeless compared to 1% among left lungs. Twenty percent of right lungs had 2 completely formed lobes and 77% were tri‐lobed. Ninety‐four percent of left lungs were bi‐lobed and 5% had three completely formed lobes. Only 35% of horizontal fissures in the right lung were full depth. One in 5 right lungs had 2 completely formed lobes, and approximately 3 in 10 lungs have a lobe count that differs from the traditional 3:2 Left: Right pattern. The incidence of unusual patterning is sufficiently significant to warrant caution by clinicians for patients with pulmonary diseases.

Support or Funding Information

None
Diabetes Mellitus Reduces The Expression Of Betatrophin In Pancreatic Islet Cells
Authors: Adeghate Ernest , D'Souza Crystal , Al Balooshi Mohammed
Published: November 2023

Betatrophin, a peptide hormone expressed in liver and fat cells, has been reported to increase the rate of pancreatic β‐cell proliferation and β‐cell mass expansion. The present study determines whether the pancreatic content of betatrophin is reduced after the onset of diabetes mellitus (DM). DM was induced in adult male rats by a single intraperitoneal injection of streptozotocin (STZ) at a dose of 60 mg/kg body weight. Pancreatic tissue fragments were fixed overnight in freshly prepared Zamboni's fixative. The fixed tissue samples were embedded in paraffin wax. Sections of 6 μm thickness were cut on a microtome and processed for immunofluorescence. For immunoelectron microscopy, pancreatic tissue fragments (2 mm3) were fixed in McDowell's fixative and embedded in resin. Nickel grids with sections of pancreatic tissue were rinsed in 0.01 M sodium citrate buffer at 90°C for 5 minutes, cooled and jet‐washed with de‐ionized water. The sections were later immunostained using antibodies against either a combination betatrophin/insulin or betatrophin/glucagon. DM caused a significant reduction in the expression of betratrophin in pancreatic islet cells. Moreover, betatrophin was localized with insulin and glucagon in pancreatic islet cells. Betatrophin was found mainly in the secretory granules of insulin‐ and glucagon‐producing cells. These findings suggest a possible role of betatrophin in pancreatic endocrine function.

Support or Funding Information

This study was supported by a research grant from the UAEU
Hepato‐Diaphragmatic Interposition of the Cecum: A Rare Variant
Authors: Castellanos Bedia , Velavan Sumathilatha Sakthi , Rich Sushama
Published: November 2023

The cecum is a blind intestinal pouch usually situated in the right iliac fossa. Malrotation of gut causes congenital abnormalities of the intestines such as the subhepatic cecum. The antero‐hepatic location of the cecum which is unique among the described variations with the Chilaiditi sign makes this case report of high relevance for liver and intestinal procedures. During routine dissection of the abdomen of an 89‐year‐old male cadaver, a rare variant location of the cecum was found. Further dissection of the cecum, large intestines, liver, gallbladder and their blood supply was performed, and the specimen was photographed. The cecum with appendix, ascending colon and hepatic flexure was present on the upper right quadrant, anterior to the right lobe of the liver and gallbladder leaving an impression on the right lobe. The ascending colon was short. The arterial supply to the antero‐hepatic cecum was from the ileocolic, the terminal branch of the superior mesenteric artery and it was directed towards the right hypochondrium. The rare antero‐hepatic interposition of the cecum should be known to gastroenterologists, radiologists, and surgeons because of the following reasons: Due to its position, intestinal movements could be minimized. The pain in the unusual hepatic position of the cecum and appendix could generate confusion and delay in the diagnosis and treatment of appendicitis. Also, it may lead to misinterpretation of barium enema and computed tomographic scan findings.
Colonic mucosa is affected by gastric restriction in an animal model
Authors: Fontes Luiz Gustavo , Itezerote Ana , Saleh Samir , Hojaij Flávio , Andrade Mauro , Martinez Carlos Augusto Real , Akamatsu Flávia Emi , Jacomo Alfredo Luiz
Published: November 2023

Gastric reduction procedures are currently employed to treat morbid obesity and there are few reports concerning the consequent effects in large intestine.

We devised an experimental model of gastric restriction using rats. The animals were submitted to surgical gastrostomy and a cylindrical loofah is inserted in the stomach. Surgical procedure is described in detail elsewhere.

We studied 30 adult male Wistar rats divided in three groups: the stomach reduction group (R10), the sham group (S10), which underwent the same procedure except for the loofah insertion and the control group (C10). Animals were fed and kept in separate cages. They were weighed every other day until being sacrificed on day 10.

Sections of the colon were obtained and stained with hematoxylin‐eosin and analyzed for the length of the crypts, mucous cells and inflammatory cells.

The data were submitted to the Kolmogorov‐Smirnov test to verify the type of distribution. Data with normal distribution are presented as mean ± standard deviation. In this case, to compare groups, variance analysis was performed (ANOVA) followed by Bonferroni multiple comparisons. The tests were performed with 5% significance level.

The analysis of goblet cells count on R10 group indicated a statistically significant reduction of goblet cells and the crypts were shallower as compared to the C10. There were no difference regarding inflammatory cells. These findings might be a result of colonic mucosae atrophy secondary to the effects of gastric restriction in this model.
Angiogenic, oxidative and hormonal responses of the prostatic microenvironment in high fat diet‐fed aging mice
Authors: Cagnon Valeria Helena , de Almeida Lamas Celina , Hermes Tulio , Kido Larissa Akemi , Minatel Elaine , Collares‐Buzato Carla , Marostica Mario Roberto
Published: November 2023

Aging and obesity are associated with prostatic lesion induction. Cellular proliferation, angiogenesis and oxidative stress could be altered in both processes. Thus, the aim of the study herein was to evaluate different molecules related to angiogenesis, oxidative stress and hormonal metabolism, considering aging and high‐fat diet intake on the mice prostate. FVB mice (30) were divided into the following groups: Young group (YNG ‐ 3 months old), Senile group (SE ‐ 11 months old), Senile and high‐fat diet (SHE ‐ 11 months old + high‐fat diet). YNG and SE groups received a normolipid diet (22% protein, 53% carbohydrate, 4.5% lipids and 2.9 Kcal/g) and SEH group, received a high‐fat and high‐calorie diet (20% protein, 50% carbohydrate, 21% lipids and 4.7 Kcal/g). After 60 days, the mice were anesthetized and the ventral prostate were collected and submitted to morphological analysis; and to immunohistochemical and immunoblotting evaluation for androgen and estrogen receptor (AR, ERα), vascular endothelial growth factor (VEGF), 4HNE and catalase. Weight gain, food and energy intake were analyzed. The results showed reduced weight gain and increased energy intake in SE group compared to YNG group. The high‐fat diet intake during aging led to increased weight gain and energy intake, despite diminishing food intake in relation to SE group. The prostatic morphology in SE group showed increased cellular proliferation, well‐differentiated adenocarcinoma, microacini, inflammatory cells and hypertrophied fibromuscular stroma. The high‐fat diet intake by aging mice aggravated the prostatic injuries in relation to SE group, showing increased cell proliferation, well‐differentiated adenocarcinoma, microacini and fibromuscular stroma hypertrophy. The inflammatory cell level was elevated in SHE group despite not significantly differing from SE group. In addition, reduced AR immunolabeling and increased ERα, VEGF, 4HNE and Catalase levels were verified in SE group as compared to YNG group. The high‐fat intake during aging led to an AR, ERα, VEGF, 4HNE and Catalase increase as compared to SE group. Thus, we concluded that the aging process led to harmful changes in the prostatic microenvironment, favoring glandular lesions. Also, the high‐fat intake in association with aging increased the microenvironment molecular imbalance, compromising glandular stromal‐epithelial interaction. The association of hormonal imbalance as well as angiogenic and oxidative processes due to aging and high‐fat diet intake dysregulated important signaling pathways in the prostate, particularly related to cell proliferation and inflammation, leading to pre‐malignant lesions. The glandular microenvironment ERα and angiogenic signaling stimuli, contributed to the glandular dynamic rupture.

Support or Funding Information

Sao Paulo Research Foundation (Fapesp‐2015 25714‐1
Clinical Anatomy of the Perineum Underlies Outcomes of Prostatectomy and Episiotomy
Authors: Plochocki Jeffrey H , Rodriguez‐Sosa Jose R , Ruiz Saul , Hall Margaret I
Published: November 2023

Clinical anatomy of the perineum has been surprisingly understudied. In particular, anatomical correlates of surgical outcomes with perineal structure have been poorly investigated, especially for surgical approaches to prostatectomy in males and episiotomy in females. Perineal radical prostatectomy is one surgical option to excise primary tumors of the prostate. Although associated with less blood loss than the suprapubic approach, the perineal approach is associated with increased complication rates related to potency and fecal continence. Episiotomy is performed using one of three surgical approaches. The median or midline approach is more common in the US and is more closely associated with anal sphincter laceration. The mediolateral approach is more common in Europe and Asia and may be associated with higher rates of perineal pain and dyspareunia. The J incision is a hybrid of the median and mediolateral approaches and is less commonly used. In this study, we use dissection of 42 human cadavers (26 males, 16 females) to study clinical anatomy of the perineum. Our results suggest normal patterns of perineal neuromuscular anatomy underlie common complications of prostatectomy and episiotomy.
Heat Induced by Visible Light Promotes Anti‐Aging Effect in the Skin of Mice
Authors: Monte‐Alto‐Costa Andréa , Santos‐Silva Marco Aurélio , Schanuel Fernanda Seabra , Saguie Bianca , Romana‐Souza Bruna
Published: November 2023

It is well known that the exposition to sun light induces skin aging, recently it was shown that heat induced by infra‐red can also induce skin aging. However, the effects of heat from visible light on skin are not known. The aim of this study was to investigate the effects of heat induced by visible light on mice skin. Mice were divided into two groups exposed at 23°C or 43°C in a thermal chamber for 30 minutes on alternate days for 13 days. On day 14, mice were killed and skin was analyzed. The heat induced by visible light caused an increase in epidermal and dermal thickness. It also increased gene and protein expression of transforming growth factor‐β (Tgfβ1 and TGF‐β1/2/3) and it has not changed the number of inflammatory cells, neutrophils and macrophages. The heat increased the area of collagen fiber, and decreased gene expression of Col1a1 and protein collagen type I. However, heat increased the Col3a1 gene expression and protein type III collagen. Heat increased the area of the elastic fibers and gene expression of fibrillin‐1 and elastin. In conclusion, acute heat exposure induced by visible light may be an extrinsic factor with anti‐aging effects in skin of mice.

Support or Funding Information

This study was supported by FAPERJ, CAPES and CNPq.
The Relationship Between the Facial Vessels and the Deep Fascia of the Infraorbital Region: A New Concept
Authors: Amodeo Chiara Andretto , Chevallier Jean‐Marc , Delmas Vincent , Keller Gregory
Published: November 2023

The Superficial Musculo‐Aponeurotic System (SMAS) has been considered for decades the carrying layer of the facial vessels. Recently the existence of a deep fascial layer in the infraorbital region has been shown and this finding seems to change some classic anatomical concepts related to the facial vessels as well.

Materials and Methods

20 hemifaces have been dissected at the Centre du Don des Corps de l'Université Paris DesCartes in Paris to study the relationship between the facial artery and vein and the deep fascia of the infraorbital region, that continues from the temporal region and covers the mimetic muscles of the infraorbital area.

Results

The vessels were identified in all the specimens and the facial artery was followed from the anterior border of the masseter muscle. In the midface its path was always superficial to the deep fascial layer, in the plane between the SMAS and the deep fascia, on the contrary the facial vein started its path deep to the deep fascia just medial to the medial border of the levetor labii superioris muscle, running in a deeper plane than the artery.

Conclusions

In all the specimens in the midface the facial vessels were in relationship with the expansion of the superficial layer of the deep temporal fascia. The facial artery ran always superficial to it, on the contrary the facial vein in its path toward the lower third of the face ran in a deeper plane than the artery, deep to the deep fascial layer of the infraorbital region.
Using 3D‐Printing to Evaluate Trabecular Bone Mechanical Properties
Authors: Barak Meir M , Black Arielle M
Published: November 2023

Introduction

Trabecular bone structure is essential to the normal mechanical behavior of whole bones. Studies have shown that osteoporosis negatively affects trabecular bone structure, mostly by reducing trabecular number and decreasing the thickness of the remaining trabeculae. The end effect of these phenomena is an increase in fracture risk. A major difficulty in assessing and quantifying the effect of trabecular structural deterioration on the mechanical behavior of whole bones is that no two trabecular structures are identical. Thus, when we compare a group of healthy vs. osteoporotic samples we only get the general trend. 3D‐printing is a new technology that can assist in overcoming this issue. Here we present a preliminary study that compares a healthy 3D‐printed trabecular bone model with the same model after osteoporosis was simulated (i.e. trabecular number and thickness were reduced). Since the osteoporotic model is derived from the healthy one, it is possible for the first time to directly estimate (percentage wise) the decrease of tissue stiffness and strength as a result of trabecular bone structural deterioration.

Methods

A cubical volume of interest (4.5×4.5×4.5 mm) was cropped and segmented from a micro‐CT scan of a chimpanzee's metacarpal head using Amira 6.0. To simulate the onset of osteoporosis (loss of about 10% of bone mass), a second model was created by raising the gray‐scale threshold during segmentation. Next, the “healthy” and “osteoporotic” models were printed in scale (1:1 to real life size) 30 times each, using a 3D‐printer (ProJet 1200). Finally, all samples were tested in compression until failure (Instron 5942) and trabecular bone tissue strength and stiffness was calculated.

Results and discussion

Our results demonstrate that the “osteoporotic” trabecular structure was significantly less strong and stiff than the original intact (healthy) structure (P<0.01). Structural strength decreased by 47%, from an average of 4.13±2.04 MPa to 2.19±0.77 MPa, while structural stiffness decreased by 35% from an average of 71.82±20.30 MPa to 45.36±12.73 MPa. Despite the fact that these 3D models are made of printing resin and not bone, they enable us to compare the exact same trabecular structure before and after the onset of trabecular tissue structural damage. Our results demonstrate that a relatively small decrease in bone volume (about 10% of bone mass) leads to a dramatic decrease in structural strength (47%) and stiffness (35%).

Conclusions

This study demonstrates that 3D‐printing is a valuable tool for estimating the mechanical properties of trabecular structures. In the future, 3D‐printing may help us to attain better personal fracture risk assessments and consequently improve life quality for people suffering from Osteopenia and osteoporosis.

Support or Funding Information

The study was supported by the Winthrop University Research Council Grant (SC15014).