bluuebunny/crossref_metadata_2025 huggingface dataset:
The flavonol quercetin modulates the chemical barrier of innate immunity in endometrium
Authors: Deachapunya Chatsri , Poonyachoti Sutthasinee
Published: June 2021

Epithelial cells lining the uterine cavity provide both physical and chemical barrier to pathogens invading into the body system. Quercetin, the most abundant dietary flavonoid, shows the promotive and protective effects on intestinal tight junction barrier; however, information regarding its effect on chemical barrier function as secretions of fluid and anti‐microbial peptide β‐defensin in endometrium. Therefore, the effects of the flavonoid quercetin on electrolyte secretion and expression and secretion of β‐defensin (BD)‐2 were investigated in immortalized endometrial epithelial cells (PEG). Using Ussing chamber techniques, quercetin (1, 10 and 100 mM) showed the concentration‐dependent increase in Cl‐ secretion. Parallel to the Cl‐ secretion, high concentration of quercetin acutely stimulates BD‐2 secretion. Treatment of filter‐grown PEG cells with quercetin for 48 h was found to increase the synthesis of BD‐2 protein by Western blot analysis. The increased BD‐2 by quercetin was related to the secretion of BD‐2 into the luminal, but not basolateral compartment as assessed by ELISA. Although the significant role of uterine fluid secretion in innate immunity remains to be determined, our results indicate the potential role of quercetin on promotion of chemical barrier against microbial infections in endometrium.
mTOR: a possible Signaling Intermediate in the Leptin‐Kisspeptin Pathway during the Pubertal Transition in Female Rats
Authors: Hall William , Trevathan Taylor , Maze TD
Published: June 2021

While leptin and kisspeptin have both been implicated in the onset of puberty in mammals, the pathway linking leptin and kisspeptin is still not completely understood. Such knowledge could play an important role in treating or preventing infertility, both in humans, for the purpose of child bearing, and in other mammals, for agricultural reasons. Recent studies have suggested that mTOR, a ubiquitous serine/threonine kinase involved in cell and tissue growth and also a target of leptin signaling in the paraventricular and arcuate nuclei of the hypothalamus, may act as a signaling intermediate in the leptin‐kisspeptin pathway. Therefore, increases in mTOR in the hypothalamus may correlate with increases of leptin and kisspeptin in the hypothalamus as well. In this experiment, the gene expression of leptin, kisspeptin, and mTOR were examined using reverse‐transcriptase and polymerase chain reaction (RT‐PCR) from the hypothalami of female rats in ten day intervals beginning on postnatal day‐10 through postnatal day‐60. An increase in mTOR expression at day 40 correlated with increased expression in both leptin and kisspeptin. These findings suggest that mTOR could be involved in the leptin‐kisspeptin pathway and, therefore, the onset of puberty. This research was supported by a Lander University Foundation Grant.
Diminished M Currents Contribute to Hyperactivity of Corticotrophin‐Releasing Hormone Neurons in Acute Stress
Authors: Zhou Jing‐Jing , Gao Yong‐Gang , Kosten Therese A. , Li De‐Pei
Published: June 2021

Corticosterone‐releasing hormone (CRH) neuron in the paraventricular nucleus (PVN) of hypothalamus is the essential component of hypothalamic‐pituitary‐adrenal (HPA) axis in regulating endocrine responses to stress. M‐current, generated through KCNQ2/3 channel, plays a key role in controlling neuronal excitability. In this study, we test a hypothesis that acute stress diminishes M currents to stimulate CRH neurons. The adeno‐associated viral (AAV) vector was microinjected into the PVN prior to acute stress, which carries sequence of green fluorescent protein (GFP) driven by CRH promoter. GFP‐tagged CRH neurons displayed positive immunoreactivity with a specific antibody against CRH. Compared to unstressed rats, acute restraint stress significantly elevated serum corticosterone levels; and the basal firing rate of GFP‐tagged CRH neurons was significantly higher in acute restraint rats. Meanwhile blocking KCNQ2/3 with XE991 induced greater depolarization and firing frequency in GFP‐tagged CRH neurons of unstressed rats, but not stressed rats. Furthermore, M‐currents were markedly decreased in PVN‐CRH neurons in acute restraint rats. Acute restraint stress significantly decreased protein and mRNA expression of KCNQ3, but not KCN2 in PVN. Collectively, our data suggest that diminished M current results in hyperactivity of CRH neuron in acute stress.

This study was supported by NIMH grants MH096086.
Factors Associated with Anastrozole‐Induced Musculoskeletal Adverse Effects in Post‐menopausal Breast Cancer Women: A Preliminary Report
Authors: Abubakar Murtala , Bhavaraju Venkata Murali , Gan Siew
Published: June 2021

Anastrozole (Anas) is one of the drugs of choice in the treatment of estrogen‐receptor (ER) positive post‐menopausal (PM) breast cancer patients. However, Anas‐associated musculoskeletal adverse effects (MAE) (joint pain/stiffness and bone pain) are common and can lead to withdrawal of many patients from treatment. This is a cross‐sectional study of ER PM Women (n=35) with stage I to IV breast cancer receiving Anas. Simple logistic regression analyses were conducted to examine the associations between MAE and tumour grade, progesterone receptor (PR) and human epidermal growth factor (HER2) status, age at menarche, age at menopause and years since menopause, history of contraceptives use and duration of Anas administration. Women with grade I tumours and less than 5 years of menopause tend to have lower odds of MAE [odds ratio (OR) 0.75, confidence interval (CI) 0.08 to 6.71, p =0.797; and OR 0.83, CI 0.09 to 7.68, p =0.87 respectively]. PR and HER2 positive women had a tendency for higher odds of MAE (OR 1.33, CI 0.23 to 7.80, p =0.750 and OR 1.60, CI 0.39 to 6.62, p= 0.517 respectively). Similarly, women with history of contraceptive use and less than 3 years of use of Anas tend to have higher odds of having MAE (OR 1.93, CI 0.43 to 8.61, p = 0.391 and OR 1.13, CI 0.06 to 21.09, p=0.006 respectively). The present study shows that tumour grade, host hormonal environment, duration of Anas treatment and past history of contraceptive use may contribute to the pathophysiology of MAE. However, our findings require further confirmation by using larger sample size and conducting multivariable analyses.
Effects of a Neonatal Immune Challenge on Reproductive Development and Associated Behaviors in Siberian Hamsters (Phodopus sungorus)
Authors: Sylvia Kristyn , Demas Gregory
Published: June 2021

Environmental stressors have the potential to disrupt early development in ways that could adversely impact fitness. Studies have demonstrated that animals exposed to postnatal lipopolysaccharide (LPS) show signs of delayed puberty, such as delayed vaginal opening and first estrus. This study investigated the effects of a neonatal immune challenge on subsequent adult reproductive physiology and behavior, and explored possible mediating mechanisms. Hamsters received LPS or saline injections on postnatal day (pnd) 3 and 5, as there is heightened sensitivity of the GnRH pulse generator at these time points. Female reproductive maturity was determined by monitoring for vaginal patency, beginning on pnd 25 and every five days thereafter until maturity. Male reproductive maturity was determined by using the left testis length and width to estimate testis weight beginning on pnd 25 and each subsequent week until reproductive maturity. At pnd 75 animals were placed in staged mating pairs with reproductively mature individuals of the opposite sex. Rejection, grooming and sniffing behaviors were scored for all females, and the lordosis quotient was calculated for receptive females. Mounting, intromission and ejaculation were scored in males. Preliminary data showed a decrease in food intake and body mass, as well as delay in reproductive maturity for animals treated with LPS. Female receptivity and other reproductive behaviors were varied by the LPS challenge. The results of this study contribute to a greater understanding of the behavioral responses to early immune challenges and possible ways in which animals may adjust to this common stressor.
Conditional Knockout of the Androgen Receptor in Ovarian Theca Cells Reveals Altered Steroidogenesis in Aged Mice
Authors: Chen Yi , Childress Shameka , Andrisse Stanley , Wu Sheng
Published: June 2021

Women with polycystic ovary syndrome (PCOS) exhibit symptoms of hyperandrogenism, oligo/amenorrhea and polycystic ovaries. PCOS is also commonly associated with metabolic syndrome, hyperinsulimia, and insulin resistance in metabolic tissues. It has been reported that elevated androgen levels in women can lead to infertility; however the target organs impacted by the elevated androgen levels are not yet fully known. The aims of the study were to determine the role of androgen signaling in the ovary on the development and reproductive function. Our model system used the cre‐lox system to generate ovarian theca specific androgen receptor knockout (ThARKO) mice. This study examined puberty, cyclicity and fertility in female mice. There was no difference in the age of puberty between control and ThARKO littermates, assessed by the age of vaginal opening and first estrus. Cyclicity and fertility were also studied, and there were no significant differences between control and ThARKO mice. Ovarian gene expression and fertility were compared between 3 months old mice and 8 months old mice. We observed decreased cyp19 (aromatase) mRNA levels in both 3 and 8 moths old groups of the ThARKO compared to control littermates. However, cyp17 (rate limiting enzyme for androgen synthesis) mRNA expression was only significantly reduced (P<0.05) in 8 months old ThARKO mice compared to control littermates. Although fertility was not altered in ThARKO mice, the AR in theca cells may play a role in steroidogenesis of aged mice.
In Vitro Effects of FBS and Ovarian Steroids on Osteoblast Viability
Authors: Brancaglião Lucas , Gonçalves Vítor , Lemos José , Rocha Nícolas , Aquino Renata , Amaral André , Montrezor Luís
Published: June 2021

We evaluated the effects of different concentrations (0, 10‐8 M and 10‐7M) of progesterone (P4), testosterone (T) and estradiol (E2) on the osteoblast viability in vitro. Osteoblast lineages (OSTEO‐1) were cultured in 96‐well plates in DMEM medium a density of 5 x 103 cells/100 μL medium, with or without 10% fetal bovine serum (FBS). Cells were maintained at 37 ºC, with 5% CO2, for up to 48 hours. Cell viability was analyzed by MTT tetrazolium assay. The cells cultured with 10% FBS were more viable than those cultured without FBS. When all hormones were put together, the cell viability was reduced at the 10‐7M concentrations compared with the control and 10‐8 M. The viability of cells cultured without FBS was a) stimulated by E2 (10‐7 M and 10‐8 M (0.1048 ± 0.0227 and 0.1069 ± 0.0124, respectively)) compared with the control group (0.0566 ± 0.008); b) stimulated by P4 (10‐7 M (0.1088 ± 0.0124)) compared with the control group (0.0566 ± 0.008) and 10‐8 M (0.0924 ± 0.022); and c) stimulated by both concentrations of T (10‐7 M (0.0908 ± 0.0153) and 10‐8 M (0.0924 ± 0.0022)) compared with the control group (0.0566 ± 0.008). Our results demonstrated that FBS stimulated osteoblast viability, and P4 (10‐7 M), and both concentrations of T and E2 stimulated the viability of the cells cultured without FBS, suggesting that these steroid hormones may be important at the onset of osteoblast cells viability in vitro for up to 48 hours.
Investigating the Adaptive Role of Brain Mitochondria in a Mammalian Hibernator
Authors: Ballinger Mallory , Schwartz Christine , Bjork James , Andrews Matthew
Published: June 2021

During the hibernation season, thirteen‐lined ground squirrels (Ictidomys tridecemlineatus) regularly cycle between bouts of torpor and interbout arousal (IBA). This presents a unique seasonal change in energy requirements in the brain. Most of the brain is electrically quiescent during torpor, but regains activity upon arousal to IBA, resulting in extreme oscillations in energy demand during the hibernation season. We predicted that brain mitochondria undergo a seasonal change in function to accommodate the variable energy demands of hibernation. To address this hypothesis, we examined mitochondrial bioenergetics of brain in thirteen‐lined ground squirrels across four time points: Summer (SU), Fall (FA), Hibernation (HIB) and Spring (SP). Respiration rates of isolated brain mitochondria were measured using an oxygen electrode with three substrates: Glutamate/Malate, Succinate, and Glycerol‐3‐Phosphate. Membrane potential (mV) and proton leak were measured simultaneously using a TPP+ electrode. Glutamate/Malate‐fueled respiration was significantly higher in HIB than in both SU and FA (p<0.05). Succinate‐fueled respiration was significantly lower (p<0.05) in SP and SU than in HIB. We found no significant difference in mV between SP, SU and FA. These data imply that brain mitochondrial bioenergetics are not static across the year, and suggest that the brain requires more fuel and resources to function efficiently during hibernation. This study provides essential underpinnings to understanding the overall energy requirements of a hibernator's brain and provides clues to into the neuroprotective strategies employed by a mammalian hibernator.
Continuing Medical Education Learning Module for the Primary Care and Emergency Medicine Physicians: Musculoskeletal Assessment of the Knee and Shoulder Joints
Authors: Hines Kelsey , Aagaard Eva
Published: June 2021

Primary care physicians (PCPs) are often responsible for evaluating, treating and further referring musculoskeletal (MSK) disorders and injuries. The objective of this learning module is to provide PCP and Emergency Medicine physicians with an online training resource regarding the assessment and treatment of common and important knee and shoulder injuries. A web‐based survey was sent to general internal medicine, family medicine and emergency medicine physicians via email. A total of 66 responses were received. Results revealed that 32‐50% of the physicians felt ‘not at all confident’ or 'somewhat confident’ in evaluating, treating and referring a variety of knee and shoulder disorders and injuries. The physicians' responses revealed they were the least confident in evaluating meniscal tears, patellofemoral pain, adhesive capsulitis and shoulder impingement. Additionally there is an overall interest in a learning module addressing these conditions. This needs assessment will provide information to drive the development of an online training module to supplement providers' current level of training, and increase confidence in approaching MSK disorders and injuries.
Cadavers as Educators: an Innovative Approach to Health Behavior and Preventable Disease Education
Authors: Stauder Erich , Swartz Jessa , Stevens Sam , Huerta Miguel , Hoagland Todd
Published: June 2021

Objective

Cadavers as Educators maximizes body donors' educational potential by using medical students (MS) to teach a hands‐on curriculum that increases high school students (HSS) understanding of preventable chronic disease and health behaviors, and provides health careers information.

Methods

After a MCW tour and intro to the anatomy lab, groups of 3 HSS rotate through thorax, abdomen, extremities and brain curriculum stations staffed by MS. Then, a multidisciplinary panel addresses HSS questions about health careers. Pre‐ and post‐tests are used for curriculum evaluation. HSS complete a confidential survey of their experience using open‐ended questions. A qualitative analysis of the HSS responses using standard methodology identifies themes. MS complete a survey about their experience, and chaperones of the HSS evaluate MS as teachers for internal validity.

Results

Short term outcomes for HSS included “better understanding” (69%) and “very positive experience” (63%), long term outcomes included “influence future/career” (44%), “influenced health perception/choices” (50%) and “shared learning with others” (84%), and pre and post tests indicated curriculum increased anatomical and health behavior knowledge. MS teaching skills were improved and anatomical knowledge was reinforced.

Conclusions

This novel program optimizes educational value of body donors. It influenced health behavior perceptions and encouraged HSS to share knowledge, and may impact health professions recruitment. Educational impact of body donors on MS is seen through enhancing teaching skills and solidifying anatomical knowledge. Future studies will include health behavior impact and will include rural and urban HSS.
Website www.cadavereducators.org
Effects of Dissection Experience on Student Application to Allied Health Programs
Authors: Carroll Melissa
Published: June 2021

This pilot study set out to investigate influential factors for students during their application to an entry‐level allied health training program. Specific factors of interest were prior exposure to dissection materials. Research shows that allied health students perceive the dissection process as valuable, however student evaluation of the required anatomical coursework during the application process has never been examined. A total of 160 questionnaires were received, and 113 valid responses gave an overall response rate of 71%. One hundred percent (N=113) of the respondents had just completed the application and enrollment process or were a few semesters removed ‐ 31.9% from the recently accepted entering cohort (RAE), and 68.1% from the first year cohort (Y1). The majority of the respondents (n=101, 89.4%) had at least one prior dissection experience, most (n=57, 50.4%) having just one. Most respondents had previous experience with fetal pig dissections (n=64, 56.6%), and only 4.9% (n=5) had prior exposure to a cadaver. When looking at respondent's prior experience dissecting fetal pigs and the influence of a required human gross anatomy course there was a significant association (Χ2 (1) = 7.24, p<0.01). Further analysis revealed that this association was particularly significant (p<0.001) in the Y1 group. For respondents that indicated human gross anatomy was influential to their decision to apply 68.4% also indicated the presence and required participation in cadaver lab was influential. Results indicate that prior dissection experience, specifically fetal pig dissection, produces a positive perception of the human anatomy required in a graduate curriculum. This could indicate that certain prerequisite coursework benefits the overall perception of anatomy in graduate training.
A Comparative Assessment of Hard Palate Thickness using Micro‐CT and Gross Cadaveric Measurements: Implications for the Safe Placement of Orthodontic Miniscrews
Authors: Phillips Jillian , Bourassa Carine , Almadhoun Heba , Hosein Yara , Johnson Marjorie , Willmore Katherine , Tassi Ali , Galil Khadry
Published: June 2021

The hard palate is a preferred area for orthodontic miniscrew (OMS) insertion due to easy surgical access and favorable anatomical configuration. However, accurate measurement of palatal bone thickness (BT) is crucial for choosing appropriate OMS lengths and insertion sites. The aim of this study is to determine the accuracy of micro‐computed tomography (micro‐CT) for assessing palatal BT, and to establish which sites commonly provide adequate BT for safe OMS placement.

Ten cadaveric hard palates (52‐98 years) were cleaned of soft tissue and imaged using micro‐CT. Bone thickness was measured from sagittal micro‐CT image slices at pre‐determined sites beginning 3mm posterior to the incisive foramen and 4mm lateral to the midpalatal suture. Micro‐CT analysis was carried out using MicroView Image Viewer and Analysis tool. The same sites on each palate will also be measured from sagittal sections using digital caliper.

Initial micro‐CT results indicate that palatal bone thickness is heterogeneous. The palate thins from anterior to posterior and also medio‐laterally when comparing sites 4 mm vs. 8mm adjacent to the midline. It is expected that similar results will also be observed from caliper measurements of palatal bone thickness. Early findings suggest that BT is favorable for OMS insertion in the anterior palate and that the posterior palate should be avoided.
The Clinical Significance of Nasal Index in Ethno‐Racial Specific Rhinoplasty
Authors: Otobo Tarimobo , Tarimobo‐Otobo Rugina
Published: June 2021

Congruency of the nasal septum to the philtrum, the height and width of the nose bears great significance in nasal reconstruction. Therefore establishing base line nasal parameters for specific race and ethnicity has become valuable in rhinoplasty. Nasal length, nasal heights are among the most important cephalometric measurement which are also useful in forensic medicine, clinical diagnosis and treatment plan.

Five hundred (500) well body volunteer subjects (218 males and 282 females) of urhobo extract of southern Nigeria were the subjects for this study. The nasal length and nasal height of each subject was measured using standard methods and the nasal index calculated as the percentage ratio of the nasal width to the nasal height. Male Urhobo subjects have significantly higher nasal dimensions than the female Urhobo subjects (P<0.05). There was also the prevalence of platyrrhirine nose type among the Urhobo's. This peculiarity has further buttress the poor aesthetic post‐surgical outcome of nasal reconstruction when racial specific nasal index is not applied.

Therefore this study has provided standard base line nasal parameters for reference when nasal surgical reconstruction is envisaged within the study population.
Bilateral Duplication of the Foramen Spinosum: Implications for the Surgical Management of Neurofibromatosis Type II and Intracranial Aneurysms
Authors: Laslo Jillian , Cyrus Leah , Zdilla Matthew
Published: June 2021

The foramen spinosum (FS) is located within the middle cranial fossa of the sphenoid bone. The FS has been observed to transmit the middle meningeal artery (MMA). Unilateral duplication of the FS has been reported to occur in between 0% and 6% of human crania. This report documents a rare occurrence of an asymmetrical bilateral duplication of the FS in a male cranium. Neurofibromatosis type II and intracranial aneurysms often require bilateral surgeries involving the FS and MMA; therefore, the asymmetrical bilateral duplication of the FS may be disorienting to the surgeon. Knowledge of the bilateral duplication of the FS may prevent adverse surgical events, including intracranial hemorrhage. Research was supported by funding from the WV Research Challenge Fund [HEPC.dsr.14.13].
Adipocytic Templating of Bone Matrix Deposition in Osteoarthropathies
Authors: Taylor Adam , Platt Chris , Wilson Peter , Ranganath Lakshminarayan , Gallagher James , Boyde Alan
Published: June 2021

Alkaptonuria (AKU), the first human disorder recognised to conform to Mendelian inheritance, is accompanied by early onset, rapidly progressing osteoarthropathy. Novel anatomical and microanatomical structures found in AKU in joint tissues have subsequently been seen in other human arthropathy samples. One type of trabecular excrescence shows a close relationship with adipocytes, incongruent with typical views of osteoblastic bone formation.

Joint samples, obtained with ethical approval were fixed and prepared routinely for histological, immunohistochemical and ultrastructural examination.

Histology and ultrastructural analysis of such excrescences show their scalloped surfaces to be continuous with marrow adipocytes fitting the contours of the bone surface. Immunohistochemistry shows excrescences and their marrow surfaces to contain collagen VI, an ECM protein produced by adipocytes but not seen in mature bone matrix.

These results demonstrate a variety of bone matrix deposition templated and modulated by adipocytes. The data provide strong support for the view that adipocytes rather than inactive osteoblasts are de facto lining cells on some bone surfaces
Thyroid Hormone Receptor Regulation of Tooth Development in Newts
Authors: Miwa Yoko , Sunohara Masataka , Sato Iwao
Published: June 2021

Objective

Thyroid hormone receptor and thyroid hormone are contribute to the development of the teeth and the regeneration of alveolar bone following amputation in newts. However, the relationship between the mRNA transcript levels of thyroid hormone receptor in alveolar bone is unknown in blocking the effect of thyroid hormone.

Method: Propylthiouracil (PTU) is a thiouracil‐derived drug used to blocking the effect of thyroid hormone. Japanese newts (Cynops pyrrhogaster) were maintained in aqueous solutions with or without PTU for one month and tracked the sequential development of the tooth cap, the tooth bud, and ultimately the maturation of the sequential tooth germ. Fifty days after the amputation procedure of the right mandible alveolar bone, the newts were observed the effect of PTU by the expression levels of mRNA of thyroid hormone receptor detected in‐situ hybridization and real time RT‐PCR.

Result: The amputated mandible sites were observed microscopically. The level of mineralized area of alveolar bone in amputation with PTU treatment was significantly smaller than that in the amputation in blocking the effect of thyroid hormone. The expression levels of mRNA of thyroid hormone receptor was significantly increased in regenerated area of alveolar bone by real time RT‐PCR(Student's t‐test, p<0.001).

Conclusion

Our data suggests that thyroid horme may affect the tooth germ development and the regeneration of alveolar bone in newts.
A Histological Examination of the Ovarian Ganglia and Prehypogastric Ganglion of the Aortic Plexus in Females
Authors: Beveridge Tyler , Johnson Marjorie , Power Adam , Power Nicholas , Allman Brian
Published: June 2021

The aortic plexus is a symmetrically organized network of sympathetic nerves positioned along the infrarenal abdominal aorta. Recently, we characterized the aortic plexus and its ganglia (inferior mesenteric, left/right spermatic, and prehypogastric ganglion) in males; however, the literature minimally describes its anatomy in females. In the present study, we conducted the first histological examination of the left/right ovarian ganglia, and investigated whether females, like males, exhibit a prehypogastric ganglion. The ganglia were dissected from embalmed (n=4) and fresh (n=1) human cadavers, and H&E staining confirmed that all ganglia contained neuronal cell bodies. Comparable to the topographic arrangement in males, our preliminary results show that the left/right ovarian ganglia are positioned in close relation to their respective ovarian artery, whereas the prehypogastric ganglion was positioned within the right cord of the aortic plexus, inferior to the right ovarian ganglion in all specimens. Moreover, using immunohistochemistry, we found that all three constituent ganglia from the fresh cadaver stained positively for tyrosine hydroxylase, thereby confirming their sympathetic nature. Having provided the first topographical and histological characterization of the ovarian and prehypogastric ganglia in females, our future studies will seek to determine their specific function.
Innervation of the Psoas Major Muscle
Authors: Sanders Luke , Guan Jian , Morton David , Mahan Mark
Published: June 2021

The specific innervation of the psoas major muscle (PMM) fluctuates among anatomy reference materials. Descriptions include a variety of arrangements of the L1‐L5 ventral rami, which is expected from a muscle possessing multiple segmental attachments. However, this lack of specificity may result in denervation of the PMM during a transpsoas surgical approach to the lumbar vertebrae. In order to better understand the PMM's segmental innervation we examined 30 embalmed cadavers and documented the segmental innervation of the psoas major muscle from the ventral rami of lumbar 1 through 5. The largest branch from the ventral rami arose from L3 in the majority of cadavers. The femoral nerve provided one branch to the psoas in the majority of cases, providing an additional branch from lumbar 3 and 4. The branches to the psoas passed obliquely through the muscle in an anterolateral direction, and crossed the intervertebral disk in all specimens. Knowledge of the branch pattern and spinal levels supplying the psoas major may aid surgeons prevent denervation of the psoas during transpsoas approaches to the lumbar spine.
Landmarks of the Glossopharyngeal Nerve for Head and Neck Surgeries
Authors: Morrill Seth , Mehta Vikas , Cosetti Maura , Glover Mitzi
Published: June 2021

Although the general course of the glossopharyngeal nerve has been established for many years, this nerve is often damaged during head and neck surgeries. Individuals suffering from damage to the glossopharyngeal nerve (GPN) will experience significant oropharyngeal dysphagia (difficulty swallowing) and partial loss of taste. One survey suggests that as many as 75% of cancer patients suffer from symptoms of dysphagia following head and neck surgery. The objective of this study was to create a logistical map of reliable bony landmarks in relationship to the GPN to enable surgeons to better predict the location of this ‘hidden’ nerve and avoid inadvertent damage. Measurements of the GPN in relation to bony landmarks and measurements along the nerve path itself were recorded from cadaveric dissections done through various common surgical approaches which involve the GPN: transcervical, transoral and transmastoid. Additionally, nerve variations, sex differences, and side of the body (right vs. left) differences were noted and assessed for significance. Data collected were used to produce a predictive map of the path and location of the GPN. The map produced in this study should provide a useful tool in head and neck surgeries to prevent oropharyngeal dysphagia associated with GPN damage.
Unexpected cone position in 6‐hydroxydopamine‐treated dark‐adapted goldfish retina
Authors: Thapa Sophie , Baldridge William
Published: June 2021

Dopamine (DA) is an important modulator of light‐adaptation in the vertebrate retina. A known source of DA in the retina is amacrine or interplexiform cells, but another potential source is the retinal pigmented epithelium (RPE). The neurotoxin 6‐hydroxydopamine (6‐OHDA) has been used extensively to ablate DAergic retinal neurons and could be used to distinguish between neuronal and RPE sources of DA. We have, therefore, examined first the impact of 6‐OHDA on light‐induced cone contraction, a phenomenon mediated by D2 DA receptors. Under MS‐222 anesthesia, adult goldfish (C. auratus) received two 50 μg intraocular injections of 6‐OHDA on consecutive days. After 10 days, control (uninjected) or 6‐OHDA‐treated fish were placed in the light (>100 lux) or in complete darkness for 1 hr and then sacrificed, eyes removed and fixed in glutaraldehyde. Retinas were then isolated, cones labeled with anti‐zrp1 (ZIRC, Eugene, OR) and cone length determined from confocal z‐stack reconstruction. In control light‐adapted retinas, cones were contracted, with a length of 55 ± 3 µm (mean ± SD), compared to cones from dark‐adapted retinas (115 ± 7 µm). In light‐adapted retinas, treated with 6‐OHDA, cones were contracted (55 ± 1 µm) but in dark‐adapted 6‐OHDA‐treated retinas cones were partially contracted (82 ± 5 µm). A previous study reported similar results and suggested that the partially contracted cone position in dark‐adapted 6‐OHDA‐treated retina indicated a role for DA in dark‐adaptation. Another possibility is that DAergic neurons damaged, but not destroyed by 6‐OHDA, have increased tonic DA release. To investigate this further, we are currently determining to what extent cone position in 6‐OHDA‐treated retinas is affected by treatment with D2 DA receptor agonists and antagonists. Funded by the NSERC.
Plasma Autoantibodies from Human Diabetic Depression Patients Inhibit Neuritogenesis and Induce Depression‐Like Behavior in Mice
Authors: Behnke Joseph , Alder Janet , Thakker‐Varia Smita , Zimering Mark
Published: June 2021

Type 2 diabetes mellitus (DM) substantially increases susceptibility to the affective mood disorder depression. However, the underlying mechanism for this association is unclear. Previous studies demonstrated significant associations between autoantibodies (AB) that inhibit neuronal and endothelial function and specific diabetic microvascular complications. In the current study, we tested the hypothesis that diabetic depression AB affect hippocampal neuritogenesis and induce a depression‐like phenotype in mice. Diabetic depression AB significantly inhibited bFGF‐stimulated PC12 cell process outgrowth (n=12; P<0.001), and hippocampal culture neuritogenesis (n=4; P<0.01) compared to diabetic, no depression AB (n=20) or no AB (n=2), respectively. Diabetic depression AB‐mediated inhibition of hippocampal neuritogenesis was significantly (P<0.01) prevented by Y27632, a selective Rho kinase inhibitor (10 µM). Mice (n=16 in each subgroup) given a single intracerebroventricular infusion of diabetic depression plasma AB (4 µg/mL) isolated from two different patients exhibited a depressive‐like behavioral phenotype, as indicated by a reduced preference for sucrose (P<0.027) compared to mice administered AB (4 ug/mL) from two non‐depressed diabetic patients. These data suggest a possible causal role for autoantibodies which can inhibit hippocampal neuritogenesis in depression in older adult type 2 DM.
Satiety and Reward: Dichotomy of Cocaine‐ and Amphetamine‐Regulated Transcript Peptide's Function During Binge Eating
Authors: Bharne Ashish , Borkar Chandrashekhar , Subhedar Nishikant , Kokare Dadasaheb
Published: June 2021

Since cocaine‐ and amphetamine‐regulated transcript peptide (CART) mediates feeding as well as reward, we investigated its role in binge eating (BE), a clinical condition which disrupts satiety. BE was induced in rats by providing 2‐h access to high fat‐sweet palatable diet (HFSPD) on alternate days for 4 weeks. Effect of drug treatments on HFSPD intake and CART immunoreactive profile in reward and satiety regulating nuclei was studied. Rats fed on HFSPDshowed explosive BE. Higher doses of CART or rimonabant was required to reduce BE, as compared to that of normal chow intake in naïve rats. At the mid‐point during BE, CART immunoreactivity was significantly up‐regulated in the arcuate (ARC), lateral (LH) nucleus, paraventricular nucleus of thalamus (PVT), and nucleus accumbens shell (AcbSh) but not in the paraventricular (PVN) nucleus. At mid‐binge time‐point, the rimonabant treated rats showed increased CART expression in ARC and LH, while that in PVT and AcbSh was decreased. Increase in co‐expression of CART and synaptophysin in LH and cornu ammonis 1 of hippocampus suggested neuroplastic changes in CART system in BE rats. We suggests that BE enhanced the CARTergic signaling in the ARC/LH‐PVT‐AcbSh axis and suppressed the ARC‐PVN pathway. The net result may be the reward pathway overriding the satiety circuit. Opposite may happen following treatment with rimonabant. Further, CART seems to participate in the memory formation pertaining to HFSPD‐related reward.
Diabetes Impairs Visual Function and Reduces Cytoprotective Nrf2 Protein Content in Retinas of Rats
Authors: Nasralah Zeinab , Barber Alistair
Published: June 2021

Purpose

To determine the effect of diabetes and metabolic stress on retinal nuclear factor E2‐related factor‐2 (Nrf2) protein content after light and dark adaptation, and its effect on vision in rats. Darkness was used as a stressor because the retina is more metabolically active in the dark.

Methods

Long‐Evans and Sprague‐Dawley rats were made diabetic by streptozotocin (STZ) injection and compared to age‐matched controls (CNT). One group of STZ and CNT rats was sacrificed in light‐adapted conditions; the second group was sacrificed after 24 hr dark adaptation. Retinal Nrf2 protein was determined by immunoblot after 6 and 10 weeks of STZ‐diabetes. Behavioral optokinetic testing was used to measure visual function (spatial frequency threshold and contrast sensitivity) after 6 and 10 weeks of diabetes. Statistical analysis was by ANOVA and Newman‐Keuls test.

Results

There was significantly less Nrf2 after 6 weeks of STZ‐diabetes (p<0.05), and visual function was also significantly reduced after 6 and 10 weeks of STZ‐diabetes compared to CNT (p<0.05).

Conclusion

Diabetes impairs visual function in rats and reduces retinal Nrf2 protein content under metabolic stress.
Panax notoginseng and Ginsenoside‐Rg1 contribute to down‐regulation of P‐glycoprotein level after the cerebral ischemia/reperfusion in rats
Authors: Yang Li , Li Jie , Wang Xiaojuan , Yu Jianyun , Chen Bo , Guo Zeyun
Published: June 2021

The blood‐brain barrier possesses active transporters carrying brain‐permeable xenobiotics, including many kinds of medicine, back into the blood against injuries. P‐glycoprotein(P‐gp), one kind of important multidrug resistance transporter, is upregulated on capillary endothelium after cerebral ischemia, which may refer as to protect the brain from the poison but may result in the treatment failure of the stroke. Panax notoginseng, a traditional Chinese medicine, has been used for thousands of years to treat ischemic patients. Panax notoginsenoside (PNS) is primarily composed of ginsenosides. Ginsenoside ‐Rg1 is an important part of saponin components in PNS. As such, here we aimed to study the role of PNS and ginsenosides Rg1 against overexpression of P‐glycoprotein in experiment induced cerebral ischemia–reperfusion (I/R) adult in rats. Male SD rats were randomly divided into sham‐injured, vehicle, PNS or Rg1 groups. The expression of P‐gp in cortex, hippocampus, striatum were detected by Imunohisochemistry, Western blot and RT‐PCR. The results show that PNS or Rg1 signiﬁcantly reduced P‐gp in cortex and striatum infarction area caused by cerebral I/R. The increased expressions of P‐gp caused by cerebral I/R were restored with PNS treatment groups, as well as in Rg1 treatment groups. These results suggest that PNS and Rg1 have similar roles in adjusting overexpression of P‐gp from ischemic/reperfusion damage. PNS could be considered as an inhibitor of P‐gp in brain injuries therapy strategy for use in the case of cerebral ischemic stroke.
The Effect of Noise Exposure on Inhibitory Neurotransmission in the Auditory, Visual and Multisensory Cortices in Rats
Authors: Fitzpatrick Sarah , Sirek Paul , Schormans Ashley , Rajakumar Raj , Allman Brian
Published: June 2021

It is well‐established that high‐intensity noise exposure can induce structural and physiological changes in the primary auditory cortex, such as impaired GABA neurotransmission which leads to a reduced level of GABA‐synthesizing enzymes (i.e., GAD65/67). At present, however, it remains unknown how partial hearing loss affects GABA neurotransmission in areas of the cortex that process sound as well as other sensory modalities (e.g., visual stimuli). In the present study, we are using a rat model to investigate our working hypothesis that noise‐induced hearing loss causes a differential effect on GAD67 levels in the various cortical areas capable of sound processing, such that the multisensory cortex will not show the same dramatic reduction as in the primary auditory cortex. Adult male rats were exposed to loud noise (0.8‐20 kHz at 120 dB SPL for 2h), which caused a 27 ± 9 dB elevation of their hearing threshold 14 days following the noise exposure. Using immunohistochemistry, the level of GAD67 was compared between noise‐exposed rats and age‐matched controls in multiple auditory, visual and multisensory cortical areas. Consistent with our hypothesis, preliminary findings suggest that the multisensory cortex does not experience the same degree of impaired GABA neurotransmission as the primary auditory cortex following noise‐induced hearing loss.
Using an Optical Clearing Technique for Visualizing the Midbrain Cholinergic System in Mice
Authors: De Santis‐Smith Alexandria , Conciatori Tristan , Allman Brian , Rogers Kem , Schmid Susanne
Published: June 2021

The 3D visualization of the midbrain cholinergic system is key for understanding its function and its relationship with other brain areas. In preliminary experiments, our lab used an optical clearing technique, CLARITY, along with confocal microscopy, to image cholinergic cells and projections in up to 4 mm thick brain slices. Brains from transgenic mice expressing YFP under the choline aceteyltransferase 1 (CHaT1) promotor were harvested and sliced into coronal sections of different thicknesses. The samples were then embedded into a hydrogel monomer solution for 3 hours and left to incubate at 37°C. Afterwards, the tissue samples were left in a clearing solution for lipid membrane removal and left to incubate at 37 °C between 19 to 44 days.When qualitatively studied, passive CLARITY was found to effectively clear coronal sections of 1, 2, 3 and 4 mm thick after 19, 26, 35 and 44 days of incubation, respectively. Confocal microscopy confirmed sufficient expression of YFP to visualize thin axons and single axon terminals of cholinergic neurons within the rostral regions of the mouse brain. Based on our preliminary results, our ultimate goal is to construct a 3D visualization of the entire midbrain cholinergic system and its projections in the mouse brain.
Technical approach for visualization of the arterial and venous brain vasculature
Authors: Tonnelet Romain , Perez Manuela , Krebs Marine , Arnoux Jean‐Michel , Labrousse Marc , Braun Marc
Published: June 2021

Introduction

We present an original method for post‐mortem study of macro‐ and micro‐vascular of the arterial et venous bed of the brain based on 3D angiographic acquisition and micro‐radiography.

Material & Method

Six brains were used for this study collecting by the Anatomy Laboratory of Université de Lorraine.

For arterial preparation, removal of the brain was carried out at early stage. No formalin solution was used before injection, the latter being performed as soon as the brain was removed and injected with a mixture gelatin‐barium.Injections were made using soft tipped rubber trocars introduced in the two carotids and vertebrals arteries. The same protocol were used for the venous preparation, but the two internal jugular veins were cathterized and injected.

Angiographic acquisition were done on C‐arm Flat‐Panel for each specimens (isotropic resolution ‹ 200 microns). Then brains were fixed for two months in a 4% Formaldehyde solution. They were sliced in sagittal or frontal plane. Finally micro‐radiographs were done on each sections by use of a Mammograph (pixel resolution ∼ 85 microns).

Results

We obtained 3D volumic acquisition of the whole brain , and macro‐vascular pattern was studied on a Advantage Workstation for multiplanar and 3D‐Volume‐Rendering visualization.

Micro‐radiographics acquisition showed us the micro‐vascular pattern, especially the transcerebral arteries or veins in cortico‐sub‐corticals and periventricular areas.

Conclusion

We used the same technique as described by Salamon and Theron for study of the brain vasculature by used of modern radiographics materials allowing a sub‐millimetric visualization of brain vessels.
Investigation of the Role of CD4+ T cells and Interleukin‐10 in Immune‐Mediated Neuroprotection
Authors: Olmstead Deborah , Sanders Virginia , Jones Kathryn
Published: June 2021

Previous studies demonstrate that immunodeficient mice suffer significantly more motoneuron (MN) loss after facial nerve axotomy (FNA), and CD4+ T cells and interleukin‐10 (IL‐10) are the key mediators for MN survival. The objective of this study is to investigate the role of CD4+ T cells and IL‐10 in immune‐mediated neuroprotection. Our hypothesis is that the CD4+ T cells protect MN survival by regulating glial activation via microglia‐derived IL‐10.

To study the role of CD4+ T cells, WT, immunodeficient RAG‐2 KO, and CD4+ T cell‐reconstituted RAG‐2 KO mice received a FNA, and qPCR analysis of the facial motor nucleus was conducted to compare gene expression profiles. Preliminary findings reveal that a robust MN regeneration response is present in all 3 groups. However, there is significant dysregulation in the glial response to FNA in the RAG‐2 KO mice compared to the WT and CD4+ reconstituted mice. These data suggest that CD4+ T cells regulate the glial response to injured MN, and this factor likely contributes to MN survival.

To study the the role of IL‐10, mice expressing an IL‐10/GFP hybrid protein received a FNA, and immunohistochemistry was performed to identify colocalization of the IL‐10/GFP with microglia or astrocytes. The results demonstrate that microglia are the cellular source of IL‐10. In situ hybridization and qPCR of IL‐10 mRNA expression will also be performed. In summary, the current working hypothesis is that CD4+ T cells induce IL‐10 production in microglia which, in turn, regulates glial activation and creates an anti‐inflammatory environment that promotes MN survival after injury.
Improved functional recovery following spinal cord compression in rats treated with losartan is associated with reduced T cell influx into the injury site
Authors: Jones T Bucky , Robbins Emily , Hanyu‐Deutmeyer Aaron , Jones Carleton
Published: June 2021

Inhibition of the renin‐angiotensin system (RAS) is neuroprotective in a variety of CNS disorders, including Parkinson disease, Alzheimer disease and stroke. One proposed mechanism for protective effects of RAS inhibition is modulation of inflammation. Post‐injury inflammation has been implicated in degenerative cascades initiated by mechanical trauma to the spinal cord, thus we sought to determine whether a similar protective effect of RAS inhibition would occur following spinal cord injury (SCI). Rats were treated with losartan or vehicle (i.p., sid), beginning one day after lateral compression SCI. Functional recovery was assessed using a standardized scale. Rats were sacrificed at 7, 14 or 28 days post injury (dpi) and the tissues processed for PCR or immunohistochemical analyses. We show that rats treated with losartan have improved functional recovery compared to vehicle‐treated rats, beginning at 5 dpi. Quantitative PCR revealed that treatment with losartan decreased the intraspinal expression of CCL5, a chemokine that promotes T cell infiltration into tissues. Decreased expression of CCL5 was associated with a significant decrease in the number of T cells within the injury site at 7 dpi and maintained to 28 dpi. Collectively, these data suggest that beneficial effects of RAS inhibition in this spinal cord injury model may be due to a reduction in the T cell response within the injury site.

This study was supported by MWU Office of Research and Sponsored Programs (E.R., A.H‐D.), MWU College of Health Sciences (CBJ), and Arizona College of Osteopathic Medicine (TBJ).
Human PrimPol: A Novel Mechanism of Antiviral Toxicity
Authors: Mislak Andrea , Anderson Karen
Published: June 2021

Although significant advances in treating the nearly one million Americans infected with HIV‐1 have been achieved with the use of antiviral nucleoside reverse transcriptase inhibitors (NRTIs), NRTI‐associated mitochondrial toxicities and side effects pose serious risks of non‐HIV related morbidity and challenge patient adherence to the daily drug regimens necessary to maintain reduced viral loads and prevent viral transmission. Prominent NRTI‐associated toxicities arise from viral versus host polymerase selectivity, wherein NRTIs not only function to halt viral replication by chain termination for reverse transcriptase (RT) but can also serve as substrates for host polymerases and result in severe mitochondrial dysfunction. The recent discovery of a novel human primase‐polymerase, PrimPol, operating in the mitochondria suggests a novel mechanism of antiviral toxicity that has yet to be explored. Biochemical experiments have been conducted to investigate mechanisms of PrimPol's catalytic activities and evaluate its potential as a mechanism of mitochondrial NRTI‐associated toxicity. As there is no cure for HIV‐1 infection, the life‐long administration of NRTIs is necessary and addressing the mechanisms of toxicity is critical to the effective care of HIV‐1 infected patients.