bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiple changes in teaching procedures increase student engagement and success in gross anatomy during revision of a medical curriculum
Authors: Davies David Lewis , Akhter Noor , Benes Helen , Daniel Joseph C. , Garrett Judith E. , Hayes Helen R. , Kandavalli Naveen B. , Newton Bruce W. , Phelan Kevin D. , Syed Mohsin M. , Watson LaShundra N.
Published: June 2021

To improve medical education and student performance, our institution is revamping its preclinical curriculum in two phases. The aim of the first phase is to increase active‐learning strategies and lessen contact hours; followed by a second phase during which discipline‐based courses will evolve into system‐based modules. Here we report the impact of changes in teaching procedures made in a gross anatomy course during the first transitional phase when contact hours were reduced by 25%. Multiple steps were taken to meet curricular goals and still increase student engagement, performance and morale. These included: a) reducing lecture time by 35% and organizing lectures on clinical themes, b) cutting scheduled lab time by 20%, c) increasing dissection team size, d) adding access to a whole body prosection, e) dedicating a lab area for the study of anatomical models and previously dissected regional specimens, f) starting a dissection inspection program, g) issuing team worksheets to document dissection findings and assess preparedness, h) incorporating aspects of team‐based instruction to reinforce or replace lectures, i) holding structured weekly lab reviews. Qualitative faculty assessment indicates that lecture and laboratory participation and performance on intramural examinations are improved, and morale is better.

Supported by: UAMS Dept. of Neurobiology and Developmental Sciences.
Translation attenuation via 3′ terminal codon usage in bovine csn1s2 is responsible for the difference in αs2‐ and β‐casein profile in milk
Authors: Kim Julie J , Yu Jaeju , Bakovic Marica , Cant John P
Published: June 2021

αs2‐casein mRNA (csn1s2) is translated at 25% of the efficiency of β‐casein transcripts (csn2); however, the molecular mechanisms governing the difference are unknown. The main objective of this study was to identify molecular mechanisms that explain differential translational regulation between bovine β‐ and αs2‐ casein by assessing the role of putative translational regulatory factors in both cellular and cell‐free translation systems. Sequence analysis indicated that the two transcripts share similar primary and secondary structures around the coding region. Deleting and exchanging untranslated regions (UTRs) on the transcripts suggested that the 3′ UTR of csn2 and the 5′ UTR of csn1s2 exert stimulatory effects on translation yet their effectiveness depends on the upstream and downstream sequences with which they are associated. A stronger effect on translational efficiency was found in the coding region of csn1s2 which displays unfavourable codons at the 3′ terminus. Deletion of a 28‐codon fragment from the 3′ terminus of the csn1s2 coding region increased translation to a par with csn2. We conclude that the last 28 codons of csn1s2 is the main regulatory element that attenuates its expression and is responsible for the different translational expression of β‐ and αs2‐ casein mRNA.

This research was supported by NSERC Canada.
Response to short‐term folic acid intake in relation to the body composition of women of reproductive age
Authors: Anderson Alex Kojo , da Silva Vanessa R , Lewis Richard D , Rathbun Stephen , Hausman Dorothy B , Bailey Lynn B
Published: June 2021

Epidemiological studies have reported maternal obesity and folic acid status in early pregnancy as risk factors for neural tube defects in the offspring, but the current RDA for folic acid for women of childbearing age is 400 mcg irrespective of weight or adiposity. The aim of this study was to investigate the relationship between adiposity (%BF) and the short‐term pharmacokinetic response to an oral dose of folic acid in women of childbearing age. Thirty‐two healthy Caucasian females (mean age 25.78±5.02 yrs) were administered 400 mcg of folic acid orally after an overnight fast, blood samples were collected for 10 hours post dose to measure serum folate. Participant body composition was assessed using the BOD POD and subsequent analysis was performed according to %BF (normal < 32%, n=12; high ≥ 32% n=20). There was significant difference between %BF and baseline red blood cell (RBC) folate (p=0.046) with participants with high %BF having higher RBC folate levels, but not baseline serum folate (p=0.411) although, participants with normal %BF had slightly higher serum folate levels. Serum folate response differed between normal %BF and high %BF, with a higher post dose peak observed for participants with normal %BF. Our findings suggest the rate of absorption and distribution of folic acid in women of childbearing age is influenced by adiposity and may need to be considered in folic acid intake recommendation to reduce the risk of NTD in the offspring of obese women.
Sports drink consumption and associated knowledge and characteristics among U.S. adults
Authors: Zytnick Deena , Park Sohyun , Onufrak Stephen , Kingsley Beverly , Sherry Bettylou
Published: June 2021

Consumption of regular sports drinks, which contain added sugars and sodium, is increasing in the U.S. This cross‐sectional study examined knowledge about the sugar content of sports drinks and whether this knowledge as well as sociodemographic and physical activity characteristics are associated with sports drink intake among 3,929 U.S. adults using the 2011 HealthStyles Survey data. Multivariable logistic regression analysis was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for adults consuming sports drinks ≥1 time/week. Most adults (71%) agreed that sports drinks contain sugars and about 22% of adults consumed sports drinks ≥1 time/week. The odds for drinking sports drinks ≥1 times/week were significantly higher among 18–24, 25–44, and 45–64 year olds (OR=5.46, 3.52, and 2.71, respectively, vs. ≥65 years); males (OR=2.09 vs. females); high school graduates (OR=1.52 vs. college graduates); adults who were highly active (moderate intensity‐equivalent of >;300 minutes of physical activity during a usual week) (OR=2.09 vs. inactive). However, adults’ agreement that most sports drinks contain sugar was not significantly associated with their sports drink intake. Understanding why some demographic groups consume sports drinks more often than others may help in the development of education about overall beverage consumption.
Childhood cancer survivors and adherence to the American Cancer Society guidelines on nutrition and physical activity
Authors: Berdan Chloe , Tangney Christy C , Scala Celina M , Stolley Melinda
Published: June 2021

The objective of this study was to assess adherence of African American, Hispanic, and non‐Hispanic white childhood cancer survivors (CCS) to the American Cancer Society (ACS) Guidelines on Nutrition and Physical Activity. CCS (n= 413) and controls (n=361) completed a structured, health‐focused interview as part of the Chicago Healthy Living Study. Responses were scored based on ACS guidelines with comparisons made between CCS and controls and also among racial‐ethnic groups. There was no difference in overall ACS adherence scores between CCS and controls (4.3 ± 1.5 vs. 4.2 ± 1.5, p=0.54). CCS compared to controls had a lower BMI (27.9 ± 7.0 vs. 29.3 ± 7.8, p=0.01) and consumed less fiber (−0.5g/1000 kcal, p=0.05). Among CCS, Hispanics had higher BMI compared to whites (29.2 ± 7.4 vs. 26.2 ± 5.3 kg/m2 respectively, p=0.001). ACS adherence scores did not differ among racial‐ethnic groups. However, median alcoholic drinks per day was greater in whites when compared to the other racial‐ethnic groups (p<0.017 for all comparisons). Compared to controls, CCS are not practicing healthier behaviors. Further information on health behavior interventions for CCS is warranted.
Impact of sphingomyelin‐supplemented diet on phospholipid composition in diaphragm of mdx mice
Authors: Zibamanzarmofrad Maral , Basic Admir , Doering Jonathan , Schmelz Eva M , Grange Robert W , LeBlanc Paul J
Published: June 2021

Duchenne Muscular Dystrophy (DMD) is characterized by progressive muscle degeneration which outpaces regeneration, yielding fragile membranes with phospholipids high in 18:1 and low in 18:2n6. Central to the regenerative process are sphingolipids, specifically sphingosine‐1‐phosphate (S1P), which promote satellite cell proliferation and muscle regeneration. In mdx mice, a model of DMD, S1P is deficient. Thus the purpose of this study was to examine the impact of a dietary source of sphingolipids on muscle membrane phospholipid composition in mdx mouse. C57BL10 (WT) and mdx mice were fed either an AIN76A (CON) or AIN76A with 0.1% sphingomyelin (SM) diet for 7 wks starting at age 4 wks. Phospholipids were extracted and analyzed using thin layer‐gas chromatography. Diaphragm muscle from mdx demonstrated significantly higher percent mole fraction of monoenes (specifically 18:1) and lower polyenes (specifically 18:2n6) in the three major membrane phospholipid species (phosphatidylcholine, PC; phosphatidylethanolamine, PE; cardiolipin, CL) compared to WT. SM significantly increased both n3 (specifically PE 22:6n3) and n6 (specifically CL 18:2n6) polyenes and decreased monoenes (specifically CL 18:1) compared to CON. These results suggest that dietary sphingolipids influence membrane phospholipid composition. The project was funded by NSERC (PJL) and VBI/Fralin (VT) Seed Research Fund (RWG & EMS).
Almond consumption reduces diastolic blood pressure in men with type 2 diabetes
Authors: Petersen Katherine N , Ricklefs Kristin , Alanbagy Samer S , Johnston Carol S , Sweazea Karen L
Published: June 2021

Type 2 diabetes (T2D) affects approximately 7.3% of Americans, leading to debilitating and life‐threatening comorbidities. Estrogen and testosterone concentrations have been linked to inflammation, oxidative stress, as well as glucose and insulin concentrations. The phytoestrogen content of almonds may lead to estrogenic activity. The present study will investigate the link between sex hormone concentrations and phytoestrogen exposure related to daily almond ingestion among subjects with T2D. Subjects were randomized to an intervention group, which received 1.5 oz. almonds daily for 12 weeks or to the control group, which maintained their current diet. In addition to hormone measurements, change in diabetic and cardiovascular biomarkers will be examined. To date, 12 participants have completed the intervention, 5 almond and 7 controls. Preliminary results suggest that gender may impact the change in biomarkers. In men only, a significant reduction in diastolic blood pressure was observed for the almond group versus controls (−8% vs. 4%, p=0.021). Although not statistically significant, almond ingestion appears to favorably impact hemoglobin A1c in women but not men. Enrollment continues in the trial through March 2013. This trial will provide further evidence regarding the efficacy of daily almond ingestion for managing the diabetic condition. This study was funded by The Almond Board of California.
The effects of ambient temperature on egg quality of native Thai chickens
Authors: Chaiseha Yupaporn , Rasee Wasana , Chokchaloemwong Duangsuda
Published: June 2021

The effect of increased ambient temperature on egg quality is well known in commercial layers, whereas in native Thai chicken has not been elucidated. This study investigated the relationship between the ambient temperature and egg quality in the native Thai chicken. Laying native Thai hens were used. Groups 1, 2, and 3, were reared in the close housed under 35 ± 2 °C, 31 ± 2 °C, and 27 ± 2 °C, respectively. Group 4 (control group) was reared in the open housed. Eggs were randomly collected and weighed from each group. Ten samples of eggshell from each group were taken from sharp, blunt, and equatorial parts. Shell thickness was measured using scanning electron microscope. The results revealed that egg weight (g) and eggshell weight (g) were higher in the control group (45.69 ± 0.65 and 4.77 ± 0.08) than those of the treatment groups (27 ± 2 °C, P<0.05; 42.85 ± 0.76 and 4.35 ± 0.08; 31 ± 2 °C, P>;0.05; 44.58 ± 0.52 and 4.73 ± 0.06; 35 ± 2 °C, P>;0.05; 43.95 ± 0.64 and 4.60 ± 0.06). The shell thickness (μm) tended to decrease in the groups that reared under high temperature (35 ± 2 °C; 302.73 ± 6.62, 31 ± 2 °C; 316.13 ± 10.98, 27 ± 2 °C; 317.80 ± 7.75) when compared to the control group (316.20 ± 6.04). These findings provide the evidence that changed ambient temperature had a negative effect on egg weight, eggshell weight, and shell thickness in the native Thai chickens. Supported by The Research and Development Fund, Suranaree University of Technology
Benefits Of Thermal Suturing Technology For Hemorrhoidectomy
Authors: Volchkova Irina Sergeevna , Mironyuk Igor
Published: June 2021

To evaluate the results of hemorrhoidectomy using thermal suturing technology. We used an electrosurgical device made by «FOTEK». The unit has a “THERMAL SUTURING” mode. In contrast to traditional bipolar coagulation in the “THERMAL SUTURING” when the power supply to tissue under automatic control while compression the vascular wall proteins formed a solid homogeneous absorbable seals (collagenate). We analyzed the results of the 100 cases of the hemorrhoidectomy. In 70 cases, was used thermal suturing (group 1), and in 30 cases – the traditional Milligan‐Morgan's method (group 2). The mean operative time in the first group was 19,7 ± 3,7 minutes, in the second group ‐ 32,9 ± 5,4 minutes. The level of postoperative pain (at 3, 6, 12, 24 and 72 hours after the operation) was significantly lower in the first group. No one case of urinary retention and the problems with the first defecation of patients of the first group. Average duration of hospitalization in the first group was 5,7 ± 0,7 days, in the second group ‐ 5,7 ± 0,7 days.

1. Features of the thermal suturing provide quality hemostasis, absence of suture material in the wound, minimal pain and faster healing. 2. The cases of using thermal suturing marked decrease in the average duration of the operation (by 1.6 times), and reduce the length of hospital stay.
Calpain‐1 inhibitor prevent loss of dystrophin in experimental septic cardiomyopathy induced by cecal ligation and puncture (CLP)
Authors: Freitas Ana C.S. , Figueiredo Maria J , Ferezin Patricia , Campos Erica C. , Rossi Marcos A. , Celes Mara R
Published: June 2021

This study was designed to test the hypothesis that N‐Acetyl‐Lleucyl‐L‐leucyl‐L‐norleucinal (ALLN), calpain‐1 inhibitor, could attenuate dystrophin disruption and cardiac contractile proteins loss/reduction in experimental sepsis induced by CLP. Male C57Bl/6 mice were subjected to sham and severe septic injury (SSI) induced by CLP. Half of animals from each group were treated with ALLN (3mg/kg, SSI+ALLN; SH+ALLN) 4hs after surgery. In SSI+ALLN mice reduced amounts of myocardial calpain‐1 were associated with increased actin/myosin expression as compared to SSI mice. Additionally, ALLN treatment of septic mice significantly prevented loss of dystrophin and â‐dystroglycan as compared to SSI mice. Concurrently, SSI+ALLN mice presented an increased survival rate.

Calpain inhibitor, ALLN, suppressed the increased calpain‐1 expression and prevented myocardial structural injury caused by experimental severe sepsis. These observations reinforce the concept that calpain‐1 activation represents a key target in dystrophin disruption behind cardiac dysfunction in severe sepsis/septic shock. Further studies are needed to elucidate this mechanism that may provide new interventional pathways to prevent septic cardiomyopathy.
Chronic intermittent hypoxia induces endothelial dysfunction in mice fed a high fat diet but not in mice fed a normal diet
Authors: Badran Mohammad , Laher Ismail , Golbidi Saeid , Ayas Najib
Published: June 2021

Objective

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (IH). OSA is prevalent in obese subjects, and is associated with endothelial dysfunction and cardiovascular disorders. We evaluated whether the effects of IH could be modulated by diet.

Methods

Adult (8–10 wk) male C57BL/6J mice were divided into 4 groups: IH or intermittent air (IA) and fed either a high‐fat (HF) or regular chow (RC) diet for 6 weeks. Endothelial dependent vasodilatation of the aorta was assessed using a wire myograph. Serum malondialdehyde (MDA) and C‐reactive protein (CRP) were also measured.

Results

Endothelial function was impaired in the HFIH group (Emax: 78.0 ±2.4% of induced tone) compared to the other three groups (P<0.0001). Basal NO activity was also reduced in HFIH when compared to HFIA group as measured by Emax constriction before and after L‐NAME (Emax: 145.6±9.9% vs. 183.7±7.7%P<0.01). MDA and CRP levels were elevated in IH (MDA: 0.67±0.05 vs. 0.42±0.04 μM, P<0.05)(CRP: 10.39±0.38 vs. 8.7±0.22 μg/ml, P<0.01), and were more pronounced in the HFIH (MDA: 0.83±0.08 μM ‐ CRP: 11.87±0.32 μg/ml).

Conclusion

IH causes endothelial dysfunction in mice fed high fat diet but not normal chow. Inflammation and oxidative stress are increased in IH and is exacerbated by a high fat diet. (CIHR Team Grant)
Luteolin inhibits human cultured keratinocyte inflammatory cytokine release and proliferation
Authors: Weng Zuyi , Theoharides Theoharis C
Published: June 2021

Psoriasis is characterized by keratinocyte hyperproliferation and chronic inflammation, with increased skin expression of tumor necrosis factor (TNF) and vascular endothelial growth factor (VEGF). Flavonoids, such as luteolin, are potent anti‐inflammatory compounds, but their actions on keratinocytes are unknown. The study objective was to examine the effect of luteolin, and its structural derivative methoxyluteolin, on keratinocyte cytokine production and proliferation. Human HaCaT keratinocytes preincubated with luteolin or methoxyluteolin (1–100 μM for up to 24 h) were stimulated with TNF (50 ng/mL, 6 or 24 h). IL‐6, IL‐8 and VEGF mRNA and protein expression were assayed by PCR and ELISA, as well as cell proliferation by XTT. Luteolin and methoxyluteolin (10–100 μM) significantly reduced TNF‐triggered mRNA and protein expression of IL‐6, IL‐8 and VEGF, as well as keratinocyte proliferation. Luteolin and methoxyluteolin also inhibited TNF‐induced activation of nuclear factor‐kappa B (NF‐κB) and mitogen‐activated protein kinase (MAPK). In conclusion, luteolin and methoxyluteolin are promising candidates for treatment of inflammatory skin diseases, such as psoriasis. Supported by NIH grant AR47652.
Effects of Perilla frutescens Extract on Cytochrome P450 Expression in Oxidative Stress‐induced Liver
Authors: Kang Jeong Han , Yang Sung Yong , Yang Jae Eon , Seol Hae Min , Lee Kwang‐won
Published: June 2021

We have previously reported protective effect of Perilla frutescens extract (PLE) against tert‐butyl hydroperoxide (t‐BHP)‐induced liver oxidative damage in rats. t‐BHP induces lipid peroxidation in rat liver microsomes and it is reported that t‐BHP can be metabolized to free radical intermediates by cytochrome P450 (CYP), which can subsequently initiate lipid peroxidation. We speculate that lipid peroxidation in rat liver microsomes was induced by t‐BHP is closely linked with the oxidative metabolism mediated by CYP1A1/2 and CYP 3A/2E1. We examined the effect of the PLE on CYP activities including Ethoxyresorufin‐O‐deethylase (EROD, CYP1A1), Methoxyresorufin‐O‐deethylase (MROD, CYP1A2), Erythromycin‐N‐demethylase (ERDM, CYP3A) and p‐nitrophenol hydroxylase (PNPH, CYP2E1) under oxidative stress in rat liver. The pretreatment of rats with PLE (250, 500 and 1000 mg/kg b.w.) for 5 days before a single dose of t‐BHP (i.p.; 0.5 mmol/kg), PLE was found to be a potent inhibitory effect CYP 1A1/2 of oxidative stress‐induced liver microsomes. Kinetic analysis of CYP 1A1/2 activity of t‐BHP‐induced microsomes demonstrated that PLE inhibited enzyme activities by competitive or noncompetitive mechanism. These data suggest that selective control of CYP by PLE might contribute to protective effect of liver through inhibitory CYP activities against oxidative stress in rat liver.
Mobilization of angiogenic monocytes in response to induced remote ischemia in healthy subjects
Authors: Resende Micheline M , Gahremanpour Amir , Cabreira‐Hansen Maria Graca , Wang Xiaohong , Willerson James T , Silva Guilherme , Perin Emerson
Published: June 2021

Mobilization of circulating progenitor cells (CPC) or discrete hematopoietic cell subsets (HCS) has been studied in a variety of scenarios. Variability in ischemia duration and lack of appropriate controls are challenges in interpreting the often‐conflicting results of these studies. We studied the ischemia‐induced changes in CPC and HCS in healthy adults (age 18–25). Changes in PC and HCS levels were compared between normal physiological (N=4) conditions and induced transient ischemia (N=8) by flow cytometry and colony‐forming assay (CFU‐Hill). Ischemia was induced by 5 cycles of ischemia‐reperfusion using a pressure cuff around the thigh. Number of CFU‐HIL, levels of CPC, HCS were analyzed at baseline, 6, 24, 48, 72 hours and 7days post‐ischemia. In contrast to the controls, there was a rise in angiogenic monocytes, Tie‐2+ CD14+ CD16mid cells (ANM) at 48h (0.19 ± 0.09 vs 0.40 ± 0.007% p<0.05) compared to baseline, while other populations remained unchanged. ANM have an important role in the maintenance of the endothelial integrity after ischemia by recruiting endothelial cells. In conclusion, our study is the first to show that ANM are mobilized in response to tissue ischemia in healthy subjects. This may reflect normal function of the vascular endothelium in response to ischemia, and suggests that this non‐invasive maneuver may be used as a potential new approach to access the role of ANM in vascular biology.
LITTER SIZE MANIPULATION ALTERS THE PLASMATIC AND ADIPOSE ANGIOTENSIN II CONCENTRATION
Authors: Mecawi Andre S , Marangon Paula B , Elias Lucila LK , Antunes‐Rodrigues Jose
Published: June 2021

Litter size manipulation results in body weight gain alterations, such phenotype remains until the adulthood. Several studies have demonstrated the importance of the angiotensin II (ANGII) in the obesity development, as well as its correlation with cardiovascular diseases. Using the model of reduction or enhance the litter size, this work aimed to investigate the alterations in plasma and adipose ANGII concentrations in rats. The litters were divided into 3 groups: Normal Litter (NL, 10 pups), Small Litter (SL, 3 pups) and Large Litter (LL, 16 pups). The reduction and enhance of the litter size, led to an increase and decrease of the weight gaining in SL (~25%) and LL (~19%) groups, respectively, at the weaning (21st day) till adulthood (60th day). Plasma ANGII levels were higher in both SL (~40%) and LL (~120%) groups in relation to the NL at the weaning. We have also observed a significant rise in the ANGII levels in epididymal and retroperitoneal white adipose tissue (~40%) in LL group in relation to NL group at the weaning. On the other hand, there was a significant enhancing in the ANGII concentration in the interscapular brown adipose tissue in the SL group in relation to NL at weaning (~25%) and adulthood (~200%). Our results show that the litter size manipulation can program not only the weight gain but also the renin‐angiotensin system activity in plasma and adipose tissue.
Moderate exercise prevents chronic stress induced intestinal barrier dysfunction by promoting hypoxia inducible factor‐1α expression
Authors: Luo Beibei , Nieman David C. , Xiang Dao , Chen Peijie
Published: June 2021

Chronic stress induces intestinal barrier dysfunction and impairs mucosal defenses against luminal bacteria. The purpose of this study was to investigate the effect of moderate exercise on intestinal barrier function during chronic stress in a mouse model. Balb/c mice (6 week) were randomized into 5 groups (n=6/group): group C functioned as controls; group R was subjected to 6‐hour per day repeated restraint stress (RRS) for 10 consecutive days; group S received 30 min of swimming prior to RRS; group D was injected with hypoxia inducible factor‐1α (HIF‐1α) stabilizer dimethyloxalylglycine (DMOG) before RRS; group P was injected with saline before RRS as a placebo control. Intestinal tissue was biopsied after the first treatment for analysis of HIF‐1α gene and protein expression. Bacterial translocation was determined by 16s rRNA based fluorescence in situ hybridization. FITC‐dextran was used as a measure of intestinal permeability. Thirty minutes of swimming or DMOG injection before RRS prevented bacterial translocation and maintained intestinal permeability (P<.01). HIF‐1α gene and protein expression were significantly increased after swimming and DMOG treatment (P<.05). In conclusion, moderate exercise prevented chronic stress‐induced intestinal barrier dysfunction in mice, in part due to promoting the expression of transcription factor HIF‐1α.

Supported by Grant yjscx2012007 and xsxr2012045
The effects of aqueous extraction Rosmarinus officinalis L. on rat bladder contractions in vitro
Authors: Çelebi Fikret , Pengül Emin , Gelen Volkan
Published: June 2021

Objective

. To evaluate the effect of Rosmarinus officinalis L (Labiatae ), an effective and herbal reputed plant for the treatment of urinary ailments, on rat bladder contractility

Method

Animal experiments were performed in accordance with the national guidelines for use and care of laboratory animals and approved by the local animal care committee of Ataturk University. Urinary bladders were removed from adult male Sprague ‐ Dawley rats. Strips were cut from the bladder body and placed in organ baths containing Krebs solution. The effects of four different doses (150, 300, 600 and 1200 μg/ml) of Rosmarinus officinalis L were investigated on rat bladder contractility induced by 60 mmol/L KCl and 10−4 mol acetylcholine.

Results

Contractile tensions were normalized by using the percentage contraction induced by 60 mmol/L KCl and 10−4 mol acetylcholine. The effect of Rosmarinus officinalis L on the urinary bladder contractility induced Ach and KCl. There is no statistical difference between groups (n=6, P>;0.05)

Conclusion

Any effect of Rosmarinus officinalis L was not observed on the contractions of the urinary bladder of rat that are induced by both Ach and KCl. It can be expressed that Rosmarinus officinalis L which is used in the herbal treatment of some urinary disease does not affect the activity of smooth muscles of urinary bladder.

This study was supported by Ataturk University Research Foundation
Teaching Anatomy in the Simulation Center
Authors: Jones Daniel B.
Published: June 2021

Models and simulators have replaced the cadaver lab and vivarium to teach anatomy relevant to perform procedures and operations. 3D jet printers and teleconferencing have changed the way we see anatomical relationships. My talk will introduce the ACS‐ASE Skills‐based Simulation Curriculum for Medical School Years 1‐3 and the ACS‐ APDS curriculum for residents. We will share data on using teleconferencing technology to enhance anatomy teaching in the preclinical years, during the 3rd year Surgery Clerkship, and MIS fellowships. Realistic 3D models of the liver, lung, aorta and breast pathology may transform how we train and prepare for an operation .
Enteral Obestatin influences on Intestinal Contractility in Neonatal Wistar Rats ‐ in vitro Studies
Authors: Woliński Jarosław , Słupecka Monika
Published: June 2021

Obestatin is a 23‐amino acid peptide encoded by the ghrelin gene. Substantial amount of this peptide has been found in colostrum and milk. We have investigated the intestinal contractility of neonatal rats enterally treated with obestatin (125nmol/kg b.wt. LO; 250 nmol/kg b.wt, HO) or saline (C), (n=12 for each group), for 7 days. Duodenal and middle jejunum whole‐thickness preparations from 21 day old rats were studied in an organ bath, for isometric recording under treatment with acetylocholine (ACh), atropine and tetradotoxin (TTX). The electrical field stimulation (EFS) was performed (90 V, duration 10 sec) at three frequencies: 0.5, 5 and 50Hz with 1 min intervals. Significant decrease in amplitude was observed after treatment with higher doses of obestatin (HO) for EFS–stimulated as well as spontaneous contractile activity in both studied intestinal segments. In the lower dose (LO) obestatin treatment resulted in decrease in amplitude both for EFS ‐ stimulated as well as spontaneous contractility but only in the middle jejunum. In obestatin treated animals injection of atropine did not result in a significant decrease of amplitude of spontaneous contractility of both intestinal segments. In all experimental groups the amplitude of EFS –stimulated off‐contractions and spontaneous contractility was sensitive to treatment with TTX. These results indicate the importance of peripheral obestatin in the programming of intestinal contractility in rats during suckling period. Moreover this effect is dose dependent and independent of cholinergic pathways.

Project of Polish National Science Centre 2011/03/D/NZ9/03697
Ammonia Modulates Enteric Neuromuscular Transmission in the Mouse, Pig, and Human Intestine.
Authors: Fried David , Gulbransen Brian
Published: June 2021

Ammonia is a waste product of protein metabolism that is primarily produced by gut bacteria. Accumulation of ammonia occurs in many metabolic disorders and the neurotoxic effects of ammonia can cause severe nervous system dysfunction. Our objective was to test the hypothesis that local buildup of ammonia alters neuromuscular control of intestinal function. The effects of ammonia on neurogenic relaxations and contractions evoked by electrical field stimulation (EFS; 2‐30 Hz, 0.5 ms, 20 V) and pharmacologic agents were studied in segments of mouse, pig and human small intestine in vitro using isometric tension recordings. Specific effects of ammonia on enteric neurons and glia were studied using in situ Ca2+ imaging of mouse ileal myenteric plexus. Ammonia increased carbachol induced longitudinal muscle contractions in small intestine segments of all species (p<0.05 all groups). EFS induced frequency‐dependent contractions and relaxations that were abolished by tetrodotoxin (TTX, 0.3 μM) (p<0.001 all groups). The amplitude of EFS evoked ileal and jejunal longitudinal muscle contractions were larger in the presence of ammonia and relaxations (10 μM scopolamine tone) were reduced in the presence of ammonia in all groups as compared to control (p<0.05 all groups). The enhanced excitatory response was significantly attenuated, but not abolished by PAPA NONOate (100 μM), a nitric oxide donor (P<0.05 human jejunum). Visualization of cellular activity in the mouse ileal myenteric plexus with Ca2+ imaging revealed that enteric glial cells are activated by ammonia. Our data support the hypothesis that ammonia toxicity in human, porcine, and murine small intestine disrupts nitrergic inhibitory neuromuscular transmission leading to increased smooth muscle contractility.
Brainstem Dopamine Controls Gastric Tone And Motility
Authors: Toti Luca , Travagli R.Alberto
Published: June 2021

Gastrointestinal (GI) dysfunctions, such as gastroparesis, are prodromic to Parkinson's disease (PD). Upper GI functions are modulated by neurons in the dorsal vagal complex (DVC); recently, we reported a monosynaptic dopaminergic connection between the substantia nigra pars compacta (SNpc) and the DVC, activation of which modulates gastric tone and motility via dopamine (DA)1 receptors. The effects of DVC application of DA on gastric tone and motility, however, have not been characterized.

Gastric tone & motility were recorded in rats using strain gauges sewn onto the anterior gastric wall. DA (0.1pmoles‐10nmoles/60nL; N=10‐16) microinjected in the left DVC decreased tone & motility in both the corpus (at 1nmole, tone: ‐152±21mg; motility: ‐57±6% of baseline) and in the antrum (at 1nmole, tone: ‐222±22 mg; motility: ‐41±6% of baseline, respectively; P<0.05 for all).

Equivalent doses of DA induced a larger decrease in antrum compared to corpus tone, while motility was affected similarly. The effects of DA were blocked by ipsilateral vagotomy (N=4) and by application of DA2 (L741626), but not DA1 (SCH23390), antagonists (both at 45nM, N=7).

DVC application of the dopamine uptake inhibitor, benztropine (100nmoles, N=2‐6), decreased tone (‐76±24 and ‐245±85mg) but increased motility (23±7 and 41±18% of baseline) in corpus and antrum, respectively.

Our data indicate that the dopaminergic innervation of the DVC modulates gastric tone and motility differentially: when exogenous DA is applied, the effects are mediated mainly via DA2 receptors, which are also tonically active in setting gastric tone; conversely, a tonic DA1 input modulates gastric motility. We would like to suggest that this latter pathway is involved in the reduced gastric motility observed in PD.
UDCA modulates monocyte/epithelial cell interactions
Authors: O Dwyer Aoife , Ward Joseph , Greene Catherine , Keely Stephen
Published: June 2021

Monocytes play a key role in the pathogenesis of inflammatory bowel disease (IBD) as they release pro‐inflammatory mediators that can compromise epithelial barrier function. Among these mediators is IL‐8, which has been implicated in the initiation and perpetuation of IBD. UDCA is a naturally occurring bile acid, which is used for the treatment of liver inflammation. The current study aimed to investigate the effects of UDCA on IL‐8 release from monocytes and examine its effects on monocyte induced loss of barrier function.

IL‐8 release from U937 monocytes was induced with either lipopolysaccharide (LPS) [1 µg/mL] or the pro‐inflammatory cytokine, TNFα[5 ng/mL] for 24 hrs, either in the absence or presence of UDCA. Supernatants were then analysed for IL‐8 by ELISA. IL‐8 mRNA expression was assessed by qPCR. Epithelial barrier function was measured by transepithelial resistance (TER). Statistical analysis was performed by one way ANOVA with the Tukey‐Kramer post test.

Treatment of U937 monocytes with TNFα or LPS induced 9.8 ± 1.2 and 7.9 ± 1.6 fold increases in IL‐8 release, respectively (n = 5–7; p < 0.001). UDCA [100 µM] reduced TNFα‐driven IL‐8 release to 3.5 ± 0.4 fold (n = 5; p < 0.001) and inhibited IL‐8 mRNA expression (n = 4; p < 0.05). In contrast, UDCA had no effect on LPS‐driven IL‐8 release. UDCA also specifically reduced TNFa‐, but not LPS‐, induced activation of NFkB (n = 4; p < 0.05). In further experiments, co‐culture of U937 monocytes with T84 cell monolayers resulted in a loss of barrier function, as indicated by a 68.9 ± 3.8% drop in TER. This effect was reversed by co‐treatment with UDCA (n = 5; p < 0.05).

Taken together, our data suggest that UDCA, by virtue of its anti‐inflammatory effects on monocytes and consequential protective effects on epithelial cells, may prove to be a useful therapeutic target for IBD.
Genetic Variation in SLC30A2 and Associated Alterations in Enteric Microbiota in Preterm Infants
Authors: Hamidi Maryam , Podany Abigail , Alam Samina , Santos Mary , Gallagher Carla , Vijay‐Kumar Matam , Wright Justin , Lamendella Regina , Kelleher Shannon
Published: June 2021

Necrotizing enterocolitis (NEC) is a devastating intestinal disease of preterm infants. Defects in Paneth cells (PC), which are specialized secretory cells that release antimicrobial peptides, cytokines, and zinc (Zn) to maintain enteric microbiota, are associated with NEC. We recently found that the Zn transporter ZnT2 (SLC30A2) is critical for PC function and that non‐synonymous genetic variation (GV) in SLC30A2 occurs in ~35% of the population. Here we aimed to determine if a relationship exists between GV in SLC30A2 and the composition of enteric microbiota in preterm infants. DNA and fecal samples were collected from 20 infants (mean gestational age 33 weeks). The entire coding region of SLC30A2 and fecal genomic DNA were sequenced. 74,332 sequences were retrieved and data revealed that the fecal microbial community was dominated by Enterobacteriaceae (44%). Three unknown species in the Enterobacteriaceae family strongly correlated (p<0.05) with a region of dense GV in the C‐terminus, after accounting for multiple testing via FDR correction. These species were each approximately 5‐fold more abundant in infants with GV than in those without. Recent studies highlight the importance of establishing normal microbiota after birth, especially in preterm infants. Because several members of Enterobacteriaceae are known pro‐inflammatory opportunistic pathogens, our study suggests that GV in SLC30A2 affects the establishment of normal microbiota, which could potentially increase risk for enteric infections.
Lacking vitamin D receptor leads to intestinal dysbiosis
Authors: Jin Dapeng , Wu Shaoping , Zhang Yong‐guo , Lu Rong , Sun Jun
Published: June 2021

The microbiome modulates numerous aspects of human physiology and is critical in development of diseases. Vitamin D and its receptor VDR are associated with various diseases. We hypothesize that VDR status alters the composition and functions of microbiota. Fecal and cecal stool samples were harvested from VDR knockout mice and intestinal epithelial VDR conditional knockout (VDRΔIEC) mice. After 454 pyrosequencing, the sequences were clustered into OTUs. PICRUSt, together with HUMAnN were used to analyze the metagenomics and to compare abundances of genes involved in metabolic pathways by reference to KEGG and Clusters of Orthologous Groups databases. In VDR‐/‐ KO mice, Lactobacillus was depleted in fecal stool, whereas Clostridium and Bacteroides were enriched. In cecal stool, Alistipes and Odoribacter were depleted, and Eggerthella was enriched. A comparison between WT and VDR‐/‐ revealed 72 (41 enriched, 31 depleted) and 40 (26 enriched, 14 depleted) functional modules that were significantly altered in fecal and cecal microbiome, respectively. VDRΔIEC mice had enriched Eubacterium, Allobaculum, Prevotella, Limbacter, Anaplasma and depleted Akkermansia in fecal stool, and enriched Roseburia, Pseudoflavonifractor, Allobaculum, Prevotella, Alistipes and Eggerthella, and depleted Lactobacillus and Streptomyces in cecal stool. The numbers of functional modules significantly altered were 75 (33 enriched, 42 depleted) and 89 (47 enriched, 42 depleted) in fecal and cecal microbiome, respectively. Functional alterations regarded synthesis/metabolism of amino acids, carbohydrates and fatty acids, detoxification, infection, and cancer. Effects of VDR in maintaining host‐microbe interactions are critical for intestinal homeostasis. The insights can be exploited to develop novel strategies by restoring VDR in illness.
Endogenous Glucocorticoids Regulate Hepatic Inflammation and Apoptosis in a Sexually Dimorphic Manner
Authors: Quinn Matthew , Cidlowski John
Published: June 2021

Autoimmunity of the liver constitutes a large fraction of liver pathologies in human and display a higher prevalence in females. Synthetic glucocorticoids are used for the treatment of autoimmune diseases due to their anti‐inflammatory and immunosuppressive effects, however, the role of endogenous glucocorticoids in the etiology of hepatic autoimmunity has not been empirically examined. The aims of this study were to characterize the effects of long‐term glucocorticoid deficiency on male and female mouse liver. Male and female C57Bl/6 mice were adrenalectomized for four months. Following adrenalectomy male mice have normal liver histology indicated by H&E staining, however H&E staining of female mice show the presence of inflammatory cell foci. Global inflammatory gene expression in liver was assayed in adrenalectomized mice by Nanostring. Female adrenalectomized mice display a wider range of inflammatory genes being altered by adrenalectomy compared to male adrenalectomized mice which have much more subtle changes. This inflammatory milieu leads to cell death in the liver as demonstrated by TUNEL staining. To test if endogenous estrogens are responsible for the sexual dimorphism in hepatitis female mice were adrenalectomized or adrenalectomized and ovariectomized. Mice that had dual surgeries were protected from the inflammatory phenotype of adrenalectomy. This data indicates estrogens drive hepatic inflammation and apoptosis in the absence of endogenous glucocorticoids. These data together indicate targeting estrogen signaling may enhance the effects of synthetic glucocorticoids in combating inflammation and apoptosis in hepatic autoimmune diseases.
Marked Hyperfructosemia without Fructose‐Induced Hyperglycemia and Diabetes in Fructokinase‐deficient Mice
Authors: Patel C , Sugimoto K , Shah A , Parikh S , Douard V , Inui H , Yamanouchi T , Ferraris R
Published: June 2021

Management of fructose (F)‐linked metabolic disorders requires an understanding of F homeostasis, yet the important roles of dietary F, of the F transporter GLUT5, and of fructokinase (FK) in simultaneously regulating serum levels of F have not been studied. Wildtype (WT) and FK‐/‐ mice were fed for 7 d isocaloric 0% or 20% F diets, fasted overnight, then killed 0 to 7.5 h after initial feeding at the onset of the dark phase when feeding activity was greatest. Analysis by HPLC showed portal and systemic F levels in WT mice fed 0% F to be < 0.1 mM, similar to those of GLUT5‐/‐ mice naively fed F, and independent of time after feeding. WT mice consuming 20% F had fasting serum F levels similar to, and postprandial levels 3‐fold greater than, those eating 0% F. Deletion of FK resulted in ~80‐fold greater serum F levels (~4 mM) than those in WT and GLUT5‐/‐ mice. In FK‐/‐ mice fed 20% F, systemic was paradoxically ~2‐fold greater than portal serum F, suggesting that F accumulated in the systemic circulation. Significant F‐induced hyperglycemia in WT mice was prevented by FK deletion. Systemic serum F levels remained low (< 0.05 mM) in WT after chronic consumption ad libitum of 0 or 20 % F for 12 wk, but increased to > 1 mM in phenotypically normal FK‐/‐ mice. The chronic F‐induced hyperglycemia in WT, but not the chronic hyperfructosemia in FK‐/‐ mice, increased in HbA1c levels. Finally, in WT, GLUT5‐/‐ and FK‐/‐ mice fed 0% F, there seems to be a FK‐ and GLUT5‐independent, significant endogenous synthesis of F. FK is required to prevent hyperfructosemia as well as F‐induced hyperglycemia and diabetes (NSF1121049).
Exploring GPCR Biased Signaling from inside and outside the Cell
Authors: Trejo JoAnn
Published: June 2021

G protein‐coupled receptors (GPCRs) are the largest family of cell surface receptors expressed in the mammalian genome and mediate vast physiological responses, making this receptor class the target of most drugs used clinically. GPCRs are dynamic molecules that assume multiple active states that bias signaling towards distinct G‐protein subtypes and beta‐arrestins. However, the mechanisms that regulate GPCR bias signaling remains unclear. Towards understanding the molecular basis of GPCR biased signaling, we examined the role of post‐translational modifications and plasma membrane compartmentalization. We discovered that N‐linked glycosylation of protease‐activated receptor‐1 (PAR1), a GPCR for the coagulant protease thrombin, regulates preferential coupling to specific G‐protein subtypes that control stress fiber formation and cellular proliferation. We also found that PAR1 distribution into caveolae in endothelial cells is critical for biased signaling induced by thrombin versus activated Protein C, an anti‐coagulant protease. Thrombin‐activated PAR1 coupled to G‐proteins and induced endothelial barrier permeability. In contrast, APC‐activated PAR1 signaled preferentially through beta‐arrestins to promote endothelial barrier stabilization, which required compartmentalization in caveolae. These studies reveal two different mechanisms that regulate GPCR biased signaling from inside and outside of the cell.
In addition to her research, Dr. JoAnn Trejo is an experienced educator and leader of diversity efforts. She will also discuss the untapped potential: diversity and the advancement of science.
Administration of Probiotics Normalizes Deficits in the Microbiota‐Gut‐Brain Axis Induced by DSS‐Colitis
Authors: Huynh Kevin , Emge Jake , Reardon Colin , Barrett Kim , Gareau Melanie
Published: June 2021

Altered behavior and mood disorders, including anxiety, depression and cognitive dysfunction, occur in the context of intestinal diseases such as inflammatory bowel disease (IBD) and affect patient quality of life. Our aim was to determine whether colonic inflammation precipitates behavioral defects and whether these changes can be ameliorated by probiotics. Dextran sodium sulfate (DSS) was administered to 6‐7 week old C57BL/6 mice via drinking water for 5 days followed by either 3 days (8 d post‐DSS) or 9 days (14 d post‐DSS) of normal drinking water. A subset of mice was given probiotics (Lactobacillus rhamnosus [R0011] and L. helveticus [R0052]; 109 CFU/ml orally) starting 7 days prior to DSS and continuing until the end of the experiment. Changes in weight, colon length, behavior and microbiota were assessed. At 8 d post‐DSS, weight loss and colonic shortening (both p<0.01) were observed, indicating colonic disease. Dysbiosis was also observed. DSS mice (vs. controls) demonstrated impairments in recognition memory (p<0.01) and the presence of anxiety‐like behavior (p<0.05), which were both resolved by 14 d post‐DSS. Probiotics ameliorated colonic disease (p<0.05) and defects in behavior (p<0.05), and partially restored the microbiota. Taken together, these findings indicate the presence of dysregulation of the microbiota‐gut‐brain axis in the setting of DSS‐induced colitis that can be prevented by treatment with probiotics.
Intestinal divalent metal‐ion transporter‐1 is required for iron homeostasis in the neonatal mouse
Authors: Prakash Shahana , Shawki Ali , Niespodzany Eric , Mackenzie Bryan
Published: June 2021

Iron deficiency in neonates and infants results in growth retardation and neurodevelopmental disorders that persist into later life; however, little is known about the mechanisms of intestinal iron absorption in neonates. Divalent metal‐ion transporter‐1 (DMT1) is a H+‐coupled iron transporter that is critical for iron absorption in the adult mammal but its role in neonates is untested. We tested the hypothesis that intestinal DMT1 is required for iron homeostasis in the suckling mammal by examining hematological variables and iron status in a conditional intestinal DMT1 knockout mouse model (DMT1int/int) at postnatal days 7, 14, and 21. We observed in DMT1int/int mice at day 21 a moderate frank iron‐deficiency anemia characterized by low hematocrit [33% (SD 5%) in male DMT1int/int mice (n = 18) cf. 46% (SD 3%) in wildtype (n = 13), P < 0.001], microcytosis, and depleted liver nonheme iron stores cf. wildtype. Female, but not male, DMT1int/int mice were also slightly hypochromic by day 21. Female DMT1int/int mice exhibited low serum iron at day 14 and 21 cf. wildtype. Our data reveal an important role for intestinal DMT1 in iron acquisition by the neonatal mouse. DK080047