bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the efficacy of popular weight loss programs in sedentary overweight women I: body composition and resting energy expenditure
Authors: Baetge C , Lockard B , Mardock M , Simbo S , Jung Y , Galvan E , Levers K , Byrd M , Koozehchian M , Khanna D , Sanchez B , Jagim A , Oliver J , Kresta J , Horrell K , Leopold T , Cho M , Rasmussen C , Kreider R
Published: June 2021

126 sedentary women (44±12 yr, 44.8±5% body fat, 35.4±6 kg/m2) were randomized to participate in a control group (C) or the Curves Complete® 90‐day Challenge (CC), Weight Watchers® Points Plus (WW), Jenny Craig® (JC), or Nutrisystem® Advance Select™ (NS) weight loss programs for 12‐wks. Body mass, DEXA body composition, and resting energy expenditure (REE) measurements were obtained at 0, 4, 8, & 12 wks and analyzed by MANOVA. Data are presented as changes from baseline after 12‐wks. Participants in the diet groups lost similar amounts of body mass (C −0.1±3.1; CC −5.1±4.2; WW −4.0±3.4; JC −5.3±3.8; NS −5.1±4.5 kg, p=0.001). However, participants in the CC group experienced significantly greater loss in fat mass (C −0.1±3.1; CC −4.2±4.0; WW −2.2±2.7; JC −3.5±3.3; NS −2.3±2.5 kg, p=0.001), less loss in FFM (C −0.0±2.2; CC −0.6±2.4; WW −1.6±2.1; JC −1.8±2.1; NS −2.4±2.2 kg, p=0.001), and greater reductions in percent body fat (C 0.03±1.7; CC −2.9±3.6; WW −0.8±2.4; JC −1.4±2.4; −0.2±1.7%, p=0.001). No significant differences were observed among groups in changes in REE (C 36±195; CC −96±180; WW −93±147; JC −21±212; −49±207 kcal/d, p=0.37). Results indicate that participation in the CC program promotes more favorable changes in body composition than participation in other popular weight loss programs. Supported by Curves International, Waco, TX
Optimizing dietary recommendations among Pacific Land Grant Association jurisdictions
Authors: Luick Bret
Published: June 2021

National dietary recommendations do not reflect local practices, especially in remote regions. The current objective was to investigate the feasibility of using detailed food groupings and regional dietary recalls as a basis for formulating nutrition public health messages. Diet recalls from the EFNEP program were evaluated for Alaska, Guam, Hawaii, Mariana Islands, and Micronesia. EFNEP diet recalls were merged with the FNDDS nutrient database and the USDA CNPP food price database. Foods were grouped using the first two digits of the USDA SR numbering system. A Thrifty Food Plan like nonlinear optimization model was built using GAMS with weighting against less utilized and more expensive foods. Across the regions, non‐whole grains, starchy, potato based and other vegetables and non‐citrus fruits predominated among grains, vegetables and fruits, respectively. Meats and meat equivalents were heavily relied upon across jurisdictions. Economical model solutions which met both serving and nutrient guidelines were feasible. Using the low fruit and vegetable intakes among Alaska based recalls as an example, model solutions indicated that if whole (low) and non‐whole grain (high) intakes were reversed with constrained saturated fat and added sugar intakes, dietary guidelines could be met within SNAP benefit limits.
EPIC modification of within‐meal eating behaviors for healthy weight management
Authors: Matsumoto Carolyn N , Greene Geoffrey W , Sebelia Linda M , Melanson Kathleen J
Published: June 2021

Improving within‐meal eating behaviors has been shown to reduce food intake in the laboratory. The objective of this study was to extend these findings to individuals interested in healthy weight management. A 5‐week one‐on‐one intervention of modifying within‐meal eating behaviors, the Eating Pace Instructional Classes (EPIC), was developed. Twenty‐three healthy women (20.0±2.6 years, with body mass index 31.8±2.6 kg/m2) were randomized into intervention or non‐intervention groups. Assessment visits before and after the intervention included an ad libitum lunch from which meal duration and intake were covertly measured. Repeated‐measures analysis of variance (ANOVA) indicated that eating rate significantly decreased (F=5.29; p=.032) and energy intake significantly decreased (F=6.19; p=.022) after participation in the EPIC intervention. Paired‐samples t‐tests indicated a significant increase in meal duration for the experimental group (t=−2.34; p=.039) but not for the control group (t=‐.83; p=.428) after participation in the EPIC intervention. Our EPIC approach is successful at slowing eating and lowering food intake in young women. Future studies should test other delivery methods and apply EPIC approaches to more diverse community populations for weight management and obesity prevention. The current work was supported by a CELS CARES research grant from the University of Rhode Island.
Effect of Oral Administration of Water Soluble Extract from Citrus Peel (Citrus unshiu) on Suppressing Alcohol Induced Fatty Liver in Rats
Authors: Park Yongkon , Choi Inwook , Park Ho-young
Published: June 2021

Water soluble citrus peel extract (WCE) from Citrus unshiu was investigated on its anti‐alcoholic fatty liver activities through chronic oral administration to Sprague Dawley (SD) rats. WCE, which was prepared by ultrasound‐assisted extraction (UAE), was co‐supplemented with ethanol (2.87 ml/rat/day) at low and high dosages (278 and 576 mg/rat/day, respectively) for 6 weeks. Ethanol consumption significantly elevated both total cholesterol (TC) and triglyceride (TG) concentrations in the serum of SD rats otherwise co‐administration of WCE lowered both serum TG and TC levels. Ethanol consumption caused hepatic lipid content of 227.0 mg/g liver after 6 weeks whereas co‐administration of WCE, especially at high dosage, significantly reduced it to 186.9 mg/g liver. Analysis of hepatic fatty acids revealed that WCE suppressed conjugation of oleic acid into TG. These results support probable application of WCE as an anti‐alcoholic fatty liver agent.
Severe muscular waste in university student of nutrition science
Authors: Anaya-Loyola Miriam Aracely , Vega ANA Maria , Ronquillo Dolores , Nieves Christian
Published: June 2021

The aim of this study was to evaluate the protein status of young students of Nutrition attending to the University of Querétaro in central México. A total of 39 students, (35 women and 4 men), aged between 19 and 25 years old participated in this study. The average age of participants was 20.8±1.3 years. The average body mass index (BMI) was 22.1±4.1 kg/m2 (within normal range); however, 14.3% of women were underweight and 11.4% presented overweight and/or obesity. In contrast, 33% of men were overweight. 42% of women and 33% of the men had elevated body fat. Over 94% of participants had some type of muscle wasting with the diagnosis of creatinine‐height index. Of those who had normal weight, 36% of them had severe muscle wasting and an additional 20% showed moderate wear, which indicates that, the students of nutrition in order to maintain a healthy weight; they are succeeding at the expense of muscle protein. It is necessary to pay more attention to maintain body compartments and not just the weight of people, avoiding to compromise important structural and metabolic roles.

University of Querétaro‐CONCYTEQ
The response score is a tool that measures patients’ response to ketogenic therapy
Authors: Allen Hannah J , Devabhaktuni Divya , Borum Peggy R
Published: June 2021

Background

Ketogenic Therapy (KT) is a high fat, low carbohydrate, adequate protein diet used to treat patients with intractable epilepsy with the goal of eliminating seizures and the need for anti‐epileptic drugs (AEDs).

Objective

To develop a tool to measure seizure response and need for AEDs during treatment.

Methods

Ranking numbers are given to five seizure parameters (frequency, type, severity, length, and characteristics), and summed to give the seizure point total (SPT). The seizure score (SS) is the daily SPT as a percent change from the baseline SPT. The medication load (ML) is the prescribed AED dosage divided by the minimum AED dosage. The medication score (MS) is the daily ML as a percent change from the baseline ML. The response score (RS) is the average of the daily SS and MS.

Results

In our practice we have observed that SS and MS may both decrease, only SS may decrease, or neither parameter may decrease during treatment. The SS, MS, and RS for three patients at the end of the first year on KT are presented in the table below.

Conclusion

The RS presents an overall change and can be used to stratify patients into responders and non‐responders to KT.

Supported in part by the National Institutes of Health (NIH) and National Center for Research Resources (NCRR) CTSA grant 1UL1RR029890
Insufficient folate intake increased arterial stiffness in former smokers with type 2 diabetes
Authors: Kim Yeonsoo , Choi Young Ju , Huh Kap Bum , Chang Namsoo
Published: June 2021

The objective of the present study was to investigate the interaction between smoking cessation and nutrient intake on arterial stiffness in patients with type 2 diabetes. A cross‐sectional study was conducted with 322 patients with type 2 diabetes (216 never smokers and 106 former smokers). Anthropometric, biochemical, dietary data and brachial‐ankle pulse wave velocity (baPWV) were collected. BaPWV was higher in type 2 diabetic, former smokers who consumed sufficient dietary folate that those who consumed insufficient dietary folate although baPWV was not significaly different in never smokers based on sufficient intake of folate. Moreover, in correlation analyses adjusted for age, sex, and BMI, there was borderline significant correlation between vegetable, a major food source of folate, and baPWV in former smokers with type 2 diabetes. The results of the current study showed that insufficient folate intake, which is lower than the estimated average requirement, increased arterial stiffness in former smokers with type 2 diabetes. The results of the current study warrant future studies to explore any mechanisms involved in beneficial effects of dietary folate intake on arterial vessel stiffness in former smokers with type 2 diabetes.
Nutrition Education for Practicing Physicians
Authors: Kohlmeier Martin , Adams Kelly M , Zeisel Steven H
Published: June 2021

Physicians encounter nutrition challenges in their clinical practice on a daily basis. They need an easily accessible training source. The Nutrition in Medicine project is already providing nutrition education for a majority of US medical schools and many international schools. A new series of online nutrition instruction modules is now available for medical residents. Brief segments teach important clinical nutrition skills. Longer modules cover the foundations of nutrition science. All of our online materials are available free of charge for medical students and physicians in training anywhere in the world.

We asked during registration about preparedness for nutrition challenges in clinical practice. Of 120 physicians, 95 responded about their preparedness for nutrition counseling. The majority (54%) indicated not to be knowledgeable enough to counsel at least half of their patients on nutritional prevention and treatment of cancer. Half of 114 responders reported that they calculated and interpreted the BMI for only half or fewer of their patients. All of these busy physicians (82% cared for more than 50 patients in the prior 3 months) were interested in adding to their clinical nutrition skills by using our online materials. We will ask them again three months later to find out whether use of our instruction improved their skills and practice patterns.

Supported by a grant from the National Cancer Institute.
Use of dietary supplements containing 1,3 dimethylamylamine by military personnel
Authors: Austin Krista Gail , McGraw Susan , Carvey Christina , Lieberman Harris R.
Published: June 2021

Dietary supplement (DS) manufacturers have incorporated sympathomimetic ingredients, including 1,3 dimethylamylamine (DMAA), into body building and weight‐loss DS products. Bodybuilding DS are consumed by approximately 21% of military personnel and 18% report using weight‐loss DS. Recently, concerns regarding the safety of DMAA products have been raised. Therefore, we examined the prevalence of DMAA DS use in this population. Surveys (N=1642) regarding DS use over the past 6 months were collected from a convenience sample of Air Force (n =1159) and Army (n=483) personnel. Air Force personnel were surveyed in multiple locations throughout the US and abroad; Army personnel were surveyed in Kuwait and Afghanistan. Twenty‐two percent of survey respondents [Air Force = 23%; Army = 18%] used a DS containing DMAA. Frequency of DMAA DS use was: > 1×/month 6% [Airforce = 7% ; Army = 5%]; > 1×/week 10% [Air Force = 11% ; Army = 9%]; daily 5% [Air Force = 5% ; Army = 4%]. Given the popularity of DMAA DS in military and perhaps civilian populations, research examining the pathophysiologic effects of DMAA and possible adverse health effects related to its consumption is essential.

(Support: US Army Medical Research & Materiel Command, Department of Defense Center Alliance for Dietary Supplement Research)
Legume consumption and bone mass in ovariectomized rats
Authors: Moon Hyoun Jung , Park Yongsoon
Published: June 2021

This study was examined the effect of consuming soybean, mung bean, cowpea, or adzuki bean on bone mineral density (BMD) and bone biomarkers in ovariectomized (OVX) rats. Sprague‐Dawley rats were either sham‐operated (Sham) or surgically ovariectomized., and then fed AIN‐93M diet (OVX) or AIN‐93M containing soybean (OVX‐S), mung bean (OVX‐M), cowpea (OVX‐C), or adzuki beans (OVX‐A) for 12 weeks. BMDs of the right femur, tibia and lumbar spine were measured using DEXA, and bone morphometric parameters by micro‐CT. The BMD and bone volume of the femur in OVX‐S and OVX‐M groups were significantly higher than OVX group. The expressions of TNF‐α and IL‐6 were significantly lower, while the expressions of osteoprotegerin/RANKL ratio were significantly higher in all bean consumed rats than OVX groups. Serum alkaline phosphatase in OVX‐S and OVX‐M groups was significantly lower, and serum osteocalcin was significantly higher in the OVX‐S, OVX‐M, and OVX‐A groups as compared with OVX group. However, bean consumption had no significant effects on IL‐1β expression, and urinary calcium and deoxypridinoline. In conclusion, soybean and mung bean may prevent bone loss in the OVX rats by reducing TNF‐ α and IL‐6, and increasing osteoprotegerin. (This work was supported by a grant from the KDRA, Agricultural R&D 15th Agenda PJ006983201005.)
Effect of diets with Cucurbita moschata, Jobˈs tears and Cudrania tricuspidata powder supplement on body fat, fecal amount, intestinal length and serum lipid contents in rats fed a high fat diet
Authors: Han Chan-Kyu , Park Ju-Hun , Cho Kyung-Dong , Lee Kyoung-Won , Sung Ki-Seung , Lee Bog-Hieu
Published: June 2021

This study was performed to investigate the effects of mixed‐diet with three functional food ingredients (Cucurbita moschata Duch.: CM, Jobˈs tears: JT, Cudrania tricuspidata: CT) on body fat, fecal amount, intestinal length and serum lipid contents in rats fed a high fat diet. Male SD rats were fed a high‐fat diet (D12492, 45 kcal fat) for 5 weeks during the first phase. In the second phase, which lasted 5 weeks, the rats were fed a high‐fat diet only (A, control), high‐fat diet with 10% mixed‐powder in the same ratio CM, JT and CT (B), and its mixed‐powder 20% (C), and 30% (D), respectively. Body weight gain and FER was lower in the group B, C, and D than in group A, but was not significantly different among the groups. The organ weights were similar in the experimental groups, and adipose tissue weights in groups with CM, JT, CT mixed‐powder were significantly lower than in the group A (p<0.05). The fecal weights of groups C and D increased significantly during the second phase compared to the group A (p<0.05), and the length of large intestine was significantly longer in the group C than in group A (p<0.05). The serum total cholesterol, LDL‐cholesterol and glucose contents were significantly decreased in the diet groups with mixed‐powder supplement than in the group A (p<0.05). These results indicate that supplementation with CM, JT, and CT seemed to be effective in decreasing body fat, blood lipid and glucose levels, and also in increasing fecal amount in rats fed a high‐fat diet.
(−)‐Nyasol, isolated from Anemarrhena asphodeloides suppresses neuroinflammatory response through the inhibition of I‐[kappa]B[alpha]degradation in LPS‐stimulated BV‐2 microglial cells
Authors: Li Hua , Lee Yu-ih , Chang Hee Ryun , Ryu Jae-Ha
Published: June 2021

Activation of microglia has been associated with pathological hallmarks of several neurodegenerative diseases. The regulation of microglial activation by inhibiting the production of pro‐inflammatory molecules can be useful therapeutic approach against neurodegenerative disorders.

Anemarrhena asphodeloides Bunge (Liliaceae) has been used as an anti‐pyretic, anti‐inflammatory and anti‐diabetic agent in traditional medicine in Korea, China and Japan. (−)‐Nyasol, a norlignan isolated from Anemarrhena asphodeloides, showed anti‐inflammatory potential in LPS‐activated BV‐2 microglial cells. (−)‐Nyasol suppressed the mRNA levels of tumor necrosis factor α (TNF‐α) and Interleukin 1β (IL‐1β) in activated microglial cells. It also inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) by down‐regulation of inducible nitric oxide synthase (i‐NOS) and cyclooxygenase‐2 (COX‐2), respectively. These inhibitory effects were correlated with the suppression of LPS‐induced nuclear factor κB (NF‐κB) nuclear translocation through the inactivation of p38 mitogen‐activated protein kinase (MAPK). These results suggest that (−)‐nyasol can be a modulator in neuro‐inflammatory conditions induced by microglial activation.
The effects of retinoblastoma (Rb) deletion on intestinal lipid absorption
Authors: Wandu Sylvia , Leinicke Jennifer , Erwin Christopher , Warner Brad
Published: June 2021

Background

The Retinoblastoma protein (Rb) may play a role in modulating the absorption of lipids within the small bowel. Rb null mice are characterized by an increased intestinal surface area compared to wild‐type (WT) mice. This study investigates the effects of Rb deficiency on lipid absorptive capacity with normal and high fat diets.

Methods

Rb null and WT mice were maintained on normal and high fat diets for short and long–term periods. Mice where weighted weekly. Fat absorption and fecal fat were determined using an extraction protocol. Lean mass and body fat were determined via nuclear magnetic resonance

Results

No differences in weight were found between Rb null and WT mice. The Rb null mice on normal chow had higher fecal fat compared to WT; however no significant difference in fat absorption was seen between the groups. Similar results were observed after the same mice were placed on a short‐term high fat diet. An extended high fat diet showed Rb null mice maintained a higher fecal fat while fat absorption increased in WT mice. No significant differences in body fat or lean mass were found between Rb null and WT mice on a prolonged high fat diet.

Conclusion

Regardless of the type of diet given, Rb null mice absorb lipids at a lower capacity compared to WT mice. Enhanced bowel surface area seems to serves no advantage in regards to lipid absorption.

Research supported by NIH grant DK 59288‐06A2
Hepatoprotective activity of ethanolic extract of Acanthopanax koreanum Nakai in induced liver injury model in Wistar rats
Authors: Jung Myung Ji , Wang Lin , Kim Ji Yeon , Kwon Oran
Published: June 2021

This study was performed to examine the effect of ethanolic extract of Acanthopanax koreanum Nakai (AE) and Acanthoic acid (AA) in D‐galactosamine/lipopolysaccharide (D‐GalN/LPS) liver injury model in 6 week‐old Wistar rat. Rats were randomly divided into 5 groups (Normal control, AE0%, AE1%, AE3%, AA) based on body weight. After the experimental diets were fed for 15 days, the experimental groups were injected D‐GalN (250mg/kg b.w)/LPS (10ug/kg b.w). Liver injury was assessed by plasma glutamic oxaloacetic transminase (GOT) and glutamic‐pyruvic transaminase (GPT) activities. We evaluated the inflammation indicators, such as TNF‐alpha, IL‐6, and NO. In the AE and AA treat groups, GPT, TNF‐alpha, IL‐6 in plasma significantly reduced as well as NO in the liver. Results of this study revealed that ethanolic extract of Acanthopanax koreanum Nakai could afford a significant protection against liver injury. This experiment suggests that ethanolic extract of Acanthopanax koreanum Nakai can be available for enhancing liver condition as a functional food. *This study was supported by JEJU TECHNOPARK (Project No.2011‐0655‐1)
Berry anthocyanin fractions inhibit LPS‐induced expression of inflammatory mediators in RAW 264.7 macrophages
Authors: Lee Sang Gil , Park Young-ki , Lee Jiyoung , Koo Sung I. , Chun Ock K.
Published: June 2021

Considerable attention has been directed to the health benefits of berries in preventing chronic diseases. The benefits are mainly attributed to the antioxidant and anti‐inflammatory properties of anthocyanins in berries. Since individual anthocyanins have different antioxidant properties, it is probable that berries having different anthocyanin compositions exert different biological and physiological effects. This study aimed to compare the anti‐inflammatory effects of three types of berries differing in major anthocyanins (malvidin in blueberry, cyanidin in blackberry, and delphinidin in blackcurrant, respectively). Anthocyanin fractions of blueberry, blackberry and blackcurrant were obtained by solid phase extraction from 80 % methanol crude extracts. RAW 264.7 macrophages were treated with 5, 10, and 25 ug/mL berry extracts for 12 h. Then, cells were treated with LPS for 12 h and mRNA abundance of TNF‐alpha and IL‐1beta was determined by real‐time PCR. Blackberry fraction suppressed the gene expression by 15–20% at 25 ug/mL. The other berry fractions also suppressed TNF‐alpha and IL1‐beta to a lesser extent. The findings suggest that anti‐inflammatory effects of berries vary depending on their anthocyanin compositions and that blackberry anthocyanin fraction may possess a more potent anti‐inflammatory property than the blueberry and blackcurrant fractions.
Human MUC2 mucin inhibits the antimicrobial activity of β‐defensin 2
Authors: Cobo Eduardo Ruben , Kissoon-Singh Vanessa , Trusevych Elizabeth , Moreau France , Chadee Kris
Published: June 2021

The intestinal epithelium is layered by a barrier composed of MUC2 mucin produced by goblet cells and β‐defensin 2, an inducible peptide produced by epithelial cells that exhibits antimicrobial and chemotactic activity. Bacteria infections and Ulcerative colitis and Crohn's diseases are associated with less MUC2 and altered defensin expression. In this study, we quantified the interaction between MUC2 mucin and β‐defensins. Human colonic mucin co‐incubated with β‐defensin 2 impaired defensin antimicrobial activities against Escherichia coli. However, addition of mucin 10–30 minutes following bacterial incubation with β‐defensin 2 did not alter antimicrobial activity. Mucin protective function on bacteria was partially abrogated by digesting the mucin terminal sialic acid residues with neuraminidases and oxidizing carbohydrate residues with sodium metaperiodate. Expression of murine β‐defensin 4 mRNA, an orthologue of human β‐defensin 2, was constitutively increased in the colons of mice deficient in MUC2 (Muc2−/−) and in dextran sodium sulfate induced colitis. These studies suggest that MUC2 abrogates the antimicrobial effect of β‐defensin in the intestinal mucosa by binding bacteria and therefore, mucin may shape the normal microflora by limiting β‐defensin antimicrobial activity. In contrast, β‐defensins are up regulated during mucosal damage when the mucus barrier is breached.
Cellular Stress Directs IGF‐Binding Protein‐3 (IGFBP‐3) to the Nucleus in Mammary Epithelial Cells
Authors: Agostini-Dreyer Allyson , Cohick Wendie S.
Published: June 2021

IGFBP‐3 has both mitogenic and apoptotic functions in normal mammary epithelial cells (MEC) as well as breast cancer cell lines. The factors that determine whether IGFBP‐3 promotes cellular survival or death are unclear. Since both the mitogen IGF‐I and the apoptotic inducer anisomycin (ANS) increase IGFBP‐3 production in MEC, we proposed that cellular localization may determine IGFBP‐3 action. While both IGF‐I and ANS stimulated the release of IGFBP‐3 into conditioned media, only ANS induced nuclear localization of IGFBP‐3. Time course analysis showed that ANS induced nuclear localization of IGFBP‐3 and caspase activation across a similar time line, with significant increases in each parameter observed by 3 hr. Knockdown of IGFBP‐3 with small interfering (si)RNA reduced nuclear IGFBP‐3 and attenuated ANS‐induced apoptosis measured by cleavage of caspase‐3 and‐7 and PARP. A pan‐caspase inhibitor had no effect on ANS‐induced nuclear localization of IGFBP‐3, suggesting that nuclear entry of IGFBP‐3 precedes caspase activation. Although IGFBP‐3 has a nuclear localization sequence, siRNA knockdown of the nuclear transport protein importin‐β did not affect nuclear localization of IGFBP‐3 in response to ANS, indicating it does not utilize importin‐β for nuclear entry. In summary, our data indicate that localization of IGFBP‐3 is a controlled event regulated by cellular stress. This project was supported by National Research Initiative Competitive Grant no. 2009‐35206‐05210 from the USDA National Institute of Food and Agriculture to WSC.
Activation of Na,KATPase signaling protects against glomerulo‐tubular disconnection
Authors: Burlaka Ievgeniia , Holtback Ulla , Liu Xiao Li , Eklof Ann-Christine , Fogo Agnes , Aperia Anita
Published: June 2021

Glomerulo‐tubular disconnection and formation of atubular glomeruli is a common feature in glomerular and tubular disorders and is believed to contribute to progression of renal disease. Apoptosis of proximal tubular cells caused by proteinuria is considered a main cause of the disconnection. Our group has identified a novel signaling system in the kidney that is activated by ouabain and involves Na,K‐ATPase and the inositol 1,4,5‐triphosphate receptor. Downstream effects include activation of antiapoptotic factor Bcl‐xL and protection from apoptosis. Here we have examined whether chronic ouabain treatment prevents glomerulo‐tubular disconnections in rats with Passive Heymann Nephritis (PHN), followed for 4 months. Rats received ouabain (15 μg/kg/day) or vehicle via mini pumps. The number of apoptotic cells at the glomerulo‐tubular disconnection, number of atubular glomeruli and serum creatinine were significantly lower in PHN/ouabain than in PHN/vehicle rats.

Conclusion

Proteinuria‐induced apoptosis and glomerulo‐tubular disconnection can be alleviated by the antiapoptotic signaling pathway triggered by ouabain.
Protective effect of dietary flaxseed oil on bleomycin‐induced pulmonary fibrosis
Authors: Choi Seojin , Lin Dingbo , Molteni Agostino , Wang Weiqun , Baybutt Richard
Published: June 2021

Dietary flaxseed oil, containing n‐3 fatty acids, has been previously found in our study to protect against bleomycin‐induced pulmonary fibrosis. This study further reported the time‐course effect and potential underlying mechanisms. Forty Sprague‐Dawley rats were assigned into four groups with either corn oil (15% w/w) or flaxseed oil (15% w/w) in the diet for one month prior to treating with bleomycin at 8 U/kg oropharyngeally. Half of the rats were sacrificed 7 days after bleomycin treatment, and the others were sacrificed 21 days after the treatment. Both interleukin‐6 (IL‐6), a protein associated with fibrotic inflammation in the lung, and renin, an enzyme related to renin‐angiotensin system, were examined by Western blot. The time‐dependent increase of IL‐6 and renin proteins in response to bleomycin treatment was significantly reversed by flaxseed oil diet. In addition, the profiles of fatty acids in both liver and kidney tissues as measured by lipidomics demonstrated a significant increase of n‐3:n‐6 ratio in flaxseed oil‐fed groups. These results indicated for the 1st time that n‐3 fatty acid‐enriched flaxseed oil might inhibit the formation of pulmonary fibrosis via suppressing inflammation and renin‐angiotensin system.
Exogenous Calcium Induces Autophagy via Classical Autophagic Machinery and Recruits Endoplasmic Reticulum Membranes to Form Autophagosomes
Authors: Chen Xi , Li Min , Gao Wentao , Yin Xiao-Ming
Published: June 2021

Calcium plays a role in regulation of autophagy. We have reported that exogenously added calcium as the calcium phosphate precipitate (CPP) induces autophagy. Here we further show that CPP‐induced autophagy applies classical autophagic machinery including LC3 conjugation molecules Atg4, Atg5 and Atg3, and autophagosome nucleation molecules FIP200 and Beclin1; however, Atg9 is not involved. CPP does not induce mTOR inhibition, neither over‐production of radical oxygen species, and only slightly increases endoplasmic reticulum (ER) stress. CPP activates DFCP1 in a PI3k and calcium dependent manner, and increases the association of DFCP1 with autophagosomes. ER membrane, but not Golgi and mitochondria membranes, comprises part of the LC3 positive autophagsomes. These data suggests CPP works through non‐mTOR dependent mechanisms to activate downstream classical autophagosome nucleation and expansion molecules, and the growth of autophagosomes induced by CPP is closely related to ER.
GSK3 negatively regulates stress response mediated by transcription factor Nrf1, resulting in increased neuronal apoptosis and neurodegeneration
Authors: Biswas Madhurima , Chan Jefferson Y.
Published: June 2021

Oxidative and endoplasmic reticulum (ER) stress play an important role in the pathogenesis of neurodegenerative diseases. Nuclear factor E2‐related factor 1 (Nrf1), a member of the Cap n Collar basic‐leucine zipper family of transcription factor, is highly expressed in neuronal cells, and directs expression of genes encoding antioxidants and proteins that make up the proteasome. We found that glycogen synthase kinase 3 (GSK3), which has been implicated in the causation of neurodegenerative disorders, negatively regulates Nrf1 expression by targeting it for ubiquitination and proteosomal degradation. Nrf1 knockdown neuronal cells are sensitized to ER and oxidative stress‐induced apoptosis. Mutation of GSK3 phosphorylation sites on Nrf1 leads to protein stabilization, and protects against stress‐induced apoptosis. Over expression of kinase dead mutant of GSK3 reduces stress‐mediated apoptosis in the Nrf1 knock down cell line. These studies demonstrate a mechanism by which Nrf1 expression is regulated and how Nrf1 impacts on stress‐mediated apoptosis of neuronal cells.

Source of Funding – NIH grant.
Incidence of Common Coronary Artery Variants and Anomalies and the Implications Thereof
Authors: Neufeld Ethan , Escobar-Poni Bertha Corina
Published: June 2021

The coronary arteries have many variant branching patterns and anomalies. Knowledge of these is crucial to physicians as they impact cardiac pathology and may themselves be pathologic. We aimed to assess the coronary anatomy of all 45 available cadavers at our institution for these entities. Right, left or co‐dominance was determined in each heart via the posterior descending (PDA) and AV nodal arteries. The presence of bridging, hypoplasia and duplication of the major branches was assessed. 35(78%) of the hearts were left dominant, 5(11%) were right dominant and 5(11%) were co‐dominant. A conus branch was seen in 34 hearts. In 21(62%) it arose from the right coronary artery (RCA) and in 13(38%) from the aorta. A sinoatrial artery was seen in 36 hearts. In 25(69%) it arose from the RCA and in 11(31%) from the left circumflex artery. A ramus intermedius was seen in 11(24%). 1 heart had a high origin of the left coronary artery. 1 heart had bridging of the left anterior descending artery (LAD). 1 heart had duplication of the LAD and 2 had duplication of the PDA. 1 heart had a hypoplastic LAD with collaterals from the PDA and 1 had a hypoplastic PDA with collaterals from the LAD. Based on this set of hearts we report an incidence of the common anatomical variants in keeping with the current literature. Knowledge of these entities and is crucial to accurately treat pathologies and to avoid unnecessary interventions. The source of research support is from the division of Anatomy, Department of Pathology and Human Anatomy, School of Medicine, Loma Linda University, Loma Linda, CA.
A DUB, Ubiquitin C‐terminal Hydrolase‐L3 Affects Osteoblast Formation
Authors: KIM JI YOUNG , Ahn Sang-Ho , Wada Keiji , Cho Je-Yoel
Published: June 2021

Deubiquitination, the reversal of ubiquitination, is the action of deubiquitinating enzymes (DUBs). Its mechanism is essential in various biological processes and diseases. Mutations in genes expressing DUBs have been implicated in a number of diseases including cancer, neurodegeneration, and osteoporosis. Our recent study showed that ubiquitin C‐terminal hydrolase L3 (Uch‐L3), a DUB, regulates Smad1 ubiquitination and bone morphogenetic protein 2‐induced osteoblast differentiation. In this study, for the first time, we observed the specific function of Uch‐L3 in bone metabolism in vivo. Uch‐L3 knock‐out mice have the osteoporotic phenotype, such as less bone mass than that of control group. The decreased activity of osteoblast was also observed in Uch‐L3 knock‐out mice by the analysis of calcein double labeling. In primary osteoblast cells, the deficiency of Uch‐L3 gave the delayed mineralization. An amazing observation, furthermore, was the increased expression of Uch‐L3 during the osteoblastogenesis. Therefore, these results suggest Uch‐L3 might be an important modulator of osteoblast formation in the maintenance of bone homeostasis. [This research was supported by a grant from the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. 2010‐0011231).]
Effect of Glycated LDL on Monocyte Adhesion on Vascular Endothelial Cells: Role of Plasminogen Activator Inhibitor‐1
Authors: Shen Garry , Zhao Ruozhi , Ren Song , Moghadasian Mohammed
Published: June 2021

Diabetes accelerates the development of atherosclerotic cardiovascular diseases. Inflammation on endothelium plays a key role in atherosclerosis. Monocyte adhesion is the earliest event of vascular inflammation. Elevated levels of glycated low density lipoprotein (gLDL) were detected in diabetic patients. We previously demonstrated that gLDL increased the expression of plasminogen activator inhibitor‐1 (PAI‐1) in vascular endothelial cells (EC). PAI‐1 is the physiological inhibitor of tissue and urokinase activators, and a marker of inflammation and endothelial dysfunction. The results of the present study demonstrated that pre‐incubation with gLDL significantly increased the adhesion of THP‐1 monocytes on the surface of cultured human umbilical vein EC (HUVEC) with a peak at 100 μg/ml for 6 h. Transfection of short interference RNA (siRNA) for PAI‐1 to EC prevented gLDL‐induced monocyte adhesion on EC. Scrumble siRNA did not inhibit gLDL‐induced monocyte adhesion on EC. Increased monocyte adhesion on aorta was detected in leptin receptor‐deficient (db/db) diabetic mice. The results of the present study suggest that diabetes‐associated metabolic disorders may promote the adhesion of monocytes to vascular endothelium, and PAI‐1 is required for glyLDL‐induced monocyte adhesion to vascular EC (supported by CDA and CIHR).
The influenza virus hemagglutinin mediates secondary bacterial otitis media by inducing middle ear inflammation
Authors: Wijburg Odilia , Reading Patrick , Browne Lorena , Pedersen John , Gilbertson Brad , Hermans Peter , DIavatopoulos Dimitri , Short Kirsty
Published: June 2021

Otitis media (OM) is an inflammatory disease of the middle ear that affects almost every child under the age of five and can lead to fatal meningitis or permanent hearing loss. We investigated the role of influenza A virus (IAV) surface proteins in inducing bacterial otitis media, using a novel infant mouse model and a panel of reassortant virus strains.

Our results showed that the viral hemagglutinin (HA) facilitates pneumococcal OM. Of the two HA subtypes currently circulating in the community, only H3 viruses induced disease. The ability of H3 viruses to induce pneumococcal OM reflected their ability to induce middle ear inflammation, which was dependent on virus replication and enhanced viral titers in the middle ear following an H3, rather than H1, infection. The clinical relevance of these data was confirmed in vitro using human middle ear epithelial cells where we demonstrated that the HA of Udorn/72 mediated increased viral infection and inflammation. We conclude that the H3 HA plays a key role in the development of pneumococcal OM. These data provide an exciting contrast to previous studies on pneumococcal pneumonia and suggest that monitoring the HAs of circulating IAV strains may play an important role in predicting the likely incidence of bacterial OM. Thus, targeting the influenza HA may represent a novel therapeutic approach to prevent pneumococcal disease including OM. Supported by Australian NHMRC.
Effect of neutrophils from septic patients on endothelial barrier function
Authors: Fox Elizabeth , Heffernan Daithi , Reichner Jonathan
Published: June 2021

BACKGROUND

Sepsis is marked by systemic activation of the inflammatory system. With ongoing inflammation, integrity of the endothelium is compromised, leading to vascular leak, hypotension, and organ hypoperfusion. The effect of neutrophils obtained from septic patients on the integrity of the endothelial monolayer was examined and compared to naïve and fMLP‐activated cells.

METHODS

Blood was obtained from septic patients and healthy volunteers. Neutrophils were purified from whole blood using anti‐CD15 affinity bead purification. Human umbilical vein endothelial cells were grown to confluence and activated with TNFα. The relative effect of neutrophils on endothelial barrier function was determined by endothelial cell‐substrate impedance sensing.

RESULTS

All neutrophil populations decreased monolayer resistance; however, the kinetics and extent of effect varied according to cell source and treatment. Neutrophils from septic patients caused less decrease in barrier function and exhibited a more biphasic response over time, compared to naïve and activated neutrophils.

CONCLUSIONS

Neutrophils from septic patients manifest a distinctly different effect on endothelial barrier function when compared to fully activated or naïve cells. Supported by NIHGM066194.
BMP signaling promotes lateral vessel branching
Authors: Chong Diana C , Wiley David M , Bautch Victoria L
Published: June 2021

Bone morphogenetic protein (BMP) signaling is required for the growth and differentiation of multiple organs during embryonic development, including the cardiovascular system. However, its involvement in vascular development, in particular angiogenesis, has yet to be fully characterized. Previous work in the Bautch and Jin labs showed that BMP signaling is required for venous vessel sprouting during zebrafish development. Recent follow‐up studies showed that while a vessel's ability to respond to BMP is not restricted to arterial or venous vascular beds in mammalian vessels, BMP promotes lateral branching in these scenarios. Currently, we are examining mechanisms. Our results show that BMP signaling affects tip cell dynamics, and BMP also stimulates a subpopulation of stalk cells to sprout. Thus using multiple model systems, we show that BMP signaling increases lateral branching in vessel networks.
Circulating genotypes of influenza virus in India and their correlation with clinical features and metereological factors
Authors: Jain Amita , Dangee Tanushree , jain Bhawna , Singh Kaleshwar Prasad , Singh Jaiveer , Singh Ajai , Dwivedi Mukesh
Published: June 2021

The present study was undertaken to investigate the prevalent genotypes of influenza viruses in India and study their correlation with meteorological factors and clinical features. A total of 1175 patients were enrolled and divided into two severity groups; influenza like illness (ILI; 961) and severe acute respiratory illness (SARI; 214). Confirmation of influenza A and B positives was done by one step real‐time RT‐PCR using group specific primers. Influenza A positives were further subtyped into H1, H3 and pandemic H1 and correlated with various environmental factors to determine seasonality. Association of Influenza A and B infection with clinical parameters was also studied. Prevalence of influenza virus infection during study period was 12.37% (145/1175); influenza A was more prevalent (8.7%) than influenza B (3.7%). Positivity for influenza virus was significantly higher in ILI patients (13.9%, 134/961) than SARI patients (5.14%, 11/214). Positivity of influenza peaks significantly correlated with rainfall and dew point while temperature difference and atmospheric pressure were inversely related. No significant correlation was found with humidity and wind speed. Nasal discharge is significantly associated with Influenza A infection while seizers and vomiting are significantly associated with influenza B infection.

Pandemic (2009) H1N1 was circulating till October 2010 which was entirely replaced by H3N2 genotype of influenza A. The seasonality of influenza virus infection varies from region to region is associated with environmental factors.
The effect of industrial pollution from a smeltery of heavy metals in Mitrovica (Kosova) on the duration of Drosophila melanogaster preadult development
Authors: Bajrakti Ismet Dervish , Alija Avdulla , Gashi Agim , Halili Fetah
Published: June 2021

The effect of enormous environmental pollution by heavy metals on genes controlling the duration of wild type Drosophila melanogaster preadult development in the region of a lead and zinc smeltery in Mitrovica (Kosova) was investigated. Also the natural population of this species from the vicinity of Prizren, which represents an unpolluted area, was exposed near the smeltery of heavy metals for intervals of 100 and 175 days. The second chromosome of wild type flies was isolated and transferred either in homozygous (+′/+′) and heterozygous (+′/+″) state using Cy/Pm line. Individuals of this line contain dominant mutations (Cy – curly wings and Pm – plum eyes) and long inversions, which prevent recombination with analyzed chromosomes, with the end result of stable heredity in the descendants.

The shorter total duration of preadult development (9,5 days) had the population exposed to pollution for 100 days; whereas the population exposed for 175 days and that from the region with enormous pollution had a very similar total means values of duration of preadult development (10,5 days respectively 10,8 days) as the control (10,7 days).

We propose that such enormous environmental pollution by heavy metals for 100 days exposure caused a high number of dominant mutations on genes controlling duration of D. melanogaster preadult development on the second chromosome. However, such mutations with their carriers are eliminated by natural selection after 175 days exposure.
Rare Case of Multicentric Castlemanˈs Disease and Progressive Multifocal Leukoencephalopathy in a Severely Immunocompromised Patient
Authors: Solieman Noha , Chapman Sherita , Mehta Preema , Kurukumbi Mohankumar
Published: June 2021

Background

HIV‐associated Multicentric Castleman's Disease (MCD) is a rare malignant lymphoproliferative disorder in which human herpes virus 8 (HHV8) has been found to be a universal factor. Progressive multifocal leukoencephalopathy (PML) is a rare disease of the central nervous system white matter, which has an increased risk in severely immunocompromised patients. Here we present an interesting patient with newly diagnosed HIV infection with PML and Castleman's disease.

Case Presentation

Forty‐six year old female presented with progressive speech difficulty and left facial droop. Clinical examination was normal except for axillary lymphadenopathy, mild motor dysphagia, and decreased visual acuity on the left eye. Imaging revealed a left temporal lesion and significant cervical lymphadenopathy. HIV testing was positive with CD‐4 count of twenty‐six. Cerebrospinal fluid analysis was negative for malignancy; few scattered lymphoid cells present and JC virus (John Cunningham virus) was detected. Biopsy of axillary nodes showed atypical lymphoid hyperplasia with regressed germinal centers, paracortical expansion and increased plasma cells, suggestive of Castleman's disease. Immunohistochemical stain with HHV8 was negative.

Conclusion

This case is presented because of the rarity of occurrence of HIV infection, PML and MCD that has never been reported in the literature.
Exposing timed pregnant rats to shipping stress during late, but not early gestation, leads to offspring with increased activity in the novel open field
Authors: Philpot Rex M , Engberg Melanie E , Wecker Lynn
Published: June 2021

Prenatal stress produces offspring with altered behavioral, neurochemical and endocrine system characteristics, but the impact of shipping pregnant animals during different times of gestation has not been evaluated. To assess the impact of shipping stress, novel open field activity was compared between the offspring of rats bred on‐site and offspring from timed pregnant dams (TPD) shipped on gestational days (GD) 3–5 or 17–19. Adolescent rats born from dams shipped during GD 17–19 moved further and faster (p<0.05) and engaged in less freezing behavior than rats born from dams either bred on‐site or shipped during GD 3–5. To ascertain whether these divergent behaviors reflected differences in stress responses induced by placement in the novel open field, serum corticosterone (CS) levels were determined. A negative linear correlation (p<0.05) was apparent between open field activity and serum CS during the 60 min period following open field exposure. Results indicate that the stress of shipping pregnant dams during late gestation leads to offspring that experience reduced stress in the novel open field, resulting in increased exploration and decreased avoidance behavior. Supported by NIAAA 016449
Immature serotonergic regulation of anxiety‐like behavior in adolescent male rats
Authors: Arrant Andrew E , Kuhn Cynthia M
Published: June 2021

Novelty seeking and risk taking peak during adolescence. The goal of this study was to investigate whether immature serotonergic function contributes to adolescent risk taking using the light/dark (LD) test as a model of rodent behavior in an aversive environment.

Adult (PN67–70) and adolescent (PN28–32) male rats were given a single dose of fluoxetine (10 mg/kg), the 5‐HT1A agonist 8‐hydroxy‐2‐(dipropylamino)tetralin (8‐OH DPAT, 0.25 or 0.5 mg/kg), the 5‐HT2 agonist meta‐chlorophenylpiperazine (mCPP, 0.5 or 1 mg/kg), or vehicle and placed in the LD box. The latency to emerge into the light and time in the light compartment were measured for 15 minutes. The effects of fluoxetine (2.5, 5, and 10 mg/kg i.p.) on extracellular serotonin in the medial prefrontal cortex (mPFC) were measured by microdialysis followed by HPLC. Adolescents were less sensitive to the anxiogenic effects of fluoxetine and 8‐OH DPAT, but not mCPP. There was no age difference in the increase in mPFC serotonin after fluoxetine. Adolescents treated with 8‐OH DPAT exhibited reduced activation of the central amygdala and paraventricular hypothalamus, as shown by c‐Fos immunostaining.

These data show that serotonergic induction of behavioral inhibition in the LD test is deficient in adolescent rats. This may be due to immature 5‐HT1A receptor modulation of the neural circuits mediating LD behavior.

Supported by DA019114 and F31DA032532