bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Physical Exercise on a Sub‐Sample of Obese Children in Enugu South Local Government Area of Enugu State, Nigeria
Authors: Olyalawuba Nkeiruka , Nnam Ngozi
Published: June 2021

Study Objective

Assess the effect of physical exercise on a sub‐sample of the subjects weight

Statement of Methods

The study used a cross‐sectional descriptive comparative design. A Multi‐stage stratified random sampling technique was used in selecting 10 schools out of 54 and 2000 children out of 13,981 that were used for the study.

Anthropometric measurements (weight, height and triceps) were obtained in the subjects to determine obesity. High‐energy physical exercise was carried out for a period of two months on a sub‐sample of thirty obese children and the data were compared with a control group who did not receive any exercise. Table 1 shows the influence of exercise on weight loss of the children n=30

Total time spent
Initial weight
Final weight
Weight loss

Male
2784.44+/‐95.02
62.89+/‐11.21
52.39+/‐5.62
10.50+/‐3.11

Female
2718.17+/‐67.15
55.23+/‐15.08
46.70+/‐4.12
8.53+/‐2.16

t‐value(p‐value)
2.23(0.03)
1.51(0.15)
0.63(0.54)
0.56(0.57)

6‐8 years
2749.14a
53.66b
45.60a
8.06a

9‐10years
2767.13a
59.91ab
48.11a
11.80a

11‐12years
2764.13a
70.53a
47.36a
23.16a

F‐value(p‐value)
0.12(0.89)
5.41(0.01)
0.11(0.90)
1.417(0.26)

Combined
2757.93+/‐89.97
59.06+/‐13.21
49.23+/‐12.35
9.52+/‐20.69

Summary of Results

Physical exercise resulted to a significant (p<0.05) weight loss by the children. Their initial mean weight was 59.06kg and final mean weight was 49.23kg, with a mean weight loss of 9.52kg. The total time spent by the male children was significantly (p<0.05) longer, relative to the female on the exercise. Table 1 shows the influence of exercise on weight loss of children, n=30 and table 2 shows the BMI classification of children after the exercise. Table 2 shows the classification of BMI by sex of the children after the exercise .

Classification of BMI
Intervention Group
Control. Group

Male. Female. Total
Male. Female. Total

F. %. F. %. F. %
F. %. F. %. F. %

Obesity
10.55.6. 4. 33.3. 14. 46.7
20. 95.2. 9. 100. 29. 96.7

Overweight
8. 44.4. 8. 66.7. 16. 53.3
1. 4.8. 1. 3.3

Total
18. 12. 30
21. 9. 30

100.0. 100.0. 100.0.
100.0. 100.0. 100.0

Statement of Conclusion

After the exercise, percentage of obese children dropped from 100,00% to 47.00% while in the control group there was no significant effect (p>0.05). This reduction explains that in addition to dietary modification, there is need to include physical exercise in the life style of children.
Food Insecurity among Undergraduate Students
Authors: Davidson Alana , Morrell Jesse
Published: June 2021

In 2013, 49.1 million Americans lived in food insecure households. Of these, 15.8 million were children. As college students are excluded from national surveillance data, it is difficult to characterize the prevalence of food insecurity among this population. The purpose of this study was to determine the prevalence of food insecurity among undergraduate students and what characteristics are associated with food insecurity. Students (18‐24 years) were recruited from the ongoing College Health and Nutrition Assessment Survey at the University of New Hampshire (UNH). A 26‐item online survey was developed by combining the USDA 6‐item Short Form U.S. Household Food Security Survey, the USDA Child Food Security Survey, and 11 UNH‐specific questions related to food access. The survey was administered to all students enrolled in a general nutrition class in fall 2014 (n = 418); response rate=50.5% (n=211, 84% female). Survey results indicated 11.4% of students reported low food security and 6.2% reported marginal food security during their childhood. During the past 12‐months, 12.4% reported experiencing low food security and 5.7% reported marginal food security; 2.8% reported currently or previously receiving food assistance. Students who lived in on‐campus housing were more likely to report food security as compared to those living in off‐campus apartments (86% vs 57%, p<.05); no differences in race, sex, marital status or parents' education were observed between students who were food secure vs. insecure. The findings of this study suggest that food insecurity exists on the UNH campus and further research related to food availability and education is needed. Due to the lack of data, other college campuses may benefit from assessing food insecurity prevalence among students.
Role of Arginase 1 in Diabetes‐Induced Senescence of Endothelial Cells and Macrophages
Authors: Xu Zhimin , Shosha Esraa , Narayanan S.Priya , Lemtalsi Tahira , Xing Ji , Caldwell Robert , Caldwell Ruth
Published: June 2021

Cellular senescence has been considered as a contributing factor to diabetes related complications. The present study was undertaken to evaluate involvement of the ureahydrolase enzyme arginase 1 (A1) in diabetes‐induced senescence of vascular and bone marrow cells. Studies were performed using retinas and bone marrow cells from wild type (WT) and A1 knockout diabetic and control mice and cultured bovine retinal endothelial (BRE) cells treated with high glucose or transduced with arginase 1. Cellular senescence, as indicated by increases in senescence‐associated beta galactosidase (SA‐β‐gal) activity was increased in bone marrow cells, macrophages and retinal vessels from WT diabetic mice. The SA‐β‐gal activity in retinal vessels, bone marrow cells and macrophages was markedly reduced by deleting one copy of A1 in the diabetic mice (p<0.01) and was similar to those in the non‐diabetic control mice. Overexpression of A1 or high glucose treatment of BRE cells resulted in elevated levels of SA‐β‐gal and increases in cleaved caspase 3, phosphorylated p38MAPK and P21 (a senescence marker), as compared to the controls transduced with mutant arginase or treated with normal glucose media. Our results suggest that A1 plays an important role in diabetes‐induced cellular senescence. Inactivation of A1 may offer a therapeutic strategy for preventing vascular injury and cellular senescence in diabetes.
Activation of Phospho Signaling Pathways in Human Colorectal Cell Lines in Response to Cytokines
Authors: Fasler‐Kan Elizaveta , Sautbayeva Zarina , Barteneva Natasha
Published: June 2021

Abstract Colorectal carcinoma (CRC) tumors are classified in two groups: approximately 75% of patients have CRC tumors of sporadic origin and 25 % of patients have a hereditary contribution. Understanding the underlying molecular mechanisms is a prerequisite for developing therapeutic strategies. We investigated cytokine‐induced changes of the JAK‐STAT signaling pathways in several CRC ell lines.

Methods Human colorectal cell lines (HCT‐15, Colo 205, LS ‐180, SW480 and SW620) were used to study modulation of MHC class I and class II expression in response to human recombinant interferon alpha and interferon gamma. The nuclear translocation of STAT proteins was analyzed by confocal laser microscopy and flow cytometry.

Results We have observed that several colon carcinoma cell lines do not express MHC proteins. Strong activation of STAT1 was observed in response to interferon gamma. Human recombinant IL‐6 and IL‐4 activated STAT3 and STAT6, respectively. Confocal microscopy identified the nuclear translocation of the STAT proteins.

Conclusions Our data demonstrate the up‐regulation of the members of the JAK‐STAT signaling pathway in colon carcinoma cell lines.
Writing on the Board versus PowerPoint: What do Students Prefer and Why?
Authors: Brandl Katharina , Schneid Stephen , Armour Chris
Published: June 2021

Introduction

Since the introduction of the presentation software PowerPoint, the vast majority of university teachers use this program to deliver their lectures instead of writing on a chalkboard or whiteboard. While PowerPoint has some advantages, many of the benefits of writing on the board have been lost.

Research Questions

Do students prefer lectures that are delivered by writing on the board or by PowerPoint and what are their reasons for their preferences?

Methods

Undergraduate biology students and second‐year pharmacy students were surveyed about whether they prefer lectures taught by “writing on the board” or using PowerPoint. The students were also asked to explain their preferred teaching method. Data was collected over four years with 900 students participating.

Results

Over 85% of the students indicated the preference for “writing on the board” compared to PowerPoint. Common themes in favor for “writing on the board” included (1) more active engagement, (2) more appropriate pace, and (3) presentation of less extraneous material. For students who preferred PowerPoint, the main reasons were accessibility of the lecture notes if absent and less uncertainty of whether the notes they had were complete.

Discussion

It is clear that writing on the board is the preferred lecture format among students. The data indicate that if PowerPoint presentations are going to be used, then the shortcomings of this approach need to be addressed. We therefore recommend that lectures should be developed as if they were going to be written on the board and then converted to PowerPoint.
Controlling Sulfuryl‐Transfer In Vivo One Compound at a Time
Authors: Cook Ian , Feng Lei , Wang Hua , Kopp Felix , Wang Ting , Wu Peng , Marlow Florence , Leyh Thomas
Published: June 2021

Sulfonation is a reversible modification that regulates the binding of endogenous and xenobiotic small‐molecules to receptors, controls their half‐lives and is intimately linked to human disease and drug efficacy. In humans, these reactions are catalyzed by a small (13 member) family of broad‐specificity enzymes, the cytosolic sulfotransferases (SULTs). Here, molecular principles of SULT and nuclear‐receptor ligand‐specificity are used to create, for the first time, a design strategy that is capable of preventing the sulfation of a single compound in vivo without inhibiting SULTs or significantly altering the receptor‐binding functions of the compound. Unlike classical inhibition approaches, this new strategy prevents sulfonation without inhibiting SULTs and thus maintains their homeostatic functions. The strategy is demonstrated for the nuclear‐receptor family in an ex‐vivo structure‐activity study based on the scaffold of raloxifene (Evista®) ‐ an FDA‐approved nuclear‐receptor agonist – and is shown to dramatically enhance the efficacy of apomorphine (an FDA‐approved dopamine‐receptor agonist) in zebrafish. The results indicate that sulfuryl‐transfer and its attendant biology can now be controlled in vivo on a compound‐by‐compound basis. These concepts are expected to lead to new highly specific in vivo probes of sulfuryl‐transfer biology, improvements in drug design and substantial enhancements in the efficacy of numerous FDA approved drugs.
Tea Inhibits Hageman Factor
Authors: Madkhali H , Tarawneh A , ALI Z , Cutler S , Khan I , Shariat‐Madar Zia
Published: June 2021

Plasma prekallikrein (PK)activation exerts both physiological and pathological effects within the cardiovascular system and CNS. Activated PK (kallikrein) controls cytokine release from human mononuclear cells, and controls both the intrinsic blood coagulation and the alternative complement cascades. The uncontrolled activation of these cascades results in the development of pathological pain and angioedema. PK is involved with the repair processes that replace injured/damaged tissue. Under pathological conditions, the activation of PK is triggered to be excessively robust. Kallikrein levels are indicated to be associated with hereditary angioedema and myocardial infarction, whereby kallikrein amplifies the generation of activated factor XII (FXIIa) and bradykinin (BK). We hypothesized that kallikrein inhibitors represent a novel class of drugs for curbing inflammation with a broad spectrum of activity. We sought to test the anti‐inflammatory effects of medicinal plants, known for their anti‐inflammatory properties in a system of BK‐forming capacity in endothelial cells and amidolytic kallikrein/FXIIa assay method. The water extracts of tea (Camellia sinensis) inhibited kallikrein and FXIIa with IC50s of 200 and 27 mg/mL. 50mg/mL crude water extracts did not influence cell viability. The extracts inhibited FXIIa ‐induced cell migration. Bioassay guided fractionation was performed on the water extracts to isolate the active compounds. Known polyphenols were ineffective in inhibiting kallikrein and FXIIa. The purified fraction displayed FXIIa inhibition of 88 ±1.5% at a concentration of 700 mg/mL. The bioactive composition comprising the aqueous extract and active fraction of tea may be used for the purpose of reducing FXIIa‐dependent inflammation and thrombosis.
Caloric Restriction and Dietary Curcumin Improve Functional Outcomes of Aging in Mice
Authors: Sarker Marjana , Franks Susan , Sumien Nathalie , Forster Michael
Published: June 2021

Curcumin, from Curcuma Longa, has antioxidant and anti‐inflammatory effects that are hypothesized to benefit impaired functional capacity related to normal aging. The following results are from an ongoing study of dietary curcumin alone and in combination with caloric restriction, testing functional and biochemical outcomes in late middle age (MAG) (15 months) and senescent (AG) (20 months) C57BL/6J male and female mice. Mice were assigned in treatment groups to receive: (i) base diet ad libitum (AL), (ii) weight stable caloric restriction (CR), (iii) curcumin in the base diet (7200 mg/kg diet) (CURAL) or (iv) curcumin plus CR (CURCR). At 8 weeks of treatment, all mice were tested for spatial memory and cognitive flexibility. Cognitive flexibility, tested using a serial reversal task, was significantly better for MAG males under CR and CURAL compared to AL but not under CURCR, suggesting an antagonistic interaction. On the other hand, MAG and AG female experimental groups did significantly better than AL. No interaction of CR and CUR was observed in AG males, with CURAL and CR yielding comparable benefits. None of the treatments had a significant effect on hippocampus‐ dependent spatial memory performance in MAG or AG. These results suggest that when implemented separately, both CR and CUR treatments have an ameliorative effect on impaired frontal cortical function present in late middle age and senescence. These effects were similar across different behavioral tasks and were non‐interactive or antagonistic, suggesting that they could involve the same or similar mechanisms. Therefore, curcumin intake may mimic the effect of CR in the absence of diminished energy intake and weight loss.
Bioreversible Protein Labeling For Cellular Delivery
Authors: Andersen Kristen , Smith Thomas , Raines Ronald
Published: June 2021

A growing number of potential chemotherapeutic agents are proteins. A major challenge to the use of proteins as intracellular drugs is their traversal of the negatively charged glycocalyx and cell membrane. Many methods have been developed over the past several decades to try to overcome this obstacle, including liposome carriers, various polymers, cell‐penetrating peptides, and changes to the protein itself. All of these methods have downsides, including cytotoxicity, low delivery yields, and irreversible changes to the proteins. Here, we present two complementary methods of bioreversible protein modification that endow cell permeability, and we demonstrate their efficacy using the green fluorescent protein (GFP). The first method labels lysine residues with a module that combines the trimethyl lock scaffold to enable bioreversibility in the presence of cellular esterases, and a boronic acid moiety to promote cellular entry by increasing contact with the glycocalyx. This modification enables cellular uptake of GFP through endocytosis. The second method uses a fluorenyl diazo compound to label carboxylic acids of the target protein, forming ester bonds that are labile to cellular esterases. The pendant fluorenyl groups endow GFP with high levels of cytosolic delivery. Both strategies enhance delivery of a native protein into a cell, which is critical for clinical utility.
Functional Characterization of HC11 Mouse Mammary Epithelial Cells Transduced with Abcg2
Authors: Wu Alex , Dalvi Pooja , Earl Brian , Yang Mingdong , Harper Patricia , Ito Shinya
Published: June 2021

The Breast Cancer Resistance Protein (BCRP/ABCG2) is a multidrug efflux transporter that is highly expressed in certain cancer cells and at biological barriers such as the intestine. ABCG2 is also dramatically upregulated in mammary epithelial cells during lactation where it plays a role in the transfer of drugs and toxins into breast milk. Despite the large number of cell lines that overexpress ABCG2, none are suitable models for ABCG2‐mediated drug excretion into breast milk. We report here the creation of a non‐tumorigenic mouse mammary epithelial cell line that expresses high levels of functional ABCG2. Prolactin‐responsive HC11 mouse mammary epithelial cells, which form globular acinar‐like structures with a central lumen (called mammosphere) in Matrigel®, were transduced with a lentiviral vector encoding mouse Abcg2. One of the 48 clones isolated (designated HC11.Abcg2.C10) showed high levels of ABCG2. HC11.Abcg2.C10 displayed significantly lower intracellular retention of ABCG2 substrates BODIPY‐Prazosin and Hoechst 33342 compared to parent HC11 cells. We then identified an optimal Matrigel‐based culture condition, which supports these cells to form mammosphere structures. Future work will focus on developing methods to measure drug accumulation in the acinar lumen as a model for ABCG2‐mediated drug excretion into breast milk. This work is supported by the Canadian Institutes of Health Research.
Inhibition of Endoplasmic Reticulum Stress Normalizes Augmented Myogenic Response in Coronary Arteris of the Spontaneously Hypertensive Rats
Authors: Choi Soo‐Kyoung , Lim Mihwa , Yeon Soo‐In , Lee Young‐Ho
Published: June 2021

Endoplasmic reticulum (ER) stress has been shown to play a critical role in the pathogenesis of cardiovascular complications. However, the role and mechanisms of ER stress in hypertension remain unclear. Thus, we hypothesized that enhanced ER stress contributes to the maintenance of hypertension in spontaneously hypertensive rats (SHRs). We investigated this hypothesis by suppressing ER stress in SHRs and their normotensive controls, Wistar‐Kyoto rats (WKYs) with ER stress inhibitor (taurine‐conjugated ursodeoxycholic acid, TUDCA). Sixteen‐week old male SHRs and WKYs were treated with TUDCA (100 mg/kg/day, IP injection) or PBS (control, 300 μl/day, IP injection) for two weeks. There was a decrease in systolic blood pressure in SHR treated with TUDCA but not in SHR treated with PBS. The myogenic response is potentiated in coronary arteries of SHRs compared to WKYs. Interestingly, treatment of ER stress inhibitor normalized myogenic responses in SHRs. These data were associated with an increase in ER stress marker expression (Bip, CHOP, ATF6, XBP‐1, and phosphorylated‐eIF2α) in coronary arteries of SHRs, which were reduced by TUDCA treatment. In conclusion, ER stress inhibition decreases systolic blood pressure and normalizes myogenic response in SHRs. Moreover, ER stress inhibition reduces expression of ER stress markers. Therefore, we suggest that ER stress could be a potential target for hypertension.
Trait Aggression (TA) Correlates with Increased Blood Pressure in the Wistar‐Kyoto Rat
Authors: Rana Samir , Stringfellow Sara , Pugh Phyllis , White Roger , Stauss Harald , Wyss J. Michael , Kerman Ilan
Published: June 2021

Classical studies have implicated specific personality traits as predictive of adverse cardiovascular function, yet biological mechanisms that contribute to such associations remain elusive. We investigated potential impact of early‐life experience on the emergence of TA and cardiovascular function. Male Wistar‐Kyoto rats that experienced either maternal separation or neonatal handling during postnatal days 1‐14 were instrumented for continuous blood pressure (BP) recording as adults. They were then single‐housed and scored on aggressive behavior in response to a 10‐min. exposure to a conspecific male. Rats were then sacrificed and thoracic aortas were harvested for functional and structural studies, along with plasma and end organs. Half of the animals regardless of their early‐life experience demonstrated TA (scored as clinch attack). TA rats exhibited significant elevations of mean and systolic (SBP) blood pressures along with increased low‐frequency power of SBP variability, an index of sympathetic modulation of vascular tone. Hearts from TA rats had a greater norepinephrine content, and their aortas exhibited a significantly lower EC50 to phenylephrine‐induced contractions along with an increased wall‐to‐lumen ratios. Taken together these data indicate that TA may be an inborn emotionality trait that develops independently of early‐life experience in rats. Furthermore, it correlates with alterations in vascular structure and function that lead to increased BP, and which may be mediated by alterations in the activity of the sympathetic nervous system.

Support: R00MH081927 (IAK), 13PRE16940050 (SR), P30NS47466 (UAB core)
MicroRNA‐301a Alters Dicer Expression in Primary Human Atrial Cells and Bone Marrow‐Derived Mesenchymal Progenitor Cells: Implications for Cardiac Fibrosis
Authors: Muller Alison , Freed Darren
Published: June 2021

It is known that multiple cell types can contribute to cardiac fibrosis including both atrial fibroblasts (AFs) and bone marrow‐derived progenitor cells (MPCs). We have previously shown that MPCs display a myofibroblast phenotype in vitro that is linked to altered microRNA(miR)‐301 expression, a miR affiliated with maintaining proliferation in many cell types. We have also shown that miR‐301a influences a dichotomous phenotype in MPCs isolated from patients undergoing open heart surgery. The objective of this experiment was to further understand how this phenotype change may be influenced. We performed a microarray analysis investigating potential targets of miR‐301a. From this screen, Dicer was identified as a potential target of mir‐301a. Dicer is responsible for activating miRs in the cell, therefore altering protein expression and ultimately influencing phenotype. As both MPCs and AFs display a dichotomous phenotype where each cell type displays a phenotype that pathologically contributes to fibrosis, we transfected both MPCs and AFs with miR‐301a. AFs were also isolated from patients undergoing open heart surgery. We performed qRT‐PCR analysis and found that the mRNA of Dicer was significantly reduced in transfected cells, and observed decreases in levels of both mRNA and protein of collagen I and non‐muscle myosin IIA (NMMIIA). These proteins are present in myofibroblasts, the cell type predominantly responsible for causing cardiac fibrosis. Our results provide insight into a possible cellular mechanism that governs the pro‐fibrotic phenotypes of AFs and MPCs, which could be partially caused by altered Dicer expression with its attendant effect on miRNA processing in the cell.
Persistent cAMP Signaling via Vasopressin V2 Receptors Imaged in 3D Cultures Using Lightsheet Microscopy
Authors: Jiang Jason , Kuo Ivana , Abi‐Jaoude Joanne , Lemos Fernanda , Yang Yi , Curci Silvana , Ehrlich Barbara , Hofer Aldebaran
Published: June 2021

Elevated intracellular cAMP is a key factor in cyst enlargement in the inherited disorder known as polycystic kidney disease (PKD). Therapeutic strategies are actively being sought to reduce cAMP production in cells lining the cyst. Antagonists of the cAMP‐linked V2R vasopressin receptor such as the competitive inhibitor tolvaptan have been assessed in clinical trials for the treatment of PKD, albeit with inconsistent results. Here we used a sensitive, new‐generation circularly permuted ratiometric cAMP sensor to monitor cAMP signals in response to arginine vasopressin (AVP) in LLC‐PK1 cells. This probe proved valuable both in epifluorescence measurements of cAMP in 2D cultures, as well as in Lightsheet microscopy of polarized 3D spheroids. We observed that brief (5 min.) treatment with AVP induced a long‐lasting cAMP increase (more than 1 hr), which was not reversed by washing or by acute addition of tolvaptan, as measured in both 2D and 3D cultures. In contrast, pretreatment with tolvaptan completely prevented the AVP response. The persistent intracellular cAMP increase triggered by AVP also led to primary cilia elongation and phosphorylation of downstream PKA targets such as CREB. Our results are consistent with a model in which endogenous V2R receptors continue to signal from endosomal compartments (as described previously for overexpressed V2R). Our results may have implications for optimizing dosing regimens for V2R antagonists, with increased efficacy predicted in hydrated (i.e. low circulating AVP) patients.
Аffect of uranium ore dust on separate indexes of nitrous exchange of rat liver using Lacryc radices root extract
Authors: Jakenova A.S. , Jumasheva R.T. , Abdirasilova D.D.
Published: June 2021

Purpose of the research ‐ to reveal peculiarities of metabolic break of nitrous exchange of rat liver tissue at long‐term inhalation affect of uranium dust in different terms and to evaluate effectiveness of corrective effect of radices root extract. It is determined, that at inhalation of uranium dust in doses, equivalent to 5 maximum‐allowed concentration, during 120 days process of albumen synthesis is activated in liver, that is confirmed by regular increase of albumen concentration in blood serum for 2 times to the end of observation in term of its fixed content in liver tissue. Pointed changes coincide with depression of processes of urea‐formation almost in 2 times, consequent depression of aspartataminotraspherase (AsAT) and gammaglutamiltranspeptidase (GGTP) activity in liver in 2 times. level of adaptive activation of albumen synthesis reduces for 38 and 13,6%, depression affect on process of urea‐formation increases for 16,1%, activity of AsAT and AlAT in liver reduces for 18,2% and 16%, and top of hyperalbumenemia reduces for 30 days. At increasing of doze load for 10 times, duration of exchange processes acutely reduced, effects of albumen content increase for 55% is kept only for the first 7 days, and it coincides with depression of AsAT activity for 36,6% and strengthening of hyperfermentemia of AsAT for 4,9 times and AlAT for 2,5–4 times. It is determined, that water extract of lacryc radices root possesses corrective effects, improving indexes of albumen‐synthetic, fermentative and urea‐formative function of liver. It is showed, that lacryc radices root extract stably increases content of general albumen for 15‐11%, synthesis of urea for 13‐28%, activity of AsAT for 46% and for 2,4 times, and AlAT – for 3‐4 times in liver.
Decreased Bacterial Activity on Nano‐patterned PDMS Replica for Catheter‐associated Infection Prevention
Authors: Liu Luting , Ercan Batur , Webster Thomas
Published: June 2021

Experiment

Here, a nano‐patterned polydimethylsiloxane (PDMS, a commonly used catheter material) replica was fabricated by using nanotubular anodized titanium (ATi) as the template. In vitro bacterial studies using S. aureus, E. coli, P. aeruginosa and S. epidermidis were conducted to assess the effectiveness of the nano‐patterned PDMS (nano‐PDMS) at inhibiting bacterial growth. In addition, human fibroblast and endothelial cell assays were conducted to determine the influence of the nanostructure on mammalian cell behavior as a measurement of toxicity. To elucidate the mechanisms of how surface topographies affect cell/ bacteria adhesion, the protein interactions with different surfaces were also investigated by using the bicinchoninic acid (BCA) protein assay.

Results

As expected, the nano‐patterned structures were fabricated successfully on PDMS surface. Results showed that nano‐PDMS inhibited the growth of all the four types of bacteria after 24h and 48h, respectively. Moreover, data suggested the effectiveness of bacteria inhibition reached above 50%, all without employing an antibiotic (Fig. 1). It was also found that nano‐PDMS increased both fibroblast and endothelial cell adhesion and, thus, were non‐toxic to mammalian cells (Fig. 2). BCA results indicated that the amount of total proteins adhered on the nano–PDMS surfaces was slightly higher than on plain PDMS surfaces, presumably due to the increased surface area and change of adhesion sites.

image

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Conclusions

The nano topography on PDMS could inhibit bacterial growth significantly while remaining non‐toxic to mammalian cells, and thus should strongly be considered for use in catheters.
Formin conformations during processive actin elongation
Authors: D'Ausilio Morgan , Briones Sofia , Li Ellen , Marone Caroline , Mayer Jake , Moseson Sarah , Patel Parth , Scherl Samuel , Sharma Kartikeya , Kull F.
Published: June 2021

Formins are a class of actin binding proteins that regulate the elongation and nucleation of actin filaments and they are key to maintaining cellular morphology. The mammalian formin‐like 3 (FMNL3) protein is essential for the formation of filopodia, projections of the plasma membrane that enable cell motility. Formins contain a highly conserved formin homology 2 (FH2) domain that dimerizes through interactions of the lasso and post subdomains. These dimers bind to actin filament barbed ends to mediate elongation and prevent inhibition of filament growth by capping proteins, thereby ensuring the formation of long, linear actin filaments. The FH2 dimer is able to remain associated with the growing end of the filament during elongation through the flexibility of linker regions that connect the FH2 subunits. A previous structural study of the yeast formin Bni1p FH2 domain was found to form a complex with three adjacent actin subunits, supporting a simple stepping model of formin‐mediated actin polymerization. The X‐ray crystal structure of the FMNL3 FH2 domain was solved in complex with monomeric actin. In this structure, the FH2 dimer forms a symmetric and stable complex with only two actin monomers through primary interactions between the knob and coiled‐coil FH2 subdomains and actin. These recent findings support the existence of an additional step in the formin‐mediated processive elongation mechanism. The Pingry School 2014‐2015 SMART team has created a model to further examine the structure and function of formin FH2 domains in complex with actin.
Stimulation of Cystathionine‐γ‐lyase (CSE) Activity and Generation of Hydrogen Sulfide in Gastrointestinal Smooth Muscle via NO/cGMP/PKG pathway
Authors: Nalli Ancy , Grider John , Murthy Karnam
Published: June 2021

Hydrogen sulfide (H2S) plays an important role in the regulation of gastrointestinal motility and secretion. H2S is synthesized mainly from L‐cysteine via cystathionine‐γ‐lyase (CSE) and cystathionine‐β‐synthase (CBS). We showed that smooth muscle cells of stomach and colon of rabbit, mouse and human express CSE, but not CBS. Activation of CSE causes inhibition of Rho kinase activity and muscle contraction and the inhibition was blocked by CSE siRNA and by a selective CSE inhibitor, propargylglycine (PPG).

Aim

To identify the mechanism of activation of CSE in gastrointestinal smooth muscle cells.

Methods

Activation of CSE was analyzed by the measurement of H2S in response to L‐cysteine and NO donor sodium nitroprusside (SNP) in gastric and colonic muscle of rabbit and human. Filter paper disks dipped in zinc acetate were exposed to H2S trapped in N2‐perfused glass vials and the amount of reduced zinc acetate in the presence of H2S was measured spectrophotometrically.

Results

The basal levels of H2S in gastric and colon muscle from rabbit and human were ~20‐25 nM/mg. L‐Cysteine (10 mM) increased H2S generation up to 50 nM/mg; the effect of L‐cysteine was inhibited by PPG. L‐cysteine‐induced H2S generation was augmented in the presence of SNP and cGMP analog, 8‐bromo cGMP to 125 µM/g and 120 nM/mg, respectively. Augmentation of CSE activity in response to SNP and 8‐br‐cGMP was blocked by the cGMP‐dependent protein kinase (PKG) inhibitor, Rp‐cGMPS, suggesting phosphorylation‐dependent activation.

Conclusion

We have identified a mechanism of stimulation of CSE activity in gastric and colonic muscle involving cGMP‐dependent activation of PKG.
No Therapeutic Effects of Resistance Exercise Training in a Severe Cancer‐Induced Skeletal Muscle Wasting Rat Model
Authors: das Neves Willian , Alves Christiano , de Almeida Ney , Campos‐Ferraz Patricia , Guimarães Fátima , Ramires Paulo , Brum Patricia , Lancha Antonio
Published: June 2021

The current study aimed to assess the effects of resistance exercise training upon skeletal muscle trophicity and function in a severe cancer cachexia rat model. Male Wistar rats were assigned into four experimental groups: 1) untrained control rats (Control; n = 10), 2) control rats submitted to resistance training (Control + RT; n = 10), 3) untrained rats injected with 106 Walker 256 tumor cells in the bone marrow (Walker; n = 8) and 4) rats injected with 106 Walker 256 tumor cells in the bone marrow and submitted to resistance training (Walker + RT; n = 8). A total of 8 resistance exercise sessions for hind limb (squat) were performed using an electrical stimulation (10‐15 V, 0.3‐s duration, at 4‐s intervals). Each session included three sets of 10 repetitions at the intensity of ~65% 1RM. Tumor size, body mass, food intake, skeletal muscle fibers cross sectional area, in vivo (deambulation test) and ex vivo (force frequency protocol in isolated EDL) skeletal muscle function were assessed. Experimental groups were compared by ANOVA followed by Tukey pos hoc. As expected, Walker group displayed decreased food intake (‐55%), EDL (‐20%) and plantaris atrophy (‐21%), and in vivo and ex vivo skeletal muscle dysfunction (~‐30% for both) 12 to 14 days post tumor cells injection when compared to the Control rats (p < 0.05 for all). However, no differences were observed between Walker and Walker + RT groups for all measured variable (p > 0.05 for all), suggesting that the current resistance exercise training protocol was ineffective to counteract cancer‐induced skeletal muscle wasting in our cancer cachexia model.

Financial Support by FAPESP 2013/04744‐4
The Ebola Virus Glycoprotein: An Essential Envelope Protein for the Life Cycle of Ebola Virus
Authors: Foresman James , Lackamp Bill , McAfee Adrian , Montague Marie , Mungula Daniel , Wilbur Keaton , Zegar Irene
Published: June 2021

The recent Ebola virus outbreak was traced to a two‐year old boy from Guinea who died shortly after contracting the virus. This disease has a mortality rate of 50‐90%. Currently, FDA‐approved vaccines for humans are virtually nonexistent. The Ebola viral glycoprotein (GP) consists of two subunits, GP1 and GP2, and mediates host recognition, attachment to and entry into the host cell as well as provide protection from immune defenses. A pre‐fusion crystal structure of GP bound to a human survivor antibody (KZ52) reveals that three GP1 and GP2 subunits interact to form a chalice‐like assembly of a trimer of GP1‐GP2 dimers. It is believed that the putative receptor‐binding site resides within the inner bowl of the chalice. The structure also reveals that three KZ52 antibodies are attached to the outer bowl of the chalice through multiple Hydrogen‐bonding and van der Waals interactions. Contact points between KZ52 and GP include residues 505‐514 and 549‐556 of GP2, and residues 42 and 43 of GP1. Insight into the structure suggests that the neutralization activity of the antibody results from those tight interactions, preventing GP from rearranging to its fusion form. The Pittsburg High School SMART TEAM used 3D technology to design the Ebola virus GP bound to KZ52 in order to understand the link between its structure and the role it plays in the life cycle of the virus. New insights gained from this structure may facilitate the development of effective vaccines against this deadly virus.
Isolated Intercostal Muscle Fibers as a Human Skeletal Muscle Ex Vivo Model
Authors: Olsson Karl , Cheng Arthur , Alam Seher , Westerblad Håkan , Lanner Johanna , Bruton Joseph , Gustafsson Thomas
Published: June 2021

At present, ex vivo models of human intact skeletal muscle cells are limited to the use of myotubes in which force measurements are not possible and the intracellular Ca2+ handling is inadequately characterized. In the present study we established an alternative human skeletal muscle ex vivo model utilizing single intact intercostal muscle fibers and compared the intracellular Ca2+ handling in intact fibers to that in myotubes.

Single intact muscle fibers were dissected from intercostal muscle biopsies obtained during thoracotomies performed as part of the treatment for non‐small cell lung carcinoma. Myoblasts were isolated form vastus lateralis biopsies and differentiated into myotubes. Both the isolated muscle fibers and differentiated myotubes responded to electrical stimulation by an increase in intracellular free Ca2+ ([Ca2+]i), but only the single fibers contracted in response to electrical stimulation. In comparison to the muscle fibers, Ca2+ handling proteins in the myotubes were expressed at a lower level and the structural organization of Ca2+ handling proteins was less elaborate. The decay of the [Ca2+]i transient was markedly longer in the myotubes.

Although a maturation of the intracellular Ca2+ handling is evident in differentiated myotubes compared to myoblasts, our results show marked differences in intracellular Ca2+ handling and contractile ability between adult muscle fibers and myotubes. Thus, differentiated myotubes are not an adequate representative model for studies of Ca2+‐dependent functions in adult human muscle.
Assessment of Social and Hygienic Characteristics of Disabled People Due to Circulatory System Diseases
Authors: Alikhanova K.A. , Abugaliyeva T.O. , Omarkulov V.A.
Published: June 2021

According to WHO (2008), in Kazakhstan, the death rate from diseases of the circulatory system (SBR) was 650 per 100 000 population, which requires a careful study of the social and hygienic features of patients with cardiovascular disease. The aim of the study was assessment of social‐hygienic features of the contingent of disabled people due to cardiovascular disease as an example in the region of Karaganda region. In general, the level of primary disability (PI), due to the Ivory Coast in the Karaganda region in 2012 decreased by 2.3%. PI due to cerebrovascular diseases in the Karaganda region, by contrast, tended to increase: from 47.1% in 2007 to 50.4% in 2012 (+ 3.3%), with annual average of 48.7%. The total number of PI for the first time in the country increased from 7747 people in 2007 to 9577 people in 2011 and declined slightly in 2012 to 9479 people. The study of population dynamics of VPI due to SBR in the Karaganda region in the period from 2007 to 2012 showed that she had a tendency to decrease from 994 people in 2007 to 474 people in 2012, with some burst in 2011 to 1044 people. As for the structure of the studied contingent of persons with disabilities by sex in the Karaganda region, in the analyzed period the proportion of women was significantly less than men, and was in 2007 ‐ 30.1% 2008 ‐ 30.5% 2009 ‐ 30.1% 2010 ‐ 30.1% 2011 ‐ 28.5% 2012 ‐ 27.1%.Thus, analysis of the distribution VPI depending on the severity of the disability in the Karaganda region showed that prevailed disabled of I and II group (in 2007 ‐ 77.9% 2008 ‐ 75.1% 2009 ‐ 76.5 %, 2010 ‐ 75.1% 2011 ‐ 74.3% 2012 ‐ 75.1%). And in the last 2 years has been an increase of 1 group disability by 1.3% in 2011 and 3.3% in 2012.
Teaching Physiology to Homeschool Students in Rural Mississippi
Authors: Gillis Ellen , Dasinger John Henry
Published: June 2021

Purpose

To engage children in grades K‐12 in interactive demonstrations and activities to learn about the structure and function of the heart, lungs, and digestive system.

Methods

The event was coordinated with the Laurel Christian Home Educators at the Southeastern Baptist College in Laurel, MS. Five didactic and interactive sections were developed. In the first section, instructors introduced students to the daily routine of a scientist, including an appropriate safety protocol. In the second activity, participants were introduced to the basics of cardiovascular physiology, followed by an experiment measuring heart rate under various conditions. The third section focused on respiratory physiology, with a hands‐on activity to measure lung capacity. Participants learned about the digestive system in the fourth section, and also had an activity to walk them through the entire digestive process. For the final station, participants were able to explore various organ models and fixed tissue samples of the systems covered that day. A total of 4 volunteers, including 2 graduate students and 2 faculty members, organized this event which took place on a Tuesday from 1pm to 3pm.

Results and Conclusion

We were able to reach an estimated 120 participants (92 students and approximately 30 parents). Success was dependent upon efforts to ensure that activities appealed to all ages. Older students were recruited during the event to help the younger students with activities such as data acquisition and data plotting.
Mixed tumor of the parotid gland
Authors: Kozhakov B.B. , Sagyndyk H.L. , Batyrov T.W.
Published: June 2021

The tumor is characterized by slow (for years) growth can reach large proportions. Perhaps recurrence, wherein the tumor metastasis does not.

Introduction

Among the benign tumors of the salivary glands is most often found mixed tumor (adenoma polymorphic). Most often it is located in the parotid, submandibular, and rarely in sublingual salivary gland.

Research and Results

We observed 12 patients.

Discussion

According to the literature malignancy (malignancy) is observed in 3,6‐30% of cases. The diagnosis in most cases set the histopathological study only after tumor removal. Possible recurrence, as a rule, only after non‐radical operation.

Long‐term periods were traced up to 5 years. Recurrence of the disease were observed.
Ileal Pouch-anal Anastomosis Complications and Pouch Failure
Authors: Heuthorst Lianne , Wasmann Karin A. T. G. M. , Reijntjes Maud A. , Hompes Roel , Buskens Christianne J. , Bemelman Willem A.
Published: June 2021

Objective:

This systematic review aims to assess the incidence of pouch failure and the correlation between ileal pouch-anal anastomosis (IPAA)-related complications and pouch failure.

Background:

Previous studies demonstrated wide variation in postoperative complication rates following IPAA.

Methods:

A systematic review was performed by searching the MEDLINE, EMBASE, and Cochrane Library databases for studies reporting on pouch failure published from January 1, 2010, to May 6, 2020. A meta-analysis was performed using a random-effects model, and the relationship between pouch-related complications and pouch failure was assessed using Spearman’s correlations.

Results:

Thirty studies comprising 22,978 patients were included. Included studies contained heterogenic patient populations, different procedural stages, varying definitions for IPAA-related complications, and different follow-up periods. The pooled pouch failure rate was 7.7% (95% confidence intervals: 5.56–10.59) and 10.3% (95% confidence intervals: 7.24–14.30) for studies with a median follow-up of ≥5 and ≥10 years, respectively. Observed IPAA-related complications were anastomotic leakage (1–17%), pelvic sepsis (2–18%), fistula (1–30%), stricture (1–34%), pouchitis (11–61%), and Crohn’s disease of the pouch (0–18%). Pelvic sepsis (r = 0.51, P < 0.05) and fistula (r = 0.63, P < 0.01) were correlated with pouch failure. A sensitivity analysis including studies with a median follow-up of ≥5 years indicated that only fistula was significantly correlated with pouch failure (r = 0.77, P < 0.01).

Conclusions:

The single long-term determinant of pouch failure was pouch fistula, which is a manifestation of a chronic leak. Therefore, all effort should be taken to prevent an acute leak from becoming a chronic leak by early diagnosis and proactive management of the leak.

Mini abstract:

This systematic review aims to assess the incidence of pouch failure and the correlation between IPAA-related complications and pouch failure. Long-term pouch failure was correlated with fistula, suggesting that early septic complications may result in fistula formation during long-term follow-up, leading to an increased risk of pouch failure.
Communication principles and practices for making shared decisions about renal replacement therapy: a review of the literature
Authors: Saeed Fahad , Shah Amna Yousaf , Allen Rebecca Jane , Epstein Ronald M. , Fiscella Kevin A.
Published: June 2021

Purpose of review

To provide an overview of the skill set required for communication and person-centered decision making for renal replacement therapy (RRT) choices, especially conservative kidney management (CKM).

Recent findings

Research on communication and decision-making skills for shared RRT decision making is still in infancy. We adapt literature from other fields such as primary care and oncology for effective RRT decision making.

We review seven key skills: (1) Announcing the need for decision making (2) Agenda Setting (3) Educating patients about RRT options (4) Discussing prognoses (5) Eliciting patient preferences (6) Responding to emotions and showing empathy, and (7) Investing in the end. We also provide example sentences to frame the conversations around RRT choices including CKM.
Pediatric kidney transplantation, a technical update
Authors: Etesami Kambiz , Hogen Rachel , Lestz Rachel
Published: June 2021

Purpose of review

Pediatric kidney transplantation is the definitive therapy for infants and children suffering from renal failure. It is a distinct endeavor demanding specialized care for optimal results. This includes a dedicated preoperative workup accounting for unique predisposing urologic conditions, specialized surgical techniques, and careful hemodynamic monitoring and maintenance.

Recent findings

Historically, size-matched renal allografts from pediatric donors to pediatric recipients suffered from poor outcomes. Advances in surgical technique performed at high volume centers have shown that these operations can be performed safely, helping expand the donor pool for these patients. Concurrently, transplantation of increasingly small for size infants with complex medical and surgical backgrounds has become a reality.

On a policy front, efforts to expand access to size-matched organs, combined with advances in medical management and immunosuppression have seen pediatric renal transplantation reach new heights. Now, these breakthroughs are heightened by the ability to transplant such organs into the smallest infants. The net result will be diminished transplant waiting times and, accordingly, improved quality of life and longevity for children suffering from renal failure.