bluuebunny/crossref_metadata_2025 huggingface dataset:
Acid‐base regulation of intestinal oxalate transport (LB716)
Authors: Whittamore Jonathan , Freel Robert , Hatch Marguerite
Published: June 2021

Primary Hyperoxaluria (PH) is a rare, inherited disease caused by an absence of specific liver enzyme(s) leading to overproduction of oxalate (Ox2‐), kidney stones and eventual renal failure. Alongside the kidney, the intestine is capable of secreting Ox2‐ and reducing the systemic Ox2‐ burden. Preserving renal function in PH is paramount therefore the notion of extra‐renal Ox2‐ elimination should not be under‐estimated. Identification of chloride/bicarbonate (Cl‐/HCO3‐) exchangers with an affinity for Ox2‐ raises the possibility of these membrane‐bound proteins serving as future therapeutic targets for promoting Ox2‐ secretion in PH. Despite this interest, understanding how these transporters are regulated is not well defined. Components of the HCO3‐‐buffering system (pH, CO2 and HCO3‐) are important, but under‐appreciated regulators of Cl‐/HCO3‐ exchange. The objective of this study was to determine whether these acid‐base variables, and associated enzyme, carbonic anhydrase (CA), are involved in Ox2‐ handling. Isolated mouse intestinal preparations were mounted in an Ussing chamber and experiments systematically examined how changes to pH, PCO2 and [HCO3‐] impacted Ox2‐ fluxes. Results showed that Ox2‐ secretion by the distal colon requires CA activity, is sensitive to changing [HCO3‐], but not pH, and can be stimulated > 70 % by increasing PCO2. In contrast, Ox2‐ transport by the ileum was impervious to these maneuvers. This sets the foundation for more detailed studies into the identity of the transporter(s) responsible, the role of CA, and the underlying signaling pathway. These findings also highlight the heterogeneity of intestinal Ox2‐ handling, being regulated by distinct stimuli in different segments that express a similar suite of Cl‐/HCO3‐ exchangers.

Grant Funding Source: Supported by a Career Development Fellowship from the Rare Kidney Stone Consortium at the Mayo Clinic, Rochester, MN (NIH 5U54 DK083908‐05)
HEK‐293 cells expressing the cystic fibrosis transmembrane conductance regulator (CFTR): a model for studying bile acid (BA) regulation of Cl‐ transport. (LB720)
Authors: Domingue Jada , Ao Mei , Sarathy Jayashree , Nelson Deborah , Alrefai Waddah , Rao Mrinalini
Published: June 2021

While human colonic T84 cells are a good model for studying Cl‐ secretion via CFTR, they respond poorly to genetic manipulations. As an alternate model, we stably transfected human embryonic kidney 293 cells (HEK), with CFTR‐EGFP (HEKCFTR) and assessed function by the I‐ efflux assay (nmol ± SEM). Forskolin (FSK; 2‐50µM) increased I‐ efflux compared to DMSO in HEKCFTR (n=3); CFTRinh‐172 (20µM) reduced FSK’s (10µM) effect by 45% (n=4). However, FSK (10µM) did not alter I‐ efflux in HEK (n=4). Disrupting microtubules with nocodazole (NOC, 33µM) did not alter FSK action in HEKCFTR (FSK: 876±103; FSK+NOC: 872±94; n=5). We had shown that the BA, chenodeoxycholic acid stimulates I‐ efflux in HEKCFTR (EB 2013). Expression studies revealed that HEK cells possess transcript and protein of the Gαs‐coupled BA receptor, TGR5. We next examined the effects of the potent TGR5 ligand, lithocholic acid (LCA) in HEKCFTR. While LCA alone had no effect on [cAMP]i it potentiated FSK’s effect (fmol/well: DMSO: 110±30; FSK: 1162±57; 50μM LCA: 146±8; FSK+ LCA: 7793±728; n=3). The functional effects of LCA on I‐ efflux were measured. Low, [10‐100μM] but not high [250‐500μM] doses of LCA increased I‐ efflux (35%, n蠅3) and pretreatment with LCA (15min, 50μM) blocked FSK’s effect (FSK: 724±66; FSK+LCA: 354±36; n=4). In summary, HEKCFTR are a good model to study CFTR because CFTR‐EGFP is functional, FSK induced efflux is CFTR specific, CFTR’s activation by FSK is not dependent on MTs and CFTR is regulated by BAs. HEKCFTR can be used to elucidate the cross talk by signals such as BAs and FSK in CFTR regulation.

Grant Funding Source: NIH and VA
Altered TRPV5 Expression in Dahl Salt‐sensitive Rats (LB728)
Authors: Burns Rebecca , Wells Candace , Pointer MIldred
Published: June 2021

We have previously shown that urinary calcium excretion is increased in Dahl salt‐sensitive (DS) rats following a high salt diet and this higher urinary calcium excretion is associated with the elevated blood pressure observed in DS following a high salt diet. The mechanism of the calcium loss following a high salt diet is undefined. In this report we investigate whether the transient receptor potential cation channel subfamily V member 5 (TRPV5), a calcium channel protein expressed on the luminal surface of the thick ascending loop and distal tubule and involved in transcellular calcium reabsorption, expression is altered in DS rats. Dahl DS and salt‐resistant (DR) rats were placed on a high (8%) salt diet for one week. At the end of the treatment period kidneys were collected for performing western analysis for TRPV5 protein expression in renal cortical and medullary tissue. Renal medullary TRPV5 protein levels were higher in DS rats (n=3) compared to DR rats (n=3) (1.4 ± 0.3 vs. 0.03 ± 0.03 arbitrary units; p<0.05). There was no difference in renal cortical TRPV5 expression between DS and DR rats. Higher medullary TRPV5 expression in DS rats on a high salt diet suggests that there is a compensatory attempt to increase calcium reabsorption. However, the compensatory increase in TRPV5 does not appear to prevent the increased urinary calcium excretion in DS rats following a high salt diet. Further studies are needed to investigate other renal calcium transporters involved in calcium reabsorption to explain the urinary calcium loss in hypertensive DS rats.

Grant Funding Source: Supported by 2P20MD000175 and APS Frontiers in Physiology
NADPH oxidase inhibitor inhibits methylglyoxal‐induced podocyte apoptosis (LB729)
Authors: Kim Young Sook , Jung Dong Ho , Pyun Bo‐Jeong , Choi So‐Jin Choi , Kim Jin Sook Kim
Published: June 2021

Methylglyoxal (MG) is one of uremic toxins produced by glycolysis that may results in diabetic nephropathy. In this study, we investigated the effect and mechanism of MG on apoptosis in podocytes. Conditionally immortalized podocytes for differentiation were induced by culturing the cells at 37°C for 13~15 days and treated MG with various concentration (0, 50,100, 200, 400 μM). Our data show that MG induced a decrease in cell viability in a dose‐dependent manner and increased formation of dichlorofluorescein (DCF)‐sensitive intracellular reactive oxygen species (ROS). This enhanced ROS formation was significantly reduced by NADPH oxidase inhibitor (DPI, 5 μM). Furthermore, MG treatment induced apoptosis in podocyte and NADPH oxidase inhibitor inhibited MG‐induced podocytes apoptosis via cleavage inhibition of poly (ADP‐ribose) polymerase (PARP). MG treatment also induced phosphorylation of extracellular‐regulated kinase 1/2 (ERK1/2), p38 mitogen‐activated protein kinases (MAPKs), protein kinase C‐alpha and ‐ delta/zeta, and phosphoinositide‐3 kinase (PI3K). Pretreatment with these inhibitors inhibited MG‐induced phosphorylation of these molecules in podocytes. These results suggest that MG‐induced apoptosis may be mediated by signaling of ERK, MAPK, PKC and PI3K in podocyte.

Grant Funding Source: KIOM13040
MicroRNA‐30 and SOX9 participate in a negative feedback loop to regulate intestinal proliferation (LB744)
Authors: Peck Bailey , Mah Amanda , Simmons Jim , Magness Scott , Lund P. Kay , Sethupathy Praveen
Published: June 2021

Precise regulation of SOX9 expression is critical for normal proliferation and differentiation in the intestinal epithelium. microRNAs (miRNAs) have emerged as prominent fine‐tuners of gene expression. In silico sequence analyses revealed a putative binding site for SOX9 in the promoter of miR‐30, as well as a conserved target site for miR‐30 in the SOX9 3’ UTR. Therefore, we sought to test the hypothesis that miR‐30 mediates feedback control of SOX9 in intestinal epithelial cells. We first sorted functionally distinct cell populations from the jejunum of Sox9‐EGFP reporter mice based on different levels of Sox9‐EGFP. Real‐time PCR analysis on RNA from these sorted cells demonstrated that miR‐30 and Sox9 expression are positively correlated in the mouse intestine. Knockdown of SOX9 in a human intestinal epithelial cell line (HIECs) significantly decreased miR‐30 expression, suggesting that SOX9 positively regulates miR‐30 in the intestine. Antisense inhibition of miR‐30 in HIECs led to significantly elevated levels of SOX9 and reduced 3H‐thymidine incorporation into DNA. Collectively, these data point to a SOX9‐miR‐30 auto‐regulatory loop that controls proliferation in the intestinal epithelium.

Grant Funding Source: Supported by UNC GMB T32 Training Grant GM007092‐39 (B.P., NIGMS/NIH), 5R00DK0913118 (P.S., NIDDK/NIH), R01DK091427 (S.M., NIDDK/NIH), and R01DK040247 (P.K.L., NIDDK/NIH)
Comparison of Dipeptidyl‐Peptidase IV Levels in Plasma and Saliva (LB754)
Authors: Neidert Leslie , Ferguson Brian , Rogatzki Matthew , Mynard James , Kluess Heidi
Published: June 2021

Dipeptidyl‐Peptidase IV (DPP‐IV) is an enzyme present in the blood, acting as a regulator for incretin hormones, such as glucagon‐like peptide(GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP). As a result of this regulatory action, DPP‐IV has become an enzyme of interest in the pathology of Type 2 Diabetes. Currently, values are measured primarily in the plasma. It has been suggested that values can be measured in saliva; however, the relationship between DPP‐IV levels in plasma and saliva is not well researched. Plasma and saliva samples were collected from 5 healthy college aged students. Blood was collected using standard venipuncture from prominent antecubital vein. Plasma was separated by centrifugation for 10 minutes at 1,000g and 4°C. Saliva was collected by subjects spitting into a cup, then stored in 0.5mL aliquots at ‐80°C until analysis. DPP‐IV activity was determined using a fluorometric assay which measures the release of 4‐methoxy‐2‐naphthylamine. Enzymatic activity is defined as the amount of DPP‐IV that cleaves 1µmol of glycyl‐L‐proline‐4‐methoxy‐2‐nephthylamine per minute. From the activity, a linear regression analysis was performed to compare the data. Plasma samples had a mean DPP‐IV level of 36.69U/L ± 7.32, falling within normal reference values presented by Durinx et al. (2001). DPP‐IV levels were elevated in saliva samples with a mean of 43.71U/L ± 10.01. No association was found between the DPP‐IV levels in saliva and plasma (P‐value= 0.53, with significance set at 0.05). The use of saliva in the measurement of DPP‐IV does not yield results comparable to plasma.
Endothelin‐1 stimulates resistin gene expression (LB756)
Authors: Liu Chi‐Wei , Tang Ya‐Chu , Chang Hsin‐Huei , Juan Chi‐Chang , Kuo Yow‐Chii , Kao Chung‐Cheng , Huang Yao‐Ming , Kao Yung‐Hsi
Published: June 2021

Resistin and endothelin (ET)‐1 have been reported to inhibit adipogenesis and regulate adipocyte insulin resistance, respectively. Although both hormones interact with each other, the exact signaling pathway of ET‐1 to act on resistin gene expression is still unknown. Using 3T3‐L1 adipocytes, we investigated the signaling pathways involved in ET‐1‐stimulated resistin gene expression. The upregulation of resistin mRNA expression by ET‐1 depends on concentration and timing. The concentration of ET‐1 that increased resistin mRNA levels by 100‐250% was approximately 100 nM for a range of 0.25~12 h of treatment. Treatment with actinomycin D blocked ET‐1‐increased resistin mRNA levels, suggesting that the effect of ET‐1 requires new mRNA synthesis. Treatment with an inhibitor of the ET type‐A receptor (ETAR), such as BQ610, but not with the ET type‐B receptor (ETBR) antagonist BQ788, blocked ET‐1‐increased the levels of resistin mRNA and phosphorylated levels of downstream signaling molecules such as ERK1/2, JNKs, AKT, and STAT3. Moreover, pretreatment of specific inhibitors of either ERK1/2 (U0126 and PD98059), JNKs (SP600125), PI3K/AKT (LY294002 and Wortmannin), or JAK2/STAT3 (AG490) prevented ET‐1‐increased levels of resistin mRNA and reduced the ET‐1‐stimulated phosphorylation of ERK1/2, JNKs, AKT, and STAT3, respectively. However, the p38 kinase antagonist SB203580 did not alter the effect of ET‐1. These results imply that ETAR, ERK1/2, JNKs, AKT, and JAK2, but not ETBR or p38, are necessary for the ET‐1 stimulation of resistin gene expression. In vivo observations that ET‐1 increased resistin mRNA and protein levels in subcutaneous and epididymal adipose tissues support the in vitro findings.
Pro‐inflammatory and Anti‐adipogenic Activities of Ethanol Extracts from Water Dropwort (MINARY) in Raw 264 Macrophages and 3T3 adipocytes (LB778)
Authors: KANG Min Sook , Ahn Eun Mi , Kim Young , Lee Jin‐Young , Han Gwi‐Jung
Published: June 2021

In Korea, the water dropwort (MINARY) is a one of the multi frequency vegetable. This study performed to investigate the effects of ethanol Extracts from MINARY (EM) of pro‐inflammatory effects on obesity‐related inflammation in Raw 264 Macrophages and anti‐adipogenic activity using 3T3‐L1 adipocytes. EM significantly suppresses the LPS‐induced production of pro‐inflammatory factors such as MCP‐1, TNFa and NO in stimulated RAW 264 Macrophages. To investigate the effects of EM on adipocyte differentiation, at 3 days post‐confluence, 3T3 preadipocytes were induced to differentiate using differentiation medium /insulin medium with EM. EM significantly inhibits lipid accumulation in 3T3 adipocytes by Oil red O‐staining. These Results suggest that EM is a valuable medical and food component for improving the inflammatory changes in obesity condition and modulation of metabolic syndrome. This Research was supported by National Academy of Agricultural Science of Korea Grant (PJ009469) * Corresponding author

Grant Funding Source: Supported by National Academy of Agricultural Science of Korea Grant (PJ009469)
Carotid denervation does not influence autoresuscitation from hypoxic‐induced apnea in newborn rat pups (LB782)
Authors: Lun Rongzhi , Zhang Chunfen , Fewell James
Published: June 2021

Autoresuscitation (AR) failure from hypoxic‐induced apnea by gasping has been suggested to play a role in sudden infant death. Little is known, however, about the factors that influence gasping and its ability to effect AR in the newborn. The present experiments were carried out on 5 to 6 day‐old rat pups to investigate the influence of carotid denervation (CD) on gasping during a single hypoxic exposure, and on AR during repeated hypoxic exposures. CD decreased basal respiratory frequency but not heart rate as compared to sham‐operated pups and eliminated the respiratory frequency response to alveolar hypoxia. CD decreased the time to hypoxic arousal/excitement but did not significantly influence the time to primary apnea, the time to last gasp or the total number of gasps during a single unrelenting hypoxic exposure. Furthermore, CD did not alter the number of hypoxic exposures tolerated before AR failure (Sham 15±2 – CD 15±3) Our data provide evidence that although the carotid chemoreceptors mediate the respiratory and arousal/excitement responses during exposure to hypoxia they do not modulate gasping or influence the ability of gasping to effect successful AR during repeated exposure to hypoxia.

Grant Funding Source: CIHR
Heat stress increases global mitochondrial protein acetylation and steady state levels of SIRT3 (LB798)
Authors: Bloomer Steven , Kregel Kevin , Haak Jodie
Published: June 2021

Aging results in exacerbated mitochondrial damage and cellular dysfunction after exposure to physiological challenges such as heat stress. Additionally, induction of mitochondrial stress‐defense proteins is blunted after heat stress with aging. The sirtuins are deacetylase enzymes implicated in stress defense and longevity. Sirtuin‐3 (SIRT3), which has been shown to reduce oxidative injury, is a mitochondrial enzyme that deacetylates mitochondrial proteins. Since little is known about the response of hepatic SIRT3 to physiological stress, the goal of the present study was to characterize protein levels of SIRT3 in young (6 mo) and old (24 mo) Fischer 344 rats after heat stress. Animals were exposed to a two‐heat stress protocol, and liver mitochondria were isolated at 2 and 24 h after the second heat stress. Nonheated animals served as controls. SIRT3 protein expression and global protein acetylation were determined by immunoblot analysis. Aging was associated with an increase in SIRT3 protein, and a trend for a decrease in protein acetylation. In each of the two age groups, heat stress increased both SIRT3 and global protein acetylation, which suggests that the increase in protein acetylation overwhelms the deacetylase activity of SIRT3. The increase in SIRT3 suggests that it is a stress‐responsive protein and warrants further inquiry into the acetylation status of selected mitochondrial proteins.

Grant Funding Source: Supported by NIH R01 AG‐12350
Investigation of critical amino acids in c‐terminal regions for the complex sensitivity of TREK‐2 K+ channel to membrane PIP2 and pHi (LB841)
Authors: Woo Joohan , Kim Hyun Jong , Park Kyoung Sun , Shin Dong Hoon , Zhang Yin‐Hua , Nam Joo Hyun , Kim Sung Joon
Published: June 2021

TREK‐2, a member of two‐pore domain K+ channel (K2P) family, are activated by various chemical and physical stimuli; arachidonic acid (AA), intracellular acidic pH (pHi) and membrane stretch. Also, TREK channels show dual sensitivity to plasmalemmal phosphatidylinositol 4, 5‐bisphosphate (PIP2); inhibition by PIP2 higher than physiological intrinsic level, activation by partial depletion, and complete inhibition by PIP2 scavenging (e.g. poly‐L lysine). Consistently, in inside‐out (i‐o) patch clamp conditions, application of MgATP (1 mM) inhibits TREK‐2 via PI‐kinase dependent PIP2 production. To elucidate the regulatory sites interacting with PIP2, we made site‐directed mutants of Lys and Arg in TREK‐2 c‐terminal regions that are relatively ‘proximal’ and ‘distal’ to membrane. Whole‐cell patch clamp (w‐c) recordings showed that Arg residues in the ‘distal’ domain (R356, R357) are important for maintaining basal TREK‐2 activity whereas neutralization of ‘proximal’ residues (R323, K327, K328) did not affect the background current. The suppression of basal activity was most prominent by neutralizing (alanine substitution) or deleting three Arg (R355‐7). However, maximum activation by 10 μM AA was not affected. The i‐o patch clamp recording showed that TREK‐2 inhibition by 3 mM MgATP was partly prevented in K330 neutralized mutant (K330A) whereas the neutralization of ‘distal’ cationic residues did not affect the MgATP‐dependent inhibition of TREK‐2. Unexpectedly, the pHi sensitivity of TREK‐2 was also reversed in K330A (inhibition, not activation, by acidic pHi). Interestingly, neutralization of acidic amino acid (E350) that was previously reported as pHi sensor, also prevented the inhibition by MgATP in addition to reversing the pHi dependence. Taken together, both cationic and anionic amino acids in the ‘proximal’ c‐terminal region of TREK‐2 interact to provide PIP2 and pHi sensitivity. The distal arginines appear to be important for basal activity of TREK‐2
Miniaturized wearable sensors for wireless realtime vital sign recordings, cloud based data transfer, storage, and analysis (LB858)
Authors: Federico Niksha , Federico Tessya , Federico Francesca , Sternik Gabriel , Taghizadeh Farhad , Esmaeli‐Azad Babak
Published: June 2021

Wireless Real‐time continuous monitoring of vital signs via readily accessible cloud‐based web portals and apps is much needed for practical implementation of wireless mobile health and connected healthcare of the future. Several preliminary versions of such capabilities have recently been developed and commercialized for hospitalized patients. Using simple applications, physicians are able to use their mobile smart phone and tablet devices to readily access and analyze vital signs of patients that are in hospitals and in many cases the data is stored in the cloud for further analysis.

Full potential and implementation of this capability, however, will only become a reality if wearable sensor technologies could be used for every day healthy or diseased individuals and in home settings instead of the hospital. We describe here a wearable sensor technology designed to be used by non‐hospitalized individuals that accurately monitors ECG, Blood pressure, Respiration, Oxygen saturation and body temperature. The device is wearable as a watch or a chest band, has long battery life (up to 24 hrs), and is bluetooth enabled for wireless data transmission to the cloud.

Preliminary validation studies with 80 subjects using this sensor technology vs. gold standard methodologies for measurement of vital signs will be presented. Our findings demonstrate the efficacy of using this system for continuous monitoring and detection of vital signs in people of different ages, gender groups, and weight (BMI). This system is designed for home use and has direct application for mobile health diagnostics and connected care.
The Fatal Invasion of RTA: Ricin's destructive pathway to inhibiting protein synthesis. (LB86)
Authors: Doshi Ayush , Moore Melshae , Johnson‐Anthony Chasity , Spence Kecia , Spence Keiona , Ross Khadiya , Ruhashya Ashley , Parkins Asante , Stubbs Tamica , Colton Shannon
Published: June 2021

In April 2013, letters addressed to the President were laced with ricin, a deadly toxin originating from the castor bean plant. This heterodimer inhibits protein synthesis by depurinating an adenine of rRNA. Ricin A Chain (RTA) and Ricin B Chain (RTB), are connected with a disulfide bond (DB). RTB attaches to a glycoprotein located on the cell membrane, initiating endocytosis, forming a clathrin‐coated vesicle. Once inside, the protein undergoes retrograde transport through the Golgi apparatus to the endoplasmic reticulum (ER). The DB is cleaved within the ER by Human Protein Disulfide Isomerase (hPDI), which contains four domains: a, a’ b, b’. In the reduced state, two amino acids in the active site of hPDI, (C397 and C400) donate two hydrogens to the cysteines in the DB that connects RTA and RTA. This event cleaves the DB in ricin, and forms an internal DB between C397 and C400, causing additional conformational changes to hPDI as it undergoes the redox reaction. After cleavage, RTA refolds with help from hPDI,, and can then bind to the 28SrRNA. T80 and T123 of RTA’s active site bind to adenine, creating an oxycarbonium ion due to an electron flow, while G177 stabilizes the ion. Ricin is then able to render 1500 ribosomes useless per minute. The Phillip O. Berry Academy of Technology SMART Team (Students Modeling A Research Topic) modeled Ricin and hPDI using 3D printing technology.

Grant Funding Source: Supported by a grant from NIH‐SEPA and NIH‐CTSA.
Deleterious deoxyguanosinekinase (dGK) destroys lives (LB99)
Authors: Alberth Julia , Bielski Nick , Clements Dylan , Holloway Jared , Kirsch Evan , Kirsch Mitchell , Lawrence Becca , Mellor Julia , Murphy Madeline , Papendick Adam , Quist Sean , Reeves Angelica , Wermeling Zack , Williams Julia , Kao Jonathan , Kowalski Jason
Published: June 2021

Mitochondrial Deficiency Syndrome (MDS) is characterized by a deficient amount of mitochondrial DNA (mtDNA). Without sufficient copies of mtDNA, the mitochondria cannot manufacture an adequate amount of ATP, leading to failure of energy expensive tissues such as the brain, skeletal muscle, and liver, ultimately causing death in early infancy. Deoxyguanosine kinase (dGK), an enzymatic protein, plays a role in regulating the replication of mtDNA by attaching a phosphate to a sugar/nitrogen‐base nucleoside at the active site, amino acids Glu70 and Arg142. Once phosphorylated, the assembly of mtDNA proceeds. Mutations in dGK prevent the phosphorylation of mtDNA and lead to a decrease in mitochondrial function. Two point mutations have been shown to have a deleterious impact on dGK: the R142K mutation is 0.2% active when compared to the wild type, and the E227K mutation is 5.5% active when compared to the wild type. The 3D model designed by the Westosha Central SMART (Students Modeling A Research Topic) Team displays the active site, two specific mutations and additional mutations reported in MDS patients. Screening for MDS is difficult because the condition can be caused by a wide variety of dysfunctional proteins. One such protein is dGK, therefore identifying its structure can hasten an accurate diagnosis.

Grant Funding Source: The SMART team program is supported by a grant from NIH‐CTSA.
Nonstigmatizing and Precise Terminology to Describe Processes and Outcomes in Addiction Medicine
Authors: Pfund Rory A. , Peter Samuel C. , Swift Joshua K. , Witkiewitz Katie
Published: June 2021

Scholarly journals and professional organizations in addiction medicine have recently discussed the importance of adopting nonstigmatizing and precise terminology. The present commentary expands that ongoing discussion to terms related to treatment processes and outcomes. Four implicit assumptions of stigmatizing and imprecise terms related to treatment processes and outcomes are overviewed, and research evidence against these assumptions is presented. The commentary ends with recommendations for the use of positive behavioral indicators of processes and outcomes and, more importantly, accompanying them with nonevaluative, objective descriptors of patients’ behaviors.
The Effect of Changing Arterial Transducer Position on Stroke Volume Measurements Using FloTrac System Version 4.0: A Pilot Experimental Study
Authors: Ito Jiro , Kawakami Daisuke , Morimoto Takeshi , Ueta Hiroshi , Shimozono Takahiro , Mima Hiroyuki
Published: June 2021

Objectives:

We conducted a pilot study using an experimental study protocol to evaluate the measurement error of arterial pulse contour analysis-derived stroke volume due to improper transducer leveling during the passive leg raising test and the impact of such error on the determination of fluid responsiveness.

Design:

Prospective observational study.

Setting:

A medical-surgical ICU at a tertiary referral center in Kobe, Japan.

Patients:

Consecutive critically ill adult patients using the FloTrac system Version 4.0 (Edwards Lifesciences, Irvine, CA) for hemodynamic monitoring between September 1, 2018, and November 31, 2018.

Interventions:

None.

Measurements and Main Results:

Using 20 patients, we estimated the change in the zero-reference level of an arterial transducer during head-down tilting as the vertical distance between the zero-reference levels of the transducer in the 45° semi-recumbent and supine positions. Using the FloTrac system Version 4.0, we recorded the hemodynamic variables every 20 seconds for 180 seconds at each of the following three points: 1) baseline, 2) after the transducer was elevated by the predetermined distance, and 3) after the transducer had returned to baseline. With respect to the predetermined change in the transducer level, a mean value of 18 ± 3 cm resulted in an increase in stroke volume measurement (mean value, 11 mL/beat; 95% CI, 10–13). This value corresponded to 20% (95% CI, 18–23%) of the baseline value 20 seconds after changing the transducer level. A significant correlation was observed between the predetermined change in the transducer level and the increase in the measured stroke volume (r
2 = 0.58; p < 0.001).

CONCLUSIONS:

When using the FloTrac system Version 4.0, a rapid increase in stroke volume was observed after elevating the arterial transducer. Clinicians and researchers are advised that proper leveling of the arterial transducer is necessary in order to accurately assess the change in arterial pulse contour analysis-derived stroke volume during the passive leg raising test.
Nutrition in acute pancreatitis
Authors: Arvanitakis Marianna , Gkolfakis Paraskevas , Fernandez Y. Viesca Michael
Published: June 2021

Purpose of review

This review aims to discuss recent developments in different topics regarding nutrition and acute pancreatitis (AP), including oral refeeding, nutritional therapy, and implications of gut microbiota.

Recent findings

Obesity increases the risk for severe AP and mortality. Considering the worldwide obesity rates, this finding could have major implications in the global outcomes of patients admitted with AP. Recent research confirms that early oral feeding leads to shorter length of stay, fewer complications, and lower costs. In case of intolerance to oral feeding or severe disease, nutritional therapy should be offered within 24–72 h, whereas enteral nutrition (EN) has been shown superior to parenteral nutrition. EN can be administered through gastric or jejunal feeding, depending on digestive tolerance and the presence of ileus. Nevertheless, modalities of EN in patients undergoing endoscopic drainage of pancreatitis-related collections are still undetermined. Weight-loss after discharge occurs frequently and could reflect post-AP pancreatic exocrine failure. Finally, novel research regarding gut microbiota could open new therapeutic opportunities to prevent bacterial translocation and pancreatic necrosis’ infection.

Despite available evidence many questions regarding nutritional management in patients with AP remain open. Modulation of gut microbiota could play an important role in further therapeutic management.
Sarcoidosis associated pulmonary hypertension: an update
Authors: Samaranayake Chinthaka B. , McCabe Colm , Wort Stephen John , Price Laura C.
Published: June 2021

Purpose of review

Sarcoidosis associated pulmonary hypertension (SAPH) is a well-recognised complication, associated with a seven-fold increase in mortality. This comprehensive review will summarise these recent developments and proposes the use of a phenotype-based management approach in SAPH.

Recent findings

Recent registry-based studies have highlighted the adverse outcomes associated with SAPH and shown that reduced 6-min walk distance and diffusion capacity for carbon monoxide are predictive of poor prognosis. There is increasing interest in methods for early detection of SAPH, although whether early diagnosis impacts on survival remains uncertain. The pathophysiology underpinning SAPH is complex and often incorporates multiple mechanisms. Once the diagnosis is confirmed, understanding the underlying phenotypes of SAPH is key to providing the most effective management plan. There is some evidence that treating patients with precapillary PH with pulmonary vasodilators may improve some haemodynamic and quality life measures. However, more work is needed to determine whether mortality is affected.

SAPH is associated with worsened survival. A range of phenotypes are recognised in SAPH. Multimodality risk assessment in patients with SAPH is likely to be important and is an area that requires further work. Published evidence for pulmonary vasodilator therapies in SAPH with a Pulmonary arterial hypertension-like phenotype is encouraging so far, but multiple confounding factors affects the quality of the evidence. The role of immunosuppressive agents for improving pulmonary pressures is unclear. Urgent controlled trials are needed.
Complications of chronic pancreatitis in children
Authors: Perito Emily , Gonska Tanja , Bellin Melena D. , Schwarzenberg Sarah Jane
Published: June 2021

Purpose of review

In children, chronic pancreatitis is infrequent but may be associated with serious complications, including severe pain that limits activities, exocrine and endocrine pancreatic insufficiency and malnutrition. Investigation into pediatric chronic pancreatitis has transitioned from single center reports to multicenter, protocol-driven studies. As a result, we now have information on much larger numbers of children with chronic pancreatitis, allowing a more reliable understanding of the complications of chronic pancreatitis.

Recent findings

A high percentage of children with chronic pancreatitis use opioids frequently to control pain. About a quarter of children with chronic pancreatitis have exocrine pancreatic insufficiency, and about 6% have pancreatogenic diabetes. Mild malnutrition and low bone density are both common in children with chronic pancreatitis.

Large multicenter and single-center observational studies have allowed us to more accurately assess complications of chronic pancreatitis in children. These studies demonstrate the need for examination of therapies for these complications in children.
Tinea capitis: advances and a needed paradigm shift
Authors: Le Thomas K. , Cohen Bernard A.
Published: June 2021

Purpose of review

Tinea capitis, a superficial infection of the scalp, is the most common pediatric dermatophyte fungal infection worldwide and is particularly common in the USA in low-income, low-resource settings. There are still gaps in knowledge and heterogeneities in practice in terms of diagnostic and management strategies. Furthermore, there are no clinical guidelines for management and treatment of tinea capitis in the USA. This review aims to summarize recent advances, recommend optimal management for the practicing pediatrician, and identify areas for future research for tinea capitis.

Recent findings

Trichophyton tonsurans infections are best treated with terbinafine and Microsporum canis infections are best treated with griseofulvin. Trichophyton tonsurans is the predominant cause of tinea capitis in the USA, although the main gold standard of treatment in the USA is griseofulvin. Dermatophyte antifungal resistance is an active area of investigation but seems to not be of current concern for tinea capitis in the USA.

We recommend all clinical providers ascertain the causative organism in fungal infection, either through fungal culture or newer methods which may become more readily available and cost-effective in the future, such as polymerase chain reaction assay. We also recommend terbinafine as first-line treatment of tinea capitis, with adjustment as necessary after species identification.
Biofilm and its implications postfracture fixation: All I need to know
Authors: Kanakaris Nikolaos K. , Giannoudis Peter V.
Published: June 2021

Biofilm represents an organized multicellular community of bacteria having a complex 3D structure, formed by bacterial cells and their self-produced extracellular matrix. It usually attaches to any foreign body or fixation implant. It acts as a physical protective barrier of the bacteria from the penetration of antibodies, bacteriophages, granulocytes and biocides, antiseptics, and antibiotics. Biofilm-related infections will increase in the near future. This group of surgical site infections is the most difficult to diagnose, to suppress, to eradicate, and in general to manage. Multispecialty teams involved in all stages of care are an effective way to improve results and save resources and time for the benefit of patients and the health system. Significant steps have occurred recently in the prevention and development of clever tools that we can employ in this everlasting fight with the bacteria. Herein, we attempt to describe the nature and role of the “biofilm” to the specific clinical setting of surgical site infections in the field of orthopaedic trauma surgery.
Cement beads and cement spacers: indications, techniques, and clinical results
Authors: Kulkarni Govind Shivram , Kulkarni Sunil , Babhulkar Sushrut
Published: June 2021

Objectives:

To report our experience on the use of antibiotic coated nails (ACN) and cement beads for the management of bone infections.

Materials and methods:

Infected nonunion (INU) cases were classified as: Type I (mild infection with no gap), Type II (moderate with good alignment, severe infection, gap <3 cm, no deformity), Type III (severe infection with gap ≥3 cm, deformity and limb shortening). Treatment involved either the insertion of ACN and cast (Type I), insertion of ACN, beads and external fixator (Type II), or Ilizarov methodology (Type III). A subset of 28 open fractures were admitted with severe contamination or delayed presentation with established infection and treated with debridement, ACN insertion, and antibiotic beads placed in soft tissue dead space areas.

Results:

Results of 133 cases were classified excellent, good, and poor. Type I INU reported 40 excellent and 22 good results. Type II INU reported 28 (39%) excellent, 30 (43%) good, and 13 (18%) poor results. Poor results were due to uncontrolled infection and knee stiffness. Three patients required knee fusion and 1 required amputation. Fracture union was reported in 68 cases. Four of the 28 Gustilo grade III open fractures treated with ACN developed infected nonunion and had poor function caused by stiff knees.

Conclusions:

An antibiotic impregnated cement nail (ACN) fills the dead space and elutes high concentrations of antibiotics providing some mechanical stability. We recommend the adjunct use of an ACN for the management of INU cases and for use in select cases of Gustilo grade III open fractures.
Intestinal Parasitic Infections: A Rare Coinfection by Ascaris lumbricoides and Eristalis tenax in a 10-month-old Infant in Cameroon
Authors: Mekone Nkwele Isabelle , Mbono Ritha , Bissohong Grace , Djike Puepi Yolande , Nlende Mengalle Britha , Medi Sike Christiane , Ngando Laure , Ngo Um Sap Suzanne , Chiabi Andreas
Published: June 2021

We report a rare case of coinfection by intestinal parasitosis and myiasis (Ascaris lumbricoides and Eristalis tenax) in a 10-month-old female infant living in Yaounde, an urban area in a low- and middle-income country. Incidental discovery was made following symptoms of acute vomiting and diarrhea with a massive release of an estimated thirty adult A. lumbricoides worms and E. tenax larvae through nasal, buccal, and anal routes. Diagnosis was based on the macroscopic appearance of the worms and the fly larvae. Treatment with benzimidazoles was initiated, with a resolution of symptoms within one week. This case highlights the challenges of public health eradication guidelines (such as the antihelminthic drugs marketing authorization) in our setting and discusses the protocols of management in less than 1-year-old infants in sub-saharan Africa, a region of high helminthic endemicity.
Unusual Presentation of Epstein-Barr Virus-Associated Cholestatic Hepatitis in an Infant
Authors: Jadah Raafat Hammad Seroor , Shaikho Noor Mohamed Ghassan , Hasan Sara Abdulla
Published: June 2021

Epstein-Barr virus (EBV) infections are prevalent in the pediatric population but are subclinical in the majority of cases. Elevated transaminases in the acute setting rarely increase beyond 5 times the normal upper limit. We present a girl aged 1 y with fever, vomiting, and diarrhea. Although initial physical examination was unremarkable, she developed jaundice, hepatomegaly, abdominal distension, and a maculopapular rash during admission. Laboratory investigations revealed marked increase in transaminases (alanine aminotransferase 7,664.5 IU/L, aspartate aminotransferase 12,266 IU/L), elevated γ-glutamyl transferase (224 IU/L), and hyperbilirubinemia (total 130.7 µmol/L, direct 104.9 µmol/L). Abdominal ultrasound reported hepatomegaly with mild ascites. Serology revealed that both Monospot test and EBV immunoglobulin G were positive. With supportive therapy, improvement was noted within a week of symptom onset. We hereby elucidate the importance of considering EBV as a cause of acute cholestatic hepatitis in a very young pediatric patient who develops a rapid elevation of liver enzymes.
Safety, Tolerability, and Pharmacokinetics of Oral Ferric Maltol in Children With Iron Deficiency: Phase 1 Study
Authors: Allen Stephen , Auth Marcus Karl-Heinz , Kim Jon Jin , Vadamalayan Babu
Published: June 2021

Objectives:

Iron deficiency is common in children and can have negative effects on behavior and function. Standard oral ferrous iron replacement is poorly absorbed and can cause treatment-limiting gastrointestinal adverse events (AEs). Ferric maltol is formulated to improve gastrointestinal absorption and tolerability versus oral ferrous compounds. In adult phase 3 trials, it increased hemoglobin and iron stores versus placebo, with a gastrointestinal AE profile similar to placebo. Here, we assess different doses of ferric maltol in children with iron deficiency.

Methods:

This phase 1 trial involved children of age 10 to 17 years with ferritin <30 µg/L (or <50 µg/L with transferrin saturation [TSAT] <20%). Children were randomized 1:1:1 to oral ferric maltol 7.8 mg, 16.6 mg, or 30 mg twice daily for 9 days and once on day 10. The primary outcomes were iron uptake measures (serum iron and TSAT) and population pharmacokinetic analyses.

Results:

The trial included 37 children (mean age 14.0 years; baseline mean ± standard deviation ferritin 16.3 ± 8.02 µg/L). Ferric maltol increased iron uptake nondose-proportionally: serum iron and TSAT plateaued between the 2 higher doses on day 1 and were comparable across all doses on day 10. Twenty children (54%) experienced AEs (all mild/moderate, gastrointestinal 32%), with similar frequencies in each group.

Conclusions:

All 3 ferric maltol doses increased iron uptake in children with iron deficiency, even over the short study duration, and were well tolerated. Nondose-dependent changes in serum iron and TSAT indicate physiologic regulation of iron uptake to meet the body’s needs.
Revisiting the lumbosacral orthosis from the perspective of dynamical systems theory: a preliminary randomized clinical trial on patients with chronic low back pain
Authors: Hekmatfard Maryam , Sanjari Mohammad Ali , Maroufi Nader , Saeedi Hassan , Ebrahimi-Takamjani Ismail , Behtash Hamid
Published: June 2021

Background:

The prevalent method for investigating the effect of therapeutic interventions on walking in the individuals with chronic low back pain (CLBP) is component-level approach in which all measurements focus on the spine component alone. However, this approach cannot disclose information about the overall function of the movement system such as complex walking patterns, which, in turn, reveal the underlying movement control.

Objectives:

To compare the effect of 3-week wearing of lumbosacral orthosis (LSO) along with routine physical therapy with routine physical therapy alone on walking complexity in the individuals with nonspecific CLBP on the basis of the systems approach.

Study Design:

Preliminary randomized clinical trial.

Methods:

Twenty-four subjects were randomly allocated to two groups. The control group received the routine physical therapy for 3 weeks. The intervention group received the same program plus an LSO. Nonlinear analysis was used to quantify walking complexity, as behavior of the entire movement system, before and after the intervention and at 1-month follow-up.

Results:

An average of 496 strides during ten minutes of walking was used for analysis. There was no significant difference (p > 0.05) in degree of walking complexity between two groups during all evaluation periods.

Conclusions:

The administered orthotic intervention did not alter walking complexity. This suggests that therapeutic goal of current LSOs, which is not based on the systems approach, cannot recover the emergent behavior of the movement system. This may be a potential source of controversies.

Clinical Relevance:

To achieve an effective treatment, orthotists should focus on the individuals themselves, not only on their CLBP symptoms. Although the component-level approach aims to decrease the symptoms, the systems approach focuses on the whole context that fosters LBP symptoms.
Transgenerational plasticity in the eye size ofDaphnia
Authors: Walsh Matthew R. , Gillis Michael K.
Published: June 2021

It is well established that environmental signals can induce phenotypic responses that persist for multiple generations. The induction of such ‘transgenerational plasticity’ (TGP) depends upon the ability of organisms to accurately receive and process information from environmental signals. Thus, sensory systems are likely intertwined with TGP. Here we tested the link between an environmental stressor and transgenerational responses in a component of the sensory system (eye size) that is linked to enhanced vision and ecologically relevant behaviours. We reared 45 clones ofDaphnia pulicariain the presence and absence of a low-quality resource (cyanobacteria) and evaluated shifts in relative eye size in offspring. Our results revealed divergent shifts in relative eye size within- and across-generations. ParentalDaphniathat were fed cyanobacteria produced a smaller eye thanDaphniafed high-quality algae. Such differences were then reversed in the offspring generation;Daphniawhose mothers were fed cyanobacteria produced larger eyes thanDaphniathat were continually fed green algae. We discuss the extent to which this maternal effect on eye size is an adaptive response linked to improved foraging.
Eric Harold Mansfield. 24 May 1923—20 October 2016
Authors: Calladine C. R.
Published: June 2021

Eric Mansfield was a structural engineer who worked at the Royal Aircraft Establishment Farnborough from 1943 to 1983 on a wide range of problems in the field of aircraft structures. His main working tool was the mathematical theory of elasticity, which he deployed with skill, ingenuity, perseverance and imagination to investigate many problems related to the design of aircraft structures during a period of development of higher flight performance and new materials. His studies included aircraft wings and fuselages, particularly in the presence of cut-outs and openings—for which he invented the ‘neutral hole’ concept—and problems involving large-deflection structural behaviour of plates, including thermal effects such as flexural and torsional buckling of fins and wings heated in supersonic flight. He also developed the novel and powerful tension field theory for understanding the post-buckling behaviour of thin webs in shear, and the analogous inextensional bending theory of thin wings. His mathematical models were confirmed by elegant experiments. Mansfield's book
The bending and stretching of plates
contains clear descriptions of many of his research investigations; it has become a classic text. All of Mansfield's writing is incisive and clear. He was widely regarded as a seminal figure in the field of applied structural mechanics in the second half of the twentieth century.
Stimuli-responsive surfaces for switchable wettability and adhesion
Authors: Li Chang , Li Ming , Ni Zhongshi , Guan Qingwen , Blackman Bamber R. K. , Saiz Eduardo
Published: June 2021

Diverse unique surfaces exist in nature, e.g. lotus leaf, rose petal and rice leaf. They show similar contact angles but different adhesion properties. According to the different wettability and adhesion characteristics, this review reclassifies different contact states of droplets on surfaces. Inspired by the biological surfaces, smart artificial surfaces have been developed which respond to external stimuli and consequently switch between different states. Responsive surfaces driven by various stimuli, e.g. stretching, magnetic, photo, electric, temperature, humidity and pH, are discussed. Studies reporting on either atmospheric or underwater environments are discussed. The application of tailoring surface wettability and adhesion includes microfluidics/droplet manipulation, liquid transport and harvesting, water energy harvesting and flexible smart devices. Particular attention is placed on the horizontal comparison of smart surfaces with the same stimuli. Finally, the current challenges and future prospects in this field are also identified.