bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital clubbing: have we lost its anatomical form and clinical relevance
Authors: Benninger Brion 
Published: June 2021

INTRODUCTIONHippocrates first described digital clubbing (DC) in a patient with empyema in the 5th century BC. Although the majority of medical trainees and qualified clinicians are aware of DC, few can confirm its diagnosis and are unable to discuss its associations with multiple systems despite its prevalence in the population. DC can be diagnosed with the combination of observation, provocative testing, and palpation. The objective of this study was to investigate the diagnosis of DC, its associations with the body's systems, radiological diagnosis and its fate regarding treatment.METHODSLiterature search was conducted on journals, specialty texts and websites regarding DC, its medical associations, radiological diagnosis and its role in physical examination.RESULTSLiterature search revealed that DC could be confirmed using x‐ray. No contemporary articles or studies described its use during clinical examination or its fate.DISCUSSIONDC is a relatively well‐known term. Few qualified clinicians and fewer trainees can discuss its diagnosis, pathological associations, clinical exam integration or its fate. DC will subside with successful treatment of the associated pathology.CONCLUSIONThis study suggests with anatomical and etiological understanding of DC, health care providers can diagnose and link it to one of its several pathologies and monitor the pathology with the presence of DC.
Acute Oral Bryostatin‐1 Treatment Improves Morris Water Maze Acquisition in a Transgenic Mouse Model of Alzheimer's Disease
Authors: Schrott Lisa M , Yi Ping , Johnson Gabriel S , Basting Tyler , Castor Trevor P , Alexander J. Steven 
Published: June 2021

Recent research suggests that Bryostatin‐1 is neuroprotective via activation of protein kinase C isoforms, down regulation of pro‐inflammatory factors and angiogenic processes and the suppression of beta amyloid. Alzheimer's disease (AD) has been associated with these factors and therefore Bryostatin‐1 is an attractive candidate for ameliorating AD cognitive deficits. We evaluated the ability of Bryostatin‐1 to restore learning and memory in the BC3‐Tg(APPswe, PSEN1 dE9) 85Dbo/J mouse model of AD. This strain incorporates the human ‘Swedish’ (swe) amyloid precursor protein and presenilin mutations, which are associated with progressive human AD. A stable oil formulation of Bryostatin‐1 (5 μg/mouse) was administered by oral gavage 3 times the week prior to testing and then daily during 5 days of Morris Water Maze testing (4 trials per day). Treated mice were compared to untreated transgenic controls and wild‐type mice. Tg AD mice treated with Bryostatin‐1 had better performance in the water maze than untreated controls. Treated mice exhibited significantly shorter latencies and swimming distances to find the hidden platform, with no difference in their swimming speeds. The most profound effect was found in the early days of testing. The treated mice had performance nearly identical to that of the wild‐type controls. These data suggest that oral Bryostatin‐1 may be useful in treating cognitive decline associated with AD.This research was supported by a grant from the NIA and NIH (1R44AG034760‐01A1)
Central effects evoked by proline‐rich decapeptide in rats: changes in cardiovascular parameters and neuronal c‐Fos
Authors: Ianzer Danielle Alves , Xavier Carlos Henrique , Madden Christopher J. , Camargo Antonio C. , Morrison Shaun F. 
Published: June 2021

Bj‐PRO‐10c (10c) is a proline‐rich oligopeptide from Bothrops jararaca CNP brain precursor and crude venom. 10c evokes antihypertensive and bradycardic effects in SHR. In addition, 10c crosses the blood brain barrier and increases plasma levels of the nitric oxide precursor, L‐arginine. We evaluated whether centrally injected 10c changes blood pressure, heart rate (HR) and the expression of neuronal c‐Fos. 10c (7.1nmol/Kg) or vehicle (NaCl 0.9%) were icv injected in anesthetized male SHR and Wistar rats. Mean arterial pressure (MAP) and HR were recorded for 90min following injection. Brain sections were taken to evaluate c‐Fos and NOS, by double‐labeling immunohistochemistry. Although 10c reduced MAP and HR in both Wistar (ΔMAP: −2±1 saline vs. −6±1mmHg 10c, ΔHR −13±5 vs. −34±5bpm; p<0.01) and SHR (ΔMAP −7±2 saline vs. −16±3mmHg 10c, ΔHR −13±5 vs. −42±7bpm; p<0.01), the changes in MAP were greater (p<0.01) in SHR. At 90min following 10c injection, c‐Fos expression was increased in comparison to saline injections in the nucleus Ambiguus and CVL, areas, which contained neurons double‐labeled for c‐Fos + NOS. We conclude that the central administration of 10c prominently drives a bradycardia, possibly through NO‐related mechanisms.Support: Fapesp
Association between the Activation of Melanin‐concentrating Hormone (MCH) Producing Neurons and REM Sleep in Rats
Authors: Vas Szilvia , Kostyalik Diana , Katai Zita , Kitka Tamas , Adori Csaba , Molnar Eszter , Petschner Peter , Pap Dorottya , Horvath Beata , Bagdy Gyorgy 
Published: June 2021

IntroductionRapid eye movement sleep (REMS) rebound after REMS deprivation is characterized by increased time spent in REMS and the activation of melanin‐concentrating hormone (MCH) expressing neurons of the hypothalamus, known to have a central role in REMS regulation. The time spent in REMS shows strong correlation with activation of MCH cells of the hypothalamus.Materials and MethodsMale Wistar rats were selectively REMS deprived (72h, flower‐pot method), followed by a 3h rebound sleep, during which EEG, EMG and motility were recorded. Immediately after rebound, each animal was perfused. MCH/cFos immunohistochemistry (cFos as an indicator of neuronal activation) was performed on hypothalamic setions. Home cage animals were used as controls. Data were evaluated by Spearman‐correlation.ResultsDuring REMS rebound, both the number of REMS episodes and the average duration of REMS items increased. However, a positive correlation with MCH/cFos double staining was shown only in case of the number of REMS episodes.DiscussionThe activation of MCHergic hypothalamic neurons seems to be in a strong connection with the number of REMS, suggesting that REMS deficiency may be compensated via the enhancement of the number during the rebound rather than the average duration of REMS items.This work was supported by TAMOP‐2.2.1. B‐09/1/KMR‐2010‐0001
IL‐6 Indirectly Modulates The Induction Of Glyceroneogenic Enzymes In Adipose Tissue During Exercise
Authors: WAN ZHONGXIAO , Ritchie Ian , Chan Catherine B. , Wright David 
Published: June 2021

Glyceroneogenesis is an important step in the control of fatty acid re‐esterification with PEPCK and PDK4 being key enzymes in this process. It has been suggested that IL‐6 regulates adipose tissue metabolism and gene expression during exercise. The purpose of this investigation was to determine the role of IL‐6 in modulating the effects of exercise on the expression of glyceroneogenic enzymes in mouse adipose tissue. To achieve these goals, we utilized IL‐6 ex vivo treatment in cultured adipose tissue in combination with IL‐6−/−mice model. Treatment of cultured epididymal adipose tissue (eWAT), increased the phosphorylation of AMPK, ACC and STAT3 and induced SOCS3 mRNA levels while decreasing PEPCK mRNA. The activation of AMPK was independent of increases in lipolysis. An acute bout of treadmill running did not result in the induction of SOCS3 or increases in the phosphorylation of STAT3 in eWAT from WT mice. Exercise‐induced increases in PEPCK and PDK4 mRNA expression were attenuated in eWAT from IL‐6−/− mice in parallel with a greater relative increase in AMPK phosphorylation compared to exercised WT mice. These changes occurred independent of alterations in beta‐adrenergic signalling in adipose tissue from IL‐6−/− mice. Our findings question the role of IL‐6 signalling in adipose tissue during exercise and demonstrate an indirect effect of this cytokine in the regulation of adipose tissue gene expression.This work was supported by a Bridge Funding Operating Grant from the Canadian Institute of Health Research, Institute of Nutrition, Metabolism and Diabetes to David C. Wright.
Calcineurin‐NFAT signaling regulates atrogin‐1 and MuRF1 via miR‐23a during glucocorticoid induced muscle atrophy
Authors: Hudson Matthew B , Woodworth-Hobbs Myra E , Zheng Bin , Gooch Jennifer L , Price S Russ 
Published: June 2021

MicroRNAs play a critical role in biological processes including muscle atrophy. MicroRNA‐23a (miR‐23a) negatively regulates the expression of two atrophy‐related E3 ubiquitin ligases, atrogin‐1 and MuRF1, in skeletal muscle and cultured muscle cells. During atrophy miR‐23a is reduced in muscle cells. Although it was recently shown that miR‐23a expression is positively regulated by NFATc3, the mechanism of miR‐23a suppression during atrophy remains unknown. Previously, we found that the activity of calcineurin (Cn), a calcium‐activated phosphatase that regulates NFATc proteins, is decreased by diabetes. Since diabetes causes muscle atrophy, and glucocorticoids are required for this response, we investigated how the glucocorticoid dexamethasone (DEX) affects Cn activity, NFATc3 signaling, and miR‐23a expression. C2C12 or L6 myotubes were treated with 100 uM DEX to induce atrophy. Within 1 h of treatment, Cn activity was reduced and less NFATc3 was present in the nucleus. Further, the level of miR‐23a was also decreased within 30 minutes. After 48 h, expression of the NFATC3 target gene, MCIP1.4, and miR‐23a were decreased. Expression of atrogin‐1 and MuRF1 were also increased 48 h after DEX addition. Collectively, these findings indicate the Cn‐NFAT signaling pathway may play an important role in the regulation of atrogin‐1 and MuRF1 by suppressing miR23a during glucocorticoid induced muscle atrophy.Supported by the National Institutes of Health awarded to M.B. Hudson (T32 DK007656) and the American Heart Association to S.R. Price (7660020)
The Ability of Spices to Increase Vegetable Intake among Overweight Adults, Measured by a Universal Eating Monitor
Authors: Li Zhaoping , Brahe Lena K , Zerlin Alona , Rheinwald‐Jones Alexis , Krak Michael , Thames Gail , Heber David 
Published: June 2021

IntroductionThe intake of vegetables in the US remains below the recommendation in the Dietary Guidelines for Americans; particularly intake of cruciferous vegetables is often low, due to their bitter taste. The aim of this ongoing study is to examine if added spice mixtures can offset taste aversions and increase the intake of different vegetables including the cruciferous vegetables broccoli and cauliflower.MethodsTwenty healthy overweight adults (BMI: 25–30 kg/m2) with a daily intake of less than three servings of vegetables are enrolled, ensuring equality between sexes and between high and low restraint eaters, defined by the Three Factor Eating Questionnaire (TFEQ‐R21). At a total of 10 visits, a random selected vegetable, with or without added spices, is served in quantities sufficient to test intake, and a computer‐based system modified from the Universal Eating Monitor (UEM) is used to measure total food intake (g), meal duration (min) and eating rate (g/min), and to obtain VAS scores to assess sensory and hedonic qualities of the vegetable, and ratings of appetite and mood.ResultsMethod feasibility and preliminary observations have been obtained. Final statistical analysis is pending.PerspectiveThe UEM method can give valuable information on whether simple approaches as addition of spices, potentially can increase vegetable intake as recommended by the Dietary Guidelines for Americans.
Effect of Eurycoma longifolia on Stress Hormones and Psychological Mood State in Moderately Stressed Subjects
Authors: Talbott Shawn , Talbott Julie , George Annie , Pugh Michael 
Published: June 2021

Eurycoma longifolia is a medicinal plant commonly called Tongkat ali (TA) and “Malaysian ginseng.” TA roots are a traditional “anti‐aging” remedy and modern supplements are intended to improve libido, energy, sports performance and weight loss. Previous studies have shown properly‐standardized TA to stimulate release of free testosterone, improve sex drive, reduce fatigue, and improve well‐being.We assessed stress hormones and mood state in 63 subjects (32 men and 31 women) screened for moderate stress and supplemented with a standardized hot‐water extract of TA root (PhystaTM, Biotropics Malaysia) or Placebo for 4 weeks.Significant (p<0.05) improvements were found in the Physta group for Tension (−11%), Anger (−12%), and Confusion (−15%). Stress hormone profile (salivary cortisol and testosterone) was significantly (p<0.05) improved by Physta supplementation, with reduced cortisol exposure (−16%) and increased testosterone status (+37%). These results indicate that daily supplementation with Tongkat ali (Physta) improves stress hormone profile and certain mood state parameters, suggesting that this “ancient” remedy may be an effective approach to shielding the body from the detrimental effects of “modern” chronic stress.This study was funded by Biotropics Malaysia and conducted by SupplementWatch
Pressure overload amplifies IL‐18 signaling in a rabbit model of myocardial hypertrophy and failure
Authors: Yoshida Tadashi , Srinivas Mummidi , Friehs Ingeborg , del Nido Pedro J. , Somanna Naveen , Valente Anthony J. , Chandrasekar Bysani 
Published: June 2021

Sustained inflammation plays a causal role in the development and progression of LVH and its transition to failure. We hypothesized that pressure overload (PO) amplifies interleukin (IL)‐18 signaling during LVH and failure, and IL‐18 is a potent pro‐hypertrophic cytokine.ResultsUsing a rabbit model, we report that PO by constriction of the descending thoracic aorta induces LVH. Monitoring by echocardiography indicates compensated hypertrophy at 4 weeks (Mass/Volume ratio: 1.7±0.11) and ventricular dilatation indicative of failure at 6 weeks (M/V ratio: 0.7±0.04). We cloned rabbit IL‐18, IL‐18Rα and β, and IL‐18BP full‐length cDNA, and show that PO, while enhancing IL‐18 and IL‐18R expression in hypertrophied and failing hearts, markedly attenuated expression levels of the IL‐18 antagonist IL‐18 binding protein. In vitro, cyclical mechanic stretch (10% cyclic equibiaxial stretch, 1 Hz) induced hypertrophy of cardiomyocytes (CaM) and enhanced IL‐18, IL‐18Rα and ANP‐1 expression. Treatment with rhIL‐18 induced its own expression and that of IL‐18Rα via AP‐1, and CaM hypertrophy via PI3K/Akt/GATA4.ConclusionsPO enhances IL‐18 and its receptor expression in hypertrophied and failing hearts. Since IL‐18BP expression is markedly inhibited, our results indicate a positive amplification in IL‐18 inflammatory signaling, and suggest IL‐18 as a potential therapeutic target in LVH and failure.
Low respiratory quotients in chow‐fed male bonnet macaque monkeys as an indicator of metabolic stress due to single cage housing
Authors: Rising Russell , Lin Jack 
Published: June 2021

ObjectiveDetermine the metabolic affects of previously group housed male monkeys residing in single cage housing (SCH).MethodsAfter two months of SCH, 16 adult male bonnet macaque (M. radiata) monkeys (11.0 ± 1.9 kg, modified BMI = 40.0 ± 7.0 kg/crown‐rump length, m2 and 14.5 ± 3.1 years old) were each placed in the primate Enhanced Metabolic Testing Activity Chamber (EMTAC Inc. Santa Barbara, CA) for 22‐hour measurements of energy intake (kcal/kg) and expenditure (EE; kcal/kg/min), along with the respiratory quotient (RQ;VCO2/VO2). All were fed monkey chow #5038 (LabDiet Inc., Richmond, IN) ad‐libitum under a 12/12 hour light/dark cycle. Metabolic data were divided into day (8‐hours), night (12‐hours) and morning periods (2‐hours). For data analysis (SPSS Ver. 13), monkeys were divided into stressed and non‐stressed groups based on their RQ being above or below 0.70, respectively.ResultsWhen compared to their non‐stressed counterparts, stressed monkeys exhibited a lower 22‐hour mean RQ (0.66 ± 0.03 vs. 0.78 ± 0.05; p<0.05) as well as that during the day (0.69 ± 0.04 vs. 0.81 ± 0.03; p<0.05), dark (0.63 ± 0.02 vs. 0.77 ± 0.07; p<0.05) and morning (0.67 ± 0.03 vs. 0.77 ± 0.07; p<0.05) periods. Moreover, stressed monkeys had a greater EE during the morning period (4.1 ± 0.6 vs. 3.5 ± 0.3 kcal/kg; p<0.05) when compared to their non‐stressed counterparts. Finally, energy intake was reduced in the stressed (7.0 ± 8.5) compared to non‐stressed (27.0 ± 12.2) monkeys.ConclusionBesides the low energy intake, the EMTAC enabled the detection of abnormal metabolic changes associated with the apparent stress of long term SCH.
R‐type Ca2+ channels and inhibitory neuromuscular transmission in the gastrointestinal tract
Authors: Rodriguez‐Tapia Eileen , Galligan James 
Published: June 2021

Enteric inhibitory neuromuscular transmission relaxes gut smooth muscle via nitric oxide (NO) and purinergic mechanisms. In the guinea pig ileum, R‐type Ca2+ channels couple to release of NO while P/Q‐ and N‐type Ca2+ channels couple to release of the purine. In the current studies we tested the hypothesis that R‐type Ca2+ channels also couple selectively to NO release in the mouse colon by studying relaxations and inhibitory junction potentials (IJPs).MethodsLongitudinal muscle relaxations were studied using an in vitro organ bath system and intracellular recordings were conducted to study IJPs. Both responses were evoked using electrical field stimulation. The effects of drugs applied to the organ bath solution were investigated.ResultsThe R‐type Ca2+ channel blocker, NiCl2 (1–50 micromolar) did not alter neurogenic relaxation (10 Hz, 1s stimulus train) of the mouse distal colon. However, NiCl2 (50 micromolar) reduced the peak response and integrated areal of the IJP (1–60 Hz, 200 ms stimulus train).ConclusionR‐type Ca2+ channels couple to release of inhibitory neurotransmitters in the guinea pig and mouse gastrointestinal tract. The relationship between IJPs and relaxation of the mouse colon is not clear.
Reduction in peripheral blood beta arrestin1 levels during major depressive disorder in reproductive women
Authors: Nayyar Tultul , Alam Farzana , Richie William , Ansah Twum A , Bailey Rahn K 
Published: June 2021

OBJECTIVEWomen are twice as likely as men to develop major depressive disorder (MDD) during their reproductive years. G protein coupled receptor (GPCR) signaling mechanism has been implicated in both the pathogenesis and treatment of MDD. Beta arrestin (β‐AR)‐1 protein plays regulatory role in the GPCR signaling. We studied the relationship between the severities of MDD and the protein levels of β‐AR1, G protein subunits (Gαs and Gαi) in the peripheral blood mononuclear leukocytes (PBMC) of women during reproductive ages.DESIGN AND METHODSNon‐pregnant women with MDD were evaluated with Mini‐ International Neuropsychiatric Interview for Axis I Diagnostic and Statistical Manual of Mental Disorders, 4th edition, criteria (DSMIV‐TR). The severity of depression were determined by the 17‐item Hamilton Depression Rating Scale (HDRS) at two time points: (i) during depression (before taking any antidepressants/therapy) and (ii) at 8 weeks after clinical treatment with antidepressants/therapy. The protein levels of β‐AR1, Gαs and Gαi in PBMC were determined by ELISA.RESULTSSignificant inverse correlation between β‐arrestin‐1, Gαs, Gαi protein levels in the PBMC and the HDRS score were obtained.CONCLUSIONThe levels of β‐AR1 in PBMC of patients with MDD may potentially serve as a biochemical marker for the affective state of these patients. Research supported by 8 U54 RR026140 03(NIMHD).
Genotype‐phenotype relationship in patients affected by novel CLCNKB mutations
Authors: Andrini Olga , Keck Mathilde , Blanchard Anne , Vargas‐Poussou Rosa , Lourdel Stéphane , Teulon Jacques 
Published: June 2021

BackgroundThe CLCNKB gene encodes for ClC‐Kb, a renal Clchannel expressed in the basolateral membrane of the distal nephron. Mutations occurring in CLCNKB gene are the molecular cause of classic Bartter syndrome (cBS) type III, an autosomal recessive disorder characterized by salt‐wasting tubulopathy.AimFunctional characterization of 6 novel ClC‐Kb mutants and their implication in the cBS phenotype.MethodsCharacterization of ClC‐Kb mutants using heterologous expression systems. Protein abundance, surface expression and Clcurrents were collected.ResultsG246R, G424E and L439P did not carry any current whereas the others mutants showed a variable reduction of the current with respect to WT (L81P 50%; R351P 67% and V170M 63%). We investigated the sensitivities to external H+ and Ca2+, two biophysical properties of CLC‐Kb, in mutants showing residual activity. We observed no difference in half‐maximal pH inhibition (pKa) and in the stimulating effect of external Ca2+ ([Ca2+]ext ) for L81P and R351P as compared to WT. In contrast, there was a dramatic alteration in both pKa and sensitivity to [Ca2+]ext for V170M. Regarding surface expression, the mutants fell into 2 categories: (i) impaired surface expression: G246R, G424E and L439P; (ii) reduction of the plasma membrane expression: L81P, V170M and R351P.ConclusionsReduced targeting to the membrane and/or lower stability of the membrane protein is the main functional consequence of these mutations. V170M showed an altered pHext and [Ca2+]ext sensitivity. This feature can partially explain the mild phenotype of cBS, the partial impairment of plasma membrane targeting being compensated by a higher activity of the mutated channel under physiological conditions.
Renal effects produced by microinjection of kappa opioid agonist into the bed nuclei of the stria terminalis (BST)
Authors: Franklin Cynthia , Rangel Yolanda , Fortepiani Lourdes , Toney Glenn , Gottlieb Helmut 
Published: June 2021

Intracerebroventricular (ICV) injection of the kappa opioid agonist, U‐50448H (U50), produces a marked diuresis, antinatriuresis, and an increase in renal sympathetic nerve activity (RSNA). The dorsomedial BST has been show to express kappa opioid receptors (KOR) that project to the hypothalamic areas involved in water homeostasis, therefore we examined if injection of U50 into the BST would produce similar effects on renal function.MethodsRats anesthetized with urethane‐chloralose were instrumented to record arterial blood pressure (ABP), heart rate (HR) and RSNA. Catheters were placed in a femoral vein for drug delivery and infusion of isotonic saline (25 μl/min) and in the urinary bladder for urine collection. Urine was sampled during two 10 min control and six 10 min periods starting 10 min after injection of U50 or vehicle to the BST.ResultsU50 significantly increased urine excretion (n=8, P<0.05) without changing HR, mean ABP, urinary sodium excretion or RSNA. Injections of saline (n=8) were without affect.ConclusionThe ability of U50 to increase urine outflow without effecting sodium excretion and RSNA raises the possibility that BST neurons could be an important substrate through which drugs targeting Kappa opioid receptors could selectively facilitate water excretion in sodium retaining diseases such as salt‐sensitive hypertension. This work was supported by 5SC2 HL104639.