bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anatomical Variations of the Lumbrical Muscles of the Hand, Regarding Origin, Insertion, Innervation and its Clinical Significance: A Cadaveric Study
Authors: Veras Wilson R. , Hernandez Fernando , Ostolaza Kyara , Vega Carlos , Zanko Nikita 
Published: May 2022

The Lumbrical muscles originate in the hand from the tendons of the flexor digitorum profundus muscle and extend to the radial side of the metacarpophalangeal joints. Usually, the median nerve innervates the lumbrical muscles I and II, and the ulnar nerve the lumbrical muscles III and IV. Each lumbrical muscle flexes the metacarpophalangeal joint and extends the interphalangeal joints. Also, it assists in the fine motor movements of the hand.Numerous lumbrical muscle variants have been described, absence, accessory slips, variations in origin, insertion, innervation, between others. The objective of this study is to record the anatomical variations related to the origin, insertion, and innervation of this group of intrinsic muscles of the hand and discuss the clinical significance of these variations.For this study, we used ten hands of formalin embalmed cadavers from the anatomy laboratory of San Juan Bautista School of Medicine in Caguas, Puerto Rico. The hands were identified by number, right or left, and male or female. Recollection of Data of anatomical variations of the lumbrical muscles was done through delicate dissection techniques.ResultsFrom the 76 lumbrical muscles in regards to origin, insertion, and innervation. 64% of the lumbrical muscles were normal in origin, innervation, and insertion. Variations were found in various specimens. 13% of the lumbrical muscles showed a proximal origin inside the carpal tunnel. 11% showed Variations in the insertion site. 8% showed variation in the innervation regarded the third and fourth lumbricals. Also, in 4% of specimens, variations regarding the morphology of the lumbrical muscles were found.Anatomical variations of the lumbrical muscles could be associated with the development of pathologies that affect the mechanical functions of the hand. Carpal tunnel syndrome is the most common hand neuropathy in the United States, accounting for 90% of all neuropathies. One of the contributing pathogenetic factors is median nerve compression due to lumbrical muscles variations inside the carpal tunnel. Also, variant innervation of the lumbrical muscles can lead to a misdiagnosis in the event of nerve injuries at the level of the forearm or the hand.
Stretch‐induced Myocardial Injury and Inflammation After Transient Vasopressin‐Mediated Left Ventricular Pressure Overload in Swine
Authors: Rolland Tyler J. , Shihab Ronzon R. , Nsumbu Dorcas , Tajlil Arezou , Canty John M. , Weil Brian R. 
Published: May 2022

ObjectiveUsing the α1‐adrenergic agonist phenylephrine (PE), we have previously demonstrated that an acute episode of transient pressure overload (TPO) elicits stretch‐induced myocardial injury and reversible left ventricular (LV) systolic dysfunction. Although this was accompanied by leukocyte mobilization, a rise in inflammatory cytokine levels, and increased pro‐inflammatory gene expression in the heart, the extent to which this resulted from direct activation of α1‐adrenergic receptors on immune cells vs. an inflammatory response to mechanical stretch‐induced myocardial injury is unclear. Accordingly, the present study was designed to determine if an inflammatory response to myocardial injury is evident when TPO is produced by vasopressin (VP), a vasoconstrictor without direct α1‐adrenergic agonist properties.MethodsHemodynamic and echocardiographic parameters were assessed in propofol‐anesthetized swine before, during, and after a 30‐minute infusion of VP (VP‐TPO; 0.04 U/kg/min, n=7) to increase LV end‐diastolic pressure (EDP) to ~30mmHg. Serial jugular venous blood sampling was performed to quantify circulating cardiac troponin I (cTnI), leukocytes, and inflammatory cytokines (TNF‐α and IL‐6) at baseline and 3‐hours after cessation of VP‐TPO. Leukocyte and cytokine levels were compared with those observed after PE‐mediated TPO in a separate group of animals (PE‐TPO; n=6).ResultsVP elicited a significant rise in mean arterial pressure (91±5 to 165±11 mmHg) and LV EDP (10±1 to 29±2 mmHg; both p<0.05 vs. baseline). This was accompanied by a significant rise in LV end‐diastolic volume (73±5 to 110±7 mL) and end‐systolic volume (20±3 to 53±6 mL), as well as a reduction in LV ejection fraction (EF; 72±3 to 52±3 %; all p<0.05 vs. baseline). One hour after cessation of VP‐TPO, LV EF remained depressed vs. baseline (60±3 %; p<0.05) and circulating cTnI levels began to rise, reaching a concentration that was ~10‐fold higher than baseline concentrations at the 3‐hour post‐TPO timepoint (18±5 to 118±21 ng/L; p<0.05). These changes were accompanied by a significant rise in circulating neutrophils, monocytes, TNF‐α, and IL‐6 that was similar to that observed after PE‐TPO (Figure).ConclusionsVP‐TPO elicits myocardial injury, leukocyte mobilization, and an acute rise in circulating pro‐inflammatory cytokines, thereby recapitulating several features of PE‐TPO in the absence of direct α1‐adrenergic stimulation. These findings suggest that stretch‐induced myocardial injury provokes an inflammatory response that may play an important role in promoting the development of cardiac fibrosis and diastolic dysfunction after exposure to repetitive episodes of TPO.
Long Term Pulmonary Effects of E‐cigarettes on in‐utero Exposed Mice
Authors: Alghothani Omar , Aslaner David M. , Gorr Matthew W. , Miller Roy A. , Wold Loren E. 
Published: May 2022

IntroductionThe in‐utero environment is delicate, as it fosters the proper health and growth of the fetus. Negative environmental effects during gestation increase the chances of long‐term developmental consequences. As e‐cigarettes gain popularity in pregnant mothers, the aim of this study is to observe the chronic pulmonary function of adult mice exposed to e‐cigarette vapor during gestation.MethodsPregnant mice underwent exposure for 4 hours a day, 5 days a week beginning from the first day of pairing for breeding and ending at birth. Mice were separated into three exposure groups each receiving one 70 mL e‐cig vapor puff per minute of (1) E‐cig vapor with nicotine Nic(+) (2% Nic 50:50 propylene glycol:vegetable glycerin), (2) E‐cig exposure without nicotine Nic(‐) (propylene glycol: vegetable glycerin), or (3) continuous filtered air exposure (FA)HEPA filter. Resulting pups from each group were examined at adulthood (4‐5 months). Data including baseline lung mechanic scan and a dose response to different concentrations of methacholine, a drug used to induce airway hyperreactivity, were obtained via the FlexiVent FX2 (SCIREQ Inc.)ResultsMale and female offspring of mice exposed to Nic(‐) and Nic(+) witnessed a significant decrease in overall lung function as compared to the FA group. Baseline compliance (Crs) was significantly decreased in the Nic(‐) female group and Nic(‐) and Nic(+) male groups (P < 0.05 via ANOVA). Female and male mice in the Nic(‐) had greater stiffness (Ers) than the corresponding FA group (P < 0.05). Upon addition of methacholine, female mice in the Nic(‐) and male mice in the Nic(+) had an increased amount of lung resistance (Rrs)upon inhalation (P < 0.05). Female mice in the Nic(‐) had decreased forced expiratory volume (FEV0.1) in comparison with the FA group (P < 0.05).ConclusionPreliminary data supports that in‐utero exposed mice to e‐cigarette vapor with or without nicotine causes long term alterations in lung function. Future directions aim to understand the mechanisms of change through observing changes in histology, altered gene expression, protein analysis, and epigenetic changes through DNA methylation. Results of this work demonstrate that vaping may not be a safe alternative to smoking during pregnancy as the health of the offspring have detrimental pulmonary effects in adulthood.
Dent Disease in Drosophila: An Unexpected Model to Study the Relationship Between a Cl‐ Transporter and Ca2+
Authors: Reynolds Carmen , Dow Julian , Romero Michael 
Published: May 2022

Mutations in the 2Cl‐/H+ transporter CLC‐5 cause Dent Disease Type 1 (DD1) and lead to progressive renal failure by age 20‐40. A major characteristic of DD1 is the renal mishandling of Ca2+that increases urinary Ca2+ excretion, calcium oxalate (CaOx) kidney stones, and kidney calcification. Interestingly, none of the DD1 symptoms include or relate to Cl‐ homeostasis despite impaired transport function. Thus, how does a Cl‐ transporter cause Ca2+ dysregulation?Our laboratory has identified Drosophila Clc‐c to be the homolog of CLC‐5 with conserved amino acids at DD1 mutation sites. We hypothesize that Clc‐c shares functional similarities in Cl‐transport and Ca2+ homeostasis. To test our hypothesis, we used electrophysiology to measure ion transport, and then assessed CaOx crystal formation in adult fly renal tubules (Malpighian tubules, MTs) of Drosophila.Voltage clamp experiments with Xenopus oocytes show that Clc‐c is electrogenic with the same outward‐rectifying current in Cl‐ solutions as observed with human CLC‐5. Next, knockdown flies (Clc‐c‐KD) were generated by crossing Uro‐Gal4 (MT driver) with UAS‐Clc‐c‐RNAi flies, resulting in 50% Clc‐c mRNA expression in the MTs. Crystals in adult MT (7 days after eclosure) were present in 100% of Clc‐c‐KD compared to 71% of control flies. The average number of crystals in adult tubule pairs was significantly greater in Clc‐c‐KD flies (15±4 crystals per pair) than control flies (5±2 crystals, P= 0.02). When fed a diet with 2mM NaOx ClcC‐KD for 4 days, Clc‐c‐KD flies had a significantly greater number of crystals in each tubule (24±5 crystals) than controls (4±2 crystals, P=0.005). However, the KD flies did not produce more crystals than control flies when fed a supraphysiological concentration of sodium oxalate (20 mM NaOx diet) for 1 or 4 days and in ex vivo assays of dissected MTs submerged in solution containing 10 mM NaOx for 1 hour.In conclusion, Drosophila Clc‐c has both identical sequences at DD1 mutation sites and similar biophysical functions to human CLC‐5. Furthermore, Clc‐c‐KD increases incidence of CaOx crystals which corresponds to the increased risks for kidney stones in DD1 patients. With this fly‐DD1 model, we will be able to assess the relationship of Clc‐c Cl‐ transport to renal Ca deposits. Future experiments will evaluate renal pathophysiology of DD1 mutations and their relationship to Ca2+ transport in Clc‐c transgenic flies.
Central hemodynamic response during submaximal and exhaustive exercise in humans with high affinity hemoglobin and compensatory polycythemia
Authors: Webb Kevin L. , Regimbal Riley J. , Morkeberg Olaf H. , Senefeld Jonathon W. , Baker Sarah E. , Joyner Michael J. , Wiggins Chad C. 
Published: May 2022

Humans with high affinity hemoglobin (HAH) develop compensatory polycythemia, an elevated hematocrit, which increases blood viscosity and may compromise cardiac output during exercise. In addition, humans with HAH have shown alterations in muscle blood flow during exercise in normoxia and hypoxia. As such, we aimed to investigate the influence of HAH and compensatory polycythemia on the central hemodynamic response during both normoxic and hypoxic exercise.METHODSSeven humans with HAH (4 females, 36 ± 13 years) and 11 healthy controls with normal oxygen binding affinity (4 females, 39 ± 10 years) performed cycling exercise at two intensities, 1) at a power output corresponding to 15% below normoxic gas exchange threshold (GET) for four minutes and 2) at a power output requiring 85% of normoxic maximal aerobic capacity until exhaustion. This protocol was performed during both normoxia and hypoxia (21% O2 and 15% O2, respectively). Hemodynamic measurements were taken after three minutes of cycling at 15% below normoxic GET, three minutes at 85% V̇O2max, and at exhaustion. Cardiac output (Q̇) was estimated using an open‐circuit acetylene wash‐in technique. Stroke volume (SV) was calculated by dividing Q̇ by heart rate (HR). Baseline characteristics were compared between groups with student’s two‐tailed unpaired t‐tests. Hemodynamics were analyzed using a two‐way repeated measures analysis of variance to examine the effects of group and exercise intensity.RESULTSAs expected, hematocrit was ~15% greater in the HAH group than the control group (HAH: 58 ± 7 % vsCTL: 43 ± 3 %, P<0.001). Both groups elicited an increase in Q̇ and HR as exercise intensity increased during both normoxia (P<0.001 for both) and hypoxia (P<0.001 and P=0.002, respectively). There was no significant difference in Q̇ between groups during normoxia (P=0.85) or hypoxia (P=0.69). In addition, neither HR nor SV were different between groups during exercise in normoxia (P=0.13 and P=0.39, respectively) or hypoxia (P=0.89 and P=0.73, respectively). There was no group by intensity interaction for Q̇, HR, or SV during normoxia (all, P>0.42) or hypoxia (all, P>0.63).CONCLUSIONOur data suggest that cardiac output is not compromised during normoxic or hypoxic exercise in humans with HAH and compensatory polycythemia. Therefore, compensatory polycythemia may improve exercise capacity in humans with HAH by raising oxygen carrying capacity without limiting cardiac output.
Profiling the Cytochrome P450 2J2 Active Site
Authors: Motl Nicole , Smith Richard D. , Carlson Heather A. , Scott Emily E. 
Published: May 2022

Human cytochrome P450 2J2 (CYP2J2) is a membrane bound, heme‐containing monooxygenase primary expressed in the heart. This enzyme oxidizes the double bonds in polyunsaturated fatty acids such as arachidonic acid and linoleic acid to epoxides, generating epoxyeicosatrienoic acids (EETs). Various EET products are implicated in cardioprotective effects, but also the promotion of cancer tumor growth and metastasis. Additionally, CYP2J2 can act on a range of pharmaceuticals. Thus, CYP2J2 is of clinical interest, but there is no structural information to understand how the CYP2J2 active site accommodates this wide variety of ligands.In this study, the CYP2J2 active site was defined by its ability to bind an array of >75 substrates, inhibitors, and xenobiotics, including a broad panel of azole compounds. The binding modes and affinities were determined by monitoring the shifts of the CYP2J2 heme Soret absorbance, which is indicative of heme environment perturbation. From these experiments the following spectral shift responses were observed: displacement of the heme‐coordinated water (type‐I binding mode), compound coordination to the heme iron (type‐II), a red‐shifted type‐I binding mode, compound coordination to heme coordinated water (reverse type‐I binding mode), or no spectral shift. As the latter result can be consistent with no binding or binding in the active site in a way that does not perturb the heme center, such compounds were investigated via a luminescence‐based inhibition assay to verify their interaction with CYP2J2. As imidazole‐containing ligands provide a fixed, known reference point for their interaction with the CYP2J2 heme iron, cheminformatics approaches were applied to these compounds to help provide insight into the chemical makeup of the CYP2J2 active site. The physical properties of these ligands were analyzed to identify key ligand features that drive CYP2J2 ligand preference. In the absence of protein structure information, this strategy provides a route to defining the CYP2J2 ligand binding site, potentially supporting the development of selective inhibitors that can help define the role of CYP2J2 modulation in vivo and potentially facilitate therapeutic strategies.
Roles of GABAergic and Glutamatergic Prebötzinger Complex Circuits in Opioid‐Induced Respiratory Depression
Authors: Schumacker Kayla S. , Scarpellini Carolina , Montandon Gaspard 
Published: May 2022

Introduction. Opioids are widely prescribed analgesic medication but are highly addictive and can be lethal with overdose. Respiratory depression is the primary cause of death by opioid overdose, and it limits the ability to use opioid analgesics safely and effectively. Respiratory depression by opioids is mediated by the inhibition of neural circuits in the brainstem, such as the preBötzinger Complex (preBötC), a small region of the medulla involved in respiratory rhythm generation. The generation of respiratory rhythm requires the activation of excitatory and inhibitory neurons in the preBötC. Glutamate is a main excitatory neurotransmitter, and preBötC glutamatergic neurons are involved in generating respiratory rhythm. γ‐aminobutyric acid (GABA) is a main inhibitory neurotransmitter, and GABAergic neurons are found in the preBötC. Interestingly, GABAergic neurons often co‐express µ‐opioid receptors, and disinhibition of GABAergic neurons by opioid drugs is involved in opioid addiction and euphoria. Here, we aim to determine the roles of excitatory glutamatergic and inhibitory GABAergic neurons in opioid‐induced respiratory depression.MethodsTo control glutamatergic and GABAergic neurons, we expressed opsin channels in cells expressing the vesicular glutamate transporter 2 (vGLUT2) and the vesicular GABA transporter (vGAT), respectively. Using a cre‐lox recombination approach, we injected into the preBötC cre‐dependent adeno‐associated viruses to locally express the inhibitory archaerhodopsin or the excitatory channelrhodopsin in vGLUT2 or vGAT‐expressing cells. Following a 4‐week incubation period, we applied 554 nm or 470 nm lights through optical fibres focused onto the preBötC while recording diaphragm and genioglossal muscle activities in anesthetized mice. Following systemic injection of fentanyl (5µg/kg), we inhibited or activated glutamatergic or GABAergic cells, respectively.ResultsOur preliminary data indicate that inhibition of vGLUT2 cells severely depressed respiratory rate, mimicking the respiratory depression observed with the opioid fentanyl. We are currently performing optical inhibition of vGAT preBötC cells in anesthetized mice and determining their role in respiratory depression by fentanyl.DiscussionWe will identify the role of GABAergic and glutamatergic preBötC cells in coordinating respiratory rhythm in preBötC cells and whether GABAergic cells contribute to respiratory depression by opioid drugs. Understanding the role of the populations of cells involved in respiratory depression by opioid drugs is critical to identify new molecular targets to reduce respiratory depression and provide safe and reliable pain killers without the risks associated with opioid pain killers.
3D Embryonic Heart Goes Mobile: Efficacy of Mobile Application in Congenital Cardiac Embryology Education
Authors: Gustilo Katherine S. , Stratford Jennifer , Hight Marissa , Lee Lisa M. 
Published: May 2022

Mastery of embryonic heart development is challenging but critical for medical professionals due to the frequency and variety of congenital cardiac defects that arise when the process goes awry. Unfortunately, teaching and learning cardiac embryology is difficult due to a lack of accurate and effective visual resources that depict this complex spatiotemporal event. To that end, an interactive mobile application named Embryonic Virtual Heart Application (EVHA) was developed as an accessible and interactive learner platform featuring a set of anatomically accurate 3D embryonic heart models with and without congenital cardiac defects (Figure 1). The project aims to assess whether the EVHA usage leads to measurable learning outcomes for first‐year medical students in the absence of a traditional lecture on cardiac embryology and congenital cardiac defects.In a COMIRB exempt study (#21‐4827), as a part of an optional pre‐work activity prior to the cardiac embryology class, 172 first‐year medical students were given access to a pre‐quiz (Q1) on cardiac embryology before interacting with the EVHA. After the EVHA usage, a post‐quiz (Q2) comprised of a set of matched, but different, questions than the Q1 was provided. During the class, students’ retention on this topic was assessed by a set of clinically oriented questions (Q3). Lastly, students completed an optional survey on their perceived value of the EVHA after the class. The learning outcomes from the EVHA usage were assessed by a one‐way ANOVA to compare Q1, Q2, and Q3 performances. To analyze the survey results, the frequency of each Likert scale score was averaged while thematic analysis was performed on the comments.The learning outcomes analysis revealed a significant increase in quiz performance between Q1 (22% ± 19%) and Q2 (65% ± 24%) with a 43% increase in the score (p<0.001; d=0.7; n=21). In‐class performance (Q3) average (61%; n=61) for all participants was not significantly different from Q2 (p>0.05), however those students who completed all optional prework (Q1, EVHA, Q2) had a significantly higher Q3 performance (79%; p <0.05; n=9). Survey analysis indicates that students perceive EVHA as an effective learning tool with its greatest strength being the interactive 3D virtual models of the congenital cardiac defects.Despite the limitations and confounds in this project, these results indicate that the EVHA may be an effective tool contributing to significant learning outcomes independent from a formal class and can further enhance learning in the classroom and on higher‐order assessments. The impact of this project is its contribution of an accessible, portable and visually‐oriented learning resource on cardiac embryology with clinical emphasis. Based on the learning outcomes data, the project also demonstrates the potential of educational mobile applications in medical curricula in which contact hours are limited.