bluuebunny/crossref_metadata_2025 huggingface dataset:
Modiolar Proximity of Slim Modiolar Electrodes and Cochlear Duct Length: Correlation for Potential Basis of Customized Cochlear Implantation With Perimodiolar Electrodes
Authors: Lee Sang-Yeon , Jung Bae Yun , Carandang Marge , Kim Yoonjoong , Hee Han Jin , Huh Gene , Song Jae-Jin , Koo Ja-Won , Ho Lee Jun , Ha Oh Seung , Choi Byung Yoon
Published: August 2020

Objectives:

Recent studies have shown that cochlear duct length (CDL) varies among individuals and could significantly influence the final position of the electrode and its trajectory in the cochlea. Given this, we hypothesized that the degree of modiolar proximity of novel slim modiolar electrodes, such as CI532 and CI632, can also be affected by CDL. To test this hypothesis, we retrospectively evaluated individual CDL to determine if there is any significant correlation of CDL with degree of modiolar proximity.

Methods:

Fifty-one ears from 38 subjects implanted with slim modiolar electrodes by a single surgeon through the round window approach using the pull-back technique were included. Our cohort was classified according to the deafness onset (congenital versus postlingual) and the degree of modiolar proximity (less versus tight) with reference to the spiral diameter made by the slim modiolar electrodes in situ on transorbital x ray. We then analyzed the CDL and its metrics using a readily available surgical preplanning tool (OTOPLAN) to obtain comparable data.

Results:

Among 30 ears associated with congenital deafness, 9 ears (30%) showed less modiolar proximity, while none of the 21 ears from 19 subjects with postlingual deafness exhibited “less modiolar proximity” based on our criteria. In this study, CDL showed significant variation among subjects. Importantly, a significant inverse correlation between spiral diameter and CDL (ρ = −0.581, p < 0.001) was found, showing that shorter CDLs have longer spiral diameter and less modiolar proximity. Moreover, further pull-back technique characterized by pulling out the electrode a little bit more in cases with shorter CDL, if not always, exhibited tighter modiolar proximity.

Conclusion:

A preponderance of less modiolar proximity of the electrode was observed exclusively among congenital deafness cases, demonstrated by a less tight spiral configuration even under the pull-back technique. Our data suggest that shorter CDL is associated with a less tight spiral configuration of slim modiolar electrodes postoperatively. Depending on the insertion technique, the differential degree of modiolar proximity of slim modiolar electrodes can be alleviated in cases with short CDL, which justifies cochlear duct length-based customized insertion of slim modiolar electrodes.
Musical Experience Offsets Age-Related Decline in Understanding Speech-in-Noise: Type of Training Does Not Matter, Working Memory Is the Key
Authors: Zhang Lei , Fu Xueying , Luo Dan , Xing Lidongsheng , Du Yi
Published: August 2020

Objectives:

Speech comprehension under “cocktail party” scenarios deteriorates with age even in the absence of measurable hearing loss. Musical training is suggested to counteract the age-related decline in speech-in-noise (SIN) perception, yet which aspect of musical plasticity contributes to this compensation remains unclear. This study aimed to investigate the effects of musical experience and aging on SIN perception ability. We hypothesized a key mediation role of auditory working memory in ameliorating deficient SIN perception in older adults by musical training.

Design:

Forty-eight older musicians, 29 older nonmusicians, 48 young musicians, and 24 young nonmusicians all with (near) normal peripheral hearing were recruited. The SIN task was recognizing nonsense speech sentences either perceptually colocated or separated with a noise masker (energetic masking) or a two-talker speech masker (informational masking). Auditory working memory was measured by auditory digit span. Path analysis was used to examine the direct and indirect effects of musical expertise and age on SIN perception performance.

Results:

Older musicians outperformed older nonmusicians in auditory working memory and all SIN conditions (noise separation, noise colocation, speech separation, speech colocation), but such musician advantages were absent in young adults. Path analysis showed that age and musical training had opposite effects on auditory working memory, which played a significant mediation role in SIN perception. In addition, the type of musical training did not differentiate SIN perception regardless of age.

Conclusions:

These results provide evidence that musical training offsets age-related speech perception deficit at adverse listening conditions by preserving auditory working memory. Our findings highlight auditory working memory in supporting speech perception amid competing noise in older adults, and underline musical training as a means of “cognitive reserve” against declines in speech comprehension and cognition in aging populations.
Cutaneous and systemic connections in lupus
Authors: Maz Mitra P. , Michelle Kahlenberg J.
Published: August 2020

Purpose of review

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with multiple manifestations, with a majority of SLE patients having cutaneous involvement. Despite ongoing research, the relationship between SLE and cutaneous lupus erythematosus (CLE) pathogeneses remains unknown. This review will compare advances in understanding the cause and pathogenesis of SLE and CLE.

Recent findings

Recently, mechanisms by which immune cell populations contribute to the pathogenesis of SLE and CLE have been queried. Studies have pointed to transitional B cells and B-cell activating factor (BAFF) signaling as potential drivers of SLE and CLE, with belimumab clinical data supporting these hypotheses. Ustekinumab trials and an exciting regulatory T cell (Treg) adoptive transfer in an SLE patient with cutaneous disease have suggested a role for T-cell-targeted therapies. The theory that neutrophil extracellular traps may be a source of autoantigens in SLE remains controversial, while neutrophils have been suggested as early drivers of cutaneous disease. Finally, plasmacytoid dendritic cells (pDCs) have been studied as a potential therapeutic target in SLE, and anti-blood DC antigen (anti-BDCA) antibody clinical trials have shown promise in treating cutaneous disease.

Although recent findings have contributed to understanding SLE and CLE pathogenesis, the mechanistic link between these diseases remains an area requiring further research.
Acetabular labral tears in the adolescent athlete: results of a graduated management protocol from therapy to arthroscopy
Authors: Murtha Andrew S. , Bomar James D. , Johnson Kristina P. , Upasani Vidyadhar V. , Pennock Andrew T.
Published: August 2020

This study sought to determine outcomes of a graduated management protocol from therapy to arthroscopy for adolescents presenting with hip pain and an associated acetabular tear. Thirty-seven hips with an MRI confirmed labral tear were prospectively enrolled in a graduated management protocol created for adolescents. The protocol began with activity modification and focused physical therapy. Patients with persistent symptoms were offered an intraarticular corticosteroid injection. Those with continued symptoms were treated with arthroscopic surgery. The modified Harris hip score (mHHS) and nonarthritic hip score (NAHS) were recorded at the initial visit. Patients were contacted by telephone at 1, 2, and 5 years from enrollment for repeat assessment with mHHS and NAHS. At presentation, the mean mHHS and NAHS for the entire cohort was 66.4  ±  11.4 and 70.2  ±  12.6, and these values improved significantly to 89.3  ±  10.6 and 87.0  ±  11.4 at a mean follow-up of 35.7  ±  18.3 months (range 11.7–64.4 months). Forty-two percent of hips were managed with physical therapy and activity modifications alone, 28% of hips progressed to a steroid injection but did not require surgery, and 31% required arthroscopic intervention. Seventy-three percent of hips treated with activity modification alone, 80% treated with an injection, and 82% of hips treated with arthroscopic repair met the minimal clinically significant difference (MCID) (P = 0.859). At an average of 36 months follow-up, the majority (78%) of adolescent patients with an acetabular labral tear will achieve the MCID utilizing a graduated management protocol.
Highly penetrating nanobubble polymer enhances LINC00511-siRNA delivery for improving the chemosensitivity of triple-negative breast cancer
Authors: Yuan Yanchi , Li Erjing , Zhao Jing , Wu Bolin , Na Ziyue , Cheng Wen , Jing Hui
Published: August 2020

Ultrasound-mediated nanobubble destruction (UMND), which can utilize the physical energy of ultrasound irradiation to improve the transfer efficiency to target cells is becoming one of the most promising carriers for gene delivery. The purpose of this study was to establish cell-penetrating peptide (CPP)-loaded nanobubbles (CNBs) connected with long intergenic nonprotein coding RNA 00511-small interfering RNA (LINC00511-siRNA) and evaluate its feasibility for improving the chemosensitivity of triple-negative breast cancer in vitro. First, fluorescence imaging confirmed the loading of siLINC00511 on CNBs, and the CNBs-siLINC00511 were characterized by the Zetasizer Nano ZS90 analyzer and transmission electron microscopy. Next, cell counting kit 8 assay was used to detect the inhibitory activity of cisplatin on the proliferation of MDA-MB-231 cells, and the 50% inhibition concentration value before and after transfer was calculated. Finally, the silencing effect of siLINC00511 was evaluated in vitro using an apoptosis assay, transwell assay, real time-PCR and western blotting. UMND combined with CNBs could effectively transfer the siRNA to MDA-MB-231 cells, thus evidently reducing the expression of LINC00511. Furthermore, inhibitory activity of cisplatin on MDA-MB-231 cells was enhanced after downregulation of LINC00511 expression. Downregulation of LINC00511 alters expression of cell cycle-related (CDK 6) and apoptosis-related (Bcl-2 and Bax) proteins in MDA-MB-231 cells. These results suggested that siRNA-CNBs may be an ideal vector for the treatment of tumors, with high efficiency RNA interference under the combined action of UMND. It may provide a new therapeutic method for triple negative breast cancer.
Does Standard Physical Therapy Increase Quadriceps Strength in Chronically Ventilated Patients? A Pilot Study*
Authors: Supinski Gerald S. , Valentine Emily N. , Netzel Paul F. , Schroder Elizabeth A. , Wang Lin , Callahan Leigh Ann
Published: August 2020

Objectives:

Physical therapy is standard care for mechanically ventilated patients, but there is no evidence, using nonvolitional, objective measurements, that physical therapy increases muscle strength in this population. The present study tested the hypothesis that 2 weeks of standard, conventional physical therapy provided at a ventilator weaning facility would increase quadriceps strength in mechanically ventilated patients.

Design:

Prospective observational study.

Setting:

Ventilator weaning unit.

Patients:

Patients who were transferred from an acute care hospital because of failure to wean from mechanical ventilation and who were receiving physical therapy as prescribed by facility staff.

Interventions:

None.

Measurements and Main Results:

We employed a novel, nonvolitional objective technique, quadriceps twitch force generation in response to femoral nerve magnetic stimulation, to assess leg strength before and after 2 weeks of conventional physical therapy. The duration and specific exercises provided to patients were also recorded. In a subset of patients, we measured muscle activation intensity using wireless electromyogram recordings. Indices of respiratory function (maximum inspiratory pressure generation and the rapid shallow breathing index) were also assessed. Patients’ responses to 2 weeks of physical therapy were poor; on average, quadriceps twitch fell by –1.02 ± 0.71 Newtons. Neither physical therapy duration nor specific forms of exercise were identified to positively impact quadriceps twitch. Electromyogram recordings indicated that during training, muscle activation was poor. Consequently, therapists spent substantial time performing exercises that elicited little muscle activation. Physical therapy did not improve respiratory function.

Conclusions:

Standard physical therapy delivered in a ventilator weaning facility failed to improve quadriceps leg strength in a majority of mechanically ventilated patients. The fact that mechanically ventilated patients fail to achieve high levels of muscle activation during physical therapy provides a potential explanation as to why physical therapy may often be ineffective. We speculate that use of novel methods which increase muscle activation during exercise may improve responses of mechanically ventilated patients to physical therapy.
Long noncoding RNA XIST knockdown suppresses the growth of colorectal cancer cells via regulating microRNA-338-3p/PAX5 axis
Authors: Li Wei , He Yingchun , Cheng Zhaoling
Published: August 2020

Background

Colorectal cancer is one of the most common human cancers worldwide. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been reported as the regulators in cancers. The purpose of this study was to reveal the functional mechanisms of lncRNA x inactive specific transcript (XIST) and miR-338-3p in colorectal cancer cells.

Methods

The transcription level and protein level of genes were assessed by quantitative real-time PCR (qRT-PCR) and western blot assay, respectively. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry analysis were used to determine cell proliferation ability and apoptosis rate, respectively. In addition, cell migratory ability and invasive ability were measured using transwell assay. Besides, the interaction between miR-338-3p and XIST or paired box 5 (PAX5) was predicted by starBase or TargetScan and then verified by the dual-luciferase reporter assay.

Results

XIST and PAX5 expression were increased, and miR-338-3p expression was decreased in colorectal cancer tissues and cells. XIST knockdown significantly repressed cell proliferation, migration and invasion, and accelerated apoptosis in colorectal cancer cells. Interestingly, XIST directly downregulated miR-338-3p expression to increase PAX5 level. As expected, XIST knockdown inhibited colorectal cancer cell growth by modulating miR-338-3p expression. Furthermore, miR-338-3p suppressed cell growth via downregulation of PAX5 level in colorectal cancer cells.

Conclusion

Our results demonstrated that the downregulation of XIST inhibited cell proliferation, migration and invasion, and induced apoptosis through modulating miR-338-3p/PAX5 axis in colorectal cancer cells, providing potential target for the prevention and treatment of colorectal cancer.
Time of dissociation between microcirculation, macrocirculation, and lactate levels in a rabbit model of early endotoxemic shock
Authors: Zhang Hong , Li Lei , Wu Jun , Qu Hong-Ping , Tang Yao-Qing , Chen De-Chang
Published: August 2020

Background

The relationship between macrocirculation and microcirculation remains controversial. The loss of coherence between microcirculation and macrocirculation has already been found in late-stage sepsis shock. The objective of this study was to determine the earliest possible time of detecting the loss of coherence between microcirculation and macrocirculation in early-stage endotoxemic shock.

Methods

We randomized 24 female New Zealand white rabbits into two groups: endotoxemic shock group (n = 14) and control group (n = 10). Rabbits in the endotoxemic shock group were equipped with arterial and venous catheters and received an intravenous infusion of Escherichia coli lipopolysaccharide (LPS, 2 mg/kg over 10 min). Rabbits in the control group received the same dose of saline infusion. Microcirculatory perfusion parameters were assessed in the sublingual mucosa using sidestream dark-field video microscopy. Systemic hemodynamics and blood lactate levels were measured at baseline and over a 120-min period.

Results

Ninety minutes after completing LPS infusion, all animals in the endotoxemic shock group developed a hypodynamic septic condition, characterized by low cardiac output and increased systemic vascular resistance; 120 min after completing LPS infusion, the mean arterial pressure decreased by 25% (P = 0.01), confirming ongoing endotoxemic shock. However, significant decreases in sublingual microcirculatory parameters of small vessels (microvascular flow index, perfused vessel density, and proportion of small perfused vessels) were observed 30 min after completing LPS infusion (P = 0.01, for all), and threshold decreases of 30% were found 60 min after completing LPS infusion (P = 0.001, for all) in the endotoxemic shock group. Lactate levels significantly increased to more than 2 mm/L at 90 min and more than 4 mm/L at 120 min in the endotoxemic shock group (P = 0.02 and P = 0.01, respectively).

Conclusions

Changes in microcirculatory perfusion precede changes in macrocirculation and lactate levels in a rabbit model of endotoxemia shock. Microcirculation, macrocirculation, and oxygen metabolism are distinct in early-stage endotoxic shock.
Prognostic significance of the hemoglobin A1c level in non-diabetic patients undergoing percutaneous coronary intervention: a meta-analysis
Authors: Li Yan , Li Xiao-Wen , Zhang Yin-Hua , Zhang Lei-Min , Wu Qing-Qing , Bai Zhao-Run , Si Jin , Zuo Xue-Bing , Shi Ning , Li Jing , Chu Xi
Published: August 2020

Background

The predictive value of hemoglobin A1c (HbA1c) levels in non-diabetic patients with myocardial infarction undergoing percutaneous coronary intervention (PCI) is still controversial. This study aimed to evaluate whether HbA1c levels were independently associated with adverse clinical outcomes in non-diabetic patients with coronary artery disease (CAD) who had undergone PCI by performing a meta-analysis of cohort studies.

Methods

This meta-analysis included non-diabetic patients with CAD who had undergone PCI. A systematic search for publications listed in the PubMed, Embase, and Cochrane Library databases from commencement to December 2018 was conducted. Studies evaluating the adverse clinical outcomes according to abnormal HbA1c levels in non-diabetic patients diagnosed with CAD who had undergone PCI were eligible. The primary outcomes were long-term all-cause deaths and long-term major adverse cardiac events, and the secondary outcome was short-term all-cause deaths. The meta-analysis was conducted with RevMan 5.3 and Stata software 14.0. Odds ratios (ORs) were pooled using a random or fixed-effects model, depending on the heterogeneity of the included studies. Sub-group analysis or sensitivity analysis was conducted to explore potential sources of heterogeneity, when necessary.

Results

Six prospective cohort studies involving 10,721 patients met the inclusion criteria. From the pooled analysis, abnormal HbA1c levels were associated with increased risk for long-term all-cause death (OR 1.39, 95% confidence interval [CI] 1.16–1.68, P = 0.001, I
2 = 45%). Sub-group analysis suggested that abnormal HbA1c levels between 6.0% and 6.5% predicted higher long-term major adverse cardiac event (including all-cause deaths, non-fatal myocardial infarction, target lesion revascularization, target vessel revascularization, recurrent acute myocardial infarction, heart failure requiring hospitalization, and stent thrombosis) risk (OR 2.05, 95% CI 1.46–2.87, P < 0.001, I
2 = 0). Contrarily, elevated HbA1c levels were not associated with increased risk of short-term all-cause death (OR 1.16, 95% CI 0.88–1.54, P = 0.300, I
2 = 0).

Conclusions

An abnormal HbA1c level is an independent risk factor for long-term adverse clinical events in non-diabetic patients with CAD after PCI. Strict control of HbA1c levels may improve patient survival. Further studies in different countries and prospective cohort studies with a large sample size are required to verify the association.
Association of interleukin-18 gene polymorphisms with Takayasu arteritis in a Chinese Han population
Authors: Wen Dan , Zhou Xian-Liang , Du Xin , Dong Jian-Zeng , Ma Chang-Sheng
Published: August 2020

Background:

Interleukin-18 (IL18) gene polymorphisms are related to many inflammatory and autoimmune diseases. However, a correlation analysis between IL18 −607C/A and −137G/C gene polymorphisms and Takayasu arteritis (TA) is lacking.

Methods:

This study enrolled 200 patients with TA as the case group and 334 region-, age-, and sex-matched healthy subjects as the control group. We genotyped alleles and genotypes at positions −607 and −137 of the IL18 gene and analyzed the distribution frequencies. Mann-Whitney U test, t test, Chi-squared test and Hardy-Weinberg equilibrium were performed.

Results:

After adjusting for risk factors, the adjusted odds ratios and 95% confidence intervals at position −607C/A were 0.533, 0.391 to 0.880 (P = 0.010); 0.266, 0.586 to 1.002 (P = 0.051); and 0.122, 0.552 to 1.420 (P = 0.613) under the dominant, additive, and recessive models, respectively. For the −137G/C polymorphism, the adjusted odds ratios and 95% confidence intervals were 1.571, 1.068 to 2.311 (P = 0.022); 1.467, 1.086 to 1.980 (P = 0.012); and 1.815, 0.901 to 3.656 (P = 0.095) under the dominant, additive, and recessive models, respectively. Moreover, regardless of the model used, we found no statistical difference in distribution frequency between the active and quiescent states of TA for the −607C/A (P = 0.355, 0.631, and 0.705, respectively) and −137G/C polymorphisms (P = 0.205, 0.385, and 0.208, respectively).

Conclusions:

The IL18 −607C/A gene polymorphism may decrease the risk of TA, and thus is a protective factor, whereas −137G/C may increase the risk of TA, and thus is a risk factor. However, neither polymorphism was related to activity (active vs. quiescent) of TA.
Therapeutic Options for the Treatment of Coronavirus Disease (COVID-19)
Authors: Snawerdt Jessica , Finoli Lauren , Bremmer Derek N. , Cheema Tariq , Bhanot Nitin
Published: August 2020

Coronavirus disease 2019 (COVID-19) has resulted in an unprecedented pandemic, challenging practitioners to identify safe and effective therapeutic options in a limited amount of time. The rapid genomic sequencing of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provided a significant number of therapeutic targets. Repurposed and investigational agents are being studied for use in COVID-19. Although knowledge is rapidly expanding in regard to COVID-19 and there is promise with a few agents, there are no definitely proven effective therapies at this time. Supportive care remains the mainstay of therapy while ongoing clinical trials are being conducted.
Supportive Management and Interventions for Respiratory Failure Due to SARS-CoV-2
Authors: Baltaji Stephanie , Ledgerwood Chelsea , Finoli Lauren , Lyons Caitlin , Cheema Tariq
Published: August 2020

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection can vary from asymptomatic to severe symptoms. It can lead to respiratory failure and acute respiratory distress syndrome requiring intubation and mechanical ventilation. Triaging patients is key to prevent spread, conserving medical resources, and providing appropriate care. The treatment of these patients remains supportive. Respiratory failure due to the virus should be managed by providing supplemental oxygen and early intubation. Some patients develop acute respiratory distress syndrome and refractory hypoxemia. In this article, we review the 2 phenotypes of respiratory failure, mechanical ventilation and the management of refractory hypoxemia.
Systemic Complications of COVID-19
Authors: Ashraf Obaid , Young Meilin , Malik Khalid J. , Cheema Tariq
Published: August 2020

Coronavirus disease-2019 (COVID-19) creates severe respiratory distress and often a cascade of other systemic complications impacting several organ systems. The immune response includes a cytokine storm that creates many life-threatening problems including coagulopathies, arrhythmias, and secondary infections. This article discusses the multisystem responses to the physical insults created by this corona virus.
Health Care Workers' Challenges in the Care of a COVID-19 Patient
Authors: Gordon Ayla , Lyons Caitlin , Rao Sheldon , Finoli Lauren
Published: August 2020

The COVID-19 pandemic has introduced us to new challenges with personal protective equipment, long shifts, and changes in regular routines. This has placed a tremendous stress on health care workers. This article defines the various health care worker challenges, both at the bedside and on a personal front. Therapeutic strategies are discussed.
Silencing of Long Noncoding RNA Zinc Finger Antisense 1 Protects Against Hypoxia/Reoxygenation-induced Injury in HL-1 Cells Through Targeting the miR-761/Cell Death Inducing p53 Target 1 Axis
Authors: Xiang Xiaojun , Zheng Lei , Li Xuewen
Published: August 2020

Acute myocardial infarction (AMI) is a major cause of morbidity and mortality worldwide. Long noncoding RNAs have demonstrated to be associated with AMI pathogenesis. In this study, we aimed to investigate the function and mechanism of zinc finger antisense 1 (ZFAS1) on hypoxia/reoxygenation (H/R)-induced injury in HL-1 cells. The levels of ZFAS1, miR-761, and cell death–inducing p53 target 1 (CDIP1) in the serum of AMI patients and HL-1 cells were detected by quantitative real-time polymerase chain reaction or western blot. Cell viability and apoptosis were assessed by the Cell Counting Kit-8 assay and flow cytometry, respectively. Lactate dehydrogenase release, malondialdehyde content, superoxide dismutase expression, and glutathione peroxidase were evaluated using commercially corresponding assay kits. Targeted interactions among ZFAS1, miR-761, and CDIP1 were validated by dual-luciferase reporter and RNA immunoprecipitation assays. Our data indicated that ZFAS1 was upregulated and miR-761 was downregulated in the serum of patients with AMI and H/R-induced HL-1 cells. ZFAS1 silencing or miR-761 overexpression alleviated H/R-induced injury in HL-1 cells. Moreover, ZFAS1 acted as a sponge to sequester miR-761, and CDIP1 was directly targeted and inhibited by miR-761. ZFAS1 knockdown protected HL-1 cell from H/R-induced injury through miR-761, and CDIP1 mediated the alleviated effect of miR-761 overexpression on H/R-induced HL-1 cell injury. Furthermore, ZFAS1 regulated CDIP1 expression through acting as a miR-761 sponge. In addition, CDIP1 silencing protected HL-1 cell from H/R-induced injury. Our current work suggested that the knockdown of ZFAS1 protected against H/R-induced injury in HL-1 cells at least partly through the regulation of miR-761/CDIP1 axis, illuminating a novel therapeutic avenue for AMI management.
Resveratrol Stimulates the Na+–Ca2+ Exchanger on the Plasma Membrane to Reduce Cytosolic Ca2+ in Rat Aortic Smooth Muscle Cells
Authors: Yan Fuman , Lu Jun , Zhang Yunting , Li Xiao , Chan Wai-Ho , Zhao Qiannan , Kwan Hiu-Yee , Liu Haimei , Yao Xiaoqiang
Published: August 2020

Resveratrol is well known to exhibit vascular relaxant and antihypertensive effects. In this study, we determined the effects of resveratrol on the modulation of cytosolic [Ca2+] level and adenosine 5′-triphosphate–induced Ca2+ release from the sarcoplasmic reticulum (SR) in rat aortic smooth muscle cells (ASMCs) and explored its underlying mechanisms. In this article, cytosolic [Ca2+] and SR [Ca2+] in ASMCs were determined by Fluo-4/acetoxymethyl and Mag-Fluo-4/acetoxymethyl respectively. Resveratrol (20, 50, and 100 µM) caused a rapid and substantial reduction in cytosolic [Ca2+] in ASMCs bathed in normal Hank's Balanced Salt Solution or Ca2+-free Hank's Balanced Salt Solution. Pretreatment with resveratrol reduced adenosine 5′-triphosphate–induced SR Ca2+ release and SR Ca2+ content. In the cells bathed in Na+-free physiological saline, which favors the reverse mode of the Na+–Ca2+ exchanger (NCX), resveratrol induced an increase in cytosolic [Ca2+] and SR [Ca2+]. However, its effect on cytosolic [Ca2+] was inhibited by the selective NCX inhibitor, SEA0400. Our findings suggest that resveratrol reduces cytosolic [Ca2+] and SR [Ca2+] in ASMCs in normal physiological saline, which might be, at least in part, mediated by the NCX.
Myocardial Infarction–associated Transcript Knockdown Inhibits Cell Proliferation, Migration, and Invasion Through miR-490-3p/Intercellular Adhesion Molecule 1 Axis in Oxidized Low-density Lipoprotein-induced Vascular Smooth Muscle Cells
Authors: Ma Haifeng , Zheng Lingling , Qin Hao , Wang Wenwen
Published: August 2020

Emerging evidence has demonstrated that long noncoding RNAs are related to the pathogenesis of atherosclerosis. We aimed to investigate the roles and molecular mechanisms of myocardial infarction–associated transcript (MIAT) in the proliferation, migration, and invasion of oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs). Quantitative real-time polymerase chain reaction was conducted to determine the levels of MIAT, microRNA490-3p (miR-490-3p), and intercellular adhesion molecule 1 (ICAM1). Cell Counting Kit-8 assay was performed to assess cell proliferation. Transwell assay was used to evaluate cell migration and invasion. Western blot assay was performed to measure the protein levels of proliferating cell nuclear antigen, N-cadherin, matrix metalloprotein-9, and ICAM1. Dual-luciferase reporter, RNA immunoprecipitation, and RNA pull-down assays were conducted to verify the relationship between miR-490-3p and MIAT or ICAM1. MIAT was elevated in atherosclerosis patients' serum and ox-LDL–induced VSMCs. MIAT knockdown suppressed cell proliferation, migration, and invasion in ox-LDL–stimulated VSMCs. MIAT acted as a sponge of miR-490-3p, and miR-490-3p deficiency overturned the inhibition of MIAT knockdown on VSMC proliferation, migration, and invasion. ICAM1 was a direct target of miR-490-3p, and ICAM1 silencing repressed the proliferation, migration, and invasion of ox-LDL–stimulated VSMCs. Moreover, ICAM1 overexpression reversed the impacts of MIAT knockdown on ox-LDL–induced VSMC proliferation, migration, and invasion. MIAT knockdown could depress cell proliferation, migration, and invasion through miR-490-3p/ICAM1 axis in ox-LDL–induced VSMCs.
Chemokine (C-C motif) Ligand 6 Aggravates Hypoxia Reoxygenation–induced Apoptosis in H9c2 Cells Through Enhancing the Expression of Insulin-like Growth Factor 2-Antisense
Authors: Li Xiufen , Aishan Bilali , Yang Yan , Xie Yang , Lati Dilimu , Tuerxun Paerhati
Published: August 2020

Chemokine (C-C motif) ligand 6 (CCL6), one of the small cytokines in the CC chemokine family, has been reported to involve in renal ischemia–reperfusion (I/R) injury. However, the role of CCL-6 in myocardial I/R injury is nonelucidated. In this study, we used in vitro H9c2 cell model to investigate the overall contributions of CCL6 to myocardial I/R injury. We found the elevated level of CCL6 from the reanalysis of data set GSE-4105 and in hypoxia–reoxygenation (H/R)-injured H9c2 cells. CCL6 silencing attenuated the cardiomyocyte apoptosis induced by H/R injury, whereas exogenous CCL6 treatment aggravated the apoptosis of H/R-injured H9c2 cells. During CCL6 administration, the expression of numerous long noncoding RNAs was differentially regulated. Quantitative RT-Polymerase chain reaction assay demonstrated that insulin-like growth factor 2 (IGF2)-Antisense (AS) had the highest induction by CCL6 addition. IGF2-AS silencing alleviated the apoptosis of H/R-injured H9c2 cells. Collectively, we have identified a potential mechanism by which high expression of CCL6 contributes to the H/R-induced apoptosis in H9c2 cells through enhancing the expression of IGF2-AS. These findings also give evidence of the feasibility of CCL6 or long noncoding RNA IGF2-AS as a potential target for modulation or therapeutic intervention in myocardial I/R injury.
Graft Edge Reflection of a Tightly Scrolled Roll Using Endoillumination as a Simple Method for Determining Graft Orientation in Descemet Membrane Endothelial Keratoplasty
Authors: Kobayashi Akira , Yokogawa Hideaki , Mori Natsuko , Nishino Tsubasa , Sugiyama Kazuhisa
Published: August 2020

Purpose:

To describe a simple finding that can be used to determine donor tissue orientation in Descemet membrane endothelial keratoplasty (DMEK). This involves the appearance of a highly reflective round curved line from an overlapping graft edge within the anterior chamber using light from an endoilluminator. We here name this Kobayashi sign (K-sign).

Methods:

Twelve consecutive eyes from 12 patients who underwent DMEK were evaluated for the presence of a K-sign. The presence of Berrospi sign (B-sign), a double-line reflection from the peripheral curls of the Descemet membrane (DM) roll that has been reported to be useful for correct graft orientation, was also evaluated.

Results:

Of 12 cases, 3 donors showed a loosely scrolled roll soon after DM donor insertion; all 3 of these showed a positive B-sign only when the endoilluminator was used. Nine donors showed a tightly scrolled DM roll without a B-sign; among these 9 donors, a K-sign was visible in 7 cases only when the endoilluminator was used. The remaining 2 cases with a tight scroll configuration showed no K-sign even with the use of endoillumination, indicating that the roll edge was located completely downward; rotation of the roll using a small jet of fluid from paracentesis revealed K-sign in these cases.

Conclusions:

This technique is useful for determining the correct orientation of a tightly scrolled DM roll, subsequently enabling rapid DMEK surgery. For loosely scrolled DM roll, endoillumination enhanced B-sing is proven useful.
Gonioscopy-assisted Transluminal Trabeculotomy in Uveitic Glaucoma Secondary to Juvenile Idiopathic Arthritis
Authors: Sachdev Amun , Khalili Ashkan , Choi Jessy , Stead Richard E. , Sung Velota C.T.
Published: August 2020

Gonioscopy-assisted transluminal trabeculotomy (GATT) is a minimally invasive ab interno procedure, performed with guidance of an illuminating microcatheter device (iTrack). The pathophysiology of raised intraocular pressure (IOP) in uveitic glaucoma is commonly due to increased resistance at the trabecular meshwork-Schlemm canal. By removing this resistance, GATT can potentially control the IOP. In addition, the ab interno approach avoids violating the conjunctiva and reduces the risk of complications including infection, leak, and hypotony. In this series, we discuss 3 uveitic glaucoma cases secondary to juvenile idiopathic arthritis (JIA) that underwent GATT. Case 1 was a 16-year-old phakic female with a preoperative IOP of 25 to 33 mm Hg had 360-degree GATT; her IOP remained stable at 6 to 10 mm Hg over 14 months. Case 2 was a 23-year-old pseudophakic female with a preoperative IOP of 28 to 34 mm Hg had 180-degree GATT; her IOP reduced to 8 mm Hg over 10 months. Case 3 was an 8-year-old aphakic male with a preoperative IOP of 21 to 32 mm Hg had 360-degree GATT; his IOP remained stable at 13 to 15 mm Hg over 21 months. In our limited case series, GATT is very successful in controlling IOP in young uveitic patients with JIA by surgically targeting the underlying pathophysiology.
Direct Brow Lift and Skin Contraction in Facial Nerve Palsy: A Switch Technique
Authors: Nagendran Sonali T. , Butler Daniel , Malhotra Raman
Published: August 2020

The authors present a case series of 4 patients with facial nerve palsy who underwent a direct brow lift to correct brow ptosis, using the excised brow skin as a full-thickness skin graft to correct lower eyelid skin contracture, ectropion, and retraction. Functional outcomes were measured using the validated cornea, static asymmetry, dynamic function, synkinesis (CADS) grading system and by photographic assessment of lower eyelid height via margin reflex distance. Aesthetic outcomes were measured using a published grading scale specific to eyelid skin grafts.
Prevalence and predictors of burnout symptoms in multidisciplinary pain clinics: a mixed-methods study
Authors: Ashton-James Claire E. , McNeilage Amy G. , Avery Nicholas S. , Robson Luci H.E. , Costa Daniel
Published: August 2020

Frequent exposure to patient distress is associated with a higher prevalence of clinician distress and burnout. Patients with chronic pain often present with high levels of emotional distress. The current study examined the prevalence of burnout symptoms among a multidisciplinary sample of pain clinicians in Australia, the relationship between clinician confidence managing emotions and symptoms of burnout, and clinicians' perspectives on sources of stress and wellbeing at work. One hundred seventy-six clinicians from 58 multidisciplinary pain clinics across Australia completed a survey including the 22-item Maslach Burnout Inventory, a measure of clinician confidence managing patient emotions and their own emotions, and open-ended questions probing clinician perspectives on sources of stress and wellbeing at work. High levels of emotional exhaustion and depersonalisation were reported by 21.6% and 14.2% of respondents, respectively. These burnout symptoms were predicted by clinician confidence managing their own emotions. Low levels of personal accomplishment were reported by 18.8% of respondents and were predicted by clinician confidence managing patients' emotions. Consistent with these quantitative findings, qualitative data revealed that emotionally challenging patient encounters were common sources of stress. Working with a multidisciplinary team and supportive relationships with colleagues were commonly reported sources of clinician wellbeing. The results of this study are discussed in light of previous reports of burnout in pain medicine physicians. Implications for clinician training in pain management and the prevention of burnout in pain clinicians are discussed.
Novel bifunctional hybrid compounds designed to enhance the effects of opioids and antagonize the pronociceptive effects of nonopioid peptides as potent analgesics in a rat model of neuropathic pain
Authors: Piotrowska Anna , Starnowska-Sokół Joanna , Makuch Wioletta , Mika Joanna , Witkowska Ewa , Tymecka Dagmara , Ignaczak Angelika , Wilenska Beata , Misicka Aleksandra , Przewłocka Barbara
Published: August 2020

The purpose of our work was to determine the role of nonopioid peptides derived from opioid prohormones in sensory hypersensitivity characteristics of neuropathic pain and to propose a pharmacological approach to restore the balance of these endogenous opioid systems. Nonopioid peptides may have a pronociceptive effect and therefore contribute to less effective opioid analgesia in neuropathic pain. In our study, we used unilateral chronic constriction injury (CCI) of the sciatic nerve as a neuropathic pain model in rats. We demonstrated the pronociceptive effects of proopiomelanocortin- and proenkephalin-derived nonopioid peptides assessed by von Frey and cold plate tests, 7 to 14 days after injury. The concentration of proenkephalin-derived pronociceptive peptides was increased more robustly than that of Met-enkephalin in the ipsilateral lumbar spinal cord of CCI-exposed rats, as shown by mass spectrometry, and the pronociceptive effect of one of these peptides was blocked by an antagonist of the melanocortin 4 (MC4) receptor. The above results confirm our hypothesis regarding the possibility of creating an analgesic drug for neuropathic pain based on enhancing opioid activity and blocking the pronociceptive effect of nonopioid peptides. We designed and synthesized bifunctional hybrids composed of opioid (OP) receptor agonist and MC4 receptor antagonist (OP-linker-MC4). Moreover, we demonstrated that they have potent and long-lasting antinociceptive effects after a single administration and a delayed development of tolerance compared with morphine after repeated intrathecal administration to rats subjected to CCI. We conclude that the bifunctional hybrids OP-linker-MC4 we propose are important prototypes of drugs for use in neuropathic pain.
Using the Six Sigma Methodology to Reduce Missed Appointments at a Pediatric Inner-City Clinic
Authors: Knight John , Hammett Pat
Published: August 2020

Pediatric missed appointments impact patient outcomes and the financial well-being of clinics. Our purpose was to implement the Six Sigma methodology at a pediatric clinic to (1) identify significant predictor factors of missed appointments and develop a prediction model and (2) implement interventions to reduce the missed appointment rate. Binary logistic regression identified historical no-show rate, high-risk visit types, lack of insurance, the number of provider visits, and appointment lead time as significant predictor factors. Interventions led to a significant drop in the missed appointment rate and the no-show rate.
Safety of a Nurse-Driven Mobility Protocol in a Surgical Trauma Intensive Care Unit
Authors: Black Katelyn , Smith Stephanie , Frotan Mohammad , Vandertulip Kaeli , Miller Amy
Published: August 2020

Background:

Traumatically injured patients are often admitted with complex multisystem injuries requiring a lengthy stay in the intensive care unit (ICU). Mobilizing patients in the ICU has been shown to reduce the adverse effects of immobility and can reduce the patient's length of stay in the hospital. However, little information is available about the safety of mobilizing traumatically injured patients.

Local Problem:

This quality improvement project was designed to determine whether a nurse-driven mobility protocol could lead to more frequent mobilization of traumatically injured patients. We also sought to determine patient outcomes, measured by the length of stay, adverse effects, and days on mechanical ventilation.

Methods:

A multidisciplinary group developed a nurse-driven early mobility protocol. Nurses were trained on mobilization practices for injured patients; they then mobilized eligible patients on their unit for the subsequent 6 months.

Results:

Nurses mobilized close to 80% of eligible patients in the surgical trauma ICU (STICU) during the implementation period, which was an 87.14% increase in patient mobilization from the preimplementation period. No mobility-associated adverse effects were observed for the patients who were mobilized in the STICU. No significant change in length of stay or ventilator-days occurred.

Conclusion:

Interdisciplinary planning led by physical therapists can ensure that a nurse-driven mobility protocol is a safe and effective method to mobilize patients earlier and more frequently. Future studies should consider a broader range of traumatically injured patients and the long-term effects of mobilization in the STICU.
Acute Care Physical and Occupational Therapy Early Intervention Pathway After Transcatheter Aortic Valve Replacement: A Retrospective Study
Authors: Myszenski Adele , Michon Barbara , Lupcke Danielle , Melican Cynthia , Pedawi Narmean , Ahmed Nazir , Fredal Wyman Janet
Published: August 2020

Purpose:

Transcatheter aortic valve replacement (tAVR) has emerged as a less-invasive alternative to traditional surgical aortic valve replacement. The purpose of this study was to examine the effect of a novel clinical pathway with an emphasis on early physical therapy and occupational therapy on patients undergoing tAVR in the acute care setting.

Methods:

A retrospective study was conducted involving 189 patients who underwent tAVR. The control group (n = 74) included patients who underwent tAVR prior to the implementation of the pathway. The intervention group (n = 115) included patients who underwent tAVR following the implementation of the pathway. Inpatient length of stay and discharge disposition were measured.

Results:

No differences in demographics or clinical variables were found; for example, mean age was 79.5 ± 11.2 years, with 57% male in the control group versus 81.6 ± 8.4 years and 59% male in the intervention group. Length of stay was significantly lower in the intervention group (control 6.9 ± 5.4 days, intervention 4.8 ± 5.4 days, P = .009) and significantly shorter length of stay postprocedure (control 4.8 ± 2.9 days, intervention 3.5 ± 4.0, P = .015). The incidence of the patient's discharge disposition to home increased from 77% of patients in the control group to 86% of patients in the intervention group but was not statistically significant (P = .118).

Conclusions:

A clinical pathway specific to patients post-tAVR provided early mobility, targeted education, individualized functional goals, and discharge disposition recommendations. Patients in the intervention group experienced reduced hospital length of stay.
Physical Therapy Screening of Occult Cancer Presenting as Hip Pain in Acute Care Setting
Authors: Thompson Stephen R. , Krause David A. , Cloud-Biebl Beth A.
Published: August 2020

Background and Purpose:

Physical therapists (PTs) in the acute care setting evaluate patients to determine discharge plans and perform mobility-based safety evaluations. When presented with a common problem different from the referral diagnosis, in this case, hip pain, the PT must use knowledge of palpation, range of motion, special tests, and outcome tools to evaluate the patient and identify possible sources of their pain. This case report aims to describe a patient's atypical presentation of hip pain that was ultimately diagnosed as metastatic bone disease. This report includes the description of differential diagnoses based on the patient examination, details of the subsequent events leading to her final diagnosis, and discussion of the importance of screening patients beyond their diagnosis in the acute care setting.

Case Description:

A 69-year-old woman was referred to physical therapy in the hospital following aortic surgery. During the initial evaluation, she described 10/10 hip pain that had gone undocumented thus far. Examination revealed pain with passive and active motion in all directions, increased pain with weight-bearing, and impaired mobility. Current evidence for the evaluation of hip pain was used to examine differential diagnoses aligned with the patient's symptoms. Based on the PT's evaluation, subsequent referrals and imaging were warranted and led to a diagnosis of metastatic adenocarcinoma.

Conclusion:

Hip pain caused by sinister pathologies is unusual. In this case, a PT identified “red flag” symptoms during the initial evaluation and collaborated with other providers for further investigation. The skilled evaluation and timely referral led to the discovery of previously undiagnosed metastatic adenocarcinoma.
Early Rehabilitation Following Saddle Pulmonary Embolism: Perspective From Physical Therapist as Patient
Authors: Brueilly Kevin E. , Hergott Colleen G. , Fox Ashley M. , Dowling Jeffrey S.
Published: August 2020

Purpose:

Pulmonary embolism (PE) is a complication associated with the condition of deep vein thrombosis (DVT). Together, DVT and PE comprise the condition of venous thromboembolism (VTE). The presence of PE is a life-threatening acute complication, with the risk of death being 18-fold higher than that in patients with DVT alone. The long-term effects of VTE may influence a patient's ability to maintain appropriate levels of physical activity, resulting in impaired functional mobility, quality of life, and overall health and wellness. Physical therapists frequently work with patients who are at risk for or have a history of VTE across all practice settings and are often responsible for mobilizing patients after VTE. However, little guidance exists regarding optimal timing for initiation and intensity of treatment to combat the negative sequalae associated with PE.

Methods:

This case report describes the experience of a physical therapist who suffered an unprovoked submassive saddle PE.

Results:

The patient self-initiated and self-administered an exercise program with successful outcomes. The case provides a unique perspective of a physical therapist who used his clinical knowledge to make decisions, while experiencing the event through the lens of a patient.

Conclusion:

Evidence is provided to support the role of early physical therapy–directed progressive mobility to maximize long-term outcomes following PE.