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1.
J Emerg Med ; 64(1): 77-82, 2023 01.
Article in English | MEDLINE | ID: mdl-36641257

ABSTRACT

BACKGROUND: Hospitals have implemented innovative strategies to address overcrowding by optimizing patient flow through the emergency department (ED). Vertical split flow refers to the concept of assigning patients to vertical chairs instead of horizontal beds based on patient acuity. OBJECTIVE: Evaluate the impact of vertical split flow implementation on ED Emergency Severity Index (ESI) level 3, patient length of stay, and throughput at a community hospital. METHODS: Retrospective cohort study of all ESI level 3 patients presenting to a community hospital ED over a 3-month period prior to and after vertical split flow implementation between 2018 and 2019. RESULTS: In total, data were collected from 10,638 patient visits: 5262 and 5376 patient visits pre- and postintervention, respectively. There was a significant reduction in mean overall length of stay when ESI-3 patients were triaged with vertical split flow (251 min vs 283 min, p < 0.001). CONCLUSIONS: Community hospital ED implementation of vertical split flow for ESI level 3 patients was associated with a significant reduction in overall length of stay and improved throughput. This model provides a solution to increase the number of patients that can be simultaneously cared for in the ED without increasing staffing or physical space.


Subject(s)
Emergency Service, Hospital , Hospitals, Community , Humans , Retrospective Studies , Length of Stay , Patient Acuity , Triage
2.
J Intensive Care Med ; 37(9): 1146-1151, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35118909

ABSTRACT

BACKGROUND: Compared to traditional ultrasound machines, emerging handheld point-of-care-ultrasound (HPOCUS) systems exhibit superior portability and affordability. Thus, they have been increasingly embraced in the intensive care setting. However, there is scarce data on patient safety and current regulatory body guidelines are lacking. Here, we critically appraise the literature with a focus on the merits, concerns, and framework of existing POCUS guidelines. Subsequently, we provide recommendations for future regulatory guidelines. METHODS: A comprehensive literature review was conducted using the PubMed database employing the key words "point-of-care/handheld/portable ultrasound" and "guidelines" alone, in combination, and using thesaurus terms. Eligible articles were scrutinized for description of potential benefits and concerns of HPOCUS, especially from a patient safety perspective, as well as currently existing POCUS practice guidelines. Data was extracted, reported thematically using a narrative synthesis approach, then subsequently used to guide our proposed guidelines. RESULTS: The most widely reported benefits of HPOCUS include superior portability, affordability, imaging, facilitation of expedited diagnosis and management, and integration with medical workplace flow. However, major barriers to adoption include device security/patient confidentiality and patient safety. Furthermore, except for a policy published by the American College of Emergency Physicians (ACEP) in 2018, there are few other national regulatory guidelines pertaining to handheld POCUS. In light of this, we propose a framework for HPOCUS guideline development to address these and other concerns. Such guidelines include training and credentialing, bioengineering approval, and strategic integration with electronic medical record systems. CONCLUSION: HPOCUS can be a powerful tool for expedited diagnosis and management guidance. However, there is limited data regarding patient safety and current regulatory body guidelines are lacking. Our assessment illuminates that there remain many unsolved problems about HPOCUS, and in turn, we propose guidelines to address safe regulation and implementation.


Subject(s)
Point-of-Care Systems , Point-of-Care Testing , Critical Care , Humans , Ultrasonography/methods
3.
Am J Physiol Gastrointest Liver Physiol ; 321(2): G171-G184, 2021 08 01.
Article in English | MEDLINE | ID: mdl-34159811

ABSTRACT

Vitamin D deficiency is an environmental factor involved in the pathogenesis of inflammatory bowel disease (IBD); however, the mechanisms surrounding its role remain unclear. Previous studies conducted in an intestinal epithelial-specific vitamin D receptor (VDR) knockout model suggest that a lack of vitamin D signaling causes a reduction in intestinal autophagy. A potential link between vitamin D deficiency and dysregulated autophagy is microRNA (miR)-142-3p, which suppresses autophagy. In this study, we found that wild-type C57BL/6 mice fed a vitamin D-deficient diet for 5 wk had increased miR-142-3p expression in ileal tissues compared with mice that were fed a matched control diet. Interestingly, there was no difference in expression of key autophagy markers ATG16L1 and LC3II in the ileum whole tissue. However, Paneth cells of vitamin D-deficient mice were morphologically abnormal and had an accumulation of the autophagy adaptor protein p62, which was not present in the total crypt epithelium. These findings suggest that Paneth cells exhibit early markers of autophagy dysregulation within the intestinal epithelium in response to vitamin D deficiency and enhanced miR-142-3p expression. Finally, we demonstrated that treatment-naïve IBD patients with low levels of vitamin D have an increase in miR-142-3p expression in colonic tissues procured from "involved" areas of the disease. Taken together, our findings demonstrate that insufficient vitamin D levels alter expression of autophagy-regulating miR-142-3p in intestinal tissues of mice and patients with IBD, providing insight into the mechanisms by which vitamin D deficiency modulates IBD pathogenesis.NEW & NOTEWORTHY Vitamin D deficiency has a role in IBD pathogenesis, and although the mechanisms surrounding its role remain unclear, it has been suggested that autophagy dysregulation is involved. Here, we show increased ileal expression of autophagy-suppressing miR-142-3p in mice that were fed a vitamin D-deficient diet and in "involved" colonic biopsies from pediatric IBD patients with low vitamin D. miR-142-3p serves as a potential mechanism mediating vitamin D deficiency and reduced autophagy.


Subject(s)
Ileum/metabolism , Inflammatory Bowel Diseases/metabolism , MicroRNAs/genetics , Vitamin D Deficiency/metabolism , Vitamin D/metabolism , Adolescent , Animals , Autophagy , Autophagy-Related Proteins/genetics , Autophagy-Related Proteins/metabolism , Cells, Cultured , Child , HCT116 Cells , HeLa Cells , Humans , Ileum/pathology , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/genetics , Mice , Mice, Inbred C57BL , MicroRNAs/metabolism , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Paneth Cells/metabolism , Paneth Cells/pathology , Vitamin D Deficiency/complications
4.
J Cell Physiol ; 234(4): 3458-3468, 2019 04.
Article in English | MEDLINE | ID: mdl-30368811

ABSTRACT

Notochordal cells (NCs), characterized by their vacuolated morphology and coexpression of cytokeratin and vimentin intermediate filaments (IFs), form the immature nucleus pulposus (NP) of the intervertebral disc. As humans age, NCs give way to mature NP cells, which do not possess a vacuolated morphology and typically only express vimentin IFs. In light of their concomitant loss, we investigated the relationship between cytosolic vacuoles and cytokeratin IFs, specifically those containing cytokeratin-8 proteins, using a human chordoma cell line as a model for NCs. We demonstrate that the chemical disruption of IFs with acrylamide, F-actin with cytochalasin-D, and microtubules with nocodazole all result in a significant (p < 0.001) decrease in vacuolation. However, vacuole loss was the greatest in acrylamide-treated cells. Examination of the individual roles of vimentin and cytokeratin-8 IFs in the existence of vacuoles was accomplished using small interfering RNA-mediated RNA interference to knock down either vimentin or cytokeratin-8 expression. Reduction of cytokeratin-8 expression was associated with a less-vacuolated cell morphology. These data demonstrate that cytokeratin-8 IFs are involved in stabilizing vacuoles and that their diminished expression could play a role in the loss of vacuolation in NCs during aging. A better understanding of the NCs may assist in preservation of this cell type for NP maintenance and regeneration.


Subject(s)
Chordoma/metabolism , Intermediate Filaments/metabolism , Keratin-8/metabolism , Notochord/metabolism , Vacuoles/metabolism , Acrylamide/toxicity , Cell Line, Tumor , Chordoma/pathology , Cytochalasin D/toxicity , Humans , Intermediate Filaments/drug effects , Intermediate Filaments/genetics , Intermediate Filaments/pathology , Keratin-8/genetics , Nocodazole/toxicity , Notochord/drug effects , Notochord/pathology , Signal Transduction , Vacuoles/drug effects , Vacuoles/pathology
5.
J Clin Gastroenterol ; 53(8): 616-620, 2019 09.
Article in English | MEDLINE | ID: mdl-30614943

ABSTRACT

GOALS: To determine whether diabetic patients with hepatitis C virus (HCV) treated with direct-acting antiviral agents have improved diabetes, accounting for change in both hemoglobin A1c (HbA1c) and diabetes medications, and whether any improvement was sustained. BACKGROUND: HCV infection is associated with an increased risk of diabetes, with improvement in glycemic control after eradication. There remains uncertainty about the durability and magnitude of this effect. STUDY: HbA1c and diabetes medications were recorded at 6-month intervals for 1.5 years pretreatment and posttreatment for 122 patients. Subjects were classified as having improved diabetes if there was a decrease in HbA1c≥0.5% with no increase in diabetes medications or a decrease in diabetes medications with a stable HbA1c. RESULTS: HbA1c at the nearest time point before treatment was 8.4%±1.9%, compared with 7.8%±1.7% after treatment, a mean difference of 0.6% [95% CI (0.2, 0.9), P<0.01]. A linear mixed effects model incorporating each subject's repeated measurements over time also demonstrated a reduction after treatment of 0.5% [95% CI, (0.3, 0.8), P<0.001]. Accounting for both HbA1c and diabetes medications, 42 of 122 (34%) had an improvement in diabetes after HCV treatment, and 20 of 28 (71%) of these subjects sustained improvement at 1.5 years follow-up. Prescription of insulin was associated with improved diabetes. CONCLUSIONS: Treatment of HCV with direct-acting antiviral agents was associated with improved diabetes in a significant portion of patients with an average reduction in HbA1c of clinically significant magnitude. Among responders, this effect was sustained over 1.5 years of follow-up.


Subject(s)
Antiviral Agents/therapeutic use , Diabetes Mellitus, Type 2 , Hepatitis C, Chronic/drug therapy , Aged , Blood Glucose/metabolism , Female , Glycated Hemoglobin/metabolism , Humans , Male , Middle Aged , Retrospective Studies
7.
Gen Comp Endocrinol ; 246: 105-115, 2017 05 15.
Article in English | MEDLINE | ID: mdl-27292788

ABSTRACT

Teneurin C-terminal associated peptide (TCAP) is a neuropeptide that bears some structural similarity to the corticotropin-releasing factor (CRF) family of peptides. TCAP and CRF are both implicated in the regulation of stress-related behaviors, as established in rodent models. However, in vertebrates, both TCAP and CRF possess three additional paralogous forms making vertebrate models difficult to assess with respect to TCAP-CRF interaction. As a urochordate, this species possesses single homologs of TCAP and of a CRF/Diuretic-like peptide (CDLP) in the genome, thereby establishing Ciona intestinalis as an excellent model organism to examine the interaction of these peptide systems. However, the lack of C. intestinalis synthetic peptides and specific antisera has complicated experimentation. We, therefore, prepared synthetic versions of CDLP and TCAP to prepare specific antisera and to investigate their bioactivity in this species. To analyze stress-related behaviors, a novel behavioral assay was used to characterize different types of contraction-based behaviors, using buccal opening contractions, cloacal opening contractions, lateral contractions, longitudinal contractions and expulsions. Protein and mRNA expression data indicate that the mature versions of both peptides are present in a number of tissues. With respect to behavioral activity, both TCAP- and CDLP-treated animals had distinct contraction profiles under ambient conditions. Moreover, food stimulation tests revealed that whereas CDLP-treated animals displayed a strong expulsion behavior in response to feeding, TCAP-treated animals did not show this effect. These actions are consistent with previous studies done in vertebrates.


Subject(s)
Behavior, Animal/drug effects , Ciona intestinalis/drug effects , Corticotropin-Releasing Hormone/pharmacology , Diuretics/pharmacology , Feeding Behavior/drug effects , Peptide Fragments/pharmacology , Peptides/pharmacology , Animals , Antibody Formation , Blotting, Western , Ciona intestinalis/immunology , Ciona intestinalis/metabolism , Corticotropin-Releasing Hormone/genetics , Peptide Fragments/genetics , Peptide Fragments/immunology , Peptides/genetics , RNA, Messenger/genetics , Rabbits , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction
8.
J Biomech Eng ; 136(5): 051009, 2014 May.
Article in English | MEDLINE | ID: mdl-24599055

ABSTRACT

Interlamellar shear may play an important role in the homeostasis and degeneration of the intervertebral disk. Accurately modeling the shear behavior of the interlamellar compartment would enhance the study of its mechanobiology. In this study, physical experiments were utilized to describe interlamellar shear and define a constitutive model, which was implemented into a finite element analysis. Ovine annulus fibrosus (AF) specimens from three locations within the intervertebral disk (lateral, outer anterior, and inner anterior) were subjected to in vitro mechanical shear testing. The local shear stress-stretch relationship was described for the lamellae and across the interlamellar layer of the AF. A hyperelastic constitutive model was defined for interlamellar and lamellar materials at each location tested. The constitutive models were incorporated into a finite element model of a block of AF, which modeled the interlamellar and lamellar layers using a continuum description. The global shear behavior of the AF was compared between the finite element model and physical experiments. The shear moduli at the initial and final regions of the stress-strain curve were greater within the lamellae than across the interlamellar layer. The difference between interlamellar and lamellar shear was greater at the outer anterior AF than at the inner anterior region. The finite element model was shown to accurately predict the global shear behavior or the AF. Future studies incorporating finite element analysis of the interlamellar compartment may be useful for predicting its physiological mechanical behavior to inform the study of its mechanobiology.


Subject(s)
Finite Element Analysis , Intervertebral Disc , Materials Testing , Shear Strength , Animals , Biomechanical Phenomena , Elasticity , Sheep , Stress, Mechanical
9.
Biomacromolecules ; 14(2): 406-12, 2013 Feb 11.
Article in English | MEDLINE | ID: mdl-23256640

ABSTRACT

Oligopeptide hydrogels are emerging as useful matrices for cell culture with commercial products on the market, but L-oligopeptides are labile to proteases. An obvious solution is to create D-oligopeptide hydrogels, which lack enzymatic recognition. However, D-oligopeptide matrices do not support cell growth as well as L-oligopeptide matrices. In addition to chiral interactions, many cellular activities are strongly governed by charge-charge interactions. In this work, the effects of chirality and charge on human mesenchymal stem cell (hMSC) behavior were studied using hydrogels assembled from oppositely charged oligopeptides. It was found that negative charges significantly improved hMSC viability and proliferation in D-oligopeptide gels but had little effect on their interactions with L-oligopeptide gels. This result points to the possibility of using charge and other factors to engineer biomaterials whose chirality is distinct from that of natural biomaterials, but whose performance is close to that of natural biomaterials.


Subject(s)
Biocompatible Materials/pharmacology , Hydrogels/pharmacology , Mesenchymal Stem Cells/drug effects , Oligopeptides/pharmacology , Static Electricity , Biocompatible Materials/chemistry , Cell Culture Techniques , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Humans , Hydrogels/chemistry , Oligopeptides/chemistry , Viscoelastic Substances/chemistry , Viscoelastic Substances/pharmacology
10.
J Shoulder Elbow Surg ; 21(10): 1398-405, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22154306

ABSTRACT

BACKGROUND: The main theoretic advantage of proximal olecranon fracture intramedullary fixation is decreased soft-tissue irritation and, potentially, less subsequent hardware removal. Despite this possible benefit, questions remain as to whether intramedullary devices are capable of controlling olecranon fractures to the same extent as locking plates. This study evaluates the ability of a novel multidirectional locking nail to stabilize comminuted fractures and directly compares its biomechanical performance with that of locking olecranon plates. MATERIALS AND METHODS: We implanted 8 stainless steel locking plates and stainless steel intramedullary nails to stabilize a simulated comminuted fracture in 16 fresh-frozen cadaveric elbows. Flexion-extension, varus-valgus, gap distance, and rotational 3-dimensional angular displacement analysis was conducted over a 60° motion arc (30° to 90°) to assess fragment motion through physiologic cyclic arcs of motion and failure loading. Displacements in all planes were compared. RESULTS: Both implants showed less than 1° of motion in all measured planes and allowed less than 1 mm of gapping through all loads tested until ultimate failure. All failures occurred by sudden, catastrophic means. The mean failure weight for the nail was 14.4 kg compared with 8.7 kg for the plate (P = .02). The nail survived 1102 cycles, whereas the plate survived 831 cycles (P = .06). CONCLUSION: In simulated comminuted olecranon fractures, the multidirectional locking intramedullary nails sustained significantly higher maximum loads than the locking plates. The two implants showed no significant differences in fragment control or number of cycles survived. Surgeons can expect the multidirectional locking nails to stabilize comminuted fractures at least as well as locking plates.


Subject(s)
Bone Nails , Bone Plates , Elbow Joint/surgery , Fracture Fixation, Intramedullary/instrumentation , Fractures, Comminuted/surgery , Olecranon Process/injuries , Ulna Fractures/surgery , Aged , Aged, 80 and over , Biomechanical Phenomena , Cadaver , Elbow Joint/physiopathology , Female , Fractures, Comminuted/physiopathology , Humans , Male , Middle Aged , Olecranon Process/physiopathology , Olecranon Process/surgery , Prosthesis Design , Ulna Fractures/physiopathology , Elbow Injuries
11.
J Hand Surg Am ; 36(8): 1303-9, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21719211

ABSTRACT

PURPOSE: Fractures of the distal radius are among the most common injuries treated in hand surgery practice, and distal radius locking plates have become an increasingly popular method of fixation. Despite widespread use of this technology, it is unknown whether the subchondral placement of locking screws affects the loading profile of the distal radius. Our study was designed to determine whether subchondral locking screws change the articular contact pressures in the distal radius. METHODS: Twelve cadaveric forearms underwent a previously described axial loading protocol in a materials testing machine. We used an intra-articular, real-time computerized force sensor to measure peak contact pressure, total pressure, and contact area in the distal radius. Internal validation of sensor placement and reproducibility was conducted. Each specimen was tested before fixation (control), after application of a palmar distal radius locking plate, and after simulation of a metaphyseal fracture. RESULTS: We identified no statistically significant differences in maximum pressure, total pressure, and contact area among control, plated, and plated and fractured specimens. However, the contact footprint-represented by squared differences in force across the sensor-were significantly different between the control group and both plated groups. CONCLUSIONS: The technique for measuring contact pressures produces highly repeatable values. Distal radius locking plates with subchondral hardware placement do not seem to significantly change articular contact pressures.


Subject(s)
Bone Plates , Fracture Fixation, Internal/methods , Radius Fractures/surgery , Cadaver , Humans , Pressure , Stress, Mechanical , Treatment Outcome
12.
Otolaryngol Head Neck Surg ; 163(5): 1055-1060, 2020 11.
Article in English | MEDLINE | ID: mdl-32539583

ABSTRACT

OBJECTIVE: To determine the prevalence and demographics features of pediatric patients with severe obstructive sleep apnea (OSA) who would not undergo preoperative polysomnography (PSG) under current American Academy of Otolaryngology (AAO) guidelines. STUDY DESIGN: In this retrospective cohort study, we identified patients from the electronic medical record who underwent elective polysomnography for evaluation of sleep-disordered breathing between 2012 and 2018. SETTING: Urban tertiary safety net hospital. SUBJECTS AND METHODS: A total of 456 patients with a mean (SD) age of 5.7 (3.2) years (263 male, 193 female). Demographic factors (age, sex, race, language, insurance status) and clinical findings (symptom severity, tonsil size) were recorded. The data were analyzed by univariate analysis. RESULTS: Of 456 patients identified, 66 (14.5%) were found to have severe OSA. African American patients had 3.7 times the odds of severe OSA compared to white patients (95% CI, 1.2-10.8). Patients aged 2 to 3 years had 2.2 times the odds of severe OSA compared to patients aged 4 to 6 years (95% CI, 1.2-4.0). Sex, ethnicity, language, and insurance type were not significantly associated with severity of OSA. The presence of apneic episodes and tonsil size were not found to be statistically significant. CONCLUSION: Up to 14.5% of healthy pediatric patients with sleep-disordered breathing may have severe OSA; young age and African American race are statistically significant predictors. Clinical findings, such as tonsil size and symptom severity, were not found to be statistically significant predictors.


Subject(s)
Polysomnography , Sleep Apnea, Obstructive , Adolescent , Black or African American , Age Factors , Analysis of Variance , Child , Child, Preschool , Female , Humans , Male , Odds Ratio , Patient Acuity , Prevalence , Retrospective Studies , Sleep Apnea Syndromes , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/epidemiology , Sleep Apnea, Obstructive/ethnology , White People
13.
J Cell Physiol ; 220(3): 698-705, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19472213

ABSTRACT

Cells of the nucleus pulposus (NP) in the intervertebral disc are derived directly from the embryonic notochord. In humans, a shift in NP cell population coincides with the beginning of age-related changes in the extracellular matrix that can lead to spinal disorders. To begin identifying the bases of these changes, the manner by which relevant environmental factors impact cell function must be understood. This study investigated the roles of biochemical, nutritional, and physical factors in regulating immature NP cells. Specifically, we examined cell morphology, attachment, proliferation, and expression of genes associated with the notochord and immature NP (Sox9, CD24, and type IIA procollagen). Primary cells isolated from rat caudal discs were exposed to different media formulations and physical culture configurations either in 21% (ambient) or 2% (hypoxic) O2. As expected, cells in alginate beads retained a vacuolated morphology similar to chordocytes, with little change in gene expression. Interestingly, NP tissues not enzymatically digested were more profoundly influenced by oxygen. In monolayer, alpha-MEM preserved vacuolated morphology, produced the highest efficiency of attachment, and best maintained gene expression. DMEM and Opti-MEM cultures resulted in high levels of proliferation, but these appeared to involve small non-vacuolated cells. Gene expression patterns for cells in DMEM monolayer cultures were consistent with chondrocyte de-differentiation, with the response being delayed by hypoxia. Overall, results indicate that certain environmental conditions induce cellular changes that compromise the notochordal phenotype in immature NP. These results form the foundation on which the mechanisms of such changes can be elucidated.


Subject(s)
CD24 Antigen/genetics , Collagen Type II/genetics , Intervertebral Disc/metabolism , Notochord/metabolism , SOX9 Transcription Factor/genetics , Alginates/metabolism , Animals , Cell Adhesion/genetics , Cell Hypoxia , Cell Proliferation , Cell Shape/genetics , Cells, Cultured , Culture Media/metabolism , Gene Expression Regulation , Glucuronic Acid/metabolism , Hexuronic Acids/metabolism , Intervertebral Disc/cytology , Male , Notochord/cytology , Phenotype , Rats , Rats, Sprague-Dawley , Time Factors
14.
Clin Pediatr (Phila) ; 58(9): 993-999, 2019 08.
Article in English | MEDLINE | ID: mdl-31030547

ABSTRACT

Previous studies have shown low rates of screening for obstructive sleep apnea in children with Down syndrome (DS), a high-prevalence population. Our study investigated the impact of the 2011 American Academy of Pediatrics guidelines, which recommends screening for obstructive sleep apnea with polysomnogram by age 4 years. We conducted a retrospective chart review of patients 0 to 18 years of age with DS seen at a medical center between 2006 and 2016. Polysomnogram screening frequency was investigated and compared pre- and post-guideline publication. A total of 136 participants were identified. Thirty-two percent (44/136) of children with DS were referred for polysomnogram, all of whom had symptoms. Although overall referral frequency was unaffected, completion frequency by age 18 years improved after publication (30% [21/69] vs 19% [13/67]; P < .05). Notably, polysomnogram completion frequency by age 4 years improved after guidelines publication compared with prior (25% [17/69] vs 0% [0/67]; P < .0001).


Subject(s)
Down Syndrome/complications , Guideline Adherence/statistics & numerical data , Polysomnography/methods , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , Adolescent , Boston , Child , Child, Preschool , Female , Humans , Infant , Male , Practice Guidelines as Topic , Retrospective Studies
15.
J Biomed Opt ; 13(4): 044040, 2008.
Article in English | MEDLINE | ID: mdl-19021367

ABSTRACT

We developed a miniature fiber optic pressure sensor system and utilized it for in vitro intradiscal pressure measurements for rodents. One of the unique features of this work is the design and fabrication of a sensor element with a multilayer polymer-metal diaphragm. This diaphragm consists of a base polyimide layer (150 nm thick), a metal reflective layer (1 microm thick), and another polyimide layer for protection and isolation (150 nm thick). The sensor element is biocompatible and can be fabricated by simple, batch-fabrication methods in a non-cleanroom environment with good device-to-device uniformity. The fabricated sensor element has an outer diameter of only 366 microm, which is small enough to be inserted into the rodent discs without disrupting the structure or altering the intradiscal pressures. In the calibration and in vitro rodent intradiscal pressure measurements, the sensor element exhibits a linear response to the applied pressure over the range of 0-70 kPa, with a sensitivity of 0.0206 microm/kPa and a resolution of 0.17 kPa. To our best knowledge, this work is the first successful demonstration of rodent intradiscal pressure measurements.


Subject(s)
Intervertebral Disc/physiology , Manometry/instrumentation , Optical Fibers , Refractometry/instrumentation , Transducers , Equipment Design , Equipment Failure Analysis , Metals/chemistry , Polymers/chemistry , Reproducibility of Results , Sensitivity and Specificity
16.
Eur Spine J ; 17(9): 1149-59, 2008 Sep.
Article in English | MEDLINE | ID: mdl-18668268

ABSTRACT

Mechanical stress is one of the risk factors believed to influence intervertebral disc degeneration. Animal models have shown that certain regimes of compressive loading can induce a cascade of biological effects that ultimately results in cellular and structural changes in the disc. It has been proposed that both cell-mediated breakdown of collagen and the compromised stability of collagen with loss of anular tension could result in degradation of lamellae in the anulus fibrosus (AF). To determine whether this may be important in the AF, we subjected entire rings of de-cellularized AF tissue to MMP-1 digestion with or without tension. Biomechanical testing found trends of decreasing strength and stiffness when tissues were digested without tension compared with those with tension. To determine the physiologic significance of tissue level tension in the AF, we used an established in vivo murine model to apply a disc compression insult known to cause degeneration. Afterward, that motion segment was placed in fixed-angle bending to impose tissue level tension on part of the AF and compression on the contralateral side. We found that the AF on the convex side of bending retained a healthy lamellar appearance, while the AF on the concave side resembled tissues that had undergone degeneration by loading alone. Varying the time of onset and duration of bending revealed that even a brief duration applied immediately after cessation of compression was beneficial to AF structure on the convex side of bending. Our results suggest that both cell-mediated events and cell-independent mechanisms may contribute to the protective effect of tissue level tension in the AF.


Subject(s)
Collagen/metabolism , Intervertebral Disc/metabolism , Intervertebral Disc/physiopathology , Spinal Diseases/metabolism , Spinal Diseases/physiopathology , Animals , Biomechanical Phenomena , Collagen/ultrastructure , Disease Models, Animal , Male , Matrix Metalloproteinase 1/metabolism , Mice , Spinal Cord Compression/metabolism , Spinal Cord Compression/physiopathology , Stress, Mechanical
17.
Ann Biomed Eng ; 46(2): 375-376, 2018 02.
Article in English | MEDLINE | ID: mdl-29294195

ABSTRACT

This erratum is to correct the following: (1) in the Western Blotting subsection under the Materials and Methods section, the concentration of protein from each sample loaded into Criterion Tris-HCl gels was incorrectly stated as 155 µg of protein. The correct value is 9.7 µg; (2) in Fig. 1b, the bar graph showed incorrect values for semi-quantitation of Western blots. Figure 1 has been updated with a corrected graph in Fig. 1b only.

18.
Ann Biomed Eng ; 45(5): 1365-1374, 2017 05.
Article in English | MEDLINE | ID: mdl-28091965

ABSTRACT

Mesenchymal stem cells (MSCs) are being studied extensively due to their potential as a therapeutic cell source for many load-bearing tissues. Compression of tissues and the subsequent deformation of cells are just one type physical strain MSCs will need to withstand in vivo. Mechanotransduction by MSCs and their mechanical properties are partially controlled by the cytoskeleton, including vimentin intermediate filaments (IFs). Vimentin IF deficiency has been tied to changes in mechanosensing and mechanical properties of cells in some cell types. However, how vimentin IFs contribute to MSC deformability has not been comprehensively studied. Investigating the role of vimentin IFs in MSC mechanosensing and mechanical properties will assist in functional understanding and development of MSC therapies. In this study, we examined vimentin IFs' contribution to MSCs' ability to deform under external deformation using RNA interference. Our results indicate that a deficient vimentin IF network decreases the deformability of MSCs, and that this may be caused by the remaining cytoskeletal network compensating for the vimentin IF network alteration. Our observations introduce another piece of information regarding how vimentin IFs are involved in the complex role the cytoskeleton plays in the mechanical properties of cells.


Subject(s)
Intermediate Filaments/metabolism , Mechanotransduction, Cellular/physiology , Mesenchymal Stem Cells/metabolism , Vimentin/metabolism , Humans , Intermediate Filaments/genetics , Mesenchymal Stem Cells/cytology , Vimentin/genetics
19.
Orthopedics ; 40(2): e238-e241, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-27735977

ABSTRACT

Orthopedic dogma states that external fixator stiffness is improved by placing 1 pin close to the fracture and 1 as distant as possible ("near-far"). This fixator construct is thought to be less expensive than placing pins a shorter distance apart and using "pin-bar" clamps that attach pins to outriggers. The authors therefore hypothesized that the near-far construct is stiffer and less expensive. They compared mechanical stiffness and costs of near-far and pin-bar constructs commonly used for temporary external fixation of femoral shaft fractures. Their testing model simulated femoral shaft fractures in damage control situations. Fourth-generation synthetic femora (n=18) were used. The near-far construct had 2 pins that were 106 mm apart, placed 25 mm from the gap on each side of the fracture. The pin-bar construct pins were 55 mm apart, placed 40 mm from the gap. Mechanical testing was performed on a material test system machine. Stiffness was determined in the linear portion of the load-displacement curve for both constructs in 4 modes: axial compression, torsional loading, frontal plane 3-point bending, and sagittal plane 3-point bending. Costs were determined from a 2012 price guide. Compared with the near-far construct, the pin-bar construct had stiffness increased by 58% in axial compression (P<.05) and by 52% in torsional loading (P<.05). The pin-bar construct increased cost by 11%. In contrast to the authors' hypothesis and existing orthopedic dogma, the near-far construct was less stiff than the pin-bar construct and was similarly priced. Use of the pin-bar construct is mechanically and economically reasonable. [Orthopedics. 2017; 40(2):e238-e241.].


Subject(s)
Bone Nails , External Fixators/economics , Fracture Fixation/economics , Fractures, Bone/therapy , Biomechanical Phenomena , Fracture Fixation/methods , Humans , Materials Testing
20.
J Orthop Trauma ; 31(5): e137-e142, 2017 May.
Article in English | MEDLINE | ID: mdl-28079730

ABSTRACT

OBJECTIVES: Biomechanical studies of osteoporotic bone have used synthetic models rather than cadaveric samples because of decreased variability, increased availability, and overall ease of the use of synthetic models. We compared the torsional mechanical properties of cadaveric osteoporotic bone with those of currently available synthetic osteoporotic bone analogues. METHODS: We tested 12 osteoporotic cadaveric humeri and 6 specimens each of 6 types of synthetic analogues. A 5-mm fracture gap model and posterior plating technique with 4.5-mm narrow 10-hole locking compression plate were used. Torque was applied to a peak of ±10 N·m for 1000 cycles at 0.3 Hz. Data were continuously collected during cyclical and ramped loading with a servohydraulic materials testing system. RESULTS: Cadaveric bone had a 17% failure rate before completing 1000 cycles. Three osteoporotic bone models had 100% failure (P < 0.05), 2 had 17% failure, and 1 had 0% failure before 1000 cycles. Significant differences in the stiffness of the 3 types of synthetic bone models that survived cyclic loading were noted compared with the cadaveric bone model (P < 0.05). Osteoporotic bone analogues had torsional mechanical properties different from those of osteoporotic cadaveric specimens. CONCLUSIONS: The differences between osteoporotic cadaveric humeri and synthetic osteoporotic bone analogues ranged from profound with complete catastrophic failure after a few cycles to subtler differences in stiffness and strain hardening. These findings suggest that different bone analogue models vary substantially in their torsional mechanical properties and might not be appropriate substitutes for cadaveric bone in biomechanical studies of osteoporotic bone.


Subject(s)
Bone Substitutes , Fracture Fixation, Internal/methods , Osteoporotic Fractures/surgery , Aged , Aged, 80 and over , Biomechanical Phenomena , Bone Plates , Cadaver , Female , Fracture Fixation, Internal/instrumentation , Humans , Humerus/physiopathology , Humerus/surgery , Male , Models, Anatomic , Osteoporotic Fractures/physiopathology , Prosthesis Failure , Torsion, Mechanical
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