Publications by authors named "Rohan Bhimani"

30 Publications

  • Page 1 of 1

Detection of ankle fractures using deep learning algorithms.

Foot Ankle Surg 2022 May 26. Epub 2022 May 26.

Foot & Ankle Research and Innovation Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston 02114, MA, USA; Foot & Ankle Service, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston 02114, MA, USA. Electronic address:

Background: Early and accurate detection of ankle fractures are crucial for optimizing treatment and thus reducing future complications. Radiographs are the most abundant imaging techniques for assessing fractures. Deep learning (DL) methods, through adequately trained deep convolutional neural networks (DCNNs), have been previously shown to faster and accurately analyze radiographic images without human intervention. Herein, we aimed to assess the performance of two different DCNNs in detecting ankle fractures using radiographs compared to the ground truth.

Methods: In this retrospective case-control study, our DCNNs were trained using radiographs obtained from 1050 patients with ankle fracture and the same number of individuals with otherwise healthy ankles. Inception V3 and Renet-50 pretrained models were used in our algorithms. Danis-Weber classification method was used. Out of 1050, 72 individuals were labeled as occult fractures as they were not detected in the primary radiographic assessment. Single-view (anteroposterior) radiographs was compared with 3-views (anteroposterior, mortise, lateral) for training the DCNNs.

Results: Our DCNNs showed a better performance using 3-views images versus single-view based on greater values for accuracy, F-score, and area under the curve (AUC). The highest sensitivity was 98.7 % and specificity was 98.6 % in detection of ankle fractures using 3-views using inception V3. This model missed only one fracture on radiographs.

Conclusion: The performance of our DCNNs showed that it can be used for developing the currently used image interpretation programs or as a separate assistant solution for the clinicians to detect ankle fractures faster and more precisely.

Level Of Evidence: III.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fas.2022.05.005DOI Listing
May 2022

Utility of Diagnostic Ultrasound in the Assessment of Patellar Instability.

Orthop J Sports Med 2022 May 23;10(5):23259671221098748. Epub 2022 May 23.

Foot & Ankle Research and Innovation Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Background: The use of imaging to diagnose patellofemoral instability is often limited by the inability to dynamically load the joint during assessment. Therefore, the diagnosis is typically based on physical examination using the glide test to assess and quantify lateral patellar translation. However, precise quantification with this technique remains difficult.

Purpose: To quantify patellar position using ultrasound imaging under dynamic loading conditions to distinguish between knees with and without medial patellofemoral complex (MPFC) injury.

Study Design: Controlled laboratory study.

Methods: In 10 cadaveric knees, the medial patellofemoral distance was measured to quantify patellar position from 0° to 40° of knee flexion at 10° increments. Knees were evaluated at each flexion angle under unloaded conditions and with 20 N of laterally directed force on the patella to mimic the glide test. Patellar position measurements were made on ultrasound images obtained before and after MPFC transection and compared for significant differences. To determine the ability of medial patellofemoral measurements to differentiate between MPFC-intact and MPFC-deficient states, area under the receiver operating characteristic (ROC) curve analysis and the Delong test were used. The optimal cutoff value to distinguish between the deficient and intact states was determined using the Youden statistic.

Results: A significant increase in medial patellofemoral distance was observed in the MPFC-deficient state as compared with the intact state at all flexion angles ( = .005 to < .001). When compared with the intact state, MPFC deficiency increased medial patellofemoral distance by 32.8% (6 mm) at 20° of knee flexion under 20-N load. Based on ROC analysis and the statistic, the optimal threshold for identifying MPFC injury was 19.2 mm of medial patellofemoral distance at 20° of flexion under dynamic loading conditions (area under the ROC curve = 0.93, sensitivity = 77.8%, specificity = 100%, accuracy = 88.9%).

Conclusion: Using dynamic ultrasound assessment, we found that medial patellofemoral distance significantly increases with disruption of the MPFC.

Clinical Relevance: Dynamic ultrasound measurements can be used to accurately detect the presence of complete MPFC injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/23259671221098748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9134436PMC
May 2022

Deep Learning Algorithms Improve the Detection of Subtle Lisfranc Malalignments on Weightbearing Radiographs.

Foot Ankle Int 2022 Aug 19;43(8):1118-1126. Epub 2022 May 19.

Foot & Ankle Research and Innovation Laboratory (FARIL), Department of Orthopaedic Surgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.

Background: Detection of Lisfranc malalignment leading to the instability of the joint, particularly in subtle cases, has been a concern for foot and ankle care providers. X-ray radiographs are the mainstay in the diagnosis of these injuries; thus, improving the performance of clinicians in interpreting radiographs can noticeably affect the quality of health care in these patients. Here we assessed the performance of deep learning algorithms on weightbearing radiographs for detection of Lisfranc joint malalignment in patients with Lisfranc instability.

Methods: In a retrospective study, 640 patients with Lisfranc malalignment leading to instability were recruited plus 640 individuals with uninjured feet and healthy Lisfranc joint as the control group. All radiographs were screened by orthopaedic surgeons. Two deep learning models were trained, validated, and tested (in a ratio 80:10:10) using a single-view (anteroposterior) and 3-view (anteroposterior, lateral, oblique) radiographs. The performances of the models were reported as sensitivity, specificity, positive and negative predictive values, accuracy, score, and area under the curve (AUC).

Results: No significant differences were observed between the patients and the controls regarding age, gender, race, and body mass index. The best deep learning algorithm outperformed our human interpreters (<1% vs ~10% misdiagnosis), 94.8% sensitivity, 96.9% specificity, 98.6% accuracy, 95.8% score, and 99.4% AUC.

Conclusion: Deep learning methods have shown promising potential in acting as an assistant interpreter of radiographic images in patients with Lisfranc malalignment. Developing these algorithms can hasten and improve the accuracy of diagnosis and reduce further costs and burdens on the patients and health care system.

Level Of Evidence: Level III, case-control Machine Learning study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/10711007221093574DOI Listing
August 2022

Isolated injuries to the lateral ankle ligaments have no direct effect on syndesmotic stability.

Knee Surg Sports Traumatol Arthrosc 2022 May 6. Epub 2022 May 6.

Foot and Ankle Research and Innovation Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Purpose: This study aim was to detect the impact of lateral ankle ligaments injury on syndesmotic laxity when evaluated arthroscopically in a cadaveric model. The null hypothesis was that lateral ankle ligament injury does not affect the stability of syndesmosis.

Methods: Sixteen fresh-frozen above-knee amputated cadaveric specimens were divided into two groups of eight specimens that underwent arthroscopic evaluation of the distal tibiofibular joint. In both the groups, the assessment was first done with all syndesmotic and ankle ligaments intact. Thereafter, Group 1 underwent sequential transection of the three lateral ankle ligaments first to identify the effects of lateral ligament injury: (1) anterior talofibular ligament (ATFL), (2) calcaneofibular ligament (CFL), (3) posterior talofibular ligament (PTFL), then followed by the syndesmotic ligaments, (4) AITFL, (5) Interosseous ligament (IOL), and (6) PITFL. Group 2 underwent sequential transection of the (1) AITFL, (2) ATFL, (3) CFL, (4) IOL, (5) PTFL, and (6) PITFL, which represent the most commonly injured pattern in ankle sprain. In all scenarios, four loading conditions were considered under 100 N of direct force: (1) unstressed, (2) a lateral fibular hook test, (3) anterior to posterior (AP) fibular translation test, and (4) posterior to anterior (PA) fibular translation test. Distal tibiofibular coronal plane diastasis at the anterior and posterior third of syndesmosis, as well as AP and PA sagittal plane translation, were arthroscopically measured.

Results: The distal tibiofibular joint remained stable after transection of all lateral ankle ligaments (ATFL, CFL, and PTFL) as well as the AITFL. However, after additional transection of the IOL, the syndesmosis became unstable in both the coronal and sagittal plane. Syndesmosis laxity in the coronal plane was also observed after transection of the ATFL, CFL, AITFL, and IOL. Subsequent transection of the PITFL precipitated syndesmosis laxity in the sagittal plane, as well.

Conclusions: The findings from the present study suggest that lateral ankle ligament injuries itself do not directly affect the stability of syndesmosis. However, if it combines with IOL injuries, even partial injuries cause syndesmotic laxity. As a clinical relevance, accurate diagnosis is the key for surgeons to determine syndesmosis fixation whether there is only AITFL injury or combined IOL injury in concomitant acute syndesmotic and lateral ligament injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00167-022-06985-6DOI Listing
May 2022

Radiographic Landmarks for the Femoral Attachment of the Medial Patellofemoral Complex: A Cadaveric Study.

Arthroscopy 2022 08 11;38(8):2504-2510. Epub 2022 Feb 11.

Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A. Electronic address:

Purpose: To report the radiographic landmarks for the medial patellofemoral complex (MPFC) footprint on the medial femur and describe the difference between the radiographic positions corresponding to the medial quadriceps tendon femoral ligament (MQTFL) and medial patellofemoral ligament (MPFL) fibers.

Methods: In 8 unpaired cadaveric knees, the MPFC footprint was exposed on the medial femur, and the proximal and distal boundaries of the footprint were marked. Lateral fluoroscopic images of the knee were obtained and analyzed using Image J. The proximal boundary corresponding to the MQTFL, the MPFC midpoint, and distal boundary corresponding to the MPFL were described radiographically and compared for differences in position.

Results: The proximal MQTFL footprint was 0.8 ± 0.6 mm anterior (P = .013) and 5.2 ± 1.8 mm proximal to the MPFC midpoint (P <.001), whereas the distal MPFL footprint was 0.8 ± 0.7 mm posterior (P = .012) and 5.9 ± 1.1 mm distal to the radiographic MPFC midpoint (P <.001). The radiographic point corresponding to the distal MPFL footprint was 0.8 ± 0.9 mm posterior (P = .011) and 11.1 ± 2.3 mm distal to the radiographic point of the proximal MQTFL footprint (P <.001). When using the point of intersection of the posterior cortical line and the proximal posterior condyle as a reference, 91.6% of all points correlating to the MQTFL, MPFC midpoint and MPFL, were within 10 mm in any direction from this radiographic landmark.

Conclusions: On fluoroscopic imaging, the proximal MQTFL and distal MPFL fibers had significantly different radiographic positions from the MPFC midpoint on the femur. These findings should be considered when reconstructing specific components of the MPFC.

Clinical Relevance: As fluoroscopy is often used intraoperatively to guide graft placement, our findings may serve as a reference when differentiating the locations of the MPFL vs MQTFL on the femur for anatomic reconstruction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arthro.2022.01.046DOI Listing
August 2022

Distinct limbic dopamine regulation across olfactory-tubercle subregions through integration of in vivo fast-scan cyclic voltammetry and optogenetics.

J Neurochem 2022 04 5;161(1):53-68. Epub 2022 Feb 5.

Neuroscience Program, State University of New York at Buffalo, Buffalo, New York, USA.

The olfactory tubercle (OT), an important component of the ventral striatum and limbic system, is involved in multi-sensory integration of reward-related information in the brain. However, its functional roles are often overshadowed by the neighboring nucleus accumbens. Increasing evidence has highlighted that dense dopamine (DA) innervation of the OT from the ventral tegmental area (VTA) is implicated in encoding reward, natural reinforcers, and motivated behaviors. Recent studies have further suggested that OT subregions may have distinct roles in these processes due to their heterogeneous DA transmission. Currently, very little is known about regulation (release and clearance) of extracellular DA across OT subregions due to its limited anatomical accessibility and proximity to other DA-rich brain regions, making it difficult to isolate VTA-DA signaling in the OT with conventional methods. Herein, we characterized heterogeneous VTA-DA regulation in the medial (m) and lateral (l) OT in "wild-type," urethane-anesthetized rats by integrating in vivo fast-scan cyclic voltammetry with cell-type specific optogenetics to stimulate VTA-DA neurons. Channelrhodopsin-2 was selectively expressed in the VTA-DA neurons of wild-type rats and optical stimulating parameters were optimized to determine VTA-DA transmission across the OT. Our anatomical, neurochemical, and pharmacological results show that VTA-DA regulation in the mOT is less dependent on DA transporters and has greater DA transmission than the lOT. These findings establish the OT as a unique, compartmentalized structure and will aid in future behavioral characterization of the roles of VTA-DA signaling in the OT subregions in reward, drug addiction, and encoding behavioral outputs necessary for survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jnc.15577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8930533PMC
April 2022

Use of portable ultrasonography for the diagnosis of lateral ankle instability.

J Orthop Res 2022 Jan 5. Epub 2022 Jan 5.

Foot and Ankle Research and Innovation Lab (FARIL), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Portable ultrasonography is increasingly used to evaluate ankle stability at the point of care. This study aims to determine the correlation of portable-ultrasonographic and fluoroscopic measurements of ankle laxity in a cadaveric ligament transection model of ankle ligament injury. We hypothesize that there is an association between portable-ultrasonographic and fluoroscopic measurements when performing stress evaluation of lateral ankle instability. Eight fresh-frozen below-knee amputated cadaveric specimens with intact proximal fibula underwent ultrasound and fluoroscopic evaluation of the ankle during anterior drawer and talar tilt testing. The assessment was first performed with all lateral ankle ligaments intact and thereafter with sequential transection of the anterior talofibular ligament, calcaneofibular ligament, and posterior talofibular ligament. The anterior drawer test was performed with both 50N and 80N of force, and talar tilt test was performed with 1.7 Nm of torque. Correlations between (1) portable-ultrasonographic and fluoroscopic measurements and (2) sequential transection of lateral ankle ligaments were evaluated using Spearman's rank correlations. The same statistical test was used to investigate the correlation between the ultrasonographic and the fluoroscopic measurements. The inter- and intra-observer agreement was assessed using the intraclass correlation coefficient through a two-way mixed-effects model with absolute agreement. Portable-ultrasonographic and fluoroscopic measurements increased as additional ligaments of the lateral ankle were transected (Spearman's rank correlation ranged from 0.74 to 0.81, 0.74 to 0.81, p-values < 0.001). Strong positive correlations between ultrasonographic and fluoroscopic measurements were found during the lateral ankle stability evaluation using anterior drawer and talar tilt testing (Spearman's rank correlation ranged from 0.81 to 0.85, 0.81 to 0.85, p-values < 0.001). Inter-rater (0.99, 95% CI: 0.98-0.99) and intra-rater reliability (0.97, 95% CI: 0.95-0.99) for the ultrasonographic measurements were substantial. In conclusion, there was a strong correlation found between ultrasonographic and fluoroscopic values measured during simulated anterior drawer and talar tilt test in a cadaveric ligament transection model. In this model, the portable-ultrasonographic measurement was found to be reliable for repeated measurements of the talar translation and the lateral clear space distance. Based on these data, ultrasonography is likely to become a valuable point of care diagnostic tool due to its ability to readily and dynamically evaluate suspected lateral ankle instability. Clinical Significance: The use of dynamic stress ultrasound to assess the anterior translation of the talus and the lateral clear space distance appears to be a reliable and repeatable technique to evaluate lateral ankle stability with a radiation-free, noninvasive, and low-cost manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.25256DOI Listing
January 2022

Transportal versus all-inside techniques of anterior cruciate ligament reconstruction: a systematic review.

J Orthop Surg Res 2021 Dec 23;16(1):734. Epub 2021 Dec 23.

Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, USA.

Background: Transportal (TP) and all-inside techniques (AIT) are the most commonly used anterior cruciate ligament (ACL) reconstruction procedures in current clinical practice. However, there is an ongoing debate over which procedure is superior. Therefore, the purpose of this systematic review was to evaluate and compare the clinical outcomes and complications of these two techniques to propose recommendations for future application. Our primary hypothesis was that AIT is a superior ACLR technique compared to TP.

Methods: A systematic literature review, using PRISMA guidelines, was conducted using PubMed, Medline, Google Scholar, and EMBASE, up to February 2021 to identify studies focusing on AIT and TP techniques of ACL reconstruction. We excluded animal experiments, cadaveric studies, retrospective studies, case reports, technical notes, and studies without quantitative data. Patients' characteristics, surgical technical features, along with postoperative follow-up and complications were extracted and reported accordingly. Methodological quality of the included studies was assessed using the Modified Coleman Methodology Score (MCMS).

Results: A total of 44 studies were selected for this review, of which four were comparative studies. A total of 923 patients underwent AIT and 1678 patients underwent the TP technique for ACLR. A single semitendinosus graft was commonly used in the AIT compard to combined semitendinosus and gracilis graft in the TP group. The postoperative increase in International Knee Documentation Committee (IKDC), Lysholm, KT-1000, and Short Form-12 (physical and mental) scores were similar in the AIT group and the TP group. Contrastingly, the VAS pain score was significantly lower in the AIT group compared to the TP group. Furthermore, the pooled complication rates from all studies were similar between the two groups (AIT: 54 patients, 8.26% vs. PT: 55 patients, 6.62%). However, the four studies that prospectively compared AIT and TP techniques showed lesser complications in the AIT group than the TP group.

Conclusion: Since the future trend in orthopedic surgery is toward less invasive and patients' satisfaction with good outcomes, AIT is a good alternative method considering preserving bony tissue and gracilis tendon with less post-operative pain, along with more knee flexor strength and equal outcomes compared to conventional ACL reconstruction surgery. Level of Evidence II.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13018-021-02872-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705139PMC
December 2021

Utility of WBCT to Diagnose Syndesmotic Instability in Patients With Weber B Lateral Malleolar Fractures.

J Am Acad Orthop Surg 2022 Feb;30(3):e423-e433

From the Foot & Ankle Research and Innovation Laboratory, Harvard Medical School, Massachusetts General Hospital, Boston, MA (Bhimani, Ashkani-Esfahani, Lubberts, Kaiser, Waryasz, DiGiovanni, and Guss), Department of Orthopedic Surgery, Academic Medical Center, University of Amsterdam, Amsterdam Movement Sciences, Amsterdam, the Netherlands (Kerkhoffs), the Foot & Ankle Service, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, MA (Kaiser, Waryasz, DiGiovanni, and Guss), Newton-Wellesley Hospital, Harvard Medical School, Massachusetts General Hospital, Boston, MA (Kaiser, Waryasz, DiGiovanni, and Guss).

Background: Diagnosing syndesmotic instability accompanying Weber B ankle fractures can be challenging. This study aimed to evaluate the ability of weight-bearing computed tomography (WBCT) to diagnose syndesmotic instability using one-dimensional, two-dimensional, and three-dimensional measurements among patients with unilateral Weber B lateral malleolar fractures with symmetric medial clear space (MCS) on initial radiographs and yet demonstrated operatively confirmed syndesmotic instability.

Methods: The treatment group included 23 patients with unilateral surgically confirmed syndesmotic instability accompanying Weber B ankle fractures who underwent preoperative bilateral foot and ankle WBCT. The control group included 18 unilateral Weber B ankle fracture patients without syndesmotic instability who underwent bilateral WBCT. Measurements on WBCT images included the following: (1) syndesmotic area, (2) anterior, middle, and posterior distal tibiofibular distance, (3) fibular rotation, (4) distance from fibular tip to plafond, (5) fibular fracture displacement, and (6) MCS distance. In addition, the following volumetric measurements were calculated: (1) syndesmotic joint volume from the tibial plafond extending to 3 and 5 cm proximally, (2) MCS volume, and (3) lateral clear space volume. Area under the receiver operating characteristic curve analysis and Delong test were used, and optimal cutoff values to distinguish between stable and unstable syndesmosis were determined using Youden J statistic.

Results: Among patients with unilateral syndesmotic instability and Weber B ankle fractures, all WBCT measurements were significantly greater than uninjured side, except MCS distance, syndesmotic area, and anterior and posterior tibiofibular distances (P values <0.001 to 0.004). Moreover, syndesmosis volume spanning from the tibial plafond to 5 cm proximally had the largest area under the curve of 0.96 (sensitivity = 90%; specificity = 95%), followed by syndesmosis volume up to 3 cm proximally (area under the curve = 0.91; sensitivity = 90%; specificity = 90%). Except for MCS volume and distal fibular tip to tibial plafond distance, the control group showed no side-to-side difference in any parameter.

Conclusion: Syndesmotic joint volume measurements seem to be best suited to diagnose syndesmotic instability among patients with Weber B ankle fractures, compared with other two-dimensional and three-dimensional WBCT measurements.

Level Of Evidence: Level III, comparative diagnostic study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5435/JAAOS-D-21-00566DOI Listing
February 2022

The stability of total talar prosthesis-How stable to dislocation? Cadaveric study.

J Orthop Res 2021 Dec 13. Epub 2021 Dec 13.

Department of Orthopedic Surgery, Nara Medical University, Kashihara, Japan.

The aim of this study was to characterize ankle stability of total talar prosthesis (TTP) and to determine the effect of implant sizes on stability as well as the resistance to TTP dislocation. Twelve below-knee cadaveric specimens were divided into two groups. Group 1 received a size matched implant and Group 2 received downsized implant by 5%. The stability assessment under fluoroscopy was performed for each cadaver in its native state. Following TTP insertion process, each then underwent evaluation of the TTP ankle stability. The stability of pre- and post-TTP was compared. (1) Anterior drawer distance. (2) Talar tilt angle under varus and valgus stress. (3) Subtalar tilt angle under varus stress was measured. Finally, the dislocation test was performed using the aforementioned testing conditions, then the stress force was slowly increased from 0 to 350 N, during which time it was observed on fluoroscopy all the time. Compared to pre TTP ankles, varus and anterior drawer stress showed significant instability (p < 0.001-0.031). Only anterior drawer stress in smaller sized implants showed significant instability when compared to identical sized implants (p = 0.008). No dislocation was seen under varus, valgus, and subtalar stress. However, anterior dislocation was observed in all cases of smaller size implant group (p = 0.045). TTP implant was stable under valgus and subtalar stress. However, clinicians should pay attention to anterior instability. Notably, downsized implants should be considered carefully to minimize the chance of anterior dislocation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.25237DOI Listing
December 2021

Distinct dose-dependent effects of methamphetamine on real-time dopamine transmission in the rat nucleus accumbens and behaviors.

J Neurochem 2021 08 28;158(4):865-879. Epub 2021 Jul 28.

Neuroscience Program, University at Buffalo, State University of New York, Buffalo, NY, USA.

Methamphetamine (METH) is a potent psychostimulant that exerts many of its physiological and psychomotor effects by increasing extracellular dopamine (DA) concentrations in limbic brain regions. While several studies have focused on how potent, neurotoxic doses of METH augment or attenuate DA transmission, the acute effects of lower and behaviorally activating doses of METH on modulating DA regulation (release and clearance) through DA D2 autoreceptors and transporters remain to be elucidated. In this study, we investigated how systemic administration of escalating, subneurotoxic doses of METH (0.5-5 mg/kg, IP) alter extracellular DA regulation in the nucleus accumbens (NAc), in both anesthetized and awake-behaving rats through the use of in vivo fast-scan cyclic voltammetry. Pharmacological, electrochemical, and behavioral evidence show that lower doses (≤2.0 mg/kg, IP) of METH enhance extracellular phasic DA concentrations and locomotion as well as stereotypies. In contrast, higher doses (≥5.0 mg/kg) further increase both phasic and baseline DA concentrations and stereotypies but decrease horizontal locomotion. Importantly, our results suggest that acute METH-induced enhancement of extracellular DA concentrations dose dependently activates D2 autoreceptors. Therefore, these different METH dose-dependent effects on mesolimbic DA transmission may distinctly impact METH-induced behavioral changes. This study provides valuable insights regarding how low METH doses alter DA transmission and paves the way for future clinical studies on the reinforcing effects of METH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jnc.15470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8376794PMC
August 2021

Arthroscopic Patellofemoral Measurements Can Reliably Assess Patellar Instability.

Arthroscopy 2022 03 9;38(3):902-910. Epub 2021 Jul 9.

Department of Orthopaedic Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, U.S.A.

Purpose: To arthroscopically describe patellar position based on lateralization, tilt, and engagement, and compare measurements in normal, medial patellofemoral complex-(MPFC) deficient, and MPFC-reconstructed knees.

Methods: In 10 cadaveric knees, arthroscopic patellar position was assessed by performing digital measurements on arthroscopic images obtained through a standard anterolateral portal. Lateralization was measured as millimeters overhang of the patella past the lateral edge of the lateral femoral condyle, viewing from the lateral gutter. Patellar tilt was calculated as the difference in medial and lateral distances from the patella to the trochlea, viewing from the sunrise view. Patellotrochlear distance was measured as the anteroposterior distance between the central trochlear groove and patella on the sunrise view. Measurements were obtained at 10° intervals of knee flexion from 0° to 90°, in intact knees (group 1), after arthroscopically transecting the MPFC fibers (group 2), and after MPFC reconstruction (group 3). Optimal cutoff values were identified to distinguish between intact versus MPFC-deficient states.

Results: When compared to group 1, group 2 demonstrated increased patellar lateralization by 22.5% at 0°-40° knee flexion (P = .006), which corrected to baseline in group 3 (P = .006). Patellar tilt measurements demonstrated no differences between groups. Patellotrochlear distance increased by 21.0% after MPFC transection (P = .031) at 0°-40° knee flexion, with correction to baseline after MPFC reconstruction (P = .031). More than 7 mm of lateral overhang at 20°-30° flexion and >6 mm of patellotrochlear distance at 10°-20° flexion were found to indicate MPFC deficiency.

Conclusions: Utilizing standardized arthroscopic views, we identified significant increases in patellar lateralization and patellotrochlear distance in early knee flexion angles after MPFC transection, and these changes normalized after MPFC reconstruction.

Clinical Relevance: Arthroscopic assessments of patellar position may be useful in evaluating patellofemoral stability during patellar stabilization surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arthro.2021.06.022DOI Listing
March 2022

Do Coronal or Sagittal Plane Measurements Have the Highest Accuracy to Arthroscopically Diagnose Syndesmotic Instability?

Foot Ankle Int 2021 Jun 23;42(6):805-809. Epub 2021 Apr 23.

Foot & Ankle Research and Innovation Laboratory, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.

Background: To compare the accuracy of arthroscopic sagittal versus coronal plane distal tibiofibular motion toward diagnosing syndesmotic instability.

Methods: Arthroscopic assessment of the syndesmosis was performed on 21 above-knee cadaveric specimens, first with all ligaments intact and subsequently with sequential transection of the anterior inferior tibiofibular ligament, the interosseous ligament, the posterior inferior tibiofibular ligament, and the deltoid ligament. A lateral hook test, an anterior-to-posterior (AP) translation test, and a posterior-to-anterior (PA) translation test were performed under 100 N of applied force. Anterior and posterior third coronal plane diastasis and AP and PA sagittal plane fibular translations were measured relative to the static tibia.

Results: Receiver operating characteristic (ROC) curve analysis revealed that the area under the curve (AUC) was higher for the combined AP and PA sagittal measurements (AUC, 0.91; accuracy, 83.5%; sensitivity, 78%; specificity, 89%) than the coronal plane measurements (anterior third: AUC, 0.65; accuracy, 60.5%; sensitivity, 63%; specificity, 59%; posterior third: AUC, 0.73; accuracy, 68.5%; sensitivity, 80%; specificity, 57%) ( < .001), underscoring the higher accuracy of sagittal plane measurements.

Conclusion: Arthroscopic measurement of sagittal plane fibular translation is more accurate than coronal plane diastasis for evaluating syndesmotic instability.

Clinical Relevance: Clinicians should focus on distal tibiofibular motion in the sagittal plane when arthroscopically evaluating suspected syndesmotic instability.

Level Of Evidence: Biomechanical cadaveric study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/10711007211004151DOI Listing
June 2021

Volume measurements on weightbearing computed tomography can detect subtle syndesmotic instability.

J Orthop Res 2022 02 19;40(2):460-467. Epub 2021 Apr 19.

Department of Orthopaedic Surgery, Foot and Ankle Research and Innovation Laboratory, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

While weightbearing computed tomography (WBCT) allows three-dimensional (3D) visualization of the distal syndesmosis, image interpretation has largely relied on one-dimensional (1D) distance and, more recently, two-dimensional (2D) area measurements. This study aimed to (1) determine the sensitivity and specificity of 2D area and 3D volume WBCT measurements towards detecting subtle syndesmotic instability, (2) evaluate whether the patterns of changes in the 3D shape of the syndesmosis can be attributed to the type of ligament injury. A total of 24 patients with unilateral subtle syndesmotic instability and 24 individuals with uninjured ankles (controls) with bilateral ankle WBCT were assessed retrospectively. First, 2D areas at 0, 1, 3, 5, and 10 cm, and 3D volumes at 1, 3, 5, and 10 cm above the tibial plafond were measured bilaterally. Secondly, the 3D model of the distal tibiofibular space was created based on WBCT in a subset of 8 out of 24 patients in whom the type of ligament injury was recognized via magnetic resonance imaging. The 3D model of the injured side was superimposed on the uninjured contralateral side to visualize the pattern of changes in different planes. Volume measurement up to 5 cm above the tibial plafond showed the lowest p-value (<0.001 vs. other methods), higher sensitivity (95.8%, 95% confidence interval [CI]: 87.8-100), and specificity (83.3%, 95% CI: 68.4-98.2) for detection of syndesmotic instability. No specific pattern of changes in the 3D shape could be attributed to a type of ligament rupture. We suggest 3D volume measurements, best measured up to 5 cm proximal to the plafond, as a promising means of diagnosing syndesmotic instability, particularly for subtle cases that are hard to detect. Clinical significance: The ability to compare the ankle joints bilaterally in a 3D manner under physiologic weight provided by weightbearing CT has led to a more accurate diagnostic method. Using volumetric measurement up to 5 cm above the tibial plafond showed higher sensitivity and specificity for recognizing an unstable syndesmosis, especially in subtle cases. However, our preliminary investigations showed that the pattern of 3D alterations in the distal tibiofibular joint space based on WBCT images does not indicate the type of syndesmotic ligamentous injury. Our results can also help image viewing programs to improve their measurement tools to facilitate 3D measurement for the syndesmosis as well as other conditions that may benefit from 3D evaluation of the clinical images.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.25049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497639PMC
February 2022

Using area and volume measurement via weightbearing CT to detect Lisfranc instability.

J Orthop Res 2021 Nov 6;39(11):2497-2505. Epub 2021 Jan 6.

Foot & Ankle Research and Innovation Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital, Boston, Massachusetts, USA.

Weightbearing CT (WBCT) allows evaluation of the Lisfranc joint under physiologic load. We compared the diagnostic sensitivities of one-dimensional (1D) distance, two-dimensional (2D) area, and three-dimensional (3D) volumetric measurement of the injured Lisfranc joint complex (tarsometatarsal, intertarsal, and intermetatarsal) on WBCT among patients with surgically-confirmed Lisfranc instability. The experimental group comprised of 14 patients having unilateral Lisfranc instability requiring operative fixation who underwent preoperative bilateral foot and ankle WBCT. The control group included 36 patients without foot injury who underwent similar imaging. Measurements performed on WBCT images included: (1) Lisfranc joint (medial cuneiform-base of second metatarsal) area, (2) C1-C2 intercuneiform area, (3) C1-M2 distance, (4) C1-C2 distance, (5) M1-M2 distance, (6) first tarsometatarsal (TMT1) angular alignment, (7) second tarsometatarsal (TMT2) angular alignment, (8) TMT1 dorsal step off distance, and (9) TMT2 dorsal step-off distance. In addition, the volume of the Lisfranc joint in the coronal and axial plane were calculated. Among patients with unilateral Lisfranc instability, all WBCT measurements were increased on the injured side as compared to the contralateral uninjured side (p values:  <.001-.008). Volumetric measurements in the coronal and axial plane had a higher sensitivity (92.3%; 91.6%, respectively) and specificity (97.7%; 96.5%, respectively) than 2D and 1D Lisfranc joint measurements, suggesting them to be the most accurate in diagnosing Lisfranc instability. The control group showed no difference in any of the measurements between the two sides. WBCT scan can effectively differentiate between stable and unstable Lisfranc injuries. Lisfranc joint volume measurements demonstrate high sensitivity and specificity, suggesting that this new assessment has high clinical implications for diagnosing subtle Lisfranc instability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jor.24970DOI Listing
November 2021

Are Stem Cells Derived from Synovium and Fat Pad Able to Treat Induced Knee Osteoarthritis in Rats?

Int J Rheumatol 2020 13;2020:9610261. Epub 2020 Jul 13.

Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Osteoarthritis (OA) is a chronic disease and a significant cause of joint pain, tenderness, and limitation of motion. At present, no specific treatment is available, and mesenchymal stem cells (MSCs) have shown promising potentials in this regard. Herein, we aimed to evaluate the repairing potentials of stem cells derived from the synovium and fat pad in the treatment of OA.

Methods: Twenty-eight male rats (220 ± 20 g, aged 10-12 weeks), were randomly divided into four groups ( = 7): C1: nontreated group, C2: Hyalgan-treated group, E1: adipose tissue-derived stem cell-treated group, and E2: synovial membrane-based stem cell-treated group. Collagenase type II was injected into the left knee; after eight weeks, OA was developed. Then, stem cells were injected, and rats were followed for three months. Afterward, specimens and radiological images were investigated. value ≤ 0.05 was set as statistically significant.

Results: Compared to the C1 group, the E1 and E2 groups showed significantly better results in all six pathological criteria as well as joint space width and osteophytes of medial tibial, medial femoral, and medial fabellar condyles ( ≤ 0.001). Similarly, compared to the C2 group, the E1 and E2 groups had better scores regarding surface, matrix, cell distribution, and cell population viability ( < 0.05). E2 showed considerably higher scores compared to C2 regarding subchondral bone and cartilage mineralization ( < 0.05). The joint space width was similar between the C2 and E groups.

Conclusion: Treatment of OA with MSCs, particularly synovial membrane-derived stem cells, not only prevented but also healed OA of the knee to some extent in comparison to the Hyalgan and nontreatment groups.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/9610261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374223PMC
July 2020

Utility of Volumetric Measurement via Weight-Bearing Computed Tomography Scan to Diagnose Syndesmotic Instability.

Foot Ankle Int 2020 07 17;41(7):859-865. Epub 2020 May 17.

Foot & Ankle Research and Innovation Laboratory, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.

Background: Weight-bearing computed tomography (WBCT) allows evaluation of the distal syndesmosis under physiologic load. We hypothesized that WBCT volumetric measurement of the distal syndesmosis would be increased on the injured as compared to the contralateral uninjured side and that these 3-dimensional (3D) calculations would be a more sensitive determinant than 2-dimensional (2D) methodology among patients with syndesmotic instability.

Methods: Twelve patients with unilateral syndesmotic instability requiring operative fixation who underwent preoperative bilateral foot and ankle WBCT were included in the study group. The control group consisted of 24 patients without ankle injury who underwent similar imaging. On WBCT scan, 2D measurements of the syndesmosis joint were first measured 1 cm above the joint line in the axial plane via syndesmotic area and distances between the anterior, middle, and posterior quadrants. Thereafter, comparative 3D volumetric measurements of the syndesmotic joint were also calculated: (1) from the tibial plafond extending until 3 cm proximally, (2) 5 cm proximally, and (3) 10 cm proximally.

Results: In patients with unilateral syndesmotic instability, all 3 weight-bearing volumetric measurements were significantly larger on the injured side as compared to the contralateral, uninjured side ( < .001). In the control group, there was no difference between syndesmotic volumes at any level. Of these 3 anatomic reference points, the 3D measurement spanning from the tibial plafond to a level 5 cm proximally had the highest relative volumetric ratio between the injured and uninjured side, suggesting it is the most sensitive in distinguishing between stable and unstable syndesmotic injury ( < .001). Notably, this 3D volumetric measurement was also more sensitive than 2D measurements ( = .001).

Conclusion: 3D volumetric measurement of the syndesmosis joint appears to be the most effective way to diagnose syndesmotic instability, compared with more traditional 2D syndesmosis measurement.

Level Of Evidence: Level III, retrospective comparative study.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1071100720917682DOI Listing
July 2020

Arthroscopic Assessment of Syndesmotic Instability in the Sagittal Plane in a Cadaveric Model.

Foot Ankle Int 2020 02 8;41(2):237-243. Epub 2019 Oct 8.

Massachusetts General Hospital, Newton-Wellesley Hospital, Harvard Medical School, Boston, MA, USA.

Background: Syndesmotic instability is multidirectional, occurring in the coronal, sagittal, and rotational planes. Despite the multitude of studies examining such instability in the coronal plane, other studies have highlighted that syndesmotic instability may instead be more evident in the sagittal plane. The aim of this study was to arthroscopically assess the degree of syndesmotic ligamentous injury necessary to precipitate fibular translation in the sagittal plane.

Methods: Twenty-one above-knee cadaveric specimens underwent arthroscopic evaluation of the syndesmosis, first with all syndesmotic and ankle ligaments intact and subsequently with sequential sectioning of the anterior inferior tibiofibular ligament (AITFL), the interosseous ligament (IOL), the posterior inferior tibiofibular ligament (PITFL), and deltoid ligament (DL). In all scenarios, an anterior to posterior (AP) and a posterior to anterior (PA) fibular translation test were performed under a 100-N applied force. AP and PA sagittal plane translation of the distal fibula relative to the fixed tibial incisura was arthroscopically measured.

Results: Compared with the intact ligamentous state, there was no difference in sagittal fibular translation when only 1 or 2 ligaments were transected. After transection of all the syndesmotic ligaments (AITFL, IOL, and PITFL) or after partial transection of the syndesmotic ligaments (AITFL, IOL) alongside the DL, fibular translation in the sagittal plane significantly increased as compared with the intact state ( values ranging from .041 to <.001). The optimal cutoff point to distinguish stable from unstable injuries was equal to 2 mm of fibular translation for the total sum of AP and PA translation (sensitivity 77.5%; specificity 88.9%).

Conclusion: Syndesmotic instability appears in the sagittal plane after injury to all 3 syndesmotic ligaments or after partial syndesmotic injury with concomitant deltoid ligament injury in this cadaveric model. The optimal cutoff point to arthroscopically distinguish stable from unstable injuries was 2 mm of total fibular translation.

Clinical Relevance: These data can help surgeons arthroscopically distinguish between stable syndesmotic injuries and unstable ones that require syndesmotic stabilization.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1071100719879673DOI Listing
February 2020

Difference between Mechanical Alignment in Navigation and Scanogram during Total Knee Arthroplasty.

Adv Orthop 2019 1;2019:4096306. Epub 2019 Apr 1.

Department of Orthopaedics, Osmania General Hospital, Hyderabad 500012, India.

Introduction: Malpositioning of the implant results in polyethylene wear and loosing of implant after total knee arthroplasty. Scanogram is often used for measurement of limb alignment. Computer navigation provides real time measurements and thus, the aim is to see any association pre- and postoperatively between coronal alignments measured on scanogram to computer navigation during total knee arthroplasty.

Material And Methods: We prospectively gathered data of 200 patients with advanced degenerative symptomatic arthritis, who were consecutively selected for primary total knee arthroplasty with computer navigation. Every patient's pre- and postoperative scanogram were compared to the intraoperative computer navigation findings.

Results: The results show that the preoperative mean mechanical axis on navigation was 10.65° (SD ± 6.95) and on scanogram it was 10.38° (SD ± 6.89). On the other hand, the mean postoperative mechanical axis on navigation was 0.69° (SD ± 0.87) and on scanogram it was 2.73° (SD ± 2.10). Preoperatively, there was no significant difference (p value = 0.46) between the two. However, the postoperative outcomes suggest that there was a noteworthy difference, with no correlation between the mean Hip-Knee Ankle Axis (HKA) and intraoperative mechanical axis (p value <0.0001).

Conclusion: Postoperative mechanical alignment values after total knee arthroplasty are lower on navigation than measured on standing full length hip to ankle scanogram.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/4096306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6463624PMC
April 2019

Rapidly progressive hip disease-A rare entity in Korean population.

Int J Surg Case Rep 2018 24;53:486-489. Epub 2018 Nov 24.

Department of Orthopaedics, Bharati Hospital, Pune, 411043, India. Electronic address:

Introduction: The pathophysiology of rapidly progressive hip disease is still unclear. It is a rare subset of osteoarthritis that mainly affects elderly women and presents with new- onset severe hip pain and dysfunction. It is assumed to be triggered by extremely rapid osteoarthritic changes resulting in impaction of the femoral head into the acetabulum, with successive osteonecrosis and insufficiency of the femoral head.

Presentation Of The Case: A 62- year-old woman reported of right hip pain which succeeded an acetabular fracture for which open reduction and fixation was done. Initial radiographs, post fixation, showed no obvious abnormality. After 2 months of conservative therapy for her right hip pain, radiographs showed joint space reduction and subchondral bone loss. T1 MRI images revealed marrow oedema pattern and depression of the articular surface of the femoral head.

Discussion: Differential diagnosis includes conditions which potentially lead to rapid hip destruction, such as metabolic bone diseases, autoimmune inflammatory arthritis and classical osteonecrosis. In patients with rapid worsening of hip symptoms successive X-rays and a high degree of clinical suspicion towards RPHD is essential to avoid extensive joint destruction and to facilitate better arthroplasty outcomes.

Conclusion: The authors propose that this case represent an uncommon subset of osteoarthritis. Regular review, both clinically and radiologically, is required to assess speed of progression and to prevent rapid loss of bone stock without the surgeon being aware.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijscr.2018.11.055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6279998PMC
November 2018

Double-Tension Wire Management of Nonunion Patella with Severe Quadriceps Contracture.

Case Rep Orthop 2018 6;2018:1364129. Epub 2018 Sep 6.

Department of Orthopaedics, Bharati Hospital, Pune 411043, India.

Introduction: Nonunion patella with quadriceps contracture is an unusual orthopaedic finding. Very few cases have been recorded in the past with this complication. We present a case of a 40-year-old male with nonunion patella with quadriceps contracture secondary to trauma A 40-year-old male with posttraumatic nonunion patella with quadriceps contracture since 6 months presented with complaints of defect in the left knee with restriction of movements. X-ray of the left knee confirmed our findings. He underwent quadricepsplasty with double-tension band wiring for the patella followed by rigorous physiotherapy to achieve the current level of the knee flexion of 110 degrees.

Conclusion: We conclude that quadricepsplasty with tension band wiring and neutralization wire is one of the good modalities of treatment for a nonunion patella associated with quadriceps contracture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/1364129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146672PMC
September 2018

Relation between Level of Serum Transferrin and Postoperative Wound Drainage in Closed Long Bone Fractures.

Adv Med 2018 11;2018:8612828. Epub 2018 Jul 11.

Department of Orthopaedics, Osmania General Hospital, Hyderabad 500012, India.

Objective: To report association between the serum transferrin level and postoperative wound drainage in closed long bone fractures.

Summary Of Background Data: There is an old association between the serum transferrin level and wound drainage leading to peri-implant infection. There is no literature available on the ideal treatment for wound drainage. In the majority of the cases, wound drainage usually stops in 3-5 days postoperatively. However, very few cases have been described in the literature about wound drainage following closed long bone fractures.

Methods: A prospective review of the patient's serum transferrin levels and postoperative wound drainage is done.

Results: We reviewed records of 100 patients in whom levels of serum transferrin were checked preoperatively and correlated with postoperative wound discharge. Out of the 100 patients whose serum transferrin levels were checked, 23 patients had low serum transferrin levels and 19 patients had postoperative wound discharge. Out of these 19 patients, 16 patients had low serum transferrin levels. Thus, sensitivity of the test was 84.2% and specificity was 91.3%. In addition, the positive predictive value was 70% and negative predictive value was 96%.

Conclusion: We report that preoperative serum transferrin levels can be used as a good marker to judge postoperative wound drainage in closed long bone fractures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/8612828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079574PMC
July 2018

Proteomic Changes in Chick Brain Proteome Post Treatment with Lathyrus Sativus Neurotoxin, β-N-Oxalyl-L-α,β-Diaminopropionic Acid (L-ODAP): A Better Insight to Transient Neurolathyrism.

Toxicol Res 2018 Jul 15;34(3):267-279. Epub 2018 Jul 15.

Department of Biochemistry, University College of Science, Osmania University, Hyderabad, Telangana, India.

Neurolathyrism is a neurodegenerative disorder characterized by spastic paraplegia resulting from the excessive consumption of (Grass pea). β-N-Oxalyl-L-α,β-diaminopropionic acid (L-ODAP) is the primary neurotoxic component in this pea. The present study attempted to evaluate the proteome-wide alterations in chick brain 2 hr and 4 hr post L-ODAP treatment. Proteomic analysis of chick brain homogenates revealed several proteins involved in cytoskeletal structure, signaling, cellular metabolism, free radical scavenging, oxidative stress and neurodegenerative disorders were initially up-regulated at 2 hr and later recovered to normal levels by 4 hr. Since L-ODAP mediated neurotoxicity is mainly by excitotoxicity and oxidative stress related dysfunctions, this study further evaluated the role of L-ODAP in apoptosis using human neuroblastoma cell line, IMR-32. The studies carried out at 200 μM L-ODAP for 4 hr indicate minimal intracellular ROS generation and alteration of mitochondrial membrane potential though not leading to apoptotic cell death. L-ODAP at low concentrations can be explored as a stimulator of various reactive oxygen species (ROS) mediated cell signaling pathways not detrimental to cells. Insights from our study may provide a platform to explore the beneficial side of L-ODAP at lower concentrations. This study is of significance especially in view of the Government of India lifting the ban on cultivation of low toxin Lathyrus varieties and consumption of this lentil.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5487/TR.2018.34.3.267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057293PMC
July 2018

Chemogenetic activation of ventral tegmental area GABA neurons, but not mesoaccumbal GABA terminals, disrupts responding to reward-predictive cues.

Neuropsychopharmacology 2019 01 22;44(2):372-380. Epub 2018 May 22.

Department of Pharmacology and Toxicology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, 14203, USA.

Cues predicting rewards can gain motivational properties and initiate reward-seeking behaviors. Dopamine projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) are critical in regulating cue-motivated responding. Although, approximately one third of mesoaccumbal projection neurons are GABAergic, it is unclear how this population influences motivational processes and cue processing. This is largely due to our inability to pharmacologically probe circuit level contributions of VTA-GABA, which arises from diverse sources, including multiple GABA afferents, interneurons, and projection neurons. Here we used a combinatorial viral vector approach to restrict activating Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to GABA neurons in the VTA of wild-type rats trained to respond during a distinct audiovisual cue for sucrose. We measured different aspects of motivation for the cue or primary reinforcer, while chemogenetically activating either the VTA-GABA neurons or their projections to the NAc. Activation of VTA-GABA neurons decreased cue-induced responding and accuracy, while increasing latencies to respond to the cue and obtain the reward. Perseverative and spontaneous responses decreased, yet the rats persisted in entering the reward cup when the cue and reward were absent. However, activation of the VTA-GABA terminals in the accumbens had no effect on any of these behaviors. Together, we demonstrate that VTA-GABA neuron activity preferentially attenuates the ability of cues to trigger reward-seeking, while some aspects of the motivation for the reward itself are preserved. Additionally, the dense VTA-GABA projections to the NAc do not influence the motivational salience of the cue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41386-018-0097-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6300533PMC
January 2019

Subdural Hemorrhage after Scoliosis and Detethering of Cord Surgery.

Case Rep Med 2018 2;2018:5061898. Epub 2018 Apr 2.

Department of Orthopaedics, Osmania General Hospital, Hyderabad 500012, India.

Introduction: Intracranial hypotension may occur when CSF leaks from the subarachnoid space. Formation of intracranial, subdural, and subarachnoid hemorrhage has been observed after significant CSF leak as seen in lumbar puncture or ventricular shunt placement. However, very few cases, referring to these remote complications following spine surgery, have been described in literature. We present a case of a 10-year-old male child operated for idiopathic scoliosis with low-lying conus medullaris who postoperatively developed subdural hemorrhage.

Case Report: A case of a 10-year-old male operated for idiopathic scoliosis with low-lying conus medullaris is presented. To correct this, detethering was done at the L3 level, laminectomy was done from L2 to L3 with pedicular screw fixation from T3 to L2, and bone grafting with right costoplasty was done from the 3rd to the 6th ribs. On the 5th day postoperatively, the patient developed convulsions and drowsiness and recovered subsequently by postoperative day 7.

Conclusion: We report a rare case of an acute intracranial subdural hemorrhage caused by intracranial hypotension following scoliosis and detethering of cord surgery. This report highlights the potential morbidity associated with CSF leak occurring after this surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2018/5061898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5902091PMC
April 2018

Drug-sensitive Reward in Crayfish: Exploring the Neural Basis of Addiction with Automated Learning Paradigms.

Behav Processes 2018 Jul 13;152:47-53. Epub 2018 Mar 13.

JP Scott Center for Neuroscience, Mind & Behavior, Department of Biological Sciences, Bowling Green State University, Bowling Green, OH, 43403, USA.

Results of recent work from our labs and those of others have broadened perspectives on addiction beyond a human-specific, cognitive phenomenon. Addictive plant alkaloids are defensive compounds which have arisen to counter herbivory. With insects the true targets of the coevolutionary arms race, humans may be little more than collateral damage when impacted by 'human' drugs of abuse. The present paper summarizes recent contributions, with a primary focus on our own research in crayfish, where we characterize the behavioral and neural consequences resulting from chronic and acute exposure to psychostimulant and addictive drugs. Substituted phenethylamines, like amphetamine and cocaine, exhibit a wide range of effects in crayfish with direct parallels to those described from mammalian preparations. Unconditioned effects include intoxication and psychostimulation, where repeated exposure is accompanied by tolerance and sensitization, respectively. Psychostimulants exhibit powerful reinforcing properties in conditioned place preference, subject to extinction and reinstatement. Crayfish readily self-administer amphetamines using instrumental learning approaches. With a nervous system modular and uniquely accessible to neural probing, crayfish offer unique opportunities for studying the basic biological mechanisms of drug effects, for exploring how the appetitive disposition is implemented, and for examining how this is related to the rewarding action of drugs of abuse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.beproc.2018.03.015DOI Listing
July 2018

Role of trace amine-associated receptor 1 in nicotine's behavioral and neurochemical effects.

Neuropsychopharmacology 2018 11 5;43(12):2435-2444. Epub 2018 Feb 5.

Department of Pharmacology and Toxicology; Program in Neuroscience, University at Buffalo, Buffalo, NY, 14214, USA.

Nicotine addiction and abuse remains a global health issue. To date, the fundamental neurobiological mechanism of nicotine addiction remains incompletely understood. Trace amine-associated receptor 1 (TAAR1) is thought to directly modulate dopaminergic system and are thought to be a neural substrate underlying addictive-like behaviors. We aimed to investigate the role of TAAR1 in nicotine addictive-like behaviors. TAAR1 expression after nicotine treatment was evaluated by western blotting. c-Fos immunofluorescence and in vivo fast-scan cyclic voltammetry were used to examine the activation of brain regions and dopamine release, respectively. We then thoroughly and systematically examined the role of TAAR1 in mediating nicotine-induced sensitization, nicotine discrimination, nicotine self-administration, nicotine demand curve, and the reinstatement of nicotine-seeking. Local pharmacological manipulation was conducted to determine the role of TAAR1 in the nucleus accumbens (NAcs) in the reinstatement of nicotine-seeking. We found that the expression of TAAR1 protein was selectively downregulated in the NAc, with no change in either dorsal striatum or prefrontal cortex. TAAR1 activation was sufficient to block nicotine-induced c-Fos expression in the NAc, while also reducing nicotine-induced dopamine release in the NAc. Systemic administration of TAAR1 agonists attenuated the expression and development of nicotine-induced sensitization, nicotine self-administration, the reinstatement of nicotine-seeking, and increased the elasticity of nicotine demand curve, while intra-NAc infusions of a TAAR1 agonist was sufficient to attenuate nicotine reinstatement. Moreover, TAAR1-knockout rats showed augmented cue-induced and drug-induced reinstatement of nicotine-seeking. These results indicated that modulation of TAAR1 activity regulates nicotine addictive-like behaviors and TAAR1 represents a novel target towards the treatment of nicotine addiction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41386-018-0017-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180004PMC
November 2018

Noradrenergic Modulation of Dopamine Transmission Evoked by Electrical Stimulation of the Locus Coeruleus in the Rat Brain.

ACS Chem Neurosci 2017 09 21;8(9):1913-1924. Epub 2017 Jun 21.

Department of Biotechnical and Clinical Laboratory Sciences and ‡Neuroscience Program, University at Buffalo, State University of New York , Buffalo, New York 14214-3005, United States.

Central norepinephrine (NE) and dopamine (DA) are involved in a variety of physiological functions and behaviors. Accumulating evidence suggests that NE neurons originating from the locus coeruleus (LC) innervate DA neurons of the ventral tegmental area (VTA) and influence VTA-DA neural activity. However, the underlying mechanisms of how LC-NE regulates DA transmission via VTA-DA neurons remain largely unexplored. Herein, we investigated how electrical stimulation of the LC modulates VTA-DA neurotransmission in the nucleus accumbens (NAc). For this study, catecholamine release in the NAc and VTA evoked by electrical stimulation of the LC in urethane-anesthetized rats was simultaneously monitored with carbon-fiber microelectrodes using in vivo multichannel fast-scan cyclic voltammetry for comparison of its extracellular regulation. Pharmacological, anatomical, and electrochemical evidence suggest that electrical stimulation of the LC evokes NE release in the VTA and activates VTA-DA neurons, resulting in DA release in the NAc. The electrically evoked DA in the NAc was regulated by D2 receptors and DA transporters (DAT) as well as α-adrenergic receptors in the VTA, whereas NE release in the VTA was regulated by α-adrenergic receptors and NE transporters (NET) not by D2 receptors or DAT. These results suggest that electrical stimulation of LC modulates VTA-DA neurons and DA transmission in the NAc via NE receptors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acschemneuro.7b00078DOI Listing
September 2017

Heterogeneous extracellular dopamine regulation in the subregions of the olfactory tubercle.

J Neurochem 2017 08 20;142(3):365-377. Epub 2017 Jun 20.

Neuroscience Program, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, New York, USA.

Recent studies show that dense dopamine (DA) innervation from the ventral tegmental area to the olfactory tubercle (OT) may play an important role in processing multisensory information pertaining to arousal and reward, yet little is known about DA regulation in the OT. This is mainly due to the anatomical limitations of conventional methods of determining DA dynamics in small heterogeneous OT subregions located in the ventral most part of the brain. Additionally, there is increasing awareness that anteromedial and anterolateral subregions of the OT have distinct functional roles in natural and psychostimulant drug reinforcement as well as in regulating other types of behavioral responses, such as aversion. Here, we compared extracellular DA regulation (release and clearance) in three subregions (anteromedial, anterolateral, and posterior) of the OT of urethane-anesthetized rats, using in vivo fast-scan cyclic voltammetry following electrical stimulation of ventral tegmental area dopaminergic cell bodies. The neurochemical, anatomical, and pharmacological evidence confirmed that the major electrically evoked catecholamine in the OT was DA across both its anteroposterior and mediolateral extent. While both D2 autoreceptors and DA transporters play important roles in regulating DA evoked in OT subregions, DA in the anterolateral OT was regulated less by the D2 receptors when compared to other OT subregions. Comparing previous data from other DA rich ventral striatum regions, the slow DA clearance across the OT subregions may lead to a high extracellular DA concentration and contribute towards volume transmission. These differences in DA regulation in the terminals of OT subregions and other limbic structures will help us understand the neural regulatory mechanisms of DA in the OT, which may elucidate its distinct functional contribution in the ventral striatum towards mediating aversion, reward and addiction processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jnc.14069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849378PMC
August 2017

Operant avoidance learning in crayfish, Orconectes rusticus: Computational ethology and the development of an automated learning paradigm.

Learn Behav 2016 09;44(3):239-49

J.P. Scott Center for Neuroscience, Mind & Behavior, Department of Biological Sciences, Bowling Green State University, Life Sciences Building, Bowling Green, OH, 43403, USA.

Research in crustaceans offers a valuable perspective for studying the neural implementation of conserved behavioral phenomena, including motivation, escape, aggression, and drug-sensitive reward. The present work adds to this literature by demonstrating that crayfish successfully learn to respond to spatially contingent cues. An integrated video-tracking system automatically delivered a mild electric shock when a test animal entered or remained on a substrate paired with punishment. Following a few instances of shock delivery, crayfish quickly learned to avoid these areas. Comparable changes in substrate preference were not exhibited by yoked controls, but locomotion differed significantly from both pre-conditioning levels and from those of their masters receiving shock in a contingent fashion. The results of this work provide valuable insights into the principles governing avoidance learning in an invertebrate system and provide a behavioral template for exploring the neural changes during associative learning. Serving as a case study, this project introduces a new computer framework for the automated control of learning paradigms. Based on routines contained within the JavaGrinders library (free download at iEthology.com), it integrates real-time video tracking with robotic interfaces, and provides a suitable framework for implementing automated learning paradigms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3758/s13420-015-0205-yDOI Listing
September 2016
-->