Ultrasonically Responsive Tissue Engineering Scaffolds for the Temporal Control over Osteo-Inductive Growth Factor Delivery

In 2012, approximately 6.8 million people in the United States were diagnosed with orthopedic injuries or diseases. Over 500,000 people in the United States underwent bone grafting procedures, which cost 2.5 billion dollars per year and can result in complications. Polymer-based grafting scaffolds can facilitate 3D bone tissue growth in a localized, sustained manner. However, bone regeneration requires the orchestration of a sequence of events. Current scaffolds based on degradation and diffusion cannot provide sequential deliveries. We aimed to design a polymer scaffold that can release one payload diffusively at early time points, followed by ultrasonically triggered release of a second payload. The ability to deliver sequential payloads on demand (using ultrasonic stimulation) can more accurately mimic natural biological responses. Calcium alginate hydrogels were loaded with model drugs (fluorescently labeled dextrans of various charges and sizes) in order to characterize drug release due to diffusion, compared to when stimulated by different ultrasonic signals. Dextran release was quantitatively measured on a plate reader against a standard curve by measuring fluorescence at 525 nm. These studies uncovered optimal ultrasonic stimulation parameters (20 kHz signal for 3 minutes at 20% amplitude) that resulted in statistically significant drug release compared to controls while (i) preserving the 3D structure of the hydrogel scaffold and (ii) minimizing rises in temperatures to maintain the bio-activity of bio-molecular payloads. Furthermore, these studies identified trends of uncharged drugs diffusing out of the scaffold prior to stimulation while small, charged drugs being retained and ultrasonically released in an on-demand manner

Machine Operator with Central Cord Syndrome: A Case Report

Setting: Outpatient pain management office Case Diagnosis: A 30-year-old man presents with central cord syndrome (CCS) after cervical spine trauma. Introduction: Central cord syndrome (CCS) is most commonly caused by cervical spine trauma with an incidence of 11,000 cases annually in the United States. Despite CCS being the most common type of incomplete spinal cord injury, treatment is still controversial and varies from conservative management to early surgical intervention. Case Description: After sustaining a closed head trauma by 350 lb lead object at work, the patient presented with weakness, numbness, and tingling in the bilateral upper and lower extremities and demonstrated the typical signs of CCS where the motor impairment of upper extremities was disproportionate compared to the lower extremities. Imaging studies and clinical examination findings were used to support the diagnosis of CCS with neurological level of injury at C4 along with neurogenic bladder and bowel. On day 6, he underwent C3-C4 posterior cervical laminectomy for spinal cord decompression. After surgery, he regained movement in his upper and lower extremities and went through rehabilitation, physical therapy, and occupational therapy. Treatment included pregabalin, lidocaine patch, diclofenac gel, infrared heating pad, and medical marijuana. Results: Magnetic resonance imaging (MRI) of cervical spine showed focal cord edema at C4 level, likely due to contusion. At 7 months post C3-C4 laminectomy, patient continued to demonstrate decreased sensation in the upper and lower extremities bilaterally (left \u3e right), clonus in left upper extremity, and brisk reflexes in both upper and lower extremities but improved muscle strength. Occupational therapist noted slow progression with improving hand grip strength. Discussion: This case illustrates that early surgical intervention can prevent paralysis after a spinal cord injury and improve recovery of CCS. Rapid recognition of neurological deficits and diagnosis of CCS is important for the early management of incomplete spinal cord injury and the patient’s prognosis and recovery

Spontaneous Retroperitoneal Hematoma in a Patient on Lifelong Anticoagulation with Secondary Femoral Neuropathy: A Case Report

Setting: Outpatient pain management office Case Diagnosis: A 52-year-old man presents with spontaneous retroperitoneal hematoma and secondary femoral neuropathy. Introduction: While traumatic retroperitoneal injury is common, spontaneous retroperitoneal hematoma (SRH) is relatively rare with a documented rate of 0.6-6.6%. Spontaneous retroperitoneal hematoma typically presents with pain of the abdomen, hip, or leg. Rarely, symptoms associated with lumbosacral plexus compression are present. Leg numbness and weakness are present in less than 10% of cases. Today, treatment remains largely conservative with a low percentage of patients requiring angioembolization. Case Description: A 52-year-old male with significant past medical history of mechanical aortic valve requiring lifelong Coumadin presented to the orthopedics office following a visit to the emergency department (ED) for low back pain. He had low back pain radiating to the right anterior thigh associated with weakness for a duration of 1 week. He was wheelchair bound due to pain. There was no history of trauma. Two weeks later, his pain continued, but he required a wheelchair only for assistance. Treatment included cyclobenzaprine, steroids, and physical therapy. An electromyography (EMG) of lower extremities and magnetic resonance imaging (MRI) of lumbar spine and pelvis were ordered. He was diagnosed with L4 radiculopathy in the right lower extremity by the orthopedist and referred to pain management for epidural steroid foraminal injections. Results: In addition to multilevel spondylosis, lumbar spine MRI showed 7.2cm x 4.7cm x 4.0cm hyperintense lesion in the right iliacus consistent with unclear etiology. Pelvic MRI showed a 6.0cm x 3.1cm x 3.7cm collection in the right iliacus most consistent with hematoma. After 5 months since onset of symptoms, the patient presented to the pain management office. On exam, he had 4/5 strength in the right quadriceps, reduced sensation along the right medial thigh, calf, and ankle, and absent right patellar reflex. He was diagnosed with femoral neuropathy secondary to retroperitoneal hematoma. He was scheduled for follow-up in 4 weeks to see if his symptoms have improved. Discussion: Studies have shown that the incidence of spontaneous retroperitoneal hematoma is rare, occurring 0.6-6.6% of the time with \u3c10% of the cases having symptoms of leg pain and weakness. Many cases are only found in case reports. This patient presented with low back pain, leg pain, and secondary femoral neuropathy. From this case, we can learn to keep a broad differential for low back pain particularly when imaging can point to multiple explanations for back pain. The history of present illness over time showed improvement in pain and weakness concordant with hematoma reabsorption. This diagnosis changed management from potential epidural steroid foraminal injection to conservative management

Impact of wind and solar production on electricity prices: Quantile regression approach

This is is an Accepted Manuscript of an article published by Taylor & Francis in Journal of the Operational Research Society on 5 August 2019, available online: http://www.tandfonline.com/10.1080/01605682.2019.1634783.We study the impact of fuel prices, emission allowances, demand, past prices, wind and solar production on hourly day-ahead electricity prices in Germany over the period from January 2015 until June 2018. Working within a linear regression, ARX-EGARCH and quantile regression framework we compare how different pricing factors influence the mean and quantiles of the electricity prices. Contrary to the existing literature, we find that short-term price fluctuations on the fuel markets and emission allowances have little effect on the electricity prices. We also find that day-of-the-week as well as monthly effects have significant impact on the electricity prices in Germany and should not be ignored in model specifications. Three main factors are found to drive extreme prices: price persistence, expected demand and expected wind production. Our findings contribute to understanding of extreme price movements, which can be used in pricing models and hedging strategies.acceptedVersio

Multicenter assessment of quantitative sensory testing (QST) for the detection of neuropathic-like pain responses using the topical capsaicin model

Background: The use of quantitative sensory testing (QST) in multicenter studies has been quite limited, due in part to lack of standardized procedures among centers. Aim: The aim of this study was to assess the application of the capsaicin pain model as a surrogate experimental human model of neuropathic pain in different centers and verify the variation in reports of QST measures across centers. Methods: A multicenter study conducted by the Quebec Pain Research Network in six laboratories allowed the evaluation of nine QST parameters in 60 healthy subjects treated with topical capsaicin to model unilateral pain and allodynia. The same measurements (without capsaicin) were taken in 20 patients with chronic neuropathic pain recruited from an independent pain clinic. Results: Results revealed that six parameters detected a significant difference between the capsaicin-treated and the control skin areas: (1) cold detection threshold (CDT) and (2) cold pain threshold (CPT) are lower on the capsaicin-treated side, indicating a decreased in cold sensitivity; (3) heat pain threshold (HPT) was lower on the capsaicin-treated side in healthy subjects, suggesting an increased heat pain sensitivity; (4) dynamic mechanical allodynia (DMA); (5) mechanical pain after two stimulations (MPS2); and (6) mechanical pain summation after ten stimulations (MPS10), are increased on the capsaicin-treated side, suggesting an increased in mechanical pain (P < 0.002). CDT, CPT and HPT showed comparable effects across all six centers, with CPT and HPT demonstrating the best sensitivity. Data from the patients showed significant difference between affected and unaffected body side but only with CDT. Conclusion: These results provide further support for the application of QST in multicenter studies examining normal and pathological pain responses

Barriers to Recruitment for a THC Study

Due to ongoing efforts to increase inclusion of under-represented racial and ethnic minorities in clinical studies, researchers have conducted studies to gain greater understanding as to why members of these groups have had limited enrollment. 1 Previous research indicated a widespread lack of trust in the medical community regarding clinical studies, particularly in populations of color due to knowledge of the Tuskegee study.2 Specifically, to date, there appears to be no investigation which explores reasons for hesitation to volunteer to participate in a study utilizing delta-9-tetrahydrocannabinol (THC) to reduce chronic neuropathic pain. Our PCOM IRB-approved project will attempt to uncover whether there is a significant degree of skepticism, and what factors comprise any such reluctance. It is predicted that there will be a higher rate of declination to participate in the study by minority patients. It is also predicted that those belonging to a minority group who demonstrate interest in proceeding will express some reluctance due to mistrust in the intentions of our research. Discussion of the subjects’ concerns may reveal possible reasons for reluctance to participate in clinical trials. This information will increase researchers\u27 awareness of barriers and factors that will potentially affect a person\u27s decision to participate in a clinical trial. Subjects will be identified as potentially eligible study patients if they have recent documentation of neuropathic pain in their medical records. Eligibility will be determined using a code search (G62.9) for polyneuropathy at one of the three PCOM Healthcare Centers. Patients will be contacted in advance of their next primary care appointment to determine interest in taking a survey. For those who agree, this questionnaire will be provided immediately prior to their scheduled medical examination. Information requested includes: past and present marijuana use past and present pain management interventions for neuropathic pain demographic information (age, gender, ethnicity) current pain intensity and interference with daily activities via PEG scale feedback regarding their interest in participating in a clinical research project involving THC use If there is a response to learn more about a clinical study on campus, \u27Administration of THC to improve analgesia in patients with neuropathic pain\u27, they will be provided with a flyer and Informed Consent Form for recruitment for this investigation. One hundred potential study subjects will be screened, and the data collected will be analyzed. This study started March 7, and to date, seven patients completed the questionnaire, three of whom have indicated a decision to participate in the THC investigation