Twisting electrospun nanofiber fine strips into functional sutures for sustained co-delivery of gentamicin and silver.

Surgical site infections (SSIs) represent the most common nosocomial infection among surgical patients. In order to prevent SSIs in a sustained manner and lessen side effects, we developed a twisting method for generation of nanofiber-based sutures capable of simultaneous delivery of silver and gentamicin. The prepared sutures are composed of core-sheath nanofibers with gentamicin/pluronic F127 in the core and silver/PCL in the sheath produced by co-axial electrospinning. The diameters of obtained sutures range from ~80 µm to ~1.2 mm. The in vitro release profiles of silver and gentamicin exhibit an initial burst followed by a sustained release over 5 weeks. The co-encapsulated sutures were able to kill bacteria much more effectively than gentamicin or silver alone loaded nanofiber sutures, without showing obvious impact on proliferation and migration of dermal fibroblasts and keratinocytes. The gentamicin and silver co-loaded PCL nanofiber sutures may hold great potential for prevention of SSIs.

Patient-Controlled Fentanyl Iontophoretic Transdermal System Improved Postoperative Mobility Compared to Intravenous Patient-Controlled Analgesia Morphine: A Pooled Analysis of Randomized, Controlled Trials.

BACKGROUND: Postoperative pain management protocols that use patient-controlled analgesia (PCA) can hinder mobility due to attached machinery and tubing. Immobility in the postoperative setting can increase complications, length of stay (LOS), and costs. Early and enhanced mobilization can reduce the cost of care while improving patient outcomes. A needle-free, compact, patient-activated, and portable fentanyl iontophoretic transdermal system (fentanyl ITS, IONSYS; The Medicines Company, Parsippany NJ) has been shown to provide comparable efficacy and tolerability to intravenous (IV) PCA morphine that promotes improved mobility. METHODS: This pooled analysis of 1,882 patients across three randomized, controlled trials compared fentanyl ITS to IV PCA morphine for postoperative pain management. Outcomes of patient mobility were assessed by a validated Patient Ease of Care Questionnaire that was given to patients, patients' nurses, and physical therapists involved in patient care. Safety was assessed via spontaneously reported treatment-emergent adverse events (TEAE). RESULTS: Fentanyl ITS significantly improved overall patient mobility, each mobility subscore (P < 0.0001) across all demographics (male/female; elderly/non-elderly; normal BMI/overweight/obese/morbidly obese) and surgery types, and was consistent across nurses and physical therapists mobility assessments. TEAEs were generally similar between the two groups. However, more patients reported an opioid-related TEAE with morphine IV PCA than with fentanyl IV PCA (P = 0.003). CONCLUSION: Due to improved mobility with fentanyl ITS, complications are expected to be less frequent than with IV PCA and epidural PCA. Incorporation of this strategy into postoperative pain management protocols may reduce LOS and total hospital costs.

Hip Pain in the Pre-Arthritic Patient: A Guide for the Primary Care Physician.

Adolescents and young adults (less than 30 years of age) with pre-arthritic hip pain constitute a diagnostic dilemma for the primary care physician. The most common underlying diagnoses range from benign muscle strains/joint sprains to stress reactions, insufficiency fractures, and tears involving the articular cartilage/labrum in the setting of femoroacetabular impingement, a hip shape abnormality that is present in up to 90% of this age group. Undetected or left untreated these seemingly innocuous disorders can result in significant loss of function and, in some cases, irreversible joint damage. Despite sharing common predisposing factors, many of the above diagnoses can be identified with a focused history and physical examination. Conservative management may be safely initiated without advanced imaging, reserving orthopaedic consultation for refractory cases or more serious diagnoses. The presented focused hip clinical examination has 98% sensitivity in localizing intra-articular hip pathology and will be helpful to direct appropriate referrals. This article will serve as a guide for primary care physicians undertaking the difficult task of evaluating and treating a young patient with hip pain.

Improving Rural Bone Health and Minimizing Fracture Risk in West Virginia: Validation of the World Health Organization FRAX Assessment Tool as a Phone Survey for Osteoporosis Detection.

West Virginia ranks second nationally in population ≥ 65 years old placing our state at greater risk for osteoporosis and fracture. The gold standard for detecting osteoporosis is dual X-ray absorptiometry (DXA), yet over half of West Virginia's counties do not have this machine. Due to access barriers, a validated phone-administered fracture prediction tool would be beneficial for osteoporosis screening. The World Health Organization's FRAX fracture prediction tool was administered as a phone survey to 45 patients; these results were compared to DXA bone mineral density determination. Results confirmed that the FRAX phone survey is as reliable as DXA in detecting osteoporosis or clinically significant osteopenia: 92% positive predictive value, 100% negative predictive value, 100% sensitivity and 91% specificity when compared to the gold standard. These promising results allow for the development of telephone-based protocols to improve osteoporosis detection, referral and treatment especially in areas with health care access barriers.

Local Sustained Delivery of 25-Hydroxyvitamin D3 for Production of Antimicrobial Peptides.

PURPOSE: This study seeks to develop fiber membranes for local sustained delivery of 25-hydroxyvitamin D3 to induce the expression and secretion of LL-37 at or near the surgical site, which provides a novel therapeutic approach to minimize the risk of infections. METHODS: 25-hydroxyvitamin D3 loaded poly(L-lactide) (PLA) and poly(ε-caprolactone) (PCL) fibers were produced by electrospinning. The morphology of obtained fibers was characterized using atomic force microscope (AFM) and scanning electron microscope (SEM). 25-hydroxyvitamin D3 releasing kinetics were quantified by enzyme-linked immunosorbent assay (ELISA) kit. The expression of cathelicidin (hCAP 18) and LL-37 was analyzed by immunofluorescence staining and ELISA kit. The antibacterial activity test was conducted by incubating pseudomonas aeruginosa in a monocytes' lysis solution. RESULTS: AFM images suggest that the surface of PCL fibers is smooth, however, the surface of PLA fibers is relatively rough, in particular, after encapsulation of 25-hydroxyvitamin D3. The duration of 25-hydroxyvitamin D3 release can last more than 4 weeks for all the tested samples. Plasma treatment can promote the release rate of 25-hydroxyvitamin D3. Human keratinocytes and monocytes express significantly higher levels of hCAP18/LL-37 after incubation with plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers than the cells incubated with around ten times amount of free drug. After incubation with this fiber formulation for 5 days LL-37 in the lysis solutions of U937 cells can effectively kill the bacteria. CONCLUSIONS: Plasma treated and 25-hydroxyvitamin D3 loaded PCL fibers induce significantly higher levels of antimicrobial peptide production in human keratinocytes and monocytes without producing cytotoxicity.

Smartphone Mobile Applications to Enhance Diagnosis of Skin Cancer: A Guide for the Rural Practitioner.

Primary care physicians occupy a vital position to impact many devastating conditions, especially those dependent upon early diagnosis, such as skin cancer. Skin cancer is the most common cancer in the United States and despite improvements in skin cancer therapy, patients with a delay in diagnosis and advanced disease continue to have a grave prognosis. Due to a variety of barriers, advanced stages of skin cancer are more prominent in rural populations. In order to improve early diagnosis four things are paramount: increased patient participation in prevention methods, establishment of screening guidelines, increased diagnostic accuracy of malignant lesions, and easier access to dermatologists. Recent expansion in smartphone mobile application technology offers simple ways for rural practitioners to address these problems. More than 100,000 health related applications are currently available, with over 200 covering dermatology. This review will evaluate the newest and most useful of those applications offered to enhance the prevention and early diagnosis of skin cancer, particularly in the rural population.

Primary Care Fall Risk Assessment for Elderly West Virginians.

West Virginia is ranked second nationally for the percent of its population 65 years of age. The elderly are especially susceptible to falls with fall risk increasing as age increases. Because falls are the number one cause of injury-related morbidity and mortality in the West Virginia elderly, evaluation of fall risk is a critical component of the patient evaluation in the primary care setting. We therefore highlight fall risk assessments that require no specialized equipment or training and can easily be completed at an established office visit. High quality clinical practice guidelines supported by the American Geriatric Society recommend yearly fall risk evaluation in the elderly. Those seniors at greatest risk of falls will benefit from the standardized therapy protocols outlined and referral to a balance treatment center. Patients with low-to-moderate fall risk attributed to muscle weakness or fatigue should be prescribed lower extremity strengthening exercises, such as kitchen counter exercises, to improve strength and balance.

Primary Care Management of Plantar Fasciitis.

Plantar fasciitis (PF) is present in 10% of the population and is the most common cause of plantar heel pain. PF is painful, can alter daily activities and presents as a sharp pain localized to the plantar foot and medial heel. The underlying etiology involves microtrauma to the plantar fascia, specifically at its insertion point on the calcaneus. Successful management of plantar fasciitis is typically achieved with the conservative therapy approaches discussed.

Preventing falls with vitamin D.

Falls are the number one cause for injury-related morbidity and mortality in West Virginia's seniors. Multiple independent variables contribute to the risk of a fall: previous falls, alterations in balance and vision, impairments in gait and strength, and medications most highly correlate with the risk for a fall. Vitamin D supplementation is emerging as an easy, safe and well-tolerated fall reduction/prevention strategy due to the beneficial effects on the musculoskeletal system with improvements in strength, function and navigational abilities. From meta-analysis data, maximal fall reduction benefit in seniors is achieved when correcting vitamin D deficiency and when using adjunctive calcium supplementation. It is therefore recommended that practitioners in our state screen for fall risks and consider the addition of supplementation protocols that provide sufficient vitamin D and calcium to our seniors.

Smartphone medical applications useful for the rural practitioner.

Like other similarly situated rural states, West Virginia's patients and practitioners often experience access barriers to current medical expertise for multiple disciplines. This article was generated to help bridge this gap and highlights the best-rated mobile medical applications (Apps) for smartphone use. From finding drug interactions and dosing schedules to discussing patients in HIPAA-compliant formats, Apps are becoming integral to the practice of 21st Century medicine. The increased use of these Apps by physicians-in-training and established practitioners highlights the shift from reliance upon the medical library to the easy to use mobile-based technology platforms. This article provides our practitioners, physician extenders, medical trainees, and office staff a guide to access and assess the utility of some of the best rated medical and HIPAA compliant Apps.

Too smart to fail: guide for the struggling medical student.

Medicine is a vocation of perpetual independent learning; long-term success is critically dependent on finding the right resources and establishing effective study methods and test-taking strategies. Students who struggle with the academic transition in medical school have common risk factors and characteristics. We highlight key resources that are available for struggling medical students with an emphasis on West Virginia's HELP, ASPIRE, and STAT programs.

Antibiotic-like actions of vitamin D.

Vitamin D is a secosteroid hormone that has expanding importance for a healthy lifestyle and disease prevention. A multitude of studies have highlighted that vitamin D acts not only in bone and calcium homeostasis but is critically important for human immunity. The discovery that the storage form of vitamin D (25-hydroxyvitamin D3) can be locally converted to the active form (1,25-hydroxyvitamin D3) in immune cells, epithelial cells and numerous other non-renal tissues highlights the importance of maintaining sufficient stores. When responding to a specific external stimulus, like bacterial invasion, intracrine synthesis of active vitamin D has the ability to regulate gene expression providing a specific response and directing cellular actions. These responses include the generation of antimicrobial peptides with production of these peptides dependent on vitamin D status. Vitamin D deficiency is associated with an increased rate of infection. This paper highlights the antibiotic like actions of vitamin D and importance of vitamin D sufficiency.

Physical education in West Virginia schools: are we doing enough to generate peak bone mass and promote skeletal health?

Peak bone mass (PBM) is attained at 25-35 years of age, followed by a lifelong decline in bone strength. The most rapid increase in bone mass occurs between the ages of 12-17. Daily school physical education (PE) programs have been shown to produce measurable increases in PBM, but are not federally mandated. Increases in PBM can decrease the lifelong risk of osteoporosis and fractures; critical for West Virginia prevention programs. Nationally only 1 in 6 schools require PE three days per week, with 4% of elementary schools, 8% of middle schools and 2% of high schools providing daily PE. In 2005, West Virginia passed the Healthy Lifestyles Act that returned physical education to the K-12 curriculum. This law requires only one credit of PE from grades 9-12 and provides only 35% of the recommended PE for grades K-12. This article highlights the relationship of PE to PBM and discusses the potential impact on West Virginia skeletal health.

Extraskeletal effects of vitamin D: potential impact on WV disease morbidity and mortality.

Vitamin D is an essential nutrient and a secosteroid hormone that regulates many physiologic processes beyond calcium and bone homeostasis. These "extraskeletal" effects are impacted by the circulating levels of the storage form of vitamin D, 25-hydroxyvitamin D3. Levels of vitamin D can be detected after completing a simple 25(OH)D blood test. Vitamin D deficiency (< 30 ng/mL) is associated with a higher risk of many chronic diseases including, but not limited to, fourteen types of cancers, type 1 and 2 diabetes mellitus, obesity, cardiovascular disease, hypertension, stroke, and asthma. This article explores the association between vitamin D deficiency and the burden of chronic diseases in West Virginia.

Targeting the Gut Microbiome for Inflammation and Pain Management in Orthopedic Conditions.

The human gut microbiome can be altered with probiotics, prebiotics, synbiotics, and anti-inflammatory foods and spices as part of an evidence-based strategy that targets inflammation and pain in common orthopedic conditions. Implementing these strategies avoids adverse effects associated with nonsteroidal anti-inflammatory drugs and minimizes the potential for opioid use. This review focuses exclusively on human trials studying the effects of gut microbiome alterations to address pain and inflammatory markers in common orthopedic conditions: osteoarthritis, rheumatoid arthritis, fractures/osteoporosis, and bone pain associated with chemotherapy. Individualized supplementation strategies can be further explored with the information in this review. [Orthopedics. 2022;45(5):e226-e234.].

Defining bone health and fracture risk in West Virginia: the World Health Organization FRAX assessment tool.

This article highlights the expanding burden of osteoporosis in West Virginia. WV ranks second nationally in the percentage of its population that is > or = 65 years of age. Our older population increases the risk of osteoporosis and fracture; the most recent data indicates that 77% of our women age 50 and older have osteoporosis or low bone mass. The lifetime risk of osteoporotic related fracture is alarming and occurs in 50% of females and 25% of males age 50 and older. The risk of osteoporosis related hip fracture in women is equal to the combined risk of breast, uterine or ovarian cancer with the annual risk of osteoporotic fracture greater than the combined risk of breast cancer, stroke and heart attack. Detecting individuals at risk for fracture has been aided by an internationally validated fracture prediction tool from the World Health Organization -- FRAX. The FRAX tool can be incorporated into protocols to help minimize barriers to effective osteoporosis screening and treatment in WV.

A Soft Robotic Sleeve for Compression Therapy of the Lower Limb.

'We present the development of a soft robotic-inspired device for lower limb compression therapy with application in the treatment of lymphedema. This device integrates the control capabilities of pneumatic devices with the wearability and low cost of compression garments. The design consists of a three-layered soft robotic sleeve that ensures safe skin contact, controls compression, and secures the device to the patient limb. The expandable component is made of interconnected pockets of various heights, which passively create a graduated compression profile along the lower limb. The system is inflated by a pump and a microcontroller-actuated valve, with force sensors embedded in the sleeve that monitor the pressure applied to the limb. Testing on healthy individualsq demonstrated the ability to reach clinically relevant target pressures (30, 40, 50 mmHg) and establish a distal-to-proximal descending pressure gradient of approximately 40 mmHg. Device function was shown to be robust against variations in subject anatomy.Clinical Relevance- This system provides controllable, graduated, compression therapy to lymphedema patients in an economical, portable, and customizable package.

Human SUMO fusion systems enhance protein expression and solubility.

A major challenge associated with recombinant protein production in Escherichia coli is generation of large quantities of soluble, functional protein. Yeast SUMO (small ubiquitin-related modifier), has been shown to enhance heterologous protein expression and solubility as fusion tag, however, the effects of human SUMOs on protein expression have not been investigated. Here we describe the use of human SUMO1 and SUMO2 as a useful gene fusion technology. Human SUMO1 and SUMO2 fusion expression vectors were constructed and tested in His-tag and ubiquitin fusion expression systems. Two difficult-to-express model proteins, matrix metalloprotease-13 (MMP13) and enhanced green fluorescence protein (eGFP) were fused to the C-terminus of the human SUMO1 and SUMO2 expression vectors. These constructs were expressed in E. coli and evaluation of MMP13 and eGFP expression and solubility was conducted. We found that both SUMO1 and SUMO2 had the ability to enhance the solubility of MMP13 and eGFP, with the SUMO2 tag having a more significant effect. Since fusion tags produce varying quantities of soluble proteins, we assessed the effect of SUMO2 coupled with ubiquitin (Ub). SUMO2-ubiquitin and ubiquitin-SUMO2 fusion expression plasmids were constructed with eGFP as a passenger protein. Following expression in E. coli, both plasmids could improve eGFP expression and solubility similar to the SUMO2 fusion and better than the ubiquitin fusion. The sequential order of SUMO2 and ubiquitin had little effect on expression and solubility of eGFP. Purification of eGFP from the gene fusion product, SUMO2-ubiquitin-eGFP, involved cleavage by a deubiquitinase (Usp2-cc) and Ni-Sepharose column chromatography. The eGFP protein was purified to high homogeneity. In summary, human SUMO1 and SUMO2 are useful gene fusion technologies enhancing the expression, solubility and purification of model heterologous proteins.

Retrograde femoral nailing: computed tomography angiogram demonstrates no relative safe zone for prevention of small diameter arterial vascular injury during proximal anteroposterior interlocking.

BACKGROUND: Reported iatrogenic injury to the proximal femoral vascular structures is rare after retrograde femoral nailing. Previous cadaveric dissections have recommended placement of proximal interlocking screws above the level of the lesser trochanter. METHODS: This study is designed to define the arterial vascular anatomy anterior to the proximal medullary canal of the femur, which could be damaged with the placement of anteroposterior (AP) proximal interlocking screws. RESULTS: Computed tomography angiograms of the structures anterior to the proximal femur demonstrate the presence of arterial branches >2 mm diameter in 100% of study patients at or above the level of the lesser trochanter. CONCLUSIONS: No true safe zone corridor exists anteriorly for placement of AP interlocking screws in this region. Surgical technique modifications are suggested to minimize the potential risks of iatrogenic arterial injury during retrograde femoral nail AP proximal interlocking.