A regulatory pathway model of neuropsychological disruption in Havana syndrome.

Introduction: In 2016 diplomatic personnel serving in Havana, Cuba, began reporting audible sensory phenomena paired with onset of complex and persistent neurological symptoms consistent with brain injury. The etiology of these Anomalous Health Incidents (AHI) and subsequent symptoms remains unknown. This report investigates putative exposure-symptom pathology by assembling a network model of published bio-behavioral pathways and assessing how dysregulation of such pathways might explain loss of function in these subjects using data available in the published literature. Given similarities in presentation with mild traumatic brain injury (mTBI), we used the latter as a clinically relevant means of evaluating if the neuropsychological profiles observed in Havana Syndrome Havana Syndrome might be explained at least in part by a dysregulation of neurotransmission, neuro-inflammation, or both. Method: Automated text-mining of >9,000 publications produced a network consisting of 273 documented regulatory interactions linking 29 neuro-chemical markers with 9 neuropsychological constructs from the Brief Mood Survey, PTSD Checklist, and the Frontal Systems Behavior Scale. Analysis of information flow through this network produced a set of regulatory rules reconciling to within a 6% departure known mechanistic pathways with neuropsychological profiles in N = 6 subjects. Results: Predicted expression of neuro-chemical markers that jointly satisfy documented pathways and observed symptom profiles display characteristically elevated IL-1B, IL-10, NGF, and norepinephrine levels in the context of depressed BDNF, GDNF, IGF1, and glutamate expression (FDR < 5%). Elevations in CRH and IL-6 were also predicted unanimously across all subjects. Furthermore, simulations of neurological regulatory dynamics reveal subjects do not appear to be "locked in" persistent illness but rather appear to be engaged in a slow recovery trajectory. Discussion: This computational analysis of measured neuropsychological symptoms in Havana-based diplomats proposes that these AHI symptoms may be supported in part by disruption of known neuroimmune and neurotransmission regulatory mechanisms also associated with mTBI.

Assessing the Effects of Pulsed Electromagnetic Therapy on Painful Diabetic Distal Symmetric Peripheral Neuropathy: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Significant complications of diabetes include pain and the loss of sensation in peripheral limbs. Pain management of diabetic symmetric peripheral neuropathy (DSPN) remains challenging. This study reports on utilizing pulsed electromagnetic field therapy (PEMF) to reduce pain and improve skin perfusion pressure (SPP) in subjects with DSPN. METHODS: A randomized, sham-controlled, double-blind, clinical trial was conducted on subjects afflicted with foot pain associated with DSPN. Following informed consent, 182 subjects with diabetes and confirmed DSPN were entered into the trial for a period of 18 weeks. Subjects were randomized into active PEMF treatment or nonactive sham and instructed to treat to their feet for 30 minutes, twice daily and report daily pain scores. Some patients in the active arm experienced a transient low field strength notification (LFSN) due to improper pad placement during treatment. Skin perfusion pressure measurements were also collected at two and seven weeks to assess peripheral arterial disease effects via measurement of local microcirculatory flow and blood pressure. RESULTS: Patients in the active arm who did not receive an LFSN experienced a clinically significant 30% reduction in pain from baseline compared to sham (P < .05). Though not statistically significant, SPP in the active group trended toward improvement compared to sham. CONCLUSIONS: Pulsed electromagnetic field therapy appears effective as a nonpharmacological means for reduction of pain associated with diabetic peripheral neuropathy and holds promise for improvement of vascular physiology in microcirculatory dysfunction associated with diabetic peripheral arterial disease.

Recent Progress in Electrochemical Upgrading of Bio-Oil Model Compounds and Bio-Oils to Renewable Fuels and Platform Chemicals.

Sustainable production of renewable carbon-based fuels and chemicals remains a necessary but immense challenge in the fight against climate change. Bio-oil derived from lignocellulosic biomass requires energy-intense upgrading to produce usable fuels or chemicals. Traditional upgrading methods such as hydrodeoxygenation (HDO) require high temperatures (200−400 °C) and 200 bar of external hydrogen. Electrochemical hydrogenation (ECH), on the other hand, operates at low temperatures (<80 °C), ambient pressure, and does not require an external hydrogen source. These environmental and economically favorable conditions make ECH a promising alternative to conventional thermochemical upgrading processes. ECH combines renewable electricity with biomass conversion and harnesses intermediately generated electricity to produce drop-in biofuels. This review aims to summarize recent studies on bio-oil upgrading using ECH focusing on the development of novel catalytic materials and factors impacting ECH efficiency and products. Here, electrode design, reaction temperature, applied overpotential, and electrolytes are analyzed for their impacts on overall ECH performance. We find that through careful reaction optimization and electrode design, ECH reactions can be tailored to be efficient and selective for the production of renewable fuels and chemicals. Preliminary economic and environmental assessments have shown that ECH can be viable alternative to convention upgrading technologies with the potential to reduce CO2 emissions by 3 times compared to thermochemical upgrading. While the field of electrochemical upgrading of bio-oil has additional challenges before commercialization, this review finds ECH a promising avenue to produce renewable carbon-based drop-in biofuels. Finally, based on the analyses presented in this review, directions for future research areas and optimization are suggested.

Rock-Climbing Shoes: A Survey of Attitudes and Practices.

BACKGROUND: There is a paucity of literature regarding rock climbing footwear. Rock climbers anecdotally voice numerous complaints regarding their current footwear. In an effort to improve existing rock-climbing footwear, implementation of a survey tool assessing the attitudes and practices of rock climbers was undertaken. METHODS: A Web-based survey was developed to assess the demographics, attitudes, and practices of individuals active in rock climbing, with a focus on footwear. RESULTS: Forty-five of the 417 respondents were male and 55% were female. The average years climbing was 7, with a majority of respondents in the 18- to 34-year-old category. The majority climbed 5 to 10 hours/week. Eighty percent identified as intermediate or advanced climbers. Climbing shoes were an average of 0.83 size smaller than the climber's street shoes. The more elite the climber, the greater the mismatch. Overall satisfaction with current rock-climbing shoes was 88%; however, as the age of climber and number of years of participation increased, the level of satisfaction decreased. The most frequently reported problems with shoes included inconsistent sizing between brands and poor heel fit. The most commonly reported locations of pain were the toes and heel. CONCLUSIONS: The authors concluded the following: 1) a surprisingly high satisfaction with current rock-climbing shoes was reported; 2) the difference in size between climbing shoes and street shoes was less than expected; 3) more shoe fitting problems were experienced by those with the most experience in climbing and those who spend the most time climbing; 4) the most common locations for experiencing pain were the toes and the posterior heel or Achilles tendon; 5) higher than expected satisfaction levels with climbing shoes contrasted with the very high number of specific complaints and recommendations for improvement; and 6) because of the increasing popularity of rock climbing, foot care providers should learn about the various types of climbing and the shoe gear needs that result therefrom.

Remote Temperature Monitoring of the Diabetic Foot: From Research to Practice.

INTRODUCTION: Diabetic foot ulcers (DFUs) are devastating, common, and costly. The mortality of veterans following a DFU is sobering with ulceration recognized as a significant marker of disease severity. Given the dramatic impact of diabetic foot complications to the veteran and the US health care system, the US Department of Veterans Affairs (VA) has long recognized the importance of preventive care for those at risk. Telemedicine has been suggested as a modality to reach veterans at high risk of chronic wound formation. OBSERVATIONS: The purpose of this review is to: (1) present the evidence supporting once-daily remote temperature monitoring (RTM), a telemedicine approach critical to improving both veteran access to care and diabetic foot outcomes; (2) summarize a 2017 study published by VA providers who have advanced clinical understanding of RTM; (3) present previously unpublished data from this study comparing high-risk VA and non-VA cohorts, highlighting the opportunity for additional focus on DFU prevention within the VA; and (4) report on recent VA use of a RTM technology based on this research, emphasizing lessons learned and best practices. CONCLUSIONS: There is a significant opportunity to shift diabetic foot care from treatment to prevention, improving veteran outcomes and reducing resource utilization. RTM is an evidence-based, recommended, but underused telemedicine solution that can catalyze this needed paradigm shift.

Use of a Remote Temperature Monitoring Mat for the Early Identification of Foot Ulcers.

INTRODUCTION: Diabetic foot ulcers (DFUs) are responsible for considerable morbidity, mortality, and cost. Remote temperature monitoring (RTM) is an evidenced-based and recommended component of standard foot care for at-risk patients. Although previous research has demonstrated the value of RTM for foot ulcer prevention, its benefits related to the early identification of diabetic foot complications may be underappreciated. OBJECTIVE: This article presents a case series supporting the use of RTM for early identification of DFUs. MATERIALS AND METHODS: The cases of 4 veteran patients who presented consecutively with inflammation, which was detected by a telemedicine temperature monitoring mat, are reported. The authors collected subjective history from each patient via telephone outreach and triaged these patients according to standard diabetic foot care recommendations. RESULTS: Each patient required a clinical exam prompted by the mat and the patient's subjective history. In each case, the patient required callus debridement upon which a pre-ulcerative lesion or partial-thickness wound was discovered. The DFUs in these 4 cases healed quickly and without complication. In 2 of the cases, the outreach prompted by the mat reestablished specialist foot care after a prolonged period without routine exam. CONCLUSIONS: In each of these cases, the RTM mat detected inflammation accompanying a preulcerative lesion or a partial-thickness wound, allowing for timely intervention and treatment, including debridement and offloading, which may have the potential to improve care and reduce morbidity, mortality, and costs.

It's Not Your Father's Podiatry School Advances in Podiatric Medical Education.

This paper discusses the innovative changes in podiatric medical education found in today's schools and colleges of podiatric medicine, including changes in philosophy, resources and technology, curriculum, delivery methods, the role of faculty, and assessment tools, and the changing expectations of the students themselves. There is an emphasis on the shift from a teacher-centered approach to professional education to a student-centered approach. Technological advances have had a tremendous impact on the educational process and have opened doors to many new forms of educational delivery that better meet the needs of today's students. We believe that the podiatric medical education of today is the equivalent of allopathic and osteopathic education in quality and depth. The future holds the promise of many more exciting changes to come.

Interprofessional podiatric surgical simulation a pilot study.

BACKGROUND: Interprofessional collaboration is key to quality outcomes in the health-care systems of today. Simulation is a common tool in podiatric medical education, and interprofessional education has become more common in podiatric medicine programs. Interprofessional simulation is the blending of these educational strategies. METHODS: A quantitative design was used to determine the impact of an isolated interprofessional podiatric surgical simulation between nurse anesthesia and podiatric medical students. RESULTS: Statistically significant differences were observed among participants between preintervention and postintervention surveys using the revised Interdisciplinary Education Perception Scale. CONCLUSIONS: Interprofessional simulation can be an effective educational opportunity for podiatric medical and nurse anesthesia students.

Interrater and intrarater reliability in the measurement of ankle joint dorsiflexion is independent of examiner experience and technique used.

BACKGROUND: Goniometric measurement is currently being used as a diagnostic and outcomes assessment tool for ankle joint dorsiflexion. Despite its common use, its interrater and intrarater reliability has been questioned. METHODS: This is a prospective study examining whether the experience of the examiner or the technique used affects the interrater and intrarater reliability for measuring ankle joint dorsiflexion. Fourteen asymptomatic individuals (8 male and 6 female) with a mean age of 28.2 years (range, 23-52) were enrolled into this study. The years of clinical experience of the five examiners averaged 10.4 years (range, 0-26). Four examiners used a modified Root, Weed and Orien method of measuring ankle joint dorsiflexion. The fifth examiner utilized a nonstandardized technique. A standard goniometer was used for bilateral measurements of ankle joint dorsiflexion with the knee extended and flexed. All five examiners repeated each measurement three times during each of the three sessions, with each session spaced at least 1 week apart. RESULTS: The interclass correlation coefficient reveals a moderate intrarater and poor interrater reliability in ankle joint dorsiflexion measurements using a standard goniometer. More importantly, further analysis indicates that the use of a standardized technique for measurement of ankle joint dorsiflexion or years of clinical experience does not increase the intrarater or interrater reliability. CONCLUSIONS: The utility of the goniometric measurement of ankle joint dorsiflexion may be limited.

Ciclopirox 8% nail lacquer topical solution for the treatment of onychomycosis in patients with diabetes: a multicenter, open-label study.

BACKGROUND: An open-label, noncomparative study was conducted to assess the safety and efficacy of ciclopirox 8% nail lacquer topical solution in patients with type 2 diabetes mellitus. METHODS: Forty-nine diabetic patients with distal subungual onychomycosis were treated once daily for 48 weeks with ciclopirox 8% nail lacquer, a topical nail solution approved for the treatment of patients with mild-to-moderate onychomycosis. RESULTS: Treatment resulted in clinical improvement in 63.4% of patients. Most patients (85.7%) had a mycologic outcome of improvement or cure, with 54.3% attaining mycologic cure. Consideration of mycologic and clinical outcomes generated a treatment outcome of improvement, success, or cure in 84.4% of patients. Moreover, patients experienced improvement in the diseased area of the nail (63.4%), nail surface (56.1%), nail color (48.8%), and nail thickness (65.9%). Ciclopirox 8% nail lacquer was safe, with treatment-related adverse events limited to infection in one patient, which resolved in 15 days; the patient completed the study. No treatment-related serious adverse events were observed. CONCLUSION: Ciclopirox 8% nail lacquer is a safe and effective treatment for distal subungual onychomycosis in patients with type 2 diabetes mellitus receiving insulin or oral hypoglycemic therapy.

Retrospective analysis of negative pressure wound therapy in open foot wounds with significant soft tissue defects.

OBJECTIVE: To compare treatment outcomes of open foot wounds with significant soft tissue defects using either negative pressure wound therapy (NPWT) or standard wet-to-moist saline-soaked gauze dressings. SUBJECTS: : Forty-seven subjects with open wounds with significant soft tissue defects. DESIGN: A retrospective analysis of sequentially selected records of patients treated with NPWT or standard wet-to-moist dressings. RESULTS: Risk of complications, subsequent foot surgeries, and hospital readmissions (secondary outcomes) were all reduced by 70% or more for the patients treated with NPWT. Length of stay during readmissions tended to be shorter; rates of wound cavity filling and wound healing (primary outcomes) tended to be greater with NPWT, although the differences were not statistically significant. CONCLUSION: Patients included in the study treated with NPWT had fewer foot-related complications, less additional foot surgery, and fewer readmissions for the study foot than did patients treated with standard therapy. Further research using randomized clinical trials is needed to confirm the findings of the current study's data. CLINICAL RELEVANCE: Wound cavity filling time and time to complete closure were similar in both study groups, despite the fact that patients receiving NPWT were older, had larger wounds, and had poorer nutrition. NPWT may be an effective modality for the healing of open wounds with significant defects and for reducing subsequent care.

Insulin-degrading activity in wound fluid.

Patients with diabetes are at great risk of developing lower extremity ulcers. The management of diabetic foot ulcers typically includes early recognition and appropriate clinical care. Recent advances in wound treatment include topical growth factor therapy, which has been successful in diabetic wounds. Growth factors are decreased in wound fluid; this may be due to decreased supply, increased binding, or increased degradation of the naturally occurring growth factors. This study investigates the activity of the insulin-degrading enzyme in wound fluid. Wound fluid was obtained from patients with (n = 17) and without (n = 4) diabetes. Insulin degradation was assayed by incubating [(125)I]insulin with wound fluid and precipitation in trichloroacetic acid. Fluid from nondiabetics degraded 2.22 +/- 0.73%, whereas diabetic fluid degraded significantly more (6.13 +/- 1.48%; P < 0.05). In patients with diabetes, the degradation of insulin by wound fluid correlated with glucose control (hemoglobin A(1c); r(2) = 0.5353; P < 0.001), and patients with worse outcomes (i.e. amputation) had higher wound fluid insulin degradation. The biochemical characteristics of insulin degradation in the wound fluid were consistent with the characteristics of insulin-degrading enzyme. These data suggest that glucose control is a critical factor in wound healing, but a reduction in the insulin-degrading activity in the wound fluid is also a potential therapeutic target.

Static magnetic field therapy for symptomatic diabetic neuropathy: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To determine if constant wearing of multipolar, static magnetic (450G) shoe insoles can reduce neuropathic pain and quality of life (QOL) scores in symptomatic diabetic peripheral neuropathy (DPN). DESIGN: Randomized, placebo-control, parallel study. SETTING: Forty-eight centers in 27 states. PARTICIPANTS: Three hundred seventy-five subjects with DPN stage II or III were randomly assigned to wear constantly magnetized insoles for 4 months; the placebo group wore similar, unmagnetized device. INTERVENTION: Nerve conduction and/or quantified sensory testing were performed serially. MAIN OUTCOME MEASURES: Daily visual analog scale scores for numbness or tingling and burning and QOL issues were tabulated over 4 months. Secondary measures included nerve conduction changes, role of placebo, and safety issues. Analysis of variance (ANOVA), analysis of covariance (ANCOVA), and chi-square analysis were performed. RESULTS: There were statistically significant reductions during the third and fourth months in burning (mean change for magnet treatment, -12%; for sham, -3%; P<.05, ANCOVA), numbness and tingling (magnet, -10%; sham, +1%; P<.05, ANCOVA), and exercise-induced foot pain (magnet, -12%; sham, -4%; P<.05, ANCOVA). For a subset of patients with baseline severe pain, statistically significant reductions occurred from baseline through the fourth month in numbness and tingling (magnet, -32%; sham, -14%; P<.01, ANOVA) and foot pain (magnet, -41%; sham, -21%; P<.01, ANOVA). CONCLUSIONS: Static magnetic fields can penetrate up to 20mm and appear to target the ectopic firing nociceptors in the epidermis and dermis. Analgesic benefits were achieved over time.

Critiquing clinical research of new technologies for diabetic foot wound management.

Healing the diabetic foot ulcer has been a challenge. Over the past 20 years, researchers have gained significant knowledge about the biochemical mechanisms that underlie the process of wound repair. A literature review of the latest advanced technologies, devices, and therapies is provided. In addition, clinical decision-making insights for clinicians to evaluate research and to assist in choosing the correct modality for each of their diabetic foot ulcer patients are discussed.