Podiatric conditions observed in Special Olympics athletes: Contrasting data from a USA versus an international population.

OBJECTIVES: Persons with intellectual disabilities frequently have podiatric conditions. Findings from the 2018 United States Summer games (USA) venues are compared to those from athletes screened at the 2019 Special Olympics World Summer Games in Abu Dhabi, United Arab Emirates (UAE). METHODS: Data from Fit Feet screenings from 2445 United Arab Emirates (UAE) participants were compared to 1244 US participants. RESULTS: A sampling of results that reflect significant differences in findings between the USA cohort and Abu Dhabi cohort include ankle joint range of motion, excessive abduction, hallux abducto valgus and pes planus. The overall shoe to foot mismatch was found to be 52.2%. A professional referral was recommended 27.7% of the time in the USA data and 28.5% in the Abu Dhabi data. An urgent referral was requested 5.1% of the time for the USA data and 3.7% of the time in the Abu Dhabi data. CONCLUSION: Special Olympics athletes experience a greater prevalence of identifiable podiatric conditions as compared to the general population. Several of the conditions investigated in this study differed significantly between the international Special Olympics cohort and the USA cohort. Assessment of the feet of Special Olympics athletes can help to better appreciate the podiatric conditions in a population of individuals with intellectual disabilities. The variance identified between populations of Special Olympics athletes may be a reflection on the lack of standardization of conditions that are assessed for as well as the disparate characteristics of the clinical volunteers. Future Fit Feet events may wish to consider significant improvements in objectivity and standardization as it pertains to the conditions that are evaluated for in the Fit Feet exam.

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.

Levonorgestrel release rates measured through analysis of two-rod contraceptive explants.

OBJECTIVE: The objective was to characterize and compare in vivo rates of levonorgestrel (LNG) release from Sino-implant (II) and Jadelle® contraceptive implants. STUDY DESIGN: We sampled 48 Sino-implant (II) and 49 Jadelle® explant sets for residual LNG content from participants treated for up to 51 months in a randomized contraceptive efficacy trial in the Dominican Republic (DR). Additional Sino-implant (II) explants were obtained from 8 women who became pregnant in the DR trial and 10 who contributed 3 to 5 years of use in a cohort study in China. Baseline LNG loads were estimated from five unused implant sets per device type. Release profiles were estimated using mixture models that captured initial burst fractions and compared with efficacy and pharmacokinetics data from the DR trial. RESULTS: Estimated baseline LNG loads for Sino-implant (II) and Jadelle® were 142.8 mg and 150.5 mg, respectively (vs. the labeled 150 mg). There was an initial burst release of drug (5.6% and 7.9%, respectively) followed by an exponential decrease in LNG content evident for each device. Release rates were significantly lower for Sino-implant (II) throughout the treatment period, with estimated rates after 3 years of 24.2 mcg/day and 29.0 mcg/day for Sino-implant (II) and Jadelle®, respectively. The estimated Sino-implant (II) rate after 3 years was similar to the predicted rate after 5 years (23.6 mcg/day) for Jadelle® (rate ratio: 1.03; 95% confidence interval: 0.92-1.13). CONCLUSIONS: Sino-implant (II) LNG release rates were significantly lower than Jadelle® with Sino-implant (II) rates through year 3 comparable to Jadelle® rates through year 5. These results reinforce the 3-year duration of action for which Sino-implant (II) was prequalified by the World Health Organization. IMPLICATIONS: This analysis confirms the WHO prequalification of Sino-implant (II) for 3 years of use and supports different durations of action for Jadelle® and Sino-implant (II). It provides additional evidence that this approach can complement efficacy trials in determining duration of action of hormonal contraceptives in general.

Hiking with DiabetesRisks and Benefits.

BACKGROUND: Exercise is highly beneficial for persons with diabetes. Similar to many other patients, those with diabetes may be reluctant to exercise given a lack of motivation and proper instruction regarding an exercise prescription. In general, medical providers are poorly equipped to develop an exercise prescription and furnish motivation. Attempts to find activities that not only provide effective aerobic challenges but also are enjoyable to participate in are fraught with difficulty. Hiking as a potential option for a safe and enjoyable activity is discussed, including the possible downsides. METHODS: Multiple publications were reviewed using key words. RESULTS: A review of the literature uncovered limited publications or controlled trials that discussed the use of hiking per se as an activity for the management of diabetes. Newer studies reviewing weightbearing exercise and diabetic polyneuropathy and those discussing the advantages of trekking poles for balance and proprioception are cited in support of the recommendation for hiking as an activity for those with diabetes. CONCLUSIONS: Exercise has been shown to substantially benefit individuals with diabetes, but convincing patients with diabetes to exercise is daunting. Hiking, unlike other, more tedious exercise programs, may be an exercise option that persons with diabetes might find enjoyable. Hiking may encourage balance training and reduced ground reaction forces. These benefits may be augmented by trekking poles, which may likewise counter the concerns of the uneven surfaces that present challenges to the hiker with diabetes.

Exercise and Diabetes: A Narrative Review.

Persons with diabetes might experience significant benefits through regular exercise. Not unlike the general population, those with diabetes could also lack motivation to participate in an exercise program. Often, those treating persons with diabetes lack training and/or interest in exercise prescription and are therefore unable to provide the needed information and encouragement. In many cases, reluctance to exercise could result from an inability to find an enjoyable exercise activity. Attempts to find activities that, not only provide effective aerobic challenges, but are also enjoyable to participate in are fraught with difficulty. Three electronic databases were searched in January 2017. Evidence for the merits of exercise for those with diabetes was robust. Numerous reports have addressed the degree of noncompliance to exercise recommendations and the barriers reported for this nonadherence. Additional studies concluded that most medical providers are deficient in formal training in the prescription of an exercise program. Newer studies are evaluating the effects of exercise and vitamin D supplementation and their interplay with diabetic peripheral neuropathy and ulceration. Exercise confers remarkable benefits to those with diabetes; however, the challenges to compelling patients with diabetes to exercise are formidable. An improved focus on exercise prescription and related motivation during provider training must be undertaken.

In vivo release of levonorgestrel from Sino-implant (II) ­ an innovative comparison of explant data.

OBJECTIVES: Measuring the amount of progestin remaining in contraceptive implants used for different lengths of time provides useful information on in vivo release kinetics including change over time. We compared estimated in vivo levonorgestrel (LNG) release rates derived from Sino-implant (II) explants with similar data from removed Jadelle. STUDY DESIGN: We measured LNG remaining in 44 sets of Sino-implant (II) used for up to 7 years and removed in four Chinese clinics. Results were compared with published data for Jadelle explants used for up to 36 months. We estimated and compared monthly and daily LNG release rates for the two products using prediction models for drug release. We also estimated the dissolution profile similarity factor, f2, for LNG release. RESULTS: Both Sino-implant (II) and Jadelle release approximately 30% of total LNG load after 3 years. Results of fitting the data to a biologically plausible modified Higuchi prediction model indicate comparable release through 3 years. An estimated similarity factor of 80.6 (90% confidence interval: 70.8-85.7) indicates similarity in the dissolution profiles of the two implants. CONCLUSIONS: LNG release in vivo measured through explant analysis suggest that Sino-implant (II) and Jadelle may perform similarly through 3 years of use and could remain highly effective beyond this time point. These results align with published data for Jadelle and Sino-implant (II) showing high effectiveness for 5 years. Ongoing clinical studies comparing the products over 5 years present an opportunity to verify this supportive measure of clinical effectiveness. IMPLICATIONS: This innovative approach provides evidence that Sino-implant (II) may perform clinically similarly to Jadelle over 3 years and remain a highly effective contraceptive beyond this time point. Data from explant analyses show promise for investigating the equivalence of elusion profiles of contraceptive implants.

The podiatrist as a member of the sports medicine team.

This article reviews the history of sports medicine highlighting the "jogging boom" of the 1970s and the advocacy of Dr George Sheehan, which boosted the position of podiatry in sports medicine. Significant events in mainstream sports medicine that promoted the rise of podiatric medicine are discussed. Reasons as to why podiatric medicine should be a member of the sports medicine team are outlined, and lastly, examples that highlight podiatric medicine as participants alongside other specialties in the evaluation and care of athletes are given.

Prevalence of podiatric conditions seen in Special Olympics athletes: a comparison of USA data to an international population.

BACKGROUND: Persons with intellectual disabilities frequently have podiatric conditions. Limited information exists on their prevalence in international cohorts of Special Olympics (SO) athletes. Findings from multiple United States (US) venues are compared to those from athletes screened at the 2011 Special Olympics World Summer Games in Athens, Greece (ATHENS). METHODS: Data from Fit Feet screenings from 2096 ATHENS participants was compared to 7192 US participants. RESULTS: Frequently noted in the ATHENS population were motion restriction in both the ankle and the first metatarsal phalangeal joint (1st MTPJ), pes planus, metatarsus adductus, brachymetatarsia, hallux abducto valgus (HAV), onychomycosis, onychocryptosis, and tinea pedis. ATHENS differed from the US cohort as HAV and restricted ankle joint and 1st MTPJ joint motion was less frequent. Significantly more tinea pedis, xerosis, and hyperhidrosis were present in the ATHENS population. DISCUSSION/CONCLUSION: SO athletes have a higher prevalence of podiatric structural conditions compared to the general population, and some vary between ATHENS versus US. Less prevalent in ATHENS was HAV, and restricted motion in both the ankle and 1st MTPJ. This may reflect differences due to varied clinical observers. The higher rates of several dermatological conditions in ATHENS may reflect venue seasonal climate, or social factors.

Novel neutralizing hedgehog antibody MEDI-5304 exhibits antitumor activity by inhibiting paracrine hedgehog signaling.

The hedgehog pathway has been implicated in the tumorigenesis, tumor progression, and metastasis of numerous human cancers. We generated the first fully human hedgehog antibody MEDI-5304 and characterized its antitumor activity and preclinical toxicology. MEDI-5304 bound sonic hedgehog (SHH) and Indian hedgehog (IHH) with low picomolar affinity and neutralized SHH and IHH activity in cellular mGLI1 reporter assays. The antibody inhibited transcription of hedgehog target genes and osteoblast differentiation of C3H10T1/2 cells. We evaluated the activity of MEDI-5304 in vivo in model systems that allowed us to evaluate two primary hypotheses of hedgehog function in human cancer, paracrine signaling between tumor and stromal cells and cancer stem cell (CSC) self-renewal. MEDI-5304 displayed robust pharmacodynamic effects in stromal cells that translated to antitumor efficacy as a single agent in an HT-29/MEF coimplantation model of paracrine hedgehog signaling. MEDI-5304 also improved responses to carboplatin in the HT-29/MEF model. The antibody, however, had no effect as a single agent or in combination with gemcitabine on the CSC frequency or growth of several primary pancreatic cancer explant models. These findings support the conclusion that hedgehog contributes to tumor biology via paracrine tumor-stromal signaling but not via CSC maintenance or propagation. Finally, the only safety study finding associated with MEDI-5304 was ondontodysplasia in rats. Thus, MEDI-5304 represents a potent dual hedgehog inhibitor suitable for continued development to evaluate efficacy and safety in human patients with tumors harboring elevated levels of SHH or IHH.

Potent reversible inhibition of myeloperoxidase by aromatic hydroxamates.

The neutrophil enzyme myeloperoxidase (MPO) promotes oxidative stress in numerous inflammatory pathologies by producing hypohalous acids. Its inadvertent activity is a prime target for pharmacological control. Previously, salicylhydroxamic acid was reported to be a weak reversible inhibitor of MPO. We aimed to identify related hydroxamates that are good inhibitors of the enzyme. We report on three hydroxamates as the first potent reversible inhibitors of MPO. The chlorination activity of purified MPO was inhibited by 50% by a 5 nm concentration of a trifluoromethyl-substituted aromatic hydroxamate, HX1. The hydroxamates were specific for MPO in neutrophils and more potent toward MPO compared with a broad range of redox enzymes and alternative targets. Surface plasmon resonance measurements showed that the strength of binding of hydroxamates to MPO correlated with the degree of enzyme inhibition. The crystal structure of MPO-HX1 revealed that the inhibitor was bound within the active site cavity above the heme and blocked the substrate channel. HX1 was a mixed-type inhibitor of the halogenation activity of MPO with respect to both hydrogen peroxide and halide. Spectral analyses demonstrated that hydroxamates can act variably as substrates for MPO and convert the enzyme to a nitrosyl ferrous intermediate. This property was unrelated to their ability to inhibit MPO. We propose that aromatic hydroxamates bind tightly to the active site of MPO and prevent it from producing hypohalous acids. This mode of reversible inhibition has potential for blocking the activity of MPO and limiting oxidative stress during inflammation.

Development and validation of a 'universal' HPLC method for pyrethroid quantification in long-lasting insecticidal mosquito nets for malaria control and prevention.

OBJECTIVES: To outline the development and validation of a universal method for quantifying deltamethrin, permethrin and alpha-cypermethrin levels in a variety of long-lasting insecticidal mosquito nets. METHODS: Using the HPLC conditions found in the CIPAC method for deltamethrin quantification, the method is based on a simple extraction technique for sample preparation (heating in isooctane at approximately 100 °C for 15 min). The method was validated for linearity, specificity, accuracy, precision, insecticide stability to extraction conditions and required extraction time for insecticide removal. RESULTS: The method was found valid for insecticide quantifications for various types of nets, namely for deltamethrin coated on polyester nets, deltamethrin incorporated into polyethylene nets, permethrin incorporated into polyethylene nets, alpha-cypermethrin coated on polyester nets and alpha-cypermethrin incorporated into polyethylene nets. CONCLUSIONS: This method will provide a more simplified approach to testing a variety of nets (different types of fibre) containing deltamethrin, permethrin or alpha-cypermethrin.

MEDI0639: a novel therapeutic antibody targeting Dll4 modulates endothelial cell function and angiogenesis in vivo.

The Notch signaling pathway has been implicated in cell fate determination and differentiation in many tissues. Accumulating evidence points toward a pivotal role in blood vessel formation, and the importance of the Delta-like ligand (Dll) 4-Notch1 ligand-receptor interaction has been shown in both physiological and tumor angiogenesis. Disruption of this interaction leads to a reduction in tumor growth as a result of an increase in nonfunctional vasculature leading to poor perfusion of the tumor. MEDI0639 is an investigational human therapeutic antibody that targets Dll4 to inhibit the interaction between Dll4 and Notch1. The antibody cross-reacts to cynomolgus monkey but not mouse species orthologues. In vitro MEDI0639 inhibits the binding of Notch1 to Dll4, interacting via a novel epitope that has not been previously described. Binding to this epitope translates into MEDI0639 reversing Notch1-mediated suppression of human umbilical vein endothelial cell growth in vitro. MEDI0639 administration resulted in stimulation of tubule formation in a three-dimensional (3D) endothelial cell outgrowth assay, a phenotype driven by disruption of the Dll4-Notch signaling axis. In contrast, in a two-dimensional endothelial cell-fibroblast coculture model, MEDI0639 is a potent inhibitor of tubule formation. In vivo, MEDI0639 shows activity in a human endothelial cell angiogenesis assay promoting human vessel formation and reducing the number of vessels with smooth muscle actin-positive mural cells coverage. Collectively, the data show that MEDI0639 is a potent modulator of Dll4-Notch signaling pathway.

Foot-to-shoe mismatch and rates of referral in Special Olympics athletes.

BACKGROUND: Improperly fitted shoes are frequently seen in athletes participating in Special Olympics competitions. This foot-to-shoe mismatch may result in deformities as well as discomfort and reduced performance or injuries in competitions. A primary purpose for providing medical screenings is to identify conditions unknown and to promptly refer to an appropriate provider for evaluation and care. This study attempts to determine the prevalence of improperly fitted shoes and the rate of referral for Special Olympics athletes screened at Fit Feet venues. METHODS: To evaluate the foot-to-shoe mismatch and rate of referral, 4,094 Fit Feet screenings of Special Olympics athletes participating in US competitions in 2005 to 2009 were analyzed. The participants were 58.5% male and 41.5% female, with a median age of 25.6 years. A power analysis and the χ(2) test were used. The athletes voluntarily underwent a foot screening that followed the standardized Special Olympics Fit Feet protocol. The Brannock Device for measuring feet was used to assess proper fit. RESULTS: A proper fit was found in 58.56% of the athletes, with 28.60% wearing shoes too big and 12.84% wearing shoes too small. Unrelated to shoe fit, 20% of the athletes required referrals for professional follow-up based on abnormal clinical findings. CONCLUSIONS: There is a significant (41.44%) mismatch of foot to shoe in Special Olympics athletes. The most common mismatch is a shoe too big, with a much smaller number of athletes having shoes too small. Awareness of this foot-to-shoe incompatibility may be useful for the development of shoes better designed for athletes with a foot structure not consistent with conventional shoes. Because 20% of the athletes required a referral for professional follow-up, Fit Feet examinations are important for identifying athletes with conditions that can be more readily evaluated and treated, thus improving the athletes' comfort and performance. Beyond knowing the rate of referral, future studies can determine the conditions or findings that necessitate a referral and the ultimate outcome of that referral.

Barefoot running claims and controversies: a review of the literature.

BACKGROUND: Barefoot running is slowly gaining a dedicated following. Proponents of barefoot running claim many benefits, such as improved performance and reduced injuries, whereas detractors warn of the imminent risks involved. METHODS: Multiple publications were reviewed using key words. RESULTS: A review of the literature uncovered many studies that have looked at the barefoot condition and found notable differences in gait and other parameters. These findings, along with much anecdotal information, can lead one to extrapolate that barefoot runners should have fewer injuries, better performance, or both. Several athletic shoe companies have designed running shoes that attempt to mimic the barefoot condition and, thus, garner the purported benefits of barefoot running. CONCLUSIONS: Although there is no evidence that either confirms or refutes improved performance and reduced injuries in barefoot runners, many of the claimed disadvantages to barefoot running are not supported by the literature. Nonetheless, it seems that barefoot running may be an acceptable training method for athletes and coaches who understand and can minimize the risks.

Prevalence of podiatric conditions seen in Special Olympics athletes: Structural, biomechanical and dermatological findings.

BACKGROUND: Podiatric conditions are frequently seen in persons with intellectual disabilities. Unfortunately, many are not detected or addressed. This study attempts to determine the prevalence of a variety of selected podiatric conditions in Special Olympics athletes and compare the findings to studies of a similarly matched general population. METHODS: Screenings from 1580 Special Olympics athletes participating in a sampling of United States competitions in 2004-2006 were used for the analysis. The athletes voluntarily underwent a foot screening which followed the standardized Special Olympics Fit Feet protocol. RESULTS: The most commonly identified conditions included overpronated gait, abducted gait, restriction in both the ankle and the first metatarsal phalangeal joint, pes planus, metatarsus adductus, brachymetatarsia, hallux abducto valgus, onychomycosis, onychocryptosis and tinea pedis. DISCUSSION/CONCLUSION: The prevalence of all the structural conditions was notably higher than a similarly matched general population and both conditions and biomechanical/gait findings associated with ligamentous laxity like pes planus and hallux abducto valgus had especially high prevalence rates. Restricted motion in the ankle and first metatarsal phalangeal joint was surprising and may indicate some athletes have intellectual disabilities with contractures. The higher rates of dermatophyte related conditions may reflect increased exposure from the athletic competition environment, immunocompromise, issues with hygiene or both. Higher rates of onychocryptosis in the athletes may be due to ill fitting shoes and/or hygiene issues.

Reduced community access to a key contraceptive: public health consequence from false suspicion of HIV-contaminated injectables.

BACKGROUND: This study was conducted to investigate a report of positive test results with DMPA on an HIV rapid test. Suspecting HIV contamination, the Zambian Ministry of Health initiated a product withdrawal pending full evaluation. STUDY DESIGN: DMPA was evaluated for compliance to product specifications. Contamination with HIV and blood components was investigated with PCR and human IgG ELISA. The performance of Genie II, Unigold and Determine HIV rapid tests was evaluated using DMPA. RESULTS: DMPA was found compliant with product specifications and negative for HIV and human IgG. DMPA impaired the performance of HIV rapid tests resulting in false-positive/indeterminant results. Rapid test results using polysorbate 80 (formulation component of DMPA) mimicked results obtained with DMPA. CONCLUSIONS: The DMPA sample was negative for HIV and human IgG. Formulation components may have led to the interpretation of false-positive results, reinforcing the need to validate the sample type used in any test. DMPA use was reinstated in Zambia, minimizing the public health impact that resulted from the initial rapid test results.

Regulation of calcitonin gene-related peptide release from rat trigeminal nucleus caudalis slices in vitro.

Calcitonin gene-related peptide (CGRP) released from trigeminal primary afferents has been implicated in the pathophysiology of migraine. Here, we have used an in vitro slice preparation to investigate its release from nerve terminals in the rat trigeminal nucleus caudalis. Extracellular-calcium dependent CGRP release was stimulated by both capsaicin and neuronal depolarization with KCl. The capsaicin (1 microM)-evoked CGRP release was blocked by capsazepine and was also attenuated in the presence of the cyclooxygenase inhibitor, indomethacin, an effect that was reversed when slices were stimulated with capsaicin in the presence of the cyclooxygenase metabolite, prostaglandin E(2). Taken together, these data further highlight the importance of prostaglandins as enhancers of neuropeptide release and suggest that CGRP released from the central terminals of trigeminal neurones has the potential to be involved in the transmission of nociceptive information of relevance to migraine headache.

Characterization of bradykinin-induced prostaglandin E2 release from cultured rat trigeminal ganglion neurones.

Bradykinin and prostaglandins are both local mediators strongly implicated in pain and inflammation. Here, we have investigated the effects of bradykinin on the release of prostaglandin E(2) from cultured neurones derived from adult rat trigeminal ganglia. Bradykinin was a potent inducer of prostaglandin E(2) release, an effect that was likely mediated by bradykinin B(2) receptors, as the bradykinin-induced prostaglandin E(2) release was attenuated by the bradykinin B(2) receptor-selective antagonist, arginyl-L-prolyl-trans-4-hydroxy-L-prolylglycyl-3-(2-thienyl)-L-alanyl-L-seryl-D-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-L-(2 alpha, 3 beta, 7a beta)-octahydro-1H-indole-2-carbonyl-L-arginine (HOE 140), but not by the bradykinin B(1) receptor-selective antagonist, des-Arg(9),[Leu(8)]-bradykinin. Furthermore, bradykinin-induced prostaglandin E(2) release was inhibited following treatment with the phospholipase A(2) inhibitor, arachidonyltrifluoromethyl ketone (AACOCF(3)), the nonselective cyclooxygenase inhibitor, piroxicam, the mitogen-activated protein kinase kinase-1 (MEK1) inhibitor, 2'-amino-3'-methoxyflavone (PD98059), and the protein kinase C inhibitor, bisindolylmaleimide XI (Ro320432). Taken together, these data suggest that bradykinin, acting via bradykinin B(2) receptors, induces prostaglandin E(2) release from trigeminal neurones through the protein kinase C and mitogen-activated protein kinase-dependent activation of phospholipase A(2) and consequent stimulation of cyclooxygenases.