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Vertebrate limbs start to develop as paired protrusions from the lateral plate mesoderm at specific locations of the body with forelimb buds developing anteriorly and hindlimb buds posteriorly. During the initiation process, limb progenitor cells maintain active proliferation to form protrusions and start to express Fgf10 , which triggers molecular processes for outgrowth and patterning. Although both processes occur in both types of limbs, forelimbs (Tbx5), and hindlimbs (Isl1) utilize distinct transcriptional systems to trigger their development. Here, we report that Sall1 and Sall4 , zinc finger transcription factor genes, regulate hindlimb initiation in mouse embryos. Compared to the 100% frequency loss of hindlimb buds in TCre; Isl1 conditional knockouts, Hoxb6Cre; Isl1 conditional knockout causes a hypomorphic phenotype with only approximately 5% of mutants lacking the hindlimb. Our previous study of SALL4 ChIP-seq showed SALL4 enrichment in an Isl1 enhancer, suggesting that SALL4 acts upstream of Isl1. Removing 1 allele of Sall4 from the hypomorphic Hoxb6Cre; Isl1 mutant background caused loss of hindlimbs, but removing both alleles caused an even higher frequency of loss of hindlimbs, suggesting a genetic interaction between Sall4 and Isl1. Furthermore, TCre -mediated conditional double knockouts of Sall1 and Sall4 displayed a loss of expression of hindlimb progenitor markers (Isl1, Pitx1, Tbx4) and failed to develop hindlimbs, demonstrating functional redundancy between Sall1 and Sall4. Our data provides genetic evidence that Sall1 and Sall4 act as master regulators of hindlimb initiation. [ABSTRACT FROM AUTHOR]

The fibrillinopathies represent a group of diseases in which the 10–12 nm extracellular microfibrils are disrupted by genetic variants in one of the genes encoding fibrillin molecules, large glycoproteins of the extracellular matrix. The best-known fibrillinopathy is Marfan syndrome, an autosomal dominant condition affecting the cardiovascular, ocular, skeletal, and other systems, with a prevalence of around 1 in 3,000 across all ethnic groups. It is caused by variants of the FBN1 gene, encoding fibrillin-1, which interacts with elastin to provide strength and elasticity to connective tissues. A number of mouse models have been created in an attempt to replicate the human phenotype, although all have limitations. There are also natural bovine models and engineered models in pig and rabbit. Variants in FBN2 encoding fibrillin-2 cause congenital contractural arachnodactyly and mouse models for this condition have also been produced. In most animals, including birds, reptiles, and amphibians, there is a third fibrillin, fibrillin-3 (FBN3 gene) for which the creation of models has been difficult as the gene is degenerate and nonfunctional in mice and rats. Other eukaryotes such as the nematode C. elegans and zebrafish D. rerio have a gene with some homology to fibrillins and models have been used to discover more about the function of this family of proteins. This review looks at the phenotype, inheritance, and relevance of the various animal models for the different fibrillinopathies. [ABSTRACT FROM AUTHOR]

Objective The objective of this scoping review was to characterize and identify knowledge gaps about the changes in skeletal muscle fiber type proportion and cross-sectional area (CSA) after stroke. Methods This scoping review followed previously proposed frameworks. A systematic search was conducted for articles examining muscle fiber type proportion and CSA in individuals with stroke in EMBASE, MEDLINE, PsycINFO, CINAHL, SPORTDiscus, and Web of Science databases from inception to December 20, 2022. Two independent authors screened and extracted the data. Results were discussed using theories proposed by the authors of the included studies. Results Of 13 studies (115 participants), 6 (46%) were case studies or case series, 6 (46%) were cross-sectional studies, and 1 (8%) was an experimental study. Studies had small sample sizes (1–23 participants) and various muscle sampling sites (6 different muscles). All 13 studies examined muscle fiber type distributions, and 6 (46%) examined CSA. Ten (77%) studies examined differences between paretic and nonparetic muscles, and 5 (38%) compared people with stroke to people without stroke. Results from 9 of 13 studies (69%) supported a greater proportion of type II muscle fibers in the paretic limb. Of those, 4 studies (42 participants), 3 studies (17 participants), and 1 study (1 participant) saw no differences, preferential type II and type I CSA loss between limbs, respectively. Conclusion Of the limited available evidence, stroke appears to result in a shift to a higher proportion of type II muscle fibers in the paretic muscles. There are mixed results for effects on muscle fiber CSA, but there is some evidence of specific atrophy of type II muscle fibers. Impact Changes in paretic skeletal muscle fibers of individuals with stroke may explain, in part, the substantial losses in strength and power in this population. Interventions to restore type II muscle fiber size may benefit people with stroke. [ABSTRACT FROM AUTHOR]

The turtle locomotor system is heavily modified owing to the severe impact of development of the shell on the body plan of these reptiles. Although limb and girdle osteology of the earliest, Triassic turtles is relatively well understood in general, the exact impacts of variability, ontogeny and preservation (e.g. deformation) on the observed morphologies have rarely been considered in detail. Here, we describe in detail and document the osteology and intraspecific variability of the limbs and girdles of Proterochersis spp. the basalmost true turtles (Testudinata). We also provide a synthesis of currently available data and detailed comparisons with other Triassic stem turtles to gain a better understanding of the diagnostic value of the early turtle appendicular skeleton and to pave the way for future biomechanical and functional studies. Our data suggest that Proterochersis spp. could be at least partly aquatic and could change their preferred habitat during ontogeny, with larger (and, presumably, older) specimens presenting more characters suggestive of a more terrestrial environment. [ABSTRACT FROM AUTHOR]

The article describes the case of 61-year-old female admitted to a hospital on August 22, 2022, with weakness of the extremities for five years, with re-exacerbation for three months and was diagnosed with inflammatory myopathy after a muscle biopsy five years ago. Topics include medication given to the patient, laboratory which supported the diagnosis, and improvement in the patient's condition after ofatumumab administration.

Objective Determine the correlation between post–sympathetic block temperature change and immediate- and intermediate-term pain relief. Design Retrospective analysis. Setting Academic setting. Subjects Seventy-nine patients with complex regional pain syndrome who underwent sympathetic block. Methods Pre- and post-block temperatures in the affected extremity and pain scores immediately (based on 6-hour pain diary) after the block and at the intermediate-term 4- to 8-week follow-up were recorded. Post-block pain reductions of 30–49% and ≥50% were designated as partially sympathetically maintained pain and sympathetically maintained pain, respectively. A decrease in pain score ≥2 points lasting ≥4 weeks was considered a positive intermediate-term outcome for sympathetic block. Results A weak correlation was found between immediate-term pain relief and the extent of temperature rise for the cohort (R  = 0.192, P  = 0.043). Greater immediate-term pain reduction was reported among patients who experienced a temperature increase ≥7.5°C (mean 4.1; 95% confidence interval [CI]: 3.33 to 4.76) than among those who experienced a temperature increase <2°C (2.3; 95% CI: 1.36 to 3.31) or ≥2°C to <7.5°C (2.9; 95% CI: 1.8 to 3.9; P  = 0.036). The correlations between temperature increase and intermediate-term pain score reduction at 4–8 weeks (R  = 0.052, P  = 0.329) and between immediate- and intermediate-term pain relief (R  = 0.139, P  = 0.119) were not statistically significant. Conclusions A weak correlation was found for those who experienced greater temperature increases after the block to also experience greater immediate pain relief. Higher temperature increase cutoffs than are typically used might be necessary to determine whether a patient with complex regional pain syndrome has sympathetically maintained pain. [ABSTRACT FROM AUTHOR]

Background: Very few recent nationwide studies have assessed the epidemiology of cleft lip with or without palate (CL/P). The purpose of this study was to identify the prevalence, risk of premature births, mortality and cause of death of CL/P.Methods: This nationwide population-based cohort study evaluated all 5 747 830 live births in South Korea, including CL/P infants, from 2006 to 2018. The prevalence with trend analysis, risk of premature births, mortality and cause of death of CL/P with or without associated syndromes (non-syndromic, syndromic CL/P) and subgroups (cleft lip only, cleft palate only, cleft lip with palate) were evaluated.Results: Among 5 747 830 live births, 11 284 children were identified as having CL/P during the study period. The annual prevalence was 1.96 per 1000 births. The prevalence ratio, which shows the trend during the period, was 1.021. Both non-syndromic and syndromic CL/P children had higher risk of premature births compared with children without CL/P (odds ratio: non-syndromic 1.43, syndromic 5.29). The mortality rates per 1000 person-years were 0.39 for children without CL/P, 0.98 for non-syndromic CL/P children and 12.20 for syndromic CL/P children. The causes of deaths were not different for children without CL/P in non-syndromic CL/P, but the most common cause of deaths was cardiovascular anomalies in syndromic CL/P.Conclusion: The reported prevalence of 1.96 per 1000 births is one of the highest prevalences worldwide. CL/P children had high risks of premature births and risk of mortality. The most common cause of deaths was cardiovascular anomalies. [ABSTRACT FROM AUTHOR]

Dressage Dressage is a judged sport in which horses perform gymnastic exercises showing different gaits, speeds, and directions of movement. When jumping a vertical fence (1.60 m high) and a spread fence (1.50 m high ×1.80 m wide), horses had significantly higher COM vertical velocity, COM peak height, and average trunk angular velocity but significantly lower COM horizontal velocity compared with jumping a water jump (4.5 m wide). Her interests span the kinetics and kinematics of equine gait, hoof-horse-surface interactions, muscle activity during movement, horse/rider interactions and hoof structure, growth and mechanics. Implications • Horses are exceptional athletes that compete in a wide range of sports each requiring a unique combination of speed, power, balance, and gymnasticism. [Extracted from the article]

Objectives To assess the prevalence of avascular necrosis (AVN) in a large cohort of patients with idiopathic inflammatory myopathies (IIM) and define the major associated risk factors. Methods We retrospectively reviewed the electronic medical records of all patients with a definitive diagnosis of IIM enrolled in our registry between 2003 and 2017, and followed until 2020. Pertinent demographic, clinical, serologic and imaging data were collected. A matched group of patients without AVN was then selected for comparison. Results A total of 1680 patients were diagnosed with IIM. Fifty-one patients developed AVN, with an overall prevalence of 3%. Musculoskeletal MRI was available for 1085 patients and AVN was present in 46 patients (43 lower extremities and 3 upper extremities MRI studies), with a relative prevalence of 4.2%. Most patients with AVN were Caucasian females (57%) with a mean (s. d.) age at diagnosis of 44.5 (12.4) years. Sixty-one percent had DM and 29% had PM. The median time from onset of IIM to diagnosis of AVN was 46 months. The hip joint was most commonly involved in 76% of cases, followed by the knee joint in 15% and shoulder joint in 9%. Some 81% of patients were asymptomatic. Established risk factors for AVN were not found to be associated with the development of AVN in IIM patients. Conclusion Although mostly asymptomatic and incidental, the overall prevalence of AVN in IIM was 3% and the prevalence by MRI was 4.2%. None of the established risk factors was found to be associated with AVN development. [ABSTRACT FROM AUTHOR]

Background: Military aeromedical transport evacuates critically injured patients are for definitive care, including patients with or at risk for developing traumatic compartment syndrome of the extremities (tCSoE). Compartment pressure changes of the extremities have not been determined to be associated with factors inherent to aeromedical transport in animal models, but the influence of aeromedical evacuation (AE) transport on the timing of tCSoE development has not been studied in humans. Using a registry-based methodology, this study sought to characterize the temporal features of lower extremity compartment syndrome relative to the timing of transcontinental AE. With this approach, this study aims to inform practice in guidelines relating to the timing and possible effects of long-distance AE and the development of lower extremity compartment syndrome. Using patient care records, we sought to characterize the temporal features of tCSoE diagnosis relative to long-range aeromedical transport. In doing so, we aim to inform practice in guidelines relating to the timing and risks of long-range AE and postulate whether there is an ideal time to transport patients who are at risk for or with tCSoE.Methods: We performed a retrospective record review of patients with a diagnosis of tCSoE who were evacuated out of theater from January 2007 to May 2014 via aeromedical transport. Data abstractors collected flight information, laboratory values, vital signs, procedures, in-flight assessments, and outcomes. We used the duration of time from injury to arrival at Landstuhl Regional Medical Center (LRMC) to represent time to transport. We compared groups based on time of tCSoE (inclusive of upper and lower extremity) diagnosis relative to injury day and time of transport (preflight versus postflight). We used descriptive statistics and multivariable regression models to determine the associations between time to transport, time to tCSoE diagnosis, and outcomes.Results: Within our study window, 238 patients had documentation of tCSoE. We found that 47% of patients with tCSoE were diagnosed preflight and 53% were diagnosed postflight. Over 90% in both groups developed tCSoE within 48 hours of injury; the time to diagnosis was similar for casualties diagnosed pre- and postflight (P = .65). There was no association between time to arrival at LRMC and day of tCSoE diagnosis (risk ratio, 1.06; 95% CI, 0.96-1.16).Conclusion: The timing of tCSoE diagnosis is not associated with the timing of transport; therefore, AE likely does not influence the development of tCSoE. [ABSTRACT FROM AUTHOR]

Aims Peripheral artery disease (PAD) revascularization can be performed by either endovascular or open surgical approach. Despite increasing use of endovascular revascularization, it is still uncertain which strategy yields better long-term outcomes. Methods and results This retrospective cohort study evaluated patients hospitalized with PAD in Australia and New Zealand who underwent either endovascular or surgical revascularization between 2008 and 2015, and compared procedures using a propensity score-matched analysis. Hybrid interventions were excluded. The primary endpoint was mortality or major adverse limb events (MALE), defined as a composite endpoint of acute limb ischaemia, urgent surgical or endovascular reintervention, or major amputation, up to 8 years post-hospitalization using time-to-event analyses 75 189 patients fulfilled eligibility (15 239 surgery and 59 950 endovascular), from whom 14 339 matched pairs (mean ± SD age 71 ± 12 years, 73% male) with good covariate balance were identified. Endovascular revascularization was associated with an increase in combined MALE or mortality [hazard ratio (HR) 1.13, 95% confidence interval (CI): 1.09–1.17, P < 0.001]. There was a similar risk of MALE (HR 1.04, 95% CI: 0.99–1.10, P = 0.15), and all-cause urgent rehospitalizations (HR 1.01, 95% CI: 0.98–1.04, P = 0.57), but higher mortality (HR 1.16, 95% CI: 1.11–1.21, P < 0.001) when endovascular repair was compared to surgery. In subgroup analysis, these findings were consistent for both claudication and chronic limb-threatening ischaemia presentations. Conclusion Although the long-term risk of MALE was comparable for both approaches, enduring advantages of surgical revascularization included lower long-term mortality. This is at odds with some prior PAD studies and highlights contention in this space. [ABSTRACT FROM AUTHOR]

Objective Complex regional pain syndrome (CRPS) is a painful limb condition known to cause significant disability and distress. However, little previous research has explored CRPS from a patient perspective. The present qualitative study aimed to describe the experiences of people living with CRPS. Subjects Forty-eight people with CRPS participated in this research. Methods Participants completed a face-to-face or telephone interview about their perceptions and experiences of CRPS and completed three drawings to illustrate their experiences. Data were analyzed through reflexive thematic analysis, and images in drawings were grouped and coded by theme. Results Three overarching themes encapsulated the data, including that 1) people experience CRPS as a source of severe symptoms and emotional difficulties, 2) CRPS undermines personal and social identity, and 3) this results in psychological responses that protect against the emotional and social impact of severe symptoms. Psychological responses include: a) searching for an explanation, b) "nothing is my fault," emphasizing a lack of personal responsibility and personal control, and c) detaching the limb from the self. Conclusions CRPS is experienced as highly threatening to physical ability, psychological state, and identity. In response to these threats, people may develop their own explanations for CRPS and may mentally detach themselves from responsibility, control, and the painful limb itself. Future research could explore the impact of these factors on psychological well-being and CRPS symptoms and outcomes. [ABSTRACT FROM AUTHOR]

The article presents case study of 52-year-old woman who presented to pain medicine clinic initially in 2012 due to painful lower extremity spasticity and increasing spasms in the upper extremities. It mentions diagnosis of neurosarcoidosis, a multi-organ system granulomatous disease that, when untreated, can cause significant morbidity and mortality.

Background and Objective: Porcine translational models have become the gold-standard translational tool to study the effects of major injury and hemorrhagic shock because of their similarity to the human immunologic response to trauma. Segmental bone defects (SBDs) typically occur in warfighters with associated severe limb trauma. The purpose of this study was to develop a translational porcine diaphyseal SBD model in Yucatan minipigs (YMPs), which could be used in bone healing investigations that simulate injury-relevant conditions. We were specifically working toward developing a critical sized defect (CSD).Methods: We used an adaptive experimental design in which both 25.0 mm and 40.0 mm SBDs were created in the tibial mid-diaphysis in skeletally mature YMPs. Initially, eight YMPs were subjected to a 25.0 mm SBD and treated with intramedullary nailing (intramedullary nail [IMN] 25mm). Due to unanticipated wound problems, we subsequently treated four specimens with identical 25.0 mm defect with dual plating (open reduction with internal fixation [ORIF] 25mm). Finally, a third group of four YMPs with 40.0 mm defects were treated with dual plating (ORIF 40mm). Monthly radiographs were made until sacrifice. Modified Radiographic Union Score for Tibia fractures (mRUST) measurements were made by three trauma-trained orthopedic surgeons. CT scans of the tibias were used to verify the union results.Results: At 4 months post-surgery, mean mRUST scores were 11.7 (SD ± 1.8) in the ORIF 25mm YMPs vs. 8.5 (SD  ± 1.4) in the IMN 25mm YMPs (P < .0001). All four ORIF 25mm YMPs were clinically healed. In contrast, none of the IMN 25mm YMPs were clinically healed and seven of eight IMN 25mm YMPs developed delayed wound breakdown. All four of the ORIF 40mm YMPs had flail nonunions with complete hardware failure by 3 months after surgery and were sacrificed early. CT scanning confirmed that none of the IMN 25mm YMPs, none of the ORIF 40mm YMPs, and two of four ORIF 25mm YMPs were healed. A third ORIF 25mm specimen was nearly healed on CT scanning. Inter-rater and intra-rater reliability interclass coefficients using the mRUST scale were 0.81 and 0.80, respectively.Conclusions: YMPs that had a 40 mm segment of bone removed from their tibia and were treated with dual plating did not heal and could be used to investigate interventions that accelerate bone healing. In contrast, a 25 mm SBD treated with dual plating demonstrated delayed but successful healing, indicating it can potentially be used to investigate bone healing adjuncts or conversely how concomitant injuries may impair bone healing. Pigs treated with IMN failed to heal and developed consistent delayed wound breakdown presumably secondary to chronic limb instability. The porcine YMP SBD model has the potential to be an effective translational tool to investigate bone healing under physiologically relevant injury conditions. [ABSTRACT FROM AUTHOR]

An editorial is presented on low-dose rivaroxaban plus aspirin in older patients with peripheral artery disease undergoing acute limb revascularization. Topics include clinical presentation ranging from asymptomatic, intermittent claudication, to acute limb ischaemia and critical limb ischaemia; and improving neovascularization in the context of limb ischaemia and in the protection and repair of the endothelium.

Objectives Muscle involvement in Behçet's disease (BD) is rare, and several cases have been reported in the literature. Therefore, this study aimed to describe the clinical, laboratory and imaging findings in adult patients presenting with BD-associated myositis before the diagnosis of BD. Methods We retrospectively screened patients who visited a locomotive medicine clinic presenting with myalgia, local swelling, or tenderness of extremities without an established diagnosis of BD. We enrolled patients whose pain in the extremities was proven to be suggestive of focal vasculitic myositis and who were eventually diagnosed as having BD at the initial visit or during follow-up. We thoroughly reviewed the clinical, histological and imaging findings and treatment outcomes in patients who presented with focal vasculitic myositis as the primary manifestation of BD. Results Ten adult patients with focal vasculitic myositis as the primary manifestation of BD were enrolled. The lower and upper extremities were affected in eight and two patients, respectively. The affected lower extremities were the calf (n  = 6) and thigh muscles (n  = 2). The common findings of MRI included high signal intensity of the affected muscles and intermuscular fascia on fat-suppressed images, suggestive of myofascitis and oedematous changes in the subcutaneous layer. The results of skin or muscle biopsy were suggestive of vasculitis. All the patients were pain-free at the short-term follow-up (1–3 weeks) after oral steroid therapy. Conclusion Focal vasculitic myositis can be a primary manifestation of BD warranting medical attention. BD-associated myositis responds well to oral steroid therapy. [ABSTRACT FROM AUTHOR]

Objectives: Cancer survivors with GH deficiency (GHD) receive GH therapy (GHT) after 1+ year observation to ensure stable tumor status/resolution.Hypothesis: Radiation therapy (RT) to brain, spine, or extremities alters growth response to GHT.Aim: Identify differences in growth response to GHT according to type/location of RT.Methods: The Pfizer International Growth Database was searched for cancer survivors on GHT for ≥5 years. Patient data, grouped by tumor type, were analyzed for therapy (surgery, chemotherapy, RT of the focal central nervous system, cranial, craniospinal, or total body irradiation [TBI] as part of bone marrow transplantation), sex, peak stimulated GH, age at GHT start, and duration from RT to GHT start. Kruskal-Wallis test and quantile regression modeling were performed.Results: Of 1149 GHD survivors on GHT for ≥5 years (male 733; median age 8.4 years; GH peak 2.8 ng/mL), 431 had craniopharyngioma (251, cranial RT), 224 medulloblastoma (craniospinal RT), 134 leukemia (72 TBI), and 360 other tumors. Median age differed by tumor group (P < 0.001). Five-year delta height SD score (SDS) (5-year ∆HtSDS; median [10th-90th percentile]) was greatest for craniopharyngioma, 1.6 (0.3-3.0); for medulloblastoma, 5-year ∆HtSDS 0.9 (0.0-1.9); for leukemia 5-year ∆HtSDS, after TBI (0.3, 0-0.7) versus without RT (0.5, 0-0.9), direct comparison P < 0.001. Adverse events included 40 treatment-related, but none unexpected.Conclusions: TBI for leukemia had significant impact on growth response to GHT. Medulloblastoma survivors had intermediate GHT response, whereas craniopharyngioma cranial RT did not alter GHT response. Both craniospinal and epiphyseal irradiation negatively affect growth response to GH therapy compared with only cranial RT or no RT. [ABSTRACT FROM AUTHOR]

Objective Examine the interrelationship between smoking and pain in the US population. Design A cross-sectional population-based study. Setting Nationwide survey. Methods Comprehensive pain reports categorically defined as head, spine, trunk, and limb pain; smoking history; demographics; medical history from a total of 2,307 subjects from the 2003–2004 National Health and Nutrition Examination Survey obtained from the Centers for Disease Control were analyzed. Unpaired t tests were used to analyze independent continuous variables, and chi-square tests were used to analyze categorical variables between smoker and nonsmoker groups. Weighted multivariate logistic regression analyses determined the association of current smoking with the presence of pain in various body regions. Results Smoking is most strongly associated with spine pain (odds ratio [OR] = 2.89, 95% confidence interval [CI] = 2.21–3.77), followed by headache (OR = 2.47, 95% CI = 1.73–3.53), trunk pain (OR = 2.17, 95% CI = 1.45–2.74), and limb pain (OR = 1.99, 95% CI = 1.45–2.73). Conclusions Current smoking is associated with pain in every region of the body. This association is strongest for spine and head pain. Given that pain is a strong motivator and that current smoking was associated with pain in all body regions, we recommend that these results be used to further raise public awareness about the potential harms of smoking. [ABSTRACT FROM AUTHOR]

We present a series of 6 critically ill children with multisystem inflammatory syndrome in children. Key findings of this syndrome include fever, diarrhea, shock, and variable presence of rash, conjunctivitis, extremity edema, and mucous membrane changes. [ABSTRACT FROM AUTHOR]

Primate limb morphology is often described as either generalized, that is, suited to a range of locomotor and positional behaviors, or specialized for unique locomotor behaviors such as brachiation or bipedalism. The evolution of highly specialized limb morphology may result in loss of evolvability, that is, in a decreased capacity of the locomotor skeleton to evolve in response to selection towards alternative ecomorphological niches. Using evolutionary simulations, I show that the highly specialized limb anatomy of hominoids is associated with a significant loss of evolvability, defined as the number of generations to reach alternative adaptive peaks, and in parallel an increased risk of extinction, particularly in simulated evolution toward generalized quadrupedal limb proportions. Loss of evolvability in apes and humans correlates with three factors: (1) decreased correlation among limb bone lengths (i.e., integration), which slows the rate of change along lines of least evolutionary resistance; (2) limb specialization, which places apes and humans in relatively remote areas of morphospace; and (3) increased skeletal size as a proxy for body size. Thus, locomotor over‐specialization can lead to evolutionary dead‐ends that significantly increase the probability of hominoid populations going extinct before evolving new adaptive morphologies. [ABSTRACT FROM AUTHOR]

Introduction: Tourniquet application is an urgent life-saving procedure. Previous studies demonstrated several drawbacks in tourniquet design and application methods that limit their efficacy; among them, loose application of the device before windlass twisting is a main pitfall. A new generation of modern combat tourniquets was developed to overcome these pitfalls. The objective of this study was to assess the effectiveness of three new tourniquet designs: the CAT Generation 7 (CAT7), the SAM Extremity Tourniquet (SAM-XT), and the SOF Tactical Tourniquet Wide (SOFTT-W) as well as its correlation to the degree of slack.Materials and Methods: The three tourniquet models were applied in a randomized sequence on a HapMed leg tourniquet trainer, simulating an above-the-knee traumatic amputation by 60 military medicine track cadets. Applied pressure, hemorrhage control status, time until the bleeding stopped, estimated blood volume loss, and slack were measured.Results: The mean (±SD) pressure applied using the SAM-XT (186 mmHg ±63) or the CAT7 (175 mmHg ±79) was significantly higher compared to the pressure applied by the SOFTT-W (104 mmHg ±101, P < 0.017), with no significant difference between the first two (P > 0.05). Hemorrhage control rate was similar (P > 0.05) with SAM-XT (73.3%) and CAT7 (67.7%), and both were significantly better than the SOFTT-W (35%, P < 0.017). Slack was similar between CAT7 and SAM-XT (5.2 mm ± 3.4 vs. 5 mm ± 3.5, P > 0.05), yet significantly lower compared to the SOFTT-W (9 mm ± 5, P < 0.017). A strong negative correlation was found between slack and hemorrhage control rate (3.2 mm ± 1.5 mm in success vs. 10.5 mm ± 3.4 mm in failure, P < 0.001) and applied pressure (Pearson's correlation coefficient of -0.83, P < 0.001).Conclusions: Both SAM-XT and CAT7 demonstrated a better pressure profile and hemorrhage control rate compared to SOFTT-W, with no significant difference between the two. The better outcome measures were strongly correlated to less slack. [ABSTRACT FROM AUTHOR]

Whilst exaggerated bursts of beta frequency band oscillatory synchronization in the subthalamic nucleus have been associated with motor impairment in Parkinson's disease, a plausible mechanism linking the two phenomena has been lacking. Here we test the hypothesis that increased synchronization denoted by beta bursting might compromise information coding capacity in basal ganglia networks. To this end we recorded local field potential activity in the subthalamic nucleus of 18 patients with Parkinson's disease as they executed cued upper and lower limb movements. We used the accuracy of local field potential-based classification of the limb to be moved on each trial as an index of the information held by the system with respect to intended action. Machine learning using the naïve Bayes conditional probability model was used for classification. Local field potential dynamics allowed accurate prediction of intended movements well ahead of their execution, with an area under the receiver operator characteristic curve of 0.80 ± 0.04 before imperative cues when the demanded action was known ahead of time. The presence of bursts of local field potential activity in the alpha, and even more so, in the beta frequency band significantly compromised the prediction of the limb to be moved. We conclude that low frequency bursts, particularly those in the beta band, restrict the capacity of the basal ganglia system to encode physiologically relevant information about intended actions. The current findings are also important as they suggest that local subthalamic activity may potentially be decoded to enable effector selection, in addition to force control in restorative brain-machine interface applications. [ABSTRACT FROM AUTHOR]

Introduction: We examined antibiotic management of combat-related extremity wound infections (CEWI) among wounded U.S. military personnel (2009-2012).Methods: Patients were included if they sustained blast injuries, resulting in ≥1 open extremity wound, were admitted to participating U.S. hospitals, developed a CEWI (osteomyelitis or deep soft-tissue infections) within 30 days post-injury, and received ≥3 days of relevant antibiotic (s) for treatment.Results: Among 267 patients, 133 (50%) had only a CEWI, while 134 (50%) had a CEWI plus concomitant non-extremity infection. In the pre-diagnosis period (4-10 days prior to CEWI diagnosis), 95 (36%) patients started a new antibiotic with 28% of patients receiving ≥2 antibiotics. During CEWI diagnosis week (±3 days of diagnosis), 209 (78%) patients started a new antibiotic (71% with ≥2 antibiotics). In the week following diagnosis (4-10 days after CEWI diagnosis), 121 (45%) patients started a new antibiotic with 39% receiving ≥2 antibiotics. Restricting to ±7 days of CEWI diagnosis, patients commonly received two (35%) or three (27%) antibiotics with frequent combinations involving carbapenem, vancomycin, and fluoroquinolones.Conclusions: Substantial variation in antibiotic prescribing patterns related to CEWIs warrants development of combat-related clinical practice guidelines beyond infection prevention, to include strategies to reduce the use of unnecessary antibiotics and improve stewardship. [ABSTRACT FROM AUTHOR]

Background: Folic acid (FA) supplementation prevents neural tube defects, but there are mixed results for its ability to prevent limb reduction defects. We examined whether a preventive effect of FA supplementation exists for congenital limb reduction defects in a large population in China.Methods: Data from a large population-based cohort study in China were used to evaluate the effects of FA supplementation on birth defects. All births at 20 complete gestational weeks, including live births, stillbirths and pregnancy terminations, and all structural congenital anomalies, regardless of gestational week, were recorded. A total of 247 831 singleton live births delivered at gestational ages of 20-42 weeks to women from northern and southern China with full information on FA intake were included. Limb reduction defects were classified by subtype and maternal FA supplementation.Results: The prevalence of limb reduction defects was 2.7 per 10 000 births among women who took FA compared with 9.7 per 10 000 births among those who did not take FA in northern China; the prevalence was 4.5 and 3.8 per 10 000 births, respectively, in southern China. In both unadjusted and adjusted analyses, the estimated relative risk for upper limb reduction defects [odds ratio (OR) = 0.17, 95% confidence interval (CI): 0.04, 0.63] and total limb reduction defects (OR = 0.24, 95% CI: 0.08, 0.70) in northern China, but not for lower limb reduction defects ,was significantly decreased in association with FA supplementation in northern China. There was no association between FA supplementation and either an increased or decreased risk for limb reduction defects in southern China.Conclusions: FA supplementation successfully reduces the prevalence of limb reduction defects in northern China, whose population has low folate concentrations. [ABSTRACT FROM AUTHOR]

Background Long-term health-related quality of life (HR-QOL) of patients surviving the acute phase of purpura fulminans (PF) has not been evaluated. Methods This was a French multicenter exposed-unexposed cohort study enrolling patients admitted in 55 intensive care units (ICUs) for PF from 2010 to 2016. Adult patients surviving the acute phase of PF (exposed group) were matched 1:1 for age, sex, and Simplified Acute Physiology Score II with septic shock survivors (unexposed group). HR-QOL was assessed during a phone interview using the 36-Item Short-Form Health Survey (SF-36) questionnaire, the Hospital Anxiety and Depression (HAD) scale, the Impact of Event Scale–Revised (IES-R), and the activity of daily living (ADL) and instrumental ADL (IADL) scales. The primary outcome measure was the physical component summary (PCS) of the SF-36 questionnaire. Results Thirty-seven survivors of PF and 37 of septic shock were phone-interviewed at 55 (interquartile range [IQR], 35–83) months and 44 (IQR, 35–72) months, respectively, of ICU discharge (P =.23). The PCS of the SF-36 was not significantly different between exposed and unexposed patients (median, 47 [IQR, 36–53] vs 54 [IQR, 36–57]; P =.18). There was also no significant difference between groups regarding the mental component summary of the SF-36, and the HAD, IES-R, ADL and IADL scales. Among the 37 exposed patients, those who required limb amputation (n = 12/37 [32%]) exhibited lower PCS (34 [IQR, 24–38] vs 52 [IQR, 42–56]; P =.001) and IADL scores (7 [IQR, 4–8] vs 8 [IQR, 7–8]; P =.021) compared with nonamputated patients. Conclusions Long-term HR-QOL does not differ between patients surviving PF and those surviving septic shock unrelated to PF. Amputated patients have an impaired physical HR-QOL but a preserved mental health. Clinical Trials Registration NCT03216577. [ABSTRACT FROM AUTHOR]

Objectives Neurorehabilitation techniques using virtual reality (VR) systems have recently become widespread as a rehabilitation method for restoring phantom limb movement and alleviating phantom limb pain (PLP). However, analgesic effects have varied between studies, possibly because of differences in the characteristics of PLP between patients (e.g. cramping, burning, shooting). We aimed to reveal the relationship between VR effects and PLP characteristics using an exploratory factor analysis. Methods PLP characteristics of 19 patients were measured using the Short-Form McGill Pain Questionnaire (SF-MPQ), and all PLP patients performed the VR rehabilitation protocol for 20 minutes. During VR rehabilitation, mirror-reversed computer graphic images of an intact arm (the virtual phantom limb) were presented to patients via a head-mounted display, inducing the perception of voluntary execution of movements of their phantom limb when intending bimanual movements. Results VR rehabilitation significantly restored movement representation (P  < 0.0001) quantified using the bimanual coupling effect and significantly alleviated PLP intensity (P  < 0.0001). The factor analysis revealed that PLP characteristics could be divided into two factors: "somatosensory-related pain characteristics" and "kinesthesia-related pain characteristics." PLP alleviation via VR rehabilitation was significantly correlated with "kinesthesia-related pain characteristics" (r  = 0.47, P  = 0.02) but not "somatosensory-related pain characteristics" (r  = 0.22, P  = 0.17). Conclusions The current findings indicate that VR rehabilitation may be particularly effective for PLP associated with distorted phantom limb movement and body representations (e.g. clamping, gnawing), compared with typical neuropathic sensations (e.g. shooting, burning, dysesthesia). [ABSTRACT FROM AUTHOR]

Background Measurements of residual limb volume often guide decisions on the type and timing of prosthetic prescription. To help inform these decisions, it is important that clinicians use measurement tools that are reliable and valid. Purpose The aim of this systematic review was to investigate the reliability and validity of measurement tools for residual limb volume in people with limb amputations. Data Sources A comprehensive search on MEDLINE, EMBASE, CINAHL, Scopus, and Web of Science was performed on July 11, 2016. Study Selection Studies were included if they examined the reliability or validity of measurement tools for residual limb volume, were conducted on humans, and were published in English. Data Extraction Data were extracted from 11 reliability and 4 validity studies and included study characteristics, volumetric estimates, and reliability and validity estimates. The quality of the studies was also rated. Data Synthesis Data from 2 studies (38 participants) indicated good to excellent intrarater (intraclass correlation coefficient [ICC] ≥0.88) and interrater (ICC ≥0.88) reliability and high between-session reliability (coefficient of variation [CV] = 10%) for water displacement volumetry. One study (28 participants) reported excellent intrarater and interrater reliability (ICC ≥0.93) for the circumferential method, and data from 2 studies (19 participants) indicated high between-session reliability for the optical surface scanner (CV ≤9.8%). Three studies (26 participants) indicated good to excellent between-session reliability results for computed tomography (CV = 9.2%–10.9%). One study (7 participants) showed moderate within-session reliability (CV = 50%). Using water displacement volumetry as the gold standard, 2 studies (79 participants) indicated excellent validity for the circumferential method (r  ≥0.92; ICC ≥0.92). All studies reporting measures of reliability or validity were performed with people who had transtibial amputations. Limitations Only studies published in English and in which water displacement volumetry was used as the gold standard were included in this review. The reliability and validity of the quality rating scale used in this review have not been tested. Conclusions On the basis of a limited number of moderate- to high-quality studies with small sample sizes, circumferential and water displacement methods were found to be reliable, and the circumferential method was found to be valid in people with transtibial amputations. There are inadequate data for drawing conclusions about volume measurement methods in people with other types of limb amputations. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 68-year-old man with myasthenia gravis and widespread skin eruption while on treatment with azathioprine (AZA), oral prednisone and pyridostigmine. The patient was febrile and appeared fatigue and ill on physical examination. A diagnosis of azathioprine hypersensitivity syndrome as an adverse reaction to azathioprine. The condition of the patient improved after discontinuation of AZA.

Electrical injuries induce substantial morbidity and mortality. Amputations are often necessary to enable survival and based on tissue nonviability, development of life-threatening infection, or expected nonfunctional outcome. They analyzed occurrence and type of amputations in their institution for electrical and nonelectrical pediatric burns and the number of reconstructive operations. Patients who underwent any amputation between 1999 and 2017 were identified. Patients with electrical burns (EB) were matched regarding age, sex, and percent total body surface area (%TBSA) burned to patients with nonelectrical burns (NEB). Both groups (n = 35 EB, n = 70 NEB) were comparable regarding age (EB, 11.6 ± 4.5 years; NEB, 11.1 ± 4.5 years, P = .550) and %TBSA (36.7 ± 15.4% and 37.7 ± 12.9%, P = .738). Major amputations (above wrist or ankle) were performed in 77% of EB vs 31% of NEB (P < .001). Amputations above knee or elbow were performed in 13 (37.1%) vs two patients (2.9%, P < .001). Eight (22.9%) vs six patients (8.6%) underwent combination of two or more major amputations (P = .042). In both groups, most amputations were performed for functional reasons. Length of stay was shorter in EB group (33 ± 27 vs 47 ± 38 days, P = .040). EB patients underwent 9.9 ± 7.1 total operations compared with 14.4 ± 5.1 operations (P < .001). Of these, 6.5 ± 3.6 and 7.9 ± 3.3 (P = .023) were performed during acute stay and 3.3 ± 4.8 and 6.5 ± 3.5 after acute stay (P < .001), respectively. Mortality was comparable. EB were associated with larger extent of limb loss and more major amputations than NEB with amputations. They furthermore required a smaller number of reconstructive procedures. EB require extra attention of caregivers, because of their extensive tissue damage. [ABSTRACT FROM AUTHOR]

Hydrodynamic stability and the ability to turn are two important components of swimming performance in aquatic animals. Stability reduces the energetic costs of swimming, and turning performance facilitates both prey capture and predator avoidance. These components of locomotor performance are typically measured in adults, but juveniles also experience high demands on locomotor performance. To test how stability and turning performance change through ontogeny, we measured the swimming kinematics and performance of hatchling, juvenile and adult pink-bellied sideneck turtles (Emydura subglobosa) as they followed a prey stimulus, and compared these performance metrics in the context of morphometric differences across age classes. We found that in E. subglobosa, adults had the highest stability and lowest turning performance. Younger, smaller turtles are likely to be more susceptible to destabilizing forces and have rounder body shapes than adults, which might enhance turning performance. In contrast, the larger size and more extensive webbing of the limbs of adults might facilitate greater stability. These differences in performance and morphology might reflect common ontogenetic changes in the ecology of aquatic turtles. Hatchlings might benefit from enhanced turning performance to escape predators, whereas the larger size of adults makes them less susceptible to predators that could consume hatchlings whole. [ABSTRACT FROM AUTHOR]

Coordinated landing from a jump requires preparation, which must include appropriate positioning and configuration of the landing limbs and body to be successful. While well studied in mammals, our lab has been using the cane toad (Rhinella marinus) as a model for understanding the biomechanics of controlled landing in anurans, animals that use jumping or bounding as their dominant mode of locomotion. In this article, we report new results from experiments designed to explore how different modes of sensory feedback contribute to previously identified features of coordinated landing in toads. More specifically, animals in which vision, hindlimb proprioception, or vestibular feedback were removed, underwent a series of hopping trials while high-speed video was used to record and characterize limb movements and electromyographic (EMG) activity was recorded from a major elbow extensor (anconeus). Results demonstrate that altering any sensory system impacts landing behavior, though loss of vision had the least effect. Blind animals showed significant differences in anconeus EMG timing relative to controls, but forelimb and hindlimb movements as well as the ability to successfully decelerate the body using the forelimbs were not affected. Compromising hindlimb proprioception led to distinctly different forelimb kinematics. Though EMG patterns were disrupted, animals in this condition were also able to decelerate after impact, though with less control, regularly allowing their trunks to make ground contact during landing. Animals with compromised vestibular systems showed the greatest deficits, both in takeoff and landing behavior, which were highly variable and rarely coordinated. Nevertheless, animals in this condition demonstrated EMG patterns and forelimb kinematics similar to those in control animals. The fact that no ablation entirely eliminates all aspects of landing preparation suggests that its underpinnings are complex and that there is no single sensory trigger for its initiation. [ABSTRACT FROM AUTHOR]

Some groups have avoided early microsurgical flaps in electrical burns under the pretext of injury to the microvasculature, which could increase vascular thrombosis. However, this option frequently results in amputation of the extremity. This study aims to evaluate the early application of microsurgical flaps for the treatment of electrical burns of extremities. A case series was retrospectively evaluated including patients with electrical trauma in extremities undergoing early microsurgical reconstruction. Data were obtained from medical charts, including age, trauma location, flap type and microvascular anastomosis, the need for other procedures, postoperative complications, the length of hospital stay after the flap surgery, and patient outcomes. Five microsurgical flaps were performed in less than 30 days to trauma, one anterolateral thigh flap to cover skin failure in upper limb, and four radial forearm flaps to cover failure in feet. The patient ages had a mean of 25.8 years (from 12 to 42 years). The microsurgical procedure occurred from 21 to 27 days after the burn, with a mean of 24.2 days. Hospital discharge had a mean of 26.6 days (from 19 to 35 days after the surgery). Only one patient required reintervention for re-anastomosis. All patients had a good flap viability, avoiding amputation of the affected extremity and with a proper preservation of function. The early application of microsurgical flaps for patients with electrical burns of extremities may provide adequate, sturdy, and stable skin coverage, contributing to the treatment of noble structures exposed and avoiding amputation of the extremities. [ABSTRACT FROM AUTHOR]

Objective Findings regarding small nerve fiber damage in complex regional pain syndrome type I (CRPS-I) are not uniform, and studies have not included a matched healthy control group. The aim was to assess intraepidermal nerve fiber density (IENFD) in relation to thermal sensitivity of the same skin areas in CRPS-I patients and a gender- and age-matched healthy control group. Methods IENFD was investigated in skin biopsies from the CRPS-affected and contralateral limbs of eight CRPS-I patients and from an equivalent site in eight gender- and age-matched healthy controls (HCs). Thermal thresholds (cold/warm detection, cold- and heat-pain detection) were assessed on the affected limb, the matching contralateral limb, and on the equivalent limbs of HCs, and participants rated the intensity of cold/heat and pain to static thermal stimuli (5 °C and 40 °C). Results IENFD was significantly lower in both the affected and contralateral limbs of CRPS-I patients than HCs, but IENFD did not differ between the affected and contralateral limbs of patients. The heat pain threshold was lower in the affected CRPS-I limb than in HCs, but all other thermal thresholds were similar in both groups. CRPS-I patients rated the cold stimulus as colder and more painful in the affected limb, and the warm stimulus as hotter, bilaterally, than the HCs. Conclusions CRPS-I may be associated with bilateral small fiber damage, and perhaps small fiber neuropathy and bilateral disturbances in thermo-sensory perception. These disturbances could stem from a systemic response to injury or might increase the risk of developing CRPS-I after physical trauma. [ABSTRACT FROM AUTHOR]

In the article, the authors present a case of an 8-year-old male who was rushed to a clinic due to rashes over his lower limbs for five days to discuss monogenic disorders like autoinflammatory syndromes and primary immunodeficiency diseases. Other topics include cutaneous IgA vasculitis (cIgAV), thrombocytopaenia, Wiskott Aldrich syndrome protein expression, and germline mutations in the IKZF1 gene.

Objectives We aimed to develop and assess the reliability of a novel MRI-based scoring system for reporting the severity of MRI findings in children with suspected JDM. Methods Nine consultant paediatric radiologists independently assessed and scored 40 axial and 30 coronal thigh MR images of children with suspected JDM on two occasions using the juvenile dermatomyositis magnetic resonance Imaging Score (JIS). JIS was calculated for both reads for each plane and each limb, with possible scores ranging from 0 (normal) to 100 (severe). Inter- and intraobserver agreement was calculated using the intraclass correlation coefficient (ICC) and two- and one-way random effects models, respectively. Bland-Altman plots of the difference in JIS against the average JIS were also produced for each rater. Results Overall, the interobserver reliability and agreement was good—for axial images, JIS ranged from 46.8 to 61.0 [ICC = 0.88 (95% CI: 0.82, 0.92)] for the left limb and 47.9–61.4 [ICC = 0.87 (95% CI: 0.81, 0.92)] for the right limb. For coronal images, JIS ranged from 56.7 to 65.1 [ICC = 0.90 (95% CI: 0.85, 0.95)] for the left limb and 55.7 to 66.8 [ICC = 0.90 (95% CI: 0.84, 0.94)] for the right limb. The intraobserver reliability and agreement was good, with ICC ranging from 0.90 to 0.94. Conclusion JIS is a semi-objective scoring system with potential to serve as a reliable biomarker of disease severity and response to therapeutic interventions in children with JDM. [ABSTRACT FROM AUTHOR]

Congenital abnormalities are important causes of morbidity and mortality in children and significantly add to the burdens on healthcare in developing countries. Unfortunately, there remains a paucity of information on congenital birth defects in most developing countries. This is a 4-year prospective study that assessed the patterns and predictors of congenital anomalies among newborns at the Enugu State University Teaching Hospital, Nigeria. In total, 5830 deliveries were recorded, of which 38 had congenital anomalies, giving an incidence rate of 6.5/1000 live births. Fifty-two newborns were enrolled as nested controls. Factors significantly associated with congenital anomalies were low birth weight (p = 0.009), low socio-economic class (p = 0.011), lower maternal educational attainment (p = 0.009), parity of ≥ 5 (p = 0.002), febrile illness (p = 0.001) and the use of local concoction in index pregnancy (p = 0.009). More than half of the anomalies reported involved the musculoskeletal system. Occurrence of congenital anomalies may be prevented by curtailing risk factors identified in this study. [ABSTRACT FROM AUTHOR]

Objective. Despite the high prevalence of chronic multisite pain, there is little consensus onmethods to characterize it. Commonly used assessments report only one dimension of pain, that is, intensity, thus ignoring the spatial aspect of pain. We developed a novel pain quantification index, the Integrated Pain Quantification Index (IPQI), on a scale of 0 to 1 that integrates multiple distinct pain measures into a single value, thus representing multidimensional pain informationwith a single value. Design. Single-visit, noninterventional, epidemiological study. Setting. Fourteen outpatient multidisciplinary pain management programs. Patients. Patients with chronic pain of the trunk and/ or limbs for at least six months with average overall pain intensity of at least = on the numeric rating scale. Methods. Development of IPQI was performed in a large population (N5810) of chronic pain patients from the Multiple Areas of Pain (MAP) study. Results. Prevalence of two or more noncontiguous painful areas was at 88.3% (95% confidence interval [CI] = 0.86-0.90), with a mean of 6.3 areas (SD55.57 areas). Prevalence of more than 10% body area in pain was at 52.8% (95% CI50.49-0.56), with a mean at 16.1% (17.16%). On average, IPQI Wallace et al. values were near the middle of the scale, with mean and median IPQI at 0.52 (SD=0.13) and 0.55, respectively. The IPQI was generalizable and clinically relevant across all domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials. Conclusions. IPQI provided a single pain score for representing complex, multidimensional pain information on one scale and has implications for comparing pain populations across longitudinal clinical trials. [ABSTRACT FROM AUTHOR]

Background Work-related upper limb disorders (WRULDs) are a syndrome of symptoms affecting the upper quadrant of the body and are a significant cause of pain, disability and sickness absence among workers. Exercise therapy is considered to be a clinical and cost-effective strategy in WRULD management. Aims To evaluate the effectiveness of exercise therapy for WRULDs in sedentary workers. Methods This review follows an a priori protocol to maintain internal validity describing essential procedures to be followed (e.g. a comprehensive search strategy, duel extraction and critical appraisal). The methodological quality of the studies were assessed using Cochrane Risk of Bias Tool for all randomized controlled trials and the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool for systematic reviews. Results A total of 11 articles were selected for inclusion. There was moderate evidence to suggest exercise is effective in reducing the symptoms of pain and improved function in WRULDs in sedentary workers when compared to a control group. Conclusions The results were comparable to recent systematic reviews, which have found evidence to support the use of exercise therapy, in mixed populations of workers. There is a need for further research to highlight the most effective form of exercise, optimal dosage and delivery method. [ABSTRACT FROM AUTHOR]

Abstract: Background: The management of localized extremity soft tissue sarcomas (STS) is challenging and the role of pre‐ and postoperative chemotherapy is unclear and debated among experts. Materials and Methods: Medical oncology experts of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group were asked to participate in this survey on the use of pre‐ and postoperative chemotherapy in STS. Experts from 12 centers in Belgium, France, Germany, Great Britain, Italy, Switzerland, and The Netherlands agreed to participate and provided their treatment algorithm. Answers were converted into decision trees based on the objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies. Results: Several criteria used for decision‐making in extremity STS were identified: chemosensitivity, fitness, grading, location, and size. In addition, resectability and resection status were relevant in the pre‐ and postoperative setting, respectively. Preoperative chemotherapy is considered in most centers for marginally resectable tumors only. Yet, in some centers, neoadjuvant chemotherapy is used routinely and partially combined with hyperthermia. Although most centers do not recommend postoperative chemotherapy, some offer this treatment on a regular basis. Radiotherapy is an undisputed treatment modality in extremity STS. Conclusion: Due to lacking evidence on the utility of pre‐ and postoperative chemotherapy in localized extremity STS, treatment strategies vary considerably among European experts. The majority recommended neoadjuvant chemotherapy for marginally resectable grade 2–3 tumors; the majority did not recommend postoperative chemotherapy in any setting. Implications for Practice: The management of localized extremity soft tissue sarcomas (STS) is challenging and the role of pre‐ and postoperative chemotherapy is unclear and debated among experts. This study analyzed the decision‐making process among 12 European experts on systemic therapy for STS. A wide range of recommendations among experts regarding the use of perioperative chemotherapy was discovered. Discrepancies in the use of decision criteria were also uncovered, including the definition of what constitutes high‐risk cancer, which is a basis for many to recommend chemotherapy. Before any standardization is possible, a common use of decision criteria is necessary. [ABSTRACT FROM AUTHOR]

Objective. Identifying pain generators in tissue deep in the skin can require uncomfortable, complicated, and invasive tests. We describe pilot studies testing the hypothesis that ultrasound image-guided, intense focused ultrasound (ig-iFU) can noninvasively and differentially stimulate the end of transected nerves in the residual limbs of amputee patients. Design. We applied iFU to the transected nerve ending as individual pulses with a length of 0.1 seconds using a carrier frequency of 2.0 MHz. After targeting, we gradually increased the iFU intensity to reach consistent patient-reported stimulation of the transected nerve ending. We also stimulated the proximal nerve, tissue near the nerve ending and the intact contralateral nerve. We described the resulting sensations and correlated the results of the study participant's pre-iFU study responses to phantom and residual limb pain questionnaires. Results. iFU spatial and temporal average intensity values between 16W/cm2 and 433 W/cm2 that were applied to the transected nerve ending and proximal nerve elicited sensations, including phantom limb sensations, while the same intensity applied to control tissue centimeters away from the nerve ending, or to the intact nerve on the contralateral limb, did not. Two out of 11 study participants reported only mild and transient pain created by iFU stimulation. Successful iFU intensity values correlated with neither phantom nor residual limb pain scores. Conclusions. Transected nerves had greater sensitivity to iFU stimulation than ipsilateral and contralateral control tissue, including intact nerve. These results support the view that ig-iFU may one day help physicians identify deep, tender tissue in patients who report experiencing pain. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the efficacy of exercise prior to mammography in reducing perceived postexamination pain. Methods. An open, randomized, and controlled clinical trial was conducted. The interventions consisted of warm-up and stretching exercises of the upper or lower limbs of women who consulted at Barretos Cancer Hospital, São Paulo State, Brazil. The women were divided into three groups based on the intervention and its location: upper limbs (group 1), lower limbs (group 2), and no intervention (group 0). Quantitative variables were compared between and within groups using analysis of variance and Student's t test with a 5% significance level. Relative risk (RR) calculations and their derived measurements such as efficacy, number needed to treat (NNT), absolute risk reduction (ARR), and relative risk reduction (RRR) were taken. This study was approved by the Institutional Committee of Research Ethics. Results. A total of 198 (66 per group) women were evaluated. Sociodemographic data and level of physical activity were not found to be associated with perception of pain after mammogram. However, group 1 had the greatest reduction in postprocedure perception of pain compared with groups 2 (relative risk [RR]53.54, 95% confidence interval [CI] 5 2.12-5.51, P< 0.05) and 0 (RR51.92 (95% CI51.08-3.42, P< 0.05). Conclusions. Pre-examination upper limb exercises were most effective in reducing the perception and sensation of pain. However, women who performed lower limb exercises also had a decreased perception of pain compared with the control group. [ABSTRACT FROM AUTHOR]

Reconciling the origins of morphological diversity with the deep homology of underlying mechanisms is a question fundamental to the goals of evolutionary developmental biology ("evo-devo" or EDB). In this paper I argue that differing research agendas in evolutionary and developmental biology have hindered how we address this question, but that the limb provides ideal "common ground" for their fuller integration. To support this idea, I review two previous analyses of limb variation in mammal, bird, and reptile taxa that offer complementary approaches to explaining diversity. Specifically, I present evidence suggesting that: (1) a shared genetic architecture affects the pattern of between limb developmental integration, while their functional dissociation is linked to both increased phenotypic evolvability and diversity of interlimb proportions, and (2) within limb proportional diversity is biased such that proximal and distal segments function as tradeoffs while the middle segment is more conservative, a signal that is both evident from early in morphogenesis and suggestive of an "inhibitory cascade" model of limb proximo-distal axis development. In the first case, shared genetic mechanisms predict both observed developmental integration between limbs and patterns of cladespecific diversity. In the second case, underappreciated patterns of phenotypic diversity suggest novel insights into the underlying developmental mechanisms by which variation is generated. These studies show how insights from both evolutionary and developmental biology of the limb may be used to generate novel testable hypotheses into the origins of diversity that are broadly applicable to the integration of EDB. [ABSTRACT FROM AUTHOR]

The article reports that A 14-year-old boy of European and Latino heritage presented to the Emergency Room for an acute episode of intense ‘stabbing and burning' pain to his hands and feet. Similar episodes had been occurring almost every month for several years and lasted for a few hours. Triggers included stress and cold temperature.

Background: The identification of novel rehabilitative impairments that are risk factors for mobility limitations may improve their prevention and treatment among older adults. We tested the hypothesis that impaired rhythmic interlimb ankle and shoulder coordination are risk factors for subsequent mobility limitations among older adults.Methods: We conducted a 1-year prospective cohort study of community-dwelling older adults (N = 99) aged 67 years and older who did not have mobility limitations (Short Physical Performance Battery score > 9) at baseline. Participants performed antiphase coordination of the right and left ankles or shoulders while paced by an auditory metronome. Using multivariable logistic regression, we determined odds ratios (ORs) for mobility limitations at 1-year follow-up as a function of coordination variability and asymmetry.Results: After adjusting for age, sex, body mass index, Mini-Mental State Examination score, number of chronic conditions, and baseline Short Physical Performance Battery score, ORs were significant for developing mobility limitations based on a 1 SD difference in the variability of ankle (OR = 1.88; 95% confidence interval [CI]: 1.16-3.05) and shoulder (OR = 1.96; 95% CI: 1.17-3.29) coordination. ORs were significant for asymmetry of shoulder (OR = 2.11; 95% CI: 1.25-3.57), but not ankle (OR = 0.95; 95% CI: 0.59-1.55) coordination. Similar results were found in unadjusted analyses.Conclusions: The results support our hypothesis that impaired interlimb ankle and shoulder coordination are risk factors for the development of mobility limitations. Future work is needed to further examine the peripheral and central mechanisms underlying this relationship and to test whether enhancing coordination alters mobility limitations. [ABSTRACT FROM AUTHOR]

Background. The efficacy of risk model scores to predict venous thromboembolism (VTE) in ambulatory cancer patients is under investigation, aiming to stratify on an individual risk basis the subset of the cancer population that could mostly benefit from primary thromboprophylaxis. Materials and Methods. We prospectively assessed 843 patients with active cancers, collecting clinical and laboratory data. We screened all the patients with a duplex ultrasound (B-mode imaging and Doppler waveform analysis) of the upper and lower limbs to evaluate the right incidence of VTE (both asymptomatic and symptomatic). The efficacy of the existing Khorana risk model in preventing VTE was also explored in our population. Several risk factors associated with VTE were analyzed, leading to the construction of a risk model. The Fine and Gray model was used to account for death as a competing risk in the derivation of the new model. Results. The risk factors significantly associated with VTE at univariate analysis and further confirmed in the multivariate analysis, after bootstrap validation, were the presence of metastatic disease, the compression of vascular/lymphatic structures by tumor, a history of previous VTE, and a Khorana score >2. Time-dependent receiving operating characteristic (ROC) curve analysis showed a significant improvement in the area under the curve of the new score over the Khorana model at 3 months (71.9% vs. 57.9%, p5.001), 6 months (75.4% vs. 58.6%, p< .001), and 12 months (69.8% vs. 58.3%, p5.014). Conclusion. ONKOTEV score steps into history of cancer-related- VTE as a promising tool to drive the decision about primary prophylaxis in cancer outpatients. The validation represents the goal of the prospective ONKOTEV-2 study, endorsed and approved by the European Organization for Research and Treatment of Cancer Young Investigators Program. [ABSTRACT FROM AUTHOR]

Background: The association between history of keratinocyte carcinoma (KC, also known as nonmelanoma skin cancer) and risk of developing invasive melanoma has not been assessed comprehensively using prospective data.Methods: We followed 91 846 women in the Nurses' Health Study (NHS; 1984-2010), 114 918 women in the NHSII (1989-2011), and 48 946 men in the Health Professionals Follow-up Study (1986-2010) for diagnoses of KC and melanoma biennially. Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) of melanoma associated with history of KC, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). All statistical tests were two-sided.Results: We documented 1949 melanomas, 38 842 BCCs, and 7462 SCCs over 6.4 million person-years of follow-up. After adjustment for other risk factors, a personal history of KC was associated with an increased risk of melanoma (meta-analysis HR = 2.22, 95% CI = 1.73 to 2.85). The association was more apparent among participants with a history of both BCC and SCC (HR = 3.40, 95% CI = 1.60 to 7.19) than among participants with a history of BCC only (HR = 2.20, 95% CI = 1.80 to 2.70) or SCC only (HR = 1.56, 95% CI = 0.98 to 2.46), and there was a strong risk-increasing trend associated with a higher number of reported KCs removed by surgery ( P trend < .001). In women, KC history was more strongly associated with head/neck melanomas (HR = 4.17, 95% CI = 2.77 to 6.27) than with trunk or limb melanomas (both HRs < 2.50, P heterogeneity = .04).Conclusions: Our results provide novel insights for the relationship between KC history and risk of developing melanoma, which may be important for melanoma prevention. [ABSTRACT FROM AUTHOR]

Severe frostbite is associated with high levels of morbidity through loss of digits or limbs. The aim of this study was to examine the salvage rate following severe frostbite injury. Frostbite patients from 2006 to 2014 were identified in the prospectively maintained database at a single urban burn and trauma center. Patients with imaging demonstrating a lack of blood flow in limbs/digits were included in the analysis (N = 73). The Hennepin Frostbite Score was used to quantify frostbite injury and salvage. This score provides a single value to assess each individual patient's salvage rate. The majority of patients with perfusion deficits were male (80%) with an average age of 42 years (range 11-83 years). Patients requiring amputation tended to be older (P = .002), have more tissue impacted by frostbite (P < .001), and experienced a longer time from rewarming to thrombolytic therapy (P = .001). A majority of patients (62%) received thrombolytic treatment. The percentage of patients requiring amputation was lower and the salvage rate was higher in patients treated with thrombolytics; however, the differences failed to reach statistical significance (P = .092 and P = .061, respectively). The rate of salvage decreases as the time from rewarming to thrombolytic therapy increases. Regression analysis demonstrates an additional 26.8% salvage loss with each hour of delayed treatment (P = .006). When the amount of tissue at risk for amputation is included in the model, each hour delay in thrombolytic treatment results in a 28.1% decrease in salvage (P = .011). This study demonstrates a significant decrease in limb/digit salvage with each hour of delayed administration of thrombolytics in patients with severe frostbite. [ABSTRACT FROM AUTHOR]

In this study, the subject of whether investment in one bilateral structure was linked to investment in the homologous bilateral opposite structure was investigated. Male fiddler crabs (genus Uca, family Ocypodidae) displayed strong bilateral claw differentiation of function and size, which are used for feeding (minor claw) or display/combat (major claw). Females had similar-sized feeding claws. Linkage between claw size was investigated by estimating the deviations from an overall fitted regression of claw length to body size. The positive correlations of the deviations of claw size for major and minor claws of males and between right and left claws of females, relative to body size, suggested a linkage in investment between one claw and the corresponding claw on the other side of the body, for both monomorphic females and dimorphic males. A signal to send resources may be effectively gated to the claw complex, suggesting that positively correlated resources are allocated to both claws. Positive correlations were also found at the interspecific level. The fiddler crab model, described here, gives access to study the linkage in symmetric and asymmetric bilateral structures in the same species with a connection to the macroevolutionary level. [ABSTRACT FROM AUTHOR]