Walking performance differs between people with multiple sclerosis who perform distinct types of exercise.

Aim: To determine whether walking performance differed between people with multiple sclerosis (MS) who performed distinct types, volumes and intensities of exercise.Materials & methods: Forty-five people with relapsing-remitting MS performed two trials of the 2-min walk test, one at a preferred speed and another at a fast speed. Gait metrics were measured by wireless inertial sensors. Participants reported the type (aerobic, resistance), volume and intensity of exercise performed.Results: Walking speed reserve and gait variability were better in participants who performed combined aerobic and resistance exercises compared with those who performed aerobic-only exercise.Conclusion: Walking performance differs in people with mild MS disability based on the type and volume of exercise performed.

Exercise improves many symptoms in people living with multiple sclerosis (MS). However, the best type, intensity and amount of exercise to improve walking in people living with MS are not clear. This study aimed to determine whether walking performance differed in people with MS who performed different types and amounts of exercise. A total of 45 people with relapsing-remitting MS participated in this study. The participants reported the average amount, intensity and types (aerobic, resistance) of exercise performed on a weekly basis. The participants also performed two walking tests, one at their normal walking speed and the other at their fastest walking speed. The results showed that participants who performed both aerobic and resistance types of exercise were more stable and were able to increase their walking speed more than participants who only performed aerobic types of exercise. Regardless of exercise type, participants who performed at least 150 min of exercise per week were more stable when walking at a fast speed compared with participants who performed less than 150 min of exercise per week. These findings underscore the importance for people living with MS to perform aerobic and resistance types of exercise for at least 150 min per week to help maintain walking performance.

R2 should not be used to describe behavioral-economic discounting and demand models.

Literature concerning operant behavioral economics shows a strong preference for the coefficient of determination (R2) metric to (a) describe how well an applied model accounts for variance and (b) depict the quality of collected data. Yet R2 is incompatible with nonlinear modeling. In this report, we provide an updated discussion of the concerns with R2. We first review recent articles that have been published in the Journal of the Experimental Analysis of Behavior that employ nonlinear models, noting recent trends in goodness-of-fit reporting, including the continued reliance on R2. We then examine the tendency for these metrics to bias against linear-like patterns via a positive correlation between goodness of fit and the primary outputs of behavioral-economic modeling. Mathematically, R2 is systematically more stringent for lower values for discounting parameters (e.g., k) in discounting studies and lower values for the elasticity parameter (α) in demand analysis. The study results suggest there may be heterogeneity in how this bias emerges in data sets of varied composition and origin. There are limitations when using any goodness-of-fit measure to assess the systematic nature of data in behavioral-economic studies, and to address those we recommend the use of algorithms that test fundamental expectations of the data.

The extensive m5C epitranscriptome of Thermococcus kodakarensis is generated by a suite of RNA methyltransferases that support thermophily.

RNAs are often modified to invoke new activities. While many modifications are limited in frequency, restricted to non-coding RNAs, or present only in select organisms, 5-methylcytidine (m5C) is abundant across diverse RNAs and fitness-relevant across Domains of life, but the synthesis and impacts of m5C have yet to be fully investigated. Here, we map m5C in the model hyperthermophile, Thermococcus kodakarensis. We demonstrate that m5C is ~25x more abundant in T. kodakarensis than human cells, and the m5C epitranscriptome includes ~10% of unique transcripts. T. kodakarensis rRNAs harbor tenfold more m5C compared to Eukarya or Bacteria. We identify at least five RNA m5C methyltransferases (R5CMTs), and strains deleted for individual R5CMTs lack site-specific m5C modifications that limit hyperthermophilic growth. We show that m5C is likely generated through partial redundancy in target sites among R5CMTs. The complexity of the m5C epitranscriptome in T. kodakarensis argues that m5C supports life in the extremes.

Age- and Sex-Specific Myocardial Blood Flow Values in Patients Without Coronary Atherosclerosis on Rb-82 PET Myocardial Perfusion Imaging.

BACKGROUND: Quantitative myocardial blood flow (MBF) on positron-emission tomography myocardial perfusion imaging is a measure of the overall health of the coronary circulation. The ability to adequately augment blood flow, measured by myocardial blood flow reserve (MBFR), is associated with lower major adverse cardiovascular events and all-cause mortality. The age-specific ranges of MBFR in patients without demonstrable coronary artery disease have not been well established. We aimed to determine the effect of age and sex on MBF in a cohort of patients without demonstrable coronary artery disease. METHODS: Patients who underwent positron-emission tomography myocardial perfusion imaging studies from 2012 to 2022 on positron-emission tomography/computed tomography cameras were included if the summed stress score was 0, the coronary calcium score was 0, and the left ventricular ejection fraction was ≥50%. Those with known coronary artery disease, prior history of coronary intervention, diabetes, heart/kidney/liver transplant, cirrhosis, or chronic kidney disease stage IV+ were excluded. MBF was calculated using a net retention model (ImagenQ, Cardiovascular Imaging Technologies, Kansas City), and quantile regression models were developed to predict MBF. RESULTS: Among 2789 patients (age 59.9±13.0 years, 76.4% females), median rest MBF was 0.73 (0.60-0.91) mL/min·g, stress MBF was 1.72 (1.41-2.10) mL/min·g, and MBFR was 2.31 (1.96-2.74). Across all ages, males augmented MBF in response to vasodilator stress to a greater degree than females but achieved lower absolute stress MBF. Younger males in particular achieved a higher MBFR than their female counterparts, and this gap narrowed with increasing age. Predicted MBFR for a 20-year-old male was 3.18 and female was 2.50, while predicted MBFR for an 80-year-old male was 2.17 and female was 2.02. CONCLUSIONS: In patients without demonstrable coronary artery disease, MBFR is higher in younger males than younger females and decreases with age in both sexes. Age- and sex-specific MBFR may be important in risk prediction and guidance for revascularization and warrant further study.

Predicting severe outcomes in pediatric trauma patients: Shock index pediatric age-adjusted vs. age-adjusted tachycardia.

INTRODUCTION: When an injured patient arrives in the Emergency Department (ED), timely and appropriate care is crucial. Shock Index Pediatric Age-Adjusted (SIPA) has been shown to accurately identify pediatric patients in need of emergency interventions. However, no study has evaluated SIPA against age-adjusted tachycardia (AT). This study aims to compare SIPA with AT in predicting outcomes such as mortality, severe injury, and the need for emergent intervention in pediatric trauma patients. MATERIAL AND METHODS: This is a retrospective cross-sectional analysis of patient data abstracted from the Trauma Quality Improvement Program Participant Use Files (TQIP PUFs) for years 2013-2020. Patients aged 4-16 with blunt mechanism of injury and injury severity score (ISS) > 15 were included. 36,517 children met this criteria. Sensitivity, specificity, overtriage, and undertriage rates were calculated to compare the effectiveness of AT and elevated SIPA as predictors of severe injuries and need for emergent intervention. Emergent interventions included craniotomy, endotracheal intubation, thoracotomy, laparotomy, or chest tube placement within 24 h of arrival. RESULTS: AT classified 59% of patients as "high risk," while elevated SIPA identified 26%. Compared to AT patients, a greater proportion of patients with elevated SIPA required a blood transfusion within 24 h (22% vs. 12%, respectively; p < 0.001). In-hospital mortality was higher for the elevated SIPA group than AT (10% vs. 5%, respectively; p < 0.001) as well as the need for emergent operative interventions (43% vs. 32% respectively; p < 0.001). Grade 3 or higher liver/spleen lacerations requiring blood transfusion were also more common among elevated SIPA patients than AT patients (8% vs. 4%, respectively; p < 0.001). AT demonstrated greater sensitivity but lower specificity compared to SIPA across all outcomes. AT showed improved overtriage and undertriage rates compared to SIPA, but this is attributed to identifying a large proportion of the sample as "high risk." CONCLUSIONS: AT outperforms SIPA in sensitivity for mortality, injury severity and emergent interventions in pediatric trauma patients while the specificity of SIPA is high across these outcomes.

Hybridization in birds-of-paradise: Widespread ancestral gene flow despite strong sexual selection in a lek-mating system.

Sexual selection can directly contribute to reproductive isolation and is an important mechanism that can lead to speciation. Lek-mating is one of the most extreme forms of sexual selection, but surprisingly does not seem to preclude occasional hybridization in nature. However, hybridization among lekking species may still be trivial if selection against offspring with intermediate phenotypes prohibits introgression. Here we investigate this further by sequencing the genomes of nearly all bird-of-paradise (Paradisaeidae) species and 10 museum specimens of putative hybrid origin. We find that intergeneric hybridization indeed still takes place despite extreme differentiation in form, plumage, and behavior. In parallel, the genomes of contemporary species contain widespread signatures of past introgression, demonstrating that hybridization has repeatedly resulted in shared genetic variation despite strong sexual isolation. Our study raises important questions about extrinsic factors that modulate hybridization probability and the evolutionary consequences of introgressive hybridization between lekking species.

Heat Risk Perceptions and Coping Strategies of the Unhoused.

The escalating awareness of heat-related risks and the associated imperative to enhance preparedness strategies at various levels has spurred a growing emphasis on disseminating knowledge about heat vulnerability. These efforts aim to equip diverse stakeholders with practical heat planning and forecasting tools. The success of these communication initiatives hinges on understanding the nuanced perceptions of risk and the priority assigned to addressing heat as a health risk. This paper delves explicitly into the unhoused population's risk perceptions and coping strategies. Acknowledged as one of the most underserved and vulnerable groups to extreme heat, unhoused individuals face prolonged exposure, a heightened frequency of mental and physical health issues, and limited coping resources during extreme heat events. Despite widespread acknowledgment of their vulnerability, little attention has been directed towards researching health behavior within this demographic about excessive heat. We developed a survey instrument using the theory of planned behavior (TPB) to bridge this gap. We collected quantitative survey data from unhoused populations in Columbia, South Carolina, an area of the United States that experiences extreme heat events and has a sizeable unhoused population. Using a series of hierarchical multiple regression models, our findings indicate that TPB variables predict the intention to avoid the heat while considering additional coping strategies common among unhoused individuals. These findings offer valuable insights for public health researchers, practitioners, and community officials engaged in direct interactions with unhoused populations, informing how this underserved group manages excessive heat exposure.

Interhemispheric inhibition and gait adaptation associations in people with multiple sclerosis.

BACKGROUND: Multiple sclerosis is a neurodegenerative disease that damages the myelin sheath within the central nervous system. Axonal demyelination, particularly in the corpus callosum, impacts communication between the brain's hemispheres in persons with multiple sclerosis (PwMS). Changes in interhemispheric communication may impair gait coordination which is modulated by communication across the corpus callosum to excite and inhibit specific muscle groups. To further evaluate the functional role of interhemispheric communication in gait and mobility, this study assessed the ipsilateral silent period (iSP), an indirect marker of interhemispheric inhibition and how it relates to gait adaptation in PwMS. METHODS: Using transcranial magnetic stimulation (TMS), we assessed interhemispheric inhibition differences between the more affected and less affected hemisphere in the primary motor cortices in 29 PwMS. In addition, these same PwMS underwent a split-belt treadmill walking paradigm, with the faster paced belt moving under their more affected limb. Step length asymmetry (SLA) was the primary outcome measure used to assess gait adaptability during split-belt treadmill walking. We hypothesized that PwMS would exhibit differences in iSP inhibitory metrics between the more affected and less affected hemispheres and that increased interhemispheric inhibition would be associated with greater gait adaptability in PwMS. RESULTS: No statistically significant differences in interhemispheric inhibition or conduction time were found between the more affected and less affected hemisphere. Furthermore, SLA aftereffect was negatively correlated with both average percent depth of silent period (dSP%AVE) (r = -0.40, p = 0.07) and max percent depth of silent period (dSP%MAX) r = -0.40, p = 0.07), indicating that reduced interhemispheric inhibition was associated with greater gait adaptability in PwMS. CONCLUSION: The lack of differences between the more affected and less affected hemisphere indicates that PwMS have similar interhemispheric inhibitory capacity irrespective of the more affected hemisphere. Additionally, we identified a moderate correlation between reduced interhemispheric inhibition and greater gait adaptability. These findings may indicate that interhemispheric inhibition may in part influence responsiveness to motor adaptation paradigms and the need for further research evaluating the neural mechanisms underlying the relationship between interhemispheric inhibition and motor adaptability.

ACR Appropriateness Criteria® Sepsis.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. A search for the underlying cause of infection typically includes radiological imaging as part of this investigation. This document focuses on thoracic and abdominopelvic causes of sepsis. In 2017, the global incidence of sepsis was estimated to be 48.9 million cases, with 11 million sepsis-related deaths (accounting for nearly 20% of all global deaths); therefore, understanding which imaging modalities and types of studies are acceptable or not acceptable is imperative. The 5 variants provided include the most commonly encountered scenarios in the setting of sepsis along with recommendations and data for each imaging study. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

ACR Appropriateness Criteria® Sepsis

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. A search for the underlying cause of infection typically includes radiological imaging as part of this investigation. This document focuses on thoracic and abdominopelvic causes of sepsis. In 2017, the global incidence of sepsis was estimated to be 48.9 million cases, with 11 million sepsis-related deaths (accounting for nearly 20% of all global deaths); therefore, understanding which imaging modalities and types of studies are acceptable or not acceptable is imperative. The 5 variants provided include the most commonly encountered scenarios in the setting of sepsis along with recommendations and data for each imaging study. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Effect of Tafamidis on Renal Function in Patients With Transthyretin Amyloid Cardiomyopathy in ATTR-ACT.

Background: Chronic kidney disease (CKD) is common among patients with amyloid cardiomyopathy. Tafamidis was approved for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) based on findings from ATTR-ACT (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy). Objectives: This post hoc analysis evaluated changes in renal function among patients with ATTR-CM in ATTR-ACT. Methods: Patients were randomized to receive tafamidis (20 mg and 80 mg pooled) or placebo for 30 months. The change from baseline in the estimated glomerular filtration rate (eGFR) was compared over time. A composite endpoint of all-cause death, dialysis, kidney transplant, or ≥30% decline in eGFR from baseline was analyzed based on the time to first event. Results: The mean baseline eGFR was 57.5 ± 17.3 and 55.6 ± 16.8 mL/min/1.73 m2 in the tafamidis (n = 264) and placebo (n = 177) groups, respectively. At 30 months, patients treated with tafamidis had a significantly smaller decline in eGFR compared with placebo (least squares mean difference = 3.99 mL/min/1.73 m2; 95% CI: 1.31-6.68; P = 0.004). In patients who completed ATTR-ACT, improvement in CKD staging was more common with tafamidis vs placebo treatment (17.7% vs 7.2%; OR: 2.75; 95% CI: 1.10-6.90; P = 0.034). A lower proportion of tafamidis-treated patients reached the composite renal endpoint (crude rates 34.5% vs 44.1%; HR: 0.73, 95% CI: 0.54-0.99; P = 0.040). Conclusions: Renal function deteriorates over time in patients with ATTR-CM, and tafamidis treatment was associated with a reduction in this deterioration, and a higher incidence of improved eGFR and CKD staging over 30 months compared with placebo. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT] NCT01994889).

New technologies in therapeutic antibody development: The next frontier for treating infectious diseases.

Adaptive immunity to viral infections requires time to neutralize and clear viruses to resolve infection. Fast growing and pathogenic viruses are quickly established, are highly transmissible and cause significant disease burden making it difficult to mount effective responses, thereby prolonging infection. Antibody-based passive immunotherapies can provide initial protection during acute infection, assist in mounting an adaptive immune response, or provide protection for those who are immune suppressed or immune deficient. Historically, plasma-derived antibodies have demonstrated some success in treating diseases caused by viral pathogens; nonetheless, limitations in access to product and antibody titer reduce success of this treatment modality. Monoclonal antibodies (mAbs) have proven an effective alternative, as it is possible to manufacture highly potent and specific mAbs against viral targets on an industrial scale. As a result, innovative technologies to discover, engineer and manufacture specific and potent antibodies have become an essential part of the first line of treatment in pathogenic viral infections. However, a mAb targeting a specific epitope will allow escape variants to outgrow, causing new variant strains to become dominant and resistant to treatment with that mAb. Methods to mitigate escape have included combining mAbs into cocktails, creating bi-specific or antibody drug conjugates but these strategies have also been challenged by the potential development of escape mutations. New technologies in developing antibodies made as recombinant polyclonal drugs can integrate the strength of poly-specific antibody responses to prevent mutational escape, while also incorporating antibody engineering to prevent antibody dependent enhancement and direct adaptive immune responses.

The effect of sodium-glucose cotransporter-2 inhibitors on inflammatory biomarkers: A meta-analysis of randomized controlled trials.

AIMS: To conduct a meta-analysis of randomized controlled trials (RCTs) to assess the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on inflammatory biomarkers. METHODS: Medline, Embase and the Cochrane Library were searched for RCTs investigating the effect of SGLT2 inhibitors on inflammatory biomarkers, adipokine profiles and insulin sensitivity. RESULTS: Thirty-eight RCTs were included (14 967 participants, 63.3% male, mean age 62 ± 8.6 years) with a median (interquartile range) follow-up of 16 (12-24) weeks. Meta-analysis showed that SGLT2 inhibitors significantly improved adiponectin, interleukin-6, tumour necrosis factor receptor-1 (vs. placebo alone: standardized mean difference [SMD] 0.34 [95% confidence interval {CI} 0.23, 0.45], mean difference [MD] -0.85 pg/mL [95% CI -1.32, -0.38], SMD -0.13 [95% CI -0.20, -0.06], respectively), leptin and homeostatic model assessment of insulin resistance index (vs. CONTROL: SMD -0.20 [95% CI -0.33, -0.07], MD -0.83 [95% CI -1.32, -0.33], respectively). There were no significant changes in C-reactive protein (CRP), tumour necrosis factor-α, plasminogen activator inhibitor-1, fibroblast growth factor-21 or monocyte chemoattractant protein-1. CONCLUSIONS: Our analysis shows that SGLT2 inhibitors likely improve adipokine biomarkers and insulin sensitivity, but there is little evidence that SGLT2 inhibitors improve other inflammatory biomarkers including CRP.

Influence of Body Mass Index on Radiation Exposure Across Imaging Modalities in the Evaluation of Chest Pain.

BACKGROUND: Essential to a patient-centered approach to imaging individuals with chest pain is knowledge of differences in radiation effective dose across imaging modalities. Body mass index (BMI) is an important and underappreciated predictor of effective dose. This study evaluated the impact of BMI on estimated radiation exposure across imaging modalities. METHODS AND RESULTS: This was a retrospective analysis of patients with concern for cardiac ischemia undergoing positron emission tomography (PET)/computed tomography (CT), cadmium zinc telluride single-photon emission CT (SPECT) myocardial perfusion imaging, or coronary CT angiography (CCTA) using state-of-the-art imaging modalities and optimal radiation-sparing protocols. Radiation exposure was calculated across BMI categories based on established cardiac imaging-specific conversion factors. Among 9046 patients (mean±SD age, 64.3±13.1 years; 55% men; mean±SD BMI, 30.6±6.9 kg/m2), 4787 were imaged with PET/CT, 3092 were imaged with SPECT/CT, and 1167 were imaged with CCTA. Median (interquartile range) radiation effective doses were 4.4 (3.9-4.9) mSv for PET/CT, 4.9 (4.0-6.3) mSv for SPECT/CT, and 6.9 (4.0-11.2) mSv for CCTA. Patients at a BMI <20 kg/m2 had similar radiation effective dose with all 3 imaging modalities, whereas those with BMI ≥20 kg/m2 had the lowest effective dose with PET/CT. Radiation effective dose and variability increased dramatically with CCTA as BMI increased, and was 10 times higher in patients with BMI >45 kg/m2 compared with <20 kg/m2 (median, 26.9 versus 2.6 mSv). After multivariable adjustment, PET/CT offered the lowest effective dose, followed by SPECT/CT, and then CCTA (P<0.001). CONCLUSIONS: Although median radiation exposure is modest across state-of-the-art PET/CT, SPECT/CT, and CCTA systems using optimal radiation-sparing protocols, there are significant variations across modalities based on BMI. These data are important for making patient-centered decisions for ischemic testing.

Clinical and Molecular Spectrum of Autosomal Recessive CA8-Related Cerebellar Ataxia.

BACKGROUND: Based on a limited number of reported families, biallelic CA8 variants have currently been associated with a recessive neurological disorder named, cerebellar ataxia, mental retardation, and dysequilibrium syndrome 3 (CAMRQ-3). OBJECTIVES: We aim to comprehensively investigate CA8-related disorders (CA8-RD) by reviewing existing literature and exploring neurological, neuroradiological, and molecular observations in a cohort of newly identified patients. METHODS: We analyzed the phenotype of 27 affected individuals from 14 families with biallelic CA8 variants (including data from 15 newly identified patients from eight families), ages 4 to 35 years. Clinical, genetic, and radiological assessments were performed, and zebrafish models with ca8 knockout were used for functional analysis. RESULTS: Patients exhibited varying degrees of neurodevelopmental disorders (NDD), along with predominantly progressive cerebellar ataxia and pyramidal signs and variable bradykinesia, dystonia, and sensory impairment. Quadrupedal gait was present in only 10 of 27 patients. Progressive selective cerebellar atrophy, predominantly affecting the superior vermis, was a key diagnostic finding in all patients. Seven novel homozygous CA8 variants were identified. Zebrafish models demonstrated impaired early neurodevelopment and motor behavior on ca8 knockout. CONCLUSION: Our comprehensive analysis of phenotypic features indicates that CA8-RD exhibits a wide range of clinical manifestations, setting it apart from other subtypes within the category of CAMRQ. CA8-RD is characterized by cerebellar atrophy and should be recognized as part of the autosomal-recessive cerebellar ataxias associated with NDD. Notably, the presence of progressive superior vermis atrophy serves as a valuable diagnostic indicator. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

AICAR confers prophylactic cardioprotection in doxorubicin-induced heart failure in rats.

Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects, leading to heart failure (HF). Impaired mitochondrial function is thought to be key factor driving progression into HF. We have previously shown in a rat model of DOX-HF that heart failure with reduced ejection fraction correlates with mitochondrial loss and dysfunction. Adenosine monophosphate-dependent kinase (AMPK) is a cellular energy sensor, regulating mitochondrial biogenesis and energy metabolism, including fatty acid oxidation. We hypothesised that AMPK activation could restore mitochondrial function and therefore be a novel cardioprotective strategy for the prevention of DOX-HF. Consequently, we set out to assess whether 5-aminoimidazole-4-carboxamide 1-ß-D-ribofuranoside (AICAR), an activator of AMPK, could prevent cardiac functional decline in this chronic intravenous rat model of DOX-HF. In line with our hypothesis, AICAR improved cardiac systolic function. AICAR furthermore improved cardiac mitochondrial fatty acid oxidation, independent of mitochondrial number, and in the absence of observable AMPK-activation. In addition, we found that AICAR prevented loss of myocardial mass. RNAseq analysis showed that this may be driven by normalisation of pathways associated with ribosome function and protein synthesis, which are impaired in DOX-treated rat hearts. AICAR furthermore prevented dyslipidemia and excessive body-weight loss in DOX-treated rats, which may contribute to preservation of myocardial mass. Though it is unclear whether AICAR exerted its cardioprotective effect through cardiac or extra-cardiac AMPK-activation or via an AMPK-independent effect, these results show promise for the use of AICAR as a cardioprotective agent in DOX-HF to both preserve cardiac function and mass.

Sea Urchin Spine Embedded in the Sole of the Foot: Eight-Year Radiographic Follow-Up Without Removal.

When sea urchin puncture injuries occur during coastal recreation or work activities, they often affect extremities, such as hands and feet. There is a plethora of information on treatments for these puncture injuries, with the most common among medical professionals being the removal of all partially embedded spines and the removal of as many fully embedded spines as possible. When the spines are deeply embedded and/or fragmented, they might not be removed, especially when they are not located in critical areas such as tendons or joints. This reflects the generally held notion that smaller spines and spine fragments will eventually dissolve or be absorbed. Here we report an unusual case where the tip of a sea urchin spine became embedded in the soft tissue of the sole of the foot of a 21-year-old male after he stepped on one after falling off a kayak off the coast of Oahu, Hawai'i. The deeply embedded spine was not removed. By three weeks after the injury, the patient did not have any symptoms, and eight years later, he was still symptom-free. Radiographs taken one year after the injury showed that the spine had fragmented into two pieces. The smaller piece was about 15% of the size of the original embedded spine, and it had apparently been absorbed (it was not seen on final radiographs eight years later). Analysis of radiographs eight years after the injury showed that the main or large spine fragment was still distinctly detectable in the soft tissue; there was no visible evidence that it had undergone significant absorption or migrated from the original location. The absence of any obvious radiographic rarefaction over eight years is contrary to the lore that sea urchin spines that remain in human soft tissue will exhibit significant, or complete, absorption or dissolution over months to a few years.