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Meta-analyses suggest that the published literature represents only a small minority of the total data collected in biomedical research, with most becoming ‘dark data’ unreported in the literature. Dark data is due to publication bias toward novel results that confirm investigator hypotheses and omission of data that do not. Publication bias contributes to scientific irreproducibility and failures in bench-to-bedside translation. Sharing dark data by making it Findable, Accessible, Interoperable, and Reusable (FAIR) may reduce the burden of irreproducible science by increasing transparency and support data-driven discoveries beyond the lifecycle of the original study. We illustrate feasibility of dark data sharing by recovering original raw data from the Multicenter Animal Spinal Cord Injury Study (MASCIS), an NIH-funded multi-site preclinical drug trial conducted in the 1990s that tested efficacy of several therapies after a spinal cord injury (SCI). The original drug treatments did not produce clear positive results and MASCIS data were stored in boxes for more than two decades. The goal of the present study was to independently confirm published machine learning findings that perioperative blood pressure is a major predictor of SCI neuromotor outcome (Nielson et al., 2015). We recovered, digitized, and curated the data from 1125 rats from MASCIS. Analyses indicated that high perioperative blood pressure at the time of SCI is associated with poorer health and worse neuromotor outcomes in more severe SCI, whereas low perioperative blood pressure is associated with poorer health and worse neuromotor outcome in moderate SCI. These findings confirm and expand prior results that a narrow window of blood-pressure control optimizes outcome, and demonstrate the value of recovering dark data for assessing reproducibility of findings with implications for precision therapeutic approaches.

Conventional MRI measures of traumatic spinal cord injury severity largely rely on 2-dimensional injury characteristics such as intramedullary lesion length and cord compression. Recent advances in spinal cord (SC) analysis have led to the development of a robust anatomic atlas incorporated into an open-source platform called the Spinal Cord Toolbox (SCT) that allows for quantitative volumetric injury analysis. In the current study, we evaluate the prognostic value of volumetric measures of spinal cord injury on MRI following registration of T2-weighted (T2w) images and segmented lesions from acute SCI patients with a standardized atlas. This IRB-approved prospective cohort study involved the image analysis of 60 blunt cervical SCI patients enrolled in the TRACK-SCI clinical research protocol. Axial T2w MRI data obtained within 24 h of injury were processed using the SCT. Briefly, SC MRIs were automatically segmented using the sct_deepseg_sc tool in the SCT and segmentations were manually corrected by a neuro-radiologist. Lesion volume data were used as predictor variables for correlation with lower extremity motor scores at discharge. Volumetric MRI measures of T2w signal abnormality comprising the SCI lesion accurately predict lower extremity motor scores at time of patient discharge. Similarly, MRI measures of injury volume significantly correlated with motor scores to a greater degree than conventional 2-D metrics of lesion size. The volume of total injury and of injured spinal cord motor regions on T2w MRI is significantly and independently associated with neurologic outcome at discharge after injury.

Neuropathic pain is one of the most common secondary complications occurring after spinal cord injury (SCI), and often surpasses motor and sensory deficits in the patient population preferences of the most important aspects to be treated. Despite the better understanding of the molecular and physiological mechanisms of neuropathic pain, reliable treatments are still lacking and exhibit wide variations in efficiency. Previous reports have suggested that the most effective pain management is early treatment. To this end, we utilized the TRACK-SCI prospective clinical research database to assess the neuropathic pain status of all enrolled patients and identify acute care variables that can predict the development of neuropathic pain 6- and 12-months post SCI. 36 out of 61 patients of our study cohort reported neuropathic pain at the chronic stages post SCI. Using multidimensional analytics and logistic regression we discovered that (1) the number of total injuries the patient sustained, (2) the injury severity score (ISS), (3) the lower limb total motor score, and (4) the sensory pin prick total score together predict the development of chronic neuropathic pain after SCI. The balanced accuracy of the corresponding logistic regression model is 74.3%, and repeated 5-fold cross validation showed an AUC of 0.708. Our study suggests a crucial role of polytrauma in chronic pain development after SCI and offers a predictive model using variables routinely collected at every hospital setting.

Background: Predicting neurological recovery after spinal cord injury (SCI) is challenging. Using topological data analysis, we have previously shown that mean arterial pressure (MAP) during SCI surgery predicts long-term functional recovery in rodent models, motivating the present multicenter study in patients. Methods: Intra-operative monitoring records and neurological outcome data were extracted (n = 118 patients). We built a similarity network of patients from a low-dimensional space embedded using a non-linear algorithm, Isomap, and ensured topological extraction using persistent homology metrics. Confirmatory analysis was conducted through regression methods. Results: Network analysis suggested that time outside of an optimum MAP range (hypotension or hypertension) during surgery was associated with lower likelihood of neurological recovery at hospital discharge. Logistic and LASSO (least absolute shrinkage and selection operator) regression confirmed these findings, revealing an optimal MAP range of 76–[104-117] mmHg associated with neurological recovery. Conclusions: We show that deviation from this optimal MAP range during SCI surgery predicts lower probability of neurological recovery and suggest new targets for therapeutic intervention. Funding: NIH/NINDS: R01NS088475 (ARF); R01NS122888 (ARF); UH3NS106899 (ARF); Department of Veterans Affairs: 1I01RX002245 (ARF), I01RX002787 (ARF); Wings for Life Foundation (ATE, ARF); Craig H. Neilsen Foundation (ARF); and DOD: SC150198 (MSB); SC190233 (MSB); DOE: DE-AC02-05CH11231 (DM)., eLife digest Spinal cord injury is a devastating condition that involves damage to the nerve fibers connecting the brain with the spinal cord, often leading to permanent changes in strength, sensation and body functions, and in severe cases paralysis. Scientists around the world work hard to find ways to treat or even repair spinal cord injuries but few patients with complete immediate paralysis recover fully. Immediate paralysis is caused by direct damage to neurons and their extension in the spinal cord. Previous research has shown that blood pressure regulation may be key in saving these damaged neurons, as spinal cord injuries can break the communication between nerves that is involved in controlling blood pressure. This can lead to a vicious cycle of dysregulation of blood pressure and limit the supply of blood and oxygen to the damaged spinal cord tissue, exacerbating the death of spinal neurons. Management of blood pressure is therefore a key target for spinal cord injury care, but so far, the precise thresholds to enable neurons to recover are poorly understood. To find out more, Torres-Espin, Haefeli et al. used machine learning software to analyze previously recorded blood pressure and heart rate data obtained from 118 patients that underwent spinal cord surgery after acute spinal cord injury. The analyses revealed that patients who suffered from either low or high blood pressure during surgery had poorer prospects of recovery. Statistical models confirming these findings showed that the optimal blood pressure range to ensure recovery lies between 76 to 104-117 mmHg. Any deviation from this narrow window would dramatically worsen the ability to recover. These findings suggests that dysregulated blood pressure during surgery affects to odds of recovery in patients with a spinal cord injury. Torres-Espin, Haefeli et al. provide specific information that could improve current clinical practice in trauma centers. In the future, such machine learning tools and models could help develop real-time models that could predict the likelihood of a patient’s recovery following spinal cord injury and related neurological conditions.

Automated machine learning (AutoML) is positioned to democratize artificial intelligence (AI) by reducing the amount of human input and ML expertise needed to create prediction models. However, successful translation of ML in biomedicine requires moving beyond optimizing only for prediction accuracy and towards discovering reproducible clinical and biological inferences. Here, we present a model-agnostic framework to reinforce AutoML using strategies and tools of explainable and reproducible AI, including novel metrics for performance precision and feature instability. The framework enables clinicians to interpret AutoML-generated models for clinical and biological verifiability and consequently integrate domain expertise during model development. We applied the framework towards spinal cord injury prognostication and identified a detrimental relationship between intraoperative hypertension and patient outcome. Furthermore, our analysis captured evolving clinical practices such as faster time-to-surgery and blood pressure management that affected clinical model validation. Altogether, we illustrate how augmenting AutoML for inferential reproducibility empowers biomedical discovery and builds trust in AI processes towards effective clinical integration.

The guiding principle for data stewardship dictates that data be FAIR: findable, accessible, interoperable, and reusable. Data reuse allows researchers to probe data that may have been originally collected for other scientific purposes in order to gain novel insights. The current study reuses the Transforming Research and Clinical Knowledge for Traumatic Brain Injury (TRACK-TBI) Pilot dataset to build upon prior findings and ask new scientific questions. Specifically, we have previously used a multivariate analytics approach to multianalyte serum protein data from the TRACK-TBI Pilot dataset to show that an inflammatory ensemble of biomarkers can predict functional outcome at 3 and 6 months post-TBI. We and others have shown that there are quantitative and qualitative changes in inflammation that come with age, but little is known about how this interaction affects recovery from TBI. Here we replicate the prior proteomics findings with improved missing value analyses and non-linear principal component analysis and then expand upon this work to determine whether age moderates the effect of inflammation on recovery. We show that increased age correlates with worse functional recovery on the Glasgow Outcome Scale-Extended (GOS-E) as well as increased inflammatory signature. We then explore the interaction between age and inflammation on recovery, which suggests that inflammation has a more detrimental effect on recovery for older TBI patients.

Background Minocycline is a clinically available synthetic tetracycline derivative with anti-inflammatory and antibiotic properties. The majority of studies show that minocycline can reduce tissue damage and improve functional recovery following central nervous system injuries, mainly attributed to the drug’s direct anti-inflammatory, anti-oxidative, and neuroprotective properties. Surprisingly the consequences of minocycline’s antibiotic (i.e., antibacterial) effects on the gut microbiota and systemic immune response after spinal cord injury have largely been ignored despite their links to changes in mental health and immune suppression. Methods Here, we sought to determine minocycline’s effect on spinal cord injury-induced changes in the microbiota-immune axis using a cervical contusion injury in female Lewis rats. We investigated a group that received minocycline following spinal cord injury (immediately after injury for 7 days), an untreated spinal cord injury group, an untreated uninjured group, and an uninjured group that received minocycline. Plasma levels of cytokines/chemokines and fecal microbiota composition (using 16s rRNA sequencing) were monitored for 4 weeks following spinal cord injury as measures of the microbiota-immune axis. Additionally, motor recovery and anxiety-like behavior were assessed throughout the study, and microglial activation was analyzed immediately rostral to, caudal to, and at the lesion epicenter. Results We found that minocycline had a profound acute effect on the microbiota diversity and composition, which was paralleled by the subsequent normalization of spinal cord injury-induced suppression of cytokines/chemokines. Importantly, gut dysbiosis following spinal cord injury has been linked to the development of anxiety-like behavior, which was also decreased by minocycline. Furthermore, although minocycline attenuated spinal cord injury-induced microglial activation, it did not affect the lesion size or promote measurable motor recovery. Conclusion We show that minocycline’s microbiota effects precede its long-term effects on systemic cytokines and chemokines following spinal cord injury. These results provide an exciting new target of minocycline as a therapeutic for central nervous system diseases and injuries.

This study demonstrates how gene expression profiles of white blood cells in acute spinal cord injury patients can be utilized for the diagnosis of the injury severity and the neurological level of injury., Diagnosis of spinal cord injury (SCI) severity at the ultra-acute stage is of great importance for emergency clinical care of patients as well as for potential enrollment into clinical trials. The lack of a diagnostic biomarker for SCI has played a major role in the poor results of clinical trials. We analyzed global gene expression in peripheral white blood cells during the acute injury phase and identified 197 genes whose expression changed after SCI compared with healthy and trauma controls and in direct relation to SCI severity. Unsupervised coexpression network analysis identified several gene modules that predicted injury severity (AIS grades) with an overall accuracy of 72.7% and included signatures of immune cell subtypes. Specifically, for complete SCIs (AIS A), ROC analysis showed impressive specificity and sensitivity (AUC: 0.865). Similar precision was also shown for AIS D SCIs (AUC: 0.938). Our findings indicate that global transcriptomic changes in peripheral blood cells have diagnostic and potentially prognostic value for SCI severity.

Background: Heart failure (HF) is common in COPD and contributes to increased breathlessness and adverse clinical outcomes. Aims and Objectives: To test the hypothesis that COPD-HF patients exhibit greater impairments in respiratory mechanics and are more breathless during inspiratory threshold loading (ITL) than COPD alone,. Methods: COPD and COPD-HF patients underwent incremental ITL at 12, 24, 36, 48 and 60% of maximal inspiratory mouth pressure (PImax). Neural respiratory drive (NRD) was recorded continuously using 2nd intercostal space transcutaneous electromyography (EMGpara). NRD index (NRDI=EMGpara%max x respiratory rate), neuromechanical uncoupling (NMU=NRDI/PTPmo), mBorg breathlessness intensity and Multidimensional Dyspnea Profile (MDP) scores were compared at the highest ITL achieved. Results: 11 COPD (mean (SD) age 69 (7) years, FEV1%pred 49.3 (16.4)%, 10 male) and 12 COPD-HF patients (mean (SD) age 72 (6) years, FEV1%pred 54.3 (13.1)%, 9 male) were studied. Median (IQR) mMRC dyspnoea was significantly higher in COPD-HF (COPD-HF: mMRC=3 (2 – 3.75), COPD: mMRC=2 (1 - 3); p=0.032). NRDI/PTPmo, MDP work/effort and mental effort were significantly higher, and Pmo pressure swings lower, in COPD-HF than in COPD at peak ITL (Table 1). Conclusions: Despite lower peak ITL load, both NMU and MDP work/effort were higher in COPD-HF than COPD. Contributory factors require further study.

Task specific rehabilitation training is commonly used to treat motor dysfunction after neurological injures such as spinal cord injury (SCI), yet the use of task specific training in preclinical animal studies of SCI is not common. This is due in part to the difficulty in training animals to perform specific motor tasks, but also due to the lack of knowledge about optimal rehabilitation training parameters to maximize recovery. The single pellet reaching, grasping and retrieval (SPRGR) task (a.k.a. single pellet reaching task or Whishaw task) is a skilled forelimb motor task used to provide rehabilitation training and test motor recovery in rodents with cervical SCI. However, the relationships between the amount, duration, intensity, and timing of training remain poorly understood. In this study, using automated robots that allow rats with cervical SCI ad libitum access to self-directed SPRGR rehabilitation training, we show clear relationships between the total amount of rehabilitation training, the intensity of training (i.e., number of attempts/h), and performance in the task. Specifically, we found that rats naturally segregate into High and Low performance groups based on training strategy and performance in the task. Analysis of the different training strategies showed that more training (i.e., increased number of attempts in the SPRGR task throughout rehabilitation training) at higher intensities (i.e., number of attempts per hour) increased performance in the task, and that improved performance in the SPRGR task was linked to differences in corticospinal tract axon collateral densities in the injured spinal cords. Importantly, however, our data also indicate that rehabilitation training becomes progressively less efficient (i.e., less recovery for each attempt) as both the amount and intensity of rehabilitation training increases. Finally, we found that Low performing animals could increase their training intensity and transition to High performing animals in chronic SCI. These results highlight the rehabilitation training strategies that are most effective to regain skilled forelimb motor function after SCI, which will facilitate pre-clinical rehabilitation studies using animal models and could be beneficial in the development of more efficient clinical rehabilitation training strategies.

Biomarkers of spinal cord injury (SCI) could help determine the severity of the injury and facilitate early critical care decision making. We analyzed global gene expression in peripheral white blood cells during the acute injury phase and identified 197 genes whose expression changed after SCI compared to healthy and trauma controls and in direct relation to SCI severity. Unsupervised co-expression network analysis identified several gene modules that predicted injury severity (AIS grades) with an overall accuracy of 72.7% and included signatures of immune cell subtypes. Our findings indicate that global transcriptomic changes in peripheral blood cells have diagnostic and potentially prognostic value for SCI severity.

Rehabilitative training is one of the most successful therapies to promote motor recovery after spinal cord injury, especially when applied early after injury. Polytrauma and management of other medical complications in the acute post-injury setting often preclude or complicate early rehabilitation. Therefore, interventions that reopen a window of opportunity for effective motor training after chronic injury would have significant therapeutic value. Here, we tested whether this could be achieved in rats with chronic (8 weeks) dorsolateral quadrant sections of the cervical spinal cord (C4) by inducing mild neuroinflammation. We found that systemic injection of a low dose of lipopolysaccharide improved the efficacy of rehabilitative training on forelimb function, as assessed using a single pellet reaching and grasping task. This enhanced recovery was found to be dependent on the training intensity, where a high-intensity paradigm induced the biggest improvements. Importantly, in contrast to training alone, the combination of systemic lipopolysaccharide and high-intensity training restored original function (reparative plasticity) rather than enhancing new motor strategies (compensatory plasticity). Accordingly, electrophysiological and tract-tracing studies demonstrated a recovery in the cortical drive to the affected forelimb muscles and a restructuration of the corticospinal innervation of the cervical spinal cord. Thus, we propose that techniques that can elicit mild neuroinflammation may be used to enhance the efficacy of rehabilitative training after chronic spinal cord injury.

Prognoses of Traumatic Brain Injury (TBI) outcomes are neither easily nor accurately determined from clinical indicators. This is due in part to the heterogeneity of damage inflicted to the brain, ultimately resulting in diverse and complex outcomes. Using a data-driven approach on many distinct data elements may be necessary to describe this large set of outcomes and thereby robustly depict the nuanced differences among TBI patients' recovery. In this work, we develop a method for modeling large heterogeneous data types relevant to TBI. Our approach is geared toward the probabilistic representation of mixed continuous and discrete variables with missing values. The model is trained on a dataset encompassing a variety of data types, including demographics, blood-based biomarkers, and imaging findings. In addition, it includes a set of clinical outcome assessments at 3, 6, and 12 months post-injury. The model is used to stratify patients into distinct groups in an unsupervised learning setting. We use the model to infer outcomes using input data, and show that the collection of input data reduces uncertainty of outcomes over a baseline approach. In addition, we quantify the performance of a likelihood scoring technique that can be used to self-evaluate the extrapolation risk of prognosis on unseen patients., Comment: 12 pages, 5 figures

OBJECTIVETraumatic spinal cord injury (SCI) is a dreaded condition that can lead to paralysis and severe disability. With few treatment options available for patients who have suffered from SCI, it is important to develop prospective databases to standardize data collection in order to develop new therapeutic approaches and guidelines. Here, the authors present an overview of their multicenter, prospective, observational patient registry, Transforming Research and Clinical Knowledge in SCI (TRACK-SCI).METHODSData were collected using the National Institute of Neurological Disorders and Stroke (NINDS) common data elements (CDEs). Highly granular clinical information, in addition to standardized imaging, biospecimen, and follow-up data, were included in the registry. Surgical approaches were determined by the surgeon treating each patient; however, they were carefully documented and compared within and across study sites. Follow-up visits were scheduled for 6 and 12 months after injury.RESULTSOne hundred sixty patients were enrolled in the TRACK-SCI study. In this overview, basic clinical, imaging, neurological severity, and follow-up data on these patients are presented. Overall, 78.8% of the patients were determined to be surgical candidates and underwent spinal decompression and/or stabilization. Follow-up rates to date at 6 and 12 months are 45% and 36.3%, respectively. Overall resources required for clinical research coordination are also discussed.CONCLUSIONSThe authors established the feasibility of SCI CDE implementation in a multicenter, prospective observational study. Through the application of standardized SCI CDEs and expansion of future multicenter collaborations, they hope to advance SCI research and improve treatment.

Introduction and objectives Heart failure is a common comorbidity of COPD and contributes to increased breathlessness and adverse clinical outcomes. Neural respiratory drive (NRD) is closely related to breathlessness intensity in COPD. This study aimed to investigate the impact of comorbid left heart failure (COPD-HF) on NRD in patients with COPD. We hypothesised that NRD would be higher during an inspiratory threshold loading protocol (ITL) in COPD-HF than in COPD patients without left heart failure. Methods COPD and COPD-HF patients underwent incremental ITL at 12%, 24%, 36%, 48% and 60% of maximal inspiratory mouth pressure (PImax). NRD was recorded continuously using 2nd intercostal space transcutaneous electromyography (EMGpara). EMGpara signals were converted to root mean square (RMS), normalised to peak RMS EMGpara during maximal inspiratory manoeuvres (EMGpara%max) and multiplied by respiratory rate to calculate NRD index (NRDI). NRDI in COPD and COPD-HF were compared at each load using mixed effect model repeated measurement analysis. Results 11 COPD patients without left heart failure (mean (SD) age 69(7) years, FEV1%predicted 49.3 (16.4)%, VC%predicted 99.8 (22.0)%, PIMax 55.7 (15.8)cmH2O) and 11 COPD-HF patients (mean (SD) age 72(6) years, FEV1%predicted 54.8 (13.6)%, VC%predicted 86.8 (17.4)%), PIMax 53.1 (30.9)cmH2O) were studied. mMRC dyspnoea scores were higher in COPD-HF (median (IQR) 3 (2 – 4) than in COPD (median (IQR) 2 (1 to 3), p=0.0406). 11/11 COPD patients completed all loads of the ITL protocol to 60% PImax, compared to 4/11 patients in the COPD-HF group (p=0.0039). There were significant fixed effects of diagnosis (p=0.0136), load (p Conclusions Observations of higher levels of NRDI at equivalent inspiratory threshold loads in COPD-HF suggests that heart failure further increases the mechanical load on the respiratory muscles in COPD. Contributions of potential aetiological factors, such as reduced lung and chest wall compliance, require further study.

Secondary manifestations of spinal cord injury beyond motor and sensory dysfunction can negatively affect a person's quality of life. Spinal cord injury is associated with an increased incidence of depression and anxiety; however, the mechanisms of this relationship are currently not well understood. Human and animal studies suggest that changes in the composition of the intestinal microbiota (dysbiosis) are associated with mood disorders. The objective of the current study is to establish a model of anxiety following a cervical contusion spinal cord injury in rats and to determine whether the microbiota play a role in the observed behavioural changes. We found that spinal cord injury caused dysbiosis and increased symptoms of anxiety-like behaviour. Treatment with a fecal transplant prevented both spinal cord injury-induced dysbiosis as well as the development of anxiety-like behaviour. These results indicate that an incomplete unilateral cervical spinal cord injury can cause affective disorders and intestinal dysbiosis, and that both can be prevented by treatment with fecal transplant therapy.

Introduction: The muscle mechanomyogram (sMMG) quantifies the lateral oscillations of contracting muscle fibres. There is a close relationship between lower intercostal space sMMG (sMMGlic) and inspiratory muscle force during inspiratory threshold loading (ITL) in healthy subjects. We hypothesized that the slope of relationship between sMMGlic and inspiratory muscle force during ITL would be similar in chronic obstructive pulmonary disease (COPD) and in COPD-heart failure overlap (COPD-HF). Methods: Bilateral sMMGlic was recorded simultaneous with mouth pressure (Pmo) in 11 COPD (9 male, 66 (64-77) years, FEV1 44.7 (37.6-61.0) %pred, maximal inspiratory mouth pressure (PImax) 56.4 (49.7-74.8) cmH2O), and in 4 COPD-HF patients (3 male, 82 (72-82) years, FEV1 51.0 (41.2-70.8) %pred, PImax 35.9 (23.9-57.4) cmH2O) during ITL to 36% of PImax. sMMGlic signals were analysed using fixed sample entropy (fSampEn). Relationships between area under the curve of fSampEn sMMGlic and Pmo were assessed by correlation analysis. Results: Similar positive relationships between sMMGlic and Pmo in both COPD and COPD-HF groups (Fig. 1) were observed. Conclusions: These data suggest the potential value of sMMGlic as a novel index of inspiratory muscle activation in both COPD and COPD-HF. Further quantitative analysis of sMMGlic in COPD and COPD-HF in larger cohorts of these patients is required.

Task specific motor training is a common form of rehabilitation therapy in individuals with spinal cord injury (SCI). The single pellet grasping (SPG) task is a skilled forelimb motor task used to evaluate recovery of forelimb function in rodent models of SCI. The task requires animals to obtain food pellets located on a shelf beyond a slit at the front of an enclosure. Manually training and testing rats in the SPG task requires extensive time and often yields results with high outcome variability and small therapeutic windows (i.e., the difference between pre- and post-SCI success rates). Recent advances in automated SPG training using automated pellet presentation (APP) systems allow rats to train ad libitum 24 h a day, 7 days a week. APP trained rats have improved success rates, require less researcher time, and have lower outcome variability compared to manually trained rats. However, it is unclear whether APP trained rats can perform the SPG task using the APP system after SCI. Here we show that rats with cervical SCI can successfully perform the SPG task using the APP system. We found that SCI rats with APP training performed significantly more attempts, had slightly lower and less variable final score success rates, and larger therapeutic windows than SCI rats with manual training. These results demonstrate that APP training has clear advantages over manual training for evaluating reaching performance of SCI rats and represents a new tool for investigating rehabilitative motor training following CNS injury.

Spinal cord injury results in a wide range of behavioral changes including impaired motor and sensory function, autonomic dysfunction, spasticity, and depression. Currently, restoring lost motor function is the most actively studied and sought-after goal of spinal cord injury research. This research is rooted in the fact that although self-repair following spinal cord injury in adult mammals is very limited, there can be some recovery of motor function. This recovery is strongly dependent on the lesion size and location as well as on neural activity of denervated networks activated mainly through physical activity (i.e., rehabilitative training). Recovery of motor function is largely due to neuroplasticity, which includes adaptive changes in spared and injured neural circuitry. Neuroplasticity after spinal cord injury is extensive and includes mechanisms such as moderate axonal sprouting, the formation of new synaptic connections, network remapping, and changes to neuron cell properties. Neuroplasticity after spinal cord injury has been described at various physiological and anatomical levels of the central nervous system including the brain, brainstem, and spinal cord, both above and below injury sites. The growing number of mechanisms underlying postinjury plasticity indicate the vast complexity of injury-induced plasticity. This poses important opportunities to further enhance and harness plasticity in order to promote recovery. However, the diversity of neuroplasticity also creates challenges for research, which is frequently based on mechanistically driven approaches. The appreciation of the complexity of neuronal plasticity and the findings that recovery is based on a multitude and interlinked adaptations will be essential in developing meaningful new treatment avenues.

Low neuronal cAMP levels in adults and a further decline following traumatic central nervous system (CNS) injury has been associated with the limited ability of neurons to regenerate. An approach to increase neuronal cAMP levels post injury is electrical stimulation. Stimulation as a tool to promote neuronal growth has largely been studied in the peripheral nervous system or in spared fibers of the CNS and this research suggests that a single session of electrical stimulation is sufficient to initiate a long-lasting axonal growth program. Here, we sought to promote plasticity and growth of the injured corticospinal tract with electrical cortical stimulation immediately after its spinal injury. Moreover, given the importance of rehabilitative motor training in the clinical setting and in translating plasticity into functional recovery, we applied training as a standard treatment to all rats (i.e., with or without electrical stimulation). Our findings show that electrical cortical stimulation did improve recovery in forelimb function compared to the recovery in unstimulated animals. This recovery is likely linked to increased corticospinal tract plasticity as evidenced by a significant increase in sprouting of collaterals above the lesion site, but not to increased regenerative growth through the lesion itself.

Introduction Breathlessness is a dominant, distressing, symptom of chronic obstructive pulmonary disease (COPD) which has a significant impact on quality of life. Neural respiratory drive (NRD), quantified as diaphragm electromyogram (EMGdi) activity, is closely related to breathlessness intensity in COPD. The surface mechanomyogram (sMMG), which can be recorded using skin-surface triaxial accelerometers, measures the lateral vibration of muscle fibres and is considered to be the mechanical counterpart of the surface EMG (sEMG). The principal aim of this study was to investigate the relationship between the sMMG of the diaphragm (sMMGdi) and breathlessness in COPD. We hypothesised that there would be strong positive relationships between sMMGdi and modified Borg (mBorg) breathlessness intensity during an inspiratory threshold loading protocol. Methods Nine COPD patients (7 male, median (IQR) age 70 (64–78) years, BMI 25.6 (24.8–30.1) kg/m2, FEV144.7 (37.1–63.9)%predicted), underwent an incremental inspiratory loading protocol at 12%, 24%, 36%, 48% and 60% of maximum mouth inspiratory pressure (PImax). Left and right sEMGdi and sMMGdi activity were recorded using 2 pairs of sEMG electrodes, and one pair of triaxial accelerometers, positioned over the 7th/8th intercostal spaces in the anterior axillary lines bilaterally. sEMG and sMMG signals were analysed using fixed sample entropy (fSampEn) and the relationships with mBorg breathlessness intensity during each inspiratory load were determined using correlation analysis. Results Moderate to strong correlations were observed between mBorg breathlessness intensity and the sEMG and sMMG signals, expressed as fSampEn, recorded at all sites (table 1). Conclusion The relationships observed between mBorg breathlessness intensity and sMMGdi, and sEMGdi, expressed as fSampEn, demonstrates the potential value of sMMGdi as a complementary tool to sEMGdi for the investigation of breathlessness in COPD. sMMGdi could provide a novel non-invasive physiological correlate of breathlessness intensity in COPD and other chronic respiratory diseases.

Cell therapy for spinal cord injury (SCI) is a promising strategy for clinical application. Mesenchymal stem cells (MSC) have demonstrated beneficial effects following transplantation in animal models of SCI. However, despite the immunoprivilege properties of the MSC, their survival in the injured spinal cord is reduced due to the detrimental milieu in the damaged tissue and immune rejection of the cells. The limited survival of the engrafted cells may determine the therapy success. Therefore, we compared two strategies to increase the presence of the cells in the injured spinal cord in rats: increasing the amount of MSC transplants and using immunosuppressive treatment with FK506 after transplantation. Functional outcomes for locomotion and electrophysiological responses were assessed. The grafted cells survival and the amount of cavity and spared tissue were studied. The findings indicate that immunosuppression improved grafted cells survival. A cell–dose effect was found regarding locomotion recovery and tissue protection independent of immunosuppression. Nevertheless, immunosuppression enhanced the electrophysiological outcomes and allowed filling of the cavity formed after injury by new regenerative tissue and axons. These results indicate that MSC transplantation combined with immunosuppression prolongs the survival of engrafted cells and improves functional and morphological outcomes after SCI.

The number of elective laser and light procedures continues to grow eliciting a host of medicolegal issues. Informed consent involves a meeting of the minds as a result of a discussion between the provider and the patient. The risks, benefits and alternatives of a procedure should be disclosed to a patient and is paramount to an informed consent. Unique patient and physician concerns regarding the laser procedure should be documented when possible. The informed consent process might benefit from supplementary modes of communication such as patient questionnaires to improve retention rates. Most laser procedures require for laser individualized informed consents.

A major goal of Schwann cell (SC) transplantation for spinal cord injury (SCI) is to fill the injury site to create a bridge for regenerating axons. However, transplantation of peripheral nerve SCs requires an invasive biopsy, which may result in nerve damage and donor site morbidity. SCs derived from multipotent stem cells found in skin dermis (SKP-SCs) are a promising alternative. Regardless of source, loss of grafted SCs post-grafting is an issue in studies of regeneration, with survival rates ranging from ∼1 to 20% after ≥6 weeks in rodent models of SCI. Immune rejection has been implicated in these low survival rates. Therefore, our aim was to explore the role of the immune response on grafted SKP-SC survival in Fischer rats with a spinal hemisection injury. We compared SKP-SC survival 6 weeks post-transplantation in: (I) cyclosporine-immunosuppressed rats (n=8), (II) immunocompetent rats (n=9), and (III) rats of a different sub-strain than the SKP-SC donor rats (n=7). SKP-SC survival was similar in all groups, suggesting immune rejection was not a main factor in SKP-SC loss observed in this study. SKP-SCs were consistently found on laminin expressed at the injury site, indicating detachment-mediated apoptosis (i.e., anoikis) might play a major role in grafted cell loss.

Cell therapy for spinal cord injury (SCI) is a promising strategy for clinical application. Both bone marrow mesenchymal stromal cells (MSCs; also known as bone marrow-derived 'mesenchymal stem cells') and olfactory ensheathing cells (OECs) have demonstrated beneficial effects following transplantation in animal models of SCI. However, due to the large number of affecting parameters that determine the therapy success and the lack of methodological consensus, the comparison of different works is difficult. Therefore, we compared the effects of MSC and OEC transplants at early or delayed time after a spinal cord contusion injury in the rat. Functional outcomes for locomotion, sensory perception and electrophysiological responses were assessed. Moreover, the grafted cells survival and the amount of cavity and spared tissue were studied. The findings indicate that grafted cells survived until 7 days post-injection, but markedly disappeared in the following 2 weeks. Despite the low survival of the cells, MSC and OEC grafts provided tissue protection after early and delayed transplantation. Nevertheless, only acute MSC grafts improved locomotion recovery in treadmill condition and electrophysiological outcomes with respect to the other injured groups. These results, together with previous works, indicate that the MSC seem a better option than OEC for treatment of contusion injuries.

The reticulospinal tract (RtST) descends from the reticular formation and terminates in the spinal cord. The RtST drives the initiation of locomotion and postural control. RtST axons form new contacts with propriospinal interneurons (PrINs) after incomplete spinal cord injury (SCI); however, it is unclear if injured or uninjured axons make these connections. We completely transected all traced RtST axons in rats using a staggered model, where a hemisection SCI at vertebra T10 is followed by a contralateral hemisection at vertebra T7. In one group of the animals, the T7 SCI was performed 2 weeks after the T10 SCI (delayed; dSTAG), and in another group, the T10 and T7 SCIs were concomitant (cSTAG). dSTAG animals had significantly more RtST-PrIN contacts in the grey matter compared to cSTAG animals (p<0.05). These results were accompanied by enhanced locomotor recovery with dSTAG animals significantly outperforming cSTAG animals (BBB test;p<0.05). This difference suggests that activity in neuronal networks below the first SCI may contribute to enhanced recovery, because dSTAG rats recovered locomotor ability before the second hemisection. In conclusion, our findings support the hypothesis that the injured RtST forms new connections and is a key player in the recovery of locomotion post-SCI.

This work was supported by TERCEL and CIBERNED funds from the Instituto de Salud Carlos III of Spain, and FEDER funds from the EC. Spinal cord injury (SCI) causes loss of neural functions below the level of the lesion due to interruption of spinal pathways and secondary neurodegenerative processes. The transplant of neural stem cells (NSCs) is a promising approach for the repair of SCI. Reprogramming of adult somatic cells into induced pluripotent stem cells (iPSCs) is expected to provide an autologous source of iPSC-derived NSCs, avoiding the immune response as well as ethical issues. However, there is still limited information on the behavior and differentiation pattern of transplanted iPSC-derived NSCs within the damaged spinal cord. We transplanted iPSC-derived NSCs, obtained from adult human somatic cells, into rats at 0 or 7 days after SCI, and evaluated motor-evoked potentials and locomotion of the animals. We histologically analyzed engraftment, proliferation, and differentiation of the iPSC-derived NSCs and the spared tissue in the spinal cords at 7, 21, and 63 days posttransplant. Both transplanted groups showed a late decline in functional recovery compared to vehicle-injected groups. Histological analysis showed proliferation of transplanted cells within the tissue and that cells formed a mass. At the final time point, most grafted cells differentiated to neural and astroglial lineages, but not into oligodendrocytes, while some grafted cells remained undifferentiated and proliferative. The proinflammatory tissue microenviroment of the injured spinal cord induced proliferation of the grafted cells and, therefore, there are possible risks associated with iPSC-derived NSC transplantation. New approaches are needed to promote and guide cell differentiation, as well as reduce their tumorigenicity once the cells are transplanted at the lesion site.

Respiratory muscle dysfunction is a common problem in patients with chronic obstructive pulmonary disease (COPD) and has mostly been related to pulmonary hyperinflation [1, 2]. Associated diaphragm shortening and deleterious changes in the muscle force-length relationship cause a reduction in the muscles’ capacity to generate pressure, placing them at a mechanical disadvantage [1, 3]. Specifically, both inspiratory muscle strength and mechanical efficiency may be reduced in COPD patients [1, 4–6], although, at iso-volume, the contractile strength of the diaphragm in COPD is preserved or may even be improved in some cases [7]. The ratio between transdiaphragmatic pressure and electrical diaphragm activity has been used as a measure of respiratory muscle efficiency [8, 9]. However, in clinical practice, it is complex to measure this parameter directly, as invasive measures are required and these are uncomfortable for patients [4]. During contraction, respiratory muscle fibres vibrate laterally [10]. These vibrations are related to the mechanical activation of these muscles and can be non-invasively recorded through accelerometers positioned on the surface of the skin, proximal to the muscles: this is called respiratory muscle mechanomyogram (MMG) [11–13]. The analysis of the mechanical activation of inspiratory muscles through the MMG might be a useful alternative approach for assessing respiratory muscles function in patients with COPD [13, 14]. MMG reflects the mechanical counterpart of the neural activity measured by electromyography. Respiratory muscle MMG provide some advantages over surface diaphragmatic electromyography with regards to simplicity of use. First of all, MMG recording is easy and simple to implement: MMG is acquired using a small accelerometer attached to the skin surface, whereas electromyography typically uses three electrodes. Secondly, as it is a mechanical signal, MMG is not susceptible to bioelectrical interference. Furthermore, the signal to noise ratio of MMG is typically higher than that of the electromyography, requiring less amplification and electrical shielding. In addition, the MMG recording does not require skin preparation and it is not influenced by changes in the skin impedance. The aim of the present study was to noninvasively evaluate the mechanical activation of inspiratory muscles and its efficiency (EMMG) during tidal volume breathing in patients with severe-to-very severe COPD. With this in mind, we investigated the peak inspiratory mouth pressure (IPpeak) and respiratory muscle MMG acquired under both quiet breathing (QB) and maximal voluntary ventilation (MVV) conditions during an incremental respiratory flow protocol.

background. Near-infrared reflectance-mode confocal scanning laser microscopy (RCM) represents a novel imaging technique for microscopic analysis of skin lesions and may provide a noninvasive modality for the diagnosis of basal cell carcinoma (BCC). objective. To determine the feasibility of detecting residual or clinically equivocal BCC using RCM. methods. In this pilot study, RCM was used in three cases to characterize the histologic features of index lesions in vivo. These were subsequently correlated with corresponding hematoxylin-eosin–stained sections obtained during Mohs micrographic surgery. results. Evaluation of clinically equivocal lesions by RCM revealed features characteristic of BCC, including tightly packed nests of elongated, monomorphic, polarized nuclei and subjacent ectatic blood vessels with lymphocytes undergoing margination and rolling. Conventional histology confirmed the presence of BCC in all cases. conclusion. We report the use of RCM in the confirmation of residual BCC in two cases and the tentative diagnosis with subsequent pathologic conformation of a third case in which a biopsy was previously inadequate. Our results demonstrate that confocal microscopy may facilitate diagnosis of BCC in vivo and warrant further prospective study to quantify the sensitivity and specificity of this rapidly evolving imaging modality.

Background. Imiquimod is an immune response modifier that up-regulates cytokines and has been shown in clinical studies to reduce or clear basal cell carcinoma tumors when applied topically. Objective. The objectives were to evaluate the efficacy of 5% imiquimod cream in treating basal cell carcinoma preceding excision by Mohs micrographic surgery and to determine if reflectance-mode confocal microscopy is useful to establish the need for surgical intervention after imiquimod treatment. Methods. Subjects applied study cream to one biopsy-confirmed basal cell carcinoma tumor 5 ×/week for 2, 4, or 6 weeks in this vehicle-controlled, double-blind study. Confocal microscopy was used for the 6-week treatment group to examine the target tumor area at each interval visit and immediately before Mohs micrographic surgery. After the Mohs micrographic surgery excision, the tissue was evaluated histologically, and the excision area was measured. Confocal microscopy readings were correlated to the histologic diagnosis. Results. Tumors cleared or the target tumor area was reduced in subjects in the 4- and 6-week dosing regimens. Confocal microscopy assessments correlated well with the histologic diagnosis. conclusion. Imiquimod improved excision results relative to vehicle when used for treating basal cell carcinoma before Mohs micrographic surgery. Confocal microscopy assessments correlated well with tumor response to therapy, suggesting that confocal microscopy may help determine the need for surgery.

Primary cutaneous mucinous carcinoma is a rare adnexal malignancy with a high recurrence rate following conventional excision and the potential for aggressive local invasion.To enhance the microscopic detection of mucinous carcinoma in Mohs micrographic surgical sections by incorporating rapid immunohistochemical staining.Standard Mohs micrographic surgical technique was used in conjunction with frozen section immunohistochemistry using an antibody to low-molecular-weight cytokeratin.Rapid immunoperoxidase staining using low-molecular-weight cytokeratin detected residual foci of mucinous carcinoma that were difficult to identify on routine frozen sections. Immunostaining was strongly positive in areas with clear evidence of tumor by routine histology, as well as in adjacent areas on a subsequent stage where frozen sections were equivocal or negative. Immunostaining was distinctly negative at the final surgical margin, which was shown by en face permanent sections to be free of tumor. The patient has been free of recurrence for 3 years.Immunoperoxidase-guided Mohs micrographic surgery using low-molecular-weight cytokeratin enhances the sensitivity for detection of mucinous carcinoma, and may help contribute to complete tumor removal.

Obstructive Sleep Apnea (OSA) is currently diagnosed by a full nocturnal polysomnography (PSG), a very expensive and time-consuming method. In previous studies we were able to distinguish patients with OSA through formant frequencies of breath sound during sleep. In this study we aimed at identifying OSA patients from breath sound analysis during wakefulness. The respiratory sound was acquired by a tracheal microphone simultaneously to PSG recordings. We selected several cycles of consecutive inspiration and exhalation episodes in 10 mild-moderate (AHI=30) OSA patients during their wake state before getting asleep. Each episode's formant frequencies were estimated by linear predictive coding. We studied several formant features, as well as their variability, in consecutive inspiration and exhalation episodes. In most subjects formant frequencies were similar during inspiration and exhalation. Formant features in some specific frequency band were significantly different in mild OSA as compared to severe OSA patients, and showed a decreasing correlation with OSA severity. These formant characteristics, in combination with some anthropometric measures, allowed the classification of OSA subjects between mild-moderate and severe groups with sensitivity (specificity) up to 88.9% (84.6%) and accuracy up to 86.4%. In conclusion, the information provided by formant frequencies of tracheal breath sound recorded during wakefulness may allow identifying subjects with severe OSA.

Importance The notion that systemic isotretinoin taken within 6 to 12 months of cutaneous surgery contributes to abnormal scarring or delayed wound healing is widely taught and practiced; however, it is based on 3 small case series from the mid-1980s. Objective To evaluate the body of literature to provide evidence-based recommendations regarding the safety of procedural interventions performed either concurrently with, or immediately following the cessation of systemic isotretinoin therapy. Evidence Review A panel of national experts in pediatric dermatology, procedural/cosmetic dermatology, plastic surgery, scars, wound healing, acne, and isotretinoin was convened. A systematic PubMed review of English-language articles published from 1982 to 2017 was performed using the following search terms: isotretinoin, 13-cis-retinoic acid, Accutane, retinoids, acitretin, surgery, surgical, laser, ablative laser, nonablative laser, laser hair removal, chemical peel, dermabrasion, wound healing, safety, scarring, hypertrophic scar, and keloid. Evidence was graded, and expert consensus was obtained. Findings Thirty-two relevant publications reported 1485 procedures. There was insufficient evidence to support delaying manual dermabrasion, superficial chemical peels, cutaneous surgery, laser hair removal, and fractional ablative and nonablative laser procedures for patients currently receiving or having recently completed isotretinoin therapy. Based on the available literature, mechanical dermabrasion and fully ablative laser are not recommended in the setting of systemic isotretinoin treatment. Conclusions and Relevance Physicians and patients may have an evidence-based discussion regarding the known risk of cutaneous surgical procedures in the setting of systemic isotretinoin therapy. For some patients and some conditions, an informed decision may lead to earlier and potentially more effective interventions.

The aim of the present study was to measure bilateral asynchrony in patients suffering from Chronic Obstructive Pulmonary Disease (COPD) performing an incremental inspiratory load protocol. Bilateral asynchrony was estimated by the comparison of respiratory movements derived from diaphragm mechanomyographic (MMGdi) signals, acquired by means of capacitive accelerometers placed on left and right sides of the rib cage. Three methods were considered for asynchrony evaluation: Lissajous figure, Hilbert transform and Motto's algorithm. Bilateral asynchrony showed an increase at 20, 40 and 60% (values of normalized inspiratory pressure by their maximum value reached in the last inspiratory load) while the very severe group showed and increase at 20, 40, 80, and 100 % during the protocol. These increments in the phase's shift can be due to an increase of the inspiratory load along the protocol, and also as a consequence of distress and fatigue. In summary, this work evidenced the capability to estimate bilateral asynchrony in COPD patients. These preliminary results also showed that the use of capacitive accelerometers can be a suitable sensor for recording of respiratory movement and evaluation of asynchrony in COPD patients.

Favre-Racouchot syndrome (nodular elastosis with cysts and comedones) is a distinct variant of solar elastosis most frequently found in elderly Caucasian men. The estimated prevalence is 1.5–6 % in the general population. This syndrome is characterized by yellow nodules and plaques accentuated by enlarged, open comedones and dilated cysts, often accompanied by other cutaneous findings of actinic damage.

It is increasingly difficult to practice medicine without a clear understanding of legal issues. Although in the past, physicians found a paucity of medicolegal materials, the opposite is now the rule. Multiple excellent medicolegal textbooks are available, and most new textbooks and or major journals now include medicolegal chapters or columns. The problem may now be that physicians have been so exposed to medicolegal issues that they are either overwhelmed by the amount of information that must be understood or risk becoming complacent or overconfident about their understanding of the basic issues they need to understand. This article revisits the most basic medicolegal concepts of establishing and terminating the physician-patient relationship, obtaining informed consent/refusal, medical malpractice, and medical record keeping, providing pearls and checklists to assist the practitioner. In addition, special attention is given to the use of Food and Drug Administration-approved drugs for unapproved purposes and to the patient with human immunodeficiency virus, because these areas are receiving increasing legal attention.

Transplantation of bone marrow derived mesenchymal stromal cells (MSC) or olfactory ensheathing cells (OEC) have demonstrated beneficial effects after spinal cord injury (SCI), providing tissue protection and improving the functional recovery. However, the changes induced by these cells after their transplantation into the injured spinal cord remain largely unknown. We analyzed the changes in the spinal cord transcriptome after a contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting. The gene profiles were analyzed by clustering and functional enrichment analysis based on the Gene Ontology database. We found that both MSC and OEC transplanted acutely after injury induce an early up-regulation of genes related to tissue protection and regeneration. In contrast, cells transplanted at 7 days after injury down-regulate genes related to tissue regeneration. The most important change after MSC or OEC transplant was a marked increase in expression of genes associated with foreign body response and adaptive immune response. These data suggest a regulatory effect of MSC and OEC transplantation after SCI regarding tissue repair processes, but a fast rejection response to the grafted cells. Our results provide an initial step to determine the mechanisms of action and to optimize cell therapy for SCI.

BACKGROUND. This article continues our medicolegal series that addresses issues affecting current dermatology practice. Informed consent and informed refusal have become cornerstones of modern American healthcare, and can serve to facilitate communication and trust between physician and patient. METHODS. A format with an initial discussion of legal concepts is followed by hypothetical problems and a review of actual cases to illustrate the principles of informed consent and informed refusal. RESULTS. A valid informed consent from a competent patient should be obtained before initiating most dermatologic treatment. When a competent patient refuses a recommended medical test or procedure, the physician should make sure the patient understands the potential negative consequences of refusal. Some form of written documentation in the medical record is advised in either situation. CONCLUSION. Failure to obtain a patient's informed consent prior to beginning treatment or failing to obtain an informed refusal before accepting a patients's decision to forego a test or procedure may subject the dermatologist to multiple later allegations, most commonly negligence. Dermatol Surg 1995 ;21

Animal models of spinal cord injury (SCI) are intended to mimic the main features of human spinal cord lesions, although sometimes it becomes a difficult task to find the right technique to discriminate the severity of the lesion as well as to assess different aspects of functional recovery. For this reason, we have used several functional methods to assess gross and fine locomotion deficits, as well as electrophysiological data to study the dysfunctions underlying the behavioral changes. Moreover, an extensive study based on the quantification of alternation and coordination parameters during gait has been done. Spinal cord injuries of varying severity (mild contusion, moderate contusion and hemisection) were performed at the thoracic level in adult rats that were followed-up for 6 weeks. Lesions resulting in similar scores in the open field test (i.e. mild contusion and hemisection) caused more marked differences in fine coordination when assessed by quantitative coordination analysis based on a digitized walking treadmill. In conclusion, gross and fine deficits can be detected using a battery of tests based on the performance of the animals during tasks of different difficulty. When used appropriately, they become useful tools to study functional recovery due to spontaneous plastic changes or to therapeutic interventions after SCI, as well as to test the effects of new therapies.

The aim of this study was to evaluate the respiratory muscles efficiency during a progressive incremental flow (IF) respiratory test in healthy and Chronic Obstructive Pulmonary Disease (COPD) subjects. To achieve this, the relationship between mouth Inspiratory Pressure (IP) increment, which is a measure of the force produced by respiratory muscles, and respiratory muscular activity increment, evaluated by means of Mechanomyografic (MMG) signals of the diaphragm muscle, was analyzed. Moreover, the correlation between the respiratory efficiency measure and the obstruction severity of the subjects was also examined. Data from two groups of subjects were analyzed. One group consisted of four female subjects (two healthy subjects and two moderate COPD patients) and the other consisted of ten male subjects (six severe and four very severe COPD patients). All subjects performed an easy IF respiratory test, in which small IP values were reached. We have found that there is an increase of amplitude and a displacement towards low frequencies in the MMG signals when the IP increases. Furthermore, it has also been found that respiratory muscles efficiency is lower when greater the obstructive severity of the patients is, and it is lower in women than in men. These results suggest that the information provided by MMG signals could be used to evaluate the muscular efficiency in healthy and COPD subjects

background. This continues our series of articles addressing the many medicolegal aspects that impact the practice of dermatology. Because the physician-patient relationship is the cornerstone of every medical malpractice action, the proper termination of that relationship is very important. methods. A format of an initial discussion of legal concepts followed by hypothetical and a review of actual cases was chosen to enhance interactive learning. The subject matter is based on a review of medicolegal literature and actual recorded case law. results. Once a physician-patient relationship has been established, improper termination of that relationship may constitute abandonment. conclusion. Any termination of the physician-patient relationship must be reasonable in view of the patients' access to alternate medical care and medical problems and should be properly communicated to the patient.

The proper execution of Mohs surgery requires proper planning. Both patient and physician alike must be adequately prepared for the procedure in order to optimize outcomes and enhance safety. For the Mohs surgeon, this entails maximizing the preoperative visit, where the patient can be properly assessed for any conditions or comorbidities that may pose a real or potential risk to the patient during or after the procedure. The Mohs surgeon should be well versed on safety issues commonly encountered in skin cancer patients, such as cardiovascular complications, antibiotic prophylaxis for infections, anticoagulation issues, and anesthesia safety. Patients should also be educated about the procedure as well as their role in postoperative care. Staff must also be informed about office safety protocols and should be trained on how to respond to potential office emergencies.

Almost two thirds of US physicians can expect to be sued at least once during their career. The key, however, is not to wait until that time to start learning about medicolegal issues. A physician with preemptive knowledge about the legal system can incorporate such information into a Mohs practice, thereby enhancing patient safety while minimizing malpractice risk. Physicians armed with legal information can also be better prepared to properly respond to adverse events, such as those that can occur in Mohs surgery. Not all adverse events, however, need to proceed to litigation. When an adverse event occurs, there is much a physician can do to enhance patient well-being, restore trust, and hopefully keep the issue out of court. Should the matter in fact proceed to a lawsuit, a physician with legal knowledge can be in a better position to prevent typical missteps and mount an aggressive defense.

This off-center fold case depicts the difficult differential diagnosis for benign lichenoid keratosis. It is challenging to diagnosis this benign lesion through clinical exam, dermscopy, and even dermatopathology. Given its similar appearance to regressed melanoma, it is important to be cognizant of both and up to date on the dermatopathology clues.

Purpose To evaluate the effects on locomotion and lumbar motoneuron function after a contusion to the midthoracic spinal cord of the rat. Methods Five animals received a moderate contusion on T8, and over 28 days postoperation (dpo) locomotion and motor electrophysiological outcome were compared with five sham-operated animals. Results At 28 dpo, the contused animals supported their body weight (BBB score =11.5 ± 0.5) and stepped uncoordinatedly. Motor evoked potentials recorded in the tibialis anterior (TA) and plantar muscles (PL), and longitudinal interlimb reflexes recorded in the TA muscles were abolished. The M wave recorded in the TA showed a decrease in amplitude by 7 dpo, which remained invariable until the end of the evaluation (88 ± 3% of {preoperative} values), whereas in the PL muscle it was not affected. Injured animals presented hyperreflexia, as shown by an increased H/M ratio. Histological analysis showed similar number of retrogradely traced TA motoneurons between groups, and that contused animals presented hypertrophied astrocytes in the most rostral but not caudal segments of the lumbar enlargement. Conclusion These results indicate that after contusion to the thoracic spinal cord, the lumbar segments undergo structural and functional changes, following a rostro-caudal gradient extension.

The number of elective laser and light procedures continues to grow eliciting a host of medicolegal issues. Informed consent involves a meeting of the minds as a result of a discussion between the provider and the patient. The risks, benefits and alternatives of a procedure should be disclosed to a patient and is paramount to an informed consent.Unique patient and physician concerns regarding the laser procedure should be documented.The informed consent process might benefit from supplementary modes of communication such as patient questionnaires to improve retention rates.Most laser procedures require for lasers individualized informed consents.