Predicting Pain to Support Exercise Participation after Spinal Cord Injury

The expansion of mobile health and predictive modeling may be worthwhile tools to predict subjective pain experiences and tailor personalized approaches for health behaviors after spinal cord injury (SCI). PURPOSE: This study examined whether exercise (hybrid functional electrical stimulation rowing) and smartphone-based health and mobility data could reliably forecast changes in pain intensity among people with SCI. METHODS: Data were collected via Suunto memory belt (heart rate), rower C2 log cards (training duration/frequency) and personal smartphones (location details, self-reported mood, pain, health, mobility) among (N=12) community-living adults with SCI over 9 months. Data were combined to predict the pain in the subsequent week. We applied nonlinear random forest algorithms, first transforming absolute scores week-to-week: \u270\u27=no change or lessened pain, & \u271\u27=worsened pain. Due to potential data imbalances, we applied k-fold cross-validation for model robustness. We referenced the F1 score (\u3e0.80) to assess model predictive accuracy. RESULTS: Our analysis underscored that while exercise data alone was insufficient for accurate predictions about the forthcoming week’s pain (F1=0.40), combining it with, prior self-reported outcomes considerably enhanced predictive accuracy. We achieved notable success in forecasting pain intensity a week ahead for multiple feature groups. For example, when predicting next week’s pain, we obtained an F1 score of 0.83 using the combination of (current) pain interference, and the difference in the hours out of bed this week and rowing frequency compared to the previous week. Similarly, the triad of TRIMPS, and the difference in pain interference and anxiety this week compared to last week also yielded an F1 score of 0.83, further emphasizing the value of integrating diverse data sources. Partial Dependence Plots revealed a positive nonlinear relationship. CONCLUSION: Through a combination of various exercise, health, mood, and mobility metrics collected in-situ, we were able to predict future pain intensity among exercisers with SCI, as reflected by commendable F1-scores. This underscores the intricacies of pain experiences, and the utility of non-linear predictive models to understand and support exercise participation for those with SCI

Novel Characterization and Live Imaging of Schlemm's Canal Expressing Prox-1

Schlemm's canal is an important structure of the conventional aqueous humor outflow pathway and is critically involved in regulating the intraocular pressure. In this study, we report a novel finding that prospero homeobox protein 1 (Prox-1), the master control gene for lymphatic development, is expressed in Schlemm's canal. Moreover, we provide a novel in vivo method of visualizing Schlemm's canal using a transgenic mouse model of Prox-1-green fluorescent protein (GFP). The anatomical location of Prox-1+ Schlemm's canal was further confirmed by in vivo gonioscopic examination and ex vivo immunohistochemical analysis. Additionally, we show that the Schlemm's canal is distinguishable from typical lymphatic vessels by lack of lymphatic vessel endothelial hyaluronan receptor (LYVE-1) expression and absence of apparent sprouting reaction when inflammatory lymphangiogenesis occurred in the cornea. Taken together, our findings offer new insights into Schlemm's canal and provide a new experimental model for live imaging of this critical structure to help further our understanding of the aqueous humor outflow. This may lead to new avenues toward the development of novel therapeutic intervention for relevant diseases, most notably glaucoma

Highly stable, reactive and ultrapure nanoporous metallic films

Nanoporous metals possess unique properties attributed to their high surface area and interconnected nanoscale ligaments. They are mostly fabricated by wet synthetic methods involving solution-based dealloying processes whose purity is compromised by residual amounts of the less noble metal. Here, we demonstrate a novel dry synthesis method to produce nanoporous metals, which is based on the plasma treatment of metal nanoparticles formed by physical vapor deposition. Our approach is general and can be applied to many metals including non-noble ones. The resultant nanoporous metallic films are impurity-free and possess highly curved ligaments and nanopores. The metal films are remarkably robust with many catalytically active sites, which is highly promising for electrocatalytic applications.Comment: 40 pages (including 13 pages of supplementary information), 5 figures, submitte

Mitochondrial Ca(2+) uptake by the voltage-dependent anion channel 2 regulates cardiac rhythmicity.

Tightly regulated Ca(2+) homeostasis is a prerequisite for proper cardiac function. To dissect the regulatory network of cardiac Ca(2+) handling, we performed a chemical suppressor screen on zebrafish tremblor embryos, which suffer from Ca(2+) extrusion defects. Efsevin was identified based on its potent activity to restore coordinated contractions in tremblor. We show that efsevin binds to VDAC2, potentiates mitochondrial Ca(2+) uptake and accelerates the transfer of Ca(2+) from intracellular stores into mitochondria. In cardiomyocytes, efsevin restricts the temporal and spatial boundaries of Ca(2+) sparks and thereby inhibits Ca(2+) overload-induced erratic Ca(2+) waves and irregular contractions. We further show that overexpression of VDAC2 recapitulates the suppressive effect of efsevin on tremblor embryos whereas VDAC2 deficiency attenuates efsevin\u27s rescue effect and that VDAC2 functions synergistically with MCU to suppress cardiac fibrillation in tremblor. Together, these findings demonstrate a critical modulatory role for VDAC2-dependent mitochondrial Ca(2+) uptake in the regulation of cardiac rhythmicity

MYC and BCL2 overexpression is associated with a higher class of Memorial Sloan-Kettering Cancer Center prognostic model and poor clinical outcome in primary diffuse large B-cell lymphoma of the central nervous system

Table S1. Correlation of BCL6 expression and clinicopathological variables; Table S2. MYC translocation and copy number change in MYC positive cases. (DOCX 24 kb

A Supposedly Developed Country’s Response to a Healthcare Crisis: Lessons from the COVID-19 Pandemic for Future National Emergencies

The world has just suffered through a pandemic that was responsible for the 7 million deaths. The expectation prior to this devastation would have been those countries like the United States, which are considered “developed”, would have been prepared and able to ameliorate the effects of such a catastrophic event. However, this was not the case. In fact, many countries not necessarily considered underdeveloped or undeveloped weathered this crisis by mounting a much more organized response. This chapter will review the history of similar episodic epidemics, the failures that led to over a million deaths in the United States, and most importantly what is necessary to a similar event in the future to be dealt preventing the devastation that did occur in a most “developed” country like the United States. These lesions and their possible extrapolation worldwide, hoping will prevent a recurrence of the devastation we have recently experienced in the United States

A Case of Hypersensitivity Syndrome to Both Vancomycin and Teicoplanin

Drug hypersensitivity syndrome to both vancomycin and teicoplanin has not been previously reported. We describe here a 50-yr-old male patient with vertebral osteomyelitis and epidural abscess who developed hypersensitivity syndrome to both vancomycin and teicoplanin. Skin rash, fever, eosinophilia, interstitial pneumonitis, and interstitial nephritis developed following the administration of each drug, and resolved after withdrawing the drugs and treating with high dose corticosteroids. The vertebral osteomyelitis was successfully treated with 6-week course of linezolid without further complications. Skin patch tests for vancomycin and teicoplanin was done 2 months after the recovery; a weak positive result for vancomycin (10% aq.,+at D2 and +at D4 with erythema and vesicles; ICDRG scale), and a doubtful result for teicoplanin (4% aq.-at D2 and±at D4 with macular erythema; ICDRG scale). We present this case to alert clinicians to the hypersensitivity syndrome that can result from vancomycin and teicoplanin, with possible cross-reactivity, which could potentially be life-threatening

Strongyloidiasis Presenting as Yellowish Nodules in Colonoscopy of an Immunocompetent Patient

Strongyloides stercoralis is endemic to tropical and subtropical regions, and infections are usually asymptomatic. However, immunocompromised patients, such as those receiving immunosuppressive therapy, high-dose steroids, or chemotherapy, can develop fatal hyperinfections. An 84-year-old man without any symptoms was diagnosed with strongyloidiasis during a regular screening colonoscopy. His medical history only involved a gastric endoscopic submucosal dissection for early gastric cancer 6 months previously. Few cases have been published about asymptomatic strongyloidiasis diagnosed in an immunocompetent host via endoscopic mucosal resection with characteristic colonoscopic findings. We report a case of colon-involved asymptomatic strongyloidiasis with specific colonic findings of yellowish-white nodules. This finding may be an important marker of S. stercoralis infection, which could prevent hyperinfections

A Potent and Broad Neutralization of SARS-Cov-2 Variants of Concern by DARpins

We report the engineering and selection of two synthetic proteins-FSR16m and FSR22-for the possible treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. FSR16m and FSR22 are trimeric proteins composed of DARPin SR16m or SR22 fused with a T4 foldon. Despite selection by a spike protein from a now historical SARS-CoV-2 strain, FSR16m and FSR22 exhibit broad-spectrum neutralization of SARS-CoV-2 strains, inhibiting authentic B.1.351, B.1.617.2 and BA.1.1 viruses, with respective I

An efficient approach for estimating streamflow forecast skill elasticity

Seasonal streamflow prediction skill can derive from catchment initial hydrological conditions (IHCs) and from the future seasonal climate forecasts (SCFs) used to produce the hydrological forecasts. Although much effort has gone into producing state-of-the-art seasonal streamflow forecasts from improving IHCs and SCFs, these developments are expensive and time consuming and the forecasting skill is still limited in most parts of the world. Hence, sensitivity analyses are crucial to funnel the resources into useful modelling and forecasting developments. It is in this context that a sensitivity analysis technique, the variational ensemble streamflow prediction assessment (VESPA) approach, was recently introduced. VESPA can be used to quantify the expected improvements in seasonal streamflow forecast skill as a result of realistic improvements in its predictability sources (i.e., the IHCs and the SCFs) - termed ‘skill elasticity’ - and to indicate where efforts should be targeted. The VESPA approach is however computationally expensive, relying on multiple hindcasts having varying levels of skill in IHCs and SCFs. This paper presents two approximations of the approach that are computationally inexpensive alternatives. These new methods were tested against the original VESPA results using 30 years of ensemble hindcasts for 18 catchments of the contiguous United States. The results suggest that one of the methods, End Point Blending, is an effective alternative for estimating the forecast skill elasticities yielded by the VESPA approach. The results also highlight the importance of the choice of verification score for a goal-oriented sensitivity analysis