A Sports Medicine Clinician's Guide to the Diagnosis and Management of Distal Clavicular Osteolysis.

ABSTRACT: Weightlifting associated shoulder injuries have seen a dramatic rise in the last 20 years. Distal clavicular osteolysis, coined weightlifter's shoulder, is one such condition caused by repetitive microtrauma to the distal clavicle with subsequent, painful development of bony erosions and resorption of the distal clavicle. Diagnosis, treatment, and prevention of this condition can be challenging. In this article, we highlight evidence-based clinical recommendations for the diagnosis and management of distal clavicular osteolysis, including specific considerations for atraumatic and posttraumatic etiologies, to help clinicians better care for their patients. Activity modification and rehabilitation are the mainstays of the initial treatment. Adjuvant treatments, such as injections or surgery, may be required in refractory cases or in certain patient populations. Early recognition and treatment of weightlifter's shoulder is essential to prevent progression to acromioclavicular joint pathology or instability and to allow for continued participation in sport-specific activities.

Exploring 5-minute heart rate variability in spinal cord injury during acute inpatient rehabilitation.

To explore the use of 5-minute heart rate variability (HRV) during inpatient rehabilitation in the acute phase of traumatic spinal cord injury (SCI).Longitudinal observational study.Acute inpatient rehabilitation (AIR).10 patients with acute traumatic SCI.5-minute HRV supine recordings twice daily on three different days per patient.HRV values were evaluated (1) within a single day (Early versus Late); (2) across the inpatient admission (initial, mid, and discharge); (3) by SCI phenotypes and by clinical outcomes (ex. pressure injuries (PI)).Patients had an average age of 38 years, 80% male, and 40% with tetraplegia. There were no HRV differences between Early and Late recordings, across the inpatient admission, demographics, or SCI phenotype. However, improvement in neurologic exam was accompanied by increased parasympathetic tone (mean RR increased by 172 ms SD 61, P = .005). Patients with PI demonstrated lower sympathetic (SNS) activity (decreased LF by 472 ms2 SD 240, P = .049) and lower PNS activity (decreased RMSSD by 1.2 ms SD 0.5, P = .02), compared to no PI. Comparisons to uninjured reference values and chronic SCI suggest a changing autonomic nervous system (ANS) from uninjured to acute to chronic as measured by HRV. CONCLUSIONS: This preliminary evidence suggests HRV in acute SCI is stable across time and day during inpatient rehabilitation and may be correlated to clinical sequalae of ANS dysfunction and neurologic recovery. Comparisons to published work suggest that HRV may measure the progression in the ANS from acute to chronic phase after SCI.

Evaluation of antimicrobial, anticancer potential and Flippase induced leakage in model membrane of Centella asiatica fabricated MgONPs.

The use of chemically synthesized nanoparticles and crude plant extracts as antimicrobial -anticancer agents have many limitations. In this study, we have used Centella asiatica extract (CaE) having relatively less explored but tremendous medicinal properties, as reducing and stabilizing agents to green synthesize magnesium oxide nanoparticles (MgONPs) using magnesium nitrate. In comparison to the bulk material, capabilities of Ca-MgONPs as an improved antibacterial, antifungal, and anticancer agent in human prostatic carcinoma cells (PC3), as well as membranolytic capability in model cell membrane, were studied. The phyto-functionalized Ca-MgONPs were characterized using UV-Visible spectroscopy (UV-Vis), Transmission Electron Microscopy (TEM), Energy Dispersive X-Ray Spectroscopy (EDX), X-ray Diffraction (XRD), Fourier Transform Infra-Red Spectroscopy (FT-IR) and Atomic Force Microscopy (AFM). Observation of characteristic peaks by spectroscopic and microscopic analysis confirmed the synthesis of Ca-MgONPs. The Ca-MgONPs showed broad spectrum of bactericidal activity against both gram-positive and gram-negative bacteria and fungicidal activity against two species of the Candida fungus. The Ca-MgONPs also exhibited dose-dependent and selective inhibition of proliferating PC3 cells with IC50 of 123.65 ± 4.82 µg/mL at 24 h, however, without having any cytotoxicity toward non-cancerous HEK293 cells. Further studies aimed at understanding the probable mechanism of toxicity of Ca-MgONPs in PC3 cells, the results indicated a significant reduction in cell migration capacities, increment in cytosolic ROS, loss of mitochondrial transmembrane potential, DNA damage and S-phase cell cycle arrest. Ca-MgONPs also induced pore formation in a synthetic large unilamellar vesicle. Thus, Ca-MgONPs might be useful in the effective management of several human pathogens of concern and some more cancer types.

Untargeted Metabolomics in Piper betle Leaf Extracts to Discriminate the Cultivars of Coastal Odisha, India.

Betel leaf is consumed as a mouth freshener due to its characteristic flavor, aromaticity, and medicinal values. Abundance of phytochemicals in betel leaf contributes towards unique qualitative features. Screening of metabolites is quintessential for identifying flavoring betel leaves and their origin. Metabolomics presently lays emphasis on the cumulative application of gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopic approaches. Here we adopted different protocols based on the above-mentioned analytical metabolomics platform for untargeted plant metabolite profiling followed by multivariate analysis methods and a phytochemical characterization of Piper betel leaf cultivars endemic to coastal Odisha, India. Based on variation in the solvent composition, concentration of solvent, extraction temperature, and incubation periods, five extraction methods were followed in GC-MS and NMR spectroscopy of betel leaf extracts. Phytochemical similarities and differences among the species were characterized through multivariate analysis approaches. Principal component analysis, based on the relative abundance of phytochemicals, indicated that the betel cultivars could be grouped into three groups. Our results of FTIR-, GC-MS-, and NMR-based profiling combined with multivariate analyses suggest that untargeted metabolomics can play a crucial role in documenting metabolic signatures of endemic betel leaf varieties.

Combination Intrathecal Drug Therapy Strategies for Pain Management.

BACKGROUND: Numerous combination intrathecal drug therapy (CIDT) strategies exist and are utilized for varying pain syndromes, typically when monotherapy dose escalation or medication alternation is deemed untenable or unfeasible. Unfortunately, the supportive evidence basis for the use of these strategies and specific drug combinations is generally lacking and unclear, with many medications being used for off-label indications. OBJECTIVE: In this manuscript, we provide a robust exploration and analysis of the literature to provide an evidence-based narrative for the use of CIDT strategies in regard to clinical indications, pharmacologic parameters, specific drug combinations, safety profiles, and future directions. STUDY DESIGN: Narrative review. METHODS: This was an evidence based narrative performed after extensive review of the literature. RESULTS: Variances in intrathecal pharmacokinetics and pharmacodynamics are utilized advantageously with CIDT strategies to achieve improved analgesic benefit; however, appropriate use may be limited by increased or compounded risk of adverse effects. The supportive evidence for CIDT use for chronic pain conditions is largely lacking and limited to small, uncontrolled, observational studies, with many having various confounding factors, including a lack of standardized dosing. The most evidenced CIDT strategies include polyanalgesia with morphine-ziconotide, opioid-clonidine, and morphine-bupivacaine. Notably, in addition to pain relief, morphine-bupivacaine has been shown to decrease early opioid escalation requirements. LIMITATIONS: The supportive evidence for CIDT use for chronic pain conditions is largely lacking and limited to small, uncontrolled, observational studies, with many having various confounding factors including a lack of standardized dosing. CONCLUSIONS: CIDT strategies and polyanalgesia combinations can be effective for treating various patient populations with chronic pain. The appropriate use of these strategies may be limited by increased or compounded risk of adverse effects, both of which are highly patient and scenario dependent. Therefore, practitioners should maintain a particularly low threshold of suspicion for adverse effects in patients with CIDT such that safety profiles associated with this therapy can be favorably maintained.

Radiofrequency Ablation for Thoracic and Abdominal Chronic Pain Syndromes.

Chronic thoracic pain and chronic abdominal pain are common conditions that can significantly affect quality of life. Pain syndromes encompassing a variety of causes, including cancer pain, neuritis, and postsurgical pain, are traditionally managed by the use of pharmacologic therapy; however, many cases are refractory to these conservative methods. Radiofrequency ablation (RFA) has been increasingly used as a tool to treat resistant, chronic pain of both thoracic and abdominal origin. Multiple cases and trials have been reported that show the efficacy of RFA in the treatment of these chronic pain conditions.

Incidence, Diagnosis, and Management of Neuromas Following Radiofrequency Ablation Treatment: a Narrative Review.

OBJECTIVE: To determine the epidemiology of neuroma formation as a complication following radiofrequency ablation for chronic pain conditions as well as reviewing the diagnosis and management of neuromas. DESIGN: Evidence-based narrative review and critical appraisal of literature. RESULTS: A comprehensive review of the literature generated one case report describing neuroma formation following lumbar facet medial branch radiofrequency denervation. The rare incidence may be explained by neuroma pathophysiology and peripheral nerve injury produced by radiofrequency ablation, in combination with its asymptomatic nature. Diagnosis of neuromas is predominantly confirmed by clinical history and physical exam with potential for nerve blocks or imaging. Ultrasound has been suggested as a primary imaging modality with magnetic resonance imaging as a secondary option. Neuroma management ranges from conservative therapy to surgery with varying success rates. CONCLUSIONS: Neuroma formation following radiofrequency ablation procedures is exceedingly rare and could be a hypothetical concern in clinical practice. However, the true incidence may be inaccurate given the asymptomatic nature of neuromas.

Radiotherapy-Specific Chronic Pain Syndromes in the Cancer Population: An Evidence-Based Narrative Review.

While radiation therapy is increasingly utilized in the treatment paradigm of many solid cancers, the chronic effects of radiation therapies are poorly characterized. Notably, understanding radiation-specific chronic pain syndromes is paramount given that the diagnosis and management of these conditions can serve to prevent long-standing functional impairments, optimize quality of life, and even allow for continued radiotherapy candidacy. These radiation-specific chronic pain phenomena include dermatitis, mucositis, enteritis, connective tissue fibrosis, lymphedema, and neuropathic pain syndromes. It is necessary to maintain a low threshold of suspicion for appropriately diagnosing these conditions as there exists a variance in when these symptoms arise after radiation. However, we present key epidemiological data delineating vulnerable cancer populations for each pain syndrome along with the available evidence for the management for each specific condition.

Pain Syndromes Secondary to Cluneal Nerve Entrapment.

PURPOSE OF REVIEW: The purpose of this review is to provide an overview of the cluneal nerves, present a summary of pain syndromes secondary to clunealgia, and evaluate current literature for diagnostic and treatment modalities. RECENT FINDINGS: Multiple trials and studies have reported success with numerous modalities ranging from nerve blocks, neuroablation, and even peripheral neuromodulation with varying degrees of clinical benefit. Cluneal nerve entrapment or chronic impingement can cause buttock pain or referred pain to nearby areas including the lower back, pelvic area, or even the lower extremities. Clunealgias and associated pain syndromes can often be challenging to diagnose and differentiate. An appreciation of the pathophysiology of clunealgias can assist with patient selection for interventional pain strategies targeted towards the cluneal nerves, including nerve blocks, neuroablation, and peripheral neuromodulation. More research is needed to better delineate the efficacy of these procedures for clunealgias.

Descriptions and outcomes of cardiac evaluations in pediatric patients hospitalized for asthma.

Objective: Patients hospitalized for asthma can exhibit concurrent cardiac symptoms and undergo cardiac work up. We identify patients admitted for asthma that underwent cardiac workup and describe outcomes to evaluate the utility of cardiac testing in this population.Methods: Patients aged 4 to 17 years admitted for status asthmaticus from 2012 - 2016 were screened for EKG, ECHO, or cardiac enzyme obtainment.Results: Out of 1296 patients, 77 (6%) received cardiac testing. The most common reasons for testing were chest pain (25, 32%), blood pressure abnormalities (11, 14%), tachycardia (8, 10%), arrhythmia (6, 8%), and syncope (6, 8%). Sinus tachycardia (43, 66%) was the most common EKG finding. 4 out of 27 patients who underwent ECHOs had abnormalities: 2 with hypertrophic cardiomyopathy (HCM), 1 with vascular ring, and 1 with evidence of pulmonary hypertension. All patients who underwent an EKG to evaluate tachycardia had normalization of heart rate at discharge. Cardiac ischemia was not evident in any patients who underwent workup with cardiac enzymes to evaluate chest pain. All cases of arrhythmias resolved on discharge. Diastolic hypotension (DhTN) was found in 10 out of the 11 blood pressure abnormalities. There was mixed efficacy of fluid bolus in correcting DhTN. All DhTN resolved on discharge. One patient with syncope had a new diagnosis of HCM.Conclusions: While cardiac complications are seen in patients admitted for status asthmaticus, the etiology rarely stems from underlying cardiac disease. EKGs, ECHOs, and cardiac enzymes should have a minimal role in the management of the hospitalized asthmatic patient.

Electrophysiological Outcome Measures in Spinal Cord Injury Clinical Trials: A Systematic Review.

Background: Electrophysiological measures are being increasingly utilized due to their ability to provide objective measurements with minimal bias and to detect subtle changes with quantitative data on neural function. Heterogeneous reporting of trial outcomes limits effective interstudy comparison and optimization of treatment. Objective: The objective of this systematic review is to describe the reporting of electrophysiological outcome measures in spinal cord injury (SCI) clinical trials in order to inform a subsequent consensus study. Methods: A systematic search of PubMed and EMBASE databases was conducted according to PRISMA guidelines. Adult human SCI clinical trials published in English between January 1, 2008 and September 15, 2018 with at least one electrophysiological outcome measure were eligible. Findings were reviewed by all authors to create a synthesis narrative describing each outcome measure. Results: Sixty-four SCI clinical trials were included in this review. Identified electrophysiological outcomes included electromyography activity (44%), motor evoked potentials (33%), somatosensory evoked potentials (33%), H-reflex (20%), reflex electromyography activity (11%), nerve conduction studies (9%), silent period (3%), contact heat evoked potentials (2%), and sympathetic skin response (2%). Heterogeneity was present in regard to both methods of measurement and reporting of electrophysiological outcome measures. Conclusion: This review demonstrates need for the development of a standardized reporting set for electrophysiological outcome measures. Limitations of this review include exclusion of non-English publications, studies more than 10 years old, and an inability to assess methodological quality of primary studies due to a lack of guidelines on reporting of systematic reviews of outcome measures.

EPR and Structural Characterization of Water-Soluble Mn2+-Doped Si Nanoparticles.

Water-soluble poly(allylamine) Mn2+-doped Si (SiMn) nanoparticles (NPs) were prepared and show promise for biologically related applications. The nanoparticles show both strong photoluminescence and good magnetic resonance contrast imaging. The morphology and average diameter were obtained through transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HRTEM); spherical crystalline Si NPs with an average diameter of 4.2 ± 0.7 nm were observed. The doping maximum obtained through this process was an average concentration of 0.4 ± 0.3% Mn per mole of Si. The water-soluble SiMn NPs showed a strong photoluminescence with a quantum yield up to 13%. The SiMn NPs had significant T1 contrast with an r1 relaxivity of 11.1 ± 1.5 mM-1 s-1 and r2 relaxivity of 32.7 ± 4.7 mM-1 s-1 where the concentration is in mM of Mn2+. Dextran-coated poly(allylamine) SiMn NPs produced NPs with T1 and T2 contrast with a r1 relaxivity of 27.1 ± 2.8 mM-1 s-1 and r2 relaxivity of 1078.5 ± 1.9 mM-1 s-1. X-band electron paramagnetic resonance spectra are fit with a two-site model demonstrating that there are two types of Mn2+ in these NP's. The fits yield hyperfine splittings (A) of 265 and 238 MHz with significant zero field splitting (D and E terms). This is consistent with Mn in sites of symmetry lower than tetrahedral due to the small size of the NP's.

Enhanced hydrolytic stability of siliceous surfaces modified with pendant dipodal silanes.

Dipodal silanes possess two silicon atoms that can covalently bond to a surface. They offer a distinct advantage over conventional silanes commonly used for surface modification in terms of maintaining the integrity of surface coatings, adhesive primers, and composites in aqueous environments. New nonfunctional and functional dipodal silanes with structures containing "pendant" rather than "bridged" organofunctionality are introduced. The stability of surfaces in aqueous environments prepared from dipodal silanes with hydrophobic alkyl functionality is compared to the stability of similar surfaces prepared from the conventional silanes. In strongly acidic and brine environments, surfaces modified with dipodal silanes demonstrate markedly improved resistance to hydrolysis compared to surfaces prepared from conventional silanes. Pendant dipodal silanes exhibit greater stability than bridged dipodal silanes. The apparent equilibrium constant for the formation of silanol species by the hydrolysis of a disiloxane bond was determined as Kc = [SiOH](2)/[Si-O-Si][H2O] = 6±1×10(-5) and is helpful in understanding the enhanced hydrolytic stability of surfaces modified with dipodal silanes.

Cytotoxicity of surface-functionalized silicon and germanium nanoparticles: the dominant role of surface charges.

Although it is frequently hypothesized that surface (like surface charge) and physical characteristics (like particle size) play important roles in cellular interactions of nanoparticles (NPs), a systematic study probing this issue is missing. Hence, a comparative cytotoxicity study, quantifying nine different cellular endpoints, was performed with a broad series of monodisperse, well characterized silicon (Si) and germanium (Ge) NPs with various surface functionalizations. Human colonic adenocarcinoma Caco-2 and rat alveolar macrophage NR8383 cells were used to clarify the toxicity of this series of NPs. The surface coatings on the NPs appeared to dominate the cytotoxicity: the cationic NPs exhibited cytotoxicity, whereas the carboxylic acid-terminated and hydrophilic PEG- or dextran-terminated NPs did not. Within the cationic Si NPs, smaller Si NPs were more toxic than bigger ones. Manganese-doped (1% Mn) Si NPs did not show any added toxicity, which favors their further development for bioimaging. Iron-doped (1% Fe) Si NPs showed some added toxicity, which may be due to the leaching of Fe(3+) ions from the core. A silica coating seemed to impart toxicity, in line with the reported toxicity of silica. Intracellular mitochondria seem to be the target for the toxic NPs since a dose-, surface charge- and size-dependent imbalance of the mitochondrial membrane potential was observed. Such an imbalance led to a series of other cellular events for cationic NPs, like decreased mitochondrial membrane potential (ΔΨm) and ATP production, induction of ROS generation, increased cytoplasmic Ca(2+) content, production of TNF-α and enhanced caspase-3 activity. Taken together, the results explain the toxicity of Si NPs/Ge NPs largely by their surface characteristics, provide insight into the mode of action underlying the observed cytotoxicity, and give directions on synthesizing biocompatible Si and Ge NPs, as this is crucial for bioimaging and other applications in for example the field of medicine.

Chemical insight into the origin of red and blue photoluminescence arising from freestanding silicon nanocrystals.

Silicon nanocrystals (Si NCs) are attractive functional materials. They are compatible with standard electronics and communications platforms and are biocompatible. Numerous methods have been developed to realize size-controlled Si NC synthesis. While these procedures produce Si NCs that appear identical, their optical responses can differ dramatically. Si NCs prepared using high-temperature methods routinely exhibit photoluminescence agreeing with the effective mass approximation (EMA), while those prepared via solution methods exhibit blue emission that is somewhat independent of particle size. Despite many proposals, a definitive explanation for this difference has been elusive for no less than a decade. This apparent dichotomy brings into question our understanding of Si NC properties and potentially limits the scope of their application. The present contribution takes a substantial step forward toward identifying the origin of the blue emission that is not expected based upon EMA predictions. It describes a detailed comparison of Si NCs obtained from three of the most widely cited procedures as well as the conversion of red-emitting Si NCs to blue emitters upon exposure to nitrogen-containing reagents. Analysis of the evidence is consistent with the hypothesis that the presence of trace nitrogen and oxygen even at the parts per million level in Si NCs gives rise to the blue emission.

Development of iron-doped silicon nanoparticles as bimodal imaging agents.

We demonstrate the synthesis of water-soluble allylamine-terminated Fe-doped Si (Si(xFe)) nanoparticles as bimodal agents for optical and magnetic imaging. The preparation involves the synthesis of a single-source iron-containing precursor, Na(4)Si(4) with x% Fe (x = 1, 5, 10), and its subsequent reaction with NH(4)Br to produce hydrogen-terminated Si(xFe) nanoparticles. The hydrogen-capped nanoparticles are further terminated with allylamine via thermal hydrosilylation. Transmission electron microscopy indicates that the average particle diameter is ∼3.0 ± 1.0 nm. The Si(5Fe) nanoparticles show strong photoluminescence quantum yield in water (∼10%) with significant T(2) contrast (r(2)/r(1) value of 4.31). Electron paramagnetic resonance and Mössbauer spectroscopies indicate that iron in the nanoparticles is in the +3 oxidation state. Analysis of cytotoxicity using the resazurin assay on HepG2 liver cells indicates that the particles have minimal toxicity.

Involvement of the LSPR spectral overlap for energy transfer between a dye and Au nanoparticle.

Nanometal surface energy transfer (NSET) is a molecular ruler technique that has been utilized to optically probe long distances in biomolecular structures. We investigate the useful spectral range of donor dyes and the importance of overlap between the localized surface plasmon resonance (LSPR) and the donor photoluminescence (520-780 nm) and provide a comprehensive study of the R(0) values for the NSET processes from dyes to 2 nm Au NP (gold nanoparticle). The distance-dependent quenching results provide experimental evidence that the efficiency curve slope, R(0) value, and distance of quenching is best modeled as a surface-mediated NSET process analogous to the predictions of Persson-Lang and Chance-Prock-Silbey (CPS). The results show that the LSPR plays a very important role in the observed quenching of excited-state donors at the surface of the nanometal, and the correlation to the NSET model allows a compilation of the necessary biophysical constants for application within the toolbox of biophysics.

C-lysine conjugates: pH-controlled light-activated reagents for efficient double-stranded DNA cleavage with implications for cancer therapy.

Double-stranded DNA cleavage of light-activated lysine conjugates is strongly enhanced at the slightly acidic pH (<7) suitable for selective targeting of cancer cells. This enhancement stems from the presence of two amino groups of different basicities. The first amino group plays an auxiliary role by enhancing solubility and affinity to DNA, whereas the second amino group, which is positioned next to the light-activated DNA cleaver, undergoes protonation at the desired pH threshold. This protonation results in two synergetic effects which account for the increased DNA-cleaving ability at the lower pH. First, lysine conjugates show tighter binding to DNA at the lower pH, which is consistent with the anticipated higher degree of interaction between two positively charged ammonium groups with the negatively charged phosphate backbone of DNA. Second, the unproductive pathway which quenches the excited state of the photocleaver through intramolecular electron transfer is eliminated once the donor amino group next to the chromophore is protonated. Experiments in the presence of traps for diffusing radicals show that reactive oxygen species do not contribute significantly to the mechanism of DNA cleavage at the lower pH, which is indicative of tighter binding to DNA under these conditions. This feature is valuable not only because many solid tumors are hypoxic but also because cleavage which does not depend on diffusing species is more localized and efficient. Sequence-selectivity experiments suggest combination of PET and base alkylation as the chemical basis for the observed DNA damage. The utility of these molecules for phototherapy of cancer is confirmed by the drastic increase in toxicity of five conjugates against cancer cell lines upon photoactivation.

Tracking spatial disorder in an optical ruler by time-resolved NSET.

For biomolecular applications, potential interactions between newly developed dye molecules and the biomolecule of interest can dramatically influence the accuracy of optical ruler techniques. By utilizing nanometal surface energy transfer (NSET), an optical technique is developed that allows the nature of interactions between dyes and a biomolecule, namely DNA, to be directly assessed. To demonstrate the method, interactions between well-known molecular dyes based on carboxyfluorescein (FAM, noninteracting) and Cy5 (known intercalator) with DNA is probed. The results demonstrate that FAM exhibits no interactions with the DNA backbone and is adequately represented as a solvent exposed dye, while the commonly used near-IR dye Cy5 exhibits two discrete interactions that depend on the site of appendage and the length of the linker arm. The exact population and nature of Cy5 interaction with the DNA indicates a 37% ratio of intercalation for the internal C(6), a 42% ratio for an internal C(3) spacer length, and no evidence of interaction for terminal labeling. The results allow quantitative assignment of the site occupation of donors to be analyzed providing a powerful set of information for use of dyes in FRET based optical ruler technologies without the need of single molecule methods or the assumption of an averaged site occupation for the donor.