Targeted multifidus muscle activation reduces fibrosis of multifidus muscle following intervertebral disc injury.

PURPOSE: Aerobic exercise produces beneficial outcomes in patients with low back pain and partially attenuates the fibrotic changes to the multifidus in a model of intervertebral disc (IVD) degeneration. More targeted exercise might be required to fully attenuate these fibrotic alterations. This study aimed to investigate whether activation of the multifidus induced by neurostimulation could reduce fibrosis of the multifidus in a model of IVD degeneration in sheep. METHODS: IVD degeneration was induced in 18 merino sheep via a partial thickness unilateral annulus fibrosus lesion to the L1/2 and L3/4 IVDs. All sheep received an implantable neurostimulation device that provides stimulation of the L2 medial branch of the dorsal ramus. Three months after surgery, the animals were assigned to Injury or Activated groups. Activated animals received neurostimulation and the Injury group received no stimulation. Six months after surgery, the multifidus was harvested at L2 and L4. Van Gieson's, Sirius Red and immunofluorescence staining for Collagen-I and -III and quantitative PCR was used to examine fibrosis. Muscle harvested from a previous study without IVD injury was used as a control. RESULTS: Neurostimulation of the multifidus attenuated IVD degeneration dependent increases in the connective tissue, including Collagen-I but not Collagen-III, compared to the Injury group at L4. No measures of the multifidus muscle at L2, which received no stimulation, differed between the Injury and Activated groups. CONCLUSIONS: These data reveal that targeted activation of the multifidus muscle attenuates IVD degeneration dependent fibrotic alterations to the multifidus.

Reference interval for the C-ACT activated clotting time test in healthy dogs using a water bath and manual assessment of clot formation.

AIMS: To establish a reference range for the canine C-ACT activated clotting time (ACT) test using a water bath and visual clot assessment technique. METHODS: Healthy, privately owned dogs (n = 48) were prospectively recruited to the study. Blood samples were collected via direct jugular venipuncture for complete blood count, serum biochemistry analysis and measurement of prothrombin time (PT) and activated partial thromboplastin time (aPTT). Five animals with major abnormalities or who became agitated during phlebotomy were excluded. For the 43 remaining animals, 2 mL of blood was collected via the cephalic vein and added directly to a C-ACT tube that was shaken vigorously before being placed in a water bath at 37°C. Tubes were visually assessed for clot formation and C-ACT was recorded in seconds when the magnet within the tube lodged in the clot. RESULTS: The nonparametric reference interval (capturing the central 95% of the data) was 50-80 seconds, with a 90% CI for the lower limit of 50-55 seconds and a 90% CI for the upper limit of 75-80 seconds. The C-ACT ACT test had a positive correlation with aPTT (0.42; 95% CI = 0.13-0.64). There was no evidence of a correlation between C-ACT ACT and age, weight, PT, haematocrit, white blood cell count, platelet count or total protein. CONCLUSIONS AND CLINICAL RELEVANCE: The results of this study suggest that the normal reference interval for ACT in dogs using C-ACT tubes in a 37°C water bath is 50-80 seconds. Care should be taken extrapolating the results of this study to the general population, as the smaller study design had less control for confounders than a larger study. However, when using the described analytical methods, C-ACT tube ACT test results >80 seconds should be considered prolonged in dogs and should prompt further investigation.

Green Salad Intake Is Associated with Improved Oral Cancer Survival and Lower Soluble CD44 Levels.

Deficiencies in fruit and vegetable intake have been associated with oral cancer (oral cavity and oropharyngeal). Salivary rinses contain measurable biomarkers including soluble CD44 (solCD44) and total protein, which are known markers of oral cancer risk. This study investigates the effect of nutritional factors on solCD44 and protein levels to evaluate oral cancer risk and survival. We evaluated solCD44 and protein levels from 150 patients with oral and oropharyngeal squamous cell carcinoma and 150 frequency-matched controls. We subsequently characterized the effect of food group consumption and these biomarkers on progression-free survival (PFS) and overall survival (OS). Patients reported eating fewer servings of salad (p = 0.015), while controls reported eating fewer servings of potatoes (p < 0.001). Oral cancer patients who consumed at least one serving per week of green salad were found to have significantly lower CD44 levels than those who ate salad less frequently (mean of log2[solCD44]1.73 versus 2.25, p = 0.014). Patients who consumed at least one serving per week of "salad or other vegetables" had significantly longer PFS (median 43.5 versus 9.1 months, p = 0.003, adjusted hazard ratio (HR) = 0.39 p = 0.014) and OS (median 83.6 versus 10 months, p = 0.008, adjusted HR = 0.04 p = 0.029). These findings suggest that dietary factors, namely greater green salad and vegetable intake, may be associated with lower CD44 levels and better prognosis in oral cancer patients.

Disparities in Head and Neck Cancer: A Case for Chemoprevention with Vitamin D.

Blacks experience disproportionate head and neck cancer (HNC) recurrence and mortality compared to Whites. Overall, vitamin D status is inversely associated to HNC pointing to a potential protective linkage. Although hypovitaminosis D in Blacks is well documented it has not been investigated in Black HNC patients. Thus, we conducted a prospective pilot study accessing vitamin D status in newly diagnosed HNC patients stratified by race and conducted in vitro studies to investigate mechanisms associated with potential cancer inhibitory effects of vitamin D. Outcome measures included circulating levels of vitamin D, related nutrients, and risk factor characterization as well as dietary and supplemental estimates. Vitamin D-based in vitro assays utilized proteome and microRNA (miR) profiling. Nineteen patients were enrolled, mean circulating vitamin D levels were significantly reduced in Black compared to White HNC patients, 27.3 and 20.0 ng/mL, respectively. Whites also supplemented vitamin D more frequently than Blacks who had non-significantly higher vitamin D from dietary sources. Vitamin D treatment of HNC cell lines revealed five significantly altered miRs regulating genes targeting multiple pathways in cancer based on enrichment analysis (i.e., negative regulation of cell proliferation, angiogenesis, chemokine, MAPK, and WNT signaling). Vitamin D further altered proteins involved in cancer progression, metastasis and survival supporting a potential role for vitamin D in targeted cancer prevention.

Ethical surgical triage of patients with head and neck cancer during the COVID-19 pandemic.

BACKGROUND: Coronavirus has serially overtaken our metropolitan hospitals. At peak, patients with acute respiratory distress syndrome may outnumber mechanical ventilators. In our Miami Hospital System, COVID-19 cases have multiplied for 4 weeks and elective surgery has been suspended. METHODS: An Otolaryngologic Triage Committee was created to appropriately allocate resources to patients. Hospital ethicists provided support. Our tumor conference screened patients for nonsurgical options. Patients were tested twice for coronavirus before performing urgent contaminated operations. N95 masks and protective equipment were conserved when possible. Patients with low-grade cancers were advised to delay surgery, and other difficult decisions were made. RESULTS: Hundreds of surgeries were canceled. Sixty-five cases screened over 3 weeks are tabulated. Physicians and patients expressed discomfort regarding perceived deviations from standards, but risk of COVID-19 exposure tempered these discussions. CONCLUSIONS: We describe the use of actively managed surgical triage to fairly balance our patient's health with public health concerns.

Total intravenous anaesthesia with ketamine, medetomidine and guaifenesin compared with ketamine, medetomidine and midazolam in young horses anaesthetised for computerised tomography.

BACKGROUND: There is no information directly comparing midazolam with guaifenesin when used in combination with an alpha-2 agonist and ketamine to maintain anaesthesia via i.v. infusion in horses. OBJECTIVES: To compare ketamine-medetomidine-guaifenesin with ketamine-medetomidine-midazolam for total intravenous anaesthesia (TIVA) in young horses anaesthetised for computerised tomography. STUDY DESIGN: Prospective, randomised, blinded, crossover trial. METHODS: Fourteen weanlings received medetomidine 7 µg/kg bwt i.v. and anaesthesia was induced with ketamine 2.2 mg/kg bwt i.v. On two separate occasions horses each received infusions of ketamine 3 mg/kg bwt/h, medetomidine 5 µg/kg bwt/h, guaifenesin 100 mg/kg bwt/h (KMG) or ketamine 3 mg/kg bwt/h, medetomidine 5 µg/kg bwt/h, midazolam 0.1 mg/kg bwt/h (KMM) for 50 min. Cardiorespiratory variables and anaesthetic depth were assessed every 5-10 min. Recovery times after the infusions ceased were recorded and recovery quality was assessed using a composite score system (CSS), simple descriptive scale (SDS) and visual analogue scale (VAS). Multivariable models were used to generate mean recovery scores for each treatment and each recovery score system and provide P-values comparing treatment groups. RESULTS: Anaesthesia was uneventful with no difference in additional anaesthetic requirements and little clinically relevant differences in cardiopulmonary variables between groups. All horses recovered without incident with no significant difference in recovery times. Quality of the anaesthetic recovery was significantly better for the KMM group compared with the KMG group using the CSS (P<0.001), SDS (P<0.001) and VAS (P<0.001). MAIN LIMITATIONS: No surgical stimulus was applied and study animals may not represent general horse population. CONCLUSION: Midazolam is a suitable alternative to guaifenesin when co-infused with ketamine and medetomidine for anaesthesia in young horses undergoing noninvasive procedures. Both infusions produce a clinically comparable quality of anaesthesia; however, recovery from anaesthesia is of a better quality following an infusion of ketamine-medetomidine-midazolam.

Surface modification of bulk titanium substrates for biomedical applications via low-temperature microwave hydrothermal oxidation.

Micro-to-nanoscale surface topographies of orthopaedic and dental implants can affect fluid wetting and biological response. Nanoscale features can be superimposed on microscale roughness of titanium (Ti) surfaces at high temperatures, resulting in increased osteoblast differentiation. However, high temperatures can compromise mechanical properties of the bulk material. Here, we have developed a novel low-temperature microwave hydrothermal (MWHT) oxidation process for nanomodification of microrough (SLA) Ti surfaces. Nanoscale protuberances (20 -100 nm average diameter) were generated on SLA surfaces via MWHT treatment at 200°C in H2 O, or in aqueous solutions of H2 O2 or NH4 OH, for times ranging from 1 to 40 h. The size, shape, and crystalline content of the nanoprotuberances varied with the solution used and treatment time. The hydrophilicity of all MWHT-modified surfaces was dramatically enhanced. MG63 and normal human osteoblasts (NHOsts) were cultured on MWHT-treated SLA surfaces. While most responses to MWHT-modified surfaces were comparable to those seen on SLA controls, the MWHT-generated nanotopography reduced osteocalcin production by NHOst cells, suggesting that specific nanotopographic characteristics differentially mediate osteoblast phenotypic expression. MWHT processing provides a scalable, low-temperature route for tailoring nanoscale topographies on microroughened titanium implant surfaces with significantly enhanced wetting by water, without degrading the microscale surface structure of such implants. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 782-796, 2018.

Tunable multimodal adhesion of 3D, nanocrystalline CoFe2O4 pollen replicas.

3D replicas of sunflower pollen microparticles, comprised of a multicomponent magnetic spinel ferrite (CoFe2O4) with tailorable adhesive properties, have been synthesized for the first time via a conformal layer-by-layer (LbL) surface sol-gel (SSG) deposition process followed by organic pyrolysis and oxide compound formation at a peak temperature of 600 °C-900 °C. These high-fidelity ferrite pollen replicas exhibited multimodal (van der Waals, vdW, and magnetic) adhesion that could be tuned via control of the CoFe2O4 nanoparticle and crystal sizes. The CoFe2O4 pollen replicas exhibited a non-monotonic change in short-range (~10 nm) vdW adhesion with an increase in the peak firing temperature, which was consistent with the counteracting effects of particle coarsening on the size and number of nanoparticles present on the sharp tips of the echini (spines) on the pollen replica surfaces. The longer-range (up to ~1 mm) magnetic force of adhesion increased monotonically with an increase in firing temperature, which was consistent with the observed increases in the values of the saturation and remanent magnetization of CoFe2O4 with an increase in average nanocrystal size. By adjusting the nanocrystal/nanoparticle sizes of the CoFe2O4 pollen replicas, the total force of adhesion (vdW + magnetic) to a magnetic substrate could be increased by a factor of ~3 relative to native pollen grains.

Effect of actionable somatic mutations on racial/ethnic disparities in head and neck cancer prognosis.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and minorities have the worst survival. However, the molecular mechanisms underlying survival disparities have not been elucidated. METHODS: In a retrospective study, we assessed association between HNSCC early death (<2 years) and 208 somatic mutations of 10 cancer-related genes in 214 patients: 98 non-Hispanic whites (46%), 72 Hispanic whites (34%), and 44 African Americans (20%). RESULTS: Hispanic whites and African Americans had significantly higher mutation rates for EGFR, HRAS, KRAS, and TP53. HNSCC early death was significantly associated with 3+ mutations (odds ratio [OR] = 2.78, 95% confidence interval [CI] = 1.16, 6.69), NOTCH1 mutations in non-Hispanic whites (OR = 5.51; 95% CI = 1.22-24.83) and TP53 mutations in Hispanic whites (OR = 3.84; 95% CI = 1.08-13.68) in multivariable analysis adjusted for age, sex, tumor site, and tumor stage. CONCLUSION: We have provided the proof-of-principal data to link racial/ethnic-specific somatic mutations and HNSCC prognosis and pave the way for precision medicine to overcome HNSCC survival disparities. © 2016 Wiley Periodicals, Inc. Head Neck 38:1234-1241, 2016.