Inorganic pyrophosphate is reduced in patients with systemic sclerosis.

OBJECTIVE: The pathogenesis of calcinosis cutis, a disabling complication of SSc, is poorly understood and effective treatments are lacking. Inorganic pyrophosphate (PPi) is a key regulator of ectopic mineralization, and its deficiency has been implicated in ectopic mineralization disorders. We therefore sought to test the hypothesis that SSc may be associated with reduced circulating PPi, which might play a pathogenic role in calcinosis cutis. METHODS: Subjects with SSc and age-matched controls without SSc were recruited from the outpatient rheumatology clinics at Rutgers and Northwestern Universities (US cohort), and from the Universities of Szeged and Debrecen (Hungarian cohort). Calcinosis cutis was confirmed by direct palpation, by imaging or both. Plasma PPi levels were determined in platelet-free plasma using ATP sulfurylase to convert PPi into ATP in the presence of excess adenosine 5' phosphosulfate. RESULTS: Eighty-one patients with SSc (40 diffuse cutaneous, and 41 limited cutaneous SSc) in the US cohort and 45 patients with SSc (19 diffuse cutaneous and 26 limited cutaneous SSc) in the Hungarian cohort were enrolled. Calcinosis was frequently detected (40% of US and 46% of the Hungarian cohort). Plasma PPi levels were significantly reduced in both SSc cohorts with and without calcinosis (US: P = 0.003; Hungarian: P < 0.001). CONCLUSIONS: Circulating PPi are significantly reduced in SSc patients with or without calcinosis. Reduced PPi may be important in the pathophysiology of calcinosis and contribute to tissue damage with chronic SSc. Administering PPi may be a therapeutic strategy and larger clinical studies are planned to confirm our findings.

A Low-Sodium DASH Dietary Pattern Affects Serum Markers of Inflammation and Mineral Metabolism in Adults with Elevated Blood Pressure.

BACKGROUND: The blood pressure-lowering effects of the Dietary Approaches to Stop Hypertension (DASH) dietary pattern and reduced sodium intake are well established. The effects on other biomarkers related to vascular health are of interest and might assist in explaining the effects of the DASH diet and sodium reduction. OBJECTIVES: We hypothesized that a low-sodium DASH diet improves (lowers) biomarkers of inflammation [C-reactive protein (CRP) and soluble urokinase plasminogen activator receptor (suPAR)] and mineral metabolism [phosphorus and fibroblast growth factor-23 (FGF23)]. METHODS: We conducted a secondary analysis of the DASH-Sodium trial using frozen serum samples. This controlled feeding study randomly assigned 412 adults (≥22 y) with elevated blood pressure (120-159/80-95 mmHg) to consume either a DASH diet or control diet. Within each arm, participants received 3 sodium levels [low (1150 mg), intermediate (2300 mg), high (3450 mg)] in random sequence, each for 30 d. To maximize contrast, samples collected at the end of the low-sodium DASH (n = 198) and high-sodium control (n = 194) diets were compared. Between-diet differences in serum CRP, suPAR, phosphorus, and FGF23 concentrations were assessed using linear regression adjusted for age, sex, race, income, education, smoking status, and BMI. RESULTS: CRP concentrations did not differ between groups (P = 0.83), but suPAR was higher after the low-sodium DASH diet than the high-sodium control [geometric mean 2470 pg/mL (95% CI: 2380, 2560 pg/mL), compared with 2290 pg/mL (95% CI: 2210, 2380 pg/mL); P = 0.006]. Phosphorus was higher after the low-sodium DASH diet [geometric mean 3.50 mg/dL (95% CI: 3.43, 3.57 mg/dL)] compared with the high-sodium control diet [geometric mean 3.39 mg/dL (95% CI: 3.33, 3.46 mg/dL); P = 0.04]. FGF23 was also higher after the low-sodium DASH diet [geometric mean 35.3 pg/mL (95% CI: 33.3, 37.3 pg/mL) compared with 28.2 pg/mL (95% CI: 26.6, 29.8 pg/mL); P < 0.001]. CONCLUSIONS: Contrary to our hypothesis, biomarkers of inflammation and mineral metabolism were increased or unchanged by a low-sodium DASH diet compared with a high-sodium control diet in adults with elevated blood pressure.

The Percentage of Dietary Phosphorus Excreted in the Urine Varies by Dietary Pattern in a Randomized Feeding Study in Adults.

BACKGROUND: Urinary phosphorus excretion has been proposed as a recovery biomarker of dietary phosphorus intake. However, it is unclear whether phosphorus excretion is constant across a range of dietary and nondietary factors. OBJECTIVE: We assessed whether percentage urinary phosphorus excretion is constant across 3 dietary patterns in the Dietary Approaches to Stop Hypertension (DASH) trial. METHODS: DASH is a completed feeding study of 459 prehypertensive and stage 1 hypertensive adults (52% male, 56% black). After a 3-wk run-in on a typical American (control) diet, participants were randomly assigned to the control diet, a diet rich in fruits and vegetables (FV diet), or a diet rich in fruits, vegetables, and low-fat dairy with reduced saturated fat and cholesterol (DASH diet) for 8 wk. We estimated the percentage phosphorus excretion as urinary phosphorus excretion (from 24 h urine) divided by phosphorus intake (from analyzed food composites). Differences between group means for all 3 diets were compared by ANOVA followed by pairwise comparisons with Tukey's honest significant difference test. RESULTS: At the end of the intervention, the mean phosphorus intake was 1176 mg/d (95% CI: 1119, 1233 mg/d), 1408 mg/d (1352, 1464 mg/d), and 2051 mg/d (1994, 2107 mg/d) in the control, FV, and DASH diet, respectively (P < 0.001, all comparisons). The mean phosphorus excretion was 734 mg/d (682, 787 mg/d), 705 mg/d (654, 756 mg/d), and 872 mg/d (820, 923 mg/d) in the control, FV, and DASH diet, respectively (P = 0.74 control vs. FV, P < 0.001 all other comparisons). The mean percentage phosphorus excretion was 63% (60%, 67%), 51% (48%, 54%), and 43% (39%, 46%) in the control, FV, and DASH diet, respectively (P < 0.001, all comparisons). CONCLUSIONS: These findings in prehypertensive and stage 1 hypertensive adults strongly suggest that urinary phosphorus excretion should not be used as a recovery biomarker for dietary phosphorus intake, given the wide range of urinary phosphorus excretion across dietary patterns. This trial is registered at clinicaltrials.gov as NCT0000054.

Food security and diet quality, not vitamin D status are significantly associated with depression: Results from NHANES 2015-2018.

BACKGROUND: Observational research has suggested a link between vitamin D insufficiency and depression, while evidence from randomized trials examining the association have yielded inconsistent results. Food security and diet quality are also associated with both vitamin D insufficiency and depression. However, the potential interactions between these factors have not been well described. METHODS: In order to examine the associations between depression, vitamin D status, food security, and diet quality, data from 8988 US adults (≥20 years) in NHANES (National Health and Nutrition Examination Surveys) 2015-2018 were analyzed. Questionnaire-assessed depression, food security, and diet quality and laboratory-analyzed serum vitamin D were used. RESULTS: Lack of full food security and a 10-point decrease in Healthy Eating Index 2015 score were independently associated with higher risk of mild to severe depression (OR 3.72 and 1.20, respectively, p < 0.001). The association between insufficient serum vitamin D (<75 nmol/L) and depression was fully attenuated after adjusting for food security and diet quality (p = 0.41). LIMITATIONS: A major limitation of this paper, like all analyses of NHANES, is the inability to establish the temporality of the relationships between food security and diet quality with depression. CONCLUSIONS: Food security and diet quality, but not vitamin D status, were significantly associated with depression. This highlights how evaluating food security and diet quality are critical in research and public health interventions related to depression. Future interventions, especially into vitamin D insufficiency, as well as health policies should assess and address these factors.

Heterogeneous distribution of viscosupplements in vivo is correlated to ex vivo frictional properties of equine cartilage.

Intra-articular injections of hyaluronic acid (HA) are the cornerstone of osteoarthritis (OA) treatments. However, the mechanism of action and efficacy of HA viscosupplementation are debated. As such, there has been recent interest in developing synthetic viscosupplements. Recently, a synthetic 4 wt% polyacrylamide (pAAm) hydrogel was shown to effectively lubricate and bind to the surface of cartilage in vitro. However, its ability to localize to cartilage and alter the tribological properties of the tissue in a live articulating large animal joint is not known. The goal of this study was to quantify the distribution and extent of localization of pAAm in the equine metacarpophalangeal or metatarsophalangeal joint (fetlock joint), and determine whether preferential localization of pAAm influences the tribological properties of the tissue. An established planar fluorescence imaging technique was used to visualize and quantify the distribution of fluorescently labeled pAAm within the joint. While the pAAm hydrogel was present on all surfaces, it was not uniformly distributed, with more material present near the site of the injection. The lubricating ability of the cartilage in the joint was then assessed using a custom tribometer across two orders of magnitude of sliding speed in healthy synovial fluid. Cartilage regions with a greater coverage of pAAm, that is, higher fluorescent intensities, exhibited friction coefficients nearly 2-fold lower than regions with lesser pAAm (Rrm = -0.59, p < 0.001). Collectively, the findings from this study indicate that intra-articular viscosupplement injections are not evenly distributed inside a joint, and the tribological outcomes of these materials is strongly determined by the ability of the material to localize to the articulating surfaces in the joint.

Serial injections of 4% polyacrylamide hydrogel have no detrimental effects in equine joints following clinical, histologic, and synovial biomarker evaluation.

OBJECTIVE: Polyacrylamide hydrogel (4% PAHG) is an inert viscoelastic supplement used to manage osteoarthritis in horses. Even with a prolonged clinical effect, horses may be administered multiple doses during their performance career. The effect of the serial 4% PAHG treatments is not known. The objectives of this study were to evaluate the clinical, histologic, and synovial fluid biomarker effects following serial administration of 4% PAHG in normal equine fetlock joints. ANIMALS: 8 healthy horses. METHODS: In a blinded, controlled in vivo study, horses received serial intra-articular injections of 4% PAHG (Noltrex Vet; Nucleus ProVets LLC) and contralateral 0.9% saline control on days 0, 45, 90, and 135. Treatment and control joints were randomly assigned. Synovial fluid was collected before administration of 4% PAHG or 0.9% saline on day 0 and at study completion for cellular and biomarker evaluation. Serial physical and lameness examinations were performed throughout the study. On day 240, gross examination and harvest of cartilage and synovial membrane for histology were completed. RESULTS: There were no histologic changes in articular cartilage or synovial fluid biomarkers. The 4% PAHG was seen on the surface of the synovium in 5 of 8 treated joints 105 days after the last treatment. There are minimal effects following serial injections of 4% PAHG on normal joints in horses following administration at 0, 45, 90, and 135 days, with final evaluation on day 240. CLINICAL RELEVANCE: Serial administration of intra-articular 4% PAHG in horses may provide long-term joint lubrication with no detrimental effects.

Polyacrylamide hydrogel lubricates cartilage after biochemical degradation and mechanical injury.

Intra-articular injections of hyaluronic acid have been a mainstay of osteoarthritis treatment for decades. However, controversy surrounds the mechanism of action and efficacy of this therapy. As such, there has been recent interest in developing synthetic lubricants that lubricate cartilage. Recently, a synthetic 4 wt% polyacrylamide (pAAm) hydrogel was shown to effectively decrease lameness in horses. However, its mechanism of action and ability to lubricate cartilage is unknown. The goal of this study was to characterize the lubricating ability of this hydrogel and determine its efficacy for healthy and degraded cartilage. The study utilized previously established IL-1ß-induced biochemical degradation and mechanical impact injury models to degrade cartilage. The lubricating ability of the hydrogel was then characterized using a custom-built tribometer using a glass counterface and friction was evaluated using the Stribeck framework for articular cartilage. pAAm hydrogel was shown to significantly lower the friction coefficient of cartilage explants from both degradation models (30%-40% reduction in friction relative to controls). A striking finding from this study was the aggregation of the pAAm hydrogel at the articulating surface. The surface aggregation was observed in the histological sections of explants from all treatment groups after tribological evaluation. Using the Stribeck framework, the hydrogel was mapped to higher Sommerfeld numbers and was characterized as a viscous lubricant predominantly in the minimum friction mode. In summary, this study revealed that pAAm hydrogel lubricates native and degraded cartilage explants effectively and may have an affinity for the articulating surface of the cartilage.

Equine shock wave therapy - where are we now?

Over the past three decades, electrohydraulic extracorporeal shock wave therapy (ESWT) as a treatment modality for equine orthopaedic disorders has sparked exponential interest among practitioners, but its clinical applications are quickly evolving and a current review highlighting modernised equine clinical use is lacking. The objective of this review is to summarise the most current ESWT technology, evidence for its use, proposed mechanisms of action and clinical applications in horses while also highlighting the areas requiring further investigation. The three ways to generate a shock wave are through electrohydraulic, electromagnetic or piezoelectric mechanisms, but over the last decade, electrohydraulic systems have predominated due to the ability to focus and control a therapeutic waveform. Shock waves' primary physical effect is believed to be via mechanotransduction leading to cellular activation and downstream signalling. Experimentally, ESWT's effects on osseous, connective tissue and wound healing via various mechanisms of action have been reported both in the human and veterinary literature. Clinical trials have investigated ESWT's orthopaedic application including osteoarthritis, thoracolumbar pain, navicular syndrome, tendinopathy and proximal suspensory desmopathy, with its concomitant use with biologics representing an area of active research. Direct ESWT protocol comparisons in terms of long-term efficacy with variables of energy, depth and exposed tissue types are still lacking with evidence-based recommendations being largely anecdotal. Technical advancements to facilitate the safe and judicious use of ESWT include human and equine hearing protection, light sedation and/or patient restraint. Efforts to ensure the safe and judicious use of ESWT and its analgesic effects are ongoing.

Secular Trends in Risk Profiles Among Adults With Cardiovascular Disease in the United States.

BACKGROUND: Documenting trends in risk factors among individuals with cardiovascular disease (CVD) may inform policy and secondary prevention initiatives. OBJECTIVES: This study aimed to examine 20-year trends in risk profiles among U.S. adults with CVD and any racial/ethnic disparities. METHODS: In this serial cross-sectional analysis of 6,335 adults with self-reported CVD participating in the National Health and Nutrition Examination Survey from 1999 through 2018, we calculated age- and sex-adjusted proportions with ideal risk factor attainment. RESULTS: The proportions with ideal hemoglobin A1c (<7% if diabetes or <5.7% if not) and body mass index (<25 kg/m2) worsened from 58.7% (95% CI: 55.2%-62.1%) to 52.4% (95% CI: 48.2%-56.6%) and 23.9% (95% CI: 21.5%-26.4%) to 18.2% (95% CI: 15.6%-21.2%) from 1999-2002 to 2015-2018, respectively. After initial improvement, the proportion with blood pressure <130/80 mm Hg declined from 52.1% (95% CI: 48.9%-55.4%) in 2007-2010 to 48.6% (95% CI: 44.2%-52.7%) in 2015-2018. The proportion with non-high-density lipoprotein cholesterol levels <100 mg/dL increased from 7.3% (95% CI: 5.6%-9.5%) in 1999-2002 to 30.3% (95% CI: 25.7%-35.5%) in 2015-2018. The proportions with ideal smoking, physical activity, and diet profiles were unchanged over time, and in 2015-2018 were 77.8% (95% CI: 73.6%-81.4%), 22.4% (95% CI: 19.3%-25.9%), and 1.3% (95% CI: 0.7%-2.6%). Worsening trends were observed in Hispanic adults for cholesterol, and in Black adults for smoking (both P < 0.05 for nonlinear and linear trends). Persistently lower ideal risk factor attainment was observed for blood pressure in Black adults and for hemoglobin A1c levels in Asian adults compared with White adults (all P < 0.05 for differences). CONCLUSIONS: Trends in cardiovascular risk factor profiles in U.S. adults with CVD were suboptimal from 1999 through 2018, with persistent racial/ethnic disparities.

Effect of cold compression therapy on postoperative pain, swelling, range of motion, and lameness after tibial plateau leveling osteotomy in dogs.

OBJECTIVE: To evaluate the effect of cold compression therapy (CCT) on postoperative pain, lameness, range of motion of the stifle joint, and swelling following tibial plateau leveling osteotomy (TPLO) in dogs. DESIGN: Randomized, blinded, placebo-controlled clinical trial. ANIMALS: 34 client-owned dogs with unilateral deficiency of a cranial cruciate ligament undergoing TPLO. PROCEDURES: Dogs were assigned to 2 groups. Group 1 (n = 17 dogs) received CCT in the 24-hour period following TPLO. Group 2 (n = 17 dogs) received no CCT. Degree of lameness, range of motion, and circumference of the stifle joint were measured before surgery and 1,14, and 28 days after surgery. A modified composite Glasgow pain scale, visual analogue scale, and pain threshold score were used to evaluate signs of pain before surgery and 1,14, and 28 days after surgery. Logistic regression and linear regression analysis were used to compare the measured variables. RESULTS: No complications were observed, and all dogs tolerated CCT. Use of CCT resulted in lower values for the visual analogue scale and Glasgow pain scale and lower pain threshold scores; lower lameness scores; less swelling; and an increased range of motion 24 hours after surgery. At 14 days after surgery, there were no significant differences between groups. At 28 days after surgery, too few data sets were available for comparison. CONCLUSIONS AND CLINICAL RELEVANCE: CCT decreased signs of pain, swelling, and lameness and increased stifle joint range of motion in dogs during the first 24 hours after TPLO.

The association of dietary phosphorus with blood pressure: results from a secondary analysis of the PREMIER trial.

Inconsistent findings exist for the association between dietary phosphorus intake and blood pressure (BP). We examined the longitudinal association between urinary excretion and dietary intake of phosphorus (total, plant, animal, and added) with BP. This is a secondary analysis of PREMIER, a randomized behavioral intervention study in adults (25-79 years) with BP, measured at 6 months, as the primary outcome. We classified total phosphorus intake from dietary recalls into plant, animal, and added phosphorus. We modeled 6-month change of phosphorus intake (from 24 h dietary recalls, N = 622) and excretion (from 24 h urine collection, N = 564) on BP, using linear regression crude and adjusted for intervention, age, race, sex, income, education, study site, and change in energy intake (kcal/day), sodium intake (mg/day), fitness (heart rate, bpm), and DASH diet index. Baseline phosphorus intake was 1154 mg/day (95% CI 1126, 1182) with 38%, 53%, and 10% from plant, animal, and added phosphorus, respectively. Total phosphorus intake was not associated with significant changes in BP. Increased urinary phosphorus excretion was associated with a significant increase in DBP [0.14 mmHg/100 mg (0.01, 0.28), adjusted]. In several analyses, phosphorus type (plant, animal, or added) significantly modified the association between phosphorus intake and BP. For example, added phosphorus (but not plant or animal) was associated with increases in SBP and DBP, 1.24 mmHg/100 mg (0.36, 2.12) and 0.83 mmHg/100 mg (0.22, 1.44), respectively, crude. These findings suggest that the type of phosphorus may modify the association between phosphorus intake and BP. Trial registration NCT00000616 (clinicaltrials.gov).

Dietary intake of adults with and without diabetes: results from NHANES 2013-2016.

INTRODUCTION: Diet is a critical aspect of the management of adults with diabetes. This paper aims to compare dietary intakes of key macronutrients and micronutrients of US adults with and without diabetes and across the spectrum of diabetes. RESEARCH DESIGN AND METHODS: We compared absolute and energy-adjusted dietary intake of major macronutrients and micronutrients among those with and without diabetes and across the spectrum of glycemic control using a 24-hour dietary recall from a cross-sectional, nationally representative sample of 9939 US adults, 20+ years old (National Health and Nutrition Examination Survey 2013-2016). Diabetes was defined as an glycohemoglobin A1c (HbA1c)≥6.5%, fasting glucose ≥126 mg/dL, serum glucose at 2 hours following a 75 g glucose load (oral glucose tolerance test) ≥200 mg/dL, any diagnosis of diabetes or use of diabetes medication (self-reported). RESULTS: Percent of calories from macronutrients was similar for those with and without diabetes (p>0.05, energy adjusted and adjusted for age, race, and sex). In both groups, sugar accounted for about 20% of calories. Those with diabetes consumed about 7% more calcium (p=0.033), about 5% more sodium (p=0.026), and had lower diet quality (Healthy Eating Index-2015, p=0.021) than those without diabetes. Among those with diabetes, those with an HbA1c>9.0% consumed about 4% less magnesium (p-analysis of variance=0.007) than those with an HbA1c<6.5%. Results were similar within strata of age, race, and sex. Macronutrient intake did not vary consistently by HbA1c level. CONCLUSIONS: In this nationally representative sample, there were no substantial or consistent differences in the dietary intake of macronutrients or micronutrients between US adults with and without diabetes. Improving the diets of those with diabetes will likely require enhanced targeted efforts to improve the dietary intake of persons with diabetes, as well as broad efforts to improve the dietary intake of the general population.

Effects of extracorporeal shock wave therapy on wounds of the distal portion of the limbs in horses.

OBJECTIVE: To evaluate the effects of focused, extracorporeal shock wave therapy (ESWT) on the healing of wounds of the distal portion of the limbs in horses. DESIGN: Randomized controlled trial. ANIMALS: 6 healthy adult horses. PROCEDURES: In each horse, a 4-cm-diameter full-thickness wound that included underlying periosteum was created on the dorsomedial aspect of each metacarpus and two 3-cm-diameter full-thickness wounds that included underlying periosteum were created on the dorsomedial aspect of each metatarsus. One randomly selected metacarpal wound and a randomly selected pair of metatarsal wounds were treated once weekly with ESWT at an energy flux density of 0.11 mJ/mm(2). For metacarpal wounds, swab specimens were collected for bacterial culture on days 1, 2, and 3 and area of epithelialization and extent of wound contraction were measured at 3- to 4-day intervals. Metatarsal wounds were biopsied after 2 and 4 weeks, and immunohistochemical staining for vascular endothelial growth factor, transforming growth factor-beta1, and insulin-like growth factor-1 was performed. RESULTS: Results of bacterial culture, area of epithelialization, and percentage of wound contraction did not differ between treated and untreated wounds; however, healing time for treated wounds (mean, 76 days) was significantly shorter than healing time for untreated wounds (90 days). Staining intensity of growth factors did not differ significantly between treated and untreated wounds. CONCLUSIONS AND CLINICAL RELEVANCE: Findings suggested that ESWT may stimulate healing of wounds of the distal portion of the limbs in horses, although the mechanism by which healing was stimulated could not be identified.

Effects of Nasal Occlusion and Oral Contact on Perception of Metallic Taste from Metal Salts.

Iron and copper salts have complex olfactory and gustatory properties including a metallic flavor component that is decreased by nasal occlusion. To examine the sensory properties of ferrous sulfate and copper sulfate, a trained descriptive panel evaluated these compounds at equal molarity and perceived equal intensity with and without nasal occlusion. Ferrous sulfate exhibited a metallic taste and metallic aftertaste and copper sulfate exhibited a more pronounced metallic aftertaste. Metallic sensations were decreased by nasal occlusion, which in the absence of any orthonasal metallic smell, implies that the sensations were retronasally perceived volatiles in the nose open condition. Ferrous sulfate showed a larger effect of nasal occlusion. A second experiment isolated ferrous sulfate solutions from oral contact via a plastic barrier. In comparison to a condition in which oral contact was allowed, intensity ratings were decreased. This result is consistent with the hypothesis that rinses with solutions of metal salts, particularly ferrous sulfate, generate volatile lipid oxidation products in the mouth that are perceived retronasally as metallic flavors.

Dietary phosphorus intake and blood pressure in adults: a systematic review of randomized trials and prospective observational studies.

BACKGROUND: Elevated blood pressure (BP) is a major cause of preventable disease in the United States and around the world. It has been postulated that phosphorus intake may affect BP, with some studies suggesting a direct and others an inverse association. OBJECTIVES: We systematically reviewed the literature on the association of dietary phosphorus with BP in adults and performed a qualitative synthesis. METHODS: We included randomized and nonrandomized behavioral intervention and feeding studies (intervention studies) and prospective observational studies that measured dietary phosphorus intake or urinary phosphorus excretion and BP. We excluded studies of supplements, children, or individuals with major medical conditions. We searched PubMed, Embase, Cochrane Trials, and clinicaltrials.gov on 1 June, 2017 and 22 August, 2018. We assessed studies' risk of bias in their assessment of phosphorus exposure and BP. RESULTS: We reviewed 4759 publications and included 14 intervention studies (2497 participants), 3 prospective observational cohorts (17,795 participants), and 2 ongoing trials. No included intervention studies were designed specifically to achieve a phosphorus contrast. Two studies found a significant positive association of dietary phosphorus with systolic BP, 4 a significant inverse association, and 8 no significant association. Four studies found a significant inverse association with diastolic BP and 10 no significant associations. Two cohorts found lower risk of incident hypertension comparing the highest with the lowest quintiles of phosphorus intake and 1 found no significant difference: HR: 0.86 (95% CI: 0.75, 0.98); HR: 0.83 (95% CI: 0.68, 1.02); and HR: 0.75 (95% CI: 0.45, 1.27), respectively. CONCLUSIONS: We found no consistent association between total dietary phosphorus intake and BP in adults in the published literature nor any randomized trials designed to examine this association. This trial was registered at www.crd.york.ac.uk/prospero/ as CRD42017062489.

Pharmacokinetics of firocoxib after administration of multiple consecutive daily doses to horses.

OBJECTIVE: To determine pharmacokinetic parameters and variables, firocoxib concentrations in urine and plasma, urine-to-plasma ratios, and the urine depletion profile of firocoxib and to evaluate whether the pharmacokinetic behavior of firocoxib was governed by linear processes after multiple doses of firocoxib were administered IV and orally. ANIMALS: 6 healthy female horses (5 Paint horses and 1 Quarter Horse) in experiment 1 and 12 healthy male and female horses in experiment 2. PROCEDURES: In experiment 1, 6 horses were orally administered firocoxib paste once daily for 12 consecutive days, and plasma and urine samples were obtained and analyzed. In a second experiment, 12 horses received IV injections of firocoxib solution once daily for 9 consecutive days, and plasma was obtained and analyzed. RESULTS: Mean +/- SD clearance and steady-state volume of distribution of firocoxib were 40.5 +/- 14.7 mL/h/kg and 2.3 +/- 0.7 L/kg, respectively. Mean half-life was 44.2 +/- 21.6 hours and 36.5 +/- 9.5 hours for IV and oral administration, respectively. The urine concentration- time curve decreased in parallel with the plasma concentration-verus-time curve. Renal clearance (0.26 +/- 0.09 mL/kg/h) was low, compared with total body clearance, which indicated that the main route of elimination was hepatic clearance. CONCLUSIONS AND CLINICAL RELEVANCE: The pharmacokinetics of firocoxib during prolonged use were determined. Use of plasma or urine to ascertain drug concentrations in horses is scientifically valid because the plasma-to-urine ratio was consistent over time and among horses.

Comparison of efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis.

OBJECTIVE: To compare efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis. DESIGN: Randomized controlled clinical trial. ANIMALS: 253 client-owned horses with naturally occurring osteoarthritis. PROCEDURES: Horses were treated with firocoxib (0.1 mg/kg [0.045 mg/lb], PO, q 24 h) or phenylbutazone (4.4 mg/kg [2 mg/lb], PO, q 24 h) for 14 days. Physical examinations and lameness evaluations were performed prior to treatment and after 7 and 14 days. Clinical improvement was defined as a reduction of at least 1 lameness grade or a combined reduction of at least 3 points in scores for pain during manipulation or palpation, joint swelling, joint circumference, and range of motion. RESULTS: Proportion of horses clinically improved on day 14 for the firocoxib group (104/123 [84.6%]) was not significantly different from the proportion for the phenylbutazone group (103/119 [86.6%]). Proportion of horses that were improved on day 14 was significantly greater for horses treated with firocoxib than for horses treated with phenylbutazone with regard to score for pain on manipulation or palpation (P = 0.028), joint circumference score (P = 0.026), and range of motion score (P = 0.012), but not for overall lameness score or joint swelling score. No direct treatment-related adverse effects were detected during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that overall clinical efficacy of a paste formulation of firocoxib in horses with naturally occurring osteoarthritis was comparable to efficacy of a paste formulation of phenylbutazone.

Dietary Cholesterol Intake and Sources among U.S Adults: Results from National Health and Nutrition Examination Surveys (NHANES), 2001⁻2014.

The 2015 Dietary Guidelines for Americans recommends that individuals should minimize their dietary cholesterol intake. However, current dietary cholesterol intake and its food sources have not been well-characterized. We examined dietary cholesterol intake by age, sex, race, and food sources using 24-h dietary recall data from a nationally representative sample of 5047 adults aged 20 years or older who participated in NHANES (2013⁻2014 survey cycle). We also reported trends in cholesterol intake across the past seven NHANES surveys. Mean dietary cholesterol intake was 293 mg/day (348 mg/day for men and 242 mg/day for women) in the 2013⁻2014 survey cycle; 39% of adults had dietary cholesterol intake above 300 mg/day (46% for men and 28% for women). Meat, eggs, grain products, and milk were the highest four food sources of cholesterol, contributing to 96% of the total consumption. Both average cholesterol intake and food source varied by age, sex, and race (each p < 0.05). Mean cholesterol intake of the overall population had been relatively constant at ~290 mg/day from 2001⁻2002 to 2013⁻2014 (p-trend = 0.98). These results should inform public health efforts in implementing dietary guidelines and tailoring dietary recommendations.

A comparison of two electric taste stimulation devices.

Electrical stimulation of the tongue, commonly used in clinical evaluations of taste dysfunction, can produce a variety of sensations including reports of metallic taste. Two studies compared responses to a fabricated electrical stimulator (a 1.6 V battery, anode side exposed) and a clinical electrogustometer (Rion TR-06). Batteries placed on the anterior dorsal tongue surface produced sensations similar in intensity and quality to those produced by the clinical electrogustometer, with equal intensity on the tongue tip for the 1.6 V battery in the range of 33-56 microA from the electrogustometer. A second study examined responses on three areas of the tongue on each side. Responses declined for areas lower in fungiform papillae for both devices, but at different rates. Higher current levels were required to match the battery in lower density areas, indicating spatial summation for the larger battery surface area. A consistent pattern of lateral differences was seen in only one subject. Quality descriptions were similar in frequency whether or not a word list was provided, with metallic, sour, pain and bitter being the most frequently mentioned words for both electric stimuli. Similarities in response to the battery device and electrogustometer were evident in intensity, qualities evoked, lack of a laterality effect and decreasing response in areas with lower fungiform papillae density. The battery device may provide an inexpensive portable alternative to an electrogustometer for use in clinical testing of taste.