Exploring the relationship between gratitude and depression among older adults with chronic low back pain: a sequential mediation analysis.

Introduction: Gratitude has been identified as a key factor in a number of positive health-related outcomes; however, the mechanisms whereby gratitude is associated with well-being among older adults with chronic pain are poorly understood. Using the Positive Psychological Well-Being Model as a theoretical framework, the objective of the present study was to examine the serial mediating effects of social support, stress, sleep, and tumor necrosis factor-alpha (TNF-α) on the relationship between gratitude and depressive symptoms. Methods: A total sample of 60 community-dwelling older adults with chronic low back pain (cLBP) provided blood samples for high-sensitivity TNF-α and completed the Gratitude Questionnaire, Perceived Stress Scale, and the PROMIS Emotional Support, Sleep Disturbance, and Depression forms. Descriptive statistics, correlation analyses, and serial mediation analyses were performed. Results: Gratitude was negatively associated with perceived stress, sleep disturbance, and depression, and was positively associated with social support. No significant association was observed between gratitude and TNF-α. After controlling for age and marital status, analyses revealed that perceived stress and sleep disturbance sequentially mediated the association between gratitude and depressive symptoms. Conclusion: Perceived stress and sleep disturbance may be potential mechanistic pathways by which gratitude impacts negative well-being. Targeting gratitude as a protective resource may be a potential therapeutic tool to improve psychological and behavioral outcomes in older adults with cLBP.

Stability of finite and infinite von Kármán vortex-cluster streets.

A wake of vortices with sufficiently spaced cores may be represented via the point-vortex model from classical hydrodynamics. We use potential theory representations of vortices to examine the emergence and stability of complex vortex wakes, more particularly the von Kármán vortex street composed of regular polygonal-like clusters of same-signed vortices. We investigate the existence and stability of these streets represented through spatially periodic vortices. We introduce a physically inspired point-vortex model that captures the stability of infinite vortex streets with a finite number of procedurally generated vortices, allowing for numerical analysis of the behavior of vortex streets as they dynamically form.

Analgesic and anti-hyperalgesic effects of muscle injections with lidocaine or saline in patients with fibromyalgia syndrome.

BACKGROUND: Patients with musculoskeletal pain syndrome including fibromyalgia (FM) complain of chronic pain from deep tissues including muscles. Previous research suggests the relevance of impulse input from deep tissues for clinical FM pain. We hypothesized that blocking abnormal impulse input with intramuscular lidocaine would decrease primary and secondary hyperalgesia and FM patients' clinical pain. METHODS: We enrolled 62 female patients with FM into a double-blind controlled study of three groups who received 100 or 200 mg of lidocaine or saline injections into both trapezius and gluteal muscles. Study variables included pressure and heat hyperalgesia as well as clinical pain. In addition, placebo factors like patients' anxiety and expectation for pain relief were used as predictors of analgesia. RESULTS: Primary mechanical hyperalgesia at the shoulders and buttocks decreased significantly more after lidocaine than saline injections (p = 0.004). Similar results were obtained for secondary heat hyperalgesia at the arms (p = 0.04). After muscle injections, clinical FM pain significantly declined by 38% but was not statistically different between lidocaine and saline conditions. Placebo-related analgesic factors (e.g., patients' expectations of pain relief) accounted for 19.9% of the variance of clinical pain after the injections. Injection-related anxiety did not significantly contribute to patient analgesia. CONCLUSION: These results suggest that muscle injections can reliably reduce clinical FM pain, and that peripheral impulse input is required for the maintenance of mechanical and heat hyperalgesia of patients with FM. Whereas the effects of muscle injections on hyperalgesia were greater for lidocaine than saline, the effects on clinical pain were similar for both injectates.

Experimental pain sensitivity differs as a function of clinical pain severity in symptomatic knee osteoarthritis.

OBJECTIVE: Pain in knee osteoarthritis (OA) has historically been attributed to peripheral pathophysiology; however, the poor correspondence between objective measures of disease severity and clinical symptoms suggests that non-local factors, such as altered central processing of painful stimuli, also contribute to clinical pain in knee OA. Consistent with this notion, recent evidence demonstrates that patients with knee OA exhibit increased sensitivity to painful stimuli at body sites unaffected by clinical pain. DESIGN: In order to further investigate the contribution of altered pain processing to knee OA pain, the current study tested the hypothesis that symptomatic knee OA is associated with enhanced sensitivity to experimental pain stimuli at the knee and at remote body sites unaffected by clinical pain. We further anticipated that pain sensitivity would differ as a function of the OA symptom severity. Older adults with and without symptomatic knee OA completed a series of experimental pain assessments. A median split of the Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) was used to stratify participants into low vs high OA symptom severity. RESULTS: Compared to controls and the low symptom group, individuals in the high symptom group were more sensitive to suprathreshold heat stimuli, blunt pressure, punctuate mechanical, and cold stimuli. Individuals in the low symptomatic OA group subgroup exhibited experimental pain responses similar to the pain-free group on most measures. No group differences in endogenous pain inhibition emerged. CONCLUSIONS: These findings suggest that altered central processing of pain is particularly characteristic of individuals with moderate to severe symptomatic knee OA.

Sex differences in pain: a brief review of clinical and experimental findings.

Recent years have witnessed substantially increased research regarding sex differences in pain. The expansive body of literature in this area clearly suggests that men and women differ in their responses to pain, with increased pain sensitivity and risk for clinical pain commonly being observed among women. Also, differences in responsivity to pharmacological and non-pharmacological pain interventions have been observed; however, these effects are not always consistent and appear dependent on treatment type and characteristics of both the pain and the provider. Although the specific aetiological basis underlying these sex differences is unknown, it seems inevitable that multiple biological and psychosocial processes are contributing factors. For instance, emerging evidence suggests that genotype and endogenous opioid functioning play a causal role in these disparities, and considerable literature implicates sex hormones as factors influencing pain sensitivity. However, the specific modulatory effect of sex hormones on pain among men and women requires further exploration. Psychosocial processes such as pain coping and early-life exposure to stress may also explain sex differences in pain, in addition to stereotypical gender roles that may contribute to differences in pain expression. Therefore, this review will provide a brief overview of the extant literature examining sex-related differences in clinical and experimental pain, and highlights several biopsychosocial mechanisms implicated in these male-female differences. The future directions of this field of research are discussed with an emphasis aimed towards further elucidation of mechanisms which may inform future efforts to develop sex-specific treatments.

Assessment of blood pressure in patients with Type 2 diabetes: comparison between home blood pressure monitoring, clinic blood pressure measurement and 24-h ambulatory blood pressure monitoring.

AIMS: To compare a home blood pressure (BP) monitoring device and clinic BP measurement with 24-h ambulatory BP monitoring in patients with Type 2 diabetes mellitus (DM). METHODS: Fifty-five patients with type 2 DM had BP measured at three consecutive visits to the DM clinic by nurses using a stethoscope and mercury sphygmomanometer (CBP). Twenty-four-hour ambulatory BP was measured using a Spacelabs 90207 automatic cuff-oscillometric device (ABPM). Subjects were then instructed in how to use a Boots HEM 732B semiautomatic cuff-oscillometric home BP monitoring device and measured BP at home on three specified occasions on each of 4 consecutive days at varying times (HBPM). RESULTS: Correlations between HBPM and ABPM were r = 0.88, P < 0.001 for systolic BP and r = 0.76, P < 0.001 for diastolic BP, with correlations between CBP and ABPM being systolic r = 0.59, P < 0.001, diastolic r = 0.47, P < 0.001. HBPM agreed with ABPM more closely compared with CBP (CBP +10.9/+3.8 (95% confidence intervals (CI) 6.9, 14.8/1.6, 6.1) vs. HBPM +8.2/+3.7 (95% CI 6.0, 10.3/2.0, 5.4)). The sensitivity, specificity and positive predictive value of HBPM in detecting hypertension were 100%, 79% and 90%, respectively, compared with CBP (85%, 46% and 58%, respectively). CONCLUSIONS: In patients with Type 2 DM, home BP monitoring is superior to clinic BP measurement, when compared with 24-h ambulatory BP, and allows better detection of hypertension. It would be a rational addition to the annual review process. Diabet. Med. 18, 431-437 (2001)

Blood levodopa levels and unified Parkinson's disease rating scale function: with and without exercise.

We studied 10 regular exercising men with Parkinson's disease on levodopa (LD) under two conditions--no exercise and vigorous exercise started 1 hour after LD ingestion. We compared LD levels and motor scores on the Unified Parkinson's Disease Rating Scale (UPDRS). There was a high degree of agreement between plasma LD level and the patients' UPDRS scores 30 minutes later (mean Eta2 = 0.84) in both conditions, with no difference between the two. We conclude that LD levels accurately reflect UPDRS motor function in these patients, and that vigorous exercise started 1 hour after LD ingestion does not influence LD or motor scores.

Fluorometric quantification of low-dose fluorescein delivery to predict amputation site healing.

This retrospective study evaluated quantification of skin fluorescein delivery by fiberoptic fluorometry as a means of predicting the healing potential of an amputation site. Fluorometry uses a dual-channel fiberoptic light guide--one channel transmits blue light to excite the fluorescein in the skin under study, and the other transmits emitted fluorescence from the skin to a photomultiplier tube where it is measured. Ten minutes after intravenous administration of sodium fluorescein (4 to 8 mg/kg), fluorometric readings were obtained at more than 100 reading sites. In the 86 cases without preoperative cellulitis at the site of amputation, preoperative fluorometry clearly distinguished between healing and nonhealing sites. Healing sites averaged 79% of the fluorescence of a healthy reference area (dye fluorescence index [DFI] = 79), while failing sites averaged only 27% (p less than 0.01 by ANOVA). In all but one case where the DFI was greater than 42, the amputation healed. In all cases where the DFI was less than 38, the amputation failed. In general, uncertainty was limited to sites with values between these limits. The technique maintained its high accuracy in patients with diabetes and for distal amputations. However, it was not accurate at sites of active cellulitis (12 cases). There were no significant adverse effects from the slow injection of the low dose of fluorescein used for this technique. We conclude that fluorometry is an effective means of predicting healing in patients undergoing amputation.

Lasalocid toxicity in cattle: acute clinicopathological changes.

Thirty-six steers (148 to 500 kg) divided into six equal groups were used in a toxic syndrome study of lasalocid and monensin given as a single oral dose. One group was given a placebo, a second group received monensin (25 mg/kg body weight) and the other four groups received lasalocid at 1, 10, 50 or 100 mg/kg body weight (bw). No toxic signs developed in cattle given placebo or lasalocid at 1 or 10 mg/kg bw dose. The earliest toxic signs were muscle tremors, tachycardia and rumen atony. After 24 h, the cattle were dehydrated, anorectic and had diarrhea. Deaths occurred between d 1 and 22.5 in the groups receiving lasalocid at 50 and 100 mg/kg bw and monensin. Altered values in blood leucocytes, erythrocytes, hemoglobin, hematocrit, total protein, albumin, creatinine, urea nitrogen, total bilirubin, creatine kinase, lactic dehydrogenase, calcium, chloride and inorganic phosphate occurred 1 d after dosing: urine pH and specific gravity also changed 1 d after dosing. Maximum changes occurred at d 3. Most of the changes were indicative of dehydration rather than specific organ damage.

Aztreonam penetration into synovial fluid and bone.

Eighteen patients with uncomplicated degenerative joint disease requiring joint replacement (hip or knee) were given a single 2-g intravenous dose of aztreonam over a 5-min period preoperatively. The mean concentration in synovial fluid of 83.0 +/- 9.2 micrograms/ml averaged 0.99 times the concomitant levels in serum. The mean concentration in cancellous bone of 16.0 +/- 4.3 micrograms/g averaged 0.20 times the concomitant levels in serum.

Effects of cirrhosis on kinetics of aztreonam.

Aztreonam was administered as a single, 3-min, 1-g intravenous infusion to 18 subjects, including 6 with biopsy-proven, primary biliary cirrhosis, 6 with biopsy-proven, stable alcoholic cirrhosis, and 6 age- and sex-matched control subjects with normal hepatic functions. Aztreonam was well tolerated by all subjects. Multiple blood samples and timed, cumulative urine samples were taken for assay of aztreonam content and determination of pharmacokinetic profiles. Protein-free filtrates of serum were also assayed for drug levels. Analyses by microbiological and high-pressure liquid chromatographic procedures gave equivalent results. The kinetic data were described by an open, linear, two-compartment model. There were significant differences in elimination half-life (3.2 versus 1.9 h), serum clearance (0.8 versus 1.1 ml/min per kg), and nonrenal clearance (0.2 versus 0.4 ml/min per kg) between the alcoholic cirrhosis group and the normal control group and in elimination half-life (2.2 versus 1.9 h) between the primary biliary cirrhosis group and the normal control group. There was also a difference in nonrenal clearance between the alcoholic cirrhosis and primary biliary cirrhosis groups (0.2 versus 0.5 ml/min per kg). Although the handling of aztreonam differed in the three groups, the magnitude of the difference would warrant a change in aztreonam dosing only for the alcoholic cirrhosis group. In this group, dose adjustment might be required if long-term therapy with high doses of aztreonam is indicated.

Thiamin and niacin in the rumen.

Thiamin analogs, produced in the rumen by thiaminase I, in the presence of a cosubstrate appear to be responsible for the central nervous system disorder, polioencephalomalacia (PEM). For PEM to occur, an analog must be produced that inhibits an essential thiamin-requiring reaction, and results from a cosubstrate present in the rumen. In high concentrate diets, thiaminase I is produced by rumen microbes. However, PEM can also be caused by thiaminase I of plant origin. Based on physical characteristics and cosubstrate specificity, the thiaminase I enzymes produced by Bacillus thiaminolyticus and Clostridium sporogenes appear to be different from the enzyme produced by the rumen. Because niacin and certain antihelmentics are thiaminase I cosubstrates, they should be used cautiously. Supplementary niacin increased microbial protein synthesis in vitro and in vivo, and was more effective with urea than soybean meal. Supplementary niacin (5 to 6 g X cow-1 X d-1) increased milk production in postpartum cows but not in those in mid-lactation, and in cows fed soybean meal but not in those fed urea. We believe the heating of soybean meal during commercial processing decreased the availability of niacin for rumen protozoa. Supplementary niacin for postpartum cows increased blood glucose, decreased blood ketones and reduced the incidence of ketosis. Niacin flow to the small intestine and its absorption from the small intestine increased with niacin supplementation. Supplemental niacin prevented the postpartum decrease in red blood cell niacin observed in control cows.

Effect of dietary niacin supplementation on phlorhizin and 1,3-butanediol-induced ketonemia and hypoglycemia in steers.

1,3-Butanediol and phlorhizin were used to induce ketonemia and hypoglycemia in steers. Oral administration of butanediol increased blood beta-hydroxybutyrate (BHB) and plasma nonesterified fatty acids (NEFA) and decreased serum glucose. Subcutaneous injections of phlorhizin, given in addition to butanediol orally, further increased NEFA and BHB concentrations and decreased glucose. Dietary niacin supplementation of steers given phlorhizin and butanediol caused serum glucose concentration to increase and blood BHB and plasma NEFA concentrations to decrease.

Effect of dietary niacin supplementation on serum constituents of periparturient dairy cattle.

A total of 60 multiparous periparturient Holstein cows were used to determine the differences in serum constituents between cows given supplemental niacin in the diet and cows not given supplemental niacin. Serum inorganic phosphorus concentration was consistently higher (P less than 0.10) and serum potassium, total calcium, and sodium concentrations and alkaline phosphatase activities were consistently lower in cows given supplemental niacin than in cows not given supplemental niacin. Serum chloride, creatinine, and albumin values also tended to be lower in niacin-supplemented cows. Serum total protein tended to be slightly higher in niacin-supplemented cows. There was no consistent difference in urea nitrogen between groups of cows.

Effect of niacin supplementation on milk production and ketosis of dairy cattle.

In two experiments with Holstein cows effects of dietary supplementation of niacin to periparturient cattle on subsequent milk production and ketosis were examined. In Experiment 1, 20 cows were assigned to two groups. The treatment group received niacin at 6 g per head per day for 2 wk prepartum and 12 g per head per day for 4 wk postpartum. The control group received no niacin. In Experiment 2, 40 cows were assigned to four groups of 10 cows. One group served as the control and the other three received 3, 6, or 12 g niacin per head per day for 10 wk postpartum. In both experiments niacin-supplemented groups produced slightly more milk than controls. There were no consistent changes of milk composition with treatment. Glucose concentration in blood serum was higher for cows receiving niacin. Concentrations of beta-hydroxybutyrate and nonesterified fatty acids in blood and plasma were generally lower for niacin-supplemented groups. Niacin supplementation had no effect on feed intake or body weight changes. In Experiment 1 there was a significant reduction of niacin concentration in red blood cells of postpartum cows not receiving supplemental niacin. Insulin concentration in blood serum in Experiment 2 was unaffected by niacin supplementation.

Relation of rumen ATP concentration to bacterial and protozoal numbers.

Cultures of Streptococcus bovis and mixed populations of rumen bacteria were used to investigate the concentration of ATP and rumen bacterial numbers at various stages of growth. ATP, extracted with Tris buffer, was analyzed using the firefly luciferin-luciferase bioluminescent reaction. ATP concentrations of S. bovis and mixed cultures of rumen bacteria significantly correlated with live cell counts during the log phase of growth but not during the stationary phase. The average cellular ATP concentration of rumen bacteria was calculated to be 0.3 fg of ATP per cell. Studies done with in vivo artificial rumen apparatus revealed that the protozoal contribution to rumen fluid ATP pool size was much more substantial than was the bacterial contribution. The rumen fluid ATP concentration was greater in cattle with protozoa than in those that were defaunated. Differences in ATP concentration due to size differences of ciliate protozoa were observed. Due to the unbalanced distribution of ATP in rumen microbes, ATP appears to be an unsuitable indicator of rumen microbial biomass.

Effect of energy concentration and source of nitrogen on numbers and types of rumen protozoa.

Two rumen-fistulated Holstein heifers were fed three protein-free semipurified diets: 70% roughage, 30% concentrate; 50% roughage, 50% concentrate; and 30% roughage, 70% concentrate. Wheat straw was the roughage, and the concentrate was a pelleted mixture of corn starch, dextrose, fat, urea, vitamins, and minerals. Each animal received the three dietary treatments in a randomized complete block design. On days 1, 3, and 5 following a 21-day adaptation, rumen fluid samples were taken before feeding and at 1, 2, 3, 4, and 5 h after feeding. Total protozoa concentrations for low, medium, and high concentrate diets were 1.5, 2.5, 4.1 X 10(5)/ml. Dasytricha concentrations were not affected by diet, but Entodinium, Diplodinium, Isotricha, Epidinium, and Ophryoscolex increased with increases of the concentrate proportion of the diets. Entodinium, the predominant protozoa with all diets, increased as concentrate proportion of the diet increased. In a second experiment the two heifers from Experiment 1 were fed semipurified diets that contained either urea or soybean meal as the nitrogen source. There were larger populations of Dasytricha and Isotricha when the diet contained soybean meal, and larger populations of Charon, Entodinium, and total protozoa when the diet contained urea. In both experiments, holotrichs were highest 1 to 2 h after feeding, and entodiniomorphs were highest before feeding and 4 to 6 h after feeding. An active protozoan population can exist in the rumen of cattle fed diets virtually devoid of natural protein, and protozoa are influenced by energy and nitrogen source.

Effects of lasalocid or monensin on legume or grain (feedlot) bloat.

Doses of .66 to .99 mg monensin/kg body weight reduced legume bloat in cattle about 66% when compared with pretreatment bloat scores. Similar doses of lasalocid reduced legume bloat about 26%. A dose of 44 mg poloxalene/kg body weight (recommended dose for field use) reduced legume bloat 100%. Monensin or lasalocid combined with 25 or 50% of the recommended dose of poloxalene reduced bloat under that of the antibiotics alone, but did not achieve 100% reduction. The antibiotic thiopeptin provided no preventive effect on legume bloat. Lasalocid, monensin or an experimental polyether antibiotic (X-14,547 A) at a dose of 1.32 mg/kg body weight when tested on cattle bloated on high grain diets reduced bloat by 92, 64 and 25%, respectively. Lasalocid at .66 mg/kg effectively prevented bloat from developing when given to animals before the feeding of high grain diets; however, a 1.32-mg dose was required to control bloat in cattle that were already bloating before they were given lasalocid. A dose of 1.32 mg salinomycin was ineffective in controlling grain bloat.

Effects and handling of almitrine bismesylate in healthy subjects.

Almitrine bismesylate was administered to young, healthy, non-smoking male subjects as single oral doses, multiple oral doses and multiple oral doses with food. A variety of physiological parameters and blood parameters were tested at specified times in relationship to drug ingestion, and multiple blood samples for plasma almitrine bismesylate levels were obtained. Evaluation of the data revealed almitrine bismesylate to be safe at all doses tested, up to 400 mg per day, with symptoms of mild nausea and headache occurring most frequently when the drug was administered in the fasting state. A striking complaint of shortness of breath on exertion was reported by subjects, with increased frequency and severity related to total amount of drug ingested and level of physical activity. Increased oxygen uptake and tidal volume were found after multiple oral dosing. Plasma almitrine bismesylate levels were highly variable, and marked individual differences in peak levels and terminal phase rate constants and half lives were found. Multiple oral dosing, either fasting or with food, significantly prolonged the terminal phase half life when compared to single oral dosing.

Preliminary studies on lasalocid toxicosis in cattle.

Polyether antibiotics are gaining widespread use in the feedlot cattle industry. One such investigational antibiotic, Lasalocid, was studied at oral doses of 25, 50, 75, 100 and 125 mg/kg to determine effects of toxicosis in six cattle. Deaths occurred at 100 and 125 mg/kg body weight. The general syndrome developed as muscle tremors, increased heart rate and respiration rate followed by or concurrent with anorexia (within 24 hr) and watery, forced diarrhea (48 through 72 hr). There were signs of cardiac effects one week to ten days after administration of the drug.