BACKGROUND:Resistance exercise (RE) is also known as strength training, and it is performed to increase the strength and mass of muscles, bone strength, and metabolism. RE has been increasingly prescribed for pain relief. However, the endogenous mechanisms underlying this antinociceptive effect are still largely unexplored. Thus, we investigated the involvement of the endocannabinoid system in RE-induced antinociception.

METHODS:Male Wistar rats were submitted to acute RE in a weight-lifting model. The nociceptive threshold was measured by a mechanical nociceptive test (paw pressure) before and after exercise. To investigate the involvement of cannabinoid receptors and endocannabinoids in RE-induced antinociception, cannabinoid receptor inverse agonists, endocannabinoid metabolizing enzyme inhibitors, and an anandamide reuptake inhibitor were injected before RE. After RE, CB1 cannabinoid receptors were quantified in rat brain tissue by Western blot and immunofluorescence. In addition, endocannabinoid plasma levels were measured by isotope dilution-liquid chromatography mass spectrometry.

RESULTS:RE-induced antinociception was prevented by preinjection with CB1 and CB2 cannabinoid receptor inverse agonists. By contrast, preadministration of metabolizing enzyme inhibitors and the anandamide reuptake inhibitor prolonged and enhanced this effect. RE also produced an increase in the expression and activation of CB1 cannabinoid receptors in rat brain tissue and in the dorsolateral and ventrolateral periaqueductal regions and an increase in endocannabinoid plasma levels.

CONCLUSIONS:The present study suggests that a single session of RE activates the endocannabinoid system to induce antinociception.

The aim of this study was to evaluate the safety and potential of PCS as the anti-fatigue functional food. PCS was prepared by water extracting-alcohol precipitating method, and its chemical compositions of monosaccharide were analyzed. Then, acute toxicity and anti-fatigue activity of PCS were evaluated. PCS is composed of Rha, Arab, Xyl, Man, Glu, and Gal, its molar ratio is 0.17: 0.30: 0.26: 0.35: 1.00: 0.57. No mortality and general symptoms of toxicity were observed in the PCS treated mice (7.5, 15, and 20g/kg body weight), the body weight and food consumption were not significantly changed compared with the normal control group. The relative weights of main organ, and biochemical indicators also did not markedly change. PCS can significantly prolong the duration of the swimming time to exhaustion in mice, decrease BUN, LA levels, increase LDH activities, and the contents of HG in the PCS treated mice. The dose of 400mg/kg body weight is the optimal dose for anti-fatigue activity both in male and female mice. In conclusion, PCS is a promising traditional natural-based therapeutic remedy for relieving fatigue with high safety.

OBJECTIVES:This study aimed to characterize the association of lifestyle and nutritional risk profiles with age-related macular degeneration (AMD) in two subpopulations with differing AMD prevalence.

METHODS:This case-control study (n = 1992) included 768 patients with AMD and 1224 age- and sex-matched participants without AMD with a single visit at a primary health care unit. Enrolled participants completed a validated lifestyle and food frequency questionnaire. A score to measure adherence to the Mediterranean diet (mediSCORE; Range, 0-9) was constructed from individual food intakes, which were further analyzed by conversion to nutrient consumption.

RESULTS:Higher adherence to the Mediterranean diet (mediSCORE≥6) was significantly associated with no AMD (odds ratio [OR] = 0.73; P = 0.009). The subpopulation with lower AMD prevalence presented significantly higher adherence to the Mediterranean diet in relation to all individual food groups that comprised the mediSCORE (P < 0.014) with the exception of cereals. Food group analysis showed significant associations between the increased consumption of vegetables (OR = 0.63; P < 0.001) and fruit and nuts (OR = 0.78; P = 0.010) with no AMD. Nutrient analysis revealed that an increased ingestion of water, fibers, total fat, monounsaturated and polyunsaturated fatty acids, linoleic acid, vitamins A and C, carotene, alpha-tocopherol, folate, magnesium, iron, and zincwere significantly associated with no AMD (P < 0.0013). Finally, regular physical activity was associated with no AMD (P = 0.003).

CONCLUSIONS:High adherence to a Mediterranean diet and regular physical activity seem to be protective factors for AMD in a Portuguese population. The effect of the diet is likely driven by the increased consumption of vegetables, fruits, and nuts.

Excessive calorie intake and physical inactivity are considered key determinants of the rapid worldwide increase in obesity prevalence, however the relationship between diet and weight gain is complex. We investigated associations between adherence to a Mediterranean diet and long-term changes in weight and waist circumference in volunteers recruited to the Italian section of the prospective European Prospective Investigation into Cancer and Nutrition (EPIC). We investigated 32,119 cohort members who provided anthropometric measures at recruitment and updated information on recall a mean of 12 years later. Adherence to a Mediterranean diet was assessed using the Italian Mediterranean Index (score range 0-11). Associations between index score and weight and waist changes were assessed by multivariate linear regression models. Risks of developing overweight/obesity and abdominal obesity were investigated by multivariate logistic models. Increasing Italian Mediterranean Index score (indicating better adherence) was associated with lower 5-year weight change in volunteers of normal weight at baseline (β -0.12, 95% CI -0.16 to -0.08 for 1 tertile increase in score), but not in those overweight/obese at baseline (P interaction between Index score and BMI 0.0001). High adherence was also associated with reduced risk of becoming overweight/obese (OR 0.91, 95% CI 0.84-0.99 third vs. first tertile); smaller 5-year change in waist circumference (β -0.09, 95% CI -0.14 to -0.03 for 1 tertile increase in score); and lower risk of abdominal obesity (OR 0.91, 95% CI 0.84-0.99 third vs. first tertile). Adherence to a traditional Italian Mediterranean diet may help prevent weight gain and abdominal obesity.

PURPOSE:To characterize the lifestyle and nutritional risk profile associated with the Mediterranean diet in a Portuguese population with and without age-related macular degeneration (AMD).

METHODS:Nested case-control study (n = 883) within the Coimbra Eye Study, including 434 subjects with AMD and 449 age- and sex-matched subjects without AMD. All enrolled subjects underwent a full risk assessment, including lifestyle-related risk factors and a thorough food frequency questionnaire. This allowed us to build an adherence score to the Mediterranean diet (mediSCORE, range 0-9) constructed from individual food intakes. Food intake was also further analysed by conversion to micronutrient consumption.

RESULTS:Our results suggest that physical activity has a protective role in AMD [p = 0.018 after multivariate adjustment, OR: 0.69 (0.51-0.93)]. High (mediSCORE ≥6) was also found to be protective [p = 0.041, OR: 0.62 (95% CI: 0.38-0.97)]. Food group analysis unveiled a specific protective role for increased fruits consumption (p = 0.029). Finally, micronutrient analysisrevealed a protective role associated with increased consumption of caffeine, fibres, beta-carotene, vitamin C and vitamin E (p < 0.05).

CONCLUSION:High mediSCORE appears to confer protection against the development of AMD in a Mediterranean population. This effect is driven by increased consumption of fruits and some antioxidant micronutrients, which emerged as statistically significant protective factors. Further studies are required to establish dietary recommendations with clinical application.

BACKGROUND:A Mediterranean-style diet (MedSD) is associated with positive health outcomes, particularly reduced risk of cardiovascular disease. It is of interest to assess the feasibility of adherence to a MedSD in a subset of older adults in the United States.

OBJECTIVE:To assess the efficacy of implementing a MedSD intervention in a subset of postmenopausal women living in the United States, and to detect the influence of this dietary pattern on blood lipid levels.

DESIGN:A partial feeding, nutrition counseling, pilot study with a one-group longitudinal design.

PARTICIPANTS:Sixteen healthy, postmenopausal, American women living in suburban communities in Farmington, CT, with a mean±standard deviation age of 77±6.8 years and a body mass index of 26.1±3.1.

INTERVENTION:Participants were counseled by a registered dietitian nutritionist on how to follow a MedSD, which included increased sources of n-3 polyunsaturated fatty acids, fruits, and vegetables, and decreased saturated fat, n-6 polyunsaturated fatty acids, and simple sugars for 12 weeks. To maintain isocaloric conditions, participants were asked to substitute sources of saturated fat and refined carbohydrates for extra virgin olive oil (3 T/day), walnuts (1.5 oz/day), and fatty fish (3 to 5 servings/wk), which were provided at 3-week intervals.

MAIN OUTCOME MEASURES:Dietary adherence measures included the Mediterranean Diet Score, 3-day diet records, and serum fatty acid and lipid profiles.

STATISTICAL ANALYSES:Mixed model longitudinal analyses were conducted to assess changes over time (Weeks 0, 12, and 24) in the outcome variables.

RESULTS:Mediterranean Diet Score increased by 8.9 points (P<0.001) after the MedSD phase. Dietary sugar decreased by 10.8 g (P<0.05), total dietary n-3 increased by 1.6 g (P<0.01), total dietary n-6 increased by 5.5 g (P<0.01), and dietary n-6:n3 ratio decreased by 3.6 units (P<0.01). In serum, 22:6 (n-3), 20:5 (n-3), and 18:3 (n-3) increased (P<0.001, P<0.01, and P<0.001, respectively), and 14:0, 16:0, 17:0, 20:4 (n-6), 22:4 (n-6) declined after the intervention (P<0.01, P<0.001, P<0.01, P<0.01, and P<0.001, respectively), which support a change in dietary intake toward a MedSD. Serum high-density lipoprotein cholesterol levels increased by 3.8 mg/dL (0.098 mmol/L) (P<0.05) and serum triglyceride levels decreased by 11.6 mg/dL (0.131 mmol/L) (P<0.10).

CONCLUSIONS:A pilot study of a 12-week MedSD intervention with counseling from a registered dietitian nutritionist can favorably influence the dietary pattern and lipid profile of postmenopausal women living in the United States.

BACKGROUND:Insulin resistance is associated with higher breast cancer (BC) penetrance in BRCA mutation carriers. Metabolic syndrome (MetS), an insulin resistance syndrome, can be reversed by adhering to the Mediterranean diet (MedDiet). In a dietary intervention trial on BRCA mutation carriers, we evaluated adherence to the MedDiet, and the association with the MetS, by analyzing data from the Mediterranean Diet Adherence Screener (MEDAS).

METHODS:BRCA mutation carriers, with or without BC, aged 18 to 70 years, were eligible for the trial. After the baseline examinations, women were randomized to a dietary intervention or to a control group. Both groups completed the MEDAS at baseline and at the end of the dietary intervention.

RESULTS:A total of 163 women completed the 6 months of dietary intervention. Compared with controls, the women in the intervention group significantly reduced their consumption of red meat ( P<.01) and commercial sweets ( P<.01) and their MEDAS score rose significantly (+1.3 vs +0.55, P = .02). The number of MetS parameters decreased with increasing points of adherence to the MEDAS score ( P = .01). In the intervention group, there was a significant association with the greater reduction of MetS.

CONCLUSION:BRCA mutation carriers in the intervention group experienced greater improvement in their MedDiet and MetS parameters.

OBJECTIVE: To assess the relation between adherence to a Mediterranean diet and the incidence of diabetes among initially healthy participants.

DESIGN: Prospective cohort study with estimates of relative risk adjusted for sex, age, years of university education, total energy intake, body mass index, physical activity, sedentary habits, smoking, family history of diabetes, and personal history of hypertension. SETTING: Spanish university department.

PARTICIPANTS: 13 380 Spanish university graduates without diabetes at baseline followed up for a median of 4.4 years.

MAIN OUTCOME MEASURES: Dietary habits assessed at baseline with a validated 136 item food frequency questionnaire and scored on a nine point index. New cases of diabetes confirmed through medical reports and an additional detailed questionnaire posted to those who self reported a new diagnosis of diabetes by a doctor during follow-up. Confirmed cases of type 2 diabetes.

RESULTS: Participants who adhered closely to a Mediterranean diet had a lower risk of diabetes. The incidence rate ratios adjusted for sex and age were 0.41 (95% confidence interval 0.19 to 0.87) for those with moderate adherence (score 3-6) and 0.17 (0.04 to 0.75) for those with the highest adherence (score 7-9) compared with those with low adherence (score<3). In the fully adjusted analyses the results were similar. A two point increase in the score was associated with a 35% relative reduction in the risk of diabetes (incidence rate ratio 0.65, 0.44 to 0.95), with a significant inverse linear trend (P=0.04) in the multivariate analysis.

CONCLUSION: Adherence to a Mediterranean diet is associated with a reduced risk of diabetes.

BACKGROUND:Frailty is a common geriatric syndrome in old people. It remains controversial whether Mediterranean diet could prevent old people from developing into frailty. The aim of this study is to summarize the relevant studies and assess the effectiveness of adherence to Mediterranean diet on frailty in old people.

METHOD:A systematic search of MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials was conducted to identify all relevant studies up to Oct 2017. We included studies regarding the associations between adherence to Mediterranean diet and risk of frailty among elders. A meta-analysis was performed to explore the effects of Mediterranean diet on frailty.

RESULTS:Six studies matched the inclusion criteria, of which five were prospective and one was cross-sectional. A total of 10,210 participants from the five prospective cohort studies were included to perform the meta-analyses. In comparison with lowest adherence to Mediterranean diet, elders with highest adherence to Mediterranean diet were significantly associated with lower risk of frailty in the future (RR= 0.56, 95% CI=0.36-0.89, p=0.015). Furthermore, the pooled estimates from four studies performed among participants in western countries (European and North American) showed that higher adherence to Mediterranean diet was associated with a 52% reduced risk of frailty (RR= 0.48, 95% CI=0.32-0.72, p<0.001). However, one study showed no association between Mediterranean diet and frailty among Asian elders (RR=1.06, 95% CI=0.83-1.36, p=0.638).

CONCLUSION:A higher adherence to Mediterranean diet is associated with a lower risk of frailty in old people. Meanwhile, the benefits may be more obvious among elders from western countries.

Greater adherence to the Mediterranean diet has beneficial effects on the prevention of chronic diseases. In the current study, we investigated the association between the Mediterranean diet score (MDS) and the 6-year incidence of chronic kidney disease (CKD), conducted in the framework of the Tehran Lipid and Glucose Study with 1212 adults, aged 30-71 years. Dietary intake was assessed using a valid and reliable food-frequency questionnaire, and all subjects received scores between 0 and 8 points based on the traditional MDS. The components of the MDS were fruits and nuts, vegetables, legumes, cereals, fish, meat, dairy products and the monounsaturated to saturated fatty acid ratio. The odds ratio (OR) for the occurrence of CKD according to the quartiles of the MDS was assessed by multivariable logistic regression. The mean (s.d.) age of participants (51% male) at baseline was 43.5 (9.4) years. The median (25-75 interquartile range) of MDS for all subjects was 4 (3-5).The incidence of CKD was 19%. After adjustment for all potential confounding variables, individuals in the highest quartile of the MDS were 51% less likely to have CKD than those in the lowest quartile (OR=0.49; 95% confidence interval (CI): 0.30-0.82). Additionally, after further adjustment for baseline estimated glomerular filtration rate (GFR), the inverse association between the MDS and the 6-year incidence of CKD remained significant (OR=0.53; 95% CI: 0.31-0.91). Our findings demonstrate a significant inverse association between the MDS and the risk of incident CKD, indicating that adherence to the Mediterranean diet has favorable effects on the prevention of kidney dysfunction.Hypertension Research advance online publication, 11 August 2016; doi:10.1038/hr.2016.98.

BACKGROUND: The Mediterranean diet is protective against cardiovascular disease; a proposed mechanism is through a reduction in systemic inflammation. It is unknown to what extent the association between the Mediterranean diet and inflammation is due to genetic or other familial factors. METHODS AND RESULTS: We administered the Willett food frequency questionnaire to 345 middle-aged male twins and assessed adherence to the Mediterranean diet using a published adherence score. Fasting plasma levels of interleukin-6, C-reactive protein, and known cardiovascular risk factors were measured. Mixed-effect regression analyses were used to examine the relationship between diet score and inflammatory biomarkers after accounting for known cardiovascular risk factors. Adherence to the Mediterranean diet was associated with reduced levels of interleukin-6 (P<0.001) but not C-reactive protein (P=0.10) after adjustment for total energy intake, other nutritional factors, known cardiovascular risk factors, and use of supplements and medications. When the overall association of adherence to the diet with interleukin-6 levels was partitioned into between- and within-pair effects, the between-pair effect was not significant (P=0.9) and the within-pair effect was highly significant (P<0.0001). A 1-unit within-pair absolute difference in the diet score was associated with a 9% (95% CI, 4.5 to 13.6) lower interleukin-6 level. CONCLUSIONS: Shared environmental and genetic factors are unlikely to play a major role in the association between adherence to the Mediterranean diet and systemic inflammation. These results support the hypothesis that reduced inflammation is an important mechanism linking Mediterranean diet to reduced cardiovascular risk.

Diet plays a role in the onset and progression of metabolic disorders, including metabolic syndrome (MetS). We aimed to systematically review and conduct a quantitative meta-analysis of results from observational cross-sectional and prospective cohort studies on adherence to the Mediterranean dietary pattern and risk of MetS. Literature databases including PubMed, SCOPUS and EMBASE were searched from the beginning to May 2016. Eight cross-sectional and four prospective studies were included in this meta-analysis, accounting for a total of 33,847 individuals and 6342 cases of MetS. High adherence to the Mediterranean diet was associated with a risk of MetS (RR: 0.81, 95%CI: 0.71, 0.92). Regarding individual components of the MetS, the inverse associations were significant for waist circumference, blood pressure and low HDL-C levels. In conclusion, adoption of a Mediterranean dietary pattern was associated with lower risk of the MetS and it can be proposed for the primary prevention of the MetS.

PURPOSE:The purpose of this study was to compare the effect of standard wound care with adjunctive hyperbaric oxygen therapy (HBOT) to standard wound care alone on wound healing, markers of inflammation, glycemic control, amputation rate, survival rate of tissue, and health-related quality of life in patients with diabetic foot ulcers (DFUs).

DESIGN:Prospective, randomized, open-label, controlled study.

SUBJECTS AND SETTING:The sample comprised 38 patients with nonhealing DFUs who were deemed poor candidates for vascular surgery. Subjects were randomly allocated to an experimental group (standard care plus HBOT, n = 20) or a control group (standard care alone, n = 18). The study setting was a medical center in Kaohsiung City, Taiwan.

METHODS:Hyperbaric oxygen therapy was administered in a hyperbaric chamber under 2.5 absolute atmospheric pressure for 120 minutes; subjects were treated 5 days a week for 4 consecutive weeks. Both groups received standard wound care including debridement of necrotic tissue, topical therapy for Wagner grade 2 DFUs, dietary control and pharmacotherapy to maintain optimal blood glucose levels. Wound physiological indices were measured and blood tests (eg, markers of inflammation) were undertaken. Health-related quality of life was measured using the Medical Outcomes Study 36-Item Short Form.

RESULTS:Complete DFU closure was achieved in 5 patients (25%) in the HBOT group (n = 20) versus 1 participant (5.5%) in the routine care group (n = 18) (P = .001). The amputation rate was 5% for the HBOT group and 11% for the routine care group (χ = 15.204, P = .010). The HBOT group showed statistically significant improvements in inflammation index, blood flow, and health-related quality of life from pretreatment to 2 weeks after the last therapy ended (P<.05). Hemoglobin A1c was significantly lower in the HBOT group following treatment (P<.05) but not in the routine care group.

CONCLUSIONS:Adjunctive HBOT improved wound healing in persons with DFU. Therapy also reduced the risk of amputation of the affected limb. We assert that at least 20 HBOT sessions are required to be effective.

OBJECTIVE:In the post-sternotomy mediastinitis patients, Staphylococcus aureus is the pathogenic microorganism encountered most often. In our study, we aimed to determine the efficacy of antibiotic treatment with vancomycin and tigecycline, alone or in combination with hyperbaric oxygen treatment, on bacterial elimination in experimental S. aureus mediastinitis.

METHODS:Forty-nine adult female Wistar rats were used. They were randomly divided into seven groups, as follows: non-contaminated, contaminated control, vancomycin, tigecycline, hyperbaric oxygen, hyperbaric oxygen + vancomycin and hyperbaric oxygen + tigecycline. The vancomycin rat group received 10 mg/kg/day of vancomycin twice a day through intramuscular injection. The tigecycline group rats received 7 mg/kg/day of tigecycline twice a day through intraperitoneal injection. The hyperbaric oxygen group underwent 90 min sessions of 100% oxygen at 2.5 atm pressure. Treatment continued for 7 days. Twelve hours after the end of treatment, tissue samples were obtained from the upper part of the sternum for bacterial count assessment.

RESULTS:When the quantitative bacterial counts of the untreated contaminated group were compared with those of the treated groups, a significant decrease was observed. However, comparing the antibiotic groups with the same antibiotic combined with hyperbaric oxygen, there was a significant reduction in microorganisms identified (P<0.05). Comparing hyperbaric oxygen used alone with the vancomycin and tigecycline groups, it was seen that the effect was not significant (P<0.05).

CONCLUSION:We believe that the combination of hyperbaric oxygen with antibiotics had a significant effect on mediastinitis resulting from methicillin-resistant Staphylococcus aureus. Methicillin-resistant Staphylococcus aureus mediastinitis can be treated without requiring a multidrug combination, thereby reducing the medication dose and concomitantly decreasing the side effects.

BACKGROUND/AIMS: To test the impact of vitamin C supplementation on triple therapy for H. pylori eradication. METHODOLOGY: A total of 171 H. pylori-infected patients were randomized to receive different one-week triple therapies, including 20 mg omeprazole, 1 g amoxicillin, plus the following twice daily: (1) 250 mg clarithromycin (C250 group, n=55); (2) 250 mg clarithromycin and 500 mg vitamin C (V-C250 group, n=61); (3) 500 mg clarithromycin (C500 group, n=55). Six weeks after treatment, the success of H. pylori eradication was assessed by a 13C-urea breath test. Each collected H. pylori strain was defined as either clarithromycin susceptible or resistant by E-test. RESULTS: The demographic background, clarithromycin susceptibility of H. pylori, and drug compliance were similar among the three groups (p=NS). For clarithromycin susceptible infection, the V-C250 group had a higher eradication rate than the C250 group (ITT: 85% vs. 68% and PP: 90% vs. 73%, p = 0.03), but had an equivalent rate to the C500 group (p=NS). For clarithromycin resistant infection, all three groups had a similarly poor eradication rate of less than 34%. CONCLUSIONS: Adding vitamin C to one-week triple therapy can reduce the dosage of clarithromycin, but preserve the high eradication efficacy for clarithromycin susceptible H. pylori infection.

Three young women who developed premature ovarian insufficiency following quadrivalent human papillomavirus (HPV) vaccination presented to a general practitioner in rural New South Wales, Australia. The unrelated girls were aged 16, 16, and 18 years at diagnosis. Each had received HPV vaccinations prior to the onset of ovarian decline. Vaccinations had been administered in different regions of the state of New South Wales and the 3 girls lived in different towns in that state. Each had been prescribed the oral contraceptive pill to treat menstrual cycle abnormalities prior to investigation and diagnosis. Vaccine research does not present an ovary histology report of tested rats but does present a testicular histology report. Enduring ovarian capacity and duration of function following vaccination is unresearched in preclinical studies, clinical and postlicensure studies. Postmarketing surveillance does not accurately represent diagnoses in adverse event notifications and can neither represent unnotified cases nor compare incident statistics with vaccine course administration rates. The potential significance of a case series of adolescents with idiopathic premature ovarian insufficiency following HPV vaccination presenting to a general practice warrants further research. Preservation of reproductive health is a primary concern in the recipient target group. Since this group includes all prepubertal and pubertal young women, demonstration of ongoing, uncompromised safety for the ovary is urgently required. This matter needs to be resolved for the purposes of population health and public vaccine confidence.

Importance:Immunization of extremely low-birth-weight (ELBW) infants in the neonatal intensive care unit (NICU) is associated with adverse events, including fever and apnea or bradycardia, in the immediate postimmunization period. These adverse events present a diagnostic dilemma for physicians, leading to the potential for immunization delay and sepsis evaluations.

Objective:To compare the incidence of sepsis evaluations, need for increased respiratory support, intubation, seizures, and death among immunized ELBW infants in the 3 days before and after immunization.

Design, Setting, and Participants:In this multicenter retrospective cohort study, we studied 13 926 ELBW infants born at 28 weeks' gestation or less who were discharged from January 1, 2007, through December 31, 2012, from 348 NICUs managed by the Pediatrix Medical Group.

Exposures:At least one immunization between the ages of 53 and 110 days.

Main Outcomes and Measures:Incidence of sepsis evaluations, need for increased respiratory support, intubation, seizures, and death.

Results:Most of the 13 926 infants (91.2%) received 3 or more immunizations. The incidence of sepsis evaluations increased from 5.4 per 1000 patient-days in the preimmunization period to 19.3 per 1000 patient-days in the postimmunization period (adjusted rate ratio [ARR], 3.7; 95% CI, 3.2-4.4). The need for increased respiratory support increased from 6.6 per 1000 patient-days in the preimmunization period to 14.0 per 1000 patient-days in the postimmunization period (ARR, 2.1; 95% CI, 1.9-2.5), and intubation increased from 2.0 per 1000 patient-days to 3.6 per 1000 patient-days (ARR, 1.7; 95% CI, 1.3-2.2). The postimmunization incidence of adverse events was similar across immunization types, including combination vaccines when compared with single-dose vaccines. Infants who were born at 23 to 24 weeks' gestation had a higher risk of sepsis evaluation and intubation after immunization. A prior history of sepsis was associated with higher risk of sepsis evaluation after immunization.

Conclusions and Relevance:All ELBW infants in the NICU had an increased incidence of sepsis evaluations and increased respiratory support and intubation after routine immunization. Our findings provide no evidence to suggest that physicians should not use combination vaccines in ELBW infants. Further studies are needed to determine whether timing or spacing of immunization administrations confers risk for the developing adverse events and whether a prior history of sepsis confers risk for an altered immune response in ELBW infants.

BACKGROUND:In Canada, private purchase of human papilloma virus (HPV) vaccines has been possible since 2006. In Alberta, Canada, a publicly funded quadrivalent HPV vaccine program began in the 2008/2009 school year. There have been concerns about adverse events, including venous thromboembolism (VTE) associated with HPV vaccines. We describe the frequencies of adverse events following HPV vaccination among Alberta females aged 9 years or older and look at VTE following HPV vaccination.

METHODS:We used the Alberta Immunization and Adverse Reaction to Immunization (Imm/ARI) repository (publicly funded vaccine), the population-based Pharmaceutical Information Network (PIN) information system (dispensing of a vaccine), and the Alberta Morbidity and Ambulatory Care Abstract reporting system (MACAR) for June 1, 2006-November 19, 2014. Deterministic data linkage used unique personal identifiers. We identified all reported adverse events following immunization (AEFI) and all emergency department (ED) utilization or hospitalizations within 42 days of immunization. We calculated the frequency of AEFI by type, rates per 100,000 doses of HPV vaccine administered and the frequencies of ICD-10-CA codes for hospitalizations and emergency department visits.

RESULTS:Over the period 195,270 females received 528,913 doses of HPV vaccine. Of those receiving at least one dose, 192 reported one or more AEFI events (198 AEFI events), i.e., 37.4/100,000 doses administered (95% CI 32.5-43.0). None were consistent with VTE. Of the women who received HPV vaccine 958 were hospitalized and 19,351 had an ED visit within 42 days of immunization. Four women who had an ED visit and hospitalization event were diagnosed with VTE. Three of these had other diagnoses known to be associated with VTE; the fourth woman had VTE among ED diagnoses but not among those for the hospitalization.

CONCLUSIONS:Rates of AEFI after HPV immunization in Alberta are low and consistent with types of events seen elsewhere.

OBJECTIVE:Previous studies have shown that estrogen deficiency, arising in postmenopause, promotes endothelial dysfunction. This study evaluated the effects of aerobic exercise training on endothelial dependent vasodilation of aorta in ovariectomized rats, specifically investigating the role of nitric oxide (NO) and reactive oxygen species (ROS).

METHODS:Female Wistar rats ovariectomized (OVX - n=20) or with intact ovary (SHAM - n=20) remained sedentary (OVX and SHAM) or performed aerobic exercise training on a treadmill 5 times a week for a period of 8 weeks (OVX-TRA and SHAM-TRA). In the thoracic aorta the endothelium-dependent and -independent vasodilation was assessed by acetylcholine (ACh) and sodium nitroprusside (SNP), respectively. Certain aortic rings were incubated with L-NAME to assess the NO modulation on the ACh-induced vasodilation. The fluorescence to dihydroethidium in aortic slices and plasma nitrite/nitrate concentrations were measured to evaluate ROS and NO bioavailability, respectively.

RESULTS:ACh-induced vasodilation was reduced in OVX rats as compared SHAM (Rmax: SHAM: 86±3.3 vs. OVX: 57±3.0%, p<0.01). Training prevented this response in OVX-TRA (Rmax: OVX-TRA: 88±2.0%, p<0.01), while did not change it in SHAM-TRA (Rmax: SHAM-TRA: 80±2.2%, p<0.01). The L-NAME incubation abolished the differences in ACh-induced relaxation among groups. SNP-induced vasodilation was not different among groups. OVX reduced nitrite/nitrate plasma concentrations and increased ROS in aortic slices, training as effective to restore these parameters to the SHAM levels.

CONCLUSIONS:Exercise training, even in estrogen deficiency conditions, is able to improve endothelial dependent vasodilation in rat aorta via enhanced NO bioavailability and reduced ROS levels.