Australia was alerted to a possible increase in allergy-related adverse events following immunisation (AEFI) with 2015 seasonal trivalent influenza vaccines (TIV) by the Victorian state vaccine safety service, SAEFVIC. We describe SAEFVIC's initial investigation and upon conclusion of the 2015 influenza vaccination programme, to define the signal event and implications for vaccine programmes. Allergy-related AEFI were defined as anaphylaxis, angioedema, urticaria or generalised allergic reaction. Investigations compared 2015 TIV AEFI reports to previous years as proportions and reporting risk (RR) per 100,000, stratified by influenza vaccine brand. The initial investigation showed an increased proportion of allergy-related AEFI compared with 2014 (25% vs 12%), predominantly in adults, with insufficient clinical severity to alter the programme risk-benefit. While overall TIV AEFI RR in 2015 was similar to previous years (RR: 1.07, 95% confidence interval (CI): 0.88-1.29), we identified a near-doubling RR for allergy-related AEFI in 2015 (RR: 1.78, 95% CI: 1.14-- 2.80) from 2011 to 2014 with no difference by vaccine brand or severity increase identified. This increase in generalised allergy-related AEFI, across all used vaccine brands, supports evidence of variable reactogenicity arising from influenza vaccine strain variations. This investigation underlines the importance of effective seasonal influenza vaccine pharmacovigilance.

Food allergy is an immunologically mediated adverse reaction to food protein. Cow's milk protein allergy (CMPA) is the most frequent type and is the one that is most difficult to diagnose. This study had the objective of analyzing the accuracy of hypersensitivity and specific IgE skin tests among children with CMPA and predominantly gastrointestinal clinical manifestations. The participants in this study were 192 children aged one and five (median of 2 yr). Among these, 122 underwent open oral challenge to the suspected food. After evaluating the sensitivity, specificity and positive and negative predictive values (respectively, PPV and NPV) of skin and specific IgE tests in relation to the gold standard (open oral challenge); all the children underwent the skin prick test (SPT), specific IgE test and atopy patch test (APT) for cow's milk, eggs, wheat and peanuts and the open oral challenge for the food to which the child was sensitive or had suspected sensitivity. Presence of food allergy was confirmed for 50 children (40.9%). Among these cases, 44/50 (88%) were of allergy to cow's milk protein. Children who presented a positive response to an oral challenge to cow's milk protein were considered to be cases, while the controls were children with negative response. Twenty-two of the 44 cases (50.0%) presented symptoms within the first 4 h after the challenge. The SPT presented 31.8% sensitivity, 90.3% specificity, 66.7% PPV and 68.4% NPV. The APT presented 25.0% sensitivity, 81.9% specificity, 45.8% PPV and 64.1% NPV. The specific IgE test presented, respectively, 20.5%, 88.9%, 52.9% and 64.6%. Despite the operational difficulty and the possible exposure risk, oral challenge is the best method for diagnosing CMPA, because of the low sensitivity and PPV of skin and specific IgE tests.

All light is not equal: blue wavelengths are the most potent portion of the visible electromagnetic spectrum for circadian regulation. Therefore, blocking blue light could create a form of physiologic darkness. Because the timing and quantity of light and darkness both affect sleep, evening use of amber lenses to block blue light might affect sleep quality. Mood is also affected by light and sleep; therefore, mood might be affected by blue light blockade. In this study, 20 adult volunteers were randomized to wear either blue-blocking (amber) or yellow-tinted (blocking ultraviolet only) safety glasses for 3 h prior to sleep. Participants completed sleep diaries during a one-week baseline assessment and two weeks' use of glasses. Outcome measures were subjective: change in overall sleep quality and positive/negative affect. Results demonstrated that sleep quality at study outset was poorer in the amber lens than the control group. Two- by three-way ANOVA revealed significant (p<.001) interaction between quality of sleep over the three weeks and experimental condition. At the end of the study, the amber lens group experienced significant (p<.001) improvement in sleep quality relative to the control group and positive affect (p = .005). Mood also improved significantly relative to controls. A replication with more detailed data on the subjects' circadian baseline and objective outcome measures is warranted.

Essential oils have been used as remedies for a long time in different cultures across the world. However, scientific proof of such application is scarce. We included 72 patients between the ages of 22 and 57 while waiting for dental treatment in our study. The participants were assigned to either a control group (14 men, 23 women) or to an odor group (18 men and 17 women). Ambient odor of orange was diffused in the waiting room through an electrical dispenser in the odor group whereas in the control group no odor was in the air. We assessed by means of self-report demographic and cognitive variables, trait and state anxiety, and current pain, mood, alertness, and calmness. In this study, we report that exposure to ambient odor of orange has a relaxant effect. Specifically, compared to the controls, women who were exposed to orange odor had a lower level of state anxiety, a more positive mood, and a higher level of calmness. Our data support the previous notion of sedative properties of the natural essential oil of orange (Citrus sinensis).

The goal of this study was to investigate the impact of the essential oils of orange and lavender on anxiety, mood, alertness and calmness in dental patients. Two hundred patients between the ages of 18 and 77 years (half women, half men) were assigned to one of four independent groups. While waiting for dental procedures patients were either stimulated with ambient odor of orange or ambient odor of lavender. These conditions were compared to a music condition and a control condition (no odor, no music). Anxiety, mood, alertness and calmness were assessed while patients waited for dental treatment. Statistical analyses revealed that compared to control condition both ambient odors of orange and lavender reduced anxiety and improved mood in patients waiting for dental treatment. These findings support the previous opinion that odors are capable of altering emotional states and may indicate that the use of odors is helpful in reducing anxiety in dental patients.

Background and aim Gestational diabetes mellitus (GDM) poses a threat to the mother and child. The aim of this study was to examine the effect of acupressure on the glycemic control and insulin requirement of GDM females. Materials and methods Thirty GDM female patients were randomized to either the study group (SG; n=15), which was treated with acupressure and the standard antenatal care, or the control group (CG; n=15), which was treated with the standard antenatal care. Fasting and 2-h post-prandial blood glucose levels, requirement for insulin and insulin resistance were measured at 24 and 36 weeks' gestation (WG). Also, neonatal outcomes were registered at delivery. Results The pre intervention showed no statistically significant differences between SG and CG for baseline characteristics of participants (p>0.05). Within group analyses, after 12 weeks intervention had shown that 75 g oral glucose tolerance test (OGTT), insulin resistance, number of required insulin and measure of utilized insulin were significantly reduced (p<0.05), with significant increase in body mass index (BMI) (p<0.05) in both groups. All outcome measures were not significantly changed (p>0.05) between both groups at 24 and 36 WG. No significant differences (p>0.05) in pregnancy and neonatal outcomes between both groups at labor. Conclusions Acupressure may help to reduce gestational diabetes or insulin treatment for overweight female patients with GDM.

Polyphenols are thought to be an interesting ergogenic aid for exercise and recovery. However, most studies regarding the effects of polyphenols investigated several days of supplementations. The present work aimed to study the effects of an acute intake of grape and apple polyphenols on the capacity to maintain intense exercise, here named endurance performance. Forty-eight physically active men (31± 6 years) were included in this study. During the two testing sessions, volunteers completed an endurance test at a high percentage of their maximal aerobic power and time to exhaustion was measured. Respiratory and pain parameters were also monitored. The preceding evening and 1 h before testing,volunteers had to absorb either 500 mg of polyphenols or placebo according to randomization. In comparison with the placebo, the mean duration of the maximal endurance test was significantly increased with polyphenols (+9.7% ± 6.0%, p<0.05). The maximal perceived exertion was reached later with polyphenols (+12.8%± 6.8%, p<0.05). Practically, the present study showed the beneficial effects of grape and apple polyphenols for athletes looking for endurance performance improvements. The specifically designed profile of polyphenols appeared to enhance the capacity to maintain intensive efforts and delay perceived exertion.

BACKGROUND:Falls are associated with morbidity, loss of independence, and mortality. While land-based group exercise and Tai Chi programs reduce the risk of falls, aquatic therapy may allow patients to complete balance exercises with less pain and fear of falling; however, limited data exist.

OBJECTIVE:The objective of the study was to pilot the implementation of an aquatic group based on Ai Chi principles (Aquabalance) and to evaluate the safety, intervention acceptability, and intervention effect sizes.

DESIGN:Pilot observational cohort study.

METHODS:Forty-two outpatients underwent a single 45-minute weekly group aquatic Ai Chi-based session for eight weeks (Aquabalance). Safety was monitored using organizational reporting systems. Patient attendance, satisfaction, and self-reported falls were also recorded. Balance measures included the Timed Up and Go (TUG) test, the Four Square Step Test (FSST), and the unilateral Step Tests.

RESULTS:Forty-two patients completed the program. It was feasible to deliver Aquabalance, as evidenced by the median (IQR) attendance rate of 8.0 (7.8, 8.0) out of 8. No adverse events occurred and participants reported high satisfaction levels. Improvements were noted on the TUG, 10-meter walk test, the Functional Reach Test, the FSST, and the unilateral step tests (p<0.05). The proportion of patients defined as high falls risk reduced from 38% to 21%. The study was limited by its small sample size, single-center nature, and the absence of a control group.

CONCLUSIONS:Aquabalance was safe, well-attended, and acceptable to participants. A randomized controlled assessor-blinded trial is required.

The emergence of a novel coronavirus, termed SARS-CoV-2, and the potentially life-threating respiratory disease that it can produce, COVID-19, has rapidly spread across the globe creating a massive public health problem. Previous epidemics of many emerging viral infections have typically resulted in poor obstetrical outcomes including maternal morbidity and mortality, maternal-fetal transmission of the virus, and perinatal infections and death. This communication reviews the effects of two previous coronavirus infections - severe acute respiratory syndrome (SARS) caused by SARS-CoV and Middle East respiratory syndrome (MERS) caused by MERS-CoV - on pregnancy outcomes. In addition, it analyzes literature describing 38 pregnant women with COVID-19 and their newborns in China to assess the effects of SARS-CoV-2 on the mothers and infants including clinical, laboratory and virologic data, and the transmissibility of the virus from mother to fetus. This analysis reveals that unlike coronavirus infections of pregnant women caused by SARS and MERS, in these 38 pregnant women COVID-19 did not lead to maternal deaths. Importantly, and similar to pregnancies with SARS and MERS, there were no confirmed cases of intrauterine transmission of SARS-CoV-2 from mothers with COVID-19 to their fetuses. All neonatal specimens tested, including in some cases placentas, were negative by rt-PCR for SARS-CoV-2. At this point in the global pandemic of COVID-19 infection there is no evidence that SARS-CoV-2 undergoes intrauterine or transplacental transmission from infected pregnant women to their fetuses. Analysis of additional cases is necessary to determine if this remains true.

Visceral adipose tissue is an immunogenic tissue, which turns detrimental during obesity by activation of proinflammatory macrophages. During aging, chronic inflammation increases proportional to visceral adipose tissue (VAT) mass and associates with escalating morbidity and mortality. Here, we utilize a mouse model to investigate the inflammatory status of visceral adipose tissue in lean aging mice and assess the effects of exercise training interventions. We randomized adult (11 months; n = 21) and old (23 months; n = 27) mice to resistance training (RT) or endurance training (ET), or to a sedentary control group (S). Strikingly, we observed an anti-inflammatory phenotype in the old mice, consisting of higher accumulation of M2 macrophages and IL-10 expression, compared to the adult mice. In concordance, old mice also had less VAT mass and smaller adipocytes compared to adult mice. In both age groups, exercise training enhanced the anti-inflammatory phenotype and increased PGC1-α mRNA expression. Intriguingly, the brown adipose tissue marker UCP1 was modestly higher in old mice, while remained unchanged by the intervention. In conclusion, in the absence of obesity, visceral adipose tissue possesses a pronounced anti-inflammatory phenotype during aging which is further enhanced by exercise.

An early antenatal dietary intervention could play an important role in the prevention of metabolic diseases postpartum. The aim of this study is to evaluate whether an early, specific dietary intervention reduces women's cardiovascular risk in the"fourth trimester". This prospective cohort study compares 1675 women from the standard-care group (ScG/n = 676), who received standard-care dietary guidelines, with the intervention group (IG/n = 999), who received Mediterranean diet (MedDiet)-based dietary guidelines, supplemented with extra-virgin olive oil and nuts. Cardiovascular risk was determined by the presence of metabolic syndrome (MetS) and insulin resistance syndrome (IrS) (HOMA-IR 3.5) at 12-14 weeks postpartum. MetS was less frequent in the IG (11.3 vs. 19.3%,<0.05). The intervention was associated with a reduction in the relative risk of having MetS: 0.74 (95% CI, 0.60-0.90), but not in the risk of IrS. When analyzing the presence of having one or more components of the MetS, the IG had significantly higher rates of having 0 components and lower rates of having≥1 (-trend = 0.029). An early MedDiet-based nutritional intervention in pregnancy is associated with reductions in postpartum rates of MetS.

Serious neurological disorders reported following whole-cell pertussis in comparison to acellular pertussis vaccines were evaluated. The Vaccine Adverse Events Reporting System (VAERS) was analyzed for Emergency Department (ED) visits, life-threatening reactions, hospitalizations, disabilities, deaths, seizures, infantile spasms, encephalitis/encephalopathy, autism, Sudden Infant Death Syndrome (SIDS) and speech disorders reported with an initial onset of symptoms within 3 days following whole-cell pertussis and acellular pertussis vaccines among those residing in the US from 1997 to 1999. Controls were employed to evaluate potential biases in VAERS. Evaluations as to whether whole-cell and acellular vaccines were administered to populations of similar age and sex were undertaken because these factors might influence the study's results. Statistical increases were observed for all events examined following whole-cell pertussis vaccination in comparison to acellular pertussis vaccination, excepting cerebellar ataxia. Reporting biases were minimal in VAERS, and whole-cell and acellular pertussis vaccines were administered to populations of similar age and sex. Biologic mechanisms for the increased reactogenicity of whole-cell pertussis vaccines may stem from the fact that whole-cell pertussis vaccines contain 3,000 different proteins, whereas DTaP contains two to five proteins. Whole-cell pertussis vaccine contains known neurotoxins including: endotoxin, pertussis toxin and adenylate cyclase. Our results, and conclusions by the US Institute of Medicine, suggest an association between serious neurological disorders and whole-cell pertussis immunization. In light of the presence of a safer and at least equally efficacious acellular pertussis vaccine alternative, the Japanese and US switch to using acellular pertussis vaccine seems well justified. Other countries using whole-cell pertussis-containing vaccines should consider following suite in the near future.

OBJECTIVES: To assess the efficacy of an aromatic essential oil (1% Zingiber officinale and 0.5% Citrus sinesis) massage among the elderly with moderate-to-severe knee pain. METHOD: Fifty-nine older persons were enrolled in a double-blind, placebo-controlled experimental study group from the Community Centre for Senior Citizens, Hong Kong. The intervention was six massage sessions with ginger and orange oil over a 3-week period. The placebo control group received the same massage intervention with olive oil only and the control group received no massage. Assessment was done at baseline, post 1-week and post 4 weeks after treatment. Changes from baseline to the end of treatment were assessed on knee pain intensity, stiffness level and physical functioning (by Western Ontario and McMaster Universities Osteoarthritis index) and quality of life (by SF-36). RESULTS: There were significant mean changes between the three time-points within the intervention group on three of the outcome measures: knee pain intensity (p=0.02); stiffness level (p=0.03); and enhancing physical function (p=0.04) but these were not apparent with the between-groups comparison (p=0.48, 0.14 and 0.45 respectively) 4 weeks after the massage. The improvement of physical function and pain were superior in the intervention group compared with both the placebo and the control group at post 1-week time (both p=0.03) but not sustained at post 4 weeks (p=0.45 and 0.29). The changes in quality of life were not statistically significant for all three groups. CONCLUSION: The aroma-massage therapy seems to have potential as an alternative method for short-term knee pain relief.

The aim of the present study was to compare the potential cognitive benefits of running barefoot compared to shod. Young adults (N = 72, M age = 24.4 years, SD = 5.5) ran both barefoot and shod on a running track while stepping on targets (poker chips) and when not stepping on targets. The main finding was that participants performed better on a working memory test when running barefoot compared to shod, but only when they had to step on targets. These results supported the idea that additional attention is needed when running barefoot to avoid stepping on objects that could potentially injure the foot. Significant increases in participant's heart rate were also found in the barefoot condition. No significantdifferences were found in participants' speed across conditions. These findings suggested that working memory may be enhanced after at least 16 minutes of barefoot running if the individual has to focus attention on the ground.

BACKGROUND:In Korea, measles occurs mainly in infants<12months of age, who are unvaccinated. In addition, vaccine populations, including adolescents and young adults, can become infected though importation. Thus, the question arises whether the current level of herd immunity in Korea is now insufficient for protecting against measles infection.

METHODS:Age-specific measles seroprevalence was evaluated by performing enzyme immunoassays and plaque reduction-neutralization tests on 3050 subjects aged 0-50years (birth cohort 1964-2014) and 480 subjects aged 2-30years (birth cohort 1984-2012).

RESULTS:The overall seropositivity and measles antibody concentrations were 71.5% and 1366mIU/mL, respectively. Progressive decline in antibody levels and seropositivity were observed over time after vaccination in infants, adolescents, and young adults. The accumulation of potentially susceptible individuals in the population was confirmed by comparing data from 2010 and 2014 seroprevalence surveys. The statistical correlation between measles incidence and measles seronegativity was determined.

CONCLUSIONS:Waning levels of measles antibodies with increasing time post-vaccination suggests that measles susceptibility is potentially increasing in Korea. This trend may be related to limitations of vaccine-induced immunity in the absence of natural boosting by the wild virus, compared to naturally acquired immunity triggered by measles infection. This study provides an important view into the current measles herd immunity in Korea.

Regular endurance exercise training induces beneficial functional and health effects in human skeletal muscle. The putative contribution to the training response of the epigenome as a mediator between genes and environment has not been clarified. Here we investigated the contribution of DNA methylation and associated transcriptomic changes in a well-controlled human intervention study. Training effects were mirrored by significant alterations in DNA methylation and gene expression in regions with a homogeneous muscle energetics and remodeling ontology. Moreover, a signature of DNA methylation and gene expression separated the samples based on training and gender. Differential DNA methylation was predominantly observed in enhancers, gene bodies and intergenic regions and less in CpG islands or promoters. We identified transcriptional regulator binding motifs of MRF, MEF2 and ETS proteins in the proximity of the changing sites. A transcriptional network analysis revealed modules harboring distinct ontologies and, interestingly, the overall direction of the changes of methylation within each module was inversely correlated to expression changes. In conclusion, we show that highly consistent and associated modifications in methylation and expression, concordant with observed health-enhancing phenotypic adaptations, are induced by a physiological stimulus.

BACKGROUND:A 9-valent human papillomavirus (9vHPV) vaccine has recently been reported to be safe and highly efficacious against infection and disease related to HPV6/11/16/18/31/33/45/52/58. We evaluated the immunogenicity and safety of the 9vHPV vaccine administered concomitantly with REPEVAX (diphtheria, tetanus, acellular pertussis and inactivated poliomyelitis vaccine).

METHODS:This open-label, randomized, multicenter study enrolled 1054 males and females ages 11-15 years. Subjects were randomly assigned to each group in a 1:1 ratio. Subjects received a 0.5 mL dose of 9vHPV vaccine intramuscularly at day 1, months 2 and 6 and a 0.5 mL dose of REPEVAX either on day 1 (concomitant vaccination group; n = 526) or at month 1 (nonconcomitant vaccination group, n = 528). Serologic responses for each vaccine component were tested by 1-sided tests of noninferiority between groups. Systemic and injection-site adverse experiences (AEs) and serious AEs were monitored.

RESULTS:Noninferiority of anti-HPV geometric mean titers and seroconversion rates for all 9vHPV antigens were demonstrated for the concomitant group compared with the nonconcomitant group. Seroconversion rates for the 9vHPV vaccine types were≥99.8% in both groups at month 7. For REPEVAX, noninferiority of immune response was established for diphtheria, tetanus, all polio and pertussis antigens for both groups. There were no vaccine-related serious AEs.

CONCLUSION:Overall, concomitant administration of 9vHPV vaccine and REPEVAX was generally well tolerated and did not interfere with the immune response to either vaccine. This strategy would minimize the number of visits required to deliver each vaccine individually.

BACKGROUND: In June 2006, the Advisory Committee on Immunization Practices (ACIP) expanded its June 2005 recommendation for a second dose of varicella vaccine during outbreaks to a recommendation for routine school entry second dose varicella vaccination. In October 2006, the Arkansas Department of Health was notified of a varicella outbreak among students where some received a second dose during an outbreak-related vaccination campaign in February 2006.

METHODS: The outbreak was investigated using a school-wide parental survey with a follow-up survey of identified case patients. Vaccination status was verified using state and local immunization records. Limited laboratory testing confirmed circulation of wild-type varicella, including varicella in 2-dose vaccine recipients.

RESULTS: Vaccination information was available for 871 (99%) of the 880 children. Varicella vaccination coverage was 97% (2-dose, 39%; 1-dose, 58%). A review of the February vaccination clinic found no deficiencies; lot numbers did not differ between cases and noncases. Varicella was confirmed by PCR in 5 (42%) of 12 lesion specimens and by IgM in 1 (6%) of 16 serum specimens. Varicella was reported in 84 children, including 25 (30%) two-dose and 53 (63%) one-dose recipients. Attack rates among 2-dose recipients (10.4%) and 1-dose recipients (14.6%) were not significantly different (RR: 0.72, 95% CI: 0.44-1.15). All 2-dose recipients and 80% of 1-dose recipients reported having 50 or fewer skin lesions.

CONCLUSION: This outbreak is the first to document varicella in both 1- and 2-dose vaccine recipients; both groups had mild disease. The vaccine effectiveness of 1 and 2 doses were similar.

BACKGROUND:A quadrivalent human papillomavirus (HPV4) type 6/11/16/18 vaccine (GARDASIL/SILGARD®) has been licensed in many countries around the world for the prevention of cervical, vulvar, vaginal, and anal cancers and precancers, as well as external genital warts causally related to HPV types 6/11/16/18. Across 7 phase 3 clinical trials involving more than 29,000 males and females ages 9-45 years, vaccination was generally well tolerated. Because of its expected public health benefit in reducing cervical cancer and other HPV-related diseases, the vaccine has been implemented in the national vaccination programs of several countries, with over 178 million doses distributed worldwide.

METHODS:Extensive efforts to assess the safety of the vaccine in routine practice have been conducted over the past 9 years since licensure, including more than 15 studies in more than 1 million preadolescents, adolescents and adults from various countries. Most have been performed in the general population although there have been some in special populations (pregnant women, HIV-infected individuals and those with systemic lupus erythematosus).

RESULTS:We present a summary of the published, postlicensure safety data from active and passive surveillance. Only syncope, and possibly skin infections were associated with vaccination in the postlicensure setting. Serious adverse events, such as adverse pregnancy outcomes, autoimmune diseases (including Guillain-Barre Syndrome and multiple sclerosis), anaphylaxis, venous thromboembolism and stroke, were extensively studied, and no increase in the incidence of these events was found compared with background rates.

CONCLUSIONS:These results, along with the safety data from the prelicensure clinical trials, confirm that the HPV4 vaccine has a favorable safety profile. Key policy, medical and regulatory organizations around the world have independently reviewed these data and continue to recommend routine HPV vaccination.