Human papillomavirus vaccine effectiveness within a cervical cancer screening programme: cohort study.

OBJECTIVE: To assess the effectiveness of an HPV vaccination programme in reducing the risk of cervical abnormalities identified at subsequent screening. DESIGN: Retrospective cohort study using administrative health data. SETTING: General population of Ferrara Province, Italy. POPULATION: Female residents born in 1986-1993 and participating in the organized cervical screening programme in 2011-2018, who were eligible for HPV vaccination in catch-up cohorts. METHODS: Logistic regression to evaluate the potential association between abnormal cervical cytology and one, two, three or at least one dose of HPV vaccine. MAIN OUTCOME MEASURES: Cervical abnormalities, as predicted by low-grade or high-grade cytology, by number of vaccine doses, stratified by age. RESULTS: The sample consisted of 7785 women (mean age 27.5 years, SD 2.3). Overall, 391 (5.0%) were vaccinated with ≥1 dose and 893 (11.5%) had abnormal cytology. Women receiving at least one vaccine dose were significantly less likely to have an abnormal cytology (adjusted odds ratio 0.52; 95% confidence interval 0.34-0.79). Similar results were observed for women receiving a single dose, for both bivalent and quadrivalent vaccines, and applying buffer periods (excluding cytological outcomes within 1 month, 6 months and 1 year of the first dose). CONCLUSIONS: In the context of an organised cervical screening programme in Italy, catch-up HPV vaccination almost halved the risk of cytological abnormalities. TWEETABLE ABSTRACT: Among Ferrara women, vaccination against human papillomavirus halved the risk of screening cervical abnormalities.

Difficulty of confining recalcitrant tuberculosis patients in isolation wards in Japan, 2013-2014.

OBJECTIVES: In Japan, approximately 7000 smear-positive tuberculosis (TB) cases were reported in 2014. According to the law, such patients must be isolated in a TB ward until they become at least sputum smear-negative. However, there are some recalcitrant patients who are difficult to isolate because of problematic behaviors. This study was conducted to characterize recalcitrant TB patients and determine why they left the hospitals and how they were followed up after they left. STUDY DESIGN: Cross-sectional study. METHODS: We sent a self-administered questionnaire to the hospitals in Japan with over 11 TB isolation beds, asking about recalcitrant TB inpatients from April 2013 through March 2014, in terms of demographic information, the reasons why they left, and how they were followed up. RESULTS: A total of 38 recalcitrant patients were reported, of whom 15 (39.5%) self-discharged, eight (21.0%) were discharged, and 15 (39.5%) were transferred. Thirty-three (86.8%) were males. The main reason (52.6%) why the patients were considered recalcitrant was related to psychiatric problems. However, nine (23.6%) patients physically assaulted or insulted the staff members. Thirty-six (94.7%) were able to continue anti-TB treatment after they left the original hospital. CONCLUSION: Although the number of recalcitrant TB patients who were abusive was small, there should be TB facilities with law enforcement officials readily available to enforce isolation.

Ovarian cavity fluid of the viviparous surfperch Neoditrema ransonnetii suppresses the spontaneous cytotoxic activity of head-kidney leucocytes against xenogeneic targets.

In this study, the effect of ovarian cavity fluid (OCF) from a surfperch Neoditrema ransonnetii on the cytotoxic activity of leucocytes was investigated. In an assay targeting RTG-2, a cell line derived from rainbow trout Oncorhynchus mykiss gonads, leucocytes from both the spleen and head kidney showed spontaneous killing activity. Pre-incubation with OCF significantly suppressed the cytotoxic activity of head-kidney leucocytes towards RTG-2. This suppressive activity was due to the presence of low molecular-mass materials. These results suggest that OCF plays significant roles in pregnancy by its ability to modulate cytotoxicity with maternal leucocytes.

Long-term exposure to particulate matter and all-cause and cause-specific mortality in an analysis of multiple Asian cohorts.

BACKGROUND: Exposure to ambient air pollution is associated with a significant number of deaths. Much of the evidence associating air pollution with adverse effects is from North American and Europe, partially due to incomplete data in other regions limiting location specific examinations. The aim of the current paper is to leverage satellite derived air quality data to examine the relationship between ambient particulate matter and all-cause and cause-specific mortality in Asia. METHODS: Six cohorts from the Asia Cohort Consortium provided residential information for participants, recruited between 1991 and 2008, across six countries (Bangladesh, India, Iran, Japan, South Korea, and Taiwan). Ambient particulate material (PM2·5) levels for the year of enrolment (or 1998 if enrolled earlier) were assigned utilizing satellite and sensor-based maps. Cox proportional models were used to examine the association between ambient air pollution and all-cause and cause-specific mortality (all cancer, lung cancer, cardiovascular and lung disease). Models were additionally adjusted for urbanicity (representing urban and built characteristics) and stratified by smoking status in secondary analyses. Country-specific findings were pooled via random-effects meta-analysis. FINDINGS: More than 300,000 participants across six cohorts were included, representing more than 4-million-person years. A positive relationship was observed between a 5 µg/m (Dockery et al., 1993) increase in PM2·5 and cardiovascular mortality (HR: 1·06, 95 % CI: 0.99, 1·13). The additional adjustment for urbanicity resulted in increased associations between PM2.5 and mortality outcomes, including all-cause mortality (1·04, 95 % CI: 0·97, 1·11). Results were generally similar regardless of whether one was a current, never, or ex-smoker. INTERPRETATION: Using satellite and remote sensing technology we showed that associations between PM2.5 and all-cause and cause-specific Hazard Ratios estimated are similar to those reported for U.S. and European cohorts. FUNDING: This project was supported by the Health Effects Institute. Grant number #4963-RFA/18-5. Specific funding support for individual cohorts is described in the Acknowledgements.

Prevalence and growth kinetics of Shiga toxin-producing Escherichia coli (STEC) in bovine offal products in Japan.

Recent epidemiological data suggest a link between the consumption of bovine offal products and Shiga toxin-producing Escherichia coli (STEC) infection in Japan. This study thus examined the prevalence of STEC in various types of these foods. PCR screened 229 bovine offal products for the presence of Shiga toxin (stx) gene. Thirty-eight (16·6%) samples were stx positive, of which eight were positive for rfbE(O157) and three were positive for wzy(O26). Four O157 and one O26 STEC isolates were finally obtained from small-intestine and omasum products. Notably, homogenates of bovine intestinal products significantly reduced the extent of growth of O157 in the enrichment process compared to homogenates of beef carcass. As co-incubation of O157 with background microbiota complex from bovine intestinal products in buffered peptone water, in the absence of meat samples, tended to reduce the extent of growth of O157, we reasoned that certain microbiota present in offal products played a role. In support of this, inoculation of generic E. coli from bovine intestinal products into the homogenates significantly reduced the extent of growth of O157 in the homogenates of bovine intestinal and loin-beef products, and this effect was markedly increased when these homogenates were heat-treated prior to inoculation. Together, this report provides first evidence of the prevalence of STEC in a variety of bovine offal products in Japan. The prevalence data herein may be useful for risk assessment of those products as a potential source of human STEC infection beyond the epidemiological background. The growth characteristic of STEC O157 in offal products also indicates the importance of being aware when to test these food products.

Association of periodontal disease with breed size, breed, weight, and age in pure-bred client-owned dogs in the United States.

Despite periodontal disease (PD) being amongst the most common diagnoses in primary-care practice, the disease is generally underdiagnosed. However, the millions of clinical records generated by pet hospitals each year provide unique opportunities to generate insights about disease risk across large numbers of dogs. The objective of this study was to undertake a retrospective analysis of medical records to ascertain which sizes and breeds of dog are most frequently diagnosed with PD. Although data collection regarding PD was not consistent, it was assumed that the same inconsistencies in recording periodontal abnormalities were present across the range of bodyweight, breed categories and breeds. Over 3 million medical records across 60 breeds of dogs visiting a chain of veterinary hospitals in the United States collected over a 5-year period were analysed. Statistical analysis of a subset of these records found that extra-small (<6.5 kg) breeds of dog were up to five times more likely to be diagnosed with PD than giant breeds (>25 kg) (P <0.0001). The majority of breeds most frequently diagnosed with PD were in the extra-small, small (6.5-9 kg) and medium-small (9-15 kg) breed size categories. Additional risk factors for PD diagnosis included age, being overweight and time since last scale and polish. Veterinarians should consider targeting client education about dental health, and diagnostic efforts, towards canine patients of the small-breed size categories and those with a higher risk of developing PD (e.g. overweight).

Purification and Properties of Flavin- and Molybdenum-Containing Aldehyde Oxidase from Coleoptiles of Maize.

Aldehyde oxidase (AO; EC 1.2.3.1) that could oxidize indole-3-acetaldehyde into indole-3-acetic acid was purified approximately 2000-fold from coleoptiles of 3-d-old maize (Zea mays L.) seedlings. The apparent molecular mass of the native enzyme was about 300 kD as estimated by gel-filtration column chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the enzyme was composed of 150-kD subunits. It contained flavin adenine dinucleotide, iron, and molybdenum as prosthetic groups and had absorption peaks in the visible region (300-600 nm). To our knowledge, this is the first demonstration of the presence of flavin adenine dinucleotide and metals in plant AO. Other aromatic aldehydes such as indole-3-aldehyde and benzaldehyde also served as good substrates, but N-methylnicotinamide, a good substrate for animal AO, was not oxidized. 2-Mercaptoethanol, p-chloromercu-ribenzoate, and iodoacetate partially inhibited the activity, but well-known inhibitors of animal AO, such as menadione and estradiol, caused no reduction in activity. These results indicate that, although maize AO is similar to animal enzymes in molecular mass and cofactor components, it differs in substrate specificity and susceptibility to inhibitors. Immunoblotting analysis with mouse polyclonal antibodies raised against the purified maize AO showed that the enzyme was relatively rich in the apical region of maize coleoptiles. The possible role of this enzyme is discussed in relation to phytohormone biosynthesis in plants.

A clinical study of Japanese patients with ulcer induced by low-dose aspirin and other non-steroidal anti-inflammatory drugs.

BACKGROUND: The incidence and severity of non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastro-duodenal ulcer have not been extensively studied in Japan. AIM: We performed a prospective study to clarify NSAIDs-induced gastro-duodenal injury, focusing especially on low-dose aspirin (L-A). METHODS: Two hundred and thirty-eight patients with bleeding peptic ulcers admitted to our hospital. History of taking NSAIDs and anti-ulcer drugs was obtained from all patients who underwent endoscopic examinations. The lesion scores of patients taking L-A were classified numerically from zero (no lesion) to five (ulcer). RESULTS: The NSAIDs were associated with 28.2% of hemorrhagic ulcers. The rates of patients using L-A, loxoprofen, diclofenac, and combination of two of these drugs were 27, 16, 10 and 9%, respectively. Co-administered anti-ulcer drugs were cytoprotective anti-ulcer drugs (27%), H2 receptor antagonists (16%), PPI (4%), and none (53%). In patients taking L-A, H2 receptor antagonists were used most frequently. The HP was positive in 63% of L-A-induced ulcer cases and in 69% of NSAIDs other than low-dose aspirin-induced ulcer cases. The lesion scores of patients taking L-A with H2 receptor antagonists or PPI were significantly lower than those of patients who were taking only L-A (P < 0.05). CONCLUSIONS: Approximately one-third of hospitalized patients with NSAIDs-induced hemorrhagic ulcer showed an association with L-A. Prospective randomized controlled trials including H2 receptor antagonists are required to establish preventive efforts aimed at L-A-induced gastro-duodenal injury.

Potential Intercontinental Movement of Influenza A(H7N9) Virus into North America by Wild Birds: Application of a Rapid Assessment Framework.

A critical question surrounding emergence of novel strains of avian influenza viruses (AIV) is the ability for wild migratory birds to translocate a complete (unreassorted whole genome) AIV intercontinentally. Virus translocation via migratory birds is suspected in outbreaks of highly pathogenic strain A(H5N1) in Asia, Africa and Europe. As a result, the potential intercontinental translocation of newly emerging AIV such as A(H7N9) from Eurasia to North America via migratory movements of birds remains a concern. An estimated 2.91 million aquatic birds move annually between Eurasia and North America with an estimated AIV prevalence as high as 32.2%. Here, we present a rapid assessment to address the likelihood of whole (unreassorted)-genome translocation of Eurasian strain AIV into North America. The scope of this assessment was limited specifically to assess the weight of evidence to support the movement of an unreassorted AIV intercontinentally by migratory aquatic birds. We developed a rapid assessment framework to assess the potential for intercontinental movement of avian influenzas by aquatic birds. This framework was iteratively reviewed by a multidisciplinary panel of scientific experts until a consensus was established. Our assessment framework identified four factors that may contribute to the potential for introduction of any AIV intercontinentally into North America by wild aquatic birds. These factors, in aggregate, provide a framework for evaluating the likelihood of new forms of AIV from Eurasia to be introduced by aquatic birds into North America. Based on our assessment, we determined that the potential for introduction of A(H7N9) into North America through aquatic migratory birds is possible, but the likelihood ranges from extremely low to low.

The Burden of Diagnosed and Undiagnosed Diabetes in Native Hawaiian and Asian American Hospitalized Patients.

AIMS: Little is known about diabetes in hospitalized Native Hawaiians and Asian Americans. We determined the burden of diabetes (both diagnosed and undiagnosed) among hospitalized Native Hawaiian, Asian (Filipino, Chinese, Japanese), and White patients. METHODS: Diagnosed diabetes was determined from discharge data from a major medical center in Hawai'i during 2007-2008. Potentially undiagnosed diabetes was determined by Hemoglobin A1c ≥6.5% or glucose ≥200 mg/dl values for those without diagnosed diabetes. Multivariable log-binomial models predicted diabetes (potentially undiagnosed and diagnosed, separately) controlling for socio-demographic factors. RESULTS: Of 17,828 hospitalized patients, 3.4% had potentially undiagnosed diabetes and 30.5% had diagnosed diabetes. In multivariable models compared to Whites, Native Hawaiian and all Asian subgroups had significantly higher percentages of diagnosed diabetes, but not of potentially undiagnosed diabetes. Potentially undiagnosed diabetes was associated with significantly more hospitalizations during the study period compared to both those without diabetes and those with diagnosed diabetes. In all racial/ethnic groups, those with potentially undiagnosed diabetes also had the longest length of stay and were more likely to die during the hospitalization. CONCLUSIONS: Hospitalized Native Hawaiians (41%) and Asian subgroups had significantly higher overall diabetes burdens compared to Whites (23%). Potentially undiagnosed diabetes was associated with poor outcomes. Hospitalized patients, irrespective of race/ethnicity, may require more effective inpatient identification and management of previously undiagnosed diabetes to improve clinical outcomes.

Widespread presence of large molecular weight adrenocorticotropin-like substances in normal rat extrapituitary tissues.

ACTH activity in glacial acetic acid extracts of normal rat tissues was studied by both ACTH RIA and a sensitive in vitro bioassay. ACTH immunoactivity was found in all tissues: brain, 278 +/- 54 (mean +/- SE; picograms per mg protein); stomach, 59 +/- 4; kidney, 47 +/- 3; colon, 40 +/- 4; small intestine, 37 +/- 4; liver, 18 +/- 2; and heart, 16 +/- 3. Tissue ACTH showed parallelism with ACTH standard in the RIA. No correlation existed between tissue ACTH and plasma ACTH in normal rats. Dexamethasone treatment (0.4 mg/day for 5 days) suppressed plasma ACTH, but did not affect tissue ACTH levels. When tissue extracts were passed through Sephadex G-75-SF columns, ACTH immunoactivity was exclusively eluted in the portion of bigger molecular weight than ACTH standard, except in the brain. Based on this column chromatography, the molecular weight of the main peak of activity was estimated as 26,000. Tissue ACTH-like material contained no detectable biological activity (less than 2 pg/100 ng tissue). However, biological activity was easily detectable after exposure of the tissue extracts to trypsin. When studied by immunoassay and bioassay, this 26,000 mol wt ACTH was digested and cleaved to 4,500 mol wt and biologically active ACTH with trypsin treatment. Tissue ACTH immunoactivity does not seem to be the result of artifacts: 1) extracts were adjusted to pH 8.0 and a common osmolality (150 mosmol/liter) before assay; 2) protein contents in RIA tubes were only 0.1-1.6 mg; 3) tissue extracts incubated with [125I]iodo-ACTH for 48 h produced less than 5% damage of labeled hormone, as assessed by moderate excess of antibody binding; 4) enzyme inhibitors did not modify tissue ACTH levels; and 5) ACTH immunoactivity of tissue extracts was absorbed by anti-ACTH immunocolumns. We conclude that high molecular weight ACTH-like materials are widespread in normal rat extrapituitary tissues and are probably a precursor form of 4500 mol wt ACTH.

Inhibitory effects of corticosterone on cell proliferation and steroidogenesis in the mouse adrenal tumor cell line Y-1.

Monolayer cultures of mouse adrenal tumor cell line Y-1 have been used to investigate the effects of glucocorticoid on cell replication, [3H]thymidine incorporation into the trichloroacetic acid-precipitated cell fraction, steroidogenesis, and the ACTH receptors of adrenocortical cells. Corticosterone at a concentration of 5.0--50 micrograms/ml inhibited cell replication and [3H]thymidine incorporation into trichloroacetic acid-precipitated cell fraction in a dose-related manner. Corticosterone at a concentration of 0.5--50 micrograms/ml inhibited ACTH-induced steroidogenesis in a dose-related manner. Steroids which do not possess glucocorticoid action did not show such inhibitory effects on cell replication and steroidogenesis of Y-1 cells. The characteristics of the ACTH receptors of these cells remained unaffected by corticosterone. Our findings suggest that synthesized or secreted glucocorticoid may play an important role in the direct regulation of proliferation and function of adrenocortical cells under physiological conditions.

Direct inhibitory effect of dexamethasone on steroidogenesis of human adrenal in vivo.

A rapid ACTH test was used to investigate the direct effect of glucocorticoid on the steroidogenesis by the adrenal cortex in man. The plasma cortisol response to 250 microgram iv synthetic alpha-ACTH-(1--24) (Cortrosyn) was determined in normal subjects pretreated with 2 and 12 mg dexamethasone. The 15- and 30-min increments in plasma cortisol levels in response to ACTH injection after pretreatment with 12 mg dexamethasone were significantly suppressed compared to values obtained after pretreatment with 2 mg dexamethasone. The present study suggests that there is a direct inhibitory effect of glucocorticoid on adrenocortical steroidogenesis in man.

Hyperparathyroidism in patients with myotonic dystrophy.

This study was designed to determine the possible presence of abnormal calcium metabolism in patients with myotonic dystrophy (MyD). Twenty-five patients with MyD, 13 patients with other neuromuscular disorders (non-MyD), and 12 normal subjects were studied. The mean plasma 1,25-dihydroxyvitamin D level in the MyD patients [83.2 +/- 23.1 (+/- SD) pmol/L] was significantly higher than those in the other two groups [normal subjects, 49.7 +/- 15.4 (P less than 0.01); non-MyD patients, 51.6 +/- 27.4 (P less than 0.01)]. On the contrary, the mean plasma 24,25-dihydroxyvitamin D levels were similar in the MyD patients and the normal subjects. The increments in serum calcium levels and urinary calcium excretion after oral calcium loading in the MyD patients were significantly greater than those in the normal subjects, suggesting that intestinal calcium absorption was augmented in the MyD patients. The mean nephrogenous cAMP excretion in the MyD patients (1.71 +/- 1.08 nmol/100 mL glomerular filtrate) also was higher than those in the other two groups (0.93 +/- 0.34 in the non-MyD patients; 0.91 +/- 0.21 in normal subjects). These results suggest that parathyroid function may be increased in MyD patients.

Presence of TSH receptor in thyroid neoplasms.

The nature of the TSH receptor in adenoma and carcinoma of the thyroid gland was studied using a radioreceptor assay technique. A membrane fraction of tissue homogenate was obtained by discontinuous sucrose gradient ultracentrifugation, and 125I-TSH, labelled by a lactoperoxidase method, was purified with a receptor adsorption method. Both the capacities and the association constants of high affinity receptors (4 x 10(9) M-1) and of low affinity receptors (0.073 x 10(9) M-1) observed in the normal thyroid were almost identical to those of the thyroid of Graves' disease and those of thyroid adenoma. Although the two papillary carcinomas examined were found to have two kinds of TSH receptors, one of the carcinomas showed decreased association constants for both high affinity and low affinity receptors.

Influence of FK506 on experimental atherosclerosis in cholesterol-fed rabbits.

To investigate the role of activated T lymphocytes in the formation of atherosclerotic lesions, we studied the influence of FK506, an immunosuppressant, on the development of atherosclerosis in cholesterol-fed rabbits. New Zealand White rabbits fed on a 1.5% cholesterol diet were administered FK506 at 0.05 mg/kg (n = 12), 0.1 mg/kg (n = 12) or isotonic saline (as the control, n = 12) intramuscularly three times a week for 12 weeks. Although FK506 treatment did not affect plasma lipid levels, it caused an increase in the development of atherosclerotic lesions in a dose-dependent manner. Immunohistochemical analysis of the aorta after 8 weeks on the diet revealed that the ratio of T lymphocytes to the total number of cells in the plaques decreased significantly in the FK506 treated rabbits compared to the control rabbits. In culture, FK506 did not affect smooth muscle cell proliferation and cholesteryl ester formation in the macrophages. In contrast, culture medium from lymphocytes stimulated by concanavalin A decreased the accumulation of cholesteryl ester in the macrophages. This effect was inhibited by the culture medium in the presence of FK506. These findings suggest that activated T lymphocytes may inhibit intracellular cholesterol accumulation in atherosclerotic plaque.

Large molecular weight ACTH immunoactivity in a patient with adrenoleukomyeloneuropathy.

Very high ACTH immunoactivity was measured in a patient with adrenoleukomyeloneuropathy. The basal adrenocortical function was hyperactive, whereas the response to exogenous ACTH was depressed. Most of the ACTH immunoactivity was a large molecule (55,000 daltons), which weakly stimulated steroidogenesis of adrenocortical cells in vitro, but inhibited the binding of 125I-iodoACTH to the cells and suppressed ACTH-induced steroid production. Abnormalities in the pituitary-adrenal axis in adrenoleukomyeloneuropathy have been considered to be solely attributable to destruction of the adrenal cortex. In the current case, however, large molecular weight ACTH immunoactivity is present and might have some role in the adrenocortical dysfunction.

Autoantibody to growth hormone in a patient with myasthenia gravis.

An autoantibody to GH was detected in the serum from a patient with myasthenia gravis (MG) who had never been prescribed GH. Using an immunoprecipitation technique, this autoantibody was found to belong to the IgG class and had a kappa chain. The dissociation constant of the antibody was 56.8 nmol/l and the binding capacity was 37 nmol/l. Serum samples from another 130 patients, including 37 with MG, were examined, but the GH autoantibody could not be detected. To our knowledge, this is the first report demonstrating the presence of a GH autoantibody.

Effects of ketanserin tartrate on serum lipids in patients with essential hypertension.

Several antihypertensive agents such as thiazide diuretics and some beta-blockers have recently been shown to adversely affect lipid metabolism. Moreover, there is a growing suspicion that the adverse effect on plasma lipids might outweigh the favourable effect of lowering blood pressure. The effect of ketanserin tartrate (20 to 60 mg daily), a new antihypertensive drug, on blood lipids was evaluated in a 12-week non-comparative clinical trial in 34 patients with mild or moderate hypertension. Ketanserin reduced systolic and diastolic blood pressure by 12.2 and 9.8%, respectively, without altering heart rates. Total cholesterol and low density lipoprotein (LDL)-cholesterol levels in the fasting plasma were observed to decrease significantly by 6.3 and 8.8% respectively, whereas mean triglyceride and high density lipoprotein (HDL)-cholesterol remained almost unchanged. These changes were consistent irrespective of their initial values. Significant decrease in apolipoprotein B and E was also observed. Apolipoprotein A-I, A-II, C-II and C-III were not altered significantly. It is speculated that ketanserin affects mainly LDL-cholesterol. Based on these findings, ketanserin is considered to have a potentially beneficial effect on coronary risk profile and should be given full consideration when drug therapy is selected for patients with mild to moderate hypertension.