Long‐term effectiveness of HPV vaccination against HPV infection in young Japanese women: Real‐world data

In Japan, public funding for HPV vaccination began in 2010 for girls aged 13–16 years (birth cohort years 1994–1997) and women born in 1994 who turned 25 in 2019. We aimed to verify the long‐term effectiveness of the bivalent HPV vaccine in women aged 25 years. Subjects were women aged 25–26 years who underwent cervical cancer screening and HPV testing in Niigata from 2019 to 2020 (birth cohort years 1993–1994). Information on vaccination status and sexual behavior was obtained from a questionnaire and municipal records. We compared the HPV infection rates of the vaccinated and unvaccinated groups. Of the 429 registrants, 150 (35.0%) and 279 (65.0%) were vaccinated and unvaccinated, respectively. The average period from HPV vaccination to HPV testing was 102.7 months (8.6 years), with a median of 103 months (range 92–109 months). The HPV high‐risk infection rate was 21.3% (32/150) in the vaccinated group and 23.7% (66/279) in the unvaccinated group (P = 0.63). The HPV16/18 infection rate was 0% (0/150) in the vaccinated group and 5.4% (15/279) in the unvaccinated group, showing a significant difference (P = 0.0018), and the vaccine effectiveness was 100%. The cross‐protective type HPV31/45/52 infection rate in the vaccinated group was significantly lower than that in the unvaccinated group (3.3% vs. 10.0%, P = 0.013). There was no significant difference in the mean age at sexual debut and the number of previous sexual partners between the two groups. We have demonstrated the long‐term 9‐year effectiveness of the bivalent vaccine against HPV infection for the first time in Japan.     

Comparison Evaluation of the Biological Effects of Sterigmatocystin and Aflatoxin B1 Utilizing SOS-Chromotest and a Novel Zebrafish (Danio rerio) Embryo Microinjection Method

Aflatoxin B1 (AFB1) is a potent mycotoxin and natural carcinogen. The primary producers of AFB1 are Aspergillus flavus and A. parasiticus. Sterigmatocystin (STC), another mycotoxin, shares its biosynthetic pathway with aflatoxins. While there are abundant data on the biological effects of AFB1, STC is not well characterised. According to published data, AFB1 is more harmful to biological systems than STC. It has been suggested that STC is about one-tenth as potent a mutagen as AFB1 as measured by the Ames test. In this research, the biological effects of S9 rat liver homogenate-activated and non-activated STC and AFB1 were compared using two different biomonitoring systems, SOS-Chromotest and a recently developed microinjection zebrafish embryo method. When comparing the treatments, activated STC caused the highest mortality and number of DNA strand breaks across all injected volumes. Based on the E. coli SOS-Chromotest, the two toxins exerted the same genotoxicities. Moreover, according to the newly developed zebrafish microinjection method, STC appeared more toxic than AFB1. The scarce information correlating AFB1 and STC toxicity suggests that AFB1 is a more potent genotoxin than STC. Our findings contradict this assumption and illustrate the need for more complex biomonitoring systems for mycotoxin risk assessment.     

Comprehensive Systematic Review Update Summary: Disorders of Consciousness: Report of the Guideline Development,Dissemination, and Implementation Subcommittee of the American Academy of Neurology; the American Congress of Rehabilitation Medicine; and the National Institute on Disability,Independent Living,and Rehabilitation Research

Objective

To update the 1995 American Academy of Neurology (AAN) practice parameter on persistent vegetative state and the 2002 case definition for the minimally conscious state (MCS) by reviewing the literature on the diagnosis, natural history, prognosis, and treatment of disorders of consciousness lasting at least 28 days.

A national study on conditional survival,excess mortality and second cancer after high dose therapy with autologous stem cell transplantation for non‐Hodgkin lymphoma

This national population‐based study aimed to investigate conditional survival and standardized mortality ratios (SMR) after high‐dose therapy with autologous stem‐cell transplantation (HDT‐ASCT) for non‐Hodgkin lymphoma (NHL), and to analyse cause of death, relapses and second malignancies. All patients ≥18 years treated with HDT‐ASCT for NHL in Norway between 1987 and 2008 were included (n = 578). Information from the Cause of Death Registry and Cancer Registry of Norway were linked with clinical data. The 5‐, 10‐ and 20‐year overall survival was 61% (95% confidence interval [CI] 56–64%), 52% (95%CI 48–56%) and 45% (95%CI 40–50%), respectively. The 5‐year survival conditional on having survived 2, 5 and 10 years after HDT‐ASCT was 81%, 86% and 93%. SMRs were 12·3 (95%CI 11·0–13·9), 4·9 (95%CI 4·1–5·9), 2·4 (95%CI 1·8–3·2) and 1·0 (95%CI 0·6–1·8) for the entire cohort and for patients having survived 2, 5 and 10 years after HDT‐ASCT respectively. Of the 281 deaths observed, 77% were relapse‐related. Treatment‐related mortality was 3·6%. The 10‐year cumulative incidence of second malignancies was 7·9% and standardized incidence ratio was 2·0 (95%CI 1·5–2·6). NHL patients treated with HDT‐ASCT were at increased risk of second cancer and premature death. The mortality was still elevated at 5 years, but after 10 years mortality equalled that of the general population.     

Major life events and risk of alcohol use disorders: a prospective cohort study

Aims

To estimate associations of individual major life events as well as accumulated major life events in childhood, adult private life and adult work life with risk of alcohol use disorders (AUD).

Design

Prospective cohort study with baseline examination in 1991–93 and linkage to national registers to identify AUD at follow‐up.

Setting

Copenhagen, Denmark.

Participants

Individuals (aged 21–93 years) who participated in the Copenhagen City Heart Study in 1991–93 (n = 8758).

Measurements

The primary outcome was first registration with AUD during follow‐up (n = 249). AUD was identified in the Danish National Patient Register, in the Danish Psychiatric Central Register and in an outpatient treatment register. Major life events were assessed by a questionnaire in the Copenhagen City Heart study. Data were analysed by Cox proportional hazards models adjusted for age, sex, educational level, household income, cohabitation status and psychiatric comorbidity.

Findings

Serious family conflicts in childhood [hazard ratio (HR) = 1.35; 95% confidence interval (CI) = 1.00, 1.83] and serious economic problems in adult life (HR = 2.22; 95% CI = 1.64, 3.01) were associated significantly with increased risk of AUD. Prospective analyses did not show consistent effects of accumulation of major life events in childhood or adult life, but an additional analysis based on all AUD registrations suggested an association between accumulated childhood events and risk of AUD.

Conclusions

Serious economic problems in adult life are associated strongly with risk of alcohol use disorders, and there may be an influence of accumulated childhood events on risk of alcohol use disorders.     

Serum IL-21 levels are elevated in atopic dermatitis patients with acute skin lesions

Background

Interleukin (IL)-21 is a member of the type I cytokine family and plays a role in the pathogenesis of T helper type 2 allergic diseases. It has been reported that IL-21 expression is upregulated in acute skin lesions in atopic dermatitis (AD) patients; however, little is known about the serum IL-21 levels of AD patients. The aim of this study was to quantify the serum IL-21 levels of AD patients and to evaluate the relationships between the serum IL-21 level and disease severity, laboratory markers, and eruption type in AD patients.

Signalling pathways identified in salivary glands from primary Sjögren’s syndrome patients reveal enhanced adipose tissue development

A characteristic feature of primary Sjögren’s syndrome (pSS) is the destruction of salivary and lacrimal glands mediated by mononuclear cell infiltration. Adipocytes can also occupy a large portion of the salivary gland (SG) tissue area, although little is known about their significance in pSS. We have previously investigated adipose tissue infiltration in SG biopsies from pSS patients and non-SS sicca controls. Our findings indicated the distinct incidence of adipose tissue replacement in pSS patients, where adipocytes were detected in interleukin (IL) 6 rich regions. We now aimed to examine the development of adipocytes in the SG microenvironment, and delineate their possible involvement in immune reactions. A microarray analysis was performed on SG from 6 pSS patients and 6 non-SS controls, where the expression levels of genes involved in adipose tissue development, inflammatory responses, and lymphoma development were assessed. Real-time PCR was carried out on SG from 14 pSS patients and 15 non-SS controls to account for IL6, IL10, and IL17 mRNA levels. Immunohistochemical staining of frozen SG tissue using IL17 was also conducted. Our results indicate signalling pathways identified in SG of pSS patients displayed genes leading to prominent adipose tissue development and reduced mitochondrial fatty acid beta-oxidation (ARID5B, OXCT1, BDH1, SOX8, HMGCS2, FTO, ECHS1, PCCA, ACADL and ACADVL), inflammatory responses (IL1R1, IL7R, IL10RA, IL15, IL18RAP, CCL2, CCL5, CCL22, CXCR6, CD14, and CD48), and lymphoma development via JAK-STAT signalling (STAT2, TYK2, EBI3, FAS, TNFRSF1B, MAP3K8, HMOX1, LTB, TNF, STAT1, and BAK1). Genes involved in interferon production and signalling were also detected (IRF1, IRF9, and IRF7), in addition to IL6, IL10, and IL17. Higher mRNA levels of IL6, IL17 and IL10 were observed in the SG of pSS patients compared to controls. Moreover, IL17 positive cells were detected mostly interstitially in the SG and around adipocytes, also within the focal infiltrates. In conclusion, adipocyte development seems to be more prominent in the SG of pSS patients, where adipose tissue replacement is also evident. Whether this is due to disease progression, or the repair process, remains to be investigated. Detection of IL17 positive adipocytes in the target organ suggests their involvement in immune reactions.     

Cardiovascular,hormonal and body fluid changes during prolonged exercise

Summary During prolonged heavy exercise a gradual upward drift in heart rate (HR) is seen after the first 10 min of exercise. This secondary rise might be caused by a reduction in stroke volume due to reduced filling of the heart, which is dependent upon both hemodynamic pressure and blood volume. Swimming and bicycling differ with respect to hydrostatic pressure and to water loss, due to sweating. Five subjects were studied during 90 min of bicycle exercise, and swimming the leg kick of free style. The horizontal position during swimming resulted in a larger cardiac output and stroke volume. After the initial rise in heart rate the secondary rise followed parallel courses in the two situations. The rises were positively related to the measured increments in plasma catecholamine concentrations, which continued to increase as exercise progresssed. The secondary rise in HR could not be explained by changes in plasma volume or in water balance, nor by changes in plasma [K]. The plasma volume decreased 5–6% (225–250 ml) within the first 5 to 10 min of exercise both in bicycling and swimming, but thereafter remained virtually unchanged. The sweat loss during bicycling was four times greater than during swimming; but during swimming the hydrostatic conditions induced a diuresis, so that the total water loss was only 25% less than during bicycling.     

Trajectories and stability of self‐reported short sleep duration from adolescence to adulthood

The trajectories and stability of self‐reported sleep duration recorded at ages 13, 15, and 23 years on reported sleep duration at age 30 years among 1105 students (55% male) who participated in the Norwegian Longitudinal Health and Behaviour Study were examined. Questionnaire data were used to obtain demographic and sleep variables. Dichotomised short sleep duration was based on normative values and set as ≤8.5 h (age 13 years), ≤8 h (age 15 years) and ≤7 h (ages 23 and 30 years). Results indicated a significant overall reduction in total sleep duration (h per night) across age groups. Sleep duration (continuous) at age 15 and 23 years (whole group) was moderately but positively correlated with sleep duration at age 30 years (P < 0.01). When split by sex, at age 15 years, this association was present among females only (P < 0.01); however, at age 23 years, this association was present in both male and females (both P < 0.001). Categorical short sleep at age 23 years (whole group) was associated with short sleep at age 30 years (unadjusted odds ratio = 3.67, 95% confidence interval 2.36–5.69). Following sex stratification, this effect was significant for both males (unadjusted odds ratio = 3.77, 95% confidence interval: 2.22–6.42) and females (unadjusted odds ratio = 2.71, 95% confidence interval: 1.46–5.04). No associations were noted for categorical short sleep at ages 13 or 15 years, and subsequent short sleep at 30 years. Habitual short sleep duration during middle adulthood is not sustained from the time of early adolescence. Rather, these trends appear to be formed during early adulthood.