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AnteayerPLOS ONE Medicine&Health

Retinoic acid-stimulated ERK1/2 pathway regulates meiotic initiation in cultured fetal germ cells

by Sung-Min Kim, Toshifumi Yokoyama, Dylan Ng, Ferhat Ulu, Yukiko Yamazaki

In murine fetal germ cells, retinoic acid (RA) is an extrinsic cue for meiotic initiation that stimulates transcriptional activation of the Stimulated by retinoic acid gene 8 (Stra8), which is required for entry of germ cells into meiotic prophase I. Canonically, the biological activities of RA are mediated by nuclear RA receptors. Recent studies in somatic cells found that RA noncanonically stimulates intracellular signal transduction pathways to regulate multiple cellular processes. In this study, using a germ cell culture system, we investigated (1) whether RA treatment activates any mitogen-activated protein kinase (MAPK) pathways in fetal germ cells at the time of sex differentiation, and (2) if this is the case, whether the corresponding RA-stimulated signaling pathway regulates Stra8 expression in fetal germ cells and their entry into meiosis. When XX germ cells at embryonic day (E) 12.5 were cultured with RA, the extracellular-signal-regulated kinase (ERK) 1/2 pathway was predominantly activated. MEK1/2 inhibitor (U0126) treatment suppressed the mRNA expressions of RA-induced Stra8 and meiotic marker genes (Rec8, Spo11, Dmc1, and Sycp3) in both XX and XY fetal germ cells. Furthermore, U0126 treatment dramatically reduced STRA8 protein levels and numbers of meiotic cells among cultured XX and XY fetal germ cells even in the presence of RA. Taken together, our results suggest the novel concept that the RA functions by stimulating the ERK1/2 pathway and that this activity is critical for Stra8 expression and meiotic progression in fetal germ cells.

Molecular characterisation of genital human papillomavirus among women in Southwestern, Nigeria

by Yewande T. Nejo, David O. Olaleye, Georgina N. Odaibo


Persistent infections with high-risk genital Human papillomavirus (HPV) especially types 16 and 18, are associated with cervical cancer. However, distribution of HPV types varies greatly across geographical regions and the available vaccines target only few types. This study was designed to determine the HPV types circulating in Southwestern Nigeria, thereby providing necessary information for effective control of the virus.


Endocervical swab samples were collected from a total of 295 consenting women attending routine cervical cancer screening, STI clinics and community-based outreach programme. Viral DNA was extracted from the samples and the consensus region of the HPV DNA was amplified by PCR using GP-E6/E7 primers. Type-specific nested multiplex PCR and Sanger sequencing were used to genotype the HPV isolates.


In this study, 51 (17.3%) individuals were positive for HPV DNA using consensus primers that target the E6/E7 genes but only 48 (16.3%) were genotyped. A total of 15 HPV types (HPV-6, 16, 18, 31, 33, 35, 42, 43, 44, 52, 58, 66, 74, 81, 86) were detected, with HPV-31 being the most predominant (32.8%), followed by HPV-35 (17.2%) and HPV-16 (15.5%). Two rare HPV types; 74 and 86 were also detected. The HPV-74 isolate had three nucleotide (CCT) insertions at E7 gene that translated into amino acid proline. Highest nucleotide substitutions (n = 32) were found in HPV-44 genotype. Among positive individuals, 20.8% had dual infections and 86.2% had High-risk HPV types.


Multiple Human papillomavirus types co-circulated in the study. Most of the circulating Human papillomavirus are high-risk type with type 31 being the most predominant. Although the implication of HPV-74 with proline insertion detected for the first time is unknown, it may have effect on the transformation potential of the virus. Polyvalent HPV vaccine will be more effective for the infection control in Nigeria.

Cerebellum-mediated trainability of eye and head movements for dynamic gazing

by Akiyoshi Matsugi, Naoki Yoshida, Satoru Nishishita, Yohei Okada, Nobuhiko Mori, Kosuke Oku, Shinya Douchi, Koichi Hosomi, Youichi Saitoh


To investigate whether gaze stabilization exercises (GSEs) improve eye and head movements and whether low-frequency cerebellar repetitive transcranial magnetic stimulation (rTMS) inhibits GSE trainability.


25 healthy adults (real rTMS, n = 12; sham rTMS, n = 13) were recruited. Real or sham rTMS was performed for 15 min (1 Hz, 900 stimulations). The center of the butterfly coil was set 1 cm below the inion in the real rTMS. Following stimulation, 10 trials of 1 min of a GSE were conducted at 1 min intervals. In the GSE, the subjects were instructed to stand upright and horizontally rotate their heads according to a beeping sound corresponding to 2 Hz and with a gaze point ahead of them. Electrooculograms were used to estimate the horizontal gaze direction of the right eye, and gyroscopic measurements were performed to estimate the horizontal head angular velocity during the GSE trials. The percentage change from the first trial of motion range of the eye and head was calculated for each measurement. The percent change of the eye/head range ratio was calculated to assess the synchronous changes of the eye and head movements as the exercise increased.


Bayesian two-way analysis of variance showed that cerebellar rTMS affected the eye motion range and eye/head range ratio. A post hoc comparison (Bayesian t-test) showed evidence that the eye motion range and eye/head range ratio were reduced in the fifth, sixth, and seventh trials compared with the first trial sham stimulation condition.


GSEs can modulate eye movements with respect to head movements, and the cerebellum may be associated with eye–head coordination trainability for dynamic gazing during head movements.

Institutional differences in USMLE Step 1 and 2 CK performance: Cross-sectional study of 89 US allopathic medical schools

by Jesse Burk-Rafel, Ricardo W. Pulido, Yousef Elfanagely, Joseph C. Kolars


The United States Medical Licensing Examination (USMLE) Step 1 and Step 2 Clinical Knowledge (CK) are important for trainee medical knowledge assessment and licensure, medical school program assessment, and residency program applicant screening. Little is known about how USMLE performance varies between institutions. This observational study attempts to identify institutions with above-predicted USMLE performance, which may indicate educational programs successful at promoting students’ medical knowledge.


Self-reported institution-level data was tabulated from publicly available US News and World Report and Association of American Medical Colleges publications for 131 US allopathic medical schools from 2012–2014. Bivariate and multiple linear regression were performed. The primary outcome was institutional mean USMLE Step 1 and Step 2 CK scores outside a 95% prediction interval (≥2 standard deviations above or below predicted) based on multiple regression accounting for students’ prior academic performance.


Eighty-nine US medical schools (54 public, 35 private) reported complete USMLE scores over the three-year study period, representing over 39,000 examinees. Institutional mean grade point average (GPA) and Medical College Admission Test score (MCAT) achieved an adjusted R2 of 72% for Step 1 (standardized βMCAT 0.7, βGPA 0.2) and 41% for Step 2 CK (standardized βMCAT 0.5, βGPA 0.3) in multiple regression. Using this regression model, 5 institutions were identified with above-predicted institutional USMLE performance, while 3 institutions had below-predicted performance.


This exploratory study identified several US allopathic medical schools with significant above- or below-predicted USMLE performance. Although limited by self-reported data, the findings raise questions about inter-institutional USMLE performance parity, and thus, educational parity. Additional work is needed to determine the etiology and robustness of the observed performance differences.

Carvedilol improves glucose tolerance and insulin sensitivity in treatment of adrenergic overdrive in high fat diet-induced obesity in mice

by Linh V. Nguyen, Quang V. Ta, Thao B. Dang, Phu H. Nguyen, Thach Nguyen, Thi Van Huyen Pham, Trang HT. Nguyen, Stephen Baker, Trung Le Tran, Dong Joo Yang, Ki Woo Kim, Khanh V. Doan

Catecholamine excess reflecting an adrenergic overdrive of the sympathetic nervous system (SNS) has been proposed to link to hyperleptinemia in obesity and may contribute to the development of metabolic disorders. However, relationship between the catecholamine level and plasma leptin in obesity has not yet been investigated. Moreover, whether pharmacological blockade of the adrenergic overdrive in obesity by the third-generation beta-blocker agents such as carvedilol could help to prevent metabolic disorders is controversial and remains to be determined. Using the high fat diet (HFD)-induced obese mouse model, we found that basal plasma norepinephrine, the principal catecholamine as an index of SNS activity, was persistently elevated and highly correlated with plasma leptin concentration during obesity development. Targeting the adrenergic overdrive from this chronic norepinephrine excess in HFD-induced obesity with carvedilol, a third-generation beta-blocker with vasodilating action, blunted the HFD-induced hepatic glucose over-production by suppressing the induction of gluconeogenic enzymes, and enhanced the muscular insulin signaling pathway. Furthermore, carvedilol treatment in HFD-induced obese mice decreased the enlargement of white adipose tissue and improved the glucose tolerance and insulin sensitivity without affecting body weight and blood glucose levels. Our results suggested that catecholamine excess in obesity might directly link to the hyperleptinemic condition and the therapeutic targeting of chronic adrenergic overdrive in obesity with carvedilol might be helpful to attenuate obesity-related metabolic disorders.

Incidence patterns of orofacial clefts in purebred dogs

by Nicholas Roman, Patrick C. Carney, Nadine Fiani, Santiago Peralta

Cleft lip (CL), cleft palate (CP) and cleft lip and palate (CLP) are the most common types of orofacial clefts in dogs. Orofacial clefts in dogs are clinically relevant because of the associated morbidity and high newborn mortality rate and are of interest as comparative models of disease. However, the incidence of CL, CP and CLP has not been investigated in purebred dogs, and the financial impact on breeders is unknown. The aims of this study were to document the incidence patterns of CL, CP and CLP in different breeds of dogs, determine whether defect phenotype is associated with skull type, genetic cluster and geographic location, and estimate the financial impact in breeding programs in the United States by means of an anonymous online survey. A total of 228 orofacial clefts were reported among 7,429 puppies whelped in the 12 preceding months. Breeds in the mastiff/terrier genetic cluster and brachycephalic breeds were predisposed to orofacial clefts. Certain breeds in the ancient genetic cluster were at increased odds of orofacial clefts. Male purebred dogs were at increased odds of CPs. Results confirm that brachycephalic breeds are overrepresented among cases of orofacial clefts. Furthermore, geographic region appeared to be a relevant risk factor and orofacial clefts represented a considerable financial loss to breeders. Improved understanding of the epidemiology of orofacial clefts (frequency, causes, predictors and risk factors) may help in identifying ways to minimize their occurrence. Information gained may potentially help veterinarians and researchers to diagnose, treat and prevent orofacial clefts.

Nonalcoholic fatty liver disease is an early predictor of metabolic diseases in a metabolically healthy population

by Seokhun Yang, Soongu Kwak, Jeong-Hoon Lee, Shinae Kang, Seung-Pyo Lee


The relationship between nonalcoholic fatty liver disease and incident metabolic syndrome in metabolically healthy subjects is unknown. We aimed to investigate whether nonalcoholic fatty liver disease is a predictor of future metabolic syndrome in metabolically healthy subjects.

Materials and methods

Subjects who underwent health evaluation at least twice between 2009 and 2015 from the National Health Insurance Service-National Sample Cohort in South Korea were included. Patients without obesity who had no metabolic syndrome components were finally analyzed (n = 28,880). The definition of nonalcoholic fatty liver disease was based on both the hepatic steatosis and fatty liver indices. The incidence of metabolic syndrome, prediabetes/type 2 diabetes, hypertension, and dyslipidemia was compared between the subjects with and without nonalcoholic fatty liver disease.


The presence of nonalcoholic fatty liver disease was associated with a higher risk of incident metabolic syndrome, prediabetes/type 2 diabetes, hypertension, and dyslipidemia in the entire cohort (metabolic syndrome: adjusted hazard ratio, 2.10; 95% confidence interval, 1.18–3.71; prediabetes/type 2 diabetes: adjusted hazard ratio, 1.42; 95% confidence interval, 1.06–1.90; hypertension: adjusted hazard ratio, 2.36; 95% confidence interval, 1.35–4.12; dyslipidemia: adjusted hazard ratio, 1.49; 95% confidence interval, 1.07–2.06). A similar finding was observed in the age-, sex-, smoking status-, and body mass index-based 1:5 propensity score-matched cohort of 1,092 subjects (metabolic syndrome: adjusted hazard ratio, 3.56; 95% confidence interval, 1.79–7.07; prediabetes/type 2 diabetes: adjusted hazard ratio, 1.97; 95% confidence interval, 1.04–3.73; hypertension: adjusted hazard ratio, 2.57; 95% confidence interval, 1.35–4.88; dyslipidemia: adjusted hazard ratio, 1.61; 95% confidence interval, 1.12–2.32).


Nonalcoholic fatty liver disease is an early predictor of metabolic dysfunction even in metabolically healthy populations.

Voluntary medical male circumcision for HIV prevention among adolescents in Kenya: Unintended consequences of pursuing service-delivery targets

by Adam Gilbertson, Barrack Ongili, Frederick S. Odongo, Denise D. Hallfors, Stuart Rennie, Daniel Kwaro, Winnie K. Luseno


Voluntary medical male circumcision (VMMC) provides significant reductions in the risk of female-to-male HIV transmission. Since 2007, VMMC has been a key component of the United States President’s Emergency Plan for AIDS Relief’s (PEPFAR) strategy to mitigate the HIV epidemic in countries with high HIV prevalence and low circumcision rates. To ensure intended effects, PEPFAR sets ambitious annual circumcision targets and provides funding to implementation partners to deliver local VMMC services. In Kenya to date, 1.9 million males have been circumcised; in 2017, 60% of circumcisions were among 10-14-year-olds. We conducted a qualitative field study to learn more about VMMC program implementation in Kenya.

Methods and results

The study setting was a region in Kenya with high HIV prevalence and low male circumcision rates. From March 2017 through April 2018, we carried out in-depth interviews with 29 VMMC stakeholders, including “mobilizers”, HIV counselors, clinical providers, schoolteachers, and policy professionals. Additionally, we undertook observation sessions at 14 VMMC clinics while services were provided and observed mobilization activities at 13 community venues including, two schools, four public marketplaces, two fishing villages, and five inland villages. Analysis of interview transcripts and observation field notes revealed multiple unintended consequences linked to the pursuit of targets. Ebbs and flows in the availability of school-age youths together with the drive to meet targets may result in increased burdens on clinics, long waits for care, potentially misleading mobilization practices, and deviations from the standard of care.


Our findings indicate shortcomings in the quality of procedures in VMMC programs in a low-resource setting, and more importantly, that the pursuit of ambitious public health targets may lead to compromised service delivery and protocol adherence. There is a need to develop improved or alternative systems to balance the goal of increasing service uptake with the responsible conduct of VMMC.

One simple claudication question as first step in Peripheral Arterial Disease (PAD) screening: A meta-analysis of the association with reduced Ankle Brachial Index (ABI) in 27,945 subjects

by Arne Georg Kieback, Christine Espinola-Klein, Claudia Lamina, Susanne Moebus, Daniel Tiller, Roberto Lorbeer, Andreas Schulz, Christa Meisinger, Daniel Medenwald, Raimund Erbel, Alexander Kluttig, Philipp S. Wild, Florian Kronenberg, Knut Kröger, Till Ittermann, Marcus Dörr

Purpose and methods

A meta-analysis using data from seven German population-based cohorts was performed by the German Epidemiological consortium of Peripheral Arterial Disease (GEPArD) to investigate whether one question about claudication is more efficient for PAD screening than established questionnaires. Claudication was defined on the basis of the answer to one question asking for pain in the leg during normal walking. This simple question was compared with established questionnaires, including the Edinburgh questionnaire. The associations of claudication with continuous ABI values and decreased ABI were analyzed by linear and logistic regression analysis, respectively. The results of the studies were pooled in a random effect meta-analysis, which included data from 27,945 individuals (14,052 women, age range 20–84 years).


Meta-analysis revealed a significant negative association between claudication and ABI, which was stronger in men (β = -0.07; 95%CI -0.10, -0.04) than in women (β = -0.02; 95%CI -0.02, -0.01). Likewise, the presence of claudication symptoms was related to an increased odds of a decreased ABI in both men (Odds ratio = 5.40; 95%CI 4.20, 6.96) and women (Odds ratio = 1.99; 95%CI 1.58, 2.51).


Asking only one question about claudication was able to identify many individuals with a high likelihood of a reduced ABI with markedly higher sensitivity and only slightly reduced specificity compared to more complex questionnaires. At least in men, this question should be established as first screening step.

Psychological and physiological effects of applying self-control to the mobile phone

by David M. Markowitz, Jeffrey T. Hancock, Jeremy N. Bailenson, Byron Reeves

This preregistered study examined the psychological and physiological consequences of exercising self-control with the mobile phone. A total of 125 participants were randomly assigned to sit in an unadorned room for six minutes and either (a) use their mobile phone, (b) sit alone with no phone, or (c) sit with their device but resist using it. Consistent with prior work, participants self-reported more concentration difficulty and more mind wandering with no device present compared to using the phone. Resisting the phone led to greater perceived concentration abilities than sitting without the device (not having external stimulation). Failing to replicate prior work, however, participants without external stimulation did not rate the experience as less enjoyable or more boring than having something to do. We also observed that skin conductance data were consistent across conditions for the first three-minutes of the experiment, after which participants who resisted the phone were less aroused than those who were without the phone. We discuss how the findings contribute to our understanding of exercising self-control with mobile media and how psychological consequences, such as increased mind wandering and focusing challenges, relate to periods of idleness or free thinking.

Molecular validation of clinical <i>Pantoea</i> isolates identified by MALDI-TOF

by Craig D. Soutar, John Stavrinides

The Enterobacterial genus Pantoea contains both free-living and host-associating species, with considerable debate as to whether documented reports of human infections by members of this species group are accurate. MALDI-TOF-based identification methods are commonly used in clinical laboratories as a rapid means of identification, but its reliability for identification of Pantoea species is unclear. In this study, we carried out cpn60-based molecular typing of 54 clinical isolates that had been identified as Pantoea using MALDI-TOF and other clinical typing methods. We found that 24% had been misidentified, and were actually strains of Citrobacter, Enterobacter, Kosakonia, Klebsiella, Pseudocitrobacter, members of the newly described Erwinia gerundensis, and even several unclassified members of the Enterobacteriaceae. The 40 clinical strains that were confirmed to be Pantoea were identified as Pantoea agglomerans, Pantoea allii, Pantoea dispersa, Pantoea eucalypti, and Pantoea septica as well as the proposed species group, Pantoea latae. Some species groups considered largely environmental or plant-associated, such as P. allii and P. eucalypti were also among clinical specimens. Our results indicate that MALDI-TOF-based identification methods may misidentify strains of the Enterobacteriaceae as Pantoea.

A qualitative research synthesis of contextual factors contributing to female overweight and obesity over the life course in sub-Saharan Africa

by Ifeoma D. Ozodiegwu, Mary Ann Littleton, Christian Nwabueze, Oluwaseun Famojuro, Megan Quinn, Richard Wallace, Hadii M. Mamudu


Adult women are disproportionately affected by overweight and obesity in Sub-Saharan African (SSA) countries. Existing evidence on the sociocultural context remains unconsolidated. In this qualitative research synthesis, we aggregate research literature on contextual factors that potentially predispose adult women and adolescent girls to overweight and obesity to inform research, policies and programs over the life course.


PubMed, CINAHL, PsychInfo, ProQuest Central, EMBASE, and Web of Science were searched to locate qualitative research articles conducted in SSA countries beginning in the year 2000. After assessment for eligibility and critical appraisal, 17 studies were included in the synthesis. Textual data and quotes were synthesized using meta-aggregation methods proposed by the Joanna Briggs Institute.


The synthesized studies were conducted in South Africa, Ghana, Kenya and Botswana. The three overarching themes across these studies were body size and shape ideals, barriers to healthy eating, and barriers to physical activity, with cultural and social factors as cross-cutting influences within the major themes. Culturally, the supposedly ideal African woman was expected to be overweight or obese, and voluptuous, and this was associated with their identity. Although being overweight or obese was not acceptable to adolescent girls, they desired to be voluptuous. Healthy food choices among women and adolescent girls were hampered by several factors including affordability of nutritious foods and peer victimization. Both adult women and adolescent girls experienced ageism as a barrier to physical activity.


This is the first qualitative research synthesis to amplify the voices of women and girls in SSA countries highlighting the challenges they face in maintaining a healthy body weight. Sociocultural, institutional and peer-related factors were powerful forces shaping body size preferences, food choices and participation in physical activity. Our study findings provide insights for the design of contextually appropriate obesity prevention interventions and lay the foundation for further research studies.

Occurrence and multilocus genotyping of <i>Giardia duodenalis</i> from post-weaned dairy calves in Sichuan province, China

by Jiaming Dan, Xueping Zhang, Zhihua Ren, Liqin Wang, Suizhong Cao, Liuhong Shen, Junliang Deng, Zhicai Zuo, Shumin Yu, Ya Wang, Xiaoping Ma, Haifeng Liu, Ziyao Zhou, Yanchun Hu, Hualin Fu, Changliang He, Yi Geng, Xiaobin Gu, Guangneng Peng, Zhijun Zhong

Giardia duodenalis is a zoonotic parasitic protist and poses a threat to human and animal health. This study investigated the occurrence of G. duodenalis infection in post-weaned calves from Sichuan province, China. Faecal samples were collected from a total of 306 post-weaned calves (3–12 months old) from 10 farms, including 4 intensive feeding farms and 6 free-ranging farms. The overall infection rate of G. duodenalis was 41.2% (126/306) based on the PCR results at any of the three genetic loci: beta-giardin (bg), triose-phosphate isomerase (tpi) and glutamate dehydrogenase (gdh) genes. Giardia duodenalis assemblages E (n = 115, 91.3%), A (n = 3, 2.4%), and A mixed with E (n = 8, 6.3%) were identified among the 126 positive specimens. Multilocus sequence typing of G. duodenalis revealed 34 assemblage E multilocus genotypes (MLGs), 1 assemblage A MLG and 7 mixed assemblage (A and E) MLGs. The eBURST data showed a high degree of genetic diversity within assemblage E MLGs. The phylogenetic tree revealed that MLG E3 was the primary MLG subtype in Sichuan province and also the most widely distributed in China.

Exploring the influence of self-perceptions on the relationship between motor competence and identity in adolescents

by Amanda Timler, Fleur McIntyre, Elizabeth Rose, Beth Hands

Background and aims

A relationship exists between an adolescent’s level of motor competence and the health of their identity. As those with low motor competence (LMC) form less healthy identities, the aim of this study was to investigate if self-perceptions mediated the negative impact of LMC on identity health.


Adolescents (N = 160) completed the Adolescent Motor Competence Questionnaire (AMCQ), Assessment of Identity Development in Adolescence (AIDA) and the Self Perception Profile for Adolescence (SPPA). The mediating effect of their self-perceptions on the relationship between motor competence and identity health was examined in several ways: for the total sample, between male and females, and level of motor competence. Two motor competence groups were formed by dichotomizing their AMCQ scores ( Results

There was an indirect effect of self-perceptions of social competence, physical appearance, romantic appeal, behavioural conduct, close friendships and global self-worth on the relationship between motor competence and identity health for the total sample (N = 160, 64.4% males, Mage = 14.45 SD = .75, 12 to 16 years). No indirect effects were significant for females however close friendships and global self-worth were significant for the males. When the sample was grouped for motor competence, indirect effects of social competence, athletic competence, physical appearance, behavioural conduct, and global self-worth were significant for the high motor competence (HMC) group. The only self-perception significant for the LMC group was close friendships.


Self-perceptions in several domains mediated the relationship between motor competence and identity health, and these differed for level of motor competence but not gender. Those with LMC who had a higher self-perception in the close friendships domain had a healthier identity. Designing physical activity programs that focus on skill development and forming close friendships are important for adolescents with LMC.

Hypoxia inhibits TNF-α-induced TSLP expression in keratinocytes

by Naoyuki Tashiro, Ryosuke Segawa, Ryozo Tobita, Sanki Asakawa, Natsumi Mizuno, Masahiro Hiratsuka, Noriyasu Hirasawa

The expression of thymic stromal lymphopoietin (TSLP), a cytokine which greatly contributes to the induction of type I allergy, is upregulated in chronic inflammation such as atopic dermatitis and psoriasis. As hypoxia in the epidermis is important for maintaining skin homeostasis, we examined the regulation of TSLP expression by hypoxic conditions in normal skin epithelial tissues. TNF-α-induced expression of TSLP in human keratinocyte HaCaT and in mouse keratinocyte PAM212 cell lines were inhibited under hypoxic condition (1% O2), although the mRNA expressions of TNF-α, IL-6, IL-8, MCP-1, and VEGF-A were not inhibited. Hypoxia-mimicking conditions, which include NiCl2, CoCl2, and DMOG, an inhibitor of 2-oxoglutarate-dependent enzymes, also selectively inhibited TNF-α-induced TSLP expression. These results suggested that inactivation of prolyl hydroxylase by hypoxia and hypoxia-mimicking conditions is involved in the repression of TNF-α-induced TSLP expression. Interestingly, the inhibition of TSLP production by hypoxic treatment was significantly reversed by treatment with the HIF-2α antagonist but not with the HIF-1α inhibitor. DMOG-induced inhibition of TSLP promoter activity was dependent on the -71 to +185 bp promoter region, suggesting that the binding of HIF-2 to hypoxia response element (HRE) in this region repressed the TSLP expression. These results indicated that hypoxia and hypoxia-mimicking conditions inhibited TSLP expression via HIF-2 and HRE-dependent mechanisms. Therefore, PHD and HIF-2α could be a new strategy for treatment of atopic dermatitis and psoriasis.

Awareness of family health history in a predominantly young adult population

by Sarina Madhavan, Emily Bullis, Rachel Myers, Chris J. Zhou, Elise M. Cai, Anu Sharma, Shreya Bhatia, Lori A. Orlando, Susanne B. Haga

Family health history (FHH) is a key predictor of health risk and is universally important in preventive care. However, patients may not be aware of the importance of FHH, and thus, may fail to accurately or completely share FHH with health providers, thereby limiting its utility. In this study, we conducted an online survey of 294 young adults and employees based at a US university setting regarding their knowledge, sharing behaviors, and perceived importance of FHH, and use of electronic clinical tools to document and update FHH. We also evaluated two educational interventions (written and video) to promote knowledge about FHH and its importance to health. We found that 93% of respondents were highly aware of their FHH, though only 39% reported collecting it and 4% using an online FHH tool. Seventy-three percent of respondents, particularly women, had shared FHH with their doctor when prompted, and fewer had shared it with family members. Participants in the video group were significantly more likely to understand the benefits of FHH than those in the written group (p = 0.02). In summary, educational resources, either video or written, will be helpful to promote FHH collection, sharing, and use of online FHH tools.

A participatory community case study of periurban coastal flood vulnerability in southern Ecuador

by Erica Tauzer, Mercy J Borbor-Cordova, Jhoyzett Mendoza, Telmo De La Cuadra, Jorge Cunalata, Anna M Stewart-Ibarra


Populations in coastal cities are exposed to increasing risk of flooding, resulting in rising damages to health and assets. Adaptation measures, such as early warning systems for floods (EWSFs), have the potential to reduce the risk and impact of flood events when tailored to reflect the local social-ecological context and needs. Community perceptions and experiences play a critical role in risk management, since perceptions influence people’s behaviors in response to EWSFs and other interventions.


We investigated community perceptions and responses in flood-prone periurban areas in the coastal city of Machala, Ecuador. Focus groups (n = 11) were held with community members (n = 65 people) to assess perceptions of flood exposure, sensitivity, adaptive capacity, and current alert systems. Discussions were audio recorded, transcribed, and coded by topic. Participatory maps were field validated, georeferenced, and digitized using GIS software. Qualitative data were triangulated with historical government information on rainfall, flood events, population demographics, and disease outbreaks.


Flooding was associated with seasonal rainfall, El Niño events, high ocean tides, blocked drainage areas, overflowing canals, collapsed sewer systems, and low local elevation. Participatory maps revealed spatial heterogeneity in perceived flood risk across the community. Ten areas of special concern were mapped, including places with strong currents during floods, low elevation areas with schools and homes, and other places that accumulate stagnant water. Sensitive populations included children, the elderly, physically handicapped people, low-income families, and recent migrants. Flood impacts included damages to property and infrastructure, power outages, and the economic cost of rebuilding/repairs. Health impacts included outbreaks of infectious diseases, skin infections, snakebite, and injury/drowning. Adaptive capacity was weakest during the preparation and recovery stages of flooding. Participants perceived that their capacity to take action was limited by a lack of social organization, political engagement, and financial capital. People perceived that flood forecasts were too general, and instead relied on alerts via social media.


This study highlights the challenges and opportunities for climate change adaptation in coastal cities. Areas of special concern provide clear local policy targets. The participatory approach presented here (1) provides important context to shape local policy and interventions in Ecuador, complimenting data gathered through standard flood reports, (2) provides a voice for marginalized communities and a mechanism to raise local awareness, and (3) provides a research framework that can be adapted to other resource-limited coastal communities at risk of flooding.

Do older English adults exhibit day-to-day compensation in sedentary time and in prolonged sedentary bouts? An EPIC-Norfolk cohort analysis

by Dharani Yerrakalva, Katrien Wijndaele, Samantha Hajna, Kate Westgate, Kay-Tee Khaw, Nick Wareham, Simon J. Griffin, Soren Brage


Compensatory behaviours may be one of the reasons for the limited success of sedentary time interventions in older adults, but this possibility remains unexplored. Activity compensation is the idea that if we change activity levels at one time we compensate for them at a later time to maintain a set point. We aimed to assess, among adults aged ≥60 years, whether sedentary time and time spent in prolonged sedentary bouts (≥30 mins) on one day were associated with sedentary time and time spent in prolonged sedentary bouts (≥30 mins) on the following day. We also sought to determine whether these associations varied by sociodemographic and comorbid factors.


Sedentary time was assessed for seven days using hip-worn accelerometers (ActiGraph GT1M) for 3459 adults who participated in the EPIC-Norfolk Study between 2004 and 2011. We assessed day-to-day associations in total and prolonged bouts of sedentary time using multi-level regressions. We included interaction terms to determine whether associations varied by age, sex, smoking, body mass index, social class, retirement, education and comorbid factors (stroke, diabetes, myocardial infarction and cancer).


Participants (mean age = 70.3, SD = 6.8 years) accumulated 540 sedentary mins/day (SD = 80.1). On any given day, every 60 minutes spent in sedentary time was associated with 9.9 extra sedentary minutes on the following day (95% CI 9.0, 10.2). This association was greater in non-retired compared to retired participants (non-retired 2.57 extra minutes, p = 0.024) and in current compared to former and never-smokers (5.26 extra mins for current vs former; 5.52 extra mins for current vs never, p = 0.023 and 0.017, respectively). On any given day, every 60 minutes spent in prolonged bouts was associated with 7.8 extra minutes in these bouts the following day (95% CI 7.6, 8.4). This association was greater in older individuals (0.18 extra minutes/year of age, 95% CI 0.061, 0.29), and for retired versus non-retired (retired 2.74 extra minutes, 95% CI 0.21, 5.74).


Older adults did not display day-to-day compensation. Instead, individuals demonstrate a large stable component of day-to-day time spent sedentary and in prolonged bouts with a small but important capacity for positive variation. Therefore older adults appear to be largely habitual in their sedentary behaviour. Strategies to augment these patterns may be possible, given they may differ by age, smoking, and working status.

A localized sanitation status index as a proxy for fecal contamination in urban Maputo, Mozambique

by Drew Capone, Zaida Adriano, David Berendes, Oliver Cumming, Robert Dreibelbis, David A. Holcomb, Jackie Knee, Ian Ross, Joe Brown

Sanitary surveys are used in low- and middle-income countries to assess water, sanitation, and hygiene conditions, but have rarely been compared with direct measures of environmental fecal contamination. We conducted a cross-sectional assessment of sanitary conditions and E. coli counts in soils and on surfaces of compounds (household clusters) in low-income neighborhoods of Maputo, Mozambique. We adapted the World Bank’s Urban Sanitation Status Index to implement a sanitary survey tool specifically for compounds: a Localized Sanitation Status Index (LSSI) ranging from zero (poor sanitary conditions) to one (better sanitary conditions) calculated from 20 variables that characterized local sanitary conditions. We measured the variation in the LSSI with E. coli counts in soil (nine locations/compound) and surface swabs (seven locations/compound) in 80 compounds to assess reliability. Multivariable regression indicated that a ten-percentage point increase in LSSI was associated with 0.05 (95% CI: 0.00, 0.11) log10 fewer E. coli/dry gram in courtyard soil. Overall, the LSSI may be associated with fecal contamination in compound soil; however, the differences detected may not be meaningful in terms of public health hazards.

Association between hospital interval and survival in patients with oral cancer: A waiting time paradox

by José Luis Lopez-Cedrún, Ana Otero-Rico, Inés Vázquez-Mahía, Juan Seoane, Lucía García-Caballero, Juan Manuel Seoane-Romero, Pablo Varela-Centelles


In early diagnosis studies on symptomatic cancer, survival was the most recommended outcome. The magnitude and impact of the patient interval and primary care interval is well-known in oral cancer; however, the hospital interval and its influence on surviving this neoplasia are not well known.


To quantify the interval between the first contact with the specialist and the start of treatment for patients with oral cancer and to evaluate whether there was a link between this interval and disease survival.


We designed a hospital-based study that included 228 patients diagnosed with oral/oropharyngeal squamous cell carcinoma between 1998 and 2008 at A Coruña University Hospital (Spain) who were followed up until 2016. The data were extracted retrospectively from hospital medical charts. The study interval was defined in the context of the "pathways to treatment" model as the interval from the first specialist visit (start point) to the start of treatment (end point). We calculated the total interval (from first symptom to treatment) to evaluate the relative length of the hospital interval, and we considered the variables age, sex, location, comorbidity and tumour classification stage. Survival time was defined as the interval from the first treatment to death or censoring.


The median hospital interval was 20 days, with an interquartile range of 15–29.1 days. The most relevant prognostic variable was the tumour stage (III-IV: Exp. ß = 2.8, p = 0.001). The hospital interval was part of the multivariate model, and its association with mortality showed a V-shaped association, where patients with short hospital intervals (3–18 days) and those with long hospital intervals (26–55 days) had significantly higher mortality than those with medium hospital intervals (19–25 days).


The hospital interval represents a relevant interval for the patient’s path towards treatment, has prognostic implications and is subject to a severity bias (waiting time paradox) that should be avoided.