bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between complex multimorbidity, activities of daily living and mortality among older Norwegians. A prospective cohort study: the HUNT Study, Norway
Authors: Storeng Siri H. , Vinjerui Kristin H. , Sund Erik R. , Krokstad Steinar
Published: January 2020

Background

With increasing age, having multiple chronic conditions is the norm. It is of importance to study how co-existence of diseases affects functioning and mortality among older persons. Complex multimorbidity may be defined as three or more conditions affecting at least three different organ systems. The aim of this study was to investigate how complex multimorbidity affects activities of daily living and mortality amongst older Norwegians.

Methods

Participants were 60–69-year-olds at baseline in the Nord-Trøndelag Health Study 1995-1997 (HUNT2) n = 9058. Multinomial logistic regression models were used to investigate the association between complex multimorbidity in HUNT2, basic and instrumental activities of daily living in HUNT3 (2006–2008) and mortality during follow-up (n = 5819/5836). Risk ratios (RR) and risk differences (RD) in percentage points (pp) with 95% confidence intervals (CI) were reported.

Results

47.8% of 60–69-year-olds met the criteria of complex multimorbidity at baseline (HUNT2). Having complex multimorbidity was strongly associated with the need for assistance in IADL in HUNT3 11 years later (RR = 1.80 (1.58–2.04) and RD = 8.7 (6.8–10.5) pp) and moderately associated with mortality during the follow-up time (RR = 1.22 (1.12–1.33) and RD = 5.1 (2.9–7.3) pp). Complex multimorbidity was to a lesser extent associated with basic activities of daily living 11 years later (RR = 1.24 (0.85–1.83) and RD = 0.4 (− 0.3–1.1) pp).

Conclusions

This is the first study to show an association between complex multimorbidity and activities of daily living. Complex multimorbidity should receive more attention in order to prevent future disability amongst older persons.
Plasma levels of interleukin 27 in falciparum malaria is increased independently of co-infection with HIV: potential immune-regulatory role during malaria
Authors: Otterdal Kari , Berg Aase , Michelsen Annika E. , Patel Sam , Gregersen Ida , Sagen Ellen Lund , Halvorsen Bente , Yndestad Arne , Ueland Thor , Langeland Nina , Aukrust Pål
Published: January 2020

Background

The immune response during falciparum malaria mediates both harmful and protective effects on the host; however the participating molecules have not been fully defined. Interleukin (IL)-27 is a pleiotropic cytokine exerting both inflammatory and anti-inflammatory effects, but data on IL-27 in malaria patients are scarce.

Methods

Clinical data and blood samples were collected from adults in Mozambique with P. falciparum infection, with (n = 70) and without (n = 61) HIV-1 co-infection, from HIV-infected patients with similar symptoms without malaria (n = 58) and from healthy controls (n = 52). In vitro studies were performed in endothelial cells and PBMC using hemozoin crystals. Samples were analyzed using enzyme immunoassays and quantitative PCR.

Results

(i) IL-27 was markedly up-regulated in malaria patients compared with controls and HIV-infected patients without malaria, showing no relation to HIV co-infection. (ii) IL-27 was correlated with P. falciparum parasitemia and von Willebrand factor as a marker of endothelial activation, but not with disease severity. (iii) In vitro, IL-27 modulated the hemozoin-mediated cytokine response in endothelial cells and PBMC with enhancing effects on IL-6 and attenuating effects on IL-8.

Conclusion

Our findings show that IL-27 is regulated during falciparum malaria, mediating both inflammatory and anti-inflammatory effects, potentially playing an immune-regulatory role during falciparum malaria.
The diagnosis and treatment of adrenocortical carcinoma in pregnancy: a case report
Authors: Zhang Yuanli , Yuan Zeng , Qiu Chunping , Li Shuyi , Zhang Shiqian , Fang Yan
Published: January 2020

Background

Pregnancy complicated with adrenocortical carcinoma (ACC) is a sporadic syndrome that is characterized by hypertension, uncontrolled hypokalemia, severe heart failure, premature delivery and other adverse effects. The clinical presentation of adrenocortical carcinoma is vague and nonspecific, it is challenging to identify complications of pregnancy with adrenocortical carcinoma. Here we present a case of adrenocortical carcinoma during pregnancy. We describe how to distinguish secondary hypertension from other conditions and the importance of timely detection and treatment of such patients.

Case presentation

A 22-year-old woman 30 weeks pregnant was hospitalized with uncontrolled hypertension and hypokalemia. An ultrasound examination of the right adrenal gland revealed a large mass. She underwent transabdominal adrenalectomy, and histopathology from the sample removed revealed an adrenocortical carcinoma. Five days after surgery, the patient had a premature rupture of the fetal membranes and gave birth to a newborn girl via vaginal delivery at 32 weeks of gestation. The newborn was transferred to the neonatal pediatrics ward, and the woman started receiving chemotherapy.

Conclusions

Pregnancy with adrenocortical carcinoma is a rare condition. This case alerts the obstetricians that analysis of hypertension, hypokalemia, the plasma level and circadian rhythm of plasma cortisol provides a strategy to diagnose adrenocortical carcinoma during pregnancy.
Infant care practices and parent uptake of safe sleep messages: a cross-sectional survey in Queensland, Australia
Authors: Cole Roni , Young Jeanine , Kearney Lauren , Thompson John M. D.
Published: January 2020

Background

Globally, the incidence of sleep-related infant mortality declined dramatically following the first public health campaigns seen internationally in the 1990s to reduce the risks of sudden infant death. However, Australian Sudden Unexpected Death in Infancy (SUDI) rates have plateaued with little change in incidence since 2004 despite two further public health safe sleep campaigns. This study aims to describe contemporary infant care practices employed by families related to the current public health SUDI prevention program.

Methods

A cross-sectional survey of 3341 Queensland primary caregivers with infants approximately 3-months of age was conducted using the Queensland Registry of Births, Deaths and Marriages as a sampling frame. Surveys were returned either via reply-paid mail or online. Questionnaires explored prevalence of infant care practices and awareness of safe sleep recommendations. Univariable analysis was used to generate descriptive statistics for key variables.

Results

Overall, only 13% of families routinely practised all six ‘Safe Sleeping’ program messages. More than one third (1118, 34%) of infants had slept in a non-supine sleep position at some time. Potentially hazardous sleep environments were common, with 38% of infants sleeping with soft items or bulky bedding, or on soft surfaces. Nearly half, for either day- or night-time sleeps, were routinely placed in a sleep environment that was not designed or recommended for safe infant sleep (i.e. a bouncer, pram, beanbag). Most babies (84%) were reportedly smoke free before and after birth. Sleeping in the same room as their caregiver for night-time sleeps was usual practice for 75% of babies. Half (1600, 50%) of all babies shared a sleep surface in the last two-weeks. At 8-weeks, 17% of infants were no longer receiving any breastmilk.

Conclusions

The prevalence rates of infant care practices among this Australian population demonstrate many families continue to employ suboptimal practices despite Australia’s current safe sleep campaign. Strategic approaches together with informed decisions about pertinent messages to feature within future public health campaigns and government policies are required so targeted support can be provided to families with young infants to aid the translation of safe sleep evidence into safe sleeping practices.
Correlating maternal iodine status with neonatal thyroid function in two hospital populations in Ghana: a multicenter cross-sectional pilot study
Authors: Dei-Tutu Selorm A. , Manful Adoma , Heimburger Douglas C. , Malechi Hawa , Moore Daniel J. , Oppong Samuel A. , Russell William E. , Aliyu Muktar H.
Published: January 2020

Background

Congenital hypothyroidism is a common, yet easily treatable cause of poor growth and intellectual disability. Newborn screening programs play an important role in the early detection and treatment of congenital hypothyroidism. However, an estimated 71% of children are born in countries such as Ghana, which does not have a screening program. Iodine deficiency, a common cause of congenital hypothyroidism, is present in the Ghanaian population. Mild to moderate maternal iodine deficiency may negatively impact cognitive function in children. A structured approach to examine the association between maternal iodine levels and infant thyroid function may have important ramifications on our understanding of congenital hypothyroidism in Ghana. We investigated the hypothesis that maternal iodine deficiency impacts infant thyroid function, using Thyroid Stimulating Hormone (TSH) as a marker of thyroid function. We also explored potential opportunities and barriers to newborn screening for congenital hypothyroidism in Ghana.

Methods

This was a cross-sectional, multicenter pilot study of 250 women and their neonates recruited from post-natal clinics in Accra and Tamale, Ghana. We compared maternal urine iodine concentration and infant TSH, as well as maternal sociodemographic and nutrition information. Regression models were used to model the relationship between variables.

Results

Median infant TSH was 4.7 μIU/ml (95% CI: 3.9–5.5) in Accra. In Tamale, the median infant TSH was 3.5 μIU/ml (95%CI: 3.3 to 3.6) (Δ: 1.3 μIU/ml, 95% CI: 0.5–2.1,p = 0.002). Median maternal urine iodine concentrations were 141.0 μg/L (95% CI: 115.7 to 166.3) and 142.5 μg/L (95% CI: 125.1 to 160.0) in Accra and Tamale, respectively (Δ: − 1.5 μIU/ml, 95% CI: − 32.2 – 29.2,p = 0.925). There was a weakly positive correlation between maternal urine iodine and infant TSH (rho 0.1,p = 0.02). Almost one-third (30%) of women in both locations had biochemical evidence of iodine deficiency. Mothers with any formal education were more likely to have higher iodine levels than their counterparts who had no formal education (coefficient 0.31,p = 0.006).

Conclusions

Maternal iodine deficiency is prevalent in Ghana and is correlated to infant thyroid function. We recommend studies with larger sample sizes to assess the true scope of this relationship.
Inhibition of connexin 43 attenuates oxidative stress and apoptosis in human umbilical vein endothelial cells
Authors: Ma Jia-wei , Ji Dan-dan , Li Qian-qian , Zhang Ting , Luo Liang
Published: January 2020

Background

Previous studies demonstrated an important role for connexin 43 (Cx43) in the regulation of apoptosis by influencing mitochondrial functions. This study aimed to investigate the relationship between Cx43 and lipopolysaccharide (LPS)-induced oxidative stress and apoptosis in human umbilical vein endothelial cells (HUVECs).

Methods

Western blot was performed to determine mitochondrial Cx43 (MtCx43) protein level and phosphorylation (p-MtCx43). Gap19, a selective Cx43 inhibitor, was used to examine the effects of Cx43 on LPS-induced oxidative stress and apoptosis in HUVECs. Expression of regulatory genes associated with oxidative stress was examined by quantitative polymerase chain reaction (qPCR) and Western blot. Apoptosis was assessed by flow cytometry.

Results

LPS stimulation resulted in increased levels of MtCx43 and p-MtCx43. Interestingly, Gap19 antagonized the upregulation of glutathione S-transferase Zeta 1 (GSTZ1) and cytochrome b alpha beta (CYBB), and the downregulation of antioxidant 1 (ATOX1), glutathione synthetase (GSS) and heme oxygenase 1 (HMOX1) induced by LPS or Cx43 overexpression. Moreover, the increased production of reactive oxygen species (ROS) and apoptosis elicited by LPS or Cx43 overexpression were reduced following treatment with Gap19.

Conclusions

Selective inhibition of Cx43 hemichannels protects HUVECs from LPS-induced apoptosis and this may be via a reduction in oxidative stress production.
Factors associated with in-hospital mortality from community-acquired pneumonia in Portugal: 2000–2014
Authors: Pessoa Ezequiel , Bárbara Cristina , Viegas Laura , Costa Andreia , Rosa Matilde , Nogueira Paulo
Published: January 2020

Background

Community-acquired pneumonia (CAP) is one of the leading causes of morbidity and mortality worldwide, often leading to hospital admissions. In Portugal, the factors associated with in-hospital mortality due to CAP are not fully documented. The aim of this study was to characterize the trends of CAP hospitalization in all age groups and the factors associated with their mortality between 2000 and 2014.

Methods

We conducted a cross-sectional study using CAP hospitalization data in all age groups, in Portugal Mainland. Logistic regression was used to identify the factors associated with in-hospital mortality.

Results

Between 2001 and 2011, CAP hospitalization rate increased from 2.8 to 4.3 per 1000 population. Hospitalization rates were higher in the extreme ages ( ≤ 4 and  ≥ 75 years). However, a decrease in the hospitalization rate and its mortality was observed, in the younger ages.

A total of 548,699 hospitalization CAP episodes, between 2000 and 2014, were analyzed, with male (56.2%) and elderly ≥65 years (91.7%) predominance, resulting in 101,740 deaths (18.5%). Men had a significantly lower mean age (64.3 ± 26.4 years versus 67.9 ± 27.5 years;p < 0.001). During the studied 15 years, there was an increase of 45.2% in the number of annual hospitalizations, concomitant with the admission increase of individuals aged over 75 years. Since 2012 a decrease in hospitalizations and associated deaths were detected.

The increase in age represented a progressive and significant rise in the probability of death, except for the age group 1–4 years. The age group ≥85 years old (Adjusted OR = 124.256; 95%CI: 97.838–157.807) and males (Adjusted OR = 1.261; 95%CI: 1.243–1.280) were significantly associated with death risk for CAP hospitalization. After 2010, this risk decreased (Adjusted OR = 0.961; 95%CI: 0.940–0.982). The main factors affecting mortality were age, sex, unemployment rate, number of performed procedures and admission quinquennia.

Conclusions

Despite a trend of decrease in CAP hospitalizations and associated death since 2012, the numbers of in-hospital mortality showed, in the 15 years under analysis, an overall increase over time, mainly associated with age, in particular very old people ( ≥ 75 years), males and a higher parish unemployment rate. Therefore, the implementation of CAP preventive measures should be reinforced in these vulnerable groups.
Pulmonary inflammation-induced alterations in key regulators of mitophagy and mitochondrial biogenesis in murine skeletal muscle
Authors: Leermakers Pieter A. , Remels Alexander H. V. , Langen Ramon C. J. , Schols Annemie M. W. J. , Gosker Harry R.
Published: January 2020

Background

Both mitophagy, a selective mechanism for clearance of mitochondria, and mitochondrial biogenesis are key processes determining mitochondrial content and oxidative capacity of the musculature. Abnormalities in these processes could therefore contribute to deterioration of peripheral muscle oxidative capacity as observed in e.g. chronic obstructive pulmonary disease. Although it has been suggested that inflammatory mediators can modulate both mitophagy and mitochondrial biogenesis, it is unknown whether acute pulmonary inflammation affects these processes in oxidative and glycolytic skeletal muscle in vivo. Therefore, we hypothesised that molecular signalling patterns of mitochondrial breakdown and biogenesis temporally shift towards increased breakdown and decreased biogenesis in the skeletal muscle of mice exposed to one single bolus of IT-LPS, as a model for acute lung injury and pulmonary inflammation.

Methods

We investigated multiple important constituents and molecular regulators of mitochondrial breakdown, biogenesis, dynamics, and mitochondrial content in skeletal muscle over time in a murine (FVB/N background) model of acute pulmonary- and systemic inflammation induced by a single bolus of intra-tracheally (IT)-instilled lipopolysaccharide (LPS). Moreover, we compared the expression of these constituents between gastrocnemius and soleus muscle.

Results

Both in soleus and gastrocnemius muscle, IT-LPS instillation resulted in molecular patterns indicative of activation of mitophagy. This coincided with modulation of mRNA transcript abundance of genes involved in mitochondrial fusion and fission as well as an initial decrease and subsequent recovery of transcript levels of key proteins involved in the molecular regulation of mitochondrial biogenesis. Moreover, no solid differences in markers for mitochondrial content were found.

Conclusions

These data suggest that one bolus of IT-LPS results in a temporal modulation of mitochondrial clearance and biogenesis in both oxidative and glycolytic skeletal muscle, which is insufficient to result in a reduction of mitochondrial content.
A self-aggregating peptide: implications for the development of thermostable vaccine candidates
Authors: Cruz-Reséndiz Adolfo , Zepeda-Cervantes Jesús , Sampieri Alicia , Bastián-Eugenio Carlos , Acero Gonzalo , Sánchez-Betancourt J. Iván , Gevorkian Goar , Vaca Luis
Published: January 2020

Background

The use of biomaterials has been expanded to improve the characteristics of vaccines. Recently we have identified that the peptide PH(1–110) from polyhedrin self-aggregates and incorporates foreign proteins to form particles. We have proposed that this peptide can be used as an antigen carrying system for vaccines. However, the immune response generated by the antigen fused to the peptide has not been fully characterized. In addition, the adjuvant effect and thermostability of the particles has not been evaluated.

Results

In the present study we demonstrate the use of a system developed to generate nano and microparticles carrying as a fusion protein peptides or proteins of interest to be used as vaccines. These particles are purified easily by centrifugation. Immunization of animals with the particles in the absence of adjuvant result in a robust and long-lasting immune response. Proteins contained inside the particles are maintained for over 1 year at ambient temperature, preserving their immunological properties.

Conclusion

The rapid and efficient production of the particles in addition to the robust immune response they generate position this system as an excellent method for the rapid response against emerging diseases. The thermostability conferred by the particle system facilitates the distribution of the vaccines in developing countries or areas with no electricity.
Oral impact on daily performance (OIDP) scale for use in Sri Lankan adolescents: a cross sectional modification and validation study
Authors: Amilani Uttara , Jayasekara Prasanna , Perera Irosha R. , Carter Hannah E. , Senanayake Sameera , Kularatna Sanjeewa
Published: January 2020

Background

Oral Health Related Quality of Life (OHRQoL) measures play an important role in understanding subjective patient experiences in oral health care. The Oral Impact on Daily Performance (OIDP) scale is a validated OHRQoL tool that measures the impact and extent to which an individual’s daily activities may be compromised by their oral health. It is commonly used to facilitate oral health service planning. The aim of this study was to modify and validate a Sinhalese version of the OIDP for use in Sri Lankan adolescents.

Methods

Stage I involved cultural adaptation of the tool through translation and modification. Stage II involved the exploring factor structure, validation and a reliability assessment. After translation and cultural adaptation, stage II was conducted among 220 secondary school students aged 15–19 in the Gampaha district, Sri Lanka. Participants completed the modified OIDP scale along with questions on self-reported perceived oral health problems and treatment need which were used to assesses the concurrent validity of the modified OIDP scale. Factorability was assessed by inspection of correlation matrix and Kaiser-Meyer-Olkin and Bartlett’s Test of Sphericity tests as a measure of sampling adequacy. An exploratory factor analysis was carried out using Principal Component Analysis method and factors were rotated using the oblimin method.

Results

The Kaiser-Meyer-Olkin measure was 0.87 and Bartlett’s test of Sphericity was significant (p < 0.001) Cronbach’s alpha was calculated as 0.88, indicating a high level of internal consistency of the modified OIDP scale. The principal component analysis produced two factors with Eigen values ranging from 1.12 to 4.40, explaining 70.0% of total variance. Concurrent validity was satisfactory as the OIDP score increased when the adolescents’ perceived oral health decreased. The final modified OIDP consists of eight self-reported items which assesses the impact severity of eight daily performances over past three months. Participant scores ranged from 0 to 24 out of a worst possible score of 40, and nearly 48% of the responders reported at least one impact during past three months. The most prevalent oral health impact related to chewing and enjoying foods, reported by 36.8% of respondents.

Conclusion

This study suggests that the modified OIDP scale has promising psychometric properties and is appropriate for use among adolescents in Sri Lanka. Further research is required to test the validity of this tool in other cohorts.
Legal and ethical framework for global health information and biospecimen exchange - an international perspective
Authors: Bernasconi Lara , Şen Selçuk , Angerame Luca , Balyegisawa Apolo P. , Hong Yew Hui Damien , Hotter Maximilian , Hsu Chung Y. , Ito Tatsuya , Jörger Francisca , Krassnitzer Wolfgang , Phillips Adam T. , Li Rui , Stockley Louise , Tay Fabian , von Heijne Widlund Charlotte , Wan Ming , Wong Creany , Yau Henry , Hiemstra Thomas F. , Uresin Yagiz , Senti Gabriela
Published: January 2020

Background

The progress of electronic health technologies and biobanks holds enormous promise for efficient research. Evidence shows that studies based on sharing and secondary use of data/samples have the potential to significantly advance medical knowledge. However, sharing of such resources for international collaboration is hampered by the lack of clarity about ethical and legal requirements for transfer of data and samples across international borders.

Main text

Here, the International Clinical Trial Center Network (ICN) reports the legal and ethical requirements governing data and sample exchange (DSE) across four continents. The most recurring requirement is ethical approval, whereas only in specific conditions approval of national health authorities is required. Informed consent is not required in all sharing situations. However, waiver of informed consent is only allowed in certain countries/regions and under certain circumstances. The current legal and ethical landscape appears to be very complex and under constant evolution. Regulations differ between countries/regions and are often incomplete, leading to uncertainty.

Conclusion

With this work, ICN illuminates the unmet need for a single international collaborative framework to facilitate DSE. Harmonising requirements for global DSE will reduce inefficiency and waste in research. There are many challenges to realising this ambitious vision, including inconsistent terminology and definitions, and heterogeneous and dynamic legal constraints. Here, we identify areas of agreement and significant difference as a necessary first step towards facilitating international collaboration. We propose the establishment of a working group to continue the comparison across jurisdictions, create a standardised glossary and define a set of basic principles and fundamental requirements for DSE.
Improving the performance of spray operators through monitoring and evaluation of insecticide concentrations of pirimiphos-methyl during indoor residual spraying for malaria control on Bioko Island
Authors: Fuseini Godwin , Ismail Hanafy M. , von Fricken Michael E. , Weppelmann Thomas A. , Smith Jordan , Ellis Logan Rhiannon Agnes , Oladepo Folasade , Walker Kyle J. , Phiri Wonder P. , Paine Mark J. I. , García Guillermo A.
Published: January 2020

Background

Quality control of indoor residual spraying (IRS) is necessary to ensure that spray operators (SOs) deposit the correct concentration of insecticide on sprayed structures, while also confirming that spray records are not being falsified.

Methods

Using high-performance liquid chromatography (HPLC), this study conducted quality control of the organophosphate insecticide pirimiphos-methyl (Actellic 300CS), during the 2018 IRS round on Bioko Island, Equatorial Guinea. Approximately 60 SOs sprayed a total of 67,721 structures in 16,653 houses during the round. Houses that were reportedly sprayed were randomly selected for quality control testing. The SOs were monitored twice in 2018, an initial screening in March followed by sharing of results with the IRS management team and identification of SOs to be re-trained, and a second screening in June to monitor the effectiveness of training. Insecticide samples were adhesive-lifted from wooden and cement structures and analysed using HPLC.

Results

The study suggests that with adequate quality control measures and refresher training, suboptimal spraying was curtailed, with a significant increased concentration delivered to the bedroom (difference = 0.36, P < 0.001) and wooden surfaces (difference 0.41, P = 0.001). Additionally, an increase in effective coverage by SOs was observed, improving from 80.7% in March to 94.7% in June after re-training (McNemar’s test; P = 0.03).

Conclusions

The ability to randomly select, locate, and test houses reportedly sprayed within a week via HPLC has led to improvements in the performance of SOs on Bioko Island, enabling the project to better evaluate its own performance.
Geographical influences on the iodine status in pregnant women, neonates, and school-age children in China
Authors: Lou Xiaoming , Wang Xiaofeng , Mao Guangming , Zhu Wenming , Mo Zhe , Wang Yuanyang , Wang Zhifang
Published: January 2020

Background

Pregnant women, neonates, and school-age children are vulnerable to iodine deficiency. The iodine contents in the environment (drinking water and household salt for cooking) vary by geographical location in China. The aim of this study was to assess the iodine status in vulnerable groups from different geographical zones and analyze the iodine content in household salt and drinking water from these zones.

Methods

In coastal and inland regions of Zhejiang Province, China, samples of spot urine, drinking water, and household salt for cooking from both pregnant women and school-age children were determined for iodine concentration between 2017 and 2018. Thyroid-stimulating hormone (TSH) levels from neonates born between 2014 and 2015 were acquired from the Newborns Screening Information System. The iodine status of the vulnerable populations was assessed according to the criteria recommended by the World Health Organization.

Results

The median UIC of pregnant women was significantly lower in the coastal region (113.0 μg/L) than the inland region (134.9 μg/L; p < 0.001). The median UICs of pregnant women from these two regions were below the lower optimal iodine cutoff level of 150 μg/L. The percentage of neonates with elevated TSH (> 5 mIU/L) was significantly higher in the coastal region (15.8%) than the inland region (10.5%; p < 0.001). The percentage of neonates with elevated TSH from each region decreased within the range of mild iodine deficiency of 3–19.9%. The median UIC of the coastal school-age children was 156.0 μg/L, and the median UIC of inland children was 181.5 μg/L. Both medians fell within the recommended optimal iodine range of 100–299 μg/L. The iodine concentrations in drinking water varied from 1.0 μg/L in the inland region to 2.0 μg/L in the coastal region. The proportion of households that consumed iodized salt was lower in the coastal region (nearly 65%) than the inland region (approximately 95%).

Conclusions

In these two regions with low iodine contents in drinking water, both pregnant women and neonates were iodine-deficient, although school-age children were iodine-sufficient. Urgent efforts are needed to improve the iodine status of pregnant women and neonates.
All-cause mortality rate in China: do residents in economically developed regions have better health?
Authors: Yu Xuexin , Zhang Wei
Published: January 2020

Background

Urban-rural disparities have been extensively investigated, while most investigators overlooked urban-suburban-rural variations in population health. Although regional disparities in East-West China have been largely discussed, limited attention has been directed to the interaction between regional differences and urban-suburban-rural disparities. This study aims to analyze urban-suburban-rural variations in all-cause mortality rates across four geographic regions in China.

Methods

Data came from China’s National Census Survey and public statistical yearbooks in 2000 and 2010. Urban districts, county-level cities, and counties were respectively defined as urban, suburban, and rural areas. We obtained 2322 areas, including 2148 areas with two observations and 174 areas with only one observation. Data visualization was performed to depict geographic variations and changes in all-cause mortality rates. Five hierarchical linear regression analyses with generalized estimating equations (GEE) were employed to analyze variations in all-cause mortality rates over time. Demographic and socioeconomic attributes were introduced as covariates.

Results

Despite an overall decline in all-cause mortality rate, rural residents generally achieved worse health than urban and suburban counterparts. In contrast, urban-suburban disparities could be fully explained by demographic and socioeconomic differences. In addition, Northeastern and Central residents achieved better health than Eastern and Western residents. Last, there existed urban/suburban-rural disparities in all regions, except Northeastern, where urban/suburban-rural disparities were eliminated after controlling for socioeconomic and demographic attributes.

Conclusion

Even though suburban and rural areas were often merged, there exist urban/suburban-rural disparities in population health. Furthermore, urban/suburban-rural disparities vary across regions.
Road proximity, air pollution, noise, green space and neurologic disease incidence: a population-based cohort study
Authors: Yuchi Weiran , Sbihi Hind , Davies Hugh , Tamburic Lillian , Brauer Michael
Published: January 2020

Background

Emerging evidence links road proximity and air pollution with cognitive impairment. Joint effects of noise and greenness have not been evaluated. We investigated associations between road proximity and exposures to air pollution, and joint effects of noise and greenness, on non-Alzheimer’s dementia, Parkinson’s and Alzheimer’s disease and multiple sclerosis within a population-based cohort.

Methods

We assembled administrative health database cohorts of 45–84 year old residents (N ~ 678,000) of Metro Vancouver, Canada. Cox proportional hazards models were built to assess associations between exposures and non-Alzheimer’s dementia and Parkinson’s disease. Given reduced case numbers, associations with Alzheimer’s disease and multiple sclerosis were evaluated in nested case-control analyses by conditional logistic regression.

Results

Road proximity was associated with all outcomes (e.g. non-Alzheimer’s dementia hazard ratio: 1.14, [95% confidence interval: 1.07–1.20], for living < 50 m from a major road or < 150 m from a highway). Air pollutants were associated with incidence of Parkinson’s disease and non-Alzheimer’s dementia (e.g. Parkinson’s disease hazard ratios of 1.09 [1.02–1.16], 1.03 [0.97–1.08], 1.12 [1.05–1.20] per interquartile increase in fine particulate matter, Black Carbon, and nitrogen dioxide) but not Alzheimer’s disease or multiple sclerosis. Noise was not associated with any outcomes while associations with greenness suggested protective effects for Parkinson’s disease and non-Alzheimer’s dementia.

Conclusions

Road proximity was associated with incidence of non-Alzheimer’s dementia, Parkinson’s disease, Alzheimer’s disease and multiple sclerosis. This association may be partially mediated by air pollution, whereas noise exposure did not affect associations. There was some evidence of protective effects of greenness.
Hypoxia induced LUCAT1/PTBP1 axis modulates cancer cell viability and chemotherapy response
Authors: Huan Lin , Guo Tianan , Wu Yangjun , Xu Linguo , Huang Shenglin , Xu Ye , Liang Linhui , He Xianghuo
Published: January 2020

Background

Hypoxic tumors are refractory to DNA damage drugs. However, the underlying mechanism has yet to be elucidated. We aimed to identify lncRNAs that upregulated under hypoxia and their effects on colorectal cancer (CRC).

Methods

CRC cells were treated with 1% O2 to identify lncRNAs that upregulated under hypoxia. We integrated these lncRNAs with RNA-seq of 4 paired CRC tissues and TCGA data to get candidate lncRNAs. Multiple in vitro and in vivo assays were used to explore the role of LUCAT1 in CRC.

Results

We identified a hypoxia-induced lncRNA LUCAT1 that facilitated the growth of CRC cells and contributed to drug resistance of CRC cells both in vitro and in vivo. Mechanically, LUCAT1 interacts with polypyrimidine tract binding protein 1 (PTBP1) in CRC cells, facilitates the association of a set of DNA damage related genes with PTBP1, thus resulting in altered alternative splicing of these genes. Moreover, ectopic expression of PTBP1 in CRC cells with knockdown of LUCAT1 abrogated the effects induced by LUCAT1 knockdown. Chemotherapeutics drug combined with LUCAT1 knockdown via antisense oligonucleotides (ASO) would get a better outcome in vivo, compared with group treated with chemotherapeutic drug only. Notably, LUCAT1 is upregulated in CRC tissues, compared to adjacent normal tissues; and CRC patients with higher LUCAT1 have a worse prognosis and poorly responded to chemotherapy in the clinic.

Conclusions

Our data suggested CRC cells utilizes LUCAT1 to develop resistance to DNA damage drugs, and disrupting the LUCAT1/PTBP1 axis might be a promising therapeutic strategy for refractory hypoxic tumors.
A high-throughput screening method to identify proteins involved in unfolded protein response of the endoplasmic reticulum in plants
Authors: Alcântara André , Seitner Denise , Navarrete Fernando , Djamei Armin
Published: January 2020

Background

The unfolded protein response (UPR) is a highly conserved process in eukaryotic organisms that plays a crucial role in adaptation and development. While the most ubiquitous components of this pathway have been characterized, current efforts are focused on identifying and characterizing other UPR factors that play a role in specific conditions, such as developmental changes, abiotic cues, and biotic interactions. Considering the central role of protein secretion in plant pathogen interactions, there has also been a recent focus on understanding how pathogens manipulate their host’s UPR to facilitate infection.

Results

We developed a high-throughput screening assay to identify proteins that interfere with UPR signaling in planta. A set of 35 genes from a library of secreted proteins from the maize pathogen Ustilago maydis were transiently co-expressed with a reporter construct that upregulates enhanced yellow fluorescent protein (eYFP) expression upon UPR stress in Nicotiana benthamiana plants. After UPR stress induction, leaf discs were placed in 96 well plates and eYFP expression was measured. This allowed us to identify a previously undescribed fungal protein that inhibits plant UPR signaling, which was then confirmed using the classical but more laborious qRT-PCR method.

Conclusions

We have established a rapid and reliable fluorescence-based method to identify heterologously expressed proteins involved in UPR stress in plants. This system can be used for initial screens with libraries of proteins and potentially other molecules to identify candidates for further validation and characterization.
Antibiotic hypersensitivity and adverse reactions: management and implications in clinical practice
Authors: Jourdan Anthony , Sangha Brijit , Kim Eric , Nawaz Sohrab , Malik Vikram , Vij Radhika , Sekhsaria Sudhir
Published: January 2020

Background

Studies have shown the discrepancy between self-reported antibiotic allergies and true allergies. Inaccurate reporting of antibiotic hypersensitivities can limit treatment options and result in use of more expensive antibiotics and contribute to resistance.

Methods

This retrospective cohort chart review obtained data on 16,515 patients after obtaining IRB approval. Patients who had an antibiotic adverse reaction were identified, recorded, and their management reviewed. 7926 patients were selected from inpatient internal medicine clinics, 8042 patients from outpatient internal medicine clinics, and 547 from orthopedic clinics.

Results

The prevalence of reported antibiotic sensitivity in our study was 9.89% (n = 1624). Reported antibiotic sensitivity was 8.88% (n = 704) in inpatient settings as compared to 11.2% (n = 902) and 5.12% (n = 28) in medicine and orthopedic outpatient settings respectively. The top five antibiotic adverse reactions reported were penicillins (42%), sulfonamides (25%), fluoroquinolones (4.3%), tetracyclines (4.2%), and macrolides (3.5%). In all settings, penicillins and sulfonamides adverse reactions were the top two reportings. 11.88% (n = 193) of patients with reported adverse reactions reported sensitivities to multiple antibiotics.

Conclusion

Our study demonstrated high prevalence of reported antibiotic sensitivity in three clinical settings. However, a significant portion of these patients may not be truly hypersensitive to these antibiotics. There is a need for increased awareness among medical professionals about the importance of detailed history taking and management of self-reported antibiotic allergies to combat unnecessary use of antibiotics.
A contemporary look at allergic conjunctivitis
Authors: Dupuis Pascale , Prokopich C. Lisa , Hynes Alexander , Kim Harold
Published: January 2020

Allergic eye disease is common, yet often overlooked in North America. In the U.S., up to 40% of the population is deemed to be affected and this number is growing. Symptoms and signs of ocular allergy can lead to decreased productivity and negatively impact quality of life (QoL). Various treatment options exist to achieve symptom control. For allergic conjunctivitis, ophthalmic agents include antihistamines, mast cell stabilizers, dual-activity agents, nonsteroidal anti-inflammatory drugs (NSAIDs), steroids and some off-label treatments. Immunotherapy is recommended as a therapeutic option. This review provides a summary of the forms of ocular allergies, with a focus on symptoms and signs, impact on QoL, physical examination, diagnosis and therapeutic options of allergic conjunctivitis. Through multidisciplinary collaborations, a simplified algorithm for the treatment of allergic conjunctivitis is proposed for Canadian clinical practice.
Can supernatant from immortalized adipose tissue MSC replace cell therapy? An in vitro study in chronic wounds model
Authors: Kraskiewicz Honorata , Paprocka Maria , Bielawska-Pohl Aleksandra , Krawczenko Agnieszka , Panek Kinga , Kaczyńska Judyta , Szyposzyńska Agnieszka , Psurski Mateusz , Kuropka Piotr , Klimczak Aleksandra
Published: January 2020

Background

Mesenchymal stem cells (MSCs) secrete a cocktail of growth factors and cytokines, which could promote tissue regeneration and wound healing. Therefore, in clinical practice, post-culture MSC supernatant treatment could be a more attractive alternative to autologous stem cell transplantation. In this study, we compared the regenerative properties of supernatants harvested from four newly established human adipose tissue mesenchymal stem cell lines (HATMSCs) derived from chronic wound patients or healthy donors.

Methods

HATMSC supernatants were produced in a serum-free medium under hypoxia and their content was analyzed by a human angiogenesis antibody array. The regenerative effect of HATMSCs supernatants was investigated in an in vitro model of chronic wound, where cells originating from human skin, such as microvascular endothelial cells (HSkMEC.2), keratinocytes (HaCaT), and fibroblasts (MSU-1.1), were cultured in serum-free and oxygen-reduced conditions. The effect of supernatant treatment was evaluated using an MTT assay and light microscopy. In addition, fibroblasts and HATMSCs were labeled with PKH67 and PKH26 dye, respectively, and the effect of supernatant treatment was compared to that obtained when fibroblasts and HATMSCs were co-cultured, using flow cytometry and fluorescent microscopy.

Results

A wide panel of angiogenesis-associated cytokines such as angiogenin, growth-regulated oncogene (GRO), interleukin-6 and 8 (IL-6, IL-8), vascular endothelial growth factor (VEGF), insulin growth factor 1 (IGF-1), and matrix metalloproteinase (MMP) were found in all tested HATMSCs supernatants. Moreover, supernatant treatment significantly enhanced the survival of fibroblasts, endothelial cells, and keratinocytes in our chronic wound model in vitro. Importantly, we have shown that in in vitro settings, HATMSC supernatant treatment results in superior fibroblast proliferation than in the case of co-culture with HATMSCs.

Conclusions

Our results suggest that therapy based on bioactive factors released by the immortalized atMSC into supernatant has important effect on skin-derived cell proliferation and might preclude the need for a more expensive and difficult cell therapy approach to improve chronic wound healing.
Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke
Authors: Cunningham Catriona J. , Wong Raymond , Barrington Jack , Tamburrano Sabrina , Pinteaux Emmanuel , Allan Stuart M.
Published: January 2020

Background

Mesenchymal stem cells (MSCs) hold great potential as a therapy for stroke and have previously been shown to promote recovery in preclinical models of cerebral ischaemia. MSCs secrete a wide range of growth factors, chemokines, cytokines and extracellular vesicles—collectively termed the secretome. In this study, we assessed for the first time the efficacy of the IL-1α-primed MSC-derived secretome on brain injury and functional recovery after cerebral ischaemia.

Methods

Stroke was induced in male C57BL/6 mice using the intraluminal filament model of middle cerebral artery occlusion. Conditioned medium from IL-1α-primed MSCs or vehicle was administered at the time of reperfusion or at 24 h post-stroke by subcutaneous injection.

Results

IL-1α-primed MSC-derived conditioned medium treatment at the time of stroke led to a ~ 30% reduction in lesion volume at 48 h and was associated with modest improvements in body mass gain, 28-point neurological score and nest building. Administration of MSC-derived conditioned medium at 24 h post-stroke led to improved nest building and neurological score despite no observed differences in lesion volume at day 2 post-stroke.

Conclusions

Our results show for the first time that the administration of conditioned medium from IL-1α-primed MSCs leads to improvements in behavioural outcomes independently of neuroprotection.
Information rates of precoding for massive MIMO and base station cooperation in an indoor scenario
Authors: Dierks Stefan , Kramer Gerhard , Panzner Berthold , Zirwas Wolfgang
Published: January 2020

The performance of centralized and distributed massive MIMO deployments are studied for simulated indoor office scenarios. The distributed deployments use one of the following precoding methods: (1) local precoding with local channel state information (CSI) to the user equipments (UEs) that it serves, (2) large-scale MIMO with local CSI to all UEs in the network, (3) network MIMO with global CSI. For the distributed deployment (3), it is found that using twice as many base station antennas as data streams provides many of the massive MIMO benefits in terms of spectral efficiency and fairness. This is in contrast to the centralized and distributed deployments using (1) or (2) where more antennas are needed. Two main conclusions are that distributing base stations helps to overcome wall penetration loss; however, a backhaul is required to mitigate inter-cell interference. The effect of estimation errors on the performance is also quantified.
The existence, uniqueness and asymptotic estimates of solutions for third-order full nonlinear singularly perturbed vector boundary value problems
Authors: Lin Xiaojie , Liu Jiang , Wang Can
Published: January 2020

In this paper, we discuss third-order full nonlinear singularly perturbed vector boundary value problems. We first present the existence of solutions for the nonlinear vector boundary value problems without perturbation by using the upper and lower solutions method and topological degree theory. Then the existence, uniqueness and asymptotic estimates of solutions for the singularly perturbed vector boundary value problems are established by constructing appropriate a lower solution–upper solution pair, as well as analysis technique. Some known results are extended.
New results on global exponential stability for a periodic Nicholson’s blowflies model involving time-varying delays
Authors: Cao Qian , Wang Guoqiu , Qian Chaofan
Published: January 2020

This paper investigates a periodic Nicholson’s blowflies equation with multiple time-varying delays. By using differential inequality techniques and the fluctuation lemma, we establish a criterion to ensure the global exponential stability on the positive solutions of the addressed equation, which improves and complements some existing ones. The effectiveness of the obtained result is illustrated by some numerical simulations.
Inverse spectral problem of a class of fourth-order eigenparameter-dependent boundary value problems
Authors: Ao Ji-jun , Zhang Liang
Published: January 2020

This paper deals with a class of inverse spectral problems of fourth-order boundary value problems with eigenparameter-dependent boundary conditions. Under the equivalent conditions of the problem and a certain type of matrix eigenvalue problem some coefficient functions are reconstructed from the given three sets of interlacing real numbers and several additional conditions. The key technique is the method of inverse matrix eigenvalue problems of a two-banded matrix.