bluuebunny/crossref_metadata_2025 huggingface dataset:
Accounting for biases in survey-based estimates of population attributable fractions
Authors: Masters Ryan , Reither Eric
Published: December 2019

Background

This paper discusses best practices for estimating fractions of mortality attributable to health exposures in survey data that are biased by observed confounders and unobserved endogenous selection. Extant research has shown that estimates of population attributable fractions (PAF) from the formula using the proportion of deceased that is exposed (PAFpd) can attend to confounders, whereas the formula using the proportion of the entire sample exposed (PAFpe) is biased by confounders. Research has not explored how PAFpd and PAFpe equations perform when both confounding and selection bias are present.

Methods

We review equations for calculating PAF based on either the proportion of deceased (pd) or the proportion of the entire sample (pe) that receives the exposure. We explore how estimates from each equation are affected by confounding bias and selection bias using hypothetical data and real-world survey data from the National Health Interview Survey–Linked Mortality Files, 1987–2011. We examine the association between cigarette smoking and all-cause mortality risk in the US adult population as an example.

Results

We show that both PAFpd and PAFpe calculate the true PAF in the presence of confounding bias if one uses the “weighted-sum” approach. We further show that both the PAFpd and PAFpe calculate biased PAFs in the presence of collider bias, but that the bias is more severe in the PAFpd formula.

Conclusion

We recommend that researchers use the PAFpe formula with the weighted-sum approach when estimates of the exposure-outcome relationship are biased by endogenous selection.
NQO1 potentiates apoptosis evasion and upregulates XIAP via inhibiting proteasome-mediated degradation SIRT6 in hepatocellular carcinoma
Authors: Zhou Hong-Zhong , Zeng Han-Qing , Yuan Ding , Ren Ji-Hua , Cheng Sheng-Tao , Yu Hai-Bo , Ren Fang , Wang Qing , Qin Yi-Ping , Huang Ai-Long , Chen Juan
Published: December 2019

Background

Our previous study has demonstrated that NAD(P)H: quinone oxidoreductase 1 (NQO1) is significantly upregulated in human liver cancer where it potentiates the apoptosis evasion of liver cancer cell. However, the underlying mechanisms of the oncogenic function of NQO1 in HCC have not been fully elucidated.

Methods

Expression of NQO1, SIRT6, AKT and X-linked inhibitor of apoptosis protein (XIAP) protein were measured by western blotting and immunohistochemistry. Additionally, the interaction between NQO1 and potential proteins were determined by immunoprecipitation assays. Furthermore, the effect of NQO1 and SIRT6 on tumor growth was determined in cell model and orthotopic tumor implantation model.

Results

We found that NQO1 overexpression in HCC enhanced SIRT6 protein stability via inhibiting ubiquitin-mediated 26S proteasome degradation. High level of SIRT6 reduced acetylation of AKT which resulted in increased phosphorylation and activity of AKT. Activated AKT subsequently phosphorylated anti-apoptotic protein XIAP at Ser87 which determined its protein stability. Reintroduction of SIRT6 or AKT efficiently rescued NQO1 knock-out-mediated inhibition of growth and induction of apoptosis. In orthotopic mouse model, NQO1 knock-out inhibited tumor growth and induced apoptosis while this effect was effectively rescued by SIRT6 overexpression or MG132 treatment partially.

Conclusions

Collectively, these results reveal an oncogenic function of NQO1 in sustaining HCC cell proliferation through SIRT6/AKT/XIAP signaling pathway.
Unhealthy snack intake modifies the association between screen-based sedentary time and metabolic syndrome in Brazilian adolescents
Authors: Schaan Camila Wohlgemuth , Cureau Felipe Vogt , Salvo Deborah , Kohl Harold W. , Schaan Beatriz D.
Published: December 2019

Background

Excessive screen time has been associated with metabolic syndrome (MetS) among adolescents; however, snack intake in front of screens may play a role in this association. Therefore, our objective was to investigate the association between screen-based sedentary time with MetS and whether this association is modified by unhealthy snack intake in front of screens.

Methods

This study was a nationwide, cross-sectional, school-based survey in Brazil including adolescents aged 12 to 17 years. The frequency of snack consumption in front of screen and screen-based sedentary time (TV view, computers and videogames use) were self-reported. Thereafter, screen time was categorized (≤2, 3–5 and ≥ 6 h/day); snack consumption in front of screens was dichotomized. Metabolic syndrome diagnosis was defined based on the International Diabetes Federation criteria. Associations between screen time and MetS were investigated using logistic regression in overall sample and after stratification by snack intake in front of screens.

Results

A total of 33,900 adolescents were included in the analysis. The final adjusted model, which included sociodemographic data, physical activity, and energy intake, showed that adolescents who spent ≥6 h/day in front of screens had an increased odds ratio for MetS (OR = 1.68, 95%CI: 1.03–2.74). However, after stratifying the sample according to reported snack intake, the association between higher screen-based sedentary time and MetS remained significant only for adolescents who reported consumption of snacks in front of screens.

Conclusion

Longer screen-based sedentary times were directly associated with MetS. However, this association seems to be modified by reported snack intake in front of screens.
Do associations of sex, age and education with transport and leisure-time physical activity differ across 17 cities in 12 countries?
Authors: Mitáš Josef , Cerin Ester , Reis Rodrigo Siqueira , Conway Terry L. , Cain Kelli L. , Adams Marc A. , Schofield Grant , Sarmiento Olga L. , Christiansen Lars B. , Davey Rachel , Salvo Deborah , Orzanco-Garralda Rosario , Macfarlane Duncan , Hino Adriano Akira F. , De Bourdeaudhuij Ilse , Owen Neville , Van Dyck Delfien , Sallis James F.
Published: December 2019

Background

Leisure-time and transport activity domains are studied most often because they are considered more amenable to intervention, but to date evidence on these domains is limited. The aim of the present study was to examine patterns of socio-demographic correlates of adults’ leisure-time and transport physical activity and how these associations varied across 17 cities in 12 countries.

Methods

Participants (N = 13,745) aged 18–66 years in the IPEN Adult study and with complete data on socio-demographic and self-reported physical activity characteristics were included. Participants reported frequency and duration of leisure-time and transport activities in the last 7 days using the self-administered International Physical Activity Questionnaire-Long Form. Six physical activity outcomes were examined in relation with age, education, and sex, and analyses explored variations by city and curvilinear associations.

Results

Sex had the most consistent results, with five of six physical activity outcomes showing females were less active than males. Age had the most complex associations with self-report transport and leisure-time physical activity. Compared to older people, younger adults were less likely to engage in transport physical activity, but among those who did, younger people were likely to engage in more active minutes. Curvilinear associations were found between age and all three leisure-time physical activity outcomes, with the youngest and the oldest being more active. Positive associations with education were found for leisure-time physical activity only. There were significant interactions of city with sex and education for multiple physical activity outcomes.

Conclusions

Although socio-demographic correlates of physical activity are widely studied, the present results provide new information. City-specific findings suggest there will be value in conducting more detailed case studies. The curvilinear associations of age with leisure-time physical activity as well as significant interactions of leisure-time activity with sex and education should be further investigated. The findings of lower leisure-time physical activity among females as well as people with low education suggest that greater and continued efforts in physical activity policies and programs tailored to these high-risk groups are needed internationally.
Objectively measured physical activity in one-year-old children from a Brazilian cohort: levels, patterns and determinants
Authors: Ricardo Luiza Isnardi Cardoso , da Silva Inácio Crochemore M. , de Andrade Leão Otávio Amaral , Domingues Marlos Rodrigues , Wehrmeister Fernando C.
Published: December 2019

Background

The aim of this study is to describe objectively measured physical activity (PA) and its correlates in one-year-old children.

Methods

The current study includes participants from the 2015 Pelotas (Brazil) birth cohort. At age one, PA was assessed in a 24-h protocol during 4 days with a wrist-attached accelerometer (ActiGraph, wGT3X-BT), from which two complete days of data were analyzed, with 5-s epochs.

Results

A total of 2974 individuals provided valid accelerometry data. Infants able to walk independently spent on average 19 h per day below 50 mg of acceleration (including sleep time), and those who could not walk spent on average 21 h in this intensity category. Girls spent approximately 10 min more than boys below 50 mg daily in both walking status categories, and less activity than boys on higher intensity categories. Boys and infants whose mothers were more physically active during pregnancy presented more acceleration, regardless of walking status. Among infants who could walk by themselves, those with mothers with one to eight schooling years; adequate length-for-age (z-score); not attending daycare; and more physically active fathers also showed higher levels of acceleration.

Conclusions

Our findings demonstrate higher levels of PA among boys and those children with higher maternal PA during pregnancy, regardless of walking status. Also, among infants able to independently walk, 1–8 years of maternal schooling, adequate length-for-age (z-score), no daycare attendance and higher paternal PA are positive correlates of objectively measured PA early in life.
Elevated MR-proANP plasma concentrations are associated with sepsis and predict mortality in critically ill patients
Authors: Yagmur Eray , Sckaer Johanna Hermine , Koek Ger H. , Weiskirchen Ralf , Trautwein Christian , Koch Alexander , Tacke Frank
Published: December 2019

Background and aims

Mid-regional pro atrial natriuretic peptide (MR-proANP) is an established biomarker for heart failure, based on its key role in regulating homeostasis of water balance and blood pressure. The aim of the study was to determine the value of MR-proANP as a clinical biomarker in critical illness and/or sepsis. Upon admission to the medical intensive care unit (ICU), we investigated MR-proANP plasma concentrations in 217 critically ill patients (144 with sepsis, 73 without sepsis). Results were compared with 65 healthy controls.

Results

MR-proANP plasma levels were significantly elevated in critically ill patients, when compared to healthy controls. Notably, MR-proANP levels were significantly higher in ICU patients with sepsis. MR-proANP levels were not associated with metabolic comorbidities like diabetes or obesity. In critically ill patients, MR-proANP plasma concentrations correlated with inflammatory cytokines, markers of organ dysfunction and several adipocytokines, such as resistin, retinol-binding protein 4 (RBP4) and adiponectin. Importantly, high MR-proANP plasma levels were associated with mortality, as MR-proANP levels above 227.0 pmol/l indicated a particularly increased mortality risk in ICU patients. The association between MR-proANP and mortality was independent of single organ failure and inflammation markers.

Conclusion

Our study emphasizes the role of circulating MR-proANP as a biomarker in critically ill patients, in which high MR-proANP indicates organ dysfunction, sepsis and mortality risk. The association between high MR-proANP and inflammatory as well as adipose tissue-derived endocrine mediators warrants further pathophysiological investigations.
Inflammatory processes and elevated osteoclast activity chaperon atrophic non-union establishment in a murine model
Authors: Wagner Johannes M. , Schmidt Sonja V. , Dadras Mehran , Huber Julika , Wallner Christoph , Dittfeld Stephanie , Becerikli Mustafa , Jaurich Henriette , Reinkemeier Felix , Drysch Marius , Lehnhardt Marcus , Behr Björn
Published: December 2019

Background

Delayed bone healing, especially in long bones poses one of the biggest problems in orthopeadic and reconstructive surgery and causes tremendous costs every year. There is a need for exploring the causes in order to find an adequate therapy. Earlier investigations of human scaphoid non-union revealed an elevated osteoclast activity, accompanied by upregulated levels of TGF-beta and RANKL. Interestingly, scaphoid non-union seemed to be well vascularized.

Methods

In the current study, we used a murine femur-defect model to study atrophic non unions over a time-course of 10 weeks. Different time points were chosen, to gather insights into the dynamic processes of non-union establishment.

Results

Histological analyses as well as western blots and qRT-PCR indicated enhanced osteoclast activity throughout the observation period, paralleled by elevated levels of TGF-beta, TNF-alpha, MMP9, MMP13 and RANKL, especially during the early phases of non-union establishment. Interestingly, elevated levels of these mediators decreased markedly over a period of 10 weeks, as inflammatory reaction during non-union establishment seemed to wear out. To our surprise, osteoblastogenesis seemed to be unaffected during early stages of non-union establishment.

Conclusion

Taken together, we gained first insights into the establishment process of atrophic non unions, in which inflammatory processes accompanied by highly elevated osteoclast activity seem to play a leading role.
CXCL12 is involved in α-synuclein-triggered neuroinflammation of Parkinson’s disease
Authors: Li Yuanyuan , Niu Mengyue , Zhao Aonan , Kang Wenyan , Chen Zhichun , Luo Ningdi , Zhou Liche , Zhu Xiongwei , Lu Liming , Liu Jun
Published: December 2019

Background

The mechanisms underlying the pathogenesis and progression of Parkinson’s disease (PD) remain elusive, but recent opinions and perspectives have focused on whether the inflammation process induced by microglia contributes to α-synuclein-mediated toxicity. Migration of microglia to the substantia nigra (SN) could precede neurodegeneration inA53Tmice. We hypothesized that CXCL12 could be a mediator in the α-synuclein-induced migration of microglia.

Methods

After establishing appropriate animal and cell culture models, we explored the relationship between α-synuclein and CXCL12 inA53Tmice, primary microglia, and BV-2 cell lines. We also explored the mechanisms of these interactions and the signaling processes involved in neuroinflammation.

Results

We confirmed the positive correlation between α-synuclein and CXCL12 in the postmortem brain tissue of PD patients and the upregulated CXCR4 expression in SN microglia ofA53Tmice. In addition, as expected, α-synuclein increased the production of CXCL12 in microglia via TLR4/IκB-α/NF-κB signaling. Importantly, CXCL12/CXCR4/FAK/Src/Rac1 signaling was shown to be involved in α-synuclein-induced microglial accumulation.

Conclusions

Our study suggests that CXCL12 could be a novel target for the prevention of α-synuclein-triggered ongoing microglial responses. Blocking CXCL12/CXCR4 may be a potential therapeutic approach for PD progression.
Molecular epidemiology, genetic variability and evolution of HTLV-1 with special emphasis on African genotypes
Authors: Afonso Philippe V. , Cassar Olivier , Gessain Antoine
Published: December 2019

Human T cell leukemia virus (HTLV-1) is an oncoretrovirus that infects at least 10 million people worldwide. HTLV-1 exhibits a remarkable genetic stability, however, viral strains have been classified in several genotypes and subgroups, which often mirror the geographic origin of the viral strain. The Cosmopolitan genotype HTLV-1a, can be subdivided into geographically related subgroups, e.g. Transcontinental (a-TC), Japanese (a-Jpn), West-African (a-WA), North-African (a-NA), and Senegalese (a-Sen). Within each subgroup, the genetic diversity is low. Genotype HTLV-1b is found in Central Africa; it is the major genotype in Gabon, Cameroon and Democratic Republic of Congo. While strains from the HTLV-1d genotype represent only a few percent of the strains present in Central African countries, genotypes -e, -f, and -g have been only reported sporadically in particular in Cameroon Gabon, and Central African Republic. HTLV-1c genotype, which is found exclusively in Australo-Melanesia, is the most divergent genotype. This reflects an ancient speciation, with a long period of isolation of the infected populations in the different islands of this region (Australia, Papua New Guinea, Solomon Islands and Vanuatu archipelago). Until now, no viral genotype or subgroup is associated with a specific HTLV-1-associated disease. HTLV-1 originates from a simian reservoir (STLV-1); it derives from interspecies zoonotic transmission from non-human primates to humans (ancient or recent). In this review, we describe the genetic diversity of HTLV-1, and analyze the molecular mechanisms that are at play in HTLV-1 evolution. Similar to other retroviruses, HTLV-1 evolves either through accumulation of point mutations or recombination. Molecular studies point to a fairly low evolution rate of HTLV-1 (between 5.6E−7 and 1.5E−6 substitutions/site/year), supposedly because the virus persists within the host via clonal expansion (instead of new infectious cycles that use reverse transcriptase).
Retraining walking over ground in a powered exoskeleton after spinal cord injury: a prospective cohort study to examine functional gains and neuroplasticity
Authors: Khan Atif S. , Livingstone Donna C. , Hurd Caitlin L. , Duchcherer Jennifer , Misiaszek John E. , Gorassini Monica A. , Manns Patricia J. , Yang Jaynie F.
Published: December 2019

Background

Powered exoskeletons provide a way to stand and walk for people with severe spinal cord injury. Here, we used the ReWalk exoskeleton to determine the training dosage required for walking proficiency, the sensory and motor changes in the nervous system with training, and the functionality of the device in a home-like environment.

Methods

Participants with chronic (> 1 yr) motor complete or incomplete spinal cord injury, who were primarily wheelchair users, were trained to walk in the ReWalk for 12 weeks. Measures were taken before, during, immediately after, and 2–3 months after training. Measures included walking progression, sitting balance, skin sensation, spasticity, and strength of the corticospinal tracts.

Results

Twelve participants were enrolled with 10 completing training. Training progression and walking ability: The progression in training indicated about 45 sessions to reach 80% of final performance in training. By the end of training, participants walked at speeds of 0.28–0.60 m/s, and distances of 0.74–1.97 km in 1 h. The effort of walking was about 3.3 times that for manual wheelchair propulsion. One non-walker with an incomplete injury became a walker without the ReWalk after training. Sensory and motor measures: Sitting balance was improved in some, as seen from the limits of stability and sway speed. Neuropathic pain showed no long term changes. Change in spasticity was mixed with suggestion of differences between those with high versus low spasticity prior to training. The strength of motor pathways from the brain to back extensor muscles remained unchanged. Adverse events: Minor adverse events were encountered by the participants and trainer (skin abrasions, non-injurious falls). Field testing: The majority of participants could walk on uneven surfaces outdoors. Some limitations were encountered in home-like environments.

Conclusion

For individuals with severe SCI, walking proficiency in the ReWalk requires about 45 sessions of training. The training was accompanied by functional improvements in some, especially in people with incomplete injuries.

Trial registration

NCT02322125 Registered 22 December 2014.
In-depth analysis of the replication cycle of Orpheovirus
Authors: Souza Fernanda , Rodrigues Rodrigo , Reis Erik , Lima Maurício , La Scola Bernard , Abrahão Jônatas
Published: December 2019

Background

After the isolation of Acanthamoeba polyphaga mimivirus (APMV), the study and search for new giant viruses has been intensified. Most giant viruses are associated with free-living amoebae of the genusAcanthamoeba; however other giant viruses have been isolated inVermamoeba vermiformis, such as Faustovirus, Kaumoebavirus and Orpheovirus. These studies have considerably expanded our knowledge about the diversity, structure, genomics, and evolution of giant viruses. Until now, there has been only one Orpheovirus isolate, and many aspects of its life cycle remain to be elucidated.

Methods

In this study, we performed an in-depth characterization of the replication cycle and particles of Orpheovirus by transmission and scanning electron microscopy, optical microscopy and IF assays.

Results

We observed, through optical and IF microscopy, morphological changes inV. vermiformiscells during Orpheovirus infection, as well as increased motility at 12 h post infection (h.p.i.). The viral factory formation and viral particle morphogenesis were analysed by transmission electron microscopy, revealing mitochondria and membrane recruitment into and around the electron-lucent viral factories. Membrane traffic inhibitor (Brefeldin A) negatively impacted particle morphogenesis. The first structure observed during particle morphogenesis was crescent-shaped bodies, which extend and are filled by the internal content until the formation of multi-layered mature particles. We also observed the formation of defective particles with different shapes and sizes. Virological assays revealed that viruses are released from the host by exocytosis at 12 h.p.i., which is associated with an increase of particle counts in the supernatant.

Conclusions

The results presented here contribute to a better understanding of the biology, structures and important steps in the replication cycle of Orpheovirus.
The association of dietary macronutrients with anthropometric changes, using iso-energetic substitution models: Tehran lipid and glucose study
Authors: Hosseini-Esfahani Firoozeh , Koochakpoor Glareh , Mirmiran Parvin , Ebrahimof Samira , Azizi Fereidoun
Published: December 2019

Background

The consequences of optimal dietary macronutrient compositions especially quality of proteins on weight gain still remain controversial. The aim of the current study was to evaluate the iso-energetic substitution of dietary macronutrients in relation to anthropometric changes.

Methods

This prospective study was conducted on 2999 men and 4001 women aged 20–70 years who were followed for 3.6 years. A valid and reliable 168-item semi-quantitative food frequency questionnaire was used to assess usual dietary intakes. Weight (kg) and waist circumference (WC) (cm) changes were calculated by subtracting the weight and WC at baseline from their measurements at follow up. Participants were divided into two groups; those with no change or decrease in weight or WC and those with increase in weight or WC. Dietary macronutrients (percentage of energy) divided by 5 to calculate one unit.

Results

A one unit higher proportion of carbohydrates at the expense of all types of fatty acids was associated with weight loss in men (P < 0.05). A one unit higher proportion of plant proteins at the expense of animal protein (β = − 0.84), non-starch carbohydrates (β = − 0.86), saturated fat (β = − 0.76), mono-unsaturated fat (β = − 0.76) and poly-unsaturated fat (β = − 0.86) was associated with weight loss (P < 0.05). A one unit higher proportion of plant proteins at the expense of animal proteins (OR: 0.49), non-starch carbohydrates (OR: 0.49), saturated fat (OR: 0.49), mono-unsaturated fat (OR: 0.49), and poly-unsaturated fat (OR: 0.48) was associated with a lower risk of increase in WC (P < 0.05).

Conclusions

A higher proportion of dietary plant protein in replacement of simple carbohydrates, fats and animal proteins was associated with a lower increase in weight or WC.
Modulation of liver glucose output by free or restricted feeding in the adult rat is independent of litter size
Authors: Yamada Laís Akemi , Mariano Isabela Ramos , Sabino Vanessa Lara Rissi , Rabassi Renan Soares , Bataglini Camila , Azevedo Silvia Carla Santana Ferreira , Branquinho Nayra Thais Delatorre , Kurauti Mirian Ayumi , Garcia Rosângela Fernandes , Pedrosa Maria Montserrat Diaz
Published: December 2019

Background

Caloric restriction since birth changes glucose metabolism by the liver in overnight-fasted rats to a fed-like pattern, in which glucose output is large but gluconeogenesis is negligible. It was investigated whether these changes could be a residual effect of the nutritional condition during lactation and what could be the mechanism of such change.

Methods

NewbornWistarrat pups were arranged in litters of 6 or 12 (G6 and G12). After weaning, the male pups were divided in: G6L and G12 L, fed freely until the age of 90 days (freely-fed groups); G6R and G12R, given 50% of the GL ingestion (food-restricted groups) until 90 days of age; G6RL and G12RL, given 50% of the GL ingestion until 60 days of age and fed freely until 90 days of age (refed groups). The experimental protocols were carried out at the age of 90 days after overnight fasting. Pairs of groups were compared through t test; other statistical comparisons were made with one-way ANOVA with Tukey post hoc text.

Results

Caloric restriction was effective in decreasing body and fat weights, total cholesterol and LDL. These effects were totally or partially reversed after 30 days of refeeding (groups GRL). During liver perfusion, the high glucose output of the GRs was further enhanced by adrenaline (1 μM), but not by lactate infusion. In contrast, in groups G6L, G12 L, G6RL and G12RL glycogenolysis (basal and adrenaline-stimulated glucose output) was low and gluconeogenesis from lactate was significant. A twofold increase in liver content of PKA in group G6R suggests that liver sensitivity to glucagon and adrenaline was higher because of caloric restriction, resulting in enhanced glucose output.

Conclusions

As glucose output was not affected by litter size, liver glucose metabolism in the adult rat, in contrast to other metabolic processes, is not a programmed effect of the nutritional condition during lactation. In addition, the increased expression of PKA points to a higher sensitivity of the animals under caloric restriction to glycogenolytic hormones, a relevant condition for glucose homeostasis during fasting.
Role of Nrf2 in inflammatory response in lung of mice exposed to zinc oxide nanoparticles
Authors: Sehsah Radwa , Wu Wenting , Ichihara Sahoko , Hashimoto Naozumi , Hasegawa Yoshinori , Zong Cai , Itoh Ken , Yamamoto Masayuki , Elsayed Ahmed Ali , El-Bestar Soheir , Kamel Emily , Ichihara Gaku
Published: December 2019

Background

Zinc oxide nanoparticles (ZnO-NPs) are widely used in many industrial sectors and previous studies have reported that exposure of the lungs to ZnO-NPs induces both acute and/or chronic pulmonary inflammation, but the exact mechanism underlying such response remains elusive. This study investigated the role of nuclear factor-erythroid 2-related factor (Nrf2) in pulmonary inflammation induced by exposure to ZnO-NPs using Nrf2 null (Nrf2−/−) mice.

Methods

Twenty-four maleNrf2−/−mice and thirty male wild type C57BL/6 J mice were divided into three groups of eight and ten each respectively, and exposed once to ZnO-NPs at 0, 10, 30 μg/mouse by pharyngeal aspiration. At 14 days after the exposure to ZnO-NPs, bronchoalveolar lavage fluid (BALF) and lungs were collected to quantify protein level and the number of inflammatory cells. The mRNA levels ofNrf2-dependent antioxidant enzymes and inflammatory cytokines in lung tissue were measured.

Results

Exposure to ZnO-NPs dose-dependently increased the number of total cells, macrophages, lymphocytes and eosinophils in BALF both inNrf2−/−mice and wild type mice, but the magnitude of increase was significantly higher inNrf2−/−mice than wild type mice. The number of neutrophils in BALF increased inNrf2−/−mice, being accompanied by marginal trend of increase in mRNA expression ofMIP-2, neutrophil chemoattractant, but such changes were not observed in wild type mice. Exposure to ZnO-NPs did not dose-dependently increase mRNA level ofNrf2-dependent antioxidant enzymes both inNrf2−/−mice and wild type mice.

Conclusion

Pharyngeal aspiration of ZnO-NPs induced infiltration of inflammatory cells in the lung of mice, but minimally inducedNrf2-dependent antioxidant enzymes. The results suggest thatNrf2play a role in negative regulation on ZnO-NP exposure-induced neutrophil migration, but does not demonstrate that the regulation is through suppression of oxidative stress.
Blocking and re-arrangement of pots in greenhouse experiments: which approach is more effective?
Authors: Hartung Jens , Wagener Juliane , Ruser Reiner , Piepho Hans-Peter
Published: December 2019

Background

Observations measured in field and greenhouse experiments always contain errors. These errors can arise from measurement error, local or positional conditions of the experimental units, or from the randomization of experimental units. In statistical analysis errors can be modelled as independent effects or as spatially correlated effects with an appropriate variance–covariance structure. Using a suitable experimental design, a part of the variance can be captured through blocking of the experimental units. If experimental units (e.g. pots within a greenhouse) are mobile, they can be re-arranged during the experiment. This re-arrangement enables a separation of variation due to time-invariant position effects and variation due to the experimental units. If re-arrangement is successful, the time-invariant positional effect can average out for experimental units moved between different positions during the experiment. While re-arrangement is commonly done in greenhouse experiments, data to quantify its usefulness is limited.

Results

A uniformity greenhouse experiment with barley (Hordeum vulgare L.) to compare re-arrangement of pots with a range of designs under fixed-position arrangement showed that both methods can reduce the residual variance and the average standard error of a difference. All designs with fixed-position arrangement, which accounted for the known north–south gradient in the greenhouse, outperformed re-arrangement. An α-design with block size four performed best across seven plant growth traits.

Conclusion

Blocking with a fixed-position arrangement was more efficient in improving precision of greenhouse experiments than re-arrangement of pots and hence can be recommended for comparable greenhouse experiments.
Evaluation of methanol content of illegal beverages using GC and an easier modified Chromotropic acid method; a cross sectional study
Authors: Zamani Nasim , Rafizadeh Ali , Hassanian-Moghaddam Hossein , Akhavan-Tavakoli Alireza , Ghorbani-Samin Mahdi , Akhgari Maryam , Shariati Shahab
Published: December 2019

Background

Methanol is highly toxic to human beings and naturally exists in some beverages. Having access to an easy and cheap method for its determination is of great importance to increase the safety of use of these beverages. Our main aim is to evaluate methanol concentration of some alcoholic beverages in Iran black market and compare it with the European and US standards. Also, we evaluated the efficacy of a newly designed and produced chemical kit in determining the risk of methanol toxicity by drinking of such samples compared to gas chromatography method.

Methods

Methanol content of suspected alcoholic beverages referred to forensic toxicology laboratory, Guilan province, Iran was measured using gas chromatography and a recently designed kit based on modified colorimetric chromotropic acid method.

Results

Of 1221 samples, 145 (11.9%) had no ethanol content, while in three samples (0.25%), methanol was high enough (700,000; 870,000; 920,000 mg/L) to cause severe methanol toxicity. Median [IQR] ethanol content of the suspected samples was 9% [3.7, 32.75]. Methanol was detected in 128 (10.48%) samples using gas chromatography method and 160 samples (13.1%) with designed kit with 100% sensitivity, 97.07% specificity, and 100% negative-predictive-value.

Conclusions

Alcoholic beverages produced in local black market in Iran are not safe at all. The application of the new method is practical, rapid, easy, and accurate to evaluate the risk of methanol toxicity in suspected alcoholic drinks.
The preliminary results of proton and carbon ion therapy for chordoma and chondrosarcoma of the skull base and cervical spine
Authors: Guan Xiyin , Gao Jing , Hu Jiyi , Hu Weixu , Yang Jing , Qiu Xianxin , Hu Chaosu , Kong Lin , Lu Jiade J.
Published: December 2019

Purpose

To evaluate the short-term outcomes in terms of tumor control and toxicity of patients with skull base or cervical spine chordoma and chondrosarcoma treated with intensity-modulated proton or carbon-ion radiation therapy.

Methods

Between 6/2014 and 7/2018, a total of 91 patients were treated in our Center. The median age was 38 (range, 4–70) years. Forty-six (50.5%) patients were treated definitively for their conditions as initial diagnosis, 45 (49.5%) patients had recurrent tumors including 14 had prior radiotherapy. The median gross tumor volume was 37.0 (range, 1.6–231.7) cc. Eight patients received proton therapy alone, 28 patients received combined proton and carbon ion therapy, 55 patients received carbon-ion therapy alone.

Results

With a median follow-up time of 28 (range, 8–59) months, the 2-year local control (LC), progression free (PFS) and overall survival (OS) rates was 86.2, 76.8, and 87.2%, respectively. Those rates for patients received definitive proton or carbon-ion therapy were 86.7, 82.8, and 93.8%, respectively. On multivariate analyses, tumor volume of > 60 cc was the only significant factor for predicting PFS (p = 0.045), while re-irradiation (p = 0.012) and tumor volume (> vs < 60 cc) (p = 0.005) were significant prognosticators for OS. Grade 1–2 late toxicities were observed in 11 patients, and one patient developed Grade 3 acute mucositis.

Conclusions

Larger tumor volume and re-irradiation were related to inferior survival for this group of patients. Further follow-up is needed for long-term efficacy and safety.
Evaluation of the efficacy of prophylactic extended field irradiation in the concomitant chemoradiotherapy treatment of locally advanced cervical cancer, stage IIIB in the 2018 FIGO classification
Authors: Meng Qingyu , Liu Xiaoliang , Wang Weiping , Hou Xiaorong , Lian Xin , Sun Shuai , Yan Junfang , Liu Zhikai , Miao Zheng , Hu Ke , Zhang Fuquan
Published: December 2019

Background

The new staging system of cervical cancer issued in 2018 by the International Federation of Gynecology and Obstetrics (FIGO), calls for a new evaluation of the efficacy of prophylactic extended field irradiation (EFI) in the concomitant chemoradiotherapy/brachytherapy treatment of locally advanced cervical cancer patients (stage IIIB).

Methods

We performed a retrospective study consisting of 133 FIGO IIIB cervical cancer patients treated in the Peking Union Medical College Hospital from 2002 to 2010. The patients were distributed in two groups depending whether they were treated with EFI or pelvic only irradiation. The therapeutic efficacy, toxicity and prognostic factors of EFI were evaluated in the frame of the new FIGO staging system.

Results

When compared to patients who received pelvic only irradiation, patients who received prophylactic EFI showed significantly less distant metastasis and a significant improvement in their 5 years overall survival (OS), disease free survival (DFS), out of field recurrence free survival (OFRFS) and para-aortic lymph node metastasis free survival (PALNMFS). Multivariate analysis revealed that EFI is an independent prognosis factor for DFS, OFRFS and PALNMFS. Finally, although more acute complications were observed in the EFI group, there is no significantly worst acute toxicity in the EFI group.

Conclusion

Our retrospective analysis supports the prophylactic effect of EFI in the concomitant chemoradiotherapy treatment of IIIB patients and suggests that this prophylactic effect is associated with a clear improvement in 5-years OS, DFS, OFRFS and PALNMFS. Consequently, EFI appears to be a very valid treatment option for FIGO IIIB cervical cancer patients.
Association between the location of transposed ovary and ovarian dose in patients with cervical cancer treated with postoperative pelvic radiotherapy
Authors: Lv Xiao-juan , Cheng Xiao-long , Tu Ye-qiang , Yan Ding-ding , Tang Qiu
Published: December 2019

Background and purpose

How to protect the ovarian function during radiotherapy is uncertain. The purpose of this study was to explore the association between the location of the transposed ovary and the ovarian dose in patients with cervical cancer received radical hysterectomy, ovarian transposition, and postoperative pelvic radiotherapy.

Methods

A retrospective analysis was conducted of 150 young patients with cervical cancer who received radical hysterectomy, intraoperative ovarian transposition, and postoperative adjuvant radiotherapy in Zhejiang Cancer Hospital. Association between location of the transposed ovaries and ovarian dose was evaluated. The transposed position of ovaries with a satisfactory dose was explored using a receiver operator characteristic curve (ROC) analysis. Patients’ ovarian function was followed up 3 months and 1 year after radiotherapy.

Results

A total of 32/214 (15%) transposed ovaries were higher than the upper boundary of the planning target volume (PTV). The optimum cutoff value of > 1.12 cm above the iliac crest plane was significantly associated with ovaries above the upper PTV boundary. When the ovaries were below the upper boundary of PTV, the optimum cutoff value of transverse distance > 3.265 cm between the ovary and PTV was significantly associated with ovarian max dose (Dmax) ≤ 4Gy, and the optimum cutoff value of transverse distance > 2.391 cm was significantly associated with ovarian Dmax≤5Gy. A total of 77 patients had received complete follow-up, and 56 patients (72.7%) showed preserved ovarian function 1 year after radiotherapy, which was significantly increased compared with 3 months (44.2%) after radiotherapy.

Conclusions

The location of transposed ovaries in patients with cervical cancer is significantly correlated with ovarian dose in adjuvant radiotherapy. We recommend transposition of ovaries > 1.12 cm higher than the iliac crest plane to obtain ovarian location above PTV. When the transposed ovary is below the upper boundary of PTV, ovarian Dmax ≤4Gy may be obtained when the transverse distance between the ovary and PTV was > 3.265 cm, and the ovarian Dmax≤5Gy may be obtained when the transverse distance was > 2.391 cm.
Highlighting the gaps in quantifying the economic burden of surgical site infections associated with antimicrobial-resistant bacteria
Authors: Iskandar Katia , Sartelli Massimo , Tabbal Marwan , Ansaloni Luca , Baiocchi Gian Luca , Catena Fausto , Coccolini Federico , Haque Mainul , Labricciosa Francesco Maria , Moghabghab Ayad , Pagani Leonardo , Hanna Pierre Abi , Roques Christine , Salameh Pascale , Molinier Laurent
Published: December 2019

Antibiotics are the pillar of surgery from prophylaxis to treatment; any failure is potentially a leading cause for increased morbidity and mortality. Robust data on the burden of SSI especially those due to antimicrobial resistance (AMR) show variable rates between countries and geographical regions but accurate estimates of the incidence of surgical site infections (SSI) due to AMR and its related global economic impact are yet to be determined. Quantifying the burden of SSI treatment is an incentive to sensitize governments, healthcare systems, and the society to invest in quality improvement and sustainable development. However in the absence of a unified epidemiologically sound infection definition of SSI and a well-designed global surveillance system, the end result is a lack of accurate and reliable data that limits the comparability of estimates between countries and the possibility of tracking changes to inform healthcare professionals about the appropriateness of implemented infection prevention and control strategies. This review aims to highlight the reported gaps in surveillance methods, epidemiologic data, and evidence-based SSI prevention practices and in the methodologies undertaken for the evaluation of the economic burden of SSI associated with AMR bacteria. If efforts to tackle this problem are taken in isolation without a global alliance and data is still lacking generalizability and comparability, we may see the future as a race between the global research efforts for the advancement in surgery and the global alarming reports of the increased incidence of antimicrobial-resistant pathogens threatening to undermine any achievement.
Autologous bone marrow expanded mesenchymal stem cells in patellar tendinopathy: protocol for a phase I/II, single-centre, randomized with active control PRP, double-blinded clinical trial
Authors: Rodas Gil , Soler Robert , Balius Ramón , Alomar Xavier , Peirau Xavier , Alberca Mercedes , Sánchez Ana , Sancho Javier García , Rodellar Clementina , Romero Antonio , Masci Lorenzo , Orozco Lluís , Maffulli Nicola
Published: December 2019

Introduction

Patellar tendon overuse injuries are common in athletes. Imaging may show a change in tissue structure with tendon thickening and disruption of the intratendinous substance. We wish to test the hypothesis that both autologous bone marrow expanded mesenchymal stem cells and autologous leukocyte-poor platelet-rich plasma (LP-PRP) implanted into the area of the disrupted tendinopathic patellar tendon will restore function, but tendon regeneration tissue will only be observed in the subjects treated with autologous bone marrow expanded mesenchymal stem cells.

Methods and analysis

This is a single-centre, pilot phase I/II, double-blinded clinical trial with randomisation with active control. Twenty patients with a diagnosis of patellar tendinopathy with imaging changes (tendon thickening and disruption of the intratendinous substance at the proximal portion of the patellar tendon) will be randomised in a 1:1 ratio to receive a local injection of either bone-marrow autologous mesenchymal stem cells (MSC), isolated and cultured under GMP at The Institute of Biology and Molecular Genetics (IBGM) (Spain) or P-PRP. The study will have two aims: first, to ascertain whether a clinically relevant improvement after 3, 6 and 12 months according to the visual analogue scale (VAS), Victorian Institute of Sport Assessment for patellar tendons (VISA-P) and dynamometry scales (DYN) will be achieved; and second, to ascertain whether the proposed intervention will restore tendon structure as determined by ultrasonography (US), Doppler ultrasonography (DUS), and innovative MRI and ultrasound techniques: Magnetic Resonance T2 FAT SAT (UTE, Ultrashort Echo TE) sequence and Ultrasound Tissue Characterization (UTC). Patients who are randomised to the P-PRP treatment group but do not achieve a satisfactory primary endpoint after 6 months will be offered treatment with MSC.

Trial registration

NCT03454737.
Histopathological features of condylar hyperplasia and condylar Osteochondroma: a comparison study
Authors: Yu Jingshuang , Yang Tong , Dai Jiewen , Wang Xudong
Published: December 2019

Background

Both mandibular condylar hyperplasia and condylar osteochondroma can lead to maxillofacial skeletal asymmetry and malocclusion, although they exhibit different biological behavior. This study attempted to compare the histological features of mandibular condylar hyperplasia and condylar osteochondroma using hematoxylin-and-eosin (H&E) staining, and immunohistochemistry staining of PCNA and EXT1 with quantitative analysis method.

Results

The H&E staining showed that condylar hyperplasia and condylar osteochondroma could be divided into four histological types and exhibited features of different endochondral ossification stages. There was evidence of a thicker cartilage cap in condylar osteochondroma as compared condylar hyperplasia (P = 0.018). The percentage of bone formation in condylar osteochondroma was larger than was found in condylar hyperplasia (P = 0.04). Immunohistochemical staining showed that PCNA was mainly located in the undifferentiated mesenchymal layer and the hypertrophic cartilage layer, and there were more PCNA positive cells in the condylar osteochondroma (P = 0.007). EXT1 was mainly expressed in the cartilage layer, and there was also a higher positive rate of EXT1 in condylar osteochondroma (P = 0.0366). The thicker cartilage cap, higher bone formation rate and higher PCNA positive rate indicated a higher rate of proliferative activity in condylar osteochondroma. The more significant positive rate of EXT1 in condylar osteochondroma implied differential biological characteristic as compared to condylar hyperplasia.

Conclusions

These features might be useful in histopathologically distinguishing condylar hyperplasia and osteochondroma.
Surgical site infection leading to gangrene and amputation after ambulatory surgical care of an ingrown toenail: a case report
Authors: Noula Aimé Gilbert Mbonda , Tochie Joel Noutakdie , Tchuenkam Landry W. , Abang Desmond Aji , Essomba René
Published: December 2019

Background

Currently, the management of ingrown toenail (onychocryptosis) ranges from conservative medical management to surgical treatment. Surgical management is typically performed as an outpatient procedure due to it numerous advantages such as the simplicity of the technique and the low incidence of postoperative complications. The most common postoperative complications are recurrences and surgical site infections, whereas gangrene complicating a surgical site infection has been scarcely reported. We are reporting a rare complication following ambulatory surgery untimely requiring amputation.

Case presentation

A twelve-year-old boy was referred to our orthopedic surgical department for a surgical site infection complicating an initial surgical management of a left ingrown big toenail leading to a dry gangrene of the affected toe. The gangrene toe was amputated under peripheral nerve block and the patient was discharged home the same day on antibiotics, analgesics and with sessions of rehabilitation and psychological support planned. The postoperative course was uneventful at 6 months of follow-up.

Conclusion

The authors report this case to draw clinicians’ attention, especially wound care specialists, orthopedists and podiatrists to this rare but potentially debilitating disease.