bluuebunny/crossref_metadata_2025 huggingface dataset:
Emodin alleviates LPS-induced inflammatory response in lung injury rat by affecting the function of granulocytes
Authors: Mei Hongxia , Tao Ying , Zhang Tianhao , Qi Feng
Published: August 2020

Background

Acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) are critical life-threatening syndromes characterized by the infiltration of a large number of granulocytes (mainly neutrophils) that lead to an excessive inflammatory response. Emodin (Emo) is a naturally occurring anthraquinone derivative and an active ingredient of Chinese medicine. It is believed to have anti-inflammatory effects. In this study, we examined the impact of Emo on the pulmonary inflammatory response and the granulocytes function in a rat model of lipopolysaccharide (LPS)-induced ALI.

Results

Treatment with Emo protected rat against LPS-induced ALI. Compared to untreated rat, Emo-treated rat exhibited significantly ameliorated lung pathological changes and decreased tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). However, Emo has no protective effect on the rat model of acute lung injury with granulocyte deficiency. In addition, treatment with Emo enhanced the bactericidal capacity of LPS-induced granulocytes via the up-regulation of the ability of granulocytes to phagocytize bacteria and generate neutrophil extracellular traps (NETs). Emo also downregulated the respiratory burst and the expression of reactive oxygen species (ROS) in LPS-stimulated granulocytes, alleviating the damage of granulocytes to surrounding tissues. Finally, Emo can accelerate the resolution of inflammation by promoting apoptosis of granulocytes.

Conclusion

Our results provide the evidence that Emo could ameliorates LPS-induced ALI via its anti-inflammatory action by modulating the function of granulocytes. Emo may be a promising preventive and therapeutic agent in the treatment of ALI.
PIM1 accelerates prostate cancer cell motility by phosphorylating actin capping proteins
Authors: Santio Niina M. , Vainio Veera , Hoikkala Tuuli , Mung Kwan Long , Lång Mirka , Vahakoski Riitta , Zdrojewska Justyna , Coffey Eleanor T. , Kremneva Elena , Rainio Eeva-Marja , Koskinen Päivi J.
Published: August 2020

Background

The PIM family kinases promote cancer cell survival and motility as well as metastatic growth in various types of cancer. We have previously identified several PIM substrates, which support cancer cell migration and invasiveness. However, none of them are known to regulate cellular movements by directly interacting with the actin cytoskeleton. Here we have studied the phosphorylation-dependent effects of PIM1 on actin capping proteins, which bind as heterodimers to the fast-growing actin filament ends and stabilize them.

Methods

Based on a phosphoproteomics screen for novel PIM substrates, we have used kinase assays and fluorescence-based imaging techniques to validate actin capping proteins as PIM1 substrates and interaction partners. We have analysed the functional consequences of capping protein phosphorylation on cell migration and adhesion by using wound healing and real-time impedance-based assays. We have also investigated phosphorylation-dependent effects on actin polymerization by analysing the protective role of capping protein phosphomutants in actin disassembly assays.

Results

We have identified capping proteins CAPZA1 and CAPZB2 as PIM1 substrates, and shown that phosphorylation of either of them leads to increased adhesion and migration of human prostate cancer cells. Phosphorylation also reduces the ability of the capping proteins to protect polymerized actin from disassembly.

Conclusions

Our data suggest that PIM kinases are able to induce changes in actin dynamics to support cell adhesion and movement. Thus, we have identified a novel mechanism through which PIM kinases enhance motility and metastatic behaviour of cancer cells.

Graphical abstract
Convective forces increase rostral delivery of intrathecal radiotracers and antisense oligonucleotides in the cynomolgus monkey nervous system
Authors: Sullivan Jenna M. , Mazur Curt , Wolf Daniel A. , Horky Laura , Currier Nicolas , Fitzsimmons Bethany , Hesterman Jacob , Pauplis Rachel , Haller Scott , Powers Berit , Tayefeh Leighla , DeBrosse-Serra Bea , Hoppin Jack , Kordasiewicz Holly , Swayze Eric E. , Verma Ajay
Published: August 2020

Background

The intrathecal (IT) dosing route introduces drugs directly into the CSF to bypass the blood–brain barrier and gain direct access to the CNS. We evaluated the use of convective forces acting on the cerebrospinal fluid as a means for increasing rostral delivery of IT dosed radioactive tracer molecules and antisense oligonucleotides (ASO) in the monkey CNS. We also measured the cerebral spinal fluid (CSF) volume in a group of cynomolgus monkeys.

Methods

There are three studies presented, in each of which cynomolgus monkeys were injected into the IT space with radioactive tracer molecules and/or ASO by lumbar puncture in either a low or high volume. The first study used the radioactive tracer 64Cu-DOTA and PET imaging to evaluate the effect of the convective forces. The second study combined the injection of the radioactive tracer 99mTc-DTPA and ASO, then used SPECT imaging and ex vivo tissue analysis of the effects of convective forces to bridge between the tracer and the ASO distributions. The third experiment evaluated the effects of different injection volumes on the distribution of an ASO. In the course of performing these studies we also measured the CSF volume in the subject monkeys by Magnetic Resonance Imaging.

Results

It was consistently found that larger bolus dose volumes produced greater rostral distribution along the neuraxis. Thoracic percussive treatment also increased rostral distribution of low volume injections. There was little added benefit on distribution by combining the thoracic percussive treatment with the high-volume injection. The CSF volume of the monkeys was found to be 11.9 ± 1.6 cm3.

Conclusions

These results indicate that increasing convective forces after IT injection increases distribution of molecules up the neuraxis. In particular, the use of high IT injection volumes will be useful to increase rostral CNS distribution of therapeutic ASOs for CNS diseases in the clinic.
Redemption from plight: a qualitative study on reasons behind treatment decisions among Iranian male opioid users
Authors: Amini-Rarani Mostafa , Khedmati Morasae Esmaeil , Pashaei Tahereh , Moeeni Maryam
Published: August 2020

Background

Opioid use remains a significant cause of harm to individual health. Perceived motives are of the main factors that help lead a patient into seeking treatment voluntarily to obviate that harm. The current study expands on the literature by exploring when and how male users of opioids become motivated to voluntarily seek treatment services.

Methods

In a qualitative study in Isfahan city from January 2018 to March 2019, 55 male participants who had already started a variety of treatment services to withdraw their dependence on opioids were recruited. Selection of participants was based on a maximum variation purposive sampling strategy. Each participant took part in a unstructured interview to identify his motives for seeking opioid use treatment. Interviews were undertaken in eight different treatment centers. An inductive thematic analysis method was used to analyze the interviews.

Results

The findings highlight that Iranian male opioid users have different motivations to seek treatment. To be precise, the findings illuminate three global themes and six themes as treatment-seeking motives among the participants including; motives related to family (reasonforfamily and reasonoffamily), quality of life (adverse effects on personal lifestyle and health) and economic motives (financial failure and job failure).

Conclusions

The findings can improve our understanding of the motives for seeking treatment from the perspective of opioid patients who entered themselves into treatment. Particularly, these findings could help policymakers and treatment providers to better understand opioid-use patient’s perceived concerns and fears as motives for treatment-seeking.
Bioinformatics analysis of differentially expressed genes in subchondral bone in early experimental osteoarthritis using microarray data
Authors: Wang Zhao , Ji Yong , Bao Hong-wei
Published: August 2020

Background

Osteoarthritis (OA) is the most common arthritic disease in humans, affecting the majority of individuals over 65 years of age. The aim of this study is to identify the gene expression profile specific to subchondral bone in OA by comparing the different expression profiles in experimental and sham-operation groups.

Methods

Gene expression profile GSE30322 was downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were obtained by limma package. And Database for Annotation, Visualization and Integrated Discovery (DAVID) databases were further used to identify the potential gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Furthermore, a protein–protein interaction (PPI) network was constructed and significant modules were extracted.

Results

Totally, 588 DEGs were identified including 199 upregulated DEGs and 389 downregulated DEGs screened in OA and sham-operation. GO showed that DEGs were significantly enhanced for ribosomal subunit export from nucleus and molting cycle. KEGG pathway analysis revealed that target genes were enriched in thiamine metabolism.

Conclusion

These key candidate DEGs that affect the progression of OA, and these genes might serve as potential therapeutic targets for OA.
A possible injectable tissue engineered nucleus pulposus constructed with platelet-rich plasma and ADSCs in vitro
Authors: Zhang ZhiCheng , Ma Jian , Ren DaJiang , Li Fang
Published: August 2020

Background

Injectable tissue engineered nucleus pulposus is a new idea for minimally invasive repair of degenerative intervertebral disc. The platelet-rich plasma (PRP) and adipose-derived stromal cells (ADSCs) could be harvested from autologous tissue easily. PRP contains numerous autologous growth factors and has reticulate fibrous structure which may have the potential to make ADSCs differentiate into nucleus pulposus-like cells. The goal of this study was to explore the feasibility of constructing a possible injectable tissue engineered nucleus pulposus with PRP gel scaffold and ADSCs.

Methods

After identification with flow cytometry, the rabbit ADSCs were seeded into PRP gel and cultured in vitro. At the 2nd, 4th, and 8th week, the PRP gel/ADSCs complex was observed by macroscopy, histological staining, BrdU immunofluorescence, and scanning electron microscopy. The glycosaminoglycans (GAG) in the PRP gel/ADSCs complex were measured by safranin O staining with spectrophotometry. In PRP gel/ADSCs complex, gene expression of HIF-1α, aggrecan, type II collagen were tested by RT-PCR. The injectability of this complex was evaluated.

Results

Macroscopically, the complex was solidified into gel with smooth surface and good elasticity. The safranin O dye was almost no positive staining at 2nd week; however, the positive staining of extracellular matrix was enhanced obviously at 4th and 8th week. The HE staining and SEM demonstrated that the cells were well-distributed in the reticulate scaffold. BrdU immunofluorescence showed that ADSCs can survive and proliferate in PRP gel at each time points. The level of GAG at 4th week was higher than those at 2nd week (P < 0.05), and significant difference was also noted between 4th and 8th week (P < 0.05). HIF-1α, aggrecan, type II collagen gene expression at 4th week were much more than those at 2nd week (P < 0.05), and significant differences were also noted between 4th and 8th week (P < 0.05). The flow rate of complex was 0.287 mL/min when passed through the 19-gauge needle with the 100 mmHg injection pressure.

Conclusions

Our preliminary findings suggest that the PRP gel make it possible for rabbit ADSCs differentiated into nucleus pulposus-like cells after coculture in vitro. According to the results, it is a better feasible method for construction of autologous injectable tissue engineered nucleus pulposus.
Youth unemployment and mental health: prevalence and associated factors of depression among unemployed young adults in Gedeo zone, Southern Ethiopia
Authors: Mokona Hirbaye , Yohannes Kalkidan , Ayano Getinet
Published: August 2020

Background

The high rate of unemployment among young adults in Ethiopia, which was 25.3% in 2018, is a major social, and public health concern. The risk of mental health problems like depression is higher among the unemployed than among the employed. However, there was no study conducted on the prevalence and associated factors of depression among unemployed young adults in Ethiopia. Hence, this study was aimed to assess the prevalence and associated factors of depression among unemployed young adults in Gedeo zone, Southern Ethiopia.

Methods

Community based cross sectional study design was employed among 1452 unemployed young adults in Gedeo zone, Southern Ethiopia from May to July, 2019. In order to select the study participants, systematic random sampling technique was used. The presence of depression was assessed by using Patient Health Questionnaire-9 (PHQ-9), and data about socio-demographic characteristics of study participants were collected by using structured questionnaire. Data were coded and entered into Epi-Data version 3.1, and analyzed by SPSS version 20. A multivariable logistic regression analysis was carried out to identify factors associated with depression, and variables with p values < 0.05 were considered as statistically significant. The strength of the association was presented by adjusted odds ratio with 95% confidence interval.

Result

The overall prevalence of depression among unemployed young adults in the present study was 30.9% (95% CI: 28.4%, 33.1%). Of the total study participants with depression, 56.7% had mild depression, 36% had moderate depression, and 7.3% had severe depression. Being male (AOR = 1.40, 95% CI: 1.10, 1.80), long duration of unemployment (≥ 1 years) (AOR = 1.56, 95% CI: 1.21, 1.99), low self-esteem (AOR = 1.32, 95% CI: 1.03, 1.68), poor social support (AOR = 1.98, 95% CI: 1.34, 2.93), and current alcohol use (AOR = 1.86, 95% CI: 1.33, 2.59) were significantly associated with depression.

Conclusion

The results of our study indicated that depression is an important public health problem among unemployed young adults in Ethiopia. Therefore, our study suggested that policy makers and program planners should establish appropriate strategy for prevention, early detection and management of depression among this population. Besides, addressing the need of unemployed young people, improving access to care for depression is an important next step. Furthermore, we recommend further studies to understand the nature of depression among unemployed young people, and to strengthen the current results.
Serum D-dimer, albumin and systemic inflammatory response markers in ovarian clear cell carcinoma and their prognostic implications
Authors: Chen Wei , Zhong Siyuan , Shan Boer , Zhou Shuling , Wu Xiaohua , Yang Huijuan , Ye Shuang
Published: August 2020

Background

This study attempts to evaluate whether preoperative systemic inflammatory response (SIR) markers or other hematological variables, such as albumin, D-dimer, and carbohydrate antigen 125, play roles in predicting chemotherapy response and survival outcome in patients with ovarian clear cell carcinoma (OCCC).

Methods

Preoperative leukocyte differential counts, as well as platelet, serum albumin, plasma D-dimer and CA-125 levels, were measured in patients with FIGO IC-IV ovarian clear cell cancer. The correlations of these hematological biomarkers with clinicopathological features, chemotherapy response, and survival outcomes were further analyzed. Survival time was estimated using the Kaplan-Meier model, whereas Cox regression was conducted for multivariate analysis.

Results

Among the 84 patients, 28.6% were classified as platinum resistant, and 69.0% were platinum sensitive. Preoperative CA125, albumin, and D-dimer levels; neutrophil to lymphocyte ratios (NLR); and monocyte to lymphocyte ratios were significantly correlated with FIGO stage, residual tumor, and platinum response. Platelet to lymphocyte ratio was not related to platinum response (P = 0.060). The median follow-up time was 28 months (range, 1 to 128 months). Preoperative CA125, albumin, and D-dimer levels were significant prognostic factors for overall survival (OS) and progression-free survival (PFS). In the univariate analysis, only NLR exhibited prognostic significance for PFS (P = 0.007). Multivariate analysis indicated that D-dimer > 3.27 (P = 0.001 for OS; P = 0.040 for PFS) and albumin < 39.6 (P = 0.005 for OS and P = 0.041 for PFS) retained significance.

Conclusions

Preoperative NLR has some predictive value for platinum resistance in patients with IC-IV stage OCCC but has little predictive effect on prognosis. Elevated D-dimer and reduced albumin might be potential biomarkers for worse response to first-line platinum-based chemotherapy and poor clinical outcomes.
A mosquito feeding assay to examine Plasmodium transmission to mosquitoes using small blood volumes in 3D printed nano-feeders
Authors: Graumans Wouter , Heutink Roel , van Gemert Geert-Jan , van de Vegte-Bolmer Marga , Bousema Teun , Collins Katharine A.
Published: August 2020

Background

To understand the dynamics of malaria transmission, membrane feeding assays with glass feeders are used to assess the transmission potential of malaria infected individuals to mosquitoes. However, in some circumstances, use of these assays is hindered by both the blood volume requirement and the availability of fragile, specially crafted glass feeders. 3D printed plastic feeders that require very small volumes of blood would thus expand the utility of membrane feeding assays.

Methods

Using two 3D printing production methods, MultiJet (MJ) and Digital Light Processing (DLP), we developed a plastic version of the most commonly used standard glass feeder (the mini-feeder) with an improved design, and also a smaller feeder requiring only 60 µl of blood (the nano-feeder). Performance of the 3D printed feeders was compared to standard glass mini-feeders by assessing infectivity of gametocytes to mosquitoes in standard membrane feeding assays with laboratory reared Anopheles stephensi mosquitoes and cultured Plasmodium falciparum gametocytes. In addition, the optimum number of mosquitoes that can feed on the nano-feeder was determined by evaluating fully fed mosquitoes visually and by assessing blood- meal volume with a colorimetric haemoglobin assay.

Results

The 3D printing methods allowed quick and inexpensive production of durable feeders. Infectivity of gametocytes to mosquitoes was comparable for MJ and DLP 3D printed feeders and glass feeders, and the performance of the 3D printed feeders was not influenced by repeated washing with bleach. There was no loss in transmission efficiency when the feeder size was reduced from mini-feeder to nano-feeder, and blood-meal volume assessment indicated ~10 An. stephensi mosquitoes can take a full blood-meal (median volume 3.44 µl) on a nano-feeder.

Conclusions

Here we present 3D printed mini- and nano-feeders with comparable performance to the currently used glass mini-feeders. These feeders do not require specialized glass craftsmanship, making them easily accessible. Moreover, the smaller nano-feeders will enable evaluation of smaller blood volumes that can be collected from finger prick, thus expanding the utility of membrane feeding assays and facilitating a more thorough evaluation of the human infectious reservoir for malaria.
Dog importation and changes in canine intestinal nematode prevalence in Colorado, USA, 2013–2017
Authors: Drake Jason , Parrish Rudolph
Published: August 2020

Background

Animal rescue and animal welfare organizations are relocating thousands of dogs per year following natural disasters and in attempts to provide greater adoption opportunities. Many dogs are sourced from the southeastern USA, which historically has a high prevalence rate for many parasites and parasitic diseases. The Colorado Department of Agriculture Pet Animal Care Facilities Act (PACFA) requires animal shelters and animal welfare organizations to report annually a variety of statistics including the numbers of dogs imported into Colorado from out of state. The Companion Animal Parasite Council (CAPC) provides data nationally, down to the state and county level, on a variety of common parasitic and vector borne diseases. These data make it possible to track changes in parasite prevalence over several years.

Methods

Test results for canine roundworm, hookworm and whipworm were collected from the CAPC maps for 2013–2017. Dog importation data for 2014–2017 was collected from PACFA reports. For evaluation of the statistical significance of prevalence changes when comparing 2013 to 2017, 2 × 2 contingency tables were constructed with both positive and negative test results for each year and the data assessed using Chi-square tests to determine if the 2017 prevalence was significantly different than the 2013 prevalence for roundworm, hookworm and whipworm.

Results

Significant increases in intestinal nematode prevalence occurred in Colorado from 2013 to 2017. The prevalence of canine roundworm rose 35.60%, the prevalence of canine hookworm rose 137.33% and the prevalence of canine whipworm rose 63.68%. From 2014 to 2017, over 114,000 dogs were transported into Colorado from out-of-state, by more than 130 animal shelters and rescue organizations. Three of the larger organizations reported that the majority of their dogs were obtained from New Mexico, Texas and Oklahoma. Texas and Oklahoma have historically much higher parasite prevalence than Colorado.

Conclusions

Veterinarians in areas with historically low parasite prevalence where dogs from high parasite prevalence areas are arriving for adoption may need to reevaluate their recommendations regarding fecal examination and deworming frequencies as historic levels of intestinal parasite infection may no longer be accurate assessments of future infection risks.
The association of dietary inflammatory index with urinary risk factors of kidney stones formation in men with nephrolithiasis
Authors: Maddahi Niloofarsadat , Yarizadeh Habib , Aghamir Seyed Mohammad Kazem , Alizadeh Shahab , Yekaninejad Mir Saeed , Mirzaei Khadijeh
Published: August 2020

Objective

Inflammation plays a leading role in the pathogenesis of nephrolithiasis. The association of the dietary inflammatory index (DII) with urinary lithogenic factors is unclear. This study aimed to evaluate the relation of DII to urinary risk factors of kidney stones formation.

Results

Of 264 participants, 61.4% (n = 162), 72% (n = 190), 74.6% (n = 197), 68.6% (n = 181), and 80.3% (n = 212) had hyperoxaluria, hypercreatininuria, hypercalciuria, hyperuricosuria, hypocitraturia, respectively. There was a significant increasing trajectory in urinary calcium, uric acid, and creatinine as well as a decreasing trend in urinary citrate across tertiles of DII score (all P = ≤0.001). After multivariate adjustment for energy intake, age, physical activity and body mass index, high DII scores were associated with elevated odds of having hypercreatininuria (OR = 2.80, 95%CI: 1.10–7.12, Ptrend = 0.04), hypercalciuria (OR = 7.44, 95%CI: 2.62–21.14, Ptrend ≤ 0.001), hyperuricosuria (OR = 2.22, 95%CI: 1.001–4.95, Ptrend = 0.05), and hypocitraturia (OR = 5.84, 95%CI: 2.14–15.91, Ptrend ≤ 0.001). No association was identified between DII and hyperoxaluria.
Dual-specificity phosphatase (DUSP6) in human glioblastoma: epithelial-to-mesenchymal transition (EMT) involvement
Authors: Zuchegna Candida , Di Zazzo Erika , Moncharmont Bruno , Messina Samantha
Published: August 2020

Objective

Glioblastoma (GBM) is the most aggressive and common form of primary brain cancer. Survival is poor and improved treatment options are urgently needed. Dual specificity phosphatase-6 (DUSP6) is actively involved in oncogenesis showing unexpected tumor-promoting properties in human glioblastoma, contributing to the development and expression of the full malignant and invasive phenotype. The purpose of this study was to assess if DUSP6 activates epithelial-to-mesenchymal transition (EMT) in glioblastoma and its connection with the invasive capacity.

Results

We found high levels of transcripts mRNA by qPCR analysis in a panel of primary GBM compared to adult or fetal normal tissues. At translational levels, these data correlate with high protein expression and long half-life values by cycloheximide-chase assay in immunoblot experiments. Next, we demonstrate that DUSP6 gene is involved in epithelial-to-mesenchymal transition (EMT) in GBM by immunoblot characterization of the mesenchymal and epithelial markers. Vimentin, N-Cadherin, E-Cadherin and fibronectin were measured with and without DUSP6 over-expression, and in response to several stimuli such as chemotherapy treatment. In particular, the high levels of vimentin were blunted at increasing doses of cisplatin in condition of DUSP6 over-expression while N-Cadherin contextually increased. Finally, DUSP6 per se increased invasion capacity of GBM. Overall, our data unveil the DUSP6 involvement in invasive mesenchymal-like properties in GBM.
Self-weighing frequency and the incidence of type 2 diabetes: post hoc analysis of a cluster-randomized controlled trial
Authors: Sakane Naoki , Oshima Yoshitake , Kotani Kazuhiko , Suganuma Akiko , Nirengi Shinsuke , Takahashi Kaoru , Sato Juichi , Suzuki Sadao , Izumi Kazuo , Kato Masayuki , Noda Mitsuhiko , Kuzuya Hideshi
Published: August 2020

Objectives

Frequent self-weighing is associated with weight loss and maintenance, but the relationship between frequent self-weighing and the incidence of type 2 diabetes (T2D) remains unclear. The study aim was to examine the association between self-weighing frequency and the incidence of T2D in people with impaired fasting glucose (IFG).

Results

We tested the hypothesis that self-weighing frequency and the incidence of T2D are associated in 2607 people with IFG (1240 in the intervention arm; 1367 in the self-directed control arm). Both arms received a weighing scale with storage function. Healthcare providers offered a one-year goal-focused lifestyle intervention via phone. Participants were divided into 4 categories based on self-weighing frequency (No data sent [reference group], low: < 2 times/week, middle: 3–4 times/week, and high: 5–7 times/week). The adjusted hazard ratio (AHR) and 95% confidence interval (CI) were calculated. In the intervention arm, middle- and high-frequency self-weighing were associated with a decreased incidence of T2D relative to the reference group (AHR = 0.56, 95% CI [0.32, 0.98] and AHR = 0.43, 95% CI [0.25, 0.74], respectively). In the control arm, high-frequency self-weighing was also associated with a decreased incidence of T2D relative to the reference group (AHR = 0.54, 95% CI [0.35, 0.83]).

Trial registrationThis trial has been registered with the University Hospital Medical Information Network (UMIN000000662).
Health status, lifestyle habits, and perceived social support in long-term cancer survivors: a cross-sectional study
Authors: León-Salas Beatriz , Zabaleta-del-Olmo Edurne , Llobera Joan , Bolíbar-Ribas Bonaventura , López-Jiménez Tomás , Casajuana-Closas Marc , Esteva Magdalena
Published: August 2020

Objective

To compare the presence of comorbidities and self-perceived health and social support between long-term cancer survivors and people without a history of cancer from a clinical trial examining the effects of a multiple risk behavior intervention.

Results

Of the 4259 people studied, 190 (4.46%) were cancer survivors. They had a mean ± SD age of 62.8 ± 7 years vs. 58.7 ± 8 years (P < 0.01) for non-cancer people and were more likely to be on long-term sick leave (11.9 vs. 3.5%, P < 0.001). No differences were observed for smoking, adherence to the Mediterranean diet, physical activity, obesity, or social support. Cancer survivors were more likely to have worse self-perceived health (OR 1.82; 95% CI 1.02–2.75), more comorbidities (OR 1.68; 95% CI 1.18–2.39), COPD (OR 2.17; 95% CI 1.25–3.78), and depression (OR 1.65; 95% CI 1.06–2.57). Older age and worse self-perceived health were independent predictors of survivorship in the adjusted analysis.
Mesenchymal stromal cell therapies: immunomodulatory properties and clinical progress
Authors: Wu Xiaomo , Jiang Ju , Gu Zhongkai , Zhang Jinyan , Chen Yang , Liu Xiaolong
Published: August 2020

Mesenchymal stromal cells (MSCs) are a subset of heterogeneous non-hematopoietic fibroblast-like cells that can differentiate into cells of multiple lineages, such as chondrocytes, osteoblasts, adipocytes, myoblasts, and others. These multipotent MSCs can be found in nearly all tissues but mostly located in perivascular niches, playing a significant role in tissue repair and regeneration. Additionally, MSCs interact with immune cells both in innate and adaptive immune systems, modulating immune responses and enabling immunosuppression and tolerance induction. Understanding the biology of MSCs and their roles in clinical treatment is crucial for developing MSC-based cellular therapy for a variety of pathological conditions. Here, we review the progress in the study on the mechanisms underlying the immunomodulatory and regenerative effects of MSCs; update the medical translation of MSCs, focusing on the registration trials leading to regulatory approvals; and discuss how to improve therapeutic efficacy and safety of MSC applications for future.
Mortality and morbidity of low-grade red blood cell transfusions in septic patients: a propensity score-matched observational study of a liberal transfusion strategy
Authors: Nilsson Caroline Ulfsdotter , Bentzer Peter , Andersson Linnéa E. , Björkman Sofia A. , Hanssson Fredrik P. , Kander Thomas
Published: August 2020

Background

Red blood cell (RBC) transfusions are associated with risks including immunological reactions and volume overload. Current guidelines suggest a restrictive transfusion strategy in most patients with sepsis but based on previous randomized controlled trials and observational studies, there are still uncertainties about the safety in giving low-grade RBC transfusions to patients with sepsis.

Methods

Critically ill patients with severe sepsis or septic shock admitted to a university hospital intensive care unit between 2007 and 2018 that received less or equal to 2 units of RBCs during the first 5 days of admission were propensity score matched to controls. Outcomes were 90- and 180-day mortality, highest acute kidney injury network (AKIN) score the first 10 days, days alive and free of organ support the first 28 days after admission to the intensive care unit and highest sequential organ failure assessment score (SOFA-max).

Results

Of 9490 admissions, 1347 were diagnosed with severe sepsis or septic shock. Propensity-score matching resulted in two well-matched groups with 237 patients in each. The annual inclusion rate in both groups was similar. The median hemoglobin level before RBC transfusion was 95 g/L (interquartile range 88–104) and the majority of the patients were transfused in first 2 days of admission. Low-grade RBC transfusion was associated with increased 90- and 180-day mortality with an absolute risk increase for death 9.3% (95% confidence interval: 0.6–18%, P = 0.032) and 11% (95% confidence interval: 1.7–19%, P = 0.018), respectively. Low-grade RBC transfusion also correlated with increased kidney, circulatory and respiratory failure and higher SOFA-max score.

Conclusions

Low-grade RBC transfusion during the first 5 days of admission was associated with increased mortality and morbidity in a liberal transfusion setting. The results support the current practice of a restrictive transfusion strategy in septic critically ill patients.
Assessing the suitability of the Greenhouse Gas Protocol for calculation of emissions from public cloud computing workloads
Authors: Mytton David
Published: August 2020

Efficiency improvements over the past decade have meant that data center energy usage has decoupled from the growth in IT workloads. Much of this efficiency improvement has been attributed to innovations made by “hyperscale” public cloud vendors, where a large proportion of new IT workloads are now being deployed. However, the move to the cloud is making it more difficult to assess the environmental impact of workloads deployed there. Although the large cloud vendors are amongst the largest purchasers of renewable electricity, customers do not have access to the data they need to complete emissions assessments under the Greenhouse Gas Protocol. Data such as Power Usage Effectiveness, emissions factors and equipment embodied energy are not available from public cloud vendors. This paper demonstrates how the Greenhouse Gas Protocol method of assessment of IT emissions does not work for public cloud environments and suggests how this can be tackled by the cloud vendors themselves.
How does sediment exposure affect corals? A systematic review protocol
Authors: Tuttle Lillian J. , Johnson Craig , Kolinski Steve , Minton Dwayne , Donahue Megan J.
Published: August 2020

Background

Local management action to address coral-reef stressors can improve reef health and mitigate the effects of global climate change. Coastal development and runoff lead to sedimentation, which directly impacts coral recruitment, growth, mortality, and the ecosystem services that coral reefs provide. Decision making for reef resilience in the face of global and local stressors requires information on thresholds for management action. In response to needs identified by reef managers, we plan to conduct a systematic review and meta-analysis that will explore the effects of both deposited and suspended sediment on corals to identify single and interacting stressor thresholds. We will identify levels of sediment exposure (i.e., concentration, duration, and frequency) that cause adverse physical, physiological, behavioral, developmental, and ecological responses in coral and describe geographic and taxonomic patterns in these responses. Our ultimate goal is to provide managers with sediment exposure thresholds that can be expected to cause these responses.

Methods

Our systematic review will synthesize available evidence on the effects of suspended and deposited sediment on corals. The research questions were formulated with an advisory team to support management decisions concerning local reef stressors in waters under U.S. federal jurisdiction. While the advisory team is most concerned with reefs adjacent to U.S. Pacific Islands, our review will include studies that examine reef-building coral species around the world. We will search online databases and grey literature to obtain a list of potential studies, assess their relevance, and critically appraise them for validity and risk of bias. Provided enough data can be extracted from relevant experimental studies, we will conduct meta-analyses that examine changes in coral health and survival in response to suspended and/or deposited sediment, with the goal to define sediment thresholds for reef managers. If enough data are available from within the U.S. Pacific Islands, we will construct region-, site-, and/or species-specific thresholds to improve local management.
The effect of anatomical variables and use of the Lifts system on hearing outcomes after implantation of an active transcutaneous bone conduction device in bilateral congenital conductive hearing loss
Authors: Yang Jinsong , Zhao Chunli , Liu Yujie , Gao Mengdie , Ren Ran , Wang Danni , Huang Zhigang , Zhao Shouqin
Published: August 2020

Background

Malformations of the temporal bone present different challenges to the implantation of a transcutaneous active bone conduction device, such as Bonebridge (Med-el, Innsbruck, Austria). This study aims to describe the benefits of high-resolution computed tomography (HRCT) in preoperative assessment and to analyze whether characteristics of the mastoid process, intraoperative compression of the dura or sigmoid sinus, and the use of the Lifts system, lead to differences in audiological performance after implantation.

Methods

We examined 110 cases of congenital microtia. The structure of the temporal bone was examined using HRCT and a 3D simulation software program. The mean anteroposterior mastoid bone thickness from the external auditory canal to the sigmoid sinus was measured (a measurement referred to as “AP”, hereafter). Sound field threshold (SFT), speech reception threshold (SRT) in noise, and word recognition score (WRS) in quiet, before and after implantation, were also measured. Independent variables were recorded in all patients: mastoid type (well pneumatized or poorly pneumatized), the presence of dural or sigmoid sinus compression, and the use of the Lifts system.

Results

We found that the mean AP in the non-compression group was 16.2 ± 2.3 mm and in the compression group, 13.1 ± 2.9 mm ( p < 0.001). We analyzed the hearing improvement of patients grouped by mastoid development, dural or sigmoid sinus compression, and use of the Lifts system, and found that these factors did not interact and that they had no influence on the hearing outcomes ( p > 0.05).

Conclusions

The AP dimension in the non-compression group was significantly larger than that in the compression group. This finding combined with the ROC curve analysis revealed the AP dimension was a high-accuracy predictor of potential surgical complications involving the dura and sigmoid sinus compression. Further analysis revealed that there was no interaction between the chosen variables: mastoid type, dural or sigmoid sinus compression, and the use of the Lifts system, and that all of these factors had no significant impact on hearing performance. Bonebridge was shown to produce effective and stable bone conduction and to improve patients’ hearing performance.
Calcareous nannofossil biostratigraphy of the Lower–Middle Pleistocene boundary of the GSSP, Chiba composite section in the Kokumoto Formation, Kazusa Group, central Japan, and implications for sea-surface environmental changes
Authors: Kameo Koji , Kubota Yoshimi , Haneda Yuki , Suganuma Yusuke , Okada Makoto
Published: August 2020

The Chiba composite section (CbCS), in the middle of the Boso Peninsula in central Japan, was ratified as the Global Boundary Stratotype Section and Point (GSSP) for the Lower–Middle Pleistocene boundary, accompanied by the Matuyama–Brunhes (M–B) paleomagnetic polarity boundary in January 2020. This study examined the calcareous nannofossil biostratigraphy of the CbCS to describe potential nannofossil events and discuss sea-surface environments around the M–B paleomagnetic polarity boundary. There are no clear biohorizons at the M–B paleomagnetic polarity boundary, although a temporary disappearance of Gephyrocapsa specimens (≥ 5 μm in diameter), an important calcareous nannofossil genus in the Pleistocene, occurs just above the Lower–Middle Pleistocene boundary. Although this is a characteristic event around the M–B paleomagnetic polarity boundary, it is unclear whether the event is globally traceable.

Changes in the environmental proxy taxa of calcareous nannofossils in the CbCS revealed that sea-surface environments were driven by glacial-interglacial and millennial-scale climate forces. The time-transgressive change of the Tn value, a calcareous nannofossil temperature index, is mostly concordant with the planktonic foraminiferal oxygen isotope fluctuation. Abundant occurrences of a warm-water species, Umbilicosphaera spp., indicate that the Kuroshio Current was strong after ~ 783 ka. Even the strong influence of the Kuroshio Current, cooling events related to southward movements of the Kuroshio Front occurred every 10,000 years based on the presence of a cold-water taxon, Coccolithus pelagicus. Additionally, the inflow of coastal waters strengthened after ~ 778 ka because of abundant occurrences of Helicosphaera spp. Millennial-scale sea-surface changes were also inferred from detected floral fluctuations of less than 10,000 years.

Graphical abstract
Computational investigation, virtual docking simulation of 1, 2, 4-Triazole analogues and insillico design of new proposed agents against protein target (3IFZ) binding domain
Authors: Adeniji Shola Elijah , Arthur David Ebuka , Abdullahi Mustapha , Adalumo Olajumoke Bosede
Published: August 2020

Background

The reoccurrence of the resistant strains of Mycobacterium tuberculosis to available drugs/medications has mandated for the development of more effective anti-tubercular agents with efficient activities. Therefore, this work utilized the application of modeling technique to predict the inhibition activities of some prominent compounds which been reported to be efficient against M. tuberculosis. To accomplish the purpose of this work, multiple regression and genetic function approximation were adopted to create the model.

Results

The established model was swayed with topological descriptors: MATS7s, SM1_DzZ, TDB3v, and RDF70v. More also, interactions between the compounds and the target “DNA gyrase” were evaluated via docking approach utilizing the PyRx and Discovery Studio simulated software. Meanwhile, compound 19 has the most perceptible binding affinity of − 16.5 kcal/mol. Consequently, compound 19 served as a reference structural template and insight to design twelve novel hypothetical agents with more competent activities. Meanwhile, compound 19h was observed with high activity among the designed compounds with more prominent binding affinities of − 21.6 kcal/mol.

Conclusion

Therefore, this research recommends in vivo, in vitro screening and pharmacokinetic properties to be carried out in order to determine the toxicity of the designed compounds.
Seizures and epilepsy secondary to viral infection in the central nervous system
Authors: Zhang Peng , Yang Yuting , Zou Jialin , Yang Xinrui , Liu Qiankun , Chen Yangmei
Published: August 2020

Viral infection in the central nervous system (CNS) is a common cause of seizures and epilepsy. Acute symptomatic seizures can occur in the context of almost all types of acute CNS viral infection. However, late unprovoked seizures and epilepsy may not be frequent after viral infection of the CNS. The incidence of seizures and epilepsy after CNS viral infection is mainly dependent on the brain region of infection. It remains to be determined whether treatment of CNS viral infection using antiepileptic drugs (AEDs) can prevent seizures and subsequent epilepsy in patients, particularly with regard to the timing, drug choice and dosage, and duration of AEDs. The postoperative outcome of seizures in patients with intractable epilepsy caused by viral encephalitis primarily depends on the epileptogenic zone. In addition, neuroinflammation is known to be widely involved in the generation of seizures during CNS viral infection, and the effects of anti-inflammatory therapies in preventing seizures and epilepsy secondary to CNS viral infection require further studies. In this review, we discuss the incidence, mechanisms, clinical management and prognosis of seizures and epilepsy secondary to CNS viral infection, and summarize common CNS viral infections that cause seizures and epilepsy.
Clinical Uses and Impacts of Emergency Manuals During Perioperative Crises
Authors: Goldhaber-Fiebert Sara N. , Bereknyei Merrell Sylvia , Agarwala Aalok V. , De La Cruz Monica M. , Cooper Jeffrey B. , Howard Steven K. , Asch Steven M. , Gaba David M.
Published: August 2020

BACKGROUND:

Performing key actions efficiently during crises can determine clinical outcomes, yet even expert clinicians omit key actions. Simulation-based studies of crises show that correct performance of key actions dramatically increases when emergency manuals (EMs) are used. Despite widespread dissemination of EMs, there is a need to understand in clinical contexts, when, how, and how often EMs are used and not used, along with perceived impacts.

METHODS:

We conducted interviews with the anesthesia professionals involved in perioperative crises, identified with criterion-based sampling, occurring between October 2014 and May 2016 at 2 large academic medical centers with a history of EM training and implementation. Our convergent, mixed-methods study of the interview data extracted quantitative counts and qualitative themes of EM use and nonuse during clinical crises.

RESULTS:

Interviews with 53 anesthesia professionals yielded 80 descriptions of applicable clinical crises, with varying durations and event types. Of 69 unique patients whose cases involved crises, the EM was used during 37 (54%; 95% confidence interval [CI], 41–66). Impacts on clinician team members included decreased stress for individual anesthesia professionals (95%), enabled teamwork (73%), and calmed atmosphere (46%). Impacts on delivery of patient care included specific action improvements, including catching errors of omission, for example, turning off anesthetic during cardiac arrest, only after EM use (59%); process improvements, for example, double-checking all actions were completed (41%); and impediments (0%). In 8% of crises, EM use was associated with potential distractions, although none were perceived to harm delivery of patient care. For 32 EM nonuses (46%; 95% CI, 34–59), participants self-identified errors of omission or delays in key actions (56%), all key actions performed (13%), and crisis too brief for EM to be used (31%).

CONCLUSIONS:

This study provides evidence that EMs in operating rooms are being used during many applicable crises and that clinicians perceive EM use to add value. The reported negative effects were minimal and potentially offset by positive effects.
Perioperative Management of Children on Ketogenic Dietary Therapies
Authors: Conover Zacherie R. , Talai Afsaneh , Klockau Katherine S. , Ing Richard J. , Chatterjee Debnath
Published: August 2020

Ketogenic diet therapy (KDT) is an effective treatment modality for children with drug-resistant epilepsy and certain other metabolic and neurologic disorders. With a resurgence of interest in KDT, pediatric anesthesiologists are increasingly encountering children on KDT for a variety of surgical and medical procedures. Maintenance of ketosis is critical throughout the perioperative period, and if not managed appropriately, these patients are at an increased risk of seizures. This review article provides an overview of the clinical indications, contraindications, proposed anticonvulsant mechanisms, initiation, and monitoring of children on KDTs. Recommendations for the perioperative anesthetic management of children on KDT are summarized. A comprehensive table listing the carbohydrate content of common anesthetic drugs is also included.
Specific Binding and Cooperative Binding of Dodecylpyridinium Chloride to Water-Soluble Calix[n]arenes and Effect of Cerium and Uranyl Cations
Authors: Murakami Kiyofumi , Waizumi Kenji
Published: August 2020

Binding of dodecylpyridinium chloride (DPC) to water-soluble calix[n]arenes (n = 4, 6, 8) (CALXSn) has been studied by potentiometric titration. The binding isotherms were found to be composed of two phases; one is strong specific binding to one site and the other is cooperative binding to residual sites. Thermodynamic parameters for the specific binding suggests that the complex is stabilized by van der Waals force between the alkyl chain of DPC and hydrophobic cavity of CALXSn in addition to electrostatic force between opposite charges of DPC and CALXSn. The specific site was highly reduced in the presence of cerium cation for CALXS4 and of uranyl cation for CALXS6 and by the pH change from 7.0 to 12.5 for CALXS8. These effects were interpreted by competitive binding of the metal cations and the pyridinium cation of DPC to the specific sites of CALXS4 and CALXS6, and by deprotonation of hydroxyl group having pKa = 10.1 and/or accompanying conformational change of CALXS8. The cooperative binding takes place in one stage for CALXS4 and CALXS6 but in two stages for CALXS8. The multiple-stage cooperativity was consistent with ‘inverted double cone’ conformation of CALXS8. The results were discussed as a model of ligand binding to protein local structure.