bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo/ex vivo efficacy of artemether–lumefantrine and artesunate–amodiaquine as first-line treatment for uncomplicated falciparum malaria in children: an open label randomized controlled trial in Burkina Faso
Authors: Lingani Moussa , Bonkian Léa Nadège , Yerbanga Isidore , Kazienga Adama , Valéa Innocent , Sorgho Hermann , Ouédraogo Jean Bosco , Mens Petronella Francisca , Schallig Henk D. F. H. , Ravinetto Raffaella , d’Alessandro Umberto , Tinto Halidou
Published: January 2020

Background

Artemisinin-based combination therapy (ACT) is recommended to improve malaria treatment efficacy and limit drug-resistant parasites selection in malaria endemic areas. 5 years after they were adopted, the efficacy and safety of artemether–lumefantrine (AL) and artesunate–amodiaquine (ASAQ), the first-line treatments for uncomplicated malaria were assessed in Burkina Faso.

Methods

In total, 440 children with uncomplicated Plasmodium falciparum malaria were randomized to receive either AL or ASAQ for 3 days and were followed up weekly for 42 days. Blood samples were collected to investigate the ex vivo susceptibility of P. falciparum isolates to lumefantrine, dihydroartemisinin (the active metabolite of artemisinin derivatives) and monodesethylamodiaquine (the active metabolite of amodiaquine). The modified isotopic micro test technique was used to determine the 50% inhibitory concentration (IC50) values. Primary endpoints were the risks of treatment failure at days 42.

Results

Out of the 440 patients enrolled, 420 (95.5%) completed the 42 days follow up. The results showed a significantly higher PCR unadjusted cure rate in ASAQ arm (71.0%) than that in the AL arm (49.8%) on day 42, and this trend was similar after correction by PCR, with ASAQ performing better (98.1%) than AL (91.1%). Overall adverse events incidence was low and not significantly different between the two treatment arms. Ex vivo results showed that 6.4% P. falciparum isolates were resistant to monodesthylamodiaquine. The coupled in vivo/ex vivo analysis showed increased IC50 values for lumefantrine and monodesethylamodiaquine at day of recurrent parasitaemia compared to baseline values while for artesunate, IC50 values remained stable at baseline and after treatment failure (p > 0.05).

Conclusion

These findings provide substantial evidence that AL and ASAQ are highly efficacious for the treatment of uncomplicated malaria in children in Burkina Faso. However, the result of P. falciparum susceptibility to the partner drugs advocates the need to regularly replicate such surveillance studies. This would be particularly indicated when amodiaquine is associated in seasonal malaria chemoprophylaxis (SMC) mass drug administration in children under 5 years in Burkina Faso.

Trial registration clinicaltrials, NCT00808951. Registered 05 December 2008,https://clinicaltrials.gov/ct2/show/NCT00808951?cond=NCT00808951&rank=1
Corpus cavernosum smooth muscle cell dysfunction and phenotype transformation are related to erectile dysfunction in prostatitis rats with chronic prostatitis/chronic pelvic pain syndrome
Authors: Wang Guang-chun , Huang Tian-run , Hu Yang-yang , Wang Ke-yi , Shi Heng , Yin Lei , Peng Bo
Published: January 2020

Background

The relationship between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED) has been shown in many studies. However, the specific mechanism remains unclear. This study was to investigate the corpus cavernosum smooth muscle cell function and phenotype transformation in Experimental autoimmune prostatitis (EAP) rats.

Methods

EAP was induced in rats by using prostate protein supplemented with immuneadjuvant extraction, and the max-ICP and MAP were measured. IHC and Masson staining were done to assess inflammatory infiltration and collagen deposition in the corpus cavernosum, respectively. Subsequently, normal rat and EAP rat CCSMCs were purified by tissue block implantation and differential adherence method. The oxidative stress, smooth muscle phenotype transformation, cell cycle and intracellular calcium ion transport were also evaluated.

Results

The ratio of max ICP/MAP in EAP rats significantly reduced, and the TNF-α content and collagen deposition in the corpus cavernosum markedly increased as compared to healthy rats. High-purity rat CCSMCs were obtained. Oxidative stress was evident and the cGMP content decreased in the EAP rat CCSMCs. The expression of Cav1.2, IP3R1 and RyR2 increased, but the SERCA2 expression decreased in EAP rat CCSMCs, which was accompanied by increased intracellular calcium. Increased expression of OPN, collagen and KCa3.1, decreased Calponin expression and increased proportion of cells in the S phase were also observed in the EAP rat CCSMCs.

Conclusion

CP causes oxidative stress and imbalance of intracellular calcium in CCSMCs and promotes CCSMCs transformation from contractile to synthetic state, which may be involved in the pathogenesis of ED.
Soybean lecithin stabilizes disulfiram nanosuspensions with a high drug-loading content: remarkably improved antitumor efficacy
Authors: Li Haowen , Liu Biao , Ao Hui , Fu Jingxin , Wang Yian , Feng Yue , Guo Yifei , Wang Xiangtao
Published: January 2020

Disulfiram (DSF) has been considered as “Repurposing drug” in cancer therapy in recent years based on its good antitumor efficacy. DSF is traditionally used as an oral drug in the treatment of alcoholism. To overcome its rapid degradation and instability, DSF nanosuspensions (DSF/SPC-NSps) were prepared using soybean lecithin (SPC) as a stabilizer of high drug-loaded content (44.36 ± 1.09%). Comprehensive characterization of the nanosuspensions was performed, and cell cytotoxicity, in vivo antitumor efficacy and biodistribution were studied. DSF/SPC-NSps, having a spherical appearance with particle size of 155 nm, could remain very stable in different physiological media, and sustained release. The in vitro MTT assay indicated that the cytotoxicity of DSF/SPC-NSps was enhanced remarkably compared to free DSF against the 4T1 cell line. The IC50 value decreased by 11-fold (1.23 vs. 13.93 μg/mL, p < 0.01). DSF/SPC-NSps groups administered via intravenous injections exhibited better antitumor efficacy compared to the commercial paclitaxel injection (PTX injection) and had a dose-dependent effect in vivo. Notably, DSF/SPC-NSps exhibited similar antitumor activity following oral administration as PTX administration via injection into a vein. These results suggest that the prepared nanosuspensions can be used as a stable delivery vehicle for disulfiram, which has potential application in breast cancer chemotherapy.
Plasma retinol-binding protein 4 in the first and second trimester and risk of gestational diabetes mellitus in Chinese women: a nested case-control study
Authors: Jin Chuyao , Lin Lizi , Han Na , Zhao Zhiling , Liu Zheng , Luo Shusheng , Xu Xiangrong , Liu Jue , Wang Haijun
Published: January 2020

Background

To assess the association between plasma retinol-binding protein 4 (RBP4) levels both in the first trimester and second trimester and risk of gestational diabetes mellitus (GDM).

Methods

Plasma RBP4 levels and insulin were measured among 135 GDM cases and 135 controls nested within the Peking University Birth Cohort in Tongzhou. Multivariable linear regression analysis was conducted to assess the influence of RBP4 levels on insulin resistance. Conditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval (CI) between RBP4 levels and risk of GDM.

Results

The GDM cases had significantly higher levels of RBP4 in the first trimester than controls (medians: 18.0 μg/L vs 14.4 μg/L; P < 0.05). Plasma RBP4 concentrations in the first and second trimester were associated with fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and the quantitative insulin sensitivity check index (QUICKI) in the second trimester (all P < 0.001). With adjustment for diet, physical activity, and other risk factors for GDM, the risk of GDM increased with every 1-log μg/L increment of RBP4 levels, and the OR (95% CI) was 3.12 (1.08–9.04) for RBP4 in the first trimester and 3.38 (1.03–11.08) for RBP4 in the second trimester.

Conclusions

Plasma RBP4 levels both in the first trimester and second trimester were dose-dependently associated with increased risk of GDM.
Effect of Loureirin B on Crohn’s disease rat model induced by TNBS via IL-6/STAT3/NF-κB signaling pathway
Authors: Sun Xueliang , Wen Ke , Xu Zhizhong , He Zongqi , Wu Bensheng , Yang Xiao , Wang Xiaopeng
Published: January 2020

Background

Crohn’s disease (CD) is a chronic relapsing form of inflammatory bowel disease, seriously threatening human beings health. However, the pathogenesis of CD is still unclear and there is no specific effective drug for treatment of CD. Resina Donis (RD) obtained from Dracaena cochinchinensis (Lour.) S. C. Chen (Liliaceae), has been used for the treatment of CD clinically. Loureirin B (LB) is one of the most important chemical compositions and physiologically active ingredients of resina draconis. It has the molecular structure propan-1-one, 1-(4-hydroxyphenyl)-3-(2,4,6-trimethoxyphenyl)-1-(4-hydroxyphenyl)-3-(2,4,6-trimethoxyphenyl) propan-1-one. The aim of this study was to investigate the effect of LB on CD and explore the underlying mechanisms.

Methods and results

In this study, the result demonstrated that LB prolonged the survival time of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rats and alleviated colonic damage in a dose dependent manner. Besides, LB remarkably ameliorated TNBS-induced inflammatory response via regulation of cytokines in the colonic tissues. Moreover, LB could reverse the established fibrosis and impede the accumulation infiltration, and improve the apoptosis induced by TNBS in a dose dependent manner. Further, LB dramatically suppressed TNBS-induced the activation of IL-6/STAT3/NF-κB signaling pathway.

Conclusions

These findings suggested that LB could be beneficial regarding ameliorating TNBS-induced CD, which may represent a novel approach to treat CD and provide an alternative choice for disorders associated with CD.
The small GTPase ARF6 regulates GABAergic synapse development
Authors: Kim Hyeonho , Jung Hyeji , Jung Hyunsu , Kwon Seok-Kyu , Ko Jaewon , Um Ji Won
Published: January 2020

ADP ribosylation factors (ARFs) are a family of small GTPases composed of six members (ARF1–6) that control various cellular functions, including membrane trafficking and actin cytoskeletal rearrangement, in eukaryotic cells. Among them, ARF1 and ARF6 are the most studied in neurons, particularly at glutamatergic synapses, but their roles at GABAergic synapses have not been investigated. Here, we show that a subset of ARF6 protein is localized at GABAergic synapses in cultured hippocampal neurons. In addition, we found that knockdown (KD) of ARF6, but not ARF1, triggered a reduction in the number of GABAergic synaptic puncta in mature cultured neurons in an ARF activity-dependent manner. ARF6 KD also reduced GABAergic synaptic density in the mouse hippocampal dentate gyrus (DG) region. Furthermore, ARF6 KD in the DG increased seizure susceptibility in an induced epilepsy model. Viewed together, our results suggest that modulating ARF6 and its regulators could be a therapeutic strategy against brain pathologies involving hippocampal network dysfunction, such as epilepsy.
A reflection on the role of genetics in the concept of “epileptic encephalopathy”, as emerged from the most recent ILEA classification of epilepsy
Authors: Russo Angelo , Gobbi Giuseppe
Published: January 2020

The International League Against Epilepsy (ILAE) has been working to standardize the epilepsy classifications for over a hundred years.

The latest epilepsy classification has been recently carried out with a careful overview on several topics including the “epileptic encephalopathies” concept and several constructive discussions on this topic have taken place in the international community of epileptologists.

Here we wish to share our reflection on a statement of the ILAE commission on the “epileptic encephalopathy” concept, which in our opinion pays less attention to the “electroclinical syndromes” concept in favor of the new and very rapid genetic advances, thus generating confusion.

Our aim is both to preserve the role of electroclinical syndromes, while allowing for the association of the phenotype with specific gene mutations, and to underline the importance of bringing electroclinical syndromes back to the forefront of epileptology.

We believe the “match” is still open and for this reason we would like to share our considerations and to open a constructive debate on the “epileptic encephalopathy” concept.
High Quality Targeted Temperature Management (TTM) After Cardiac Arrest
Authors: Taccone Fabio Silvio , Picetti Edoardo , Vincent Jean-Louis
Published: January 2020

Targeted temperature management (TTM) is a complex intervention used with the aim of minimizing post-anoxic injury and improving neurological outcome after cardiac arrest. There is large variability in the devices used to achieve cooling and in protocols (e.g., for induction, target temperature, maintenance, rewarming, sedation, management of post-TTM fever). This variability can explain the limited benefits of TTM that have sometimes been reported. We therefore propose the concept of “high-quality TTM” as a way to increase the effectiveness of TTM and standardize its use in future interventional studies.
Effects of sang-qi granules on blood pressure and endothelial dysfunction in stage I or II hypertension: study protocol for a randomized double-blind double-simulation controlled trial
Authors: Shi Haoyue , Yang Deshuang , Qiao Jiajun , Sun Rui , Li Ruihan , Zhu Chunlin , Jing Ruiqing , Liu Liping , Huang Li , Li Lin
Published: January 2020

Background

Worldwide, hypertension is an important public health challenge because of its high prevalence and the concomitant risks of cardiovascular disease. It induces half of the coronary heart disease and approximately two-thirds of the cerebrovascular disease burden. Vascular endothelial dysfunction has important roles in the pathophysiology of essential hypertension. Types I and II hypertension can be treated with sang-qi granules (SQG), a Chinese herbal formula. Several experimental studies on animals have shown that SQG can lower blood pressure and myocardial fibrosis by suppressing inflammatory responses. However, no standard clinical trial has confirmed this. Whether SQG can improve endothelial cell function is unknown.

Methods/design

In this randomized double-blind double-simulation controlled trial, 300 patients with stage I or II hypertension will be recruited and randomly allocated in a 1:1:1 ratio to group A (treatment with SQG and placebo instead of Losartan), group B (treatment with Losartan and placebo instead of SQG), and group C (treatment with SQG and Losartan). In this study, 10 g of SQG (or its placebo) will be administrated twice a day and 50 mg of Losartan (or its placebo) will be administrated once in the morning. The primary endpoint is the drug efficiency for each of the three groups. The secondary endpoints are the change in average systolic and diastolic blood pressure during the day and the night, the change in the rate at which blood pressure drops at night, assessment of target organ damage (heart rate variability, ankle–brachial pressure index, and pulse wave velocity), assessment of any improvement in symptoms (Hypertension Symptom Scale, syndrome integral scale in traditional Chinese medicine, Pittsburgh Sleep Quality Index Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the 36-Item Short Form Health Survey), blood lipids, serum indicators of vascular function (changes in serum levels of ET-1, TXA2, NO, and PGI2), and safety indicators.

Discussion

This study aims to provide clinical evidence on the efficacy and safety of SQG in the treatment of hypertension. Moreover, the possible mechanism by which SQG may lower blood pressure will be explored by observing the protective effect of SQG on vascular endothelial function, as well as its effect on related clinical symptoms, risk factors, and the target organs of hypertension.

Trial registration

Chinese Clinical Trials Registry, ChiCTR1800016427. Registered on 1 June 2018.
Tailored, psychological intervention for anxiety or depression in people with chronic obstructive pulmonary disease (COPD), TANDEM (Tailored intervention for ANxiety and DEpression Management in COPD): protocol for a randomised controlled trial
Authors:   On behalf of the TANDEM Investigators, Sohanpal Ratna , Pinnock Hilary , Steed Liz , Heslop Marshall Karen , Chan Claire , Kelly Moira , Priebe Stefan , Roberts C. Michael , Singh Sally , Smuk Melanie , Saqi-Waseem Sarah , Healey Andy , Underwood Martin , White Patrick , Warburton Chris , Taylor Stephanie J. C.
Published: January 2020

Background

People with chronic obstructive pulmonary disease (COPD) are at increased risk of depression and anxiety, which greatly reduces their quality of life and is associated with worse outcomes; but these psychological co-morbidities are under-recognised and undertreated in COPD patients. Pulmonary rehabilitation (PR) improves mood for up to 6 months but health practitioners under-refer, and patients commonly fail to attend/complete PR. Research suggests that complex non-pharmacological interventions, including both psychological and exercise components, may reduce anxiety and depression in COPD.

We have developed a tailored, cognitive behavioural approach (CBA) intervention for patients with COPD and co-morbid anxiety and/or depression (‘TANDEM’), which precedes and optimises the benefits of currently offered PR. We hypothesise that such a psychological intervention, delivered by supervised, trained respiratory healthcare professionals, will improve mood in patients with mild to moderate anxiety and/or depression and encourage uptake and completion of PR.

Methods

We will conduct a multi-centre, pragmatic, randomised controlled trial of the TANDEM intervention compared to usual care across the Midlands, London, the South East and Bristol, UK.

We will train healthcare professionals familiar with COPD to deliver the manualised, tailored, face-to-face, one-to-one intervention weekly for 6–8 weeks.

We will recruit 430 participants from primary, community and secondary care with confirmed COPD and moderate to very severe airflow limitation, who are eligible for assessment for PR, and who screen positive for symptoms of mild/moderate depression and/or anxiety using the Hospital Anxiety and Depression scale (HADS). Participants will be randomised 1.25:1 (intervention: usual care).

The co-primary outcomes are the HADS anxiety and depression subscale scores at 6 months; participants will be followed up to 12 months. Secondary outcomes include uptake and completion of PR and healthcare resource use. There will be a parallel process evaluation and a health economic evaluation.

Discussion

The TANDEM intervention has the potential to optimise the unrealised synergy between a psychological intervention and PR. The CBA sessions will precede PR and target individuals’ cognitions, behaviours and symptoms associated with anxiety and depression to decrease psychological morbidity and increase effective self-management amongst patients with COPD.

Trial registration

ISRCTN, ID: ISRCTN59537391. Registered on 20 March 2017. Protocol version 6.0, 22 April 2018.
Comparing how patients value and respond to information on risk given in three different forms during dental check-ups: the PREFER randomised controlled trial
Authors: Harris R. , Lowers V. , Laverty L. , Vernazza C. , Burnside G. , Brown S. , Ternent L.
Published: January 2020

Background

This study aims to compare patient preference for, and subsequent change in, oral health behaviour for three forms of risk information given at dental check-ups (verbal advice compared to verbal advice accompanied by a traffic light (TL) risk card; or compared to verbal advice with a quantitative light fluorescence (QLF) photograph of the patient’s mouth).

Methods

A multi-centre, parallel-group, patient-randomised clinical trial was undertaken between August 2015 and September 2016. Computer-generated random numbers using block stratification allocated patients to three arms. The setting was four English NHS dental practices. Participants were 412 dentate adults at medium/high risk of poor oral health. Patients rated preference and willingness to pay (WTP) for the three types of information. The primary outcome was WTP. After receiving their check-up, patients received the type of information according to their group allocation. Follow-up was by telephone/e-mail at 6 and 12 months. Mean and median WTP for the three arms were compared using Wilcoxon signed-rank tests. Tobit regression models were used to investigate factors affecting WTP and preference for information type. Secondary outcomes included self-rated oral health and change in oral health behaviours (tooth-brushing, sugar consumption and smoking) and were investigated using multivariate generalised linear mixed models.

Results

A total of 412 patients were randomised (138 to verbal, 134 to TL and 140 to QLF); 391 revisited their WTP scores after the check-up (23 withdrew). Follow-up data were obtained for 185 (46%) participants at 6 months and 153 (38%) participants at 12 months. Verbal advice was the first preference for 51% (209 participants), QLF for 35% (145 participants) and TL for 14% (58 participants). TL information was valued lower than either verbal or QLF information (p < 0.0001). Practice attended was predictive of verbal as first preference, and being older. Practice attended, preferring TL the most and having fewer than 20 teeth were associated with increased WTP; and living in a relatively deprived area or having low literacy decreased WTP. There were no significant differences in behaviour change on follow-up.

Conclusions

Although a new NHS dental contract based on TL risk stratification is being tested, patients prefer the usual verbal advice. There was also a practice effect which will needs to be considered for successful implementation of this government policy.

Trial registration

ISRCTN, ISRCTN71242343. Retrospectively registered on 27 March 2018.
Efficacy of switching to bilastine, a histamine H1 receptor antagonist, in patients with chronic spontaneous urticaria (H1-SWITCH): study protocol for a randomized controlled trial
Authors: Fukunaga Atsushi , Oda Yoshiko , Washio Ken , Omori Takashi , Kakei Yasumasa , Hide Michihiro , Nishigori Chikako
Published: January 2020

Background

Chronic spontaneous urticaria (CSU) is characterized by the spontaneous appearance of wheals, angioedema, or both for > 6 weeks. Continuous treatment with H1-antihistamines is used as a first-line treatment for CSU. However, H1-antihistamine treatment leads to absence of symptoms in less than 50% of patients with CSU. Although Japanese guidelines for the diagnosis and treatment of urticaria recommend an increase in the H1-antihistamine dose or a switch to other H1-antihistamines, there is no evidence supporting a switch to other H1-antihistamines in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose.

Methods

We will conduct a multicenter, open-label, non-inferiority, randomized, parallel, comparison study to determine if the efficacy of bilastine 20 mg is not inferior to that of a twofold H1-antihistamine dose increase in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose. This study will be performed at 15 academic hospitals in Japan, and the administration period (increasing the H1-antihistamine dose twofold vs. switching to bilastine 20 mg) will be 7 days. Participants (n = 150) will be randomized to either an increased H1-antihistamine dose or a switch to bilastine 20 mg at a 1:1 ratio. The primary endpoint, mean of the total symptom score of 5–7 days after the intervention, will be evaluated. The secondary objective is to determine if the safety of bilastine 20 mg regarding somnolence is superior to that of a twofold dose increase of H1-antihistamines. This will be measured by a change in the Japanese version of the Epworth Sleepiness Scale from baseline to 7 days after starting the intervention.

Discussion

This multicenter, open-label, non-inferiority, randomized, parallel, comparison study will be, to our knowledge, the first well-designed clinical study to evaluate the efficacy of a switch to other H1-antihistamines in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed doses. This trial will provide evidence of the efficacy and safety of bilastine when treatment is switched in patients with refractory CSU who are unresponsive to H1-antihistamines at the licensed dose.

Trial registration

Japan Registry of Clinical Trials (jRCT), jRCTs051180105. Registered on 8 March 2019.
Acupuncture treatment on the motor area of the scalp for motor dysfunction in children with cerebral palsy: study protocol for a multicenter randomized controlled trial
Authors: Wang Jun , Shi Wei , Khiati Dhiaedin , Shi Bingpei , Shi Xiaojuan , Luo Dandan , Wang Yin , Deng Rencai , Huang Huayu , Li Jian , Yan Weili , Yang Hong
Published: January 2020

Background

Scalp acupuncture has been widely used as treatment for motor dysfunction in children with cerebral palsy in China. Previous studies have failed to provide high-quality evidence to demonstrate the effectiveness of this treatment in children with cerebral palsy. No high-quality randomized controlled trials on scalp acupuncture have been published. The aim of this study is to evaluate the effectiveness of Jiao’s scalp acupuncture when combined with routine rehabilitation treatment versus routine rehabilitation treatment alone for motor dysfunction in children with cerebral palsy.

Methods/Design

This is a four-centre randomized controlled trial. One hundred cerebral palsy patients with motor dysfunction were enrolled. Patients will be allocated in a 1:1 ratio into either an acupuncture treatment group or a control group. Cerebral palsy patients in the control group will receive conventional rehabilitation treatment, whereas patients in the acupuncture group will receive a combination of scalp acupuncture and conventional rehabilitation treatment. Thirty-six treatment sessions will be performed over a 12-week period. The Gross Motor Function Measure and the Fine Motor Function Measure Scale will be assessed as the primary outcome measures. The Paediatric Evaluation of Disability Inventory and the Cerebral Palsy Quality of Life Questionnaire for Children will be selected as secondary outcome measures. All assessments will be conducted at baseline, week 4 (treatment 12), week 8 (treatment 24), week 12 (treatment 36) and week 24 (follow-up).

Discussion

This is the first trial evaluating the efficacy and safety of scalp acupuncture as a treatment for motor dysfunction in children with cerebral palsy. The results of this trial are expected to provide relevant evidence demonstrating that scalp acupuncture can be used as an effective rehabilitation treatment method for improving motor dysfunction in children with cerebral palsy.

Trial registration

ClinicalTrials.gov, NCT03921281. Registered on 19 April 2019.
Enhanced lipid production by Yarrowia lipolytica cultured with synthetic and waste-derived high-content volatile fatty acids under alkaline conditions
Authors: Gao Ruiling , Li Zifu , Zhou Xiaoqin , Bao Wenjun , Cheng Shikun , Zheng Lei
Published: January 2020

Background

Volatile fatty acids (VFAs) can be effective and promising alternate carbon sources for microbial lipid production by a few oleaginous yeasts. However, the severe inhibitory effect of high-content (> 10 g/L) VFAs on these yeasts has impeded the production of high lipid yields and their large-scale application. Slightly acidic conditions have been commonly adopted because they have been considered favorable to oleaginous yeast cultivation. However, the acidic pH environment further aggravates this inhibition because VFAs appear largely in an undissociated form under this condition. Alkaline conditions likely alleviate the severe inhibition of high-content VFAs by significantly increasing the dissociation degree of VFAs. This hypothesis should be verified through a systematic research.

Results

The combined effects of high acetic acid concentrations and alkaline conditions on VFA utilization, cell growth, and lipid accumulation of Yarrowia lipolytica were systematically investigated through batch cultures of Y. lipolytica by using high concentrations (30–110 g/L) of acetic acid as a carbon source at an initial pH ranging from 6 to 10. An initial pH of 8 was determined as optimal. The highest biomass and lipid production (37.14 and 10.11 g/L) were obtained with 70 g/L acetic acid, whereas cultures with > 70 g/L acetic acid had decreased biomass and lipid yield due to excessive anion accumulation. Feasibilities on high-content propionic acid, butyric acid, and mixed VFAs were compared and evaluated. Results indicated that YX/S and YL/S of cultures on butyric acid (0.570, 0.144) were comparable with those on acetic acid (0.578, 0.160) under alkaline conditions. The performance on propionic acid was much inferior to that on other acids. Mixed VFAs were more beneficial to fast adaptation and lipid production than single types of VFA. Furthermore, cultures on food waste (FW) and fruit and vegetable waste (FVW) fermentate were carried out and lipid production was effectively improved under this alkaline condition. The highest biomass and lipid production on FW fermentate reached 14.65 g/L (YX/S: 0.414) and 3.20 g/L (YL/S: 0.091) with a lipid content of 21.86%, respectively. By comparison, the highest biomass and lipid production on FVW fermentate were 11.84 g/L (YX/S: 0.534) and 3.08 g/L (YL/S: 0.139), respectively, with a lipid content of 26.02%.

Conclusions

This study assumed and verified that alkaline conditions (optimal pH 8) could effectively alleviate the lethal effect of high-content VFA on Y. lipolytica and significantly improve biomass and lipid production. These results could provide a new cultivation strategy to achieve simple utilizations of high-content VFAs and increase lipid production. Feasibilities on FW and FVW-derived VFAs were evaluated, and meaningful information was provided for practical applications.
Gut microbiota is essential in PGRP-LA regulated immune protection against Plasmodium berghei infection
Authors: Gao Li , Song Xiumei , Wang Jingwen
Published: January 2020

Background

Malaria remains to be one of the deadliest infectious diseases and imposes substantial financial and social costs in the world. Mosquitoes rely on the immune system to control parasite infection. Peptidoglycan recognition proteins (PGRPs), a family of pattern-recognition receptors (PRR), are responsible for initiating and regulating immune signaling pathways. PGRP-LA is involved in the regulation of immune defense against the Plasmodium parasite, however, the underlying mechanism needs to be further elucidated.

Methods

The spatial and temporal expression patterns of pgrp-la in Anopheles stephensi were analyzed by qPCR. The function of PGRP-LA was examined using a dsRNA-based RNA interference strategy. Western blot and periodic acid schiff (PAS) staining were used to assess the structural integrity of peritrophic matrix (PM).

Results

The expression of pgrp-la in An. stephensi was induced in the midgut in response to the rapid proliferating gut microbiota post-blood meal. Knocking down of pgrp-la led to the downregulation of immune effectors that control gut microbiota growth. The decreased expression of these immune genes also facilitated P. berghei infection. However, such dsLA treatment did not influence the structural integrity of PM. When gut microbiota was removed by antibiotic treatment, the regulation of PGRP-LA on immune effectors was abolished and the knock down of pgrp-la failed to increase susceptibility of mosquitoes to parasite infection.

Conclusions

PGRP-LA regulates the immune responses by sensing the dynamics of gut microbiota. A mutual interaction between gut microbiota and PGRP-LA contributes to the immune defense against Plasmodium parasites in An. stephensi.
CACTUS: cancer image annotating, calibrating, testing, understanding and sharing in breast cancer histopathology
Authors: Aksac Alper , Ozyer Tansel , Demetrick Douglas J. , Alhajj Reda
Published: January 2020

Objective

Develop CACTUS (cancer image annotating, calibrating, testing, understanding and sharing) as a novel web application for image archiving, annotation, grading, distribution, networking and evaluation. This helps pathologists to avoid unintended mistakes leading to quality assurance, teaching and evaluation in anatomical pathology. Effectiveness of the tool has been demonstrated by assessing pathologists performance in the grading of breast carcinoma and by comparing inter/intra-observer assessment of grading criteria amongst pathologists reviewing digital breast cancer images. Reproducibility has been assessed by inter-observer (kappa statistics) and intra-observer (intraclass correlation coefficient) concordance rates.

Results

CACTUS has been evaluated using a surgical pathology application—the assessment of breast cancer grade. We used CACTUS to present standardized images to four pathologists of differing experience. They were asked to evaluate all images to determine their assessment of Nottingham grade of a series of breast carcinoma cases. For each image, they were asked for their overall grade impression. CACTUS helps and guides pathologists to improve disease diagnosis with higher confidence and thereby reduces their workload and bias. CACTUS can be useful for both disseminating anatomical pathology images for teaching, as well as for evaluating agreement amongst pathologists or against a gold standard for evaluation or quality assurance.
Regular approximation of singular Sturm–Liouville problems with eigenparameter dependent boundary conditions
Authors: Zhang Maozhu , Li Kun , Song Hongxiang
Published: January 2020

In this paper we consider singular Sturm–Liouville problems with eigenparameter dependent boundary conditions and two singular endpoints. The spectrum of such problems can be approximated by those of the inherited restriction operators constructed. Via the abstract operator theory, the strongly resolvent convergence and norm resolvent convergence of a sequence of operators are obtained and it follows that the spectral inclusion of spectrum holds. Moreover, spectral exactness of spectrum holds for two special cases.
Selective serotonin reuptake inhibitor ‘discontinuation syndrome’ or withdrawal
Authors: Massabki Ivana , Abi-Jaoude Elia
Published: January 2020

Attempts to define selective serotonin reuptake inhibitor (SSRI) withdrawal with the term ‘discontinuation syndrome’ are not supported by evidence. Acknowledging that SSRI use can result in dependence and withdrawal allows patients to be better informed around decisions related to these drugs, and helps inform strategies for safe tapering as appropriate.
Risk for Acromegaly-related Comorbidities by Sex in Korean Acromegaly
Authors: Park Kyeong Hye , Lee Eun Jig , Seo Gi Hyeon , Ku Cheol Ryong
Published: January 2020

Context

Reports on the incidence, characteristics, and comorbidity in Asian patients with acromegaly are scarce.

Objective

To evaluate the incidence of acromegaly and the risk of comorbidities in East Asia, especially South Korea.

Design

This nationwide population-based cohort study using the Korean Health Insurance Review and Assessment claims database evaluated the incidence of acromegaly, initially diagnosed from 2010 to 2013. We identified comorbidities during, before, and 2 years after diagnosis. Acromegaly and control cases (718 and 7180, respectively) were included in the analysis.

Setting

A longitudinal case-control study using a nationwide population cohort.

Results

The mean annual incidence rate of acromegaly was 3.57 cases per 1 000 000. Malignancies occurred in 61 patients with acromegaly (8.5%) during the study period and thyroid cancer was the most common malignancy (n = 38). In the acromegaly group, the overall risk of malignancy was higher: hazard ratio (HR), 2.82 (95% confidence interval [CI]: 2.12–3.74). Malignancy risk was more pronounced in females, with increased risk from the prediagnosis period that is sustained until the postdiagnosis period. Prevalence of diabetes mellitus (DM) and heart failure increased significantly in acromegalic patients. Over the entire period, DM developed in 51.1% and 57.0% of male and female acromegalic patients, respectively. Mortality risk was higher (HR 1.65, 95%; CI: 1.13–2.41) and statistically significant in females (HR 1.75, 95%; CI: 1.07–2.84).

Conclusion

Comorbidities associated with acromegaly differed by sex in Korean subjects. High malignancy and mortality risk should be considered in female patients when managing acromegaly in Korea.
Sulfonated Poly(arylene perfluoroalkylene) Terpolymers as Novel Proton Exchange Membranes for High Performance Fuel Cells
Authors: Long Zhi , Miyake Junpei , Miyatake Kenji
Published: January 2020

We herein report a series of sulfonated poly(arylene perfluoroalkylene) terpolymers (SPAF-P) containing sulfophenylene, perfluoroalkylene, and meta- or para-phenylene groups in the main chain. The SPAF-P terpolymers with reasonable molecular weight and various ion exchange capacity (IEC = 1.85–3.18 meq g−1) provided transparent and flexible membranes. Compared with our previous membrane sharing the same perfluoroalkylene groups (SPAF-MM, IEC = 1.59 meq g−1), SPAF-P achieved higher proton conductivity over a wide range of humidity because of their higher IEC values. A fuel cell with SPAF-pP 1.85 membrane exhibited slightly higher performance than that of SPAF-MM at 30% RH with H2/air because of the improved proton conductivity. After the open-circuit voltage (OCV) hold test for 1000 h, the SPAF-pP fuel cell retained high OCV value (>0.94 V), similar polarization curves, ohmic resistance curves, molecular weight and chemical structure, indicating the excellent chemical stability of the SPAF-pP 1.85 membrane.
Efficient Neighborhood Evaluations for the Vehicle Routing Problem with Multiple Time Windows
Authors: Hoogeboom Maaike , Dullaert Wout , Lai David , Vigo Daniele
Published: January 2020

In the vehicle routing problem with multiple time windows (VRPMTW), a single time window must be selected for each customer from the multiple time windows provided. Compared with classical vehicle routing problems with only a single time window per customer, multiple time windows increase the complexity of the routing problem. To minimize the duration of any given route, we present an exact polynomial time algorithm to efficiently determine the optimal start time for servicing each customer. The proposed algorithm has a reduced worst-case and average complexity than existing exact algorithms. Furthermore, the proposed exact algorithm can be used to efficiently evaluate neighborhood operations during a local search resulting in significant acceleration. To examine the benefits of exact neighborhood evaluations and to solve the VRPMTW, the proposed algorithm is embedded in a simple metaheuristic framework generating numerous new best known solutions at competitive computation times.
Strategic Network Design for Parcel Delivery with Drones Under Competition
Authors: Baloch Gohram , Gzara Fatma
Published: January 2020

This paper studies the economic desirability of unmanned aerial vehicle (UAV) parcel delivery and its effect on e-retailer distribution networks while taking into account technological limitations, government regulations, and customer behavior. We consider an e-retailer offering multiple same-day delivery services including a fast UAV service and develop a distribution network design formulation under service-based competition where the services offered by the e-retailer not only compete with the stores (convenience, grocery, etc.) but also with each other. Competition is incorporated using the multinomial logit market share model. To solve the resulting nonlinear mathematical formulation, we develop a novel logic-based Benders decomposition approach. We build a case based on New York City, carry out extensive numerical testing, and perform sensitivity analyses over delivery charge, delivery time, government regulations, technological limitations, customer behavior, and market size. The results show that government regulations, technological limitations, and service charge decisions each play a vital role in the future of UAV delivery.
O Proeja no IFSP diante das políticas curriculares para o Ensino Médio
Authors: Fernandes Jarina Rodrigues , Corti Ana Paula , Silva Michelle Chaves da
Published: January 2020

objetivo do presente artigo é apresentar um panorama de como os Projetos Pedagógicos dos Cursos (PPCs) do Proeja do Instituto Federal de Educação, Ciência e Tecnologia de São Paulo (IFSP), que integram a formação técnica de nível médio ao Ensino Médio, têm se relacionado com as políticas curriculares para o Ensino Médio no Brasil contemporâneo. Para tanto, foi realizada pesquisa de caráter documental, exploratório e descritivo dos PPCs dos referidos cursos, à luz das normativas da instituição e das políticas curriculares de cada período. Os resultados apontam para o movimento de resistência da instituição às políticas curriculares vigentes para o Ensino Médio, por meio de inserção nos PPCs de dispositivos curriculares, tais como projetos integradores e núcleos estruturantes, a fim de apoiar o desenvolvimento de currículos capazes de integrar efetivamente a educação profissional e a educação básica, em consonância com uma formação de qualidade social para as classes populares.
OFICINAS PEDAGÓGICAS NO ENSINO DE HISTÓRIA E CULTURA AFRO-BRASILEIRA: CONTRIBUIÇÕES A PARTIR DO PIBID
Authors: Marques Luiz Felipe , Stentzler Márcia Marlene
Published: January 2020

Analisamos a formação inicial do licenciando em história e cultura afro-brasileira no Ensino Fundamental e Médio por meio de oficinas realizadas pelo Programa Institucional de Bolsas de Iniciação à Docência (PIBID), para a formação de professores para a educação básica. Nossas fontes são documentos, relatórios e registros de atividades didáticas do subprojeto de História da Universidade Estadual do Paraná (Unespar), campus de Paranavaí (2015 - 2018). As oficinas foram pautadas na temática da cultura afro-brasileira e africana, Lei nº 10.639/03 e desenvolvidas em cinco escolas estaduais de Paranavaí (PR). Temos como base teórica Anastasiou e Alves (2009), Castilhos (2019), Le Goff (1990; 2003), Silva (2010), Thompson (1981; 1987), LDB/1996. Os resultados indicam oficinas com potencial para ressignificação didático-metodológica para o ensino de história e da cultura afro-brasileira[1]no Ensino Fundamental e Médio.[1] Este estudo faz parte de pesquisa de mestrado sob registro no Comitê de Ética e Pesquisa da Universidade, CAAE nº 20183319.1.0000.9247.
ESTUDANTES DE ENSINO MÉDIO E REPRESENTAÇÕES SOBRE A RELAÇÃO ESCOLACOMUNIDADE : A EDUCAÇÃO PÚBLICA COMO CENTRALIDADE
Authors: Silva Lincoln Tavares
Published: January 2020

Baseados na Teoria das Representações Sociais (Moscovici, Jodelet e Abric), buscamos conhecer melhor o que/como pensam estudantes do Ensino Médio de escolas públicas estaduais, situadas no Estado do Rio de Janeiro, sobre a relação escolacomunidade (entre os anos de 2008 e 2011). Os instrumentos aplicados forneceram informações sobre os processos que influenciam as concepções comunitárias e as relações com a escola. Analisamos que as representações e práticas amoldam-se às dinâmicas socioculturais, modificando ou transgredindo regras estabelecidas. A Educação tem centralidade nas representações. Idealizada ou não, como base, salvação, elo, fonte, meta, boa escolha, esforço, emancipação e direito. Articula-se à ajuda, à comunicação, aos alunos, ao professor e ao respeito na relação escolacomunidade, integrando e relacionando a experiência escolar às demais experiências. Tal centralidade sugere pensar em territórios educativos e não meramente escolares, ressignificando o trabalho escolar.
APRESENTAÇÃO – DOSSIÊ TEMÁTICO: ENSINO MÉDIO – PASSOS E IMPASSES NA ATUALIDADE
Authors: Frigotto Gaudêncio , Ramos Marise
Published: January 2020

A Revista e-Mosaicos, nesta 19ª edição, optou por um Dossiê Temático que trata, especialmente, do ensino médio nas suas diferentes modalidades e em diferentes aspectos.  O número de artigos enviados expressa o quanto o tema do ensino médio assume centralidade no debate da educação básica.
EM TEMPOS DE REFLEXÃO... DESPEDIDA? NÃO, CONTINUIDADE!
Authors: Fernandes Andrea Da Paixão
Published: January 2020

Chegamos à última edição de e-Mosaicos em 2019. Ela nos traz o dossiê temático “Ensino Médio: passos e impasses na atualidade”, organizado pelos professores Gaudêncio Frigotto e Marise Ramos, a quem muito agradecemos pela parceria.
O PROCESSO COLETIVO E A SUSPENSÃO DOS PROCESSOS INDIVIDUAIS: UMA ANÁLISE CONFORME O DIREITO FUNDAMENTAL DE ACESSO À JUSTIÇA
Authors: Gagno Luciano Picoli , Bufon Fernanda Porchera
Published: January 2020

O ordenamento jurídico brasileiro prevê a possibilidade de processos coletivos, que permitem a extensão da coisa julgada para beneficiar os indivíduos que possuam direitos individuais homogêneos ligados ao objeto da tutela coletiva. Nesse sentido, caso o processo coletivo e os processos individuais com objetos similares tramitem simultaneamente, há a possibilidade da suspensão do processo individual, para que se aguarde o julgamento da ação coletiva. Discute-se, entretanto, se a adoção dessa prática, sem a aquiescência das partes, violaria o direito fundamental de acesso à justiça, uma vez que impediria o indivíduo de prosseguir com a sua demanda de forma individual. Destarte, o presente estudo teve por objetivo analisar a possibilidade de aplicação da técnica de suspensão do processo individual conexo com demanda coletiva, cotejando, para tanto, um acórdão proferido em recurso especial repetitivo no Superior Tribunal de Justiça, com o direito fundamental de acesso à justiça e o consectário dever estatal de realização da melhor justiça possível. Para tanto, utilizou-se a aplicação do método dedutivo, através da exploração bibliográfica e jurisprudencial, analisando-se a possível aplicação de princípios gerais e abstratos, tais como duração razoável, isonomia, proporcionalidade e efetividade processual, para o oferecimento de um processo mais econômico, racional, célere e isonômico.
Tunable double electromagnetically induced grating with an incoherent pump field
Authors: Vafafard Azar , Sahrai Mostafa
Published: January 2020

We introduce here double electromagnetically induced grating (DEIG) using a tripod atomic structure, wherein two probe and signal fields with different frequencies simultaneously experience an atomic grating. Properties of presented DEIG can be substantially modified by the detuning of the applied fields. It has also been found that applying an incoherent pump field has a remarkable influence on the high-order diffraction efficiencies. Amplification of travelling weak lights via the incoherent pump field results in large diffraction efficiencies in the first-order and second-order directions. Such a novel scheme might open up the possibility for designing a two-qubit switch that would be advantageous to quantum information processing and quantum networking.