bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra-patient potassium variability after hypothermic cardiac arrest: a multicentre, prospective study
Authors: Pasquier M. , Blancher M. , Buse S. , Boussat B. , Debaty G. , Kirsch M. , de Riedmatten M. , Schoettker P. , Annecke T. , Bouzat P.
Published: December 2019

Background

To date, the decision to set up therapeutic extra-corporeal life support (ECLS) in hypothermia-related cardiac arrest is based on the potassium value only. However, no information is available about how the analysis should be performed. Our goal was to compare intra-individual variation in serum potassium values depending on the sampling site and analytical technique in hypothermia-related cardiac arrests.

Methods

Adult patients with suspected hypothermia-related refractory cardiac arrest, admitted to three hospitals with ECLS facilities were included. Blood samples were obtained from the femoral vein, a peripheral vein and the femoral artery. Serum potassium was analysed using blood gas (BGA) and clinical laboratory analysis (CL).

Results

Of the 15 consecutive patients included, 12 met the principal criteria, and 5 (33%) survived. The difference in average potassium values between sites or analytical method used was ≤1 mmol/L. The agreement between potassium values according to the three different sampling sites was poor. The ranges of the differences in potassium using BGA measurement were − 1.6 to + 1.7 mmol/L; − 1.18 to + 2.7 mmol/L and − 0.87 to + 2 mmol/L when comparing respectively central venous and peripheral venous, central venous and arterial, and peripheral venous and arterial potassium.

Conclusions

We found important and clinically relevant variability in potassium values between sampling sites. Clinical decisions should not rely on one biological indicator. However, according to our results, the site of lowest potassium, and therefore the preferred site for a single potassium sampling is central venous blood. The use of multivariable prediction tools may help to mitigate the risks inherent in the limits of potassium measurement.

Trial registration

ClinicalTrials.gov Identifier: NCT03096561.
High expression of miR-222-3p in children with Mycoplasma pneumoniae pneumonia
Authors: Chu Chu , Lei Xiaoli , Li Yuqin , Luo Yali , Ding Ying , Zhou Weifang , Ji Wei
Published: December 2019

Objectives

Mycoplasma pneumoniae is a leading cause of community-acquired pneumonia in children. However, its mechanism of pathogenesis is not fully understood, and microRNAs might play a role. This study aimed to explore the microRNA-222-3p (miR-222-3p) expression and its possible role in children with M.pneumoniae pneumonia (MPP).

Methods

Thirty-six children with MPP and twenty-seven age-matched controls from Children’s Hospital of Soochow University were enrolled in this study. MiR-222-3p and cluster of differentiation 4 (CD4) mRNA were detected using real-time PCR in children’s peripheral blood plasma samples. THP-1 cells and mice were stimulated with M.pneumoniae lipid-associated membrane proteins(LAMPs).

Results

Children with MPP had significantly higher levels of miR-222-3p and lower levels of CD4 in peripheral blood plasma (P <  0.05). Additionally, Sixteen children with MPP complicated with pleural effusion had higher miR-222-3p levels than those without pleural effusion. MiR-222-3p or CD4 in THP-1 cells increased or decreased, respectively, in a dose dependent manner after LAMP stimulation. In LAMP-stimulated mice massive inflammatory cells infiltrates surrounded the bronchioles, and miR-222-3p increased in the bronchoalveolar lavage fluid. In conclusion, miR-222-3p was highly expressed in children with MPP, especially those with pleural effusion.

Conclusion

Small sample studies showed that M.pneumoniae or its LAMPs could increase miR-222-3p and decrease CD4 in macrophages,both in vitro and vivo.Thus, miR-222-3p might be an MPP biomarker for the diagnosis and prognosis.
The effect of dexmedetomidine and clonidine on the inflammatory response in critical illness: a systematic review of animal and human studies
Authors: Flanders Charles A. , Rocke Alistair S. , Edwardson Stuart A. , Baillie J. Kenneth , Walsh Timothy S.
Published: December 2019

Background

The α2 agonists, dexmedetomidine and clonidine, are used as sedative drugs during critical illness. These drugs may have anti-inflammatory effects, which might be relevant to critical illness, but a systematic review of published literature has not been published. We reviewed animal and human studies relevant to critical illness to summarise the evidence for an anti-inflammatory effect from α2 agonists.

Methods

We searched PubMed, the Cochrane library, and Medline. Animal and human studies published in English were included. Broad search terms were used: dexmedetomidine or clonidine, sepsis, and inflammation. Reference lists were screened for additional publications. Titles and abstracts were screened independently by two reviewers and full-text articles obtained for potentially eligible studies. Data extraction used a bespoke template given study diversity, and quality assessment was qualitative.

Results

Study diversity meant meta-analysis was not feasible so descriptive synthesis was undertaken. We identified 30 animal studies (caecal ligation/puncture (9), lipopolysaccharide (14), acute lung injury (5), and ischaemia-reperfusion syndrome (5)), and 9 human studies. Most animal (26 dexmedetomidine, 4 clonidine) and all human studies used dexmedetomidine. In animal studies, α2 agonists reduced serum and/or tissue TNFα (20 studies), IL-6 (17 studies), IL-1β (7 studies), NFκB (6 studies), TLR4 (6 studies), and a range of other mediators. Timing and doses varied widely, but in many cases were not directly relevant to human sedation use. In human studies, dexmedetomidine reduced CRP (4 studies), TNFα (5 studies), IL-6 (6 studies), IL-1β (3 studies), and altered several other mediators. Most studies were small and low quality. No studies related effects to clinical outcomes.

Conclusion

Evidence supports potential anti-inflammatory effects from α2 agonists, but the relevance to clinically important outcomes is uncertain. Further work should explore whether dose relationships with inflammation and clinical outcomes are present which might be separate from sedation-mediated effects.
The DREAM Initiative: study protocol for a randomized controlled trial testing an integrated electronic health record and community health worker intervention to promote weight loss among South Asian patients at risk for diabetes
Authors: Lim Sahnah , Wyatt Laura C. , Mammen Shinu , Zanowiak Jennifer M. , Mohaimin Sadia , Goldfeld Keith S. , Shelley Donna , Gold Heather T. , Islam Nadia S.
Published: December 2019

Background

Electronic health record (EHR)-based interventions that use registries and alerts can improve chronic disease care in primary care settings. Community health worker (CHW) interventions also have been shown to improve chronic disease outcomes, especially in minority communities. Despite their potential, these two approaches have not been tested together, including in small primary care practice (PCP) settings. This paper presents the protocol of Diabetes Research, Education, and Action for Minorities (DREAM) Initiative, a 5-year randomized controlled trial integrating both EHR and CHW approaches into a network of PCPs in New York City (NYC) in order to support weight loss efforts among South Asian patients at risk for diabetes.

Methods/design

The DREAM Initiative was funded by the National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health). A total of 480 individuals at risk for type 2 diabetes will be enrolled into the intervention group, and an equal number will be included in a matched control group. The EHR intervention components include the provision of technical assistance to participating PCPs regarding prediabetes-related registry reports, alerts, and order sets. The CHW intervention components entail group education sessions on diabetes prevention, including weight loss and nutrition. A mixed-methods approach will be used to evaluate the feasibility, adoption, and impact (≥ 5% weight loss) of the integrated study components. Additionally, a cost effectiveness analysis will be conducted using outcomes, implementation costs, and healthcare claims data to determine the incremental cost per person achieving 5% weight loss.

Discussion

This study will be the first to test the efficacy of an integrated EHR–CHW intervention within an underserved, minority population and in a practical setting via a network of small PCPs in NYC. The study’s implementation is enhanced through cross-sector partnerships, including the local health department, a healthcare payer, and EHR vendors. Through use of a software platform, the study will also systematically track and monitor CHW referrals to social service organizations. Study findings, including those resulting from cost-effectiveness analyses, will have important implications for translating similar strategies to other minority communities in sustainable ways.

Trial registration

This study protocol has been approved and is made available on ClinicalTrials.gov by NCT 03188094 as of 15 June 2017.
ELECtric Tibial nerve stimulation to Reduce Incontinence in Care homes: protocol for the ELECTRIC randomised trial
Authors: Booth J. , Aucott L. , Cotton S. , Goodman C. , Hagen S. , Harari D. , Lawrence M. , Lowndes A. , Macaulay L. , MacLennan G. , Mason H. , McClurg D. , Norrie J. , Norton C. , O’Dolan C. , Skelton D. A. , Surr C. , Treweek S.
Published: December 2019

Background

Urinary incontinence (UI) is highly prevalent in nursing and residential care homes (CHs) and profoundly impacts on residents’ dignity and quality of life. CHs predominantly use absorbent pads to contain UI rather than actively treat the condition. Transcutaneous posterior tibial nerve stimulation (TPTNS) is a non-invasive, safe and low-cost intervention with demonstrated effectiveness for reducing UI in adults. However, the effectiveness of TPTNS to treat UI in older adults living in CHs is not known. The ELECTRIC trial aims to establish if a programme of TPTNS is a clinically effective treatment for UI in CH residents and investigate the associated costs and consequences.

Methods

This is a pragmatic, multicentre, placebo-controlled, randomised parallel-group trial comparing the effectiveness of TPTNS (target n = 250) with sham stimulation (target n = 250) in reducing volume of UI in CH residents. CH residents (men and women) with self- or staff-reported UI of more than once per week are eligible to take part, including those with cognitive impairment. Outcomes will be measured at 6, 12 and 18 weeks post randomisation using the following measures: 24-h Pad Weight Tests, post void residual urine (bladder scans), Patient Perception of Bladder Condition, Minnesota Toileting Skills Questionnaire and Dementia Quality of Life. Economic evaluation based on a bespoke Resource Use Questionnaire will assess the costs of providing a programme of TPTNS. A concurrent process evaluation will investigate fidelity to the intervention and influencing factors, and qualitative interviews will explore the experiences of TPTNS from the perspective of CH residents, family members, CH staff and managers.

Discussion

TPTNS is a non-invasive intervention that has demonstrated effectiveness in reducing UI in adults. The ELECTRIC trial will involve CH staff delivering TPTNS to residents and establish whether TPTNS is more effective than sham stimulation for reducing the volume of UI in CH residents. Should TPTNS be shown to be an effective and acceptable treatment for UI in older adults in CHs, it will provide a safe, low-cost and dignified alternative to the current standard approach of containment and medication.

Trial registration

ClinicalTrials.gov, NCT03248362. Registered on 14 August 2017.

ISRCTN, ISRCTN98415244. Registered on 25 April 2018. https://www.isrctn.com/.
Radiotherapy versus radiotherapy combined with temozolomide in high-risk low-grade gliomas after surgery: study protocol for a randomized controlled clinical trial
Authors: Wang Jingjing , Wang Ying , He Yan , Guan Hui , He Ling , Mu Xiaoli , Peng Xingchen
Published: December 2019

Background

It has been reported that radiation therapy (RT) followed by procarbazine, lomustine, and vincristine (PCV) chemotherapy could improve progression-free survival (PFS) and overall survival (OS) in patients with high-risk World Health Organization (WHO) grade 2 gliomas after surgery. However, procarbazine is not available in China. In clinical practice, Chinese doctors often use radiotherapy combined with temozolomide (TMZ) to treat these patients, although large-scale prospective studies are lacking. This trial aims to confirm whether RT combined with temozolomide can improve PFS and OS in high-risk patients with low-grade gliomas (LGGs).

Methods/design

This is a two-group, randomized controlled trial (RCT) enrolling patients who have LGGs (WHO grade 2) and are aged 40 years or older without regard to the extent of resection or are aged younger than 40 years old with subtotal resection or biopsy. An estimated 250 patients will be enrolled. Eligible participants will be randomly assigned to receive RT alone or RT plus TMZ chemotherapy in a 1:1 ratio. The same RT will be given to all eligible participants regardless of whether they are randomly assigned to the RT group or the chemoradiotherapy (CRT) group. While in the CRT group, patients will receive adjuvant TMZ with or without concurrent radiochemotherapy. The primary outcome of this trial is PFS, and it will be analyzed by the intention-to-treat approach. Secondary outcomes include OS, adverse events, and cognitive function.

Discussion

The objective of our research is to assess the effect of radiotherapy coupled with TMZ in high-risk patients with LGGs after surgery, compared with RT alone. Different histological types and molecular subtypes will be examined, and a corresponding subgroup analysis will be conducted. Our data can provide evidence for postoperative adjuvant therapy in patients with high-risk LGGs in China.

Trial registration

Chinese Clinical Trial Registry, ChiCTR1800015199. Registered on 13 March 2018.
Eye movement desensitization and reprocessing (EMDR) therapy for posttraumatic stress disorder in adults with serious mental illness within forensic and rehabilitation services: a study protocol for a randomized controlled trial
Authors: Every-Palmer Susanna , Flewett Tom , Dean Shaystah , Hansby Oliver , Colman Atalie , Weatherall Mark , Bell Elliot
Published: December 2019

Background

Eye movement desensitization and reprocessing (EMDR) is an evidenced-based treatment for posttraumatic stress disorder (PTSD). Forensic mental health services provide assessment and treatment of people with mental illness and a history of criminal offending, or those who are at risk of offending. Forensic mental health services include high, medium, and low-security inpatient settings as well as prison in-reach and community outpatient services. There is a high prevalence of PTSD in forensic settings and posttraumatic experiences can arise in people who violently offend in the context of serious mental illness (SMI). Successful treatment of PTSD may reduce the risk of relapse and improve clinical outcomes for this population. This study aims to assess the efficacy, risk of harm, and acceptability of EMDR within forensic and rehabilitation mental health services, as compared to treatment as usual (routine care).

Methods

This is a single-blind, randomized controlled trial comparing EMDR therapy to the waiting list (routine care). Adult forensic mental health service users (n = 46) with SMI and meeting the criteria for PTSD will be included in the study. Participants will be randomized after baseline assessment to either treatment as usual plus waiting list for EMDR or to treatment as usual plus EMDR. The EMDR condition comprises nine sessions, around 60 min in length delivered weekly, the first of which is a case conceptualization session. The primary outcomes are clinician and participant-rated symptoms of PTSD, and adverse events. Secondary outcomes include psychotic symptoms, social functioning, level of disability, self-esteem, depressive symptoms, post-trauma cognitions, and broad domains of complex posttraumatic difficulties. A trained assessor blinded to the treatment condition will assess outcomes at baseline, 10 weeks, and 6 months. Additionally, grounded theory qualitative methods will be used to explore participant experience of EMDR for a subset of participants.

Discussion

This study will contribute to the currently limited evidence base for EMDR for PTSD in forensic settings. It is the first randomized clinical trial to assess the efficacy, risk of harm, and acceptability of EMDR for PTSD in people with SMI in either forensic, mental health inpatient, or custodial settings.

Trial registration

Australia and New Zealand Clinical Trials Network, ACTRN12618000683235. Registered prospectively on 24 April 2018.
Efficacy and safety of tetramethylpyrazine phosphate on pulmonary hypertension: study protocol for a randomized controlled study
Authors: Chen Yuqin , He Wenjun , Ouyang Haiping , Liu Chunli , Hong Cheng , Wang Tao , Yang Kai , Lu Wenju , Wang Jian
Published: December 2019

Background

Tetramethylpyrazine (TMP), an active ingredient in the traditional Chinese herbal medicine Rhizoma Chuanxiong, has been used clinically for the prevention and treatment of cardiovascular disease. The benefits of TMP are largely attributed to its anti-oxidative and vasodilative properties. However, the efficacy of TMP in the treatment of pulmonary hypertension (PH) is unknown. We hypothesized that TMP may have a therapeutic effect in patients with PH.

Methods/design

A randomized, single-blinded, clinical study with a TMP treatment group and a control group will be conducted to evaluate the efficacy and safety of TMP intervention in patients with PH. The recruitment target is 120 subjects meeting the following criteria: (i) at rest and at sea level, mean pulmonary artery pressure above 20 mmHg and pulmonary capillary wedge pressure below 15 mmHg; (ii) type 1 or 4 PH in the stable phase; (iii) age 15–70 years; (iv) 6-min walk distance between 100 and 450 m; (v) World Health Organization (WHO) functional classification of pulmonary hypertension of II, III, or IV. Subjects will be assigned randomly into two groups at a ratio of 1:2 (control:TMP). Both groups will receive routine treatment, and the treatment group will also receive oral TMP (100 mg) three times a day for 16 weeks. All patients will be followed up for 4, 8, 12, and 16 weeks; symptoms and patient compliance will be recorded.

Discussion

We aimed to determine the efficacy and safety of TMP for the treatment of PH.

Trial registration

Chinese Clinical Trial Register, ChiCTR1800018664. Registered on 2 October 2018.
Effects of Chinese medicine on patients with acute exacerbations of COPD: study protocol for a randomized controlled trial
Authors: Zhang Hailong , Li Jiansheng , Yu Xueqing , Li Suyun , Wang Haifeng , Ruan Huanrong , Si Yimei , Xie Yang , Wang Minghang
Published: December 2019

Background

The incidence, mortality, and prevalence of chronic obstructive pulmonary disease (COPD) are high in China. Acute exacerbations of COPD (AECOPD) are important events in the management of COPD because they negatively impact health status, rates of hospitalization and readmission, and disease progression. AECOPD have been effectively treated with Chinese medicine for a long time. The aim of this proposed trial is to assess the therapeutic effect of Chinese medicine (CM) on AECOPD.

Methods/design

This proposed study is a multicenter, double-blind, parallel-group randomized controlled trial (RCT). We will randomly assign 378 participants with AECOPD into two groups in a 1:1 ratio. On the basis of health education and conventional treatment, the intervention group will be treated with CM, and the control group is given CM placebo according to CM syndrome. Patients are randomized to either receive CM or placebo, 10 g/packet, twice daily. The double-blind treatment lasts for 2 weeks and is followed up for 4 weeks. The main outcome is the COPD Assessment Test; secondary outcomes are treatment failure rate, treatment success rate, length of hospital stay, AECOPD readmission rate, intubation rate, mortality, dyspnea, the 36-item Short Form Health Survey, and the COPD patient-reported outcome scale. We will document these outcomes faithfully at the beginning of the study, 2 weeks after treatment, and at the 4 weeks follow-up.

Discussion

This high-quality RCT with strict methodology and few design deficits will help to prove the effectiveness of CM for AECOPD. We hope this trial will provide useful evidence for developing a therapeutic schedule with CM for patients with AECOPD.

Trial registration

ClinicalTrials.gov, NCT03428412. Registered on 4 February 2018.
Study of Peri-Articular Anaesthetic for Replacement of the Knee (SPAARK): study protocol for a patient-blinded, randomised controlled superiority trial of liposomal bupivacaine
Authors: Knight Ruth , Poulton Lisa , Strickland Louise H. , Hamilton Thomas W. , Beard David , Cook Jonathan , Dutton Susan J. , Leal Jose , Lamb Sarah , Cooper Cushla , Barker Karen L. , Murray David W. , Pandit Hemant G.
Published: December 2019

Background

Optimising the management of peri-operative pain and recovery following knee replacement has been identified as a patient priority. Current pain relief strategies use opiate-based analgesia; however, up to 50% of patients experience significant side effects. Local anaesthetic incisional infiltration is one alternative. The length of the duration of action is a major limiting factor of current local anaesthetic techniques. Liposomal bupivacaine has been reported to be effective for up to 72 h. This randomised controlled trial will evaluate the clinical and cost effectiveness of liposomal bupivacaine.

Methods

SPAARK is a patient-blinded, multi-centre, active comparator, superiority, two-arm, parallel-group randomised controlled trial. Five hundred patients undergoing knee replacement will be recruited and randomised to liposomal bupivacaine plus bupivacaine hydrochloride or bupivacaine hydrochloride alone. The co-primary outcomes are the Quality of Recovery 40 measured at 72 h post-surgery and also cumulative pain measured daily using a 0–10 visual analogue scale for the first 3 days following surgery. Secondary outcomes include cumulative opioid consumption, fitness for discharge, functional outcomes assessed using the Oxford Knee Score and American Knee Society Score, the EuroQol five dimensions instrument and complications. A cost utility analysis is also planned.

Discussion

The clinical effectiveness and cost effectiveness of liposomal bupivacaine have yet to be evaluated in the National Health Service, making this trial appropriate and timely.

Trial registration

ISRCTN registry, ISRCTN54191675. Registered on 14 November 2017.
Hernia reduction following laparotomy using small stitch abdominal wall closure with and without mesh augmentation (the HULC trial): study protocol for a randomized controlled trial
Authors: Heger Patrick , Feißt Manuel , Krisam Johannes , Klose Christina , Dörr-Harim Colette , Tenckhoff Solveig , Büchler Markus W. , Diener Markus K. , Mihaljevic André L.
Published: December 2019

Background

Incisional hernias are among the most frequent complications following abdominal surgery and cause substantial morbidity, impaired health-related quality of life and costs. Despite improvements in abdominal wall closure techniques, the risk for developing an incisional hernia is reported to be between 10 and 30% following midline laparotomies. There have been two recent innovations with promising results to reduce hernia risks, namely the small stitches technique and the placement of a prophylactic mesh. So far, these two techniques have not been evaluated in combination.

Methods

The HULC trial is a multicentre, randomized controlled, observer- and patient-blinded surgical effectiveness trial with two parallel study groups. A total of 812 patients scheduled for elective abdominal surgery via a midline laparotomy will be randomized in 12 centres after informed consent. Patients will be randomly assigned to the control group receiving closure of the midline incision with a slowly absorbable monofilament suture in the small stitches technique or to the intervention group, who will receive a small stitches closure followed by augmentation with a light-weight polypropylene mesh in the onlay technique. The primary endpoint will be the occurrence of incisional hernias, as defined by the European Hernia Society, within 24 months after surgery. Further perioperative parameters, as well as patient-reported outcomes, will be analysed as secondary outcomes.

Discussion

The HULC trial will address the yet unanswered question of whether a combination of small stitched fascial closure and onlay mesh augmentation after elective midline laparotomies reduces the risk of incisional hernias. The HULC trial marks the logical and innovative next step in the development of a safe abdominal closure technique.

Trial registration

German Clinical Trials Register, DRKS00017517. Registered on 24th June 2019.
Time-resolved carotenoid profiling and transcriptomic analysis reveal mechanism of carotenogenesis for astaxanthin synthesis in the oleaginous green alga Chromochloris zofingiensis
Authors: Zhang Yu , Shi Meicheng , Mao Xuemei , Kou Yaping , Liu Jin
Published: December 2019

Background

Chromochloris zofingiensis is emerging as an industrially relevant alga given its robust growth for the production of lipids and astaxanthin, a value-added carotenoid with broad applications. Nevertheless, poor understanding of astaxanthin synthesis has limited engineering of this alga for rational improvements.

Results

To reveal the molecular mechanism underlying astaxanthin accumulation in C. zofingiensis, here we conducted an integrated analysis by combining the time-resolved transcriptomes and carotenoid profiling in response to nitrogen deprivation (ND). A global response was triggered for C. zofingiensis to cope with the ND stress. Albeit the little variation in total carotenoid content, individual carotenoids responded differentially to ND: the primary carotenoids particularly lutein and β-carotene decreased, while the secondary carotenoids increased considerably, with astaxanthin and canthaxanthin being the most increased ones. The carotenogenesis pathways were reconstructed: ND had little effect on the carbon flux to carotenoid precursors, but stimulated astaxanthin biosynthesis while repressing lutein biosynthesis, thereby diverting the carotenoid flux from primary carotenoids to secondary carotenoids particularly astaxanthin. Comparison between C. zofingiensis and Haematococcus pluvialis revealed the distinctive mechanism of astaxanthin synthesis in C. zofingiensis. Furthermore, potential bottlenecks in astaxanthin synthesis were identified and possible engineering strategies were proposed for the alga.

Conclusions

Collectively, these findings shed light on distinctive mechanism of carotenogenesis for astaxanthin biosynthesis in C. zofingiensis, identify key functional enzymes and regulators with engineering potential and will benefit rational manipulation of this alga for improving nutritional traits.
Biological attributes of the kissing bug Triatoma rubrofasciata from Vietnam
Authors: Hieu Ho Viet , Do Le Thanh , Pita Sebastián , Ha Hoang , Khoa Pham Thi , Tuan Pham Anh , Mai Ta Phuong , Lien Ngo Giang , Panzera Francisco
Published: December 2019

Background

Triatoma rubrofasciata is the only kissing bug species distributed globally. In the Americas, this species transmits the parasite Trypanosoma cruzi, responsible for Chagas disease. The presence of T. rubrofasciata in several Asian countries has greatly increased recently. In Vietnam, it is found in large numbers, closely associated with human environments. Although T. rubrofasciata from Asia is not infected with Tryp. cruzi, it carries other parasites such as Trypanosoma lewisi and Trypanosoma conorhini. Reports of bites by T. rubrofasciata have increased significantly in several places of Vietnam, becoming a public health problem as it produces severe anaphylactic reactions.

Methods

Specimens of T. rubrofasciata were collected from seven provinces in central Vietnam. We analyzed different biological attributes (life-cycle, starvation resistance, feeding and reproductive capacities) and genetic characteristics (chromosomes and DNA sequences) of T. rubrofasciata from Vietnam and compared them with Brazilian specimens. Natural infection with Tryp. conorhini and Tryp. lewisi were analyzed in a sample of 100 collected insects.

Results

Species identification of T. rubrofasciata from central Vietnam was corroborated by genetic markers. Cytogenetic analyses showed that T. rubrofasciata from central Vietnam share the same chromosomal characteristics with individuals from Brazil and Hanoi. DNA sequence analyses of a mitochondrial cytochrome b gene fragment showed little variation between Old and New World specimens. Our study sample, compared with Brazilian individuals, showed a higher survival capacity revealed by a higher hatching rate (98% compared with 80.5%), a larger amount of blood taken in single meal and long-term starvation resistance. Furthermore, this species had a high natural rate of infection with Tryp. conorhini (46%) and Tryp. lewisi (27%).

Conclusions

For T. rubrofasciata of Vietnam, a high rate of fecundity throughout the year, a high capacity for starvation, and its occurrence in synanthropic environments of urban areas with a high availability of food sources are risk factors to be taken into account by vector control campaigns. The several allergic reactions caused by their bites and their high infection with Tryp. lewisi highlight the need to implement specific control programmes for T. rubrofasciata in Vietnam.
Protein profiling and network enrichment analysis in individuals before and after the onset of rheumatoid arthritis
Authors: Brink Mikael , Lundquist Anders , Alexeyenko Andrey , Lejon Kristina , Rantapää-Dahlqvist Solbritt
Published: December 2019

Background

Antibodies and upregulated cytokines and chemokines predate the onset of rheumatoid arthritis (RA) symptoms. We aimed to identify the pathways related to the early processes leading to RA development, as well as potential novel biomarkers, using multiple protein analyses.

Methods

A case-control study was conducted within the Biobank of northern Sweden. The plasma samples from 118 pre-symptomatic individuals (207 samples; median predating time 4.1 years), 79 early RA patients, and 74 matched controls were analyzed. The levels of 122 unique proteins with an acknowledged relationship to autoimmunity were analyzed using 153 antibodies and a bead-based multiplex system (FlexMap3D; Luminex Corp.). The data were analyzed using multifactorial linear regression model, random forest, and network enrichment analysis (NEA) based on the 10 most significantly differentially expressed proteins for each two-by-two group comparison, using the MSigDB collection of hallmarks.

Results

There was a high agreement between the different statistical methods to identify the most significant proteins. The adipogenesis and interferon alpha response hallmarks differentiated pre-symptomatic individuals from controls. These two hallmarks included proteins involved in innate immunity. Between pre-symptomatic individuals and RA patients, three hallmarks were identified as follows: apical junction, epithelial mesenchymal transition, and TGF-β signaling, including proteins suggestive of cell interaction, remodulation, and fibrosis. The adipogenesis and heme metabolism hallmarks differentiated RA patients from controls.

Conclusions

We confirm the importance of interferon alpha signaling and lipids in the early phases of RA development. Network enrichment analysis provides a tool for a deeper understanding of molecules involved at different phases of the disease progression.
DZ2002 ameliorates fibrosis, inflammation, and vasculopathy in experimental systemic sclerosis models
Authors: Zhang Zongwang , Wu Yanwei , Wu Bing , Qi Qing , Li Heng , Lu Huimin , Fan Chen , Feng Chunlan , Zuo Jianping , Niu Lili , Tang Wei
Published: December 2019

Background

Systemic sclerosis is a multisystem inflammatory and vascular lesion leading to extensive tissue fibrosis. A reversible S-adenosyl-l-homocysteine hydrolase (SAHH) inhibitor, DZ2002, modulates the pathologic processes of various inflammatory diseases and autoimmune diseases. This study is designed to investigate the therapeutic potentiality of DZ2002 for experimental systemic sclerosis models.

Methods

The anti-inflammatory and anti-fibrotic features of DZ2002 and its mechanisms were investigated in a bleomycin (BLM)-induced dermal fibrosis mice model. The effects of DZ2002 on expression of extracellular matrix components and TGF-β signaling in human dermal fibroblasts were analyzed. Simultaneously, the effects of DZ2002 on macrophage activation and endothelial cell adhesion molecule expression were also evaluated.

Results

DZ2002 significantly attenuated dermal fibrosis in BLM-induced mice. Consistently, DZ2002 inhibited the expression of various molecules associated with dermal fibrosis, including transforming growth factor β1, connective tissue growth factor, tumor necrosis factor-α, interferon-γ, IL-1β, IL-4, IL-6, IL-10, IL-12p40, IL-17A, and monocyte chemotactic protein 1 in the lesional skin of BLM-induced mice. Furthermore, DZ2002 decreased the proportion of macrophages, neutrophils, and T cells (especially T helper cells) in the skin tissue of BLM-induced mice. In addition, DZ2002 attenuated both M1 macrophage and M2 macrophage differentiation in vivo and in vitro. Importantly, DZ2002 directly reversed the profibrotic phenotype of transforming growth factor-β1-treated dermal fibroblasts and suppressed ICAM-1, VCAM-1, VEGF, bFGF, and ET-1 expression in endothelial cells. Finally, our investigations showed that DZ2002 relieved systemic sclerosis by regulating fibrosis TGF-β/Smad signaling pathway.

Conclusions

DZ2002 prevents the development of experimental dermal fibrosis by reversing the profibrotic phenotype of various cell types and would be a potential drug for the treatment of systemic sclerosis.
The burden of metabolic syndrome on osteoarthritic joints
Authors: Dickson Bruce M. , Roelofs Anke J. , Rochford Justin J. , Wilson Heather M. , De Bari Cosimo
Published: December 2019

Background

The prevalence of osteoarthritis (OA) increases with obesity, with up to two thirds of the elderly obese population affected by OA of the knee. The metabolic syndrome (MetS), frequently associated with central obesity and characterised by elevated waist circumference, raised fasting plasma glucose concentration, raised triglycerides, reduced high-density lipoproteins, and/or hypertension, is implicated in the pathogenesis of OA. This narrative review discusses the mechanisms involved in the influence of MetS on OA, with a focus on the effects on macrophages and chondrocytes.

Main text

A skewing of macrophages towards a pro-inflammatory M1 phenotype within synovial and adipose tissues is thought to play a role in OA pathogenesis. The metabolic perturbations typical of MetS are important drivers of pro-inflammatory macrophage polarisation and activity. This is mediated via alterations in the levels and activities of the cellular nutrient sensors 5′ adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1), intracellular accumulation of metabolic intermediates such as succinate and citrate, and increases in free fatty acids (FFAs) and hyperglycaemia-induced advanced glycation end-products (AGEs) that bind to receptors on the macrophage surface. Altered levels of adipokines, including leptin and adiponectin, further influence macrophage polarisation. The metabolic alterations in MetS also affect the cartilage through direct effects on chondrocytes by stimulating the production of pro-inflammatory and catabolic factors and possibly by suppressing autophagy and promoting cellular senescence.

Conclusions

The influence of MetS on OA pathogenesis involves a wide range of metabolic alterations that directly affect macrophages and chondrocytes. The relative burden of intra-articular versus systemic adipose tissue in the MetS-associated OA remains to be clarified. Understanding how altered metabolism interacts with joints affected by OA is crucial for the development of further strategies for treating this debilitating condition, such as supplementing existing therapies with metformin and utilising ω-3 fatty acid derivatives to restore imbalances in ω-3 and ω-6 fatty acids.
Exploring the immunomodulatory role of depot medroxyprogesterones acetate and endogenous progesterone levels in HIV infected and uninfected women
Authors: Mnqonywa Nonzwakazi , Abbai Nathlee , Ragupathy Viswanath , Ramjee Gita , Hewlett Indira , Moodley Dhayendre
Published: December 2019

Objective

The aim of this proof of concept study was to determine the effect of depot medroxyprogesterone acetate on host and viral factors in HIV infected and uninfected women.

Results

In this study, the gene expression levels for CCL5, CCR5 and CXCR4 was significantly higher in HIV positive women when compared to HIV negative women (p < 0.05). An upregulation of CCR5 and CXCR4 was evident in less than 20% of the HIV infected women and none of the HIV uninfected women. The mean fold change for CCL3 was much higher in HIV uninfected when compared to infected women with a borderline significance (p = 0.062). In HIV uninfected women, the mean fold change in CCL3, CCL4, and CCL5 gene expression was not statistically different between women on DMPA versus women not on hormonal contraception. The proportion of women with an upregulation of CCL4 and CCR5 was higher in HIV infected women on DMPA. There was no association between endogenous progesterone level and chemokines and the HIV-1 receptors. The gene expression levels in the chemokine receptors CCR5 and CXCR4 were significantly higher in the HIV infected women when compared to the women who remained HIV uninfected.
Microbiological and cytological characterization of coelomic fluid from three captive endangered amphibian Gastrotheca species with edema syndrome: preliminary analysis
Authors: Oleas-Paz Anahí , Santamaría-Naranjo Ana Cecilia , Rojas-Carrillo Maira , Merino-Viteri Andrés , Genoy-Puerto Alexander
Published: December 2019

Objective

Edema syndrome is highly prevalent but under researched in captive frogs around the world. The objective of the present study was to characterize at a basic microbiological and cytological level of the bacteria of the edema fluid of 20 individuals of the genus Gastrotheca to determine the presence of possible anaerobic and aerobic bacteria.

Results

Fourteen types of bacteria were identified in the edema fluid, 12 of them at the species level (Pasteurella haemolytica, Hafnia alvei, Enterobacter agglomerans, Aeromonas hydrophila, Pseudomonas fluorescens, Burkholderia pseudomallei, Salmonella arizonae, Enterobacter gergoviae, Enterobacter sakazakii, Yersinia enterocolitica, Klebsiella oxytoca, and Klebsiella ozaenae) and two at the genus level (Enterococcus spp. and Streptococcus spp.). The most frequently identified cells were lymphocytes (37.7% in females and 46.4% in males), erythrocytes (23.5% in females and 17.5% in males) and neutrophils (4.2% in females and 2.8% in males). Finally, no relationship was found between the data obtained and the sex of the individuals studied.
Epigenetic gestational age and trajectories of weight and height during childhood: a prospective cohort study
Authors: Bright Harold D. , Howe Laura D. , Khouja Jasmine N. , Simpkin Andrew J. , Suderman Matthew , O’Keeffe Linda M.
Published: December 2019

Background

Differences between an individual’s estimated epigenetic gestational age (EGA) and their actual gestational age (GA) are defined as gestational age acceleration (GAA). GAA is associated with increased birthweight and birth length. Whether these associations persist through childhood is yet to be investigated.

Methods

We examined the association between GAA and trajectories of height and weight from birth to 10 years (n = 785) in a British birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC). EGA of participants was estimated using DNA methylation data from cord blood using a recently developed prediction model. GAA of participants, measured in weeks, was calculated as the residuals from a regression model of EGA on actual GA. Analyses were performed using linear spline multilevel models and adjusted for maternal age, maternal pre-pregnancy BMI, maternal smoking during pregnancy, and maternal education.

Results

In adjusted analyses, offspring with a one-week greater GAA were born on average 0.14 kg heavier (95% confidence interval (CI) 0.09, 0.19) and 0.55 cm taller (95% CI 0.33, 0.78) at birth. These differences in weight persisted up to approximately age 9 months but thereafter began to attenuate. From age 5 years onwards, the association between GAA and weight reversed such that GAA was associated with lower weight and this association strengthened with age (mean difference at age 10 years − 0.60 kg, 95% CI − 1.19, − 0.01). Differences in height persisted only up to age 9 months (mean difference at 9 months 0.15 cm, 95% CI − 0.09, 0.39). From age 9 months to age 10 years, offspring with a one-week greater GAA were of comparable height with those with no GAA (mean difference at age 10 years − 0.07 cm, 95% CI − 0.64, 0.50).

Conclusions

Gestational age acceleration is associated with increased birth weight and length and these differences persist to age 9 months. From age 5 years onwards, the association of GAA and weight reverses such that by age 10 years, greater GAA is associated with lower childhood weight. Further work is required to examine whether the weight effects of GAA strengthen through adolescence and into early adulthood.
IntelliPatent: a web-based intelligent system for fast chemical patent claim drafting
Authors: Wang Pei-Hua , Tseng Yufeng Jane
Published: December 2019

The first step of automating composition patent drafting is to draft the claims around a Markush structure with substituents. Currently, this process depends heavily on experienced attorneys or patent agents, and few tools are available. IntelliPatent was created to accelerate this process. Users can simply upload a series of analogs of interest, and IntelliPatent will automatically extract the general structural scaffold and generate the patent claim text. The program can also extend the patent claim by adding commonly seen R groups from historical lists of the top 30 selling drugs in the US for all R substituents. The program takes MDL SD file formats as inputs, and the invariable core structure and variable substructures will be identified as the initial scaffold and R groups in the output Markush structure. The results can be downloaded in MS Word format (.docx). The suggested claims can be quickly generated with IntelliPatent. This web-based tool is freely accessible at https://intellipatent.cmdm.tw/.
A unit selection text-to-speech-and-singing synthesis framework from neutral speech: proof of concept
Authors: Freixes Marc , Alías Francesc , Socoró Joan Claudi
Published: December 2019

Text-to-speech (TTS) synthesis systems have been widely used in general-purpose applications based on the generation of speech. Nonetheless, there are some domains, such as storytelling or voice output aid devices, which may also require singing. To enable a corpus-based TTS system to sing, a supplementary singing database should be recorded. This solution, however, might be too costly for eventual singing needs, or even unfeasible if the original speaker is unavailable or unable to sing properly. This work introduces a unit selection-based text-to-speech-and-singing (US-TTS&S) synthesis framework, which integrates speech-to-singing (STS) conversion to enable the generation of both speech and singing from an input text and a score, respectively, using the same neutral speech corpus. The viability of the proposal is evaluated considering three vocal ranges and two tempos on a proof-of-concept implementation using a 2.6-h Spanish neutral speech corpus. The experiments show that challenging STS transformation factors are required to sing beyond the corpus vocal range and/or with notes longer than 150 ms. While score-driven US configurations allow the reduction of pitch-scale factors, time-scale factors are not reduced due to the short length of the spoken vowels. Moreover, in the MUSHRA test, text-driven and score-driven US configurations obtain similar naturalness rates of around 40 for all the analysed scenarios. Although these naturalness scores are far from those of vocaloid, the singing scores of around 60 which were obtained validate that the framework could reasonably address eventual singing needs.
A modified algorithm for computation issues in UAV-enabled wireless communications
Authors: Hu Bing , Ding Xiaojian , Yang Fan , Liu Jian
Published: December 2019

Unmanned aerial vehicles (UAVs) in wireless communication have received significant interests recently due to its low cost and flexibility in providing wireless connectivity in areas without infrastructure coverage. In this paper, we optimize the location of UAVs to maximize their coverage areas. We propose a modified artificial bee colony (MABC) incorporating bee number reallocation and a new search equation. In the proposed algorithm, a greater number of bees in the population are assigned to execute local searches near food sources to enhance solution accuracy, and the bees are guided by elite vectors to enable the algorithm to rapidly converge to a potentially globally optimal position. The deployment of UAVs is thus obtained. The experimental results show that the proposed algorithm achieves great improvements over the traditional algorithm.
Compound Poisson point processes, concentration and oracle inequalities
Authors: Zhang Huiming , Wu Xiaoxu
Published: December 2019

This note aims at presenting several new theoretical results for the compound Poisson point process, which follows the work of Zhang et al. (Insur. Math. Econ. 59:325–336, 2014). The first part provides a new characterization for a discrete compound Poisson point process (proposed by Aczél (Acta Math. Hung. 3(3):219–224, 1952)), it extends the characterization of the Poisson point process given by Copeland and Regan (Ann. Math. 37:357–362, 1936). Next, we derive some concentration inequalities for discrete compound Poisson point process (negative binomial random variable with unknown dispersion is a significant example). These concentration inequalities are potentially useful in count data regression. We give an application in the weighted Lasso penalized negative binomial regressions whose KKT conditions of penalized likelihood hold with high probability and then we derive non-asymptotic oracle inequalities for a weighted Lasso estimator.
Certain inequalities via generalized proportional Hadamard fractional integral operators
Authors: Rahman Gauhar , Abdeljawad Thabet , Jarad Fahd , Khan Aftab , Nisar Kottakkaran Sooppy
Published: December 2019

In the article, we introduce the generalized proportional Hadamard fractional integrals and establish several inequalities for convex functions in the framework of the defined class of fractional integrals. The given results are generalizations of some known results.