bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary fermented soybean meal replacement alleviates diarrhea in weaned piglets challenged with enterotoxigenic Escherichia coli K88 by modulating inflammatory cytokine levels and cecal microbiota composition
Authors: Wang Wenwen , Wang Yuan , Hao Xiran , Duan Yuanxiao , Meng Ziqi , An Xiaoping , Qi Jingwei
Published: July 2020

Background

Impaired gut microbiota leads to pathogenic bacteria infection, pro-inflammatory response and post-weaning diarrhea. Enterotoxigenic Escherichia coli (ETEC) K88 is a major cause of post-weaning diarrhea in weaned piglets. Fermented soybean meal (FSBM) could relieve diarrhea, alleviate inflammatory response, and modulate gut microbiota of weaned piglets. We used ETEC K88-challenged weaned piglet model to investigate the effects of FSBM on the growth performance, inflammatory response and cecal microbiota. Twenty-four crossbred piglets (6.8 ± 0.5 kg; 21 ± 2 days of age) were allotted into 2 treatment fed the diets with or without FSBM (6% at the expense of soybean meal). Six weaned piglets in each diet treatment were challenged by ETEC K88 (1 × 109 CFU/piglets) on day 15. The experimental period lasted for 20 days.

Results

The ETEC K88 challenge decreased (p < 0.05) fecal consistency and plasma interleukin-10 (IL-10) concentration, while increased (p < 0.05) average daily feed intake (ADFI) and plasma tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin 6 (IL-6) concentrations. After ETEC K88 challenge, dietary FSBM replacement increased (p < 0.05) final body weight (BW), average daily gain (ADG), ADFI, and fecal consistency, but decreased feed conversion ratio (FCR). The plasma IL-10 concentration of weaned piglets fed FSBM was higher (p < 0.05), while IL-1β, IL-6 and TNF-α concentrations were lower (p < 0.05). Dietary FSBM replacement attenuated the increase of plasma TNF-α concentration and the decrease of ADG induced by ETEC K88 challenge (p < 0.05). High-throughput sequencing of 16S rRNA gene V4 region of cecal microbiota revealed that ETEC K88 challenge increased (p < 0.05) Campylobacter relative abundance on genus level. Dietary FSBM replacement resulted in higher (p < 0.05) relative abundances of Bacteroidetes and Prevotellaceae_NK3B31_group, and lower (p < 0.05) relative abundances of Proteobacteria and Actinobacillus. Furthermore, dietary FSBM replacement relieved the increase of Escherichia-Shigella relative abundance in weaned piglets challenged by ETEC K88 (p < 0.05).

Conclusions

Dietary FSBM replacement improved growth performance and alleviated the diarrhea of weaned piglets challenged with ETEC K88, which could be due to modulation of cecal microbiota composition and down-regulation of inflammatory cytokines production.
Electrocardiographic safety evaluation of extended artemether-lumefantrine treatment in patients with uncomplicated Plasmodium falciparum malaria in Bagamoyo District, Tanzania
Authors: Mhamilawa Lwidiko E. , Wikström Sven , Mmbando Bruno P. , Ngasala Billy , Mårtensson Andreas
Published: July 2020

Background

Extended artemisinin-based combination therapy (ACT) for treatment of uncomplicated Plasmodium falciparum malaria with already existing drug regimens, such as artemether-lumefantrine, might be effective in tackling the emerging ACT resistance. However, given the history of cardiotoxicity among anti-malarial drugs structurally similar to lumefantrine, the potential effect of extended artemether-lumefantrine treatment on the electrocardiographic (ECG) QTc interval is of high concern.

Methods

Male and non-pregnant females aged 1–65 years, diagnosed with uncomplicated P. falciparum malaria in Bagamoyo district, Tanzania, were randomized into two arms. The intervention arm received an extended, i.e. 6-day, course of artemether-lumefantrine and an additional single low-dose primaquine (0.25 mg/kg) administered together with the last artemether-lumefantrine dose. The control arm received the standard weight-based 3-day course. ECGs were performed at day 0 and 4–5 h after the last dose at day 5. QT intervals were read manually using the tangent method and automatically. Bazett’s (QTcB) and Fridericia’s (QTcF) formulae were used for correction for heart rate. Descriptive statistics were used to calculate baseline characteristics and the number of supra-thresholds QTc intervals (QTc prolongation > 500, change in QTc interval (ΔQTc) > 60 ms). The mean change in QTc interval in and between the two arms was compared using the paired t-test and independent samples t-test, respectively.

Results

A total of 195 patients were enrolled, 103 and 92 in the intervention and control arm, respectively. No patient experienced QTc intervals > 500 ms on day 5 by both formulae. Patients with ΔQTc > 60 ms, for QTcF were 6/103 (5.8%) vs 2/92 (2.2%) and for QTcB 2/103 (1.9%) vs 1/92 (1.1%) in the intervention and control arms, respectively. The mean difference in ΔQTc interval was statistically significant between the two arms with both correction formulae, 11.4 ms (95% CI 2.7–20.0, p = 0.010) and 13.4 ms (95% CI 5.3–21.5, p = 0.001), for QTcB and QTcF, respectively.

Conclusion

The extended 6-day course of artemether-lumefantrine did not reveal clinically relevant QTc prolonging effects. However, significant QTcF prolongation and presence of patients with supra-threshold QTc values observed in the intervention arm underscore the importance of further monitoring of QTc parameters in extended artemether-lumefantrine treatment.

Trial registration ClinicalTrials.gov, NCT03241901. Registered July 27, 2017. https://clinicaltrials.gov/show/NCT03241901
Mass testing and treatment for malaria followed by weekly fever screening, testing and treatment in Northern Senegal: feasibility, cost and impact
Authors: Conner Ruben O. , Dieye Yakou , Hainsworth Michael , Tall Adama , Cissé Badara , Faye Farba , Sy Mame Demba , Ba Amadou , Sene Doudou , Ba Souleymane , Doucouré Elhadji , Thiam Tidiane , Diop Moussa , Schneider Kammerle , Cissé Moustapha , Ba Mady , Earle Duncan , Guinot Philippe , Steketee Richard W. , Guinovart Caterina
Published: July 2020

Background

Population-wide interventions using malaria testing and treatment might decrease the reservoir of Plasmodium falciparum infection and accelerate towards elimination. Questions remain about their effectiveness and evidence from different transmission settings is needed.

Methods

A pilot quasi-experimental study to evaluate a package of population-wide test and treat interventions was conducted in six health facility catchment areas (HFCA) in the districts of Kanel, Linguère, and Ranérou (Senegal). Seven adjacent HFCAs were selected as comparison. Villages within the intervention HFCAs were stratified according to the 2013 incidences of passively detected malaria cases, and those with an incidence ≥ 15 cases/1000/year were targeted for a mass test and treat (MTAT) in September 2014. All households were visited, all consenting individuals were tested with a rapid diagnostic test (RDT), and, if positive, treated with dihydroartemisinin-piperaquine. This was followed by weekly screening, testing and treatment of fever cases (PECADOM++) until the end of the transmission season in January 2015. Villages with lower incidence received only PECADOM++ or case investigation. To evaluate the impact of the interventions over that transmission season, the incidence of passively detected, RDT-confirmed malaria cases was compared between the intervention and comparison groups with a difference-in-difference analysis using negative binomial regression with random effects on HFCA.

Results

During MTAT, 89% (2225/2503) of households were visited and 86% (18,992/22,170) of individuals were tested, for a combined 77% effective coverage. Among those tested, 291 (1.5%) were RDT positive (range 0–10.8 by village), of whom 82% were < 20 years old and 70% were afebrile. During the PECADOM++ 40,002 visits were conducted to find 2784 individuals reporting fever, with an RDT positivity of 6.5% (170/2612). The combination of interventions resulted in an estimated 38% larger decrease in malaria case incidence in the intervention compared to the comparison group (adjusted incidence risk ratio = 0.62, 95% CI 0.45–0.84, p = 0.002). The cost of the MTAT was $14.3 per person.

Conclusions

It was operationally feasible to conduct MTAT and PECADOM++ with high coverage, although PECADOM++ was not an efficient strategy to complement MTAT. The modest impact of the intervention package suggests a need for alternative or complementary strategies.
Polymorphisms in Plasmodium vivax antifolate resistance markers in Afghanistan between 2007 and 2017
Authors: Rakmark Kasama , Awab Ghulam R. , Duanguppama Jureeporn , Boonyuen Usa , Dondorp Arjen M. , Imwong Mallika
Published: July 2020

Background

Plasmodium vivaxis the predominantPlasmodiumspecies in Afghanistan. National guidelines recommend the combination of chloroquine and primaquine (CQ-PQ) for radical treatment ofP. vivaxmalaria. Artesunate in combination with the antifolates sulfadoxine-pyrimethamine (SP) has been first-line treatment for uncomplicated falciparum malaria until 2016. Although SP has been the recommended treatment for falciparum and not vivax malaria, exposure of theP. vivaxparasite population to SP might still have been quite extensive because of community based management of malaria. The change in theP. vivaxantifolate resistance markers between 2007 and 2017 were investigated.

Methods

Dried blood spots were collected (n = 185) from confirmedP. vivaxpatients in five malaria-endemic areas of Afghanistan bordering Tajikistan, Turkmenistan and Pakistan, including Takhar, Faryab, Laghman, Nangarhar, and Kunar, in 2007, 2010 and 2017. Semi-nested PCR, RFLP and nucleotide sequencing were used to assess the pyrimethamine resistant related mutations inP. vivax dihydrofolate reductase(pvdhfrI13L, P33L, N50I, F57L, S58R, T61I, S93H, S117N, I173L) and the sulfonamide resistance related mutations inP. vivax dihydropteroate synthase(pvdhpsA383G, A553G).

Results

In the 185 samples genotyped forpvdhfrandpvdhpsmutations,11 distinct haplotypes were observed, which evolved over time. In 2007, wild typepvdhfrandpvdhpswere the most frequent haplotype in all study sites (81%, 80/99). However, in 2017, the frequency of the wild-type was reduced to 36%, (21/58;pvalue ≤ 0.001), with an increase in frequency of the double mutantpvdhfrandpvdhpshaplotype S58RS117N (21%, 12/58), and the singlepvdhfrmutant haplotype S117N (14%, 8/58). Triple and quadruple mutations were not found. In addition,pvdhfrmutations at position N50I (7%, 13/185) and the novel mutation S93H (6%, 11/185) were observed. Based on in silico protein modelling and molecular docking, thepvdhfrN50I mutation is expected to affect only moderately pyrimethamine binding, whereas the S93H mutation does not.

Conclusions

In the course of ten years, there has been a strong increase in the frequency pyrimethamine resistance related mutations inpvdhfrin theP. vivaxpopulation in Afghanistan, although triple and quadruple mutations conferring high grade resistance were not observed. This suggests relatively low drug pressure from SP on theP. vivaxparasite population in the study areas. The impact of two newly identified mutations in thepvdhfrgene on pyrimethamine resistance needs further investigation.
Tackling segmentation to advance universal health coverage: analysis of policy architectures of health care in Chile and Uruguay
Authors: Bernales-Baksai Pamela
Published: July 2020

Background

With the turn of the century, most countries in Latin America witnessed an increased concern with universalism and redistribution. In the health sector, this translated into a wide range of reforms to advance Universal Health Coverage (UHC) that, however, have had to cope with health systems that stratified the population since their foundation and the further segmentation inherited by market-oriented policies in the 1980s and 1990s.

Studies on social welfare stress the relevance of cross-class alliances between the middle and working classes to reach universal and sustainable social benefits. Consequently, the endurance of separate health schemes across groups of the population in most countries in Latin America may seriously hamper the efforts towards UHC.

Aim

This article addresses the potential of current policy architectures of health care to tackle segmentation between social classes in access to health services in two of the best performers of health coverage in the region, namely Chile and Uruguay.

Methods

The article is a comparative case study based on a literature review and applies an analytical framework that links universal outputs to the policy architectures of health care. The study assesses universal outputs in terms of coverage, generosity and financial protection, identifying equity gaps in each of these dimensions across groups of the population.

Findings

Latest processes of reform for UHC in Chile and Uruguay perform highly regarding population coverage. Nevertheless, equity gaps in access to quality services and financial protection remain. In both countries, such gaps relate to the eligibility criteria. In Chile, segmentation is reinforced by the persistence of separated pools of resources that hinder solidarity. Besides, the significant role of private actors and differences in quality between public and private service providers continue to push middle and upper-middle classes to private options. Uruguay’s health reform reinforced the public system and promoted financial solidarity by pooling and progressively allocating resources. Despite this, fragmentation in service provision continues the segmentation of access to health care.

Conclusions

The study shows differences in the options of reforms for UHC in Chile and Uruguay and the relevance of policy architectures to reverse, or conversely deepen, segmentation across groups of the population.
Health-related quality of life and post-traumatic stress disorder in inpatients injured in the Ludian earthquake: a longitudinal study
Authors: Yang Wanqiu , Cui Ke , Sim Timothy , Zhang Jun , Yang Yanchun , Ma Xiaohong
Published: July 2020

Background

The aim of this longitudinal study was to identify risk factors for posttraumatic stress disorder (PTSD) in inpatients injured in the Ludian earthquake and examine the relationship between PTSD symptoms and health-related quality of life (HRQoL) following the earthquake.

Methods

Three assessments were performed during an 18-month follow-up period. In total, one-hundred forty-seven inpatients of one-hundred seventy-four inpatients (85% of the initial sample) underwent all the assessments. Injured inpatients admitted to the No. 1 People’s Hospital of Zhaotong City after a severe earthquake (6.5 on the Richter scale) were enrolled in the study and assessed using the Posttraumatic Stress Disorder Checklist-Civilian Version, Clinician-Administered Posttraumatic Stress Disorder Scale, and Medical Outcomes Study Short Form-36 Scale.

Results

At the first, third and eighteenth months after the earthquake, the prevalence rates for PTSD were 23, 14, and 7%, respectively. In a regression model, bereavement, history of major diseases, and severe injury in the earthquake were associated with severe PTSD symptoms. HRQoL was negatively correlated with PTSD symptoms. Compared to that of Chinese norms, participants’ HRQoL was significantly lower in all eight HRQoL domains of the Medical Outcomes Study Short Form-36 Scale.

Conclusions

The findings suggest that a substantial proportion of inpatients injured in the earthquake experienced severe PTSD symptoms and poor HRQoL. Therefore, early preventive programs and interventions should be implemented following disasters, to reduce PTSD and improve HRQoL in injured individuals.
Subclinical cardiovascular risk signs in adults with juvenile idiopathic arthritis in sustained remission
Authors: Aranda-Valera Inmaculada Concepción , Arias de la Rosa Iván , Roldán-Molina Rosa , Ábalos-Aguilera María del Carmen , Torres-Granados Carmen , Patiño-Trives Alejandra , Luque-Tevar María , Ibáñez-Costa Alejandro , Guzmán-Ruiz Rocío , Malagón María del Mar , Escudero-Contreras Alejandro , López-Pedrera Chary , Collantes-Estévez Eduardo , Barbarroja Nuria
Published: July 2020

Background

Juvenile Idiopathic Arthritis (JIA) is one of the most common chronic diseases of childhood that often persists into adulthood and can result in significant long-term morbidity. As a long lasting chronic inflammatory disease, concern has been raised regarding the risk of premature development of cardiovascular disease (CVD) in JIA. This study aims to determine whether adults with JIA in clinical remission display clinical and subclinical signs of CVD risk: inflammatory mediators, adipokines, endothelial dysfunction and oxidative stress markers.

Methods

This is a cross-sectional study including 25 patients diagnosed with JIA according to the International League of Associations for Rheumatology criteria (ILAR 2001) and 25 age- and sex-matched controls. Remission was determined by JADAS10 < 1 and according to Wallace criteria. The presence of traditional CVD risk factors was analyzed. An extensive clinical analysis including body mass index (BMI), lipid profile, homeostatic model assessment – insulin resistance (HOMA-IR) and arterial blood pressure was performed. Intima media thickness of the common carotid artery (CIMT) was measured as a marker of subclinical atherosclerosis. Several proinflammatory cytokines, molecules involved in the endothelial dysfunction, oxidative stress and adipokines were quantified on serum by ELISA and on peripheral blood mononuclear cells (PBMCs) by RT-PCR. In vitro studies were carried out in healthy PBMCs, adipocytes and endothelial cells which were treated with serum from JIA patients under sustained remission.

Results

Mean duration of the disease was 13.47 ± 5.47 years. Mean age was 25.11 ± 7.21. Time in remission was 3.52 ± 3.33 years. Patients were in remission with no treatment (40%) and with treatments (60%). CVD risk factors and CIMT were similar in JIA patients and controls. However, cholesterol levels were significantly elevated in JIA patients. Levels of adipocytokines, oxidative stress and endothelial activation markers were elevated in serum and PBMCs from JIA patients. Serum of those JIA patients induced the activation of adipocytes, endothelial cells and healthy PBMCs.

Conclusions

JIA adult patients in remission have subclinical signs of inflammation and CVD risk, showed by an increase in the levels of inflammatory cytokines, endothelial activation and oxidative stress markers and adipokines, molecules closely involved in the alteration of the vascular system.
The paediatric global musculoskeletal task force - ‘towards better MSK health for all’
Authors: Foster Helen E. , Scott Christiaan , Tiderius Carl J. , Dobbs Matthew B.
Published: July 2020

There is increasing concern about the emerging global non-communicable diseases (NCDs) burden. The focus has mainly been on NCDs in adults but it is important that MSK morbidity in both children and adults is included in strategic planning. There have been considerable advances in the understanding and treatment options for children and young people (CYP) and clinical outcomes are improving for those who can access such high quality care. However vast inequity exists and there are many CYP who live in areas of the world with high burden of health care challenges, compounded by paucity of specialist care and limited access to treatments. The Paediatric Global Musculoskeletal Task Force aims to raise awareness about unmet needs for CYP with MSK conditions, promotion of MSK health through lifestyle and the avoidance of injury. We aim to leverage change through ‘working together better’.
Assessment of Parkinsonian gait in older adults with dementia via human pose tracking in video data
Authors: Sabo Andrea , Mehdizadeh Sina , Ng Kimberley-Dale , Iaboni Andrea , Taati Babak
Published: July 2020

Background

Parkinsonism is common in people with dementia, and is associated with neurodegenerative and vascular changes in the brain, or with exposure to antipsychotic or other dopamine antagonist medications. The detection of parkinsonian changes to gait may provide an opportunity to intervene and address reversible causes. In this study, we investigate the use of a vision-based system as an unobtrusive means to assess severity of parkinsonism in gait.

Methods

Videos of walking bouts of natural gait were collected in a specialized dementia unit using a Microsoft Kinect sensor and onboard color camera, and were processed to extract sixteen 3D and eight 2D gait features. Univariate regression to gait quality, as rated on the Unified Parkinson’s Disease Rating Scale (UPDRS) and Simpson-Angus Scale (SAS), was used to identify gait features significantly correlated to these clinical scores for inclusion in multivariate models. Multivariate ordinal logistic regression was subsequently performed and the relative contribution of each gait feature for regression to UPDRS-gait and SAS-gait scores was assessed.

Results

Four hundred one walking bouts from 14 older adults with dementia were included in the analysis. Multivariate ordinal logistic regression models incorporating selected 2D or 3D gait features attained similar accuracies: the UPDRS-gait regression models achieved accuracies of 61.4 and 62.1% for 2D and 3D features, respectively. Similarly, the SAS-gait models achieved accuracies of 47.4 and 48.5% with 2D or 3D gait features, respectively.

Conclusions

Gait features extracted from both 2D and 3D videos are correlated to UPDRS-gait and SAS-gait scores of parkinsonism severity in gait. Vision-based systems have the potential to be used as tools for longitudinal monitoring of parkinsonism in residential settings.
Next generation sequencing to decipher concurrent loss of PMS2 and MSH6 in colorectal cancer
Authors: Moreno Esther , Rosa-Rosa Juan M. , Caniego-Casas Tamara , Ruz-Caracuel Ignacio , Perna Cristian , Guillén Carmen , Palacios José
Published: July 2020

Background

Immunohistochemistry (IHQ) is commonly used for the detection of mismatch repair proteins deficiency (MMRD). One very infrequent abnormal pattern of MMR protein expression is the loss of PMS2 and MSH6, with intact expression of MLH1 and MSH2.

Case presentation

We review the frequency of this MMRD IHC pattern among 108 colorectal (CRCs) and 35 endometrial cancers in our files with loss of expression of at least one protein, and present two CRCs showing loss of PMS2 and MSH6 protein expression (1.9% of CRCs). NGS analysis of these tumours identified PMS2 mutations (R134* germline mutation in one tumour and M1R and c.1239delA somatic mutation in the other) as the primary event and somatic MSH6 mutation (c.3261dupC) as the secondary event in both tumours.

Conclusions

This study suggests that Next Generation Sequencing (NGS) tumour analysis should be considered in the algorithm of Lynch syndrome screening to detect MMR gen somatic mutation in inconclusive cases.
Effectiveness of the baby-friendly community initiative in promoting exclusive breastfeeding among HIV negative and positive mothers: a randomized controlled trial in Koibatek Sub-County, Baringo, Kenya
Authors: Samburu Betty Mogesi , Young Sera Lewise , Wekesah Frederick Murunga , Wanjohi Milkah Njeri , Kimiywe Judith , Muriuki Peter , Griffiths Paula L. , McGarvey Stephen T. , Madise Nyovani Janet , Kimani-Murage Elizabeth W.
Published: July 2020

Background

Although the baby-friendly community initiative (BFCI) has been proposed as a community-level approach to improve infant feeding practices, there is little data on its variation in effectiveness by HIV status. We conducted a study to determine the effectiveness of BFCI in changing knowledge and attitudes towards exclusive breastfeeding (EBF) and increasing the rates among HIV negative and HIV positive women in rural Kenya.

Methods

A community-based cluster-randomized controlled trial was implemented from April 2015 to December 2016 among 901 women enrolled across 13 clusters. The intervention groups received a minimum of 12 personalized home-based counselling sessions on infant feeding by trained community health volunteers from their first or second trimester of pregnancy until 6 months postpartum. Other interventions included education sessions at maternal child clinics, mother-to-mother support group meetings and bi-monthly baby-friendly gatherings targeting influencers. The control group received standard health education at the facility and during monthly routine home visits by community health volunteers not trained on BFCI. Primary outcome measures were the rates of EBF at week 1, months 2, 4 and 6 postpartum. Secondary outcomes included knowledge and attitudes regarding breastfeeding for HIV-exposed infants. Statistical methods included analysis of covariance and logistic regression.

Results

At 6 months, EBF rates among HIV negative mothers were significantly higher in the BFCI intervention arm compared to the control arm (81.7% versus 42.2%p = 0.001). HIV positive mothers in the intervention arm had higher EBF rates at 6 months than the control but the difference was not statistically significant (81.8% versus 58.4%;p = 0.504). In HIV negative group, there was greater knowledge regarding EBF for HIV-exposed infants in the intervention arm than in the control (92.1% versus 60.7%p = 0.001). Among HIV positive mothers, such knowledge was high among both the intervention and control groups (96% versus 100%,p > 0.1). HIV negative and positive mothers in the intervention arm had more favourable attitudes regarding EBF for HIV-exposed infants than the control (84.5% versus 62.1%,p = 0.001) and (94.6% versus 53.8% top = 0.001) respectively.

Conclusions

BFCI interventions can complement facility-based interventions to improve exclusive and continued breastfeeding knowledge, attitudes, and behaviours among HIV negative and positive women.
Genotype-phenotype correlation in 75 patients with small supernumerary marker chromosomes
Authors: Li Tingting , Sang Haiquan , Chu Guoming , Zhang Yuanyuan , Qi Manlong , Liu Xiaoliang , Cui Wanting , Zhao Yanyan
Published: July 2020

Background

Small supernumerary marker chromosomes (sSMCs) are rare structural abnormalities in the population; however, they are frequently found in children or fetuses with hypoevolutism and infertile adults. sSMCs are usually observed first by karyotyping, and further analysis of their molecular origin is important in clinical practice. Next-generation sequencing (NGS) combined with Sanger sequencing helps to identify the chromosomal origins of sSMCs and correlate certain sSMCs with a specific clinical picture.

Results

Karyotyping identified 75 sSMCs in 74,266 samples (0.1% incidence). The chromosomal origins of 27 of these sSMCs were detected by sequencing-related techniques (NGS, MLPA and STR). Eight of these sSMCs are being reported for the first time. sSMCs mainly derived from chromosomal X, Y, 15, and 18, and some sSMC chromosomal origins could be correlated with clinical phenotypes. However, the chromosomal origins of the remaining 48 sSMC cases are unknown. Thus, we will develop a set of economical and efficient methods for clinical sSMC diagnosis.

Conclusions

This study details the comprehensive characterization of 27 sSMCs. Eight of these sSMCs are being reported here for the first time, providing additional information to sSMC research. Identifying sSMCs may reveal genotype-phenotype correlations and integrate genomic data into clinical care.
Central venous pressure measurement is associated with improved outcomes in septic patients: an analysis of the MIMIC-III database
Authors: Chen Hui , Zhu Zhu , Zhao Chenyan , Guo Yanxia , Chen Dongyu , Wei Yao , Jin Jun
Published: July 2020

Purpose

Measurement of central venous pressure (CVP) can be a useful clinical tool. However, the formal utility of CVP measurement in preventing mortality in septic patients has never been proven.

Methods

The Medical Information Mart for Intensive Care III (MIMIC-III) database was searched to identify septic patients with and without CVP measurements. The primary outcome was 28-day mortality. Multivariate regression was used to elucidate the relationship between CVP measurement and 28-day mortality, and propensity score matching (PSM) and an inverse probability of treatment weighing (IPTW) were employed to validate our findings.

Results

A total of 10,275 patients were included in our study, of which 4516 patients (44%) underwent CVP measurement within 24 h of intensive care unit (ICU) admission. The risk of 28-day mortality was reduced in the CVP group (OR 0.60 (95% CI 0.51–0.70; p < 0.001)). Patients in the CVP group received more fluid on day 1 and had a shorter duration of mechanical ventilation and vasopressor use, and the reduction in serum lactate was greater than that in the no CVP group. The mediating effect of serum lactate reduction was significant for the whole cohort (p = 0.04 for the average causal mediation effect (ACME)) and patients in the CVP group with an initial CVP level below 8 mmHg (p = 0.04 for the ACME).

Conclusion

CVP measurement was associated with decreased risk-adjusted 28-day mortality among patients with sepsis and was proportionally mediated through serum lactate reduction.
Randomized placebo-controlled clinical trial investigating the effect of antioxidants and a vasodilator on overall safety and residual hearing preservation in cochlear implant patients
Authors: Scheper Verena , Schmidtheisler Melanie , Lasch Florian , von der Leyen Heiko , Koch Armin , Schwieger Jana , Büchner Andreas , Lesinski-Schiedat Anke , Lenarz Thomas
Published: July 2020

Background

The standard therapy for patients suffering from sensorineural hearing loss is cochlear implantation. The insertion of the electrode array into the cochlea, with potential mechanical trauma and the presence of this foreign body inside the cochlea, may lead to free radical formation and reduced blood perfusion of the cochlea which can result in a loss of residual hearing. Studies have suggested that a particular combination of the antioxidants vitamins A, C and E as well as the vasodilator magnesium (together: ACEMg) may protect the residual hearing.

Methods

The potential protective effect of ACEMg on residual hearing preservation in cochlear implant (CI) patients was investigated in a single-centre, randomized, placebo-controlled, double-blind phase II clinical trial. CI candidates with some residual hearing in low frequencies receiving MED-EL implants of different FLEX electrode array lengths were treated with ACEMg tablets or placebo respectively 2 days preoperatively and up to 3 months postoperatively. The study objective was to demonstrate that ACEMg is more efficacious than placebo in preserving residual hearing during cochlear implantation by comparing the hearing loss (change in hearing thresholds at 500 Hz from baseline) 3 months after the first fitting between the two treatment groups and to investigate the treatments’ safety.

Results

Fifty-one patients were included in the study, which had to be terminated before the recruitment goal was reached because of IMP-resupply mismanagement of one partner. In the intention-to-treat population, 25 patients were treated with ACEMg and 24 patients with placebo. The mean hearing loss at 500 Hz was (± 15.84) 30.21 dB (placebo) or (± 17.56) 26.00 dB (ACEMg) 3 months after the initial fitting. Adjusting the postoperative hearing loss for the baseline residual hearing, planned electrode length and surgeon results in 8.01 dB reduced hearing loss in ACEMg-treated patients compared to placebo-treated ones. The safety analysis revealed that ACEMg was generally well-tolerated with adverse event frequencies below the placebo level.

Conclusion

This is the first clinical trial investigating a drug effect on residual hearing in CI patients. These first-in-man data may suggest that a perioperative oral administration of ACEMg is safe and may provide protection of residual hearing in CI patients.

Trial registration

EU Clinical Trial Register No. 2012-005002-22. Registered on 6 December 2013. Funding: European Commission FP7-HEALTH-2012-INNOVATION-2.
Structural elucidation, molecular docking, α-amylase and α-glucosidase inhibition studies of 5-amino-nicotinic acid derivatives
Authors: Nawaz Muhammad , Taha Muhammad , Qureshi Faiza , Ullah Nisar , Selvaraj Manikandan , Shahzad Sumaira , Chigurupati Sridevi , Waheed Abdul , Almutairi Fadiah Ammar
Published: July 2020

In this study, 5-amino-nicotinic acid derivatives (1–13) have been designed and synthesized to evaluate their inhibitory potential against α-amylase and α-glucosidase enzymes. The synthesized compounds (1–13) exhibited promising α-amylase and α-glucosidase activities. IC50 values for α-amylase activity ranged between 12.17 ± 0.14 to 37.33 ± 0.02 µg/mL ± SEM while for α-glucosidase activity the IC50 values were ranged between 12.01 ± 0.09 to 38.01 ± 0.12 µg/mL ± SEM. In particular, compounds 2 and 4–8 demonstrated significant inhibitory activities against α-amylase and α-glucosidase and the inhibitory potential of these compounds was comparable to the standard acarbose (10.98 ± 0.03 and 10.79 ± 0.17 µg/mL ± SEM, respectively). In addition, the impact of substituent on the inhibitory potential of these compounds was assessed to establish structure activity relationships. Studies in molecular simulations were conducted to better comprehend the binding properties of the compounds. All the synthesized compounds were extensively characterized with modern spectroscopic methods including 1H-NMR, 13C–NMR, FTIR, HR-MS and elemental analysis.
Measuring mosquito control: adult-mosquito catches vs egg-trap data as endpoints of a cluster-randomized controlled trial of mosquito-disseminated pyriproxyfen
Authors: Garcia Klauss K. S. , Versiani Hanid S. , Araújo Taís O. , Conceição João P. A. , Obara Marcos T. , Ramalho Walter M. , Minuzzi-Souza Thaís T. C. , Gomes Gustavo D. , Vianna Elisa N. , Timbó Renata V. , Barbosa Vinicios G. C. , Rezende Maridalva S. P. , Martins Luciana P. F. , Macedo Glauco O. , Carvalho Bruno L. , Moreira Israel M. , Bartasson Lorrainy A. , Nitz Nadjar , Luz Sérgio L. B. , Gurgel-Gonçalves Rodrigo , Abad-Franch Fernando
Published: July 2020

Background

Aedes aegypti and Culex quinquefasciatus are the main urban vectors of arthropod-borne viruses causing human disease, including dengue, Zika, or West Nile. Although key to disease prevention, urban-mosquito control has met only limited success. Alternative vector-control tactics are therefore being developed and tested, often using entomological endpoints to measure impact. Here, we test one promising alternative and assess how three such endpoints perform at measuring its effects.

Methods

We conducted a 16-month, two-arm, cluster-randomized controlled trial (CRCT) of mosquito-disseminated pyriproxyfen (MD-PPF) in central-western Brazil. We used three entomological endpoints: adult-mosquito density as directly measured by active aspiration of adult mosquitoes, and egg-trap-based indices of female Aedes presence (proportion of positive egg-traps) and possibly abundance (number of eggs per egg-trap). Using generalized linear mixed models, we estimated MD-PPF effects on these endpoints while accounting for the non-independence of repeated observations and for intervention-unrelated sources of spatial-temporal variation.

Results

On average, MD-PPF reduced adult-mosquito density by 66.3% (95% confidence interval, 95% CI: 47.3–78.4%); Cx. quinquefasciatus density fell by 55.5% (95% CI: 21.1–74.8%), and Ae. aegypti density by 60.0% (95% CI: 28.7–77.5%). In contrast, MD-PPF had no measurable effect on either Aedes egg counts or egg-trap positivity, both of which decreased somewhat in the intervention cluster but also in the control cluster. Egg-trap data, therefore, failed to reflect the 60.0% mean reduction of adult Aedes density associated with MD-PPF deployment.

Conclusions

Our results suggest that the widely used egg-trap-based monitoring may poorly measure the impact of Aedes control; even if more costly, direct monitoring of the adult mosquito population is likely to provide a much more realistic and informative picture of intervention effects. In our CRCT, MD-PPF reduced adult-mosquito density by 66.3% in a medium-sized, spatially non-isolated, tropical urban neighborhood. Broader-scale trials will be necessary to measure MD-PPF impact on arboviral-disease transmission.
Correction to: Current status of development of methylation biomarkers for in vitro diagnostic IVD applications
Authors: Taryma-Leśniak Olga , Sokolowska Katarzyna Ewa , Wojdacz Tomasz Kazimierz
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
An exponential-trigonometric spline minimizing a seminorm in a Hilbert space
Authors: Shadimetov Kholmat M. , Boltaev Aziz K.
Published: July 2020

In the present paper, using the discrete analogue of the operator $\mathrm{d} ^{6}/\mathrm{d} x^{6}-1$

d
6

/
d

x
6

−
1
, we construct an interpolation spline that minimizes the quantity $\int _{0}^{1}(\varphi {'''}(x)+\varphi (x))^{2}\,\mathrm{d}x$

∫

0

1

(

φ
‴

(
x
)
+
φ
(
x
)
)

2

d
x
in the Hilbert space $W_{2}^{(3,0)}$

W
2

(
3
,
0
)

. We obtain explicit formulas for the coefficients of the interpolation spline. The obtained interpolation spline is exact for the exponential-trigonometric functions ${{e}^{-x}}$

e

−
x

, ${{e}^{\frac{x}{2}}}\cos ( \frac{\sqrt{3}}{2}x)$

e

x
2

cos
(

3

2

x
)
, and ${{e}^{\frac{x}{2}}}\sin ( \frac{\sqrt{3}}{2}x )$

e

x
2

sin
(

3

2

x
)
.
Dietary plant extracts modulate gene expression profiles in alveolar macrophages of pigs experimentally infected with porcine reproductive and respiratory syndrome virus
Authors: Kim Kwangwook , Ji Peng , Song Minho , Che Tung M. , Bravo David , Pettigrew James E. , Liu Yanhong
Published: July 2020

Background

Our previous study showed that 3 plant extracts enhanced the immune responses and growth efficiency of weaned pigs infected with porcine reproductive and respiratory syndrome virus (PRRSV), which is one of the most economically important disease in swine industry. However, each plant extract differently effected on growth efficiency and immune responses. Therefore, the objective of this study was conducted to characterize the effects and investigate the potential underlying mechanisms of 3 plant extracts on gene expression of alveolar macrophages in weaned pigs experimentally infected with PRRSV.

Results

PRRSV infection altered (P < 0.05) the expression of 1,352 genes in pigs fed the control (CON; 755 up, 597 down). Compared with the infected CON, feeding capsicum (CAP), garlic botanical (GAR), or turmeric oleoresin (TUR) altered the expression of 46 genes (24 up, 22 down), 134 genes (59 up, 75 down), or 98 genes (55 up, 43 down) in alveolar macrophages of PRRSV-infected pigs, respectively. PRRSV infection up-regulated (P < 0.05) the expression of genes related to cell apoptosis, immune system process, and response to stimulus, but down-regulated (P < 0.05) the expression of genes involved in signaling transduction and innate immune response. Compared with the infected CON, feeding TUR or GAR reduced (P < 0.05) the expression of genes associated with antigen processing and presentation, feeding CAP up-regulated (P < 0.05) the expression of genes involved in antigen processing and presentation. Supplementation of CAP, GAR, or TUR also enhanced (P < 0.05) the expression of several genes related to amino acid metabolism, steroid hormone synthesis, or RNA degradation, respectively.

Conclusions

The results suggest that 3 plant extracts differently regulated the expression of genes in alveolar macrophages of PRRSV-infected pigs, especially altering genes involved in immunity.
Role of biochar in promoting circular economy in the agriculture sector. Part 1: A review of the biochar roles in soil N, P and K cycles
Authors: Jindo Keiji , Audette Yuki , Higashikawa Fábio Satoshi , Silva Carlos Alberto , Akashi Kinya , Mastrolonardo Giovanni , Sánchez-Monedero Miguel Angel , Mondini Claudio
Published: July 2020

Recently, biochar has been widely used for versatile applications in agriculture and environment sectors as an effective tool to minimise waste and to increase the efficiency of circular economy. In the present work, we review the current knowledge about biochar role in N, P and K cycles. Ammonia volatilisation and N2O emission can be reduced by biochar addition. The content of available P can be improved by biochar through enhancement of solubilisation and reduction in P fixation on soil mineral, whilst high extractable K in biochar contributes to K cycle in soil. Liming effect and high CEC are important properties of biochars improving beneficial interactions with N, P and K soil cycle processes. The effectiveness of biochar on N, P and K cycles is associated with biochar properties which are mainly affected by feedstock type and pyrolysis condition.
Disparities in triage and management of the homeless and the elderly trauma patient
Authors: Schaffer Kathryn B. , Wang Jiayan , Nasrallah Fady S. , Bayat Dunya , Dandan Tala , Ferkich Anthony , Biffl Walter L.
Published: July 2020

Background

Trauma systems are designed to provide specialized treatment for the most severely injured. As populations change, it is imperative for trauma centers to remain dynamic to provide the best care to all members of the community.

Methods

A retrospective review of all trauma patients treated at one Level II trauma center in Southern CA over 5 years. Three cohorts of patients were studied: geriatric (> 65 years), the homeless, and all other trauma patients. Triage, hospitalization, and outcomes were collected and analyzed.

Results

Of 8431 patients treated, 30% were geriatric, 3% homeless and 67% comprised all other patients. Trauma activation criteria was met for 84% of all other trauma patients, yet only 61% of homeless and geriatric patients combined. Injury mechanism for homeless included falls (38%), pedestrian/bicycle related (27%) and assaults (24%), often while under the influence of alcohol and drugs. Average length of hospital stay (LOS) was greater for homeless and geriatric patients and frequently attributed to discharge planning challenges. Both the homeless and geriatric groups demonstrated increased complications, comorbidities, and death rates.

Conclusions

Homeless trauma patients reflect similar challenges in care as with the elderly, requiring additional resources and more complex case management. It is prudent to identify and understand the issues surrounding patients transported to our trauma center requiring a higher level of care yet are under-triaged upon arrival to the Emergency Department. Although a monthly review is done for all under-triaged patients, and geriatric patients are acknowledged to be a cohort continually having delays, the homeless cohort continues to be under-triaged. The admitted homeless trauma patient has similar complex case management issues as the elderly related to pre-existing health issues and challenges with discharge planning, both which can add to longer lengths of hospital stay as compared to other trauma patients. Given the lack of social support that is endemic to both populations, these cohorts represent a unique challenge to trauma centers. Further research into specialized care is required to determine best practices to address disparities evident in the homeless and elderly, and to promote health equity in marginalized populations.
Inter-observer agreement of baseline whole body MRI in multiple myeloma
Authors: Croft James , Riddell Angela , Koh Dow-Mu , Downey Kate , Blackledge Matthew , Usher Marianne , Boyd Kevin , Kaiser Martin , Messiou Christina
Published: July 2020

Background

Whole body magnetic resonance imaging (MRI) is now incorporated into international guidance for imaging patients with multiple myeloma. The aim of this study was to investigate inter-observer agreement of triple reported baseline whole-body MRI in myeloma and highlight potential pitfalls.

Methods

Fifty-seven patients with symptomatic myeloma at first presentation or relapse and planned for autologous stem cell transplant were included. All patients completed baseline whole body MRI within 2 weeks prior to starting treatment. Each scan was reported independently by 3 radiologists using a defined scoring system. Differences in observer scores were compared using analysis of variance (ANOVA) and inter-observer agreement assessed using intra class correlation coefficient (ICC).

Results

There was no significant difference in mean observer scores for whole skeleton and ICC demonstrated excellent inter-observer agreement at 0.91. ICC varied between skeletal regions with spine, pelvis and ribs showing good inter-observer agreement, whereas skull and long bones were moderate. Scans with variation in observer scores were re-examined and cause of discrepancies identified. This information was used to describe potential anatomical pitfalls in reporting .

Conclusion

Whole-body MRI has excellent inter-observer agreement in reporting symptomatic myeloma at baseline. Inter-observer agreement varied between skeletal regions highlighting specific areas of difficulty.
Correction to: The development of a performance hand wear and tools product innovation framework
Authors: Sokolowski Susan L.
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
Antioxidant and in vivo hepatoprotective effects of Gardenia gummifera L.f. fruit methanol extract
Authors: Vinaykumar N. M. , Mahmood Riaz , Krishna V. , Ravishankara B. , Shastri Sudhesh L.
Published: July 2020

Background

Gardenia gummifera L.f. (Family: Rubeacea) is used in indigenous system of medicine to cure many diseases. To authenticate the traditional medicinal claim investigation has been under taken to evaluate the antioxidant and hepatoprotective activities of Gardenia gummifera L.f. fruit methanol extract (GFME).

Method

GFME was evaluated using various antioxidant assays, including DPPH and Nitric oxide radical scavenging assays. The protective effects of GFME were studied in carbon tetrachloride reduced biochemical markers of hepatic injury such as serum glutamyl oxaloacetate transaminase (SGOT), serum glutamyl pyruvate transaminase (SGPT), alkaline phosphatase (ALP), total protein (TP), total bilirubin (TB) and direct bilirubin (DB) and in silico studies were carried out to screen the GFME phytocompounds.

Results

The extract showed significant antioxidant activity in DPPH and Nitric oxide radical scavenging with IC50 value of 131.11 and 175.95 respectively. Quantitative phytochemical assay determines the presence of alkaloids 69.1 μg/1 mg and phenolics 76.5 μg/1 mg. GC-MS analysis of aromatic extract resulted in 36 compounds. Among them, compounds 2, 3-Dihydro-3,5-dihydroxy-6-methyl-4 h-pyran-4-one, 2-furancarboxaldehyde 5-(hydroxymethyl) and Quinic acid are the major ones. The fruit methanol extract showed significant in vivo hepatoprotective activity by altering the levels of liver function biochemical parameters such as SGOT, SGPT, ALP, TP, TB and DB. Histology of the liver section also confirms the hepatoprotective activity of GFME. Molecular docking of GC-MS profiled phytocompounds with the target protein TGF-β1and PPARα also confirmed the therapeutic effect with good hydrogen bonding and hydrophobic interactions.

Conclusion

Thus the present study clearly strengthened the traditional medicinal claim of the plant Gardenia gummifera L.f. possessing the hepatoprotective drug.