bluuebunny/crossref_metadata_2025 huggingface dataset:
Equivalent change enrichment analysis: assessing equivalent and inverse change in biological pathways between diverse experiments
Authors: Thompson Jeffrey A. , Koestler Devin C.
Published: February 2020

Background

In silico functional genomics have become a driving force in the way we interpret and use gene expression data, enabling researchers to understand which biological pathways are likely to be affected by the treatments or conditions being studied. There are many approaches to functional genomics, but a number of popular methods determine if a set of modified genes has a higher than expected overlap with genes known to function as part of a pathway (functional enrichment testing). Recently, researchers have started to apply such analyses in a new way: to ask if the data they are collecting show similar disruptions to biological functions compared to reference data. Examples include studying whether similar pathways are perturbed in smokers vs. users of e-cigarettes, or whether a new mouse model of schizophrenia is justified, based on its similarity in cytokine expression to a previously published model. However, there is a dearth of robust statistical methods for testing hypotheses related to these questions and most researchers resort to ad hoc approaches. The goal of this work is to develop a statistical approach to identifying gene pathways that are equivalently (or inversely) changed across two experimental conditions.

Results

We developed Equivalent Change Enrichment Analysis (ECEA). This is a new type of gene enrichment analysis based on a statistic that we call the equivalent change index (ECI). An ECI of 1 represents a gene that was over or under-expressed (compared to control) to the same degree across two experiments. Using this statistic, we present an approach to identifying pathways that are changed in similar or opposing ways across experiments. We compare our approach to current methods on simulated data and show that ECEA is able to recover pathways exhibiting such changes even when they exhibit complex patterns of regulation, which other approaches are unable to do. On biological data, our approach recovered pathways that appear directly connected to the condition being studied.

Conclusions

ECEA provides a new way to perform gene enrichment analysis that allows researchers to compare their data to existing datasets and determine if a treatment will cause similar or opposing genomic perturbations.
Dynamic network inference and association computation discover gene modules regulating virulence, mycotoxin and sexual reproduction in Fusarium graminearum
Authors: Guo Li , Ji Mengjie , Ye Kai
Published: February 2020

Background

The filamentous fungus Fusarium graminearum causes devastating crop diseases and produces harmful mycotoxins worldwide. Understanding the complex F. graminearum transcriptional regulatory networks (TRNs) is vital for effective disease management. Reconstructing F. graminearum dynamic TRNs, an NP (non-deterministic polynomial) -hard problem, remains unsolved using commonly adopted reductionist or co-expression based approaches. Multi-omic data such as fungal genomic, transcriptomic data and phenomic data are vital to but so far have been largely isolated and untapped for unraveling phenotype-specific TRNs.

Results

Here for the first time, we harnessed these resources to infer global TRNs for F. graminearum using a Bayesian network based algorithm called “Module Networks”. The inferred TRNs contain 49 regulatory modules that show condition-specific gene regulation. Through a thorough validation based on prior biological knowledge including functional annotations and TF binding site enrichment, our network prediction displayed high accuracy and concordance with existing knowledge. One regulatory module was partially validated using network perturbations caused by Tri6 and Tri10 gene disruptions, as well as using Tri6 Chip-seq data. We then developed a novel computational method to calculate the associations between modules and phenotypes, and identified major module groups regulating different phenotypes. As a result, we identified TRN subnetworks responsible for F. graminearum virulence, sexual reproduction and mycotoxin production, pinpointing phenotype-associated modules and key regulators. Finally, we found a clear compartmentalization of TRN modules in core and lineage-specific genomic regions in F. graminearum, reflecting the evolution of the TRNs in fungal speciation.

Conclusions

This system-level reconstruction of filamentous fungal TRNs provides novel insights into the intricate networks of gene regulation that underlie key processes in F. graminearum pathobiology and offers promise for the development of improved disease control strategies.
Detrimental Effects of Filling Laryngotracheal Airways To Excessive Pressure (DEFLATE-P): a quality improvement initiative
Authors: Fritz Ashley V. , Mickus Gregory J. , Vega Michael A. , Renew J. Ross , Brull Sorin J.
Published: February 2020

Background

This quality improvement (QI) project was performed at a single center to determine the incidence of postoperative complications associated with use of cuffed airway devices. An educational program was then completed that involved training our anesthesia providers about complications related to excessive cuff pressure and how to utilize a quantitative cuff pressure measurement device (manometer). The impact of this educational initiative was assessed by comparing the incidence of postoperative complications associated with the use of airway devices before and after the training period.

Methods

After approval by our institution’s Institutional Review Board, a pre-intervention (baseline) survey was obtained from 259 adult patients after having undergone surgery with general anesthesia with the use of an endotracheal tube (ETT) or laryngeal mask airway (LMA). Survey responses were used to determine the baseline incidence of sore throat, hoarseness, and dysphagia. Once these results were obtained, education was provided to the anesthesia department members addressing the complications associated with excessive cuff pressures, appropriate cuff pressures based on manufacturer recommendations, and instructions on the use of a quantitative monitor to determine cuff pressure (manometry). Clinical care was then changed by requiring intraoperative cuff pressure monitoring throughout our institution for all surgical patients. After this educational period, 299 patients completed the same survey describing postoperative airway complications.

Results

The use of manometry reduced the incidence of moderate-to-severe postoperative sore throat in the pre- vs. post-intervention groups (35 patients vs 31 patients, p = 0.045), moderate to severe hoarseness (30 patients vs 13, patients p = 0.0001), and moderate-to-severe dysphagia (13 patients vs 5 patients, p = 0.03).

Conclusion

Caring for patients in the perioperative setting frequently entails placement of an airway device. This procedure is associated with several potential complications, including sore throat, coughing, and vocal cord damage. Our quality improvement initiative has shown that intraoperative management of intra-cuff pressure based on manometry is feasible to implement in clinical practice and can reduce postoperative airway complications.
Consecutive electrocardiographic changes during percutaneous coronary intervention for acute coronary syndrome with high-grade atrioventricular block: a case report
Authors: Sueyoshi Hiroyuki , Akita Yuzo , Oishi Yohei , Mukai Yu , Hagino Tomoko , Yutaka Kotaro , Matsui Yumie , Yoshinaga Masahiro , Karakawa Masahiro , Mori Yasukiyo
Published: February 2020

Background

Acute coronary syndrome (ACS) with high-grade atrioventricular block (HAVB) still has a poor mortality risk, even in the current percutaneous coronary intervention (PCI) era. However, early PCI for ACS with HAVB is associated with improved in-hospital survival and a 6-month survival similar to that of ACS without HAVB.

Case presentation

A 70-year-old man was admitted to our hospital for ACS with HAVB. ECG showed complete AV block, complete right bundle branch block (CRBBB), and left axis deviation. Cardiac enzymes were elevated. He underwent temporary pacemaker insertion and coronary angiography, which showed severe stenosis of the proximal right coronary artery (RCA), 99% stenosis of the distal RCA with Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow, and total occlusion of the proximal left anterior descending artery (LAD). We performed primary PCI in both the RCA and LAD, which resulted in TIMI grade 3 flow in both. After PCI, the HAVB recovered to normal sinus rhythm with CRBBB; a normal QRS interval returned within three days. The patient was discharged from the hospital without complications.

Conclusion

In this case of ACS with HAVB, early intensive coronary artery reperfusion resulted in long-term patient survival. The blood supply to the AV node and bilateral bundle branches is complex. Multivessel ischemia may compromise both primary and collateral blood flows to the AV node and septum, resulting in severe conduction impairment. Clinicians performing PCI should be aware of this anatomy and physiology.
Isolated central nervous system Aspergillosis infection in a chronic lymphocytic leukemia patient on Ibrutinib: A case report
Authors: Le Thuy-Hong , Kumar Vikas , Gondal Khubaib , Barnes Martin , Siddique Haseeb , Buttar Barjinder , Kaell Alan
Published: February 2020

Background

In patients at high risk of opportunistic infections who present with isolated.

neurological symptoms, it is lifesaving to consider Central Nervous System Aspergillosis (CNS-A). Ibrutinib use in chronic lymphocytic leukemia (CLL) has previously been associated with CNS-A. We provide a case report of a patient that presented with primary CNS-A on Ibrutinib therapy without any prior pulmonary or local paranasal signs of infection.

Case presentation

74-year-old Caucasian male with CLL and no prior chemotherapy on ibrutinib for 6 months presented with three months of unsteady gait, occipital headache, and confusion. He has a history of pulmonary sarcoidosis on chronic prednisone 5 mg daily and chronic obstructive pulmonary disease (COPD). He was found to have a “brain abscess” on imaging. Emergent craniotomy confirmed Aspergillus and patient was treated with Voriconazole for 6 months. At six-month follow up, repeat magnetic resonance imaging (MRI) confirmed complete resolution of CNS lesion.

Conclusions

Our case reinforces the importance of being vigilant for isolated CNS-A in CLL patients on ibrutinib who present with neurological symptoms and signs, without prior or co-infection of sino-pulmonary tissue.
Association between maternal sleep duration and quality, and the risk of preterm birth: a systematic review and meta-analysis of observational studies
Authors: Wang Ling , Jin Feng
Published: February 2020

Background

To assess the association of sleep duration and quality with the risk of preterm birth.

Methods

Relevant studies were retrieved from the PubMed and Web of Science databases up to September 30, 2018. The reference lists of the retrieved articles were reviewed. Random effects models were applied to estimate summarized relative risks (RRs) and 95% confidence intervals (CIs).

Results

Ten identified studies (nine cohort studies and one case-controlled study) examined the associations of sleep duration and quality with the risk of preterm birth. As compared with women with the longest sleep duration, the summary RR was 1.23 (95% CI = 1.01–1.50) for women with the shortest sleep duration, with moderate between-study heterogeneity (I2 = 57.4%). Additionally, as compared with women with good sleep quality, the summary RR was 1.54 (95% CI = 1.18–2.01) for women with poor sleep quality (Pittsburgh Sleep Quality Index > 5), with high between-study heterogeneity (I2 = 76.7%). Funnel plots as well as the Egger’s and Begg’s tests revealed no evidence of publication bias.

Conclusions

This systematic review and meta-analysis revealed that short sleep duration and poor sleep quality may be associated with an increased risk of preterm birth. Further subgroup analyses are warranted to test the robustness of these findings as well as to identify potential sources of heterogeneity.
A treat and extend protocol with Aflibercept for cystoid macular oedema secondary to central retinal vein occlusion – an 18-month prospective cohort study
Authors: O’Day Roderick , Ali Noha , Lim Lyndell L. , Sandhu Sukhpal , Chau Thuy , Wickremasinghe Sanjeewa
Published: February 2020

Background

To evaluate the safety and efficacy of a treat-and-extend protocol of aflibercept for cystoid macular oedema (CMO) secondary to central retinal vein occlusion (CRVO).

Methods

Twenty patients with CMO secondary to CRVO were included in this prospective cohort study. After 3 loading 4-weekly injections, treatment intervals were increased by 2 weeks if there was no clinical activity, to a maximum of 12 weeks. If clinical activity recurred or persisted, the interval between injections was shortened by 2 weeks, to a minimum of 4 weeks. Main outcome measures were change in visual acuity and the proportion of patients gaining 15 or more Early Treatment of Diabetic Retinopathy Study (ETDRS) letters from baseline at 6, 12 and 18 months.

Results

Mean BCVA gain from baseline was 19.7 ± 13.8, 22.2 ± 13.9 and 21.9 ± 15.8 ETDRS letters at 6, 12 and 18 months, respectively. Sixty-five percent of patients gained 15 or more ETDRS letters at 6 months, increasing to 70.6% at 12 and 18 months. Patients received 5.0 [4.0 to 6.0], 8.5 [8.0 to 10.3] and 11.0 [9.0 to 12.5] injections by 6, 12 and 18 months, respectively.

Conclusions

The visual outcomes achieved with a treat-and-extend protocol in this study were similar to the pivotal trials of aflibercept for CMO secondary to CRVO, which used monthly and then as-needed protocols.

Trial registration

Australian and New Zealand Clinical Trials Registry, registration number ACTRN12615000417583, 01/05/2015.
Distribution characteristics of cow’s milk-sIgE components in children with respiratory allergic diseases in southern China
Authors: Huang Huimin , Luo Wenting , Wei Nili , Liang Xueqing , Zheng Peiyan , Hu Haisheng , Sun Baoqing
Published: February 2020

Background

Cow’s milk (CM) is the main food allergen for toddlers and infants. Presently, studies on CM specific immunoglobulin E (sIgE) sensitization and positive distribution of CM components ALA-, CAS-, and BLG-sIgE are lacking in infants with respiratory allergic diseases, especially in southern China. This study therefore aimed to investigate the distribution of CM sensitization and the relation between its components α-lactalbumin (ALA), β-lactoglobulin (BLG) and casein (CAS) sIgE in children with respiratory allergic diseases in southern China.

Methods

A total of 1839 children (≤12 years) with respiratory diseases and detected CM-sIgE levels were included. Serum samples were collected from the Respiratory Diseases Bioresources Center of the National Center for Respiratory Diseases in southern China from August 2012 to July 2017. ALA-, BLG-, and CAS-sIgE were detected and questionnaires were completed in 103 children.

Results

A total of 36.7% children were positive for CM-sIgE. CM-sIgE levels were higher in asthmatic bronchitis (AB) group than in other allergic respiratory disease groups (all P < 0.05). Among the 103 CM-sIgE-sensitized children, 64.08% had a history of family allergies. There were 84.47% of the children who tested positive for two or more sIgE components. The average ALA-, BLG-, and CAS-sIgE levels were 1.91 kU/L, 1.81 kU/L, and 0.62 kU/L, respectively. The CM-sIgE level showed a correlation with BLG-sIgE (rs = 0.833), ALA-sIgE (rs = 0.816), and CAS-sIgE (rs = 0.573) levels (all p < 0.001).

Conclusions

In southern China, CM-sIgE levels were higher in children with AB than in those with other respiratory allergic diseases. ALA and BLG were the main allergenic components detected in CM-sIgE-sensitized children with respiratory allergic diseases.
Risk factors for low cardiac output syndrome in children with congenital heart disease undergoing cardiac surgery: a retrospective cohort study
Authors: Du Xinwei , Chen Hao , Song Xiaoqi , Wang Shunmin , Hao Zedong , Yin Lifeng , Lu Zhaohui
Published: February 2020

Background

Low cardiac output syndrome (LCOS) is an important complication of cardiac surgery. It is associated with increased morbidity and mortality. The incidence of LCOS after surgery is high in patients with congenital heart disease (CHD). Therefore, determining the risk factors of LCOS has clinical significance for the management of CHD. This study aimed to analyze the risk factors of LCOS.

Methods

We conducted a retrospective analysis of children with CHD who underwent cardiac surgery at Shanghai Children’s Medical Center between January 1, 2014, and December 31, 2017. Demographic characteristics and baseline data were extracted from the health data resource center of the hospital, which integrates clinical routine data including medical records, diagnoses, orders, surgeries, laboratory tests, imaging, nursing, and other subsystems. Logistic regressions were performed to analyze the risk factors of LCOS.

Results

Overall, 8660 infants with CHD were included, and 864 (9.98%) had LCOS after surgery. The multivariate regression analysis identified that age (OR 0.992, 95% CI: 0.988–0.997, p = 0.001), tricuspid regurgitation (1.192, 1.072–1.326, p = 0.001), Risk Adjustment in Congenital Heart Surgery-1 risk grade (1.166, 1.011–1.345, p = 0.035), aortic shunt (left-to-right: 1.37, 1.005–1.867, p = 0.046; bi-directional: 1.716, 1.138–2.587, p = 0.01), atrial shunt (left-to-right: 1.407, 1.097–1.805, p = 0.007; right-to-left: 3.168, 1.944–5.163, p < 0.001; bi-directional: 1.87, 1.389–2.519, p < 0.001), ventricular level shunt (left-to-right: 0.676, 0.486–0.94, p = 0.02; bi-directional: 2.09, 1.611–2.712, p < 0.001), residual shunt (3.489, 1.502–8.105, p = 0.004), left ventricular outflow tract obstruction (3.934, 1.673–9.254, p = 0.002), right ventricular outflow tract obstruction (3.638, 1.225–10.798, p = 0.02), circulating temperature (mild hypothermia: 1.526, 95% CI: 1.205–1.934, p < 0.001; middle and low temperature: 1.738, 1.236–2.443, p = 0.001), duration of cardiopulmonary bypass (1.009, 1.006–1.012, p < 0.001), myocardial preservation using histidine-tryptophan-ketoglutarate (1.677, 1.298–2.167, p < 0.001), and mitral insufficiency (1.714, 1.239–2.37, p < 0.001) were independent risk predictors of LCOS.

Conclusions

The incidence of postoperative LCOS in CHD children remains high. Circulation temperature, myocardial preservation using histidine-tryptophan-ketoglutarate, and usage of residual shunt after surgery were independent risk predictors for LCOS.
Delayed initiation of enteral feeds is associated with postnatal growth failure among preterm infants managed at a rural hospital in Uganda
Authors: Nakubulwa Clare , Musiime Victor , Namiiro Flavia B. , Tumwine James K , Hongella Christine , Nyonyintono James , Hedstrom Anna B. , Opoka Robert
Published: February 2020

Background

Prematurity is the leading cause of mortality in children under 5 years of age globally and is also frequently associated with postnatal growth failure (PGF). Although most preterm births occur in low resource settings, little is known about their postnatal growth outcomes especially in rural areas. We evaluated the incidence and factors associated with PGF among preterm infants managed at a rural hospital in Uganda.

Methods

Retrospective cohort study of preterm infants discharged from Kiwoko Hospital neonatal intensive care unit (NICU) from July 2017 to June 2018. Inclusion criteria included gestational age 26 up to but not including 37 weeks, admission within 24 h of birth and at least 7 days hospital stay. Exclusion criteria included major congenital anomalies and missing gestational age or birth weight. Birth and discharge weights from clinical notes were plotted on Fenton 2013 growth charts. Gestation age was determined by last normal menstruation period (LNMP), extracted from the mother’s antenatal card or early obstetric ultrasound scan reports. Postnatal growth failure was diagnosed if discharge weight was less than the 10th percentile for estimated gestational age. Other data from the clinical notes included demographic characteristics, neonatal morbidities as assigned by the attending physician and infant feeding practices. Multivariable logistic regression was used to explore factors associated with PGF.

Results

A total of 349 preterm infants with a mean gestational age of 31 (range 26 to 36) weeks were included. The incidence proportion of PGF was 254/349 (73%). Factors significantly associated with postnatal growth failure included: delayed initiation of enteral feeds [AOR = 3.70, 95% (CI 1.64 to 8.33)], sepsis [AOR = 6.76, 95% (CI 2.15 to 21.2)], multiple gestation [AOR = 1.81, 95% (CI 1.01 to 3.24)] and male gender [AOR = 1.71 95% (CI 1.01 to 2.91)].

Conclusion

Nearly three quarters of preterm infants managed at a rural hospital in Uganda had postnatal growth failure. Delayed initiation of enteral feeds and sepsis were highly associated with postnatal growth failure. Enteral feeds should be initiated as soon as possible in these infants to reduce early protein deficits and hence postnatal growth failure.
Compulsory treatment in patients’ homes in the Netherlands: what do mental health professionals think of this?
Authors: de Waardt D. A. , van der Heijden F. M. M. A. , Rugkåsa J. , Mulder C. L.
Published: February 2020

Background

Compulsory treatment in patients’ homes (CTH) will be introduced in the new Dutch mental health legislation. The aim of this study is to identify the opinions of mental health workers in the Netherlands on compulsory community treatment (CCT), and particularly on compulsory treatment in the patients’ home.

Methods

This is a mixed methods study, comprising a semi-structured interview and a survey. Forty mental health workers took part in the semi-structured interview about CCT and 20 of them, working in outpatient services, also completed a questionnaire about CTH. Descriptive analyses were performed of indicated (dis) advantages and problems of CCT and of mean scores on the CTH questionnaire.

Results

Overall, the mental health workers seemed to have positive opinions on CCT. With respect to CTH, all mean scores were in the middle of the range, possibly indicating that clinicians were uncertain regarding safety issues and potential practical problems accompanying the use of CTH.

Conclusions

The majority of the participating mental health workers in this study had a positive attitude towards CCT, but they seemed relative uncertain about potential possibilities and problems of working with CTH.
How resource limitations and household economics may compromise efforts to safeguard children during outbreaks
Authors: Myers Kellen , Redere Agnesa , Fefferman Nina H.
Published: February 2020

Background

Epidemiological models have been employed with great success to explore the efficacy of alternative strategies at combating disease outbreaks. These models have often incorporated an understanding of age-based susceptibility and severity of outcome, considering how to limit the adverse outcomes or disease burden relative to an age structure. Such models frequently recommend the preferential treatment/vaccination of children or the elderly, demonstrating how prevention of serious disease within these etiological subgroups can provide both protection within the subgroup itself and indirect protection to the broader population. However, it is most frequently the case that these target populations are consumers, rather than providers, of household resources. In areas of the globe where continued health of household members relies on continued provision of resources, these models may fail to provide the most effective overall strategies for health outcomes in both target populations and overall. This is particularly important for tropical diseases impacting rural and low-income areas in which the disease may be endemic or newly emergent, particularly in the wake of natural disasters.

Methods

We propose a modified epidemiological model with targeted treatment in resource-limited populations. We evaluate the model over a broad parameter space.

Results

This model demonstrates how economic limitations may shift the optimal strategy. It may be advantageous to treat populations at lesser direct risk if they are responsible for providing secondary protection to higher-risk population(s) by producing household resources. Evaluation of this model over the parameter space reveals that, in some cases, targeting treatment towards consumers may result in greater numbers of consumer infections.

Conclusions

Our results demonstrate how household resource limitation can drastically affect the impact of targeted treatment strategies for limiting epidemics. Depending on the economic circumstances, it is possible that focusing treatment on consumers such as children can produce a counter-intuitive outcome in which more children contract the disease.
Metatarsal metastasis from clear cell renal cell carcinoma: a case report and literature review
Authors: Wu Hongzeng , Han Ruoqi , Zhang Qianqian , Zhao Yi , Feng Helin
Published: February 2020

Background

Bone metastasis is known to occur in some patients with cancer, usually in the spine, pelvis or ribs, and less than 0.01% of patients have metastases in the foot bone, so metatarsal metastasis is quite rare. The initial symptoms of osseous metastases are swelling, pain, or both.

Case presentation

We report a 68-year-old man with solitary metatarsal metastasis 26 months after a diagnosis of renal clear cell carcinoma. The patient suffered intermittent swelling of his right foot and pain for one year due to trauma and was not treated. The doctor attributed the symptoms to trauma, administering massage therapy and a plaster cast to the patient at the local clinic. After reviewing the medical records, we found that this patient had a history of clear cell renal cell carcinoma. The patient underwent radiological examination and open biopsy of the first metatarsal bone of the right foot. These findings confirmed that the patient had a metatarsal metastasis from clear cell renal cell carcinoma. The patient subsequently underwent right foot amputation. No local recurrence or distant metastasis was found after a 6-month follow-up.

Conclusion

Clinicians should be aware of a history of renal cell carcinoma (RCC) and fully understand the patient’s past medical history. When treating patients with clear cell renal cell carcinoma who have unresolving bony pain or swelling, clinicians should always keep in mind the possibility of bone metastasis of RCC.
Intervention intended to improve public health professionals’ self-efficacy in their efforts to detect and manage perinatal depressive symptoms among Thai women: a mixed-methods study
Authors: Phoosuwan Nitikorn , Lundberg Pranee C. , Phuthomdee Sadiporn , Eriksson Leif
Published: February 2020

Background

Targeting perinatal depressive symptoms among women can reduce premature mortality. However, public health professionals (PHPs) in primary healthcare settings often have low self-efficacy for detection and management of perinatal depressive symptoms among women. This mixed-methods study was aimed at developing and evaluating a self-efficacy improvement programme (SIP) intended to increase PHPs’ self-efficacy in efforts to detect and manage perinatal depressive symptoms.

Methods

The SIP consisted of 1 day of theory and 4 weeks of practice. Sixty-six PHPs from sub-district health promotion hospitals (primary health care level) in Sakonnakhon, a north-eastern province in Thailand, were randomised into an intervention group (n = 33) and a control group (n = 33). Twenty-three of the intervention group participants also took part in focus group discussions (FGDs). Multiple linear regression and qualitative content analysis were used to analyse the data.

Results

After the SIP, the intervention group participants had higher self-efficacy score than those in the control group (p = 0.004). The FGDs resulted in four categories emerging: Having confidence, Changing knowledge and attitudes, Increasing perception of an important role, and Increasing awareness of performed function.

Conclusions

To enhance the ability of PHPs to detect and manage perinatal depressive symptoms, an intervention programme based on self-efficacy modification is recommended.
The role of cities in reducing the cardiovascular impacts of environmental pollution in low- and middle-income countries
Authors: Baumgartner Jill , Brauer Michael , Ezzati Majid
Published: February 2020

Background

As low- and middle-income countries urbanize and industrialize, they must also cope with pollution emitted from diverse sources.

Main text

Strong and consistent evidence associates exposure to air pollution and lead with increased risk of cardiovascular disease occurrence and death. Further, increasing evidence, mostly from high-income countries, indicates that exposure to noise and to both high and low temperatures may also increase cardiovascular risk. There is considerably less research on the cardiovascular impacts of environmental conditions in low- and middle-income countries (LMICs), where the levels of pollution are often higher and the types and sources of pollution markedly different from those in higher-income settings. However, as such evidence gathers, actions to reduce exposures to pollution in low- and middle-income countries are warranted, not least because such exposures are very high. Cities, where pollution, populations, and other cardiovascular risk factors are most concentrated, may be best suited to reduce the cardiovascular burden in LMICs by applying environmental standards and policies to mitigate pollution and by implementing interventions that target the most vulnerable. The physical environment of cities can be improved though municipal processes, including infrastructure development, energy and transportation planning, and public health actions. Local regulations can incentivize or inhibit the polluting behaviors of industries and individuals. Environmental monitoring can be combined with public health warning systems and publicly available exposure maps to inform residents of environmental hazards and encourage the adoption of pollution-avoiding behaviors. Targeted individual or neighborhood interventions that identify and treat high-risk populations (e.g., lead mitigation, portable air cleaners, and preventative medications) can also be leveraged in the very near term. Research will play a key role in evaluating whether these approaches achieve their intended benefits, and whether these benefits reach the most vulnerable.

Conclusion

Cities in LMICs can play a defining role in global health and cardiovascular disease prevention in the next several decades, as they are well poised to develop innovative, multisectoral approaches to pollution mitigation, while also protecting the most vulnerable.
Liraglutide treatment improves the coronary microcirculation in insulin resistant Zucker obese rats on a high salt diet
Authors: Sukumaran Vijayakumar , Tsuchimochi Hirotsugu , Sonobe Takashi , Waddingham Mark T. , Shirai Mikiyasu , Pearson James T.
Published: February 2020

Background

Obesity, hypertension and prediabetes contribute greatly to coronary artery disease, heart failure and vascular events, and are the leading cause of mortality and morbidity in developed societies. Salt sensitivity exacerbates endothelial dysfunction. Herein, we investigated the effect of chronic glucagon like peptide-1 (GLP-1) receptor activation on the coronary microcirculation and cardiac remodeling in Zucker rats on a high-salt diet (6% NaCl).

Methods

Eight-week old Zucker lean (+/+) and obese (fa/fa) rats were treated with vehicle or liraglutide (LIRA) (0.1 mg/kg/day, s.c.) for 8 weeks. Systolic blood pressure (SBP) was measured using tail-cuff method in conscious rats. Myocardial function was assessed by echocardiography. Synchrotron contrast microangiography was then used to investigate coronary arterial vessel function (vessels 50–350 µm internal diameter) in vivo in anesthetized rats. Myocardial gene and protein expression levels of vasoactive factors, inflammatory, oxidative stress and remodeling markers were determined by real-time PCR and Western blotting.

Results

We found that in comparison to the vehicle-treated fa/fa rats, rats treated with LIRA showed significant improvement in acetylcholine-mediated vasodilation in the small arteries and arterioles (< 150 µm diameter). Neither soluble guanylyl cyclase or endothelial NO synthase (eNOS) mRNA levels or total eNOS protein expression in the myocardium were significantly altered by LIRA. However, LIRA downregulated Nox-1 mRNA (p = 0.030) and reduced ET-1 protein (p = 0.044) expression. LIRA significantly attenuated the expressions of proinflammatory and profibrotic associated biomarkers (NF-κB, CD68, IL-1β, TGF-β1, osteopontin) and nitrotyrosine in comparison to fa/fa-Veh rats, but did not attenuate perivascular fibrosis appreciably.

Conclusions

In a rat model of metabolic syndrome, chronic LIRA treatment improved the capacity for NO-mediated dilation throughout the coronary macro and microcirculations and partially normalized myocardial remodeling independent of changes in body mass or blood glucose.
Evaluation of a capacity building intervention on malaria treatment for under-fives in rural health facilities in Niger State, Nigeria
Authors: Jegede Ayodele , Willey Barbara , Hamade Prudence , Oshiname Fredrick , Chandramohan Daniel , Ajayi IkeOluwa , Falade Catherine , Baba Ebenezer , Webster Jayne
Published: February 2020

Background

Despite the uptake of parasitological testing into policy and practice, appropriate prescription of anti-malarials and artemisinin-based combination therapy (ACT) in accordance with test results is variable. This study describes a National Malaria Control Programme-led capacity building intervention which was implemented in 10 States of Nigeria. Using the experience of Niger State, this study assessed the effect on malaria diagnosis and prescription practices among febrile under-fives in rural health facilities.

Methods

The multicomponent capacity building intervention consisted of revised case management manuals; cascade training from national to state level carried out at the local government area (LGA) level; and on the job capacity development through supportive supervision. The evaluation was conducted in 28, principally government-owned, health facilities in two rural LGAs of Niger State, one in which the intervention case management of malaria was implemented and the other acted as a comparison area with no implementation of the intervention. Three outcomes were considered in the context of rapid diagnostic testing (RDT) for malaria which were: the prevalence of RDT testing in febrile children; appropriate treatment of RDT-positive children; and appropriate treatment of RDT-negative children. Outcomes were compared post-intervention between intervention and comparison areas using multivariate logistic regression.

Results

The intervention did not improve appropriate management of under-fives in intervention facilities above that seen for under-fives in comparison facilities. Appropriate treatment with artemisinin-based combinations of RDT-positive and RDT-negative under-fives was equally high in both areas. However, appropriate treatment of RDT-negative children, when defined as receipt of no ACT or any other anti-malarials, was better in comparison areas. In both areas, a small number of RDT-positives were not given ACT, but prescribed an alternative anti-malarial, including artesunate monotherapy. Among RDT-negatives, no under-fives were prescribed artesunate as monotherapy.

Conclusion

In a context of significant stock-outs of both ACT medicines and RDTs, under-fives were not more appropriately managed in intervention than comparison areas. The malaria case management intervention implemented through cascade training reached only approximately half of health workers managing febrile under-fives in this setting. Implementation studies on models of cascade training are needed to define what works in what context.
Genes expression profiling of alveolar macrophages exposed to non-functionalized, anionic and cationic multi-walled carbon nanotubes shows three different mechanisms of toxicity
Authors: Nahle Sara , Cassidy Hilary , Leroux Mélanie M. , Mercier Reuben , Ghanbaja Jaafar , Doumandji Zahra , Matallanas David , Rihn Bertrand H. , Joubert Olivier , Ferrari Luc
Published: February 2020

Functionalized multi-walled carbon nanotubes (MWCNT) have become the focus of increased research interest, particularly in their application as tools in different areas, such as the biomedical field. Despite the benefits associated with functionalization of MWCNT, particularly in overcoming issues relating to solubility, several studies have demonstrated that these functionalized nanoparticles display different toxicity profiles. For this study, we aim to compare NR8383 cells responses to three well-characterized MWCNT with varying functional groups. This study employed cytotoxicity assays, transcriptomics and proteomics to assess their toxicity using NR8383 rat alveolar macrophages as an in vitro model. The study findings indicated that all MWCNT altered ribosomal protein translation, cytoskeleton arrangement and induced pro-inflammatory response. Only functionalized MWCNT alter mTOR signaling pathway in conjunction with increased Lamtor gene expression. Furthermore, the type of functionalization was also important, with cationic MWCNT activating the transcription factor EB and inducing autophagy while the anionic MWCNT altering eukaryotic translation initiation factor 4 (EIF4) and phosphoprotein 70 ribosomal protein S6 kinase (p70S6K) signaling pathway as well as upregulation Tlr2 gene expression. This study proposes that MWCNT toxicity mechanisms are functionalization dependent and provides evidence that inflammatory response is a key event of carbon nanotubes toxicity.
Comparative proteomic analysis of the brain and colon in three rat models of irritable bowel syndrome
Authors: Zhang Beihua , Xue Hong , Wang Wei , Chen Ting , Su Min , Kang Nan , Yang Jianqin , Bian Zhaoxiang , Wang Fengyun , Tang Xudong
Published: February 2020

Background

Irritable bowel syndrome (IBS) has been gradually recognized as a disorder of the brain-gut interaction, but the molecular changes in the brain and colon that occur in disease development remain poorly understood. We employed proteomic analysis to identify differentially expressed proteins in both the brain and colon of three IBS models.

Methods

To explore the relevant protein abundance changes in the brain and colon, isobaric tags for relative and absolute quantitation (iTRAQ), liquid chromatography and tandem mass spectrometry (LC-MS) and Western blotting methods were used in three IBS models, including maternal separation (MS, group B), chronic wrap restraint stress (CWRS, group C) and a combination of MS and CWRS (group D).

Results

We identified 153, 280, and 239 proteins that were common and differentially expressed in the two tissue types of groups B, C and D, respectively; 43 differentially expressed proteins showed the same expression changes among the three groups, including 25 proteins upregulated in the colon and downregulated in the brain, 7 proteins downregulated in the colon and upregulated in the brain, and 3 proteins upregulated and 8 downregulated in both tissues. Gene ontology analysis showed that the differentially expressed proteins were mainly associated with cellular assembly and organization and cellular function and maintenance. Protein interaction network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the differentiated proteins were mainly involved in the protein ubiquitination pathway and mitochondrial dysfunction.

Conclusions

Taken together, the data presented represent a comprehensive and quantitative proteomic analysis of the brain and colon in IBS models, providing new evidence of an abnormal brain-gut interaction in IBS. These data may be useful for further investigation of potential targets in the diagnosis and treatment of IBS.
Exposure to HIV risks among young people who use drugs (YPUD) in three cities in Vietnam: time to develop targeted interventions
Authors: Michel Laurent , Nguyen Linh T. , Nguyen An K. , Ekwaru John P. , Laureillard Didier , Nagot Nicolas , Phan Olivier , Khuat Oanh T. H.
Published: February 2020

Introduction

The aim of this study is to identify the profiles of young people who use drugs (YPUD) and their exposure to HIV risks in the 3 main cities of Vietnam, Haiphong, Hanoi, and Ho Chi Minh City (HCMC), in order to design a community-based intervention to prevent HIV.

Methods

A survey using respondent-driven sampling (RDS) was conducted among YPUD aged 16–24. Participants were eligible if they reported drug use, confirmed by a urine test. After obtaining informed consent, they were screened for HIV/HCV and assessed using face-to-face questionnaires and self-report. A cluster analysis was conducted, taking into account risk behaviors and confirmed HIV-positive status.

Results

Seven hundred and three YPUD aged 16–24 were recruited between October 2016 and February 2017, 584 of whom were included in the final analysis. Median age was 21 (17.7, 23.0); 79% were male, 18% female, and 2% transgender. Methamphetamines use was reported by 77%, followed by cannabis (51%) and heroin (17%); polydrug use was common; 15% had “ever” injected drugs. HIV prevalence was 7%. Among all participants, 48% reported non-consistent condom use and 1% reported needle/syringe sharing during the previous month. Four distinct profiles of HIV risk behaviors were identified: The high multiple-risk group mixed unsafe drug use with unsafe sexual practices and had higher prevalence of HIV; the second group practiced high-risk sex with non-consistent condom combined with methamphetamine use; the third group was a moderate-risk group with limited unsafe sexual practices; and the fourth was considered at “low-risk” as reportedly, most never had sex and never injected. The highest risk group included more female YPUD, living in HCMC, who used heroin and had unsafe sex with their regular partners. The second high-risk group included most of the MSM and all transgender people and frequently reported mental health disorders.

Conclusions

The profiles of YPUD who are at risk of HIV vary according to age, location, and population group. Injecting YPUD are the most exposed to risk and need immediate attention. Sexual exposure to HIV is very common. Mental health is a major concern. Interventions need to be integrated in a differentiated but holistic approach.
Evaluation of the reliability and validity of the Early Childhood Oral Health Impact Scale (ECOHIS) questionnaire translated into Malagasy
Authors: Randrianarivony Jeannot , Ravelomanantsoa Justin Jacques , Razanamihaja Noeline
Published: February 2020

The Early Childhood Oral Health Impact Scale (ECOHIS) was developed to assess the impact of oral health conditions on the quality of life of preschool children and theirs families. The ECOHIS was originally developed in English language, translated and validated in several countries but no validated transcultural version of this questionnaire is currently available in Madagascar. The objectives of this cross-cultural study were to translate, validate and analyse the psychometric properties of the Malagasy version of ECOHIS.

Method

The translation followed the forward-backward translation process. The Malagasy version obtained was pre-tested on ten mothers. Then, the questionnaire was administered by interview to 150 parents/guardians of children aged 3 to 5 years old frequenting two nursery schools in the town of Mahajanga to evaluate the reliability and validity of its psychometric characteristics. Reliability was assessed by the test-retest procedure with an interval of 15 days by using the intra-class correlation (ICC). Internal consistency was tested by Cronbach’s alpha coefficient. The validity of construct, discriminant and criterion were evaluated. Construct validity was evaluated by Spearman rank correlation and tested using exploratory factor analysis and partial confirmatory factor analysis. Discriminant validity was tested between groups of children presenting consequences of untreated decayed teeth. Clinical examination was performed using the decayed, missing, filled teeth (dmft) and the pulpal involvement, ulceration, fistula, abscess (pufa) indices for assessing dental caries and consequences of untreated decayed teeth.

Results

The cultural adaptation showed that the respondents understood the questions. The intraclass correlation coefficient for test retest was 0.91. The internal consistency demonstrated a good reliability of the Malagasy-ECOHIS version with a Cronbach’s alpha coefficient of 0.88. The convergent validity evaluated by Pearson correlation coefficients provided positive and significant correlation values between all the items ranging from 0.26 to 0.72. Significant associations between the ECOHIS scores and the global rating of oral health supported the validity of the construct. Convergent and discriminant validity were obtained by testing the association of ECOHIS scores on the child and family sections with poor parental ratings of their child’s oral health, high caries experience and untreated decayed teeth consequences which were to be statistically significant.

Conclusion

The results showed that this Malagasy version of ECOHIS questionnaire has shown good psychometric properties and could be used on Malagasy parents of preschool children to measure the impact of oral health status on the child and family quality of life.
International evidence-based guidelines on Point of Care Ultrasound (POCUS) for critically ill neonates and children issued by the POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC)
Authors: Singh Yogen , Tissot Cecile , Fraga María V. , Yousef Nadya , Cortes Rafael Gonzalez , Lopez Jorge , Sanchez-de-Toledo Joan , Brierley Joe , Colunga Juan Mayordomo , Raffaj Dusan , Da Cruz Eduardo , Durand Philippe , Kenderessy Peter , Lang Hans-Joerg , Nishisaki Akira , Kneyber Martin C. , Tissieres Pierre , Conlon Thomas W. , De Luca Daniele
Published: February 2020

Background

Point-of-care ultrasound (POCUS) is nowadays an essential tool in critical care. Its role seems more important in neonates and children where other monitoring techniques may be unavailable. POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC) aimed to provide evidence-based clinical guidelines for the use of POCUS in critically ill neonates and children.

Methods

Creation of an international Euro-American panel of paediatric and neonatal intensivists expert in POCUS and systematic review of relevant literature. A literature search was performed, and the level of evidence was assessed according to a GRADE method. Recommendations were developed through discussions managed following a Quaker-based consensus technique and evaluating appropriateness using a modified blind RAND/UCLA voting method. AGREE statement was followed to prepare this document.

Results

Panellists agreed on 39 out of 41 recommendations for the use of cardiac, lung, vascular, cerebral and abdominal POCUS in critically ill neonates and children. Recommendations were mostly (28 out of 39) based on moderate quality of evidence (B and C).

Conclusions

Evidence-based guidelines for the use of POCUS in critically ill neonates and children are now available. They will be useful to optimise the use of POCUS, training programs and further research, which are urgently needed given the weak quality of evidence available.