bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of malaria patients seeking care in different types of health facilities during the implementation of National Malaria Elimination Programme
Authors: Li Gang , Zhang Donglan , Chen Zhuo , Feng Da , Chen Xiaoyu , Tang Shangfeng , Son Heejung , Wang Zhenhua , Xi Yuanhang , Feng Zhanchun
Published: March 2020

Background

China launched the National Malaria Elimination Programme (NMEP) in 2010 and set the goal that all health facilities should be able to diagnose malaria. Additionally, hospitals at all levels could treat malaria by 2015. To provide a reference for the control of imported malaria, a study was conducted on the distribution of malaria patients seeking care in different types of health facilities.

Methods

There were two data sources. One was obtained through the Infectious Diseases Information Reporting Management System (IDIRMS), which only contained the name of health facilities and the number of cases. The other was obtained through multistage stratified cluster sampling. Descriptive statistical analysis was used to investigate the distribution of malaria patients attending different types of health facilities (hospitals, township hospitals, and Centers for Disease Control and Prevention), hospital tiers (county-level, prefecture-level, and provincial-level), and hospital levels (primary, secondary, and tertiary). Chi-square test was also used to compare the proportions of patients seeking care outside their current residence region between different types of hospitals. Point maps were drawn to visualize the spatial distribution of hospitals reporting malaria cases, and flow maps were created to show the spatial flow of malaria patients by using the ArcGIS software.

Results

The proportions of malaria patients who sought care in hospitals, township hospitals, and Centers for Disease Control and Prevention were 81.7%, 14.7%, and 3.6%, respectively. For those who sought care in hospitals, the percentages of patients who sought care in provincial-level, prefecture-level and county-level hospitals were 17.4%, 60.5% and 22.1%, correspondingly; the proportions of patients who sought care in tertiary hospitals, secondary hospitals, and primary hospitals were 59.8%, 39.9%, and 0.3%, respectively. Moreover, the proportions of patients seeking care in hospitals within county and prefectural administrative areas were 18.2%, 63.4%, respectively.

Conclusion

During the implementation of NMEP, malaria patients tended to seek care in tertiary hospitals and prefecture-level hospitals, and more than half of patients could be treated in hospitals in prefecture-level areas. In the current phase, it is necessary to establish referral system from county-level hospitals to higher-level hospitals for malaria treatment.
Insect repellents mediate species-specific olfactory behaviours in mosquitoes
Authors: Afify Ali , Potter Christopher J.
Published: March 2020

Background

The species-specific mode of action for DEET and many other mosquito repellents is often unclear. Confusion may arise for many reasons. First, the response of a single mosquito species is often used to represent all mosquito species. Second, behavioural studies usually test the effect of repellents on mosquito attraction towards human odorants, rather than their direct repulsive effect on mosquitoes. Third, the mosquito sensory neuron responses towards repellents are often not directly examined.

Methods

A close proximity response assay was used to test the direct repulsive effect of six mosquito repellents on Anopheles coluzzii, Aedes aegypti and Culex quinquefasciatus mosquitoes. Additionally, the behavioural assay and calcium imaging recordings of antennae were used to test the response of An. coluzzii mosquitoes towards two human odorants (1-octen-3-ol and benzaldehyde) at different concentrations, and mixtures of the repellents lemongrass oil and p-menthane-3,8-diol (PMD) with DEET.

Results

Anopheles coluzzii mosquitoes were repelled by lemongrass oil and PMD, while Ae. aegypti and Cx. quinquefasciatus mosquitoes were repelled by lemongrass oil, PMD, eugenol, and DEET. In addition, high concentrations of 1-octen-3-ol and benzaldehyde were repellent, and activated more olfactory receptor neurons on the An. coluzzii antennae than lower concentrations. Finally, changes in olfactory responses to repellent mixtures reflected changes in repulsive behaviours.

Conclusions

The findings described here suggest that different species of mosquitoes have different behavioural responses to repellents. The data further suggest that high-odour concentrations may recruit repellent-sensing neurons, or generally excite many olfactory neurons, yielding repellent behavioural responses. Finally, DEET can decrease the neuronal and behavioural response of An. coluzzii mosquitoes towards PMD but not towards lemongrass oil. Overall, these studies can help inform mosquito repellent choice by species, guide decisions on effective repellent blends, and could ultimately identify the olfactory neurons and receptors in mosquitoes that mediate repellency.
‘The problem is small enough, the problem is big enough’: a qualitative study of health technology assessment and public policy on drug funding decisions for children
Authors: Denburg Avram E. , Giacomini Mita , Ungar Wendy J. , Abelson Julia
Published: March 2020

Background

Public policy approaches to funding paediatric medicines in developed public health systems remain understudied. Current approaches to HTA present a variety of conceptual, methodological and practical problems in the context of child health. This study explores the technical and sociopolitical determinants of public funding decisions on paediatric drugs, through the analysis of interviews with stakeholders involved in or impacted by HTA for child health technologies at the provincial and national levels in Canada.

Methods

We undertook in-depth interviews with a purposive sample (n = 22) of stakeholders involved with or affected by drug funding decisions for children at the provincial (Ontario) and national levels in Canada. Grounded theory methods were employed to guide data collection and analysis. Theory on ‘technology-as-policy’ and the sociopolitics of health technologies served as sensitizing concepts for inductive data coding and analysis. Emergent themes informed the development of conceptual and practical insights on social values and system dynamics related to child HTA, of relevance to public policymaking on the coverage of health technologies for children in Canada.

Results

Participant reflection on the normative and systems dimensions of drug funding for children formed two broad categories: HTA paradigms and sociopolitical context. Our analysis revealed notable differences of context and substance related to child health technology production, evaluation and use. These differences spanned the major phases of HTA (from assembly to assessment to integration) and the surrounding sociopolitical milieu (from markets to governance to politics). Careful analysis of these differences sets in relief a number of substantive and procedural shortcomings of current HTA paradigms in respect of child health. Our findings suggest a need to rethink how HTA is structured and operationalized for child health technologies.

Conclusions

Current approaches to health technology assessment are not well calibrated to the realities of child health and illness. Our study presents a nuanced and contextually grounded analysis of concepts instrumental to drug funding decisions for children. The insights generated are directly applicable to the Canadian and Ontario contexts, but also yield fundamental knowledge about HTA for children that are germane to drug policy in other health systems.
Dying tumor cell-derived exosomal miR-194-5p potentiates survival and repopulation of tumor repopulating cells upon radiotherapy in pancreatic cancer
Authors: Jiang Ming-jie , Chen Yi-yun , Dai Juan-juan , Gu Dian-na , Mei Zhu , Liu Fu-rao , Huang Qian , Tian Ling
Published: March 2020

Background

Tumor repopulation is a major cause of radiotherapy failure. Previous investigations highlighted that dying tumor cells played vital roles in tumor repopulation through promoting proliferation of the residual tumor repopulating cells (TRCs). However, TRCs also suffer DNA damage after radiotherapy, and might undergo mitotic catastrophe under the stimulation of proliferative factors released by dying cells. Hence, we intend to find out how these paradoxical biological processes coordinated to potentiate tumor repopulation after radiotherapy.

Methods

Tumor repopulation models in vitro and in vivo were used for evaluating the therapy response and dissecting underlying mechanisms. RNA-seq was performed to find out the signaling changes and identify the significantly changed miRNAs. qPCR, western blot, IHC, FACS, colony formation assay, etc. were carried out to analyze the molecules and cells.

Results

Exosomes derived from dying tumor cells induced G1/S arrest and promoted DNA damage response to potentiate survival of TRCs through delivering miR-194-5p, which further modulated E2F3 expression. Moreover, exosomal miR-194-5p alleviated the harmful effects of oncogenic HMGA2 under radiotherapy. After a latent time, dying tumor cells further released a large amount of PGE2 to boost proliferation of the recovered TRCs, and orchestrated the repopulation cascades. Of note, low-dose aspirin was found to suppress pancreatic cancer repopulation upon radiation via inhibiting secretion of exosomes and PGE2.

Conclusion

Exosomal miR-194-5p enhanced DNA damage response in TRCs to potentiate tumor repopulation. Combined use of aspirin and radiotherapy might benefit pancreatic cancer patients.
Development of erianin-loaded dendritic mesoporous silica nanospheres with pro-apoptotic effects and enhanced topical delivery
Authors: Mo Canlong , Lu Lulu , Liu Danyang , Wei Kun
Published: March 2020

Background

Psoriasis is a malignant skin disease characterized as keratinocyte hyperproliferation and aberrant differentiation. Our previous work reported that a bibenzyl compound, erianin, has a potent inhibitory effect on keratinocyte proliferation. To improve its poor water-solubility, increase anti- proliferation activity, and enhance the skin delivery, erianin loaded dendritic mesoporous silica nanospheres (E/DMSNs) were employed.

Results

In this work, DMSNs with pore size of 3.5 nm (DMSN1) and 4.6 nm (DMSN2) were fabricated and E/DMSNs showed pore-size-dependent, significantly stronger anti-proliferative and pro-apoptotic effect than free erianin on human immortalized keratinocyte (HaCaT) cells, resulting from higher cellular uptake efficiency. In addition, compared to free erianin, treatment with E/DMSNs was more effective in reducing mitochondrial membrane potential and increasing cytoplasmic calcium levels, which were accompanied by regulation of mitochondria and endoplasmic reticulum stress (ERS) pathway. Porcine skin was utilized in the ex vivo accumulation and permeation studies, and the results indicated higher drug retention and less drug penetration in the skin when administered as the E/DMSNs-loaded hydrogel compared to the erianin-loaded hydrogel.

Conlusions

This work not only illustrated the further mechanisms of erianin in anti-proliferation of HaCaT cells but also offer a strategy to enhance the efficiency of erianin and the capacity of skin delivery through the DMSNs drug delivery systems.
Italian validation of the health education impact questionnaire (heiQ) in people with chronic conditions
Authors: Pozza Andrea , Osborne Richard H. , Elsworth Gerald R. , Ferretti Fabio , Coluccia Anna
Published: March 2020

Background

The health education impact Questionnaire (heiQ) measures eight self-management skills in people with chronic conditions. It seems to be important to provide cross-cultural evidence on its properties in non-English healthcare contexts. The present study assessed the psychometric properties of the heiQ in Italian adults with chronic conditions.

Methods

Two hundred ninety-nine individuals with a chronic condition (mean age = 61.4 years, 50.16% females) completed the heiQ and the Medical Outcomes Study-Short Form (SF-36). Confirmatory factor analyses, Composite Reliability Indices, and bivariate correlations were performed.

Results

Structural validity based on 8 correlated factors with good fit was in line with previous research. Concurrent validity was confirmed, as shown by moderate associations between the scores on the Constructive attitudes and approaches, Self-monitoring and insight, Health directed activities, Social integration and support, and Emotional distress subscales and the scores on SF-36 Physical functioning, General health perceptions, Vitality, Social functioning, Perceived mental health and Role limitations due to physical and emotional problems subscales.

Conclusions

The Italian heiQ has strong properties and it can be used routinely also in the Italian healthcare services.
Health related quality of life and healthcare utilization among adults with diabetes and kidney and eye complications in the United States
Authors: Meraya Abdulkarim M. , Alwhaibi Monira
Published: March 2020

Background

One-third of adults with diabetes in the United States have chronic kidney disease (CKD), and 19% of them have eye complications (ECs). However, little is known about the Health-related Quality of Life (HRQoL) of adults with both of these diabetes-related complications. Therefore, the purpose of this study is to examine differences in the HRQoL, mental health, and healthcare utilization of adults with diabetes who have CKD, ECs, both or neither.

Methods

A cross-sectional study design was implemented using data from multiple panels (2009–2015) of the Medical Expenditure Panel Survey. HRQoL was measured using the SF-12 Physical and Mental Component Summary (PCS & MCS) scores. The HRQoL, mental health, and healthcare utilization of four mutually exclusive groups: 1) diabetes with both CKD and ECs; 2) diabetes with CKD only; 3) diabetes with ECs only, and 4) diabetes with neither CKD nor ECs were compared. In all analyses, adults with neither CKD nor ECs were the reference group.

Results

There were 8415 adults with diabetes who met the inclusion criteria. Approximately, 75% of the study sample had neither CKD nor ECs, 13.3% had ECs only, 5.7% had CKD only, and 5.5% had both CKD and ECs. In the adjusted analyses, adults with both CKD and/or ECs complications exhibited significantly lower HRQoL compared to those with neither CKD nor ECs. Mental illness and psychological distress were higher among adults with both CKD and ECs compared to those with neither CKD nor ECs. Furthermore, adults with CKD and/or ECs had higher polypharmacy, inpatient and emergency services use compared to those with neither CKD nor ECs.

Conclusions

The results indicate that the presence of both CKD and/or ECs was negatively associated with poor HRQoL, poor mental health, higher psychological distress and healthcare utilization in adults with diabetes. The findings emphasize the need for routine assessment and treatment for diabetes-related CKD and/or ECs complications to improve the quality of care for individuals with diabetes.
An integrated prognosis model of pharmacogenomic gene signature and clinical information for diffuse large B-cell lymphoma patients following CHOP-like chemotherapy
Authors: Hu Jinglei , Xu Jing , Yu Muqiao , Gao Yongchao , Liu Rong , Zhou Honghao , Zhang Wei
Published: March 2020

Background

As the most common form of lymphoma, diffuse large B-cell lymphoma (DLBCL) is a clinical highly heterogeneous disease with variability in therapeutic outcomes and biological features. It is a challenge to identify of clinically meaningful tools for outcome prediction. In this study, we developed a prognosis model fused clinical characteristics with drug resistance pharmacogenomic signature to identify DLBCL prognostic subgroups for CHOP-based treatment.

Methods

The expression microarray data and clinical characteristics of 791 DLBCL patients from two Gene Expression Omnibus (GEO) databases were used to establish and validate this model. By using univariate Cox regression, eight clinical or genetic signatures were analyzed. The elastic net-regulated Cox regression analysis was used to select the best prognosis related factors into the predictive model. To estimate the prognostic capability of the model, Kaplan–Meier curve and the area under receiver operating characteristic (ROC) curve (AUC) were performed.

Results

A predictive model comprising 4 clinical factors and 2 pharmacogenomic gene signatures was established after 1000 times cross validation in the training dataset. The AUC of the comprehensive risk model was 0.78, whereas AUC value was lower for the clinical only model (0.68) or the gene only model (0.67). Compared with low-risk patients, the overall survival (OS) of DLBCL patients with high-risk scores was significantly decreased (HR = 4.55, 95% CI 3.14–6.59, log-rank p value = 1.06 × 10−15). The signature also enables to predict prognosis within different molecular subtypes of DLBCL. The reliability of the integrated model was confirmed by independent validation dataset (HR = 3.47, 95% CI 2.42–4.97, log rank p value = 1.53 × 10−11).

Conclusions

This integrated model has a better predictive capability to ascertain the prognosis of DLBCL patients prior to CHOP-like treatment, which may improve the clinical management of DLBCL patients and provide theoretical basis for individualized treatment.
The effects of rapid weight loss on skeletal muscle in judo athletes
Authors: Roklicer Roberto , Lakicevic Nemanja , Stajer Valdemar , Trivic Tatjana , Bianco Antonino , Mani Diba , Milosevic Zoran , Maksimovic Nebojsa , Paoli Antonio , Drid Patrik
Published: March 2020

Objective

To observe the effect of rapid weight loss (RWL) methods over 3 days on muscle damage in judokas.

Methods

Eighteen judokas participated in this crossover study, meaning that judo athletes were subjected to exercise-only phase (4 days) and RWL phase (3 days). Subjects were tested for myoglobin, creatine kinase, aldolase, hemoglobin, and hematocrit values on seven consecutive days. These biomarkers served as indicators of acute muscle damage.

Results

During the exercise-only phase, no significant changes were observed. Myoglobin (Mb) (p < 0.001), creatine kinase (CK) (p < 0.001) and aldolase (ALD) (p < 0.001) significantly increased only during the RWL phase, as well as hemoglobin (Hb) (p < 0.001) and hematocrit (Hct) (p < 0.005) values. It was detected that peak values for muscle damage biomarkers were reached on the sixth day, while Hct and Hb values were the highest on the seventh day of the study.

Conclusion

Our study showed significant muscle damage induced by RWL. The prevalence of RWL use by judokas is high but firm scientific evidence is lacking in the evaluation of the current practice of it. Therefore, further knowledge must be gained to evaluate the effectiveness of RWL on performance and its impact on judokas’ wellbeing.
Anorexic and metabolic effect of jojoba: potential treatment against metabolic syndrome and hepatic complications
Authors: Belhadj Sahla , Dal Stephanie , Khaskhoussi Fakhreddine , Maillard-Pedracini Elisa , Hentati Olfa , Sigrist Séverine
Published: March 2020

Background

Evaluation of the action of various traditional plants to treat metabolic syndrome are strongly studied. In our study, we investigated the effect of the Tunisian jojoba seed on a metabolic syndrome induced in rat by the High Fat diet and High Fructose (HFHF) and its renal and hepatic complications.

Methods

The rats were fed with HFHF or Normal Diet (ND) for a period of 8 weeks. After that, a switch from HFHF to ND or Normal Diet Jojoba (NDJ),(jojoba diet approach) or High Fat and High Fructose and Jojoba diet (HFHFJ) (nutraceutical approach) has been done. Metabolic disorder was evaluated by measuring the fasting body weight, glycemia and C-peptide and leptin. Oxidative stress parameters like ThioBarbituric Acid Reactive Substances (TBARS) and Total Antioxidant Capacity (TAOC) were analyzed in the plasma and renal and hepatic function were determined by the measure of creatinine and alanine transferase (ALT) respectively. Histological analysis was performed on the liver, kidney and pancreas.

Results

HFHF diet exhibited characteristics of metabolic syndrome presented by insulin resistance, hyperinsulinemia, hyperleptinemia, fat mass with hepatic steatosis and renal disorder. HFHF diet was associated with oxidative stress (OS) presented by an increase in TBARS and a decrease in TAOC. Adding jojoba seeds to HFHF rat group diet induced a decrease in body weight, fat mass (58 and 41%), insulin resistance (59 and 56%), oxidative stress (60 and 41%), liver steatosis (from a score = 3 to a score = 0) and renal complications (25 and 42%). This effect was emphasized with diet approach.

Conclusion

The results demonstrated the beneficial effect of jojoba against metabolic syndrome and oxidative stress, suggesting that jojoba could be used in the prevention and treatment of metabolic syndrome.

Graphical abstract
Liver trauma: WSES 2020 guidelines
Authors:   the WSES expert panel, Coccolini Federico , Coimbra Raul , Ordonez Carlos , Kluger Yoram , Vega Felipe , Moore Ernest E. , Biffl Walt , Peitzman Andrew , Horer Tal , Abu-Zidan Fikri M. , Sartelli Massimo , Fraga Gustavo P. , Cicuttin Enrico , Ansaloni Luca , Parra Michael W. , Millán Mauricio , DeAngelis Nicola , Inaba Kenji , Velmahos George , Maier Ron , Khokha Vladimir , Sakakushev Boris , Augustin Goran , di Saverio Salomone , Pikoulis Emanuil , Chirica Mircea , Reva Viktor , Leppaniemi Ari , Manchev Vassil , Chiarugi Massimo , Damaskos Dimitrios , Weber Dieter , Parry Neil , Demetrashvili Zaza , Civil Ian , Napolitano Lena , Corbella Davide , Catena Fausto
Published: March 2020

Liver injuries represent one of the most frequent life-threatening injuries in trauma patients. In determining the optimal management strategy, the anatomic injury, the hemodynamic status, and the associated injuries should be taken into consideration. Liver trauma approach may require non-operative or operative management with the intent to restore the homeostasis and the normal physiology. The management of liver trauma should be multidisciplinary including trauma surgeons, interventional radiologists, and emergency and ICU physicians. The aim of this paper is to present the World Society of Emergency Surgery (WSES) liver trauma management guidelines.
Removal of tumor thrombus from the azygos vein in an esophageal squamous cell carcinoma patient
Authors: Lu Qijue , Shi Bowen , Hong Jiang , Chen Hezhong , Li Chunguang
Published: March 2020

Background

Esophageal squamous cell carcinoma with tumor thrombus in the arch of the azygos vein has not been reported to date. Neoadjuvant chemotherapy can decrease the stage in patients with advanced preoperative tumor staging, regaining surgical opportunities and significantly prolonging progression-free survival and overall survival. Herein, we present a case of esophageal squamous cell carcinoma accompanied by tumor thrombus in the arch of the azygos vein, and the patient underwent radical surgery after neoadjuvant chemotherapy.

Case presentation

A 63-year-old male with esophageal squamous cell carcinoma was found to have tumor thrombus formation in the arch of the azygos vein. Four courses of neoadjuvant chemotherapy with the TP regimen (paclitaxel plus nedaplatin) were given. Reexamination revealed a significant reduction in tumor and tumor thrombus volume. Therefore, McKeown radical resection for esophageal cancer and removal of the tumor thrombus in the arch of the azygos vein were performed. Postoperative pathology suggested complete remission of the esophageal tumor and the presence of small focal cancer tissues in the arch of the azygos vein.

Conclusion

We report a case of esophageal squamous cell carcinoma with tumor thrombus formation in the azygos vein. We conducted radical resection after 4 rounds of neoadjuvant chemotherapy, and the pathological results revealed complete remission of the tumor. We report our experience addressing this rare case, and we hope to find the underlying mechanism of tumor thrombus formation and whether it has any effects on prognosis in our future study.
Fish oil protects the blood–brain barrier integrity in a mouse model of Alzheimer’s disease
Authors: Xie Youna , Yan Lingli , Zeng Haitao , Chen Weineng , Lu Jia-Hong , Wan Jian-Bo , Su Huanxing , Yao Xiaoli
Published: March 2020

Background

Alzheimer’s disease (AD) is ranked as the most prevalent neurodegenerative disease. However, the exact molecular mechanisms underlying pathophysiological alterations in AD remain unclear, especially at the prodromal stage. The decreased proteolytic degradation of Aβ, blood–brain barrier (BBB) disruption, and neuroinflammation are considered to play key roles in the course of AD.

Methods

Male APPswe/PS1dE9 C57BL/6 J double-transgenic (APP/PS1) mice in the age range from 1 month to 6 months and age-matched wild type mice were used in this study, intending to investigate the expression profiles of Aβ-degrading enzymes for Aβ degradation activities and zonula occludens-1 (zo-1) for BBB integrity at the prodromal stage.

Results

Our results showed that there were no significant genotype-related alterations in mRNA expression levels of 4 well-characterized Aβ-degrading enzymes in APP/PS1 mice within the ages of 6 months. Interestingly, a significant decrease in zo-1 expression was observed in APP/PS1 mice starting from the age of 5 months, suggesting that BBB disrupt occurs at an early stage. Moreover, treatment of fish oil (FO) for 4 weeks remarkably increased zo-1 expression and significantly inhibited the glial activation and NF-κB activation in APP/PS1 mice.

Conclusion

The results of our study suggest that FO supplement could be a potential therapeutic early intervention for AD through protecting the BBB integrity and suppressing glial and NF-κB activation.
The experience of long stay in high and medium secure psychiatric hospitals in England: qualitative study of the patient perspective
Authors: Holley Jessica , Weaver Tim , Völlm Birgit
Published: March 2020

Background

Some forensic patients in England remain in secure care for long, possibly unnecessarily prolonged, periods, raising significant ethical and resource issues. Research focused on the patients in secure care has examined quality of life and service provision but not the perspectives of patients experiencing long stays. This study explored how long stay patients experience secure care, what factors they felt influenced long stay, and its impact upon treatment engagement and motivation to progress.

Methods

Embedded within a larger epidemiological study, we conducted semi-structured interviews with a purposive sample of forty long stay patients from two high and six medium secure hospitals. Long stay was defined as a 5 years stay in medium secure careor10 years in high secure care,or15 years in a combination of high and medium secure. Transcripts were subject to thematic analysis, and narrative analysis at individual case level to explore the relationship between emergent themes.

Results

Four themes emerged illustrating participants’ attribution, outlook, approach, and readiness for change. A typology of four long stay stances was developed (dynamic acceptance, dynamic resistance, static acceptance, static resistance). These illustrate differences in the extent to which participants believed being in secure care helped them to get better, and actively work towards progression and leaving secure care. There were considerable differences in how patients adopting these stances attributed the reasons for their long stay, they viewed their future, and their motivation to progress. Negative perceptions arose from excessive restrictions, treatment repetition and changes in therapeutic relationships, leading some patients to exhibiting tokenistic engagement and low motivation to progress.

Conclusions

Planning care for long stay patients in secure psychiatric settings should take account of the differing stances patient’s adopt towards engagement and progression. Service providers should be mindful of these stances and provide patients with individualised opportunities to progress through the secure care treatment pathway, avoiding treatment repetition and maintaining continuity in key professional relationships. Refocusing on quality of life may be appropriate for some long-term patients who are unwilling or unable to move on. For some long-term patients, purpose designed long stay setting may be appropriate.
Vitamin B12 deficiency as a cause of severe neurological symptoms in breast fed infant – a case report
Authors: Dubaj Cezary , Czyż Katarzyna , Furmaga-Jabłońska Wanda
Published: March 2020

Background

Vitamin B12 (cobalamin, cbl) deficiency in children is rare and may occurs in exclusively breast fed infants of mothers on vegetarian or vegan diet with lack of appropriate supplementation. The clinical manifestation of vitamin B12 deficiency include neurological disorders, megaloblastic anemia and failure to thrive. Routine and commonly used laboratory tests such as cell blood count (CBC) or serum vitamin B12 level are sufficient for appropriate diagnosis. Typical therapy is based on intramuscular cobalamin injections. Early diagnosis and early onset of treatment are crucial factors for long-term prognosis of patients as the duration of deficiency may be correlated with the development of long lasting changes in the nervous system.

The purpose of this article is to present influence of maternal vitamin B12 deficiency as a cause of infant psychomotor retardation.

Case presentation

We report the case of a 7 months old girl whose parents sought medical advice due to pathological somnolence and developmental regression of their daughter with onset approximately 2 months prior to the visit. Following several diagnostic tests it was determined that the infant’s symptoms were due to vitamin B12 deficiency which was secondary to the mother’s latent Addison-Biermer disease. Apart from neurological symptoms the infant also showed megaloblastic anemia which is typical to cobalamin deficiencies. Intramuscular vitamin B12 supplementation resulted in instant improvement of the patient’s general condition and blood morphology. Unfortunately, psychological examination indicated long-term psychomotor retardation due to delayed diagnosis of B12 deficiency.

Conclusions

Vitamin B12 levels should be considered during differential diagnosis of neurological symptoms in exclusively breast-fed infants especially if they co-exist with megaloblastic anemia and psychomotor retardation.
Correction to: Efficacy and safety of tetramethylpyrazine phosphate on pulmonary hypertension: study protocol for a randomized controlled study
Authors: Chen Yuqin , He Wenjun , Ouyang Haiping , Liu Chunli , Hong Cheng , Wang Tao , Yang Kai , Lu Wenju , Wang Jian
Published: March 2020

After publication of our article [1] the authors have notified us of two typos in the Trial status.
Research progress of near-infrared fluorescence probes based on indole heptamethine cyanine dyes in vivo and in vitro
Authors: Sun Chunlong , Du Wen , Wang Baoqin , Dong Bin , Wang Baogui
Published: March 2020

Near-infrared (NIR) fluorescence imaging is a noninvasive technique that provides numerous advantages for the real-time in vivo monitoring of biological information in living subjects without the use of ionizing radiation. Near-infrared fluorescent (NIRF) dyes are widely used as fluorescent imaging probes. These fluorescent dyes remarkably decrease the interference caused by the self-absorption of substances and autofluorescence, increase detection selectivity and sensitivity, and reduce damage to the human body. Thus, they are beneficial for bioassays. Indole heptamethine cyanine dyes are widely investigated in the field of near-infrared fluorescence imaging. They are mainly composed of indole heterocyclics, heptamethine chains, and N-substituent side chains. With indole heptamethine cyanine dyes as the parent, introducing reactive groups to the parent compounds or changing their structures can make fluorescent probes have different functions like labeling protein and tumor, detecting intracellular metal cations, which has become the hotspot in the field of fluorescence imaging of biological research. Therefore, this study reviewed the applications of indole heptamethine cyanine fluorescent probes to metal cation detection, pH, molecules, tumor imaging, and protein in vivo. The distribution, imaging results, and metabolism of the probes in vivo and in vitro were described. The biological application trends and existing problems of fluorescent probes were discussed.
Local and regional temporal trends (2013–2019) of canine Ehrlichia spp. seroprevalence in the USA
Authors: Gettings Jenna R. , Self Stella C. W. , McMahan Christopher S. , Brown D. Andrew , Nordone Shila K. , Yabsley Michael J.
Published: March 2020

Background

In the USA, there are severalEhrlichiaspp. of concern includingEhrlichia canis,Ehrlichia ewingii,Ehrlichia chaffeensis,Ehrlichia muris eauclarensis, and “Panola MountainEhrlichia”. Of these,E. canisis considered the most clinically relevant for domestic dogs, with infection capable of causing acute, subclinical, and chronic stages of disease. Changes in climate, land use, habitats, and wildlife reservoir populations, and increasing contact between both human and dog populations with natural areas have resulted in the increased risk of vector-borne disease throughout the world.

Methods

A Bayesian spatio-temporal binomial regression model was applied to serological test results collected from veterinarians throughout the contiguous USA between January 2013 and November 2019. The model was used to quantify both regional and local temporal trends of canineEhrlichiaspp. seroprevalence and identify areas that experienced significant increases in seroprevalence.

Results

Regionally, increasing seroprevalence occurred within several states throughout the central and southeastern states, including Missouri, Arkansas, Mississippi, Alabama, Virginia, North Carolina, Georgia and Texas. The underlying local trends revealed increasing seroprevalence at a finer scale. Clusters of locally increasing seroprevalence were seen from the western Appalachian region into the southern Midwest, along the Atlantic coast in New England, parts of Florida, Illinois, Wisconsin and Minnesota, and in a couple areas of the Mountain region. Clusters of locally decreasing seroprevalence were seen throughout the USA including New York and the mid-Atlantic states, Texas, the Midwest, and California.

Conclusions

CanineEhrlichiaspp. seroprevalence is increasing in both endemic and non-endemic areas of the USA. The findings from this study indicate that dogs across a wide area of the USA are at risk of exposure and these results should provide veterinarians and pet owners with the information they need to make informed decisions about prevention of tick exposure.
Co-infection, reinfection and superinfection with Anaplasma phagocytophilum strains in a cattle herd based on ankA gene and multilocus sequence typing
Authors: Langenwalder Denis B. , Silaghi Cornelia , Nieder Marion , Pfeffer Martin , von Loewenich Friederike D.
Published: March 2020

Background

Anaplasma phagocytophilum is a Gram-negative obligate intracellular bacterium that replicates in neutrophil granulocytes. It is transmitted by ticks of the Ixodes ricinus complex and causes febrile illness in humans and animals. We used multilocus sequence typing (MLST) and ankA gene-based typing to study the molecular epidemiology of the A. phagocytophilum strains circulating in a German cattle herd over one pasture season. The aim was to investigate whether co-infection with two distinct variants, reinfection with the same and/or superinfection by a different strain occurred during one pasture season. Eight genetic loci were sequenced in 47 PCR-positive samples from 15 animals.

Results

Five different sequence types (ST) and four ankA alleles were detected in the cattle herd. Three different ST caused clinically overt tick-borne fever in primary infected animals. The concordance between ST and ankA allele was 100%. Therefore, the housekeeping genes used for MLST and the highly variable ankA gene were concatenated to increase resolution. Co-infection could be proven because samples of chronologically close collection dates were included. Co-infecting A. phagocytophilum strains differed by 14 to 18 single nucleotide polymorphisms (SNPs). Most superinfecting variants varied by 14 SNPs from the previous strain and appeared in median after a free interval of 31 days. Thus, it is unlikely that superinfecting strains arose by in-animal evolution. Immunity against re- or superinfection was assumed because the cattle developed clinical signs only during primary infection.

Conclusions

The tick-pathogen-vertebrate host interaction is probably much more complex than previously thought taking into account the frequently occurring events of co-infection, reinfection and superinfection. This complex situation could not be easily simulated in an experimental infection and underlines the value of field studies.
Anopheline bionomics, insecticide resistance and transnational dispersion in the context of controlling a possible recurrence of malaria transmission in Jaffna city in northern Sri Lanka
Authors: Surendran Sinnathamby N. , Jayadas Tibutius T. P. , Tharsan Annathurai , Thiruchenthooran Vaikunthavasan , Santhirasegaram Sharanga , Sivabalakrishnan Kokila , Raveendran Selvarajah , Ramasamy Ranjan
Published: March 2020

Background

Malaria was eliminated from Sri Lanka in 2013. However, the influx of infected travelers and the presence of potent anopheline vectors can re-initiate transmission in Jaffna city, which is separated by a narrow strait from the malaria-endemic Indian state of Tamil Nadu.

Methods

Anopheline larvae were collected from different habitats in Jaffna city and the susceptibility of emergent adults to DDT, malathion and deltamethrin investigated.

Results

Anopheline larvae were found in wells, surface-exposed drains, ponds, water puddles and water storage tanks, with many containing polluted, alkaline and brackish water.Anopheles culicifacies,An. subpictus,An. stephensiandAn. varunawere identified in the collections. Adults of the four anopheline species were resistant to DDT.Anopheles subpictusandAn. stephensiwere resistant whileAn. culicifaciesandAn. varunawere possibly resistant to deltamethrin.Anopheles stephensiwas resistant,An. subpictuspossibly resistant whileAn. varunaandAn. culicifacieswere susceptible to malathion. DNA sequencing showed a L1014F (TTA to TTC) mutation in the IIS6 transmembrane segment of the voltage-gated sodium channel protein in deltamethrin-resistantAn. subpictus—a mutation previously observed in India but not Sri Lanka.

Conclusion

Anopheles subpictusin Jaffna, likeAn. stephensi, may have recently originated in coastal Tamil Nadu. Besides infected overseas travelers, wind- and boat-borne carriage ofPlasmodium-infected anophelines across the Palk Strait can potentially reintroduce malaria transmission to Jaffna city. Adaptation to diverse larval habitats and resistance to common insecticides in anophelines are identified as potential problems for vector control should this happen.
Integrative -omics and HLA-ligandomics analysis to identify novel drug targets for ccRCC immunotherapy
Authors: Reustle Anna , Di Marco Moreno , Meyerhoff Carolin , Nelde Annika , Walz Juliane S. , Winter Stefan , Kandabarau Siahei , Büttner Florian , Haag Mathias , Backert Linus , Kowalewski Daniel J. , Rausch Steffen , Hennenlotter Jörg , Stühler Viktoria , Scharpf Marcus , Fend Falko , Stenzl Arnulf , Rammensee Hans-Georg , Bedke Jens , Stevanović Stefan , Schwab Matthias , Schaeffeler Elke
Published: March 2020

Background

Clear cell renal cell carcinoma (ccRCC) is the dominant subtype of renal cancer. With currently available therapies, cure of advanced and metastatic ccRCC is achieved only in rare cases. Here, we developed a workflow integrating different -omics technologies to identify ccRCC-specific HLA-presented peptides as potential drug targets for ccRCC immunotherapy.

Methods

We analyzed HLA-presented peptides by MS-based ligandomics of 55 ccRCC tumors (cohort 1), paired non-tumor renal tissues, and 158 benign tissues from other organs. Pathways enriched in ccRCC compared to its cell type of origin were identified by transcriptome and gene set enrichment analyses in 51 tumor tissues of the same cohort. To retrieve a list of candidate targets with involvement in ccRCC pathogenesis, ccRCC-specific pathway genes were intersected with the source genes of tumor-exclusive peptides. The candidates were validated in an independent cohort from The Cancer Genome Atlas (TCGA KIRC, n = 452). DNA methylation (TCGA KIRC, n = 273), somatic mutations (TCGA KIRC, n = 392), and gene ontology (GO) and correlations with tumor metabolites (cohort 1, n = 30) and immune-oncological markers (cohort 1, n = 37) were analyzed to characterize regulatory and functional involvements. CD8+ T cell priming assays were used to identify immunogenic peptides. The candidate gene EGLN3 was functionally investigated in cell culture.

Results

A total of 34,226 HLA class I- and 19,325 class II-presented peptides were identified in ccRCC tissue, of which 443 class I and 203 class II peptides were ccRCC-specific and presented in ≥ 3 tumors. One hundred eighty-five of the 499 corresponding source genes were involved in pathways activated by ccRCC tumors. After validation in the independent cohort from TCGA, 113 final candidate genes remained. Candidates were involved in extracellular matrix organization, hypoxic signaling, immune processes, and others. Nine of the 12 peptides assessed by immunogenicity analysis were able to activate naïve CD8+ T cells, including peptides derived from EGLN3. Functional analysis of EGLN3 revealed possible tumor-promoting functions.

Conclusions

Integration of HLA ligandomics, transcriptomics, genetic, and epigenetic data leads to the identification of novel functionally relevant therapeutic targets for ccRCC immunotherapy. Validation of the identified targets is recommended to expand the treatment landscape of ccRCC.
Iguratimod as an alternative induction therapy for refractory lupus nephritis: a preliminary investigational study
Authors: Kang Yuening , Yan Qingran , Fu Qiong , Wang Ran , Dai Min , Du Fang , Dai Qing , Ye Ping , Wu Chunmei , Lu Liangjing , Bao Chunde
Published: March 2020

Objectives

Iguratimod, a novel immunomodulatory agent for rheumatoid arthritis, has been shown to be effective against murine lupus. The aim of this study was to make a preliminary evaluation of the efficacy and safety of iguratimod as salvage therapy in patients with refractory lupus nephritis (LN).

Methods

We enrolled eligible patients with refractory LN, which we defined as having failed or relapsed on at least two immunosuppressant agents. After enrollment, we substituted iguratimod (25 mg twice daily) for their previous immunosuppressant agents without increasing the dose of steroids. The primary outcome was complete/partial remission (PR/CR) at week 24. Patients who achieved remission continued iguratimod as maintenance therapy over an extended follow-up.

Results

The study cohort comprised 14 patients with refractory LN, 10 of whom had recent treatment failure and 4 repeated relapses with inadequate initial responses. At enrollment, none of the patients had detectable evidence of extra-renal involvement. The median prednisone dosage was 10 mg/d (IQR 0–10 mg/day). Thirteen patients were eligible for response evaluation, with one patient missed. The renal response rate was 92.3% (12/13) at week 24, with 38.5% (5/13) achieving CR and 53.8% (7/13) achieving PR. We then continued to follow up the responding patients for up to 144 weeks. Twenty-five percent of the patients (3/12) had renal relapse after initial PR. The estimated glomerular filtration rate of all patients maintained stable during follow-up. One patient had a severe adverse reaction (anemia) but recovered fully after stopping iguratimod.

Conclusions

Our study supports the potential of iguratimod for treatment of refractory LN. Iguratimod could be a promising candidate drug for this condition.
Effects of high intensity interval training on exercise capacity in people with chronic pulmonary conditions: a narrative review
Authors: Sawyer Abbey , Cavalheri Vinicius , Hill Kylie
Published: March 2020

Background

Exercise training is important in the management of adults with chronic pulmonary conditions. However, achieving high intensity exercise may be challenging for this clinical population. There has been clinical interest in applying interval-based training as a strategy to optimise the load that can be tolerated during exercise training. Evidence for such an approach is limited in most chronic pulmonary populations.

Main body

In this narrative review, we provide an appraisal of studies investigating whole-body high intensity interval training (HIIT) in adults with chronic obstructive pulmonary disease (COPD). This is the first review to also include studies investigating HIIT in people with conditions other than COPD. Studies undertaken in adults with a chronic pulmonary condition were reviewed when participants were randomised to receive; (i) HIIT or no exercise or, (ii) HIIT or moderate intensity continuous exercise. Data were extracted on peak rate of oxygen uptake (VO2peak; ‘cardiorespiratory fitness’) and maximal work rate (Wmax; ‘exercise capacity’).

In people with COPD, two studies demonstrated between-group differences favouring HIIT compared with no exercise. There appears to be no advantage for HIIT compared to continuous exercise on these outcomes. In people with cystic fibrosis (CF), no studies have compared HIIT to no exercise and the two studies that compared HIIT to continuous exercise reported similar benefits. In people prior to resection for non-small cell lung cancer, one study demonstrated a between-group difference in favour of HIIT compared with no exercise on VO2peak. In people with asthma, one study demonstrated a between-group difference in favour of HIIT compared with no exercise on VO2peakand one that compared HIIT to continuous exercise reported similar benefits. No studies were identified non-CF bronchiectasis or interstitial lung diseases.

Conclusions

High intensity interval training increases cardiorespiratory fitness and exercise capacity when compared with no exercise and produces a similar magnitude of change as continuous exercise in people with COPD. There is a paucity of studies exploring the effects of HIIT in other chronic pulmonary conditions.
Study determinants of increased Z-Score of Body Mass Index in preschool-age children
Authors: El-Gamal Fathi M. , Babader Rawan , Al-Shaikh Maha , Al-Harbi Amani , Al-Kaf Jumana , Al-Kaf Wafa
Published: March 2020

Objective

To determine the association between socioeconomic level, gender, stunting and other characteristics with the presence of overweight/obesity in the preschool children.

Result

BMI/Age Z score > + 2 SD was found in 19.5% of the children. It was more common among the children from areas with high socio-economic level (OR: 2.43; 95% CI 1.54, 3.84, and p < .000). Obesity was higher among the males (OR 1.76; 95% CI 1.09, 2.8, and p < .02) compared to females. The increased duration of breast feeding, was significantly associated with increased BMI/Age Z-score (b = .027, p < .004). Decreased age of the child was significantly associated with increased BMI/Age Z-score (b = −  .013, p < .004). The children with stunted growth were 6.7 times fold likely to have BMI/Age Z Score > + 2 SD compared to the normal children (OR 6.73; 95% CI 3.79, 10.80, and p < .000), after allowing for other factors. No significant association was found between allergic disorders and BMI/Age Z score > + 2 SD. Thus male gender, high socioeconomic condition, increased duration of breast feeding and stunting were significantly associated with overweight/obesity in preschool children.