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    Implementation of Audio-Computer Assisted Self-Interview (ACASI) among adolescent girls in humanitarian settings: feasibility, acceptability, and lessons learned

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    Abstract Background Audio-Computer Assisted Self- Interview (ACASI) is a method of data collection in which participants listen to pre-recorded questions through headphones and respond to questions by selecting their answers on a touch screen or keypad, and is seen as advantageous for gathering data on sensitive topics such as experiences of violence. This paper seeks to explore the feasibility and acceptability of using ACASI with adolescent girls and to document the implementation of such an approach in two humanitarian settings: conflict-affected communities in eastern Democratic Republic of Congo (DRC) and refugee camps along the Sudan-Ethiopia border. Methods This paper evaluates the feasibility and acceptability of implementing ACASI, based on the experiences of using this tool in baseline data collections for COMPASS (Creating Opportunities through Mentorship, Parental involvement, and Safe Spaces) impact evaluations in DRC ( N \u2009=\u2009868) and Ethiopia ( N \u2009=\u2009919) among adolescent girls. Descriptive statistics and logistic regression models were generated to examine associations between understanding of the survey and selected demographics in both countries. Results Overall, nearly 90% of girls in the DRC felt that the questions were easy to understand as compared to approximately 75% in Ethiopia. Level of education, but not age, was associated with understanding of the survey in both countries. Conclusions Financial and time investment to ready ACASI was substantial in order to properly contextualize the approach to these specific humanitarian settings, including piloting of images, language assessments, and checking both written translations and corresponding verbal recordings. Despite challenges, we conclude that ACASI proved feasible and acceptable to participants and to data collection teams in two diverse humanitarian settings

    Evidence-based guideline implementation in low and middle income countries: lessons for mental health care

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    Abstract Background There is a significant treatment gap in provision of effective treatment for people with mental disorders globally. In some Low and Middle Income Countries (LMICs) this gap is 90% or more in terms of untreated cases. Clinical practice guidelines (CPGs) are one tool to improve health care provision. The aim of this review is to examine studies of the effectiveness of evidence-based CPG implementation across physical and mental health care, to inform mental healthcare provision in low and middle income countries (LMICs), and to identify transferable lessons from other non-communicable diseases to mental health. Methods A systematic literature review employing narrative synthesis and utilising the tools developed by the Cochrane Effective Practice and Organisation of Care (EPOC) group was conducted. Experimental studies of CPG implementation relating to non-communicable diseases, including mental disorders, in LMICs were retrieved and synthesised. Results Few (six) studies were identified. Four cluster randomised controlled trials (RCTs) related to the introduction of CPGs for non-communicable diseases in physical health; one cluster-RCT included CPGs for both a non-communicable disease in physical health and mental health, and one uncontrolled before and after study described the introduction of a CPG for mental health. All of the included studies adopted multi-faceted CPG implementation strategies and used education as part of this strategy. Components of the multi-faceted strategies were sometimes poorly described. Results of the studies included generally show statistically significant improvement on some, but not all, outcomes. Conclusion Evidence for the effectiveness of interventions to improve uptake of, and compliance with, evidence-based CPGs in LMICs for mental disorders and for other non-communicable diseases is at present limited. The sparse literature does, however, suggest that multifaceted CPG implementation strategies that involve an educational component may be an effective way of improving guideline adherence and therefore of improving clinical outcomes. Further work is needed to examine cost-effectiveness of CPG implementation strategies in LMICs and to draw conclusions on the transferability of implementation experience in physical health care to mental health practice settings. Strategies to ensure that CPGs are developed with clear guidance for ..

    Distinct profiles of reactive and proactive aggression in adolescents: associations with cognitive and affective empathy

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    Abstract Background Aggression comprises a heterogeneous set of behavioral patterns that aim to harm and hurt others. Empathy represents a potential mechanism that inhibits aggressive conduct and enhances prosocial behavior. Nevertheless, research results on the relationship between empathy and aggression are mixed. Subtypes of aggressive behavior, such as reactive and proactive aggression might be differently related to empathy. The aim of the present study was to investigate the interrelations of cognitive and affective empathy with reactive and proactive aggression. Methods We recruited a sample of 177 (33% female, M age 15.6) adolescents from socio-educational and juvenile justice institutions and a community sample of 77 (36% female, M age 13.1) adolescents from secondary schools. Using bivariate correlation analysis and hierarchical multiple regression analysis, we firstly investigated associations between cognitive and affective empathy and reactive and proactive aggression. Subsequently, we performed cluster analysis to identify clusters of adolescents with meaningful profiles of aggressive behavior and compared derived clusters on measures of empathy. We applied the Basic Empathy Scale and the Reactive-Proactive Aggression Questionnaire. Results Bivariate analysis and hierarchical regression analysis showed that cognitive and affective empathy were negatively associated with proactive aggression, but not with reactive aggression. Cluster-analysis revealed three clusters of adolescents with distinct aggression profiles: a cluster with elevated scores on reactive and proactive aggression, a clusters with high scores on reactive aggression only, and a low aggression cluster. Cluster comparisons revealed that the reactive-proactive aggression cluster showed significantly lower scores on cognitive and affective empathy than both other clusters. Results further indicated that within the reactive-proactive aggression cluster, girls did not differ significantly from boys in empathy. Conclusions The present study extends previously published findings, and possibly explains conflicting results in prior research. Our results indicated that cognitive and affective empathy are reduced in adolescents with high levels of reactive and proactive aggression. Our study may contribute to the development of tailored clinical interventions for different aggression clusters

    Nuclear microRNAs in normal hemopoiesis and cancer

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    Abstract Since the discovery of microRNAs (miRNAs) in the early 1990s, these small molecules have been increasingly recognized as key players in the regulation of critical biological processes. They have also been implicated in many diverse human diseases. The canonical function of miRNAs is to target the 3\u2032 untranslated region (3\u2032 UTR) of cytoplasmic messenger RNA to post-transcriptionally regulate mRNA and protein levels. It has now been shown that miRNAs can also bind to the promoter regions of genes or primary miRNA transcripts to regulate gene expression. Such observations have indicated the presence of miRNAs in the nucleus and implied additional non-canonical functions. Nevertheless, the role(s) of nuclear miRNAs in normal hemopoiesis and cancer remains elusive despite a burgeoning literature. Herein, we review current knowledge concerning the abundance and/or functions of nuclear miRNAs during blood cell development and cancer biology. We also discuss ongoing challenges in order to provoke further studies into identifying key roles for nuclear miRNAs in the development of other cell lineages and human cancers

    Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma

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    Abstract Background Cholangiocarcinoma (CCA) is one of the most fatal malignant tumors with increasing incidence, mortality, and insensitivity to traditional chemo-radiotherapy and targeted therapy. Chimeric antigen receptor-modified T cell (CART) immunotherapy represents a novel strategy for the management of many malignancies. However, the potential of CART therapy in treating advanced unresectable/metastatic CCA is uncharted so far. Case presentation In this case, a 52-year-old female who was diagnosed as advanced unresectable/metastatic CCA and resistant to the following chemotherapy and radiotherapy was treated with CART cocktail immunotherapy, which was composed of successive infusions of CART cells targeting epidermal growth factor receptor (EGFR) and CD133, respectively. The patient finally achieved an 8.5-month partial response (PR) from the CART-EGFR therapy and a 4.5-month-lasting PR from the CART133 treatment. The CART-EGFR cells induced acute infusion-related toxicities such as mild chills, fever, fatigue, vomiting and muscle soreness, and a 9-day duration of delayed lower fever, accompanied by escalation of IL-6 and C reactive protein (CRP), acute increase of glutamic-pyruvic transaminase and glutamic-oxalacetic transaminase, and grade 2 lichen striatus-like skin pathological changes. The CART133 cells induced an intermittent upper abdominal dull pain, chills, fever, and rapidly deteriorative grade 3 systemic subcutaneous hemorrhages and congestive rashes together with serum cytokine release, which needed emergent medical intervention including intravenous methylprednisolone. Conclusions This case suggests that CART cocktail immunotherapy may be feasible for the treatment of CCA as well as other solid malignancies; however, the toxicities, especially the epidermal/endothelial damages, require a further investigation. Trial registration ClinicalTrials.gov NCT01869166 and NCT02541370

    How does genetic risk information for Lynch syndrome translate to risk management behaviours?

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    Abstract Background There is limited research on why some individuals who have undergone predictive genetic testing for Lynch syndrome do not adhere to screening recommendations. This study aimed to explore qualitatively how Lynch syndrome non-carriers and carriers translate genetic risk information and advice to decisions about risk managment behaviours in the Australian healthcare system. Methods Participants of the Australasian Colorectal Cancer Family Registry who had undergone predictive genetic testing for Lynch syndrome were interviewed on their risk management behaviours. Transcripts were analysed thematically using a comparative coding analysis. Results Thirty-three people were interviewed. Of the non-carriers ( n \u2009=\u200916), 2 reported having apparently unnecessary colonoscopies, and 6 were unsure about what population-based colorectal cancer screening entails. Of the carriers ( n \u2009=\u200917), 2 reported they had not had regular colonoscopies, and spoke about their discomfort with the screening process and a lack of faith in the procedure\u2019s ability to reduce their risk of developing colorectal cancer. Of the female carriers ( n \u2009=\u20099), 2 could not recall being informed about the associated risk of gynaecological cancers. Conclusion Non-carriers and female carriers of Lynch syndrome could benefit from further clarity and advice about appropriate risk management options. For those carriers who did not adhere to colonoscopy screening, a lack of faith in both genetic test results and screening were evident. It is essential that consistent advice is offered to both carriers and non-carriers of Lynch syndrome

    Lyme disease risk in southern California: abiotic and environmental drivers of Ixodes pacificus (Acari: Ixodidae) density and infection prevalence with Borrelia burgdorferi

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    Abstract Background Tick-borne diseases, particularly Lyme disease, are emerging across the northern hemisphere. In order to manage emerging diseases and predict where emergence will likely occur, it is necessary to understand the factors influencing the distribution, abundance and infection prevalence of vector species. In North America, Lyme disease is the most common vector-borne disease and is transmitted by blacklegged ticks. This study aimed to explore the abiotic and environmental drivers of density and infection prevalence of western blacklegged ticks ( Ixodes pacificus ) in southern California, an understudied and densely populated region of North America. Results Over the course of this two-year study, densities of I. pacificus adults were consistently positively associated with host availability for juvenile ticks and dense oak woodland habitat. Densities of nymphal and larval I. pacificus , on the other hand were primarily predicted by host availability for juvenile ticks in the first year of the study, and by habitat characteristics such as dense leaf litter in the second year. Infection with the causative agent of Lyme disease, Borrelia burgdorferi ( sensu stricto ), and related spirochetes was not predicted by the abiotic conditions promoting I. pacificus populations, but rather by diversity of the tick community, and in particular by the presence of two Ixodes tick species that do not generally feed on humans ( Ixodes spinipalpis and Ixodes peromysci ). Borrelia spp. infection was not detected in the I. pacificus populations sampled, but was detected in other vector species that may maintain enzootic transmission of the pathogen on the landscape. Conclusions This study identified dense oak woodlands as high-risk habitats for I. pacificus tick encounter in southern California. The shift in relative importance of host availability to habitat characteristics in predicting juvenile tick abundance occurred as California\u2019s historic drought intensified, suggesting that habitat providing suitable microclimates for tick survivorship became centrally important to patterns of abundance in the face of deleterious abiotic conditions. These results underscore the need for further investigation of the effects of climate change on tick-borne disease in California. Finally, despite low risk of human Lyme disease infection posed by I. pacificus in southern California, evidence of infection was found in other tick species, suggesting that enzootic transmission of tick-borne ..

    Avian malaria on Madagascar: bird hosts and putative vector mosquitoes of different Plasmodium lineages

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    Abstract Background Avian malaria occurs almost worldwide and is caused by Haemosporida parasites ( Plasmodium , Haemoproteus and Leucocytozoon ). Vectors such as mosquitoes, hippoboscid flies or biting midges are required for the transmission of these parasites. There are few studies about avian malaria parasites on Madagascar but none about suitable vectors. Methods To identify vectors of avian Plasmodium parasites on Madagascar, we examined head, thorax and abdomen of 418 mosquitoes from at least 18 species using a nested PCR method to amplify a 524\ua0bp fragment of the haemosporidian mitochondrial cytochrome b gene. Sequences obtained were then compared with a large dataset of haemosporidian sequences detected in 45 different bird species ( n \u2009=\u2009686) from the same area in the Maromizaha rainforest. Results Twenty-one mosquitoes tested positive for avian malaria parasites. Haemoproteus DNA was found in nine mosquitoes (2.15%) while Plasmodium DNA was found in 12 mosquitoes (2.87%). Seven distinct lineages were identified among the Plasmodium DNA samples. Some lineages were also found in the examined bird samples: Plasmodium sp. WA46 (EU810628.1) in the Madagascar bulbul, Plasmodium sp. mosquito 132 (AB308050.1) in 15 bird species belonging to eight families, Plasmodium sp. PV12 (GQ150194.1) in eleven bird species belonging to eight families and Plasmodium sp. P31 (DQ839060.1) was found in three weaver bird species. Conclusion This study provides the first insight into avian malaria transmission in the Maromizaha rainforest in eastern Madagascar. Five Haemoproteus lineages and seven Plasmodium lineages were detected in the examined mosquitoes. Complete life-cycles for the specialist lineages WA46 and P31 and for the generalist lineages mosquito132 and PV12 of Plasmodium are proposed. In addition, we have identified for the first time Anopheles mascarensis and Uranotaenia spp. as vectors for avian malaria and offer the first description of vector mosquitoes for avian malaria in Madagascar

    Regional level risk factors associated with the occurrence of African swine fever in West and East Africa

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    Abstract Background African swine fever (ASF) causes severe socio-economic impacts due to high mortality and trade restrictions. Many risk factors of ASF have been identified at farm level. However, understanding the risk factors, especially wild suid hosts, determining ASF transmission at regional level remains limited. Methods Based on ASF outbreak data in domestic pigs during 2006\u20132014, we here tested, separately for West and East Africa, which risk factors were linked to ASF presence at a regional level, using generalized linear mixed models. Results Our results show that ASF infections in the preceding year was an important predictor for ASF presence in both West and East Africa. Both pig density and human density were positively associated with ASF presence in West Africa. In East Africa, ASF outbreaks in domestic pigs were also correlated with higher percentages of areas occupied by giant forest hogs and by high-tick-risk areas. Conclusions Our results suggest that regional ASF risk in East Africa and in West Africa were associated with different sets of risk factors. Regional ASF risk in West Africa mainly followed the domestic cycle, whereas the sylvatic cycle may influence regional ASF risk in East Africa. With these findings, we contribute to the better understanding of the risk factors of ASF occurrence at regional scales that may aid the implementation of effective control measures

    Improvement of quality of life through glycemic control by liraglutide, a GLP-1 analog, in insulin-naive patients with type 2 diabetes mellitus: the PAGE1 study

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    Abstract Background In addition to achieving good glycemic control, diabetes care management aims to improve the quality of life (QOL) in patients. Treatment-associated difficulties and side effects frequently cause deterioration in QOL. Liraglutide, a GLP-1 receptor agonist, is a novel injection drug that promotes insulin secretion. It is a user-friendly, once-daily injection with fewer hypoglycemic events. In this study, we aimed to examine the effect of liraglutide therapy on QOL in patients. Methods In total, 304 insulin- and liraglutide-na\uefve patients with type 2 diabetes were enrolled in this observational study; they received liraglutide therapy for 12\ua0weeks. The main outcome measure was change in QOL from baseline, which was assessed using diabetes therapy-related QOL (DTR-QOL). Results At week 12, liraglutide significantly decreased HbA1c levels (8.7\ua0\ub1\ua01.5 vs. 7.5\ua0\ub1\ua01.3, p \ua0<\ua00.001) and BMI (27.9\ua0\ub1\ua05.3 vs. 27.3\ua0\ub1\ua05.2, p \ua0<\ua00.001). According to the QOL scores, although the treatment modality had changed from non-injection to injection therapy, liraglutide improved patient satisfaction with treatment. Significant correlations were found between change in HbA1c level and satisfaction with treatment, as well as between change in body weight and burden on social and daily activities, anxiety and dissatisfaction with treatment, and hypoglycemia. Conclusions Liraglutide significantly improved glycemic control and reduced the body weight without deteriorating QOL in obese patients with type 2 diabetes. Trial registration UMIN-CTR: UMIN00000715

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