bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing the ribosomal tandem repeat and its utility as a DNA barcode in lichen-forming fungi
Authors: Bradshaw Michael , Grewe Felix , Thomas Anne , Harrison Cody H. , Lindgren Hanna , Muggia Lucia , Clair Larry L. St. , Lumbsch H. Thorsten , Leavitt Steve
Published: December 2019

Background: Regions within the nuclear ribosomal operon are a major tool for inferring evolutionary relationships and investigating diversity in fungi. In spite of the prevalent use of ribosomal markers in fungal research, central features of nuclear ribosomal DNA (nrDNA) evolution are poorly characterized for fungi in general, including lichenized fungi. The internal transcribed spacer (ITS) region of the nrDNA has been adopted as the primary DNA barcode identification marker for fungi. However, little is known about intragenomic variation in the nrDNA in symbiotic fungi. In order to better understand evolution of nrDNA and the utility of the ITS region for barcode identification of lichen-forming fungal species, we generated nearly complete nuclear ribosomal operon sequences from nine species in the Rhizoplaca melanophthalma species complex using short reads from high-throughput sequencing. Results: We estimated copy numbers for the nrDNA operon, ranging from nine to 48 copies for members of thiscomplex, and found low levels of intragenomic variation in the standard barcode region (ITS). Monophyly of currently described species in this complex was supported in phylogenetic inferences based on the ITS, 28S, intergenic spacer region, and some intronic regions, independently; however, a phylogenetic inference based on the 18S provided much lower resolution. Phylogenetic analysis of concatenated ITS and intergenic spacer sequence data generated from 496 specimens collected worldwide revealed previously unrecognized lineages in the nrDNA phylogeny. Conclusions: The results from our study support the general assumption that the ITS region of the nrDNA is an effective barcoding marker for fungi. For the R. melanophthalma group, the limited amount of potential intragenomic variability in the ITS region did not correspond to fixed diagnostic nucleotide position characters separating taxa within this species complex. Previously unrecognized lineages inferred from ITS sequence data may represent undescribed species-level lineages or reflect uncharacterized aspects of nrDNA evolution in the R. melanophthalma species complex.
Determining the prevalence of palliative needs and exploring screening accuracy of depression and anxiety items of the Integrated Palliative care Outcome Scale – a multi-centre study
Authors: Antunes Bárbara Pereira , Rodrigues Pedro Pereira , Higginson Irene J. , Ferreira Pedro Lopes
Published: December 2019

Background: patients with palliative needs often experience high symptom burden which causes suffering to themselves and their families. Depression and psychological distress should not be considered a “normal event” in advanced disease patients and should be screened, diagnosed, acted on and followed-up. Psychological distress has been associated with greater physical symptom severity, suffering, and mortality in cancer patients. A holistic, but short measure should be used for physical and non-physical needs assessment. The Integrated Palliative care Outcome Scale is one such measure. This work aims to determine palliative needs of patients and explore screening accuracy of two items pertaining to psychological needs. Methods: multi-centred observational study using convenience sampling. Data were collected in 9 Portuguese centres. Inclusion criteria: ≥18 years, mentally fit to give consent, diagnosed with an incurable, potentially life-threatening illness. Exclusion criteria: patient in distress ("unable to converse for a period of time"), cognitively impaired. Descriptive statistics used for demographics. Receiving Operator Characteristics curves and Area Under the Curve for anxiety and depression discriminant properties against the Hospital Anxiety and Depression Scale. Results: 1703 individuals were screened between July 1st, 2015 and February 2016. A total of 135 (7.9%) were included. Main reason for exclusion was being healthy (75.2%). The primary care centre screened most individuals, as they have the highest rates of daily patients and the majority are healthy. Mean age is 66.8 years (SD 12.7), 58 (43%) are female. Most patients had a cancer diagnosis 109 (80.7%). Items scoring highest (=4) were: family or friends anxious or worried (36.3%); feeling anxious or worried about illness (13.3%); feeling depressed (9.6%). Using a cut-off score of 2/3, Area Under the Curve for depression and anxiety items were above 70%. Conclusions: main palliative needs were psychological, family related and spiritual. This suggests that clinical teams may better manage physical issues and there is room for improvement regarding non-physical needs. Using the Integrated Palliative care Outcome Scale systematically could aid clinical teams screening patients for distressing needs and track their progress in assisting patients and families with those issues. Trial Registration: Not applicable. This was not an intervention study.
Impact of Eastern Congo Ebola Outbreak on Child Health Services Delivery: Decline of Routine Child Immunization and Need for Vaccine Supplementation
Authors: Michel-Kabamba Nzaji , Christophe-Luhata Lungoyo , Ngatu Nlandu Roger , Othepa Charlotte , Bertin-Lora Mwimba , Arsene-Kabwaya Mukola , Bateyi Stephane H. , Hoff Nicole A. , Leon-Kabamba Ngombe , Muzembo Basilua Andre , Wada Koji , Ikeda Shunya , Mukamba Elisabeth , Guillaume-Ngoie Mwamba , Oscar-Luboya Numbi
Published: December 2019

Background An Ebola disaster, the deadliest in the history of Ebola in the Democratic Republic of Congo (DRC), is unfolding in North Kivu and Ituri provinces. An interdisciplinary research team investigated the impact of the Ebolavirus disease (EVD) outbreak on vital health services delivery under the coordination of DRC National Vaccination Program, Ministry of Health. We report on the impact of the ongoing Eastern Congo EVD outbreak on routine child immunization in the EVD-affected in North Kivu province, DRC. Methods This was a retrospective longitudinal study consisting in a time-trend analysis that was conducted in 40 public health facilities that organize routine child immunization in four of the 34 ‘Health Zones’ of the North Kivu province, namely Beni, Butembo, Katwa and Mabalako. Data were collected during two distinct 3-month periods: the “pre-Ebola period” (1 May through July 2018) and the “Ebola period” (1 August through October 2018), to compare the vaccination trends. Mean number of vaccine doses administered in pre-Ebola and Ebola periods were compared (unpaired t test). Results Compared to the “pre-Ebola period”, overall monthly mean vaccines uptake dropped during the “Ebola period”: BCG (157.1 ± 150.3 vs. 227.5 ± 138.4; p<0.0001), Oral polio (OPV: 505.1 ± 474.6 vs. 631.3 ± 353.9; p<0.001), Measles vaccine (147.6 ± 126.7 vs. 184.7 ± 102.5; p<0.001), pneumoccocal vaccine (PCV13: 445.8 ± 395.5 vs. 554.3 ± 299.8; p<0.001) and inactivated polio vaccine (IPV: 183.9 ± 141 vs. 153.9 ± 146.6; p<0.01). Furthermore, when considering the trend in child immunization in each of the four Health Zones during ‘Ebola period’, vaccine uptake shrank considerably in most health zones, whereas a complete disruption of vaccine delivery was observed in Mabalako health zone where the epicenter of this outbreak is located. Conclusion The ongoing Ebola outbreak has a negative impact on child health services, routine vaccination in particular. Supplementary immunization coupled with the strengthening of routine child vaccination services should be implemented to address gaps in immunity among children in affected provinces and reduce the risk of other infectious diseases outbreaks. Keywords: Democratic Republic of Congo; Ebola virus disease; Child immunization; Outbreak.
Time to recovery from moderate acute malnutrition and its predictors among 6-59 months children targeted for supplementary feeding in Shalla District, West Arsi Zone, Ethiopia,2018.
Authors: sadeta kebede kumsa , silassie Wondwosen Tekle
Published: December 2019

Background-Globally, acute malnutrition accounts for >50% cases of childhood mortality in under 5 children each year. Moderate acute malnutrition treatment would be to reduce child mortality and morbidity. Study done in Ethiopia showed treatment food share, lack of water and other factor suggested to cause lower chance of recovery at end of 16 week as per Ethiopian acute malnutrition treatment guide line . Methods- Retrospective cohort study design was conducted among children aged 6–59 months which were treated in targeted supplementary feeding program . A total of 402 children were selected from eight health posts by systematic random sampling. Data were collected by reviewing registration records and interview from January 1-10/2018. Data were analyzed using SPSS version 20, bivariate and multivariate statistical methods were used to analyze and describe the data and p < 0.05 was considered as significant. Results-the overall average timely recovery was 15 week (SD , 3.3). Children treated by super cereal were 2.44 times more likely to recover timely than children treated by corn soybean blend (AHR 2.44; 95% CI 1.85-3.21). Children that had regular follows up has 48% (AHR 1.48; 95% CI 1.09-2.00) more chance of recovery than intermittent treatment follow up, children’s from sever food in secured family had 51% lower chance to recover than moderate food insecured house hold (AHR 0.49; 95% CI 0.21-0.11) and, admission MUAC³11 . 6 cm had 1.18 times higher proportion of recovery than admission MUAC = 11.5 cm (AHR 1.18; 95% CI 1.13-1.12). Children who have no transport access has 2 times lower proportion of recovery than who have access (AHR 0.5; 95% CI 0.38-0.64). Conclusion- the mean time to recovery was 15 week which is consistent with the national standard 16 weeks. Type of treatment foods, treatment follow up status, and admission mid upper arm circumference had significant association with time recovery moderate acute malnutrition treatment. Keyword : -Time to recovery , targeted supplementary feeding, and moderate acute malnutrition
Does potentially inappropriate prescribing predict an increased risk of admission to hospital and mortality? A longitudinal study of the ‘oldest old’.
Authors: Cardwell Karen , Kerse Ngaire , Hughes Carmel M. , Teh Ruth , Moyes Simon A. , Menzies Oliver , Rolleston Anna , Broad Joanna B. , Ryan Cristín
Published: December 2019

Background: Potentially inappropriate prescribing (PIP) is associated with negative health outcomes, including hospitalisation and mortality. Life and Living in Advanced Age: a Cohort Study in New Zealand (LiLACS NZ) is a longitudinal study of Māori (the indigenous population of New Zealand) and non-Māori octogenarians. Health disparities between indigenous and non-indigenous populations are prevalent internationally and engagement of indigenous populations in health research is necessary to understand and address these disparities. Using LiLACS NZ data, this study reports the association of PIP with hospitalisations and mortality prospectively over 36-months follow-up. Methods: PIP, from pharmacist applied criteria, was reported as potentially inappropriate medicines (PIMs) and potential prescribing omissions (PPOs). The association between PIP and hospitalisations (all-cause, cardiovascular disease-specific and ambulatory-sensitive) and mortality was determined throughout a series of 12-month follow-ups using binary logistic (hospitalisations) and Cox (mortality) regression analysis, reported as odds ratios (ORs) and hazard ratios (HRs), respectively, and the corresponding confidence intervals (CIs). Results: Full demographic data were obtained for 267 Māori and 404 non-Māori at baseline, 178 Māori and 332 non-Māori at 12-months, and 122 Māori and 281 non-Māori at 24-months. The prevalence of any PIP (i.e. ≥1 PIM and/or PPO) was 66%, 75% and 72% for Māori at baseline, 12-months and 24-months, respectively. In non-Māori, the prevalence of any PIP was 62%, 71% and 73% at baseline, 12-months and 24-months, respectively. At each time-point, there were more PPOs than PIMs; at baseline Māori were exposed to a significantly greater proportion of PPOs compared to non-Māori (p=0.02). In Māori: PPOs were associated with a 1.5-fold increase in hospitalisations and mortality. In non-Māori, PIMs were associated with a double risk of mortality. Conclusions: PIP was associated with an increased risk of hospitalisation and mortality in this cohort. Omissions appear more important for Māori in predicting hospitalisations, and PIMs were more important in non-Māori in predicting mortality. These results suggest understanding prescribing outcomes across and between population groups is needed and emphasises prescribing quality assessment is useful.
Dissociated responses at initial computed tomography evaluation is a good prognostic factor in non-small cell lung cancer patients treated with anti-program cell death-1/ligand 1 inhibitors
Authors: Tozuka Takehiro , Kitazono Satoru , Sakamoto Hiroaki , Yoshida Hiroshi , Amino Yoshiaki , Uematsu Shinya , Yoshizawa Takahiro , Hasegawa Tsukasa , Uchibori Ken , Yanagitani Noriko , Horiike Atsushi , Horai Takeshi , Seike Masahiro , Gemma Akihiko , Nishio Makoto
Published: December 2019

Background: Dissociated responses (DR) are phenomena in which some tumors shrink, whereas others progress during treatment of patients with cancer. The purpose of the present study was to evaluate the frequency and prognosis of DR in non-small cell lung cancer (NSCLC) patients treated with anti-program cell death-1/ligand 1 (anti-PD-1/L1) inhibitors. Methods: This retrospective study included NSCLC patients who received anti-PD-1/L1 inhibitor as second- or later-line treatment. We excluded patients without radiological evaluation. In patients who showed progressive disease (PD) according to the RECIST 1.1 at the initial CT evaluation, we evaluated all measurable lesions in each organ to identify DR independently of RECIST 1.1. We defined DR as a disease with some shrinking lesions as well as growing or emerging new lesions. Cases not classified as DR were defined as ‘true PD’. Overall survival was compared between patients with DR and those with true PD using Cox proportional hazards models. Results: The present study included 62 NSCLC patients aged 27–82 years (median: 65 years). DR and true PD were observed in 11 and 51 patients, respectively. The frequency of DR in NSCLC patients who showed PD to anti-PD-1/L1 was 17.7%. Median overall survival was significantly longer in patients with DR versus true PD (14.0 vs. 6.6 months, respectively; hazard ratio for death: 0.40; 95% confidence interval: 0.17–0.94). Conclusions: Patients with DR exhibited a relatively favorable prognosis.
Evaluation of in vivo adhesiveness of hyaluronic acid combined with xanthan gum and carbomer [Karos® throat lozenges] to the oral cavity mucosa in human healthy subjects: a pilot study
Authors: Bandiera Giorgio , Talamonti Rita , Piccolino Gianmarco , Micaloni Andrea , Raffa Salvatore
Published: December 2019

Objective: The use of a hyaluronic acid-based product has the potential to improve the hydration status of the mucous membranes, especially in the oral cavity. This study has evaluated the in vivo adhesiveness of a product based on hyaluronic acid combined with xanthan gum and carbomer to the oral cavity mucosa in human healthy subjects. The product was administered to 10 healthy volunteers during two tests: in the first participants were asked to abstain from drinking and eating for the duration of the test; in the second participants were free to follow their daily routine. In both tests, samples were taken by brushing the oral cavity immediately after administration of the product, and then after each hour, up to 4 hours. A qualitative and quantitative analysis of the drug was carried out by observation of the samples stained with Alcian Blue at pH 2.5. Results: In both tests the analysis demonstrated the presence of the product in all collected samples, up to 4 hours after administration of the product, confirming that the combination of hyaluronic acid with xanthan gum and carbomer can provide a long-lasting, durable mucoadhesive hydrogel.Keywords: Adhesiveness, carbomer, hyaluronic acid, oral cavity mucosa, xanthan gum.
Clinical analysis of bloodstream infection of Escherichia coli in patients with pancreatic cancer
Authors: Bai Changsen , Zhang Xiuse , Yang Dong , Li Ding , Zhang Wenfang , Zhou Yunli , Zhang Qing , Zheng Shan , Ren Li , Li Yueguo
Published: December 2019

Background To study the common pathogens and cancer types of bloodstream infection (BSI) in cancer patients, find the risk factors and conduct clinical analysis.Methods The clinical data of 2302 patients with BSI in Tianjin Medical University Cancer Institute and Hospital (TMUCIH) from January 2011 to December 2018 were retrospectively analyzed. 31 pancreatic cancer patients complicated with Escherichia coli BSI and 93 pancreatic cancer patients without BSI at the same period with similar sex and age were divided into infection group and non-infection group.Results 645 strains (28%) of Escherichia coli were the main pathogens causing BSI in patients with cancer. 57 cases (8.8%) of cancer patients with Escherichia coli BSI were from pancreatic oncology department, among which 31 cases were diagnosed as pancreatic cancer by pathology. Multivariate logistic regression analysis showed that hospitalization days≥7, chemotherapy and neutrophil>5.5×10 9 /L were independent risk factors for pancreatic cancer patients complicated with BSI (P < 0.05). Quantitative analysis of serum-related indicators in infection patients and non-infection patients showed significant differences between albumin, prealbumin and neutrophils in infection and non-infection group. The ratio of Escherichia coli producing extended-spectrum ß-lactamase is 49.3 and 48.1 in pancreatic cancer and non-pancreatic patients. Escherichia coli resistant to carbapenems is rare, they were highly sensitive to Cephamycin and Piperacillin/tazobactam.Conclusions Escherichia coli, the main pathogen causing BSI of cancer patients, is more common in pancreatic cancer patients. The independent risk factors include hospitalization days≥7 days, chemotherapy and neutrophils larger than 5.5×10 9 /L. Quantitative indicators of neutrophil counts, albumin and prealbumin contribute to the early diagnosis of bloodstream infections. Early use of medication, while timely adjustment based on clinical drug sensitivity results will help reduce patient morbidity and mortality.
Interleukin (IL)-25 suppresses IL-22 induced osteoclastogenesis in rheumatoid arthritis via STAT3 and p38 MAPK/IκBα pathway
Authors: Min Hong Ki , Won Ji-Yeon , Kim Bo-Mi , Lee Kyung-Ann , Lee Seoung-Joon , Lee Sang-Heon , Kim Hae-Rim , Kim Kyoung-Woon
Published: December 2019

Background The present study aimed to evaluate the suppressive role of interleukin (IL)-25 in IL-22-induced osteoclastogenesis and receptor activator of nuclear factor κB ligand (RANKL) expression in rheumatoid arthritis (RA).Methods Serum from patients with RA and osteoarthritis (OA), and healthy controls, as well as synovial fluid from patients with RA and OA were collected, and the levels of IL-22 and IL-25 were measured. RA and OA synovial tissues were stained against IL-25. Fibroblast-like synoviocytes (FLSs) of patients with RA were cultured with IL-22, in the presence or absence of IL-25, and RANKL expression was measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured under IL-22/RANKL, with or without IL-25, and tartrate-resistant acid phosphatase (TRAP)-positive cells and osteoclast-related markers were investigated to determine osteoclastogenesis.Results Serum and synovial IL-25 levels in RA were up-regulated compared to those in OA and healthy control, and elevated expression of IL-25 in RA synovial tissue was re-confirmed. IL-25 and IL-22 levels showed significant correlation in serum and synovial fluid. Pre-treatment of FLS with IL-25 reduced IL-22-induced RANKL expression at the RNA level. The suppressive effects of IL-25 were confirmed to occur through the STAT3 and p38 MAPK/IκBα pathways. IL-25 reduced osteoclast differentiation and suppressed the expression of osteoclast-related markers.Conclusion In the current study, we demonstrated the regulatory effect of IL-25 on IL-22-induced osteoclastogenesis. Therapeutic approach involving augmentation of IL-25 regulatory response may serve as a novel treatment option for RA, especially by suppressing osteoclastogenesis.
MiR-21-5p regulates extracellular matrix degradation and angiogenesis in TMJOA by targeting Spry1.
Authors: Ma Shixing , Zhang Aobo , Li Xiaole , Zhang Shizhou , Liu Shaopeng , Zhao Haoming , Wu Shichao , Chen Lei , Ma Chuan , Zhao Huaqiang
Published: December 2019

Background: Due to the lack of research on the pathological mechanism of temporomandibular joint osteoarthritis (TMJOA), there are few effective treatment measures in the clinic. In recent years, microRNAs (miRs) have been demonstrated to play an important role in the pathogenesis of osteoarthritis (OA) by regulating a variety of target genes, and the latest evidence shows that miR-21-5p is specifically overexpressed in OA. The purpose of this project was to clarify whether miR-21-5p can regulate the TMJOA process by targeting Spry1.Methods: TMJOA was induced by a unilateral anterior crossbite (UAC) model, and the effect of miR-21-5p knockout on TMJOA was evaluated by toluidine blue and immunohistochemical staining. Primary mouse condylar chondrocytes (MCCs) were isolated, cultured and transfected with a series of mimics, inhibitors, siRNA-Spry1 or cDNA Spry1. Western blotting, RT-qPCR, immunofluorescence staining, and toluidine blue staining were used to detect the effect of miR-21-5p and its target gene Spry1 on the expression of MMP-13, VEGF and p-ERK1/2 in TMJOA. The effect of miR-21-5p on angiogenesis was evaluated by chick embryo CAM assay and Western blotting.Results: In the UAC model, the cartilage thickness and extracellular matrix of miR-21-5p knockout mice were less damaged. Luciferase experiments confirmed that Spry1 was the direct target of miR-21-5p. The expression levels of Spry1, MMP-13, VEGF and p-ERK1/2 in MCCs transfected with miR-21-5p mimic were higher than those in the inhibitor group. Under the simulated inflammatory environment of IL-1β, the expression levels of MMP-13, VEGF and p-ERK1/2 were positively correlated with miR-21-5p, while Spry1 was negatively correlated with miR-21-5p. Inhibition of miR-21-5p expression and overexpression of Spry1 enhanced the inhibition of MMP-13, VEGF and p-ERK1/2 expression. MiR-21-5p had a significant role in promoting angiogenesis in the chick embryo CAM assay, and this role was clearly mediated by the ERK-MAPK signalling pathway.Conclusion: This study verified that miR-21-5p can promote the process of TMJOA by targeting Spry1, which provides a new direction for future research on the treatment of this disease.
The Devils Hole pupfish gut microbiome and its potential role in paradoxical anaerobism
Authors: Bhute Shrikant S , Escobedo Brisa , Haider Mina , Mekonen Yididya , Ferrer Dafhner , Hillyard Stanley D. , Friel Ariel D , Breukelen Frank van , Hedlund Brian P.
Published: December 2019

Background The Devils Hole Pupfish ( Cyprinodon diabolis ) frequently enters paradoxical anaerobism in response to endogenously produced or exogenously supplied ethanol in a dose-dependent manner. To decipher the role of the gut microbiota in ethanol-associated paradoxical anaerobism, gut microbial communities were depleted using a cocktail of antibiotics and profiled using 16S rRNA gene sequencing. Results Compared to the control group (n=12), microbiota-depleted fish (n=11) spent more time in paradoxical anaerobism. Our analysis indicated that the bacterial phyla Proteobacteria , Fusobacteria , Bacteroidetes , Firmicutes , Actinobacteria , Patescibacteria , and Dependentiae dominated the pupfish gut, which is consistent with other fish gut microbiota. Although the gut microbial communities with and without antibiotic treatment were similarly diverse, they were distinct and the greatest contribution to the dissimilarity (27.38%) was the common fish commensal Cetobacterium . We speculate that Cetobacterium , a primary fermenter, also consumes ethanol through secondary fermentation via an alcohol dehydrogenase and therefore regulates the transition from paradoxical anaerobism to aerobic respiration in fish. Conclusions This study reports the first characterization of gut microbial communities of critically endangered pupfish and suggests the microbiome may play a critical role in regulating metabolic strategies that are critical for survival in extremes of temperature and oxygen concentration. Given the wide distribution and abundance of Cetobacterium in warm-water fishes, this process may be of broad importance, and suggests that the microbiome be carefully considered for both conservation and aquaculture.
Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response after Out-of-Hospital Cardiac Arrest (IMICA): study protocol for a randomized clinical trial
Authors: Meyer Martin A. S. , Wiberg Sebastian , Grand Johannes , Kjaergaard Jesper , Hassager Christian
Published: December 2019

Background: Resuscitated out-of-hospital cardiac arrest (OHCA) patients who remain comatose at admission are at high risk of morbidity and mortality. This has been attributed to the post-cardiac arrest syndrome (PCAS) which encompasses multiple interacting components, including systemic inflammation. Elevated levels of circulating interlukin-6 (IL-6), a pro-inflammatory cytokine, is associated with worse outcomes in OHCA patients, including, higher vasopressor requirements and higher mortality rates. For other indications, an IL-6 receptor antibody, tocilizumab has been approved. In this study we aim to reduce systemic inflammation after OHCA by administering a single infusion of tocilizumab. Methods: Investigator-initiated, randomized, double blind, placebo-controlled clinical trial in OHCA patients remaining unconscious after hospital admission. Intervention: Intravenous administration of an interleukin-6 receptor antibody (IL-6RA), tocilizumab, or placebo after admission. Primary endpoint: reduction in C-reactive protein (CRP). Secondary endpoints (abbreviated): cytokine levels, markers of brain, cardiac, kidney and liver damage, and hemodynamic and haemostatic function, adverse events, as well as follow-up assessment of cerebral function and mortality. Discussion: We hypothesise that reducing the effect of circulating IL-6 by administering an IL-6 receptor antibody will mitigate the systemic inflammatory response and thereby modify the severity of PCAS, in turn leading to decreased need of vasopressor support, more normal hemodynamics, as well as better organ function. A previous trial of IL6-RA in patients with non-ST elevation myocardial infarction showed a reduction in CRP and troponin levels, as well as a change in cytokine levels. Following these findings, we will be measuring a range of both pro-inflammatory and anti-inflammatory cytokines to possibly reveal a change in cytokine patterns following blockage of the IL-6 receptor, as well as investigate whether IL-6RA leads to reduced organ damage. Infection after OHCA is not uncommon and IL6-RA has previously been shown to increase the frequency of infections. Accordingly, we will monitor for infections, and patients will be treated with prophylactic antibiotics. Trial registration: ClinicalTrials.gov Identifier: NCT03863015; submitted February 22 2019, first posted March 5, 2019. EudraCT: 2018-002686-19; First entered August 10 2019.
The SPARKLE registry: a multicenter, multinational, noninterventional, prospective cohort registry study in patients with alpha-mannosidosis
Authors: Hennermann Julia , Guffon Nathalie , Cattaneo Federica , Ceravolo Ferdinando , Borgwardt Line , Lund Allan M. , Gil-Campos Mercedes , Tylki-Szymanska Anna , Muschol Nicole M.
Published: December 2019

Background Alpha-mannosidosis is a lysosomal storage disorder caused by reduced enzymatic activity of alpha-mannosidase. Intracellular accumulation of mannose-rich oligosaccharides leads to a continuum of various heterogeneous clinical symptoms. Velmanase alfa (Lamzede®) is a human recombinant alpha-mannosidase approved in Europe in 2018 as the first enzyme replacement therapy for the treatment of non-neurologic manifestations in patients with mild-to-moderate alpha-mannosidosis. SPARKLE is an alpha-mannosidosis registry study intended to obtain long-term safety and effectiveness data on the use of velmanase alfa during routine clinical care in patients with alpha-mannosidosis and is a post-approval commitment to European marketing authorization. In addition, SPARKLE will expand the current understanding of alpha-mannosidosis by collecting data on the clinical manifestations, progression, and natural history of the disease in treated and untreated patients, respectively. Results SPARKLE is a post-authorization safety and efficacy registry designed as a multicenter, multinational, noninterventional, prospective cohort study of patients with alpha-mannosidosis, starting in 2020. Patients will be followed for up to 15 years. Safety and effectiveness outcomes under routine clinical care will be evaluated. The primary safety outcomes are the rate of adverse events (anti-velmanase alfa-immunoglobulin G antibody development, infusion-related reactions, and hypersensitivity). Secondary safety outcomes include the evaluation of medical events, change in vital signs, laboratory tests, physical examination, and electrocardiogram results. The primary effectiveness outcome is a global treatment response rate, evaluated as the individual aggregate of single endpoints from pharmacodynamic, functional, and quality of life effectiveness outcomes; secondary effectiveness outcomes are to characterize the population of patients with alpha-mannosidosis with regard to clinical manifestation, progression, and natural history of the disease. Any patient in the European Union with a diagnosis of alpha-mannosidosis who is willing to participate will likely be eligible for inclusion in the registry. Publications to disseminate scientific insights from the registry are planned. Conclusion This study will provide real-world data on the long-term safety and effectiveness of velmanase alfa in patients with alpha-mannosidosis during routine clinical care and increase the understanding of the natural course, clinical manifestations, and progression of this ultra-rare disease.
Malaria Knowledge and Experiences with Community Health Workers among Recently Pregnant Women in Malawi
Authors: Malpass Ashley , Chinkhumba Jobiba , Davlantes Elizabeth , Munthali John , Wright Katherine , Ramsey Kathryn , Troell Peter , Kayange Michael , Kachale Fannie , Mathanga Don P. , Chatata Dziko , Gutman Julie R
Published: December 2019

Background The World Health Organization (WHO) recommends three or more doses of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) to mitigate the negative effects of malaria in pregnancy (MIP). Many pregnant women in Malawi are not receiving the recommended number of doses. Community delivery of IPTp (cIPTp) is being piloted as a new approach to increase coverage. This survey assessed recently pregnant women’s knowledge of MIP and their experiences with community health workers (CHWs) prior to implementing cIPTp.Methods Data were collected via a household survey in Ntcheu and Nkhata Bay Districts, Malawi, from women aged 16-49 years who had a pregnancy resulting in a live birth in the previous 12 months. Survey questions were primarily open response and utilized review of the woman’s health passport whenever possible. Analyses accounted for selection weighting and clustering at the health facility level and explored heterogeneity between districts.Results A total of 370 women were interviewed. Women in both districts found their CHWs to be helpful (77.9%), but only 35.7% spoke with a CHW about antenatal care and 25.8% received assistance for malaria during their most recent pregnancy. A greater proportion of women in Nkhata Bay than Ntcheu reported receiving assistance with malaria from a CHW (42.7% vs 21.9%, p=0.01); women in Nkhata Bay were more likely to cite IPTp-SP as a way to prevent MIP (41.0% vs 24.8%, p=0.02) and were more likely to cite mosquito bites as the only way to spread malaria (70.6% vs 62.0% p=.03). Women in Nkhata Bay were more likely to receive 3+ doses of IPTp-SP (IPTp3) (59.2% vs 41.8%, p=0.0002). Adequate knowledge was associated with increased odds of receiving IPTp3, although not statistically significantly so (adjusted odds ratio = 1.50, 95% confidence interval 0.97- 2.32, p-value 0.066).Conclusions Women reported positive experiences with CHWs, but there was not a focus on MIP. Women in Nkhata Bay were more likely to be assisted by a CHW, had better knowledge, and were more likely to receive IPTp3+. Increasing CHW focus on the dangers of MIP and implementing cIPTp has the potential to increase IPTp coverage. Keywords: Malaria Pregnancy Community Health Workers Malawi Intermittent preventive treatment Sulfadoxine-pyrimethamine
Linking insecticide mosquito nets to malaria: the roles of malaria Knowledge and household-income
Authors: Mohammed Mohammed Aliye , Hong Tao
Published: December 2019

Background: Drawing on the theory of the health belief model, this study examined the interplay of insecticide mosquito nets, malaria-knowledge, household income, and malaria. The study premised on the notion that insecticide mosquito nets proposed to be positively related to malaria, and knowledge was proposed to mediate the relationship between insecticide mosquito nets and malaria. Furthermore, household-income was anticipated to have a moderating effect on the direct and indirect relationships (through malaria knowledge) between insecticide mosquito nets and malaria. Methods: The hypothesized relationships were examined using the panel data collected from 10 regions of Ethiopia during 2011 – 2015. Structural equation modeling and random effect model used to test the articulated hypothesis. Statistical analyses were performed using Stata version 13.0. Results: The results were consistent with our proposed hypotheses, showing a significant and positive relationship between the research variables. Accordingly, our estimate suggests that malaria knowledge contributed to improving insecticide mosquito nets and malaria disease relationships. The result revealed a significant and positive effect (β = 0.47, p = 0.003) of the indirect effect where the direct effect coefficient is also positive (β = 0.28, p = 0.001). The study also reported a positive impact of household-income in strengthening the relationship between insecticide mosquito nets and malaria via knowledge with considerable value (β = 0.13, p = 0.000). Conclusion: The findings are potentially useful for the health sector to assure the success regarding infectious disease prevention and control, particularly malaria, explaining how such factors contribute to the relationship.
Secondary school students’ awareness of contraceptive methods, understanding of HIV/AIDS prevention and perception of HIV/AIDS risk in Dar es Salaam, Tanzania
Authors: Mika Nishihara , Sebalda Leshabari , Junichi Tanaka , Ohnishi Mayumi
Published: December 2019

Background To assess awareness of contraceptive methods, understanding of HIV/AIDS prevention and perception of HIV risk among secondary school students in Tanzania. Methods An anonymous self-administered questionnaire survey was conducted among secondary school students in 2017 in Tanzania. The questionnaire included sociodemographic characteristics, awareness of contraceptive methods, understanding of HIV/AIDS prevention and perception of HIV/AIDS risk. Three secondary schools in Dar es Salaam were selected considering gender balance and location, which included urban and surrounding areas. After the research objectives, methods and ethical considerations were explained, the students voluntarily completed and submitted the questionnaire in the designated place. Submission of the questionnaire was considered agreement to participate in the study. Results A total of 233 responses were collected, and 204 responses were valid for the analysis. The mean and standard deviation of age were 18.5 ± 1.0. Spearman’s rank correlation coefficient between understanding of HIV/AIDS prevention and perception of HIV/AIDS risk was ρ=0.184 (P=0.036). However, there was no correlation between awareness of contraceptive methods and understanding of HIV/AIDS prevention (ρ=0.019, P=0.782) or perception of HIV/AIDS risk (ρ=-0.138 P=0.116). Regardless of gender, age, religion, and major course of study, mother’s educational status (β=0.150, P=0.031 and β=0.232, P=0.034, respectively) and the number of information sources (β=0.584, P<0.001 and β=-0.311, P=0.006, respectively) demonstrated associations with awareness of contraceptive methods and perception of HIV/AIDS risk. Respondents who lived outside of a dormitory (β=0.295, P=0.001) and currently had a partner (β=0.243, P=0.009) demonstrated a higher understanding of HIV/AIDS prevention regardless of gender, age, religion, and major course of study. Conclusions The factors associated with awareness of contraceptive methods, understanding of HIV/AIDS prevention and perception of HIV/AIDS risk were not consistent. To improve awareness of contraceptive methods, understanding of HIV/AIDS prevention and perception of HIV/AIDS risk among secondary school students, educational programs should be integrated and holistically provided as sexual health education.
Zika outbreak, resilient health systems, and women’s sexual and reproductive health: a qualitative study in Colombia
Authors: Rivillas-García Juan Carlos , Forero-Martinez Luz Janeth , Calderon-Jaramillo Mariana , Vargas-Pinzón Victoria , Murad-Rivera Rocío , Perez Freddy
Published: December 2019

Background There is substantial evidence of the profound consequences of Zika on women's Sexual and Reproductive Health. Health system resilience begins by measuring critical capacities ahead of a crisis such as zika outbreak. Even though zika as vector-borne disease is well documented, there is dearth of studies linking Zika with women's Sexual and Reproductive Health. The main objective of this study was to analyze the national response to the Zika epidemic and its relation to women’s sexual and reproductive health matters through key implementation mechanisms in order to promote resilience of the health system in five cities in Colombia.Methods This study used a qualitative design to enable an in-depth exploration of the national response to the Zika epidemic and sexual and reproductive health matters through key implementation mechanisms (based on facilitators and gaps) within the health system. The overall data set was comprised of 31 semi-structured individual interviews (23 women and 8 men), 25 interviews with key informants responsible for the implementation of the Zika Virus Response Plan; six interviews with pregnant women diagnosed with Zika; and five focus groups discussions with communities (n=122 participants) in five cities in Colombia: Barranquilla, Cucuta, Los Patios, San Andres and Soledad.Results The findings revealed the three major facilitators that promoted the implementation of actions to address the Zika epidemic: i) the role of health care providers; ii) the development of technical equipment capabilities; and iii) inter-institutional coordination. The study also identified implementation gaps: i) absence of a human rights and sexual and reproductive health approach; ii) focus on territorial actions centered on mosquito management; and iii) limited attitudes, behaviors and knowledge at the community level.Conclusion This study provided a comprehensive insight of critical facilitating processes and gaps in the implementation of the government response during the Zika epidemic in Colombia. This study reveals that the lack of understanding of the intersection between gender, the Zika epidemic and Sexual and Reproductive Health limited the adoption, development and implementation of a more comprehensive responses to address the impact on women’s sexual and reproductive health.
Comparisons of clinical characteristics of lens-subluxated eye with or without acute angle closure: A retrospective study
Authors: Zhang Hong-Yang , Lin Hong-Liang , Qin Yong-Jie , Zhang Yu-Lin , Zhang Yu-Qiao , Niu Yong-Yi , Chen Yan-Lei , Hu Yun-Yan , Xie Wen-Juan
Published: December 2019

BackgroundTo compare clinical characteristics of lens subluxation between eyes with or without acute angle closure (AAC).MethodsThis is a retrospective and case control study. Thirty-four cases with lens subluxation were recruited from 2015 to 2017. Patients with acute angle closure were assigned to the AAC group (n=17 eyes) and those without AAC were in the non-AAC group (n=17 eyes). Quantitative anterior segment was evaluated by ultrasound biomicroscopy (UBM). Axial length (AL) was measured with IOL master. All patients underwent lens extraction surgery and were followed up for 6 months. ResultsThe history of blunt trauma was accounted for 11 (64.7%) cases in the AAC group and 14 (82.3%) cases in the non-AAC group. Nine (52.9%) patients in the AAC group had LPI or SPI treatment history, and high intraocular pressure was recurred. The UBM analysis showed that the average central ACD of affected eyes in the AAC group was 1.75 mm, which was significantly shallower than the fellow eyes (2.39 mm, P < 0.05) or both eyes in the non-AAC group (affected eye 3.24mm vs fellow eye 3.81mm). Lens vault and AOD500 also showed a remarkable difference between affected eye than fellow eye (P < 0.001) in the AAC group. The both eyes in the AAC group presented a shorter AL and shallower anterior chamber, comparing with those in the non-AAC group. Besides, the affected eyes in the AAC group presented significantly higher LV. ConclusionsThe crowded anterior chamber structure and shorter AL might be an anatomic basis for the eye with lens subluxation induced AAC. Quantitative evaluation of these ocular structures to identify zonular compromise, increased LV and shorter AL are valuable for the diagnosis of lens subluxation induced AAC.
Invasive cattle ticks in East Africa: morphological and molecular confirmation of the presence of Rhipicephalus microplus in south-eastern Uganda
Authors: Muhanguzi Dennis , Byaruhanga Joseph , Amanyire Wilson , Ndekezi Christian , Ochwo Sylvester , Nkamwesiga Joseph , Mwiine Frank Nobert , Tweyongyere Robert , Fourie Josephus , Madder Maxime , Schetters Theo , Ivan Ivan , Juleff Nick , Jongejan Frans
Published: December 2019

Background: Rhipicephalus microplus; an invasive tick species of Asian origin and the main vector of Babesia species, is considered one of the most widespread ectoparasites of livestock. The tick has spread from its native habitats on translocated livestock to large parts of the tropical world, where it has replaced some of the local populations of Rhipicephalus decoloratus ticks. Although the tick was reported in Uganda 70 years ago, it has not been found in any subsequent surveys. This study was carried out to update the national tick species distribution on livestock in Uganda as a basis for tick and tick-borne disease control, with particular reference to R.microplus.Methods: The study was carried out in Serere district, south-eastern Uganda, which is dominated by small scale livestock producers. All the ticks collected from 240 cattle were identified microscopically. Five R. microplus specimens were further processed for phylogenetic analysis and species confirmation.Results: The predominant tick species found on cattle was Rhipicephalus appendiculatus (86.9 %; n=16,509). Other species found were Amblyomma variegatum (7.2 %; n=1,377), Rhipicephalus evertsi (2.3 %; n=434) and R. microplus (3.6 %; n= 687). Phylogenetic analysis of the 12S rRNA, 16S rRNA and ITS2 gene sequences of R. microplus confirmed the morphological identification.Conclusions : It is concluded that R. microplus has replaced Rhipicephalus decoloratus, since the latter was not any longer found in this area. There is currently no livestock movement policy in force in Uganda, which could possibly limit the further spread of R. microplus ticks. Future surveys, but also retrospective surveys of museum specimens, will reveal the extent of distribution of R. microplus in Uganda and also for how long this tick has been present on livestock without being noticed.
Factors affecting under-five mortality in Ethiopia: a multi-level negative binomial model
Authors: Geremew Bisrat Misganew , Gelaye Kassahun Alemu , Melesse Alemakef Wagnew , Akalu Temesgen Yihunie , Baraki Adhanom Gebreegziabher
Published: December 2019

Introduction: Under-five mortality is a key indicator of countries’ developmental status. Even though remarkable declines in under-five mortality rates, nearly 5.6 million children still die annually worldwide before their fifth birthday. The 2016 Ethiopian Demographic and Health Survey (EDHS) report revealed that 67 children per 1,000 live births died before the fifth birthday. This study was aimed at determining factors affecting under-five mortality in Ethiopia using EDHS, 2016.Methods: The data was retrieved from the EDHS 2016. A total weighted number of 11,023 under-five children were included in this study. Descriptive statistics were done and reported using tables, graphs, and texts. The multilevel negative binomial regression model was fitted to identify significant factors of under-five mortality. Adjusted Incidence rate (AIRR) with a 95% confidence interval (CI) and p-value <0.05 in the multivariable model were reported. The goodness of fit was checked using the deviance test.Results: Mother attained higher education (AIRR=0.25, 95% CI: 0.10-0.66); female-headed household (AIRR=1.32, 95%CI:1.05-1.66); age of household head (AIRR=1.07, 95%CI: 1.03,1.11); preceding birth interval ≥48 months (AIRR=0.51, 95%CI: 0.42-0.61); child’s had history of diarrhea (AIRR=1.23, 95% CI:1.08-1.41); multiple birth type (AIRR=1.80, 95% CI:1.34-2.42); mothers delivered in health facility (IRR=0.86, 95% CI:0.73,0.94), residents of Addis Ababa (AIRR=0.52, 95%CI: 0.28-0.98), and Amhara region (AIRR=1.43, 95%CI: 1.09, 1.88) were statistically significant factors to under-five mortality in Ethiopia.Conclusion: In this study, under-five mortality remains a public health problem in Ethiopia. Mothers education level, women delivered at health institution, preceding birth interval 24-35 and ≥48, and residents of Addis Ababa have reduced the incidence of under-five mortality. On the other hand, being a female household head, age of mother at first giving birth, being employment, having multiple births and having childhood diarrhea was associated with a higher incidence of under-five mortality. This finding suggests that enhancing opportunities to female education, addressing regional disparities, and encouraging mothers to deliver at health institutions will help to combat the burden of under-five mortality. Keywords: Under-five mortality, negative binomial, multilevel analysis, Ethiopia