bluuebunny/crossref_metadata_2025 huggingface dataset:
A randomized controlled efficacy trial of an mHealth HIV prevention intervention for sexual minority young men: MyPEEPS mobile study protocol
Authors: Kuhns Lisa M. , Garofalo Robert , Hidalgo Marco , Hirshfield Sabina , Pearson Cynthia , Bruce Josh , Batey D. Scott , Radix Asa , Belkind Uri , Jia Haomiao , Schnall Rebecca
Published: January 2020

Background

Young sexual minority men in the United States have a high incidence rate of HIV infection. Early intervention among this group, that is timed to precede or coincide with sexual initiation, is of critical importance to prevent HIV infection. Despite this, there are very few published randomized controlled efficacy trials testing interventions to reduce sexual vulnerability for HIV acquisition among racially/ethnically diverse, very young, sexual minority men (aged ≤18 years). This paper describes the design of a mobile app-based intervention trial to reduce sexual risk for HIV acquisition and promote health protection in this group.

Methods

This study is a randomized controlled trial of an mHealth-based HIV prevention intervention, MyPEEPS Mobile, among diverse sexual minority cisgender young men, aged 13–18 years. The mobile intervention was adapted from a prior group-based intervention curriculum with evidence of efficacy, designed to be specific to the risk contexts and realities of young sexual minority men, and to include psychoeducational and skill-building components with interactive games and activities. Participants are recruited locally within four regional hubs (Birmingham, AL, Chicago, IL, New York City, NY, Seattle, WA) and nationwide via the Internet, enrolled in-person or remotely (via videoconference), and randomized (1:1) to either the MyPEEPS Mobile intervention or delayed intervention condition. Post-hoc stratification by age, race/ethnicity, and urban/suburban vs. rural statuses is used to ensure diversity in the sample. The primary outcomes are number of male anal sex partners and frequency of sexual acts with male partners (with and without condoms), sex under the influence of substances, and uptake of pre-and post-exposure prophylaxis, as well as testing for HIV and other sexually transmitted infections at 3-, 6- and 9-month follow-up.

Discussion

Behavioral interventions for very young sexual minority men are needed to prevent sexual risk early in their sexual development and maturation. This study will provide evidence to determine feasibility and efficacy of a mobile app-based HIV prevention intervention to reduce sexual risk among this very young group.

Trial registration

ClinicalTrials.gov number, NCT03167606, registered May 30, 2017.
Community perspectives on barriers and challenges to HIV pre-exposure prophylaxis access by men who have sex with men and female sex workers access in Nigeria
Authors: Emmanuel G. , Folayan M. , Undelikwe G. , Ochonye B. , Jayeoba T. , Yusuf A. , Aiwonodagbon B. , Bilali C. , Umoh P. , Ojemeiri K. , Kalaiwo A.
Published: January 2020

Background

Men who have sex with men (MSM), female sex workers (FSW) have critical needs for effective HIV prevention tools. This study identified perspectives of MSM, FSW and policy makers on the needs for, barriers to, and challenges with pre-exposure HIV prophylaxis (PrEP); and the logistics required to support roll-out of PrEP for MSM and FSW in Nigeria.

Methods

Qualitative and quantitative data were collected through a cross-sectional study. The quantitative data were collected through an online survey administered to 519 MSM, FSW and transgender respondents. The qualitative data were collected through 22 focus group discussions with 140 MSM and 80 FSW, and a two-day consultative workshop with 65 participants. Two open-ended questions in the online survey were also a source of qualitative data. Results of the quantitative data were reported descriptively; the qualitative data were inductively examined with a content analytic approach to construct descriptive categories. The findings from the quantitative and qualitative responses were triangulated.

Results

Four hundred and ninety-four (95.2%) online respondents had heard about PrEP through community dialogue (71.3%), and 439 (84.6%) supported its use by MSM and FSW. Fewer than half of the respondents were aware of the clinical care required for PrEP, and misconceptions about PrEP were common. Stated barriers to PrEP uptake were stigma, cost, frequency of HIV counseling and treatment services required, and possible drug-drug interactions. Concerns included possible condom migration, increased risk for sexually transmitted infections and pregnancy for FSW, and poor adherence to medication and hospital schedules. Participants felt that trained peer educators and HIV-test counselors could provide information and refer clients to clinics that provide PrEP. PrEP can be provided through peer-led facilities for MSM and FSW, though its access should be expanded to all persons who are at substantial risk for HIV to prevent negative labeling of PrEP. Public awareness about the use of antiretrovirals for HIV prevention is needed to prevent labeling of PrEP users as being HIV positive.

Conclusion

Although MSM and FSW are interested in the use of PrEP, numerous individual and structural barriers need to be addressed to facilitate access to it in Nigeria.
Expert consensus on the development of a health-related questionnaire for the pediatric field of Korean medicine: a Delphi study
Authors: Lee Jihong , Lee Sun Haeng , Chang Gyu Tae
Published: January 2020

Background

Although a variety of patient-reported outcome measures (PROMs) for children have been developed, there is no pediatric PROM specific to Korean medicine (KM) that is validated by experts in the field. The aim of this study was to collate the opinions of specialists in KM pediatrics on the development of a generic PROM that can be used by Korean medical doctors to assess the health status of children.

Methods

A three-round Delphi survey was conducted to determine the level of consensus on the development of a new PROM. Delphi questionnaires were sent by e-mail to 91 KM pediatricians on January 24, 2018. The Delphi questionnaire was composed of four sections: conceptualization, construction, items, and sources of content for a PROM. A nine-point Likert scale was used, and if more than two-thirds of the panels agreed or disagreed with a given sentence, they were considered to have reached a consensus. A draft of a PROM for the pediatric field of KM was developed in accordance with the preliminary conceptual framework.

Results

Out of 91 experts, 18 finished three rounds of the Delphi survey. The experts reached a consensus on the necessity of a KM pediatric PROM for measuring various areas including child health, and using Likert scales with a recall period of 3 months. They also agreed on specific items and sources of content. A new draft of a health questionnaire for KM pediatrics was developed based on the Delphi consensus. It contains 44 items covering 7 domains: i) functions of the digestive system, ii) functions of the respiratory system, iii) mental functions, iv) skin functions, v) pain, vi) functions of the metabolic and endocrine systems, and vii) demographic details.

Conclusions

This research represents the first step in developing a health questionnaire for the pediatric field of KM. The questionnaire can be used in clinical and research settings after verifying several types of validity and reliability.
Simulated patient’s feedback to improve communication skills of clerkship students
Authors: Qureshi Ayesha Aleem , Zehra Tabassum
Published: January 2020

Background

The changing trends of the society and revisions to medical education have changed the way medical students are trained to adroitly care for patients hence, patient centered care has become need of today’s society and communication skills are imperative in developing patient physician relationship. Increasingly, simulations are being used to aid medical students to incorporate theoretical knowledge into practice. There are innumerable studies regarding communication skills in terms of reliability, validity and feasibility but no such study has been documented using simulated patient’s feedback in improving communication skills in Pakistan. The aim of this study is to explore whether simulated patients’ feedback improves the communication skills of undergraduate medical students.

Methods

During a randomized control trail a group of eighty students in the final year clerkship at Al-Nafees Medical College have participated in pre-post Objective Structured Clinical Exam (OSCE) on communication skills. The students were selected through convenience sampling technique. Four Objective Structured Clinical Exam (OSCE) stations based on different scenarios of communication skills were developed. Each station of fifteen minutes duration was assessed by both simulated patients and faculty using a validated tool LCSAS (Liverpool Communication Skills Assessment Scale). The difference between the pre and post-tests of two groups was explored by applying independent t-test. Cronbach’s alpha was used to check the reliability of scores and effect size was calculated.

Results

Results of this study have showed that there is significant improvement in communication skills after receiving feedback from simulated patients (pvalue ≤0.05) was observed. An overall Cronbach α = 0.83 on LCSAS reveal a high internal consistency and there was adequate demonstration of effect size(r = 0.8).

Conclusion

The results on the scores of the students on the Liverpool Communication Skills Assessment Scale confirm that simulated patient’s feedback is essential to enhance the communication skills of the medical students. This study offers significant evidence towards successful conduction of a formal communication skills development initiative at Al-Nafees Medical College using simulated patient feedback during teaching and assessments.
Amelioration of bleomycin-induced pulmonary fibrosis via TGF-β-induced Smad and non-Smad signaling pathways in galectin-9-deficient mice and fibroblast cells
Authors: Hsu Yu-An , Chang Ching-Yao , Lan Joung-Liang , Li Ju-Pi , Lin Hui-Ju , Chen Chih-Sheng , Wan Lei , Liu Fu-Tong
Published: January 2020

Background

Galectin-9 is a β-galactoside-binding protein with two carbohydrate recognition domains. Recent studies have revealed that galectin-9 regulates cellular biological reactions and plays a pivotal role in fibrosis. The aim of this study was to determine the role of galectin-9 in the pathogenesis of bleomycin-induced systemic sclerosis (SSc).

Methods

Human galectin-9 levels in the serum of patients with SSc and mouse sera galectin-9 levels were measured by a Bio-Plex immunoassay and enzyme-linked immunosorbent assay. Lung fibrosis was induced using bleomycin in galectin-9 wild-type and knockout mice. The effects of galectin-9 on the fibrosis markers and signaling molecules in the mouse lung tissues and primary lung fibroblast cells were assessed with western blotting and quantitative polymerase chain reaction.

Results

Galectin-9 levels in the serum were significantly higher (9-fold) in patients compared to those of healthy individuals. Galectin-9 deficiency in mice prominently ameliorated epithelial proliferation, collagen I accumulation, and α-smooth muscle actin expression. In addition, the galectin-9 knockout mice showed reduced protein expression levels of fibrosis markers such as Smad2/3, connective tissue growth factor, and endothelin-1. Differences between the wild-type and knockout groups were also observed in the AKT, mitogen-activated protein kinase, and c-Jun N-terminal kinase signaling pathways. Galectin-9 deficiency decreased the signal activation induced by transforming growth factor-beta in mouse primary fibroblasts, which plays a critical role in fibroblast activation and aberrant catabolism of the extracellular matrix.

Conclusions

Our findings suggest that lack of galectin-9 protects against bleomycin-induced SSc. Moreover, galectin-9 might be involved in regulating the progression of fibrosis in multiple pathways.
Azithromycin has enhanced effects on lung fibroblasts from idiopathic pulmonary fibrosis (IPF) patients compared to controls
Authors: Krempaska Kristina , Barnowski Sandra , Gavini Jacopo , Hobi Nina , Ebener Simone , Simillion Cedric , Stokes Andrea , Schliep Ronja , Knudsen Lars , Geiser Thomas K. , Funke-Chambour Manuela
Published: January 2020

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic fatal lung disease without a cure and new drug strategies are urgently needed. Differences in behavior between diseased and healthy cells are well known and drug response can be different between cells isolated from IPF patients and controls. The macrolide Azithromycin (AZT) has anti-inflammatory and immunomodulatory properties. Recently anti-fibrotic effects have been described. However, the anti-fibrotic effects on primary IPF-fibroblasts (FB) directly compared to control-FB are unknown. We hypothesized that IPF-FB react differently to AZT in terms of anti-fibrotic effects.

Methods

Primary normal human lung and IPF-FB were exposed to TGF-β (5 ng/ml), Azithromycin (50 μM) alone or in combination prior to gene expression analysis. Pro-collagen Iα1 secretion was assessed by ELISA and protein expression by western blot (αSMA, Fibronectin, ATP6V1B2, LC3 AB (II/I), p62, Bcl-xL). Microarray analysis was performed to screen involved genes and pathways after Azithromycin treatment in control-FB. Apoptosis and intraluminal lysosomal pH were analyzed by flow cytometry.

Results

AZT significantly reduced collagen secretion in TGF-β treated IPF-FB compared to TGF-β treatment alone, but not in control-FB. Pro-fibrotic gene expression was similarly reduced after AZT treatment in IPF and control-FB. P62 and LC3II/I western blot revealed impaired autophagic flux after AZT in both control and IPF-FB with significant increase of LC3II/I after AZT in control and IPF-FB, indicating enhanced autophagy inhibition. Early apoptosis was significantly higher in TGF-β treated IPF-FB compared to controls after AZT. Microarray analysis of control-FB treated with AZT revealed impaired lysosomal pathways. The ATPase and lysosomal pH regulator ATP6V0D2 was significantly less increased after additional AZT in IPF-FB compared to controls. Lysosomal function was impaired in both IPF and control FB, but pH was significantly more increased in TGF-β treated IPF-FB.

Conclusion

We report different treatment responses after AZT with enhanced anti-fibrotic and pro-apoptotic effects in IPF compared to control-FB. Possibly impaired lysosomal function contributes towards these effects. In summary, different baseline cell phenotype and behavior of IPF and control cells contribute to enhanced anti-fibrotic and pro-apoptotic effects in IPF-FB after AZT treatment and strengthen its role as a new potential anti-fibrotic compound, that should further be evaluated in clinical studies.
Use of the triglyceride-glucose index (TyG) in cardiovascular disease patients
Authors: Alizargar Javad , Bai Chyi-Huey , Hsieh Nan-Chen , Wu Shu-Fang Vivienne
Published: January 2020

Da Silva et al. showed that the triglyceride-glucose (TyG) index was positively associated with a higher prevalence of symptomatic coronary artery disease (CAD). TyG has been used in healthy individuals as a marker of insulin resistance. The use of this index as a marker of atherosclerosis in cardiovascular disease (CVD) patients might be influenced by diabetes and the hyperlipidemic state that led to CVD. Certain considerations might be necessary before we conclude that the TyG index can be used as a marker of atherosclerosis in CVD patients. These factors can highlight the role of fasting blood glucose and triglyceride levels that are used in the TyG formula. Comparing the fasting blood glucose and/or triglyceride levels with the TyG index in these patients to show how much value the TyG index can add to clinical practice seems to be necessary. Conclusions of such studies might be biased by these facts. Stratification by CAD disease category cannot help achieve an understanding of the role of TyG in CVD. Correlations do not imply causation, so the use of the TyG index as an index in CAD patients is questionable.
Sustainable microbial cell nanofactory for zinc oxide nanoparticles production by zinc-tolerant probiotic Lactobacillus plantarum strain TA4
Authors: Mohd Yusof Hidayat , Mohamad Rosfarizan , Zaidan Uswatun Hasanah , Rahman Nor’Aini Abdul
Published: January 2020

Background

The use of microorganisms in the biosynthesis of zinc oxide nanoparticles (ZnO NPs) has recently emerged as an alternative to chemical and physical methods due to its low-cost and eco-friendly method. Several lactic acid bacteria (LAB) have developed mechanisms in tolerating Zn2+ through prevention against their toxicity and the production of ZnO NPs. The LAB’s main resistance mechanism to Zn2+ is highly depended on the microorganisms’ ability to interact with Zn2+ either through biosorption or bioaccumulation processes. Besides the inadequate studies conducted on biosynthesis with the use of zinc-tolerant probiotics, the understanding regarding the mechanism involved in this process is not clear. Therefore, this study determines the features of probiotic LAB strain TA4 related to its resistance to Zn2+. It also attempts to illustrate its potential in creating a sustainable microbial cell nanofactory of ZnO NPs.

Results

A zinc-tolerant probiotic strain TA4, which was isolated from local fermented food, was selected based on the principal component analysis (PCA) with the highest score of probiotic attributes. Based on the 16S rRNA gene analysis, this strain was identified as Lactobacillus plantarum strain TA4, indicating its high resistance to Zn2+ at a maximum tolerable concentration (MTC) value of 500 mM and its capability of producing ZnO NPs. The UV–visible spectroscopy analysis proved the formations of ZnO NPs through the notable absorption peak at 380 nm. It was also found from the dynamic light scattering (DLS) analysis that the Z-average particle size amounted to 124.2 nm with monodisperse ZnO NPs. Studies on scanning electron microscope (SEM), energy-dispersive X-ray (EDX) spectroscopy, and Fourier-transform infrared spectroscopy (FT-IR) revealed that the main mechanisms in ZnO NPs biosynthesis were facilitated by the Zn2+ biosorption ability through the functional groups present on the cell surface of strain TA4.

Conclusions

The strong ability of zinc-tolerant probiotic of L. plantarum strain TA4 to tolerate high Zn2+ concentration and to produce ZnO NPs highlights the unique properties of these bacteria as a natural microbial cell nanofactory for a more sustainable and eco-friendly practice of ZnO NPs biosynthesis.
Exploring association between MBL2 gene polymorphisms and the occurrence of clinical blackwater fever through a case–control study in Congolese children
Authors: Bodi Joseph M. , Nsibu Célestin N. , Longenge Roland L. , Aloni Michel N. , Akilimali Pierre Z. , Kayembe Patrick K. , Omar Ahmeddin H. , Verhaegen Jan , Tshibassu Pierre M. , Lukusa Prosper T. , Lumaka Aimé , Hirayama Kenji
Published: January 2020

Background

Blackwater fever (BWF), one of the most severe and life-threatening forms of falciparum malaria, is characterized by acute massive intravascular haemolysis, often leading to acute renal failure. Thus far, the genetics of the underlying susceptibility to develop BWF is not fully elucidated. Deficiency in the MBL protein, an important component of the innate immune system, has previously been suggested to be a susceptibility factor for the development of severe malaria. This study aimed to evaluate the association betweenMBL2gene polymorphisms, known to affect the MBL protein level/activity, and the occurrence of BWF among Congolese children.

Methods

This is a case–control study. Cases were patients with BWF, whereas controls, matched for gender and age, had uncomplicated malaria (UM). Dried blood spot was collected for genotyping.

Results

A total of 129 children were screened, including 43 BWF and 86 UM. The common allele in BWF and UM was A, with a frequency of 76.7 and 61.0%, respectively (OR: 2.67 (0.87–829) andp = 0.079). The frequency of the C allele was 18.6 and 29.1% in BWF and UM groups, respectively, withp = 0.858. Not a single D allele was encountered. Genotype AA was at higher risk for BWF whereas genotypes A0 (AB and AC) were over-represented in UM group (OR: 0.21 (0.06–0.78)) withp = 0.019. Nine haplotypes were observed in this study: 3 high MBL expression haplotypes and 6 low MBL expression haplotype. One new haplotype HYPC was observed in this study. None of these haplotypes was significantly associated with BWF.

Conclusion

This pilot study is a preliminary research onMBL2gene and infectious diseases in DRC. The study results show a higher risk for BWF in AA. This suggests that future studies on BWF should further investigate the contribution of a strong immune response to the occurrence of BWF.
The use of spatial and genetic tools to assess Plasmodium falciparum transmission in Lusaka, Zambia between 2011 and 2015
Authors: Bridges Daniel J. , Chishimba Sandra , Mwenda Mulenga , Winters Anna M. , Slawsky Erik , Mambwe Brenda , Mulube Conceptor , Searle Kelly M. , Hakalima Aves , Mwenechanya Roy , Larsen David A.
Published: January 2020

Background

Zambia has set itself the ambitious target of eliminating malaria by 2021. To continue tracking transmission to zero, new interventions, tools and approaches are required.

Methods

Urban reactive case detection (RCD) was performed in Lusaka city from 2011 to 2015 to better understand the location and drivers of malaria transmission. Briefly, index cases were followed to their home and all consenting individuals living in the index house and nine proximal houses were tested with a malaria rapid diagnostic test and treated if positive. A brief survey was performed and for certain responses, a dried blood spot sample collected for genetic analysis. Aggregate health facility data, individual RCD response data and genetic results were analysed spatially and against environmental correlates.

Results

Total number of malaria cases remained relatively constant, while the average age of incident cases and the proportion of incident cases reporting recent travel both increased. The estimated R0 in Lusaka was < 1 throughout the study period. RCD responses performed within 250 m of uninhabited/vacant land were associated with a higher probability of identifying additional infections.

Conclusions

Evidence suggests that the majority of malaria infections are imported from outside Lusaka. However there remains some level of local transmission occurring on the periphery of urban settlements, namely in the wet season. Unfortunately, due to the higher-than-expected complexity of infections and the small number of samples tested, genetic analysis was unable to identify any meaningful trends in the data.
The effectiveness of older insecticide-treated bed nets (ITNs) to prevent malaria infection in an area of moderate pyrethroid resistance: results from a cohort study in Malawi
Authors: Shah Monica P. , Steinhardt Laura C. , Mwandama Dyson , Mzilahowa Themba , Gimnig John E. , Bauleni Andy , Wong Jacklyn , Wiegand Ryan , Mathanga Don P. , Lindblade Kim A.
Published: January 2020

Background

A previous cohort study in Malawi showed that users of new insecticide-treated bed nets (ITNs) were significantly protected against malaria compared to non-users, despite moderate levels of pyrethroid resistance among the primary mosquito vectors. The present study investigated whether ITNs that were 1–2 years old continued to protect users in the same area with moderate pyrethroid resistance.

Methods

One year following a baseline cross-sectional malaria parasitaemia prevalence survey and universal distribution of deltamethrin ITNs (May 2012), a fixed cohort of 1223 children aged 6–59 months was enrolled (April 2013). Children were tested for parasitaemia at monthly scheduled visits and at unscheduled sick visits from May to December 2013 using rapid diagnostic tests. ITN use the prior night and the condition of ITNs (based on presence of holes) was assessed by caregiver self-report. The incidence rate ratio (RR) comparing malaria infection among users and non-users of ITNs was modelled using generalized estimating equations adjusting for potential confounders and accounting for repeated measures on each child. The protective efficacy (PE) of ITN use was calculated as 1 − RR.

Results

In this cohort, self-reported ITN use remained consistently high (> 95%) over the study period. Although users of ITNs were slightly more protected compared to non-users of ITNs, the difference in incidence of infection was not statistically significant (RR 0.83, 95% confidence interval [CI] 0.54–1.27). Among ITN users, malaria incidence was significantly lower in users of ITNs with no holes (of any size) compared to users of ITNs with ≥ 1 hole (RR 0.82, 95% CI 0.69–0.98).

Conclusions

There was no significant PE of using 1–2 year-old ITNs on the incidence of malaria in children in an area of moderate pyrethroid resistance, but among ITN users, the authors found increased protection by ITNs with no holes compared to ITNs with holes. Given the moderate levels of pyrethroid resistance in the primary malaria vector and recent evidence of added benefits of ITNs with synergists or non-pyrethroid insecticides, next-generation ITNs may be a useful strategy to address pyrethroid resistance and should be further explored in Malawi.
Preferred resting surfaces of dominant malaria vectors inside different house types in rural south-eastern Tanzania
Authors: Msugupakulya Betwel J. , Kaindoa Emmanuel W. , Ngowo Halfan S. , Kihonda Japhet M. , Kahamba Najat F. , Msaky Dickson S. , Matoke-Muhia Damaris , Tungu Patrick K. , Okumu Fredros O.
Published: January 2020

Background

Malaria control in Africa relies extensively on indoor residual spraying (IRS) and insecticide-treated nets (ITNs). IRS typically targets mosquitoes resting on walls, and in few cases, roofs and ceilings, using contact insecticides. Unfortunately, little attention is paid to where malaria vectors actually rest indoors, and how such knowledge could be used to improve IRS. This study investigated preferred resting surfaces of two major malaria vectors, Anopheles funestus and Anopheles arabiensis, inside four common house types in rural south-eastern Tanzania.

Methods

The assessment was done inside 80 houses including: 20 with thatched roofs and mud walls, 20 with thatched roofs and un-plastered brick walls, 20 with metal roofs and un-plastered brick walls, and 20 with metal roofs and plastered brick walls, across four villages. In each house, resting mosquitoes were sampled in mornings (6 a.m.–8 a.m.), evenings (6 p.m.–8 p.m.) and at night (11 p.m.–12.00 a.m.) using Prokopack aspirators from multiple surfaces (walls, undersides of roofs, floors, furniture, utensils, clothing, curtains and bed nets).

Results

Overall, only 26% of An. funestus and 18% of An. arabiensis were found on walls. In grass-thatched houses, 33–55% of An. funestus and 43–50% of An. arabiensis rested under roofs, while in metal-roofed houses, only 16–20% of An. funestus and 8–30% of An. arabiensis rested under roofs. Considering all data together, approximately 40% of mosquitoes rested on surfaces not typically targeted by IRS, i.e. floors, furniture, utensils, clothing and bed nets. These proportions were particularly high in metal-roofed houses (47–53% of An. funestus; 60–66% of An. arabiensis).

Conclusion

While IRS typically uses contact insecticides to target adult mosquitoes on walls, and occasionally roofs and ceilings, significant proportions of vectors rest on surfaces not usually sprayed. This gap exceeds one-third of malaria mosquitoes in grass-thatched houses, and can reach two-thirds in metal-roofed houses. Where field operations exclude roofs during IRS, the gaps can be much greater. In conclusion, there is need for locally-obtained data on mosquito resting behaviours and how these influence the overall impact and costs of IRS. This study also emphasizes the need for alternative approaches, e.g. house screening, which broadly tackle mosquitoes beyond areas reachable by IRS and ITNs.
A survey of Anopheles species composition and insecticide resistance on the island of Bubaque, Bijagos Archipelago, Guinea-Bissau
Authors: Ant Thomas , Foley Erin , Tytheridge Scott , Johnston Colin , Goncalves Adriana , Ceesay Sainey , Ndiath Mamadou Ousmane , Affara Muna , Martinez Julien , Pretorius Elizabeth , Grundy Chris , Rodrigues Amabelia , Djata Paulo , d’Alessandro Umberto , Bailey Robin , Mabey David , Last Anna , Logan James G.
Published: January 2020

Background

Bubaque is the most populous island of the Bijagos archipelago, a group of malaria-endemic islands situated off the coast of Guinea-Bissau, West Africa. Malaria vector control on Bubaque relies almost exclusively on the use of long-lasting insecticidal nets (LLINs). However, there is little information on local vector bionomics and insecticide resistance.

Methods

A survey of mosquito species composition was performed at the onset of the wet season (June/July) and the beginning of the dry season (November/December). Sampling was performed using indoor adult light-traps and larval dipping. Anopheles mosquitoes were identified to species level and assessed for kdr allele frequency by TaqMan PCR. Females were analysed for sporozoite positivity by CSP-ELISA. Resistance to permethrin and α-cypermethrin was measured using the CDC-bottle bioassay incorporating the synergist piperonyl-butoxide.

Results

Several Anopheles species were found on the island, all belonging to the Anopheles gambiae sensu lato (s.l.) complex, including An. gambiae sensu stricto, Anopheles coluzzii, Anopheles melas, and An. gambiae/An. coluzzii hybrids. Endophagic Anopheles species composition and abundance showed strong seasonal variation, with a majority of An. gambiae (50% of adults collected) caught in June/July, while An. melas was dominant in November/December (83.9% of adults collected). Anopheles gambiae had the highest sporozoite rate in both seasons, with infection rates of 13.9% and 20% in June/July and November/December, respectively. Moderate frequencies of the West African kdr allele were found in An. gambiae (36%), An. coluzzii (35%), An. gambiae/An. coluzzii hybrids (42%). Bioassays suggest moderate resistance to α-cypermethrin, but full susceptibility to permethrin.

Conclusions

The island of Bubaque maintained an An. gambiae s.l. population in both June/July and November/December. Anopheles gambiae was the primary vector at the onset of the wet season, while An. melas is likely to be responsible for most dry season transmission. There was moderate kdr allele frequency and synergist assays suggest likely metabolic resistance, which could reduce the efficacy of LLINs. Future control of malaria on the islands should consider the seasonal shift in mosquito species, and should employ continuous monitoring for insecticide resistance.
Association of PM2.5 concentration with health center outpatient visits for respiratory diseases of children under 5 years old in Lima, Peru
Authors: Davila Cordova Jennifer Estefanía , Tapia Aguirre Vilma , Vasquez Apestegui Vanessa , Ordoñez Ibarguen Luis , Vu Bryan N. , Steenland Kyle , Gonzales Gustavo F.
Published: January 2020

Background

Lima is one of the more polluted cities in Latin America. High levels of PM2.5 have been shown to increase health center outpatient visits of respiratory diseases.

Methods

Health center outpatient visits for children < 5 years for childhood respiratory disease (acute lower respiratory infections (ALRI), pneumonia and acute bronchiolitis/asthma) from 498 public clinics in Lima were available on a weekly basis from 2011 to 2015 from Peru’s Ministry of Health (MINSA). The association between the average weekly concentrations of PM2.5 was evaluated in relation to the number of weekly health center outpatient visits for children. Weekly PM2.5 values were estimated using a recently developed model that combined data observed from ground monitors, with data from space satellite and meteorology. Ground monitoring data came from 10 fixed stations of the Peruvian National Service of Meteorology and Hydrology (SENAMHI) and from 6 mobile stations located in San Juan de Miraflores by Johns Hopkins University. We conducted a time-series analysis using a negative binomial model.

Results

We found a significant association between exposure to PM2.5 and all three types of respiratory diseases, across all age groups. For an interquartile increase in PM2.5, we found an increase of 6% for acute lower respiratory infections, an increase of 16–19% for pneumonia, and an increase of 10% for acute bronchiolitis / asthma.

Conclusions

Higher emissions of environmental pollutants such as PM2,5 could be a trigger for the increase of health center outpatients visits for respiratory diseases (ALRI, pneumonia and asthma), which are themselves risk factors for mortality for children in Lima province, Peru.
lncRNA JPX/miR-33a-5p/Twist1 axis regulates tumorigenesis and metastasis of lung cancer by activating Wnt/β-catenin signaling
Authors: Pan Jinchang , Fang Shuai , Tian Haihua , Zhou Chengwei , Zhao Xiaodong , Tian Hui , He Jinxian , Shen Weiyu , Meng Xiaodan , Jin Xiaofeng , Gong Zhaohui
Published: January 2020

Background

MicroRNAs (miRNAs) and Twist1-induced epithelial-mesenchymal transition (EMT) in cancer cell dissemination are well established, but the involvement of long noncoding RNAs (lncRNAs) in Twist1-mediated signaling remains largely unknown.

Methods

RT-qPCR and western blotting were conducted to detect the expression levels of lncRNA JPX and Twist1 in lung cancer cell lines and tissues. The impact of JPX on Twist1 expression, cell growth, invasion, apoptosis, and in vivo tumor growth were investigated in lung cancer cells by western blotting, rescue experiments, colony formation assay, flow cytometry, and xenograft animal experiment.

Results

We observed that lncRNA JPX was upregulated in lung cancer metastatic tissues and was closely correlated with tumor size and an advanced stage. Functionally, JPX promoted lung cancer cell proliferation in vitro and facilitated lung tumor growth in vivo. Additionally, JPX upregulated Twist1 by competitively sponging miR-33a-5p and subsequently induced EMT and lung cancer cell invasion. Interestingly, JPX and Twist1 were coordinately upregulated in lung cancer tissues and cells. Mechanically, the JPX/miR-33a-5p/Twist1 axis participated in EMT progression by activating Wnt/β-catenin signaling.

Conclusions

These findings suggest that lncRNA JPX, a mediator of Twist1 signaling, could predispose lung cancer cells to metastasis and may serve as a potential target for targeted therapy.
Regional myocardial strain analysis via 2D speckle tracking echocardiography: validation with sonomicrometry and correlation with regional blood flow in the presence of graded coronary stenoses and dobutamine stress
Authors: Stendahl John C. , Parajuli Nripesh , Lu Allen , Boutagy Nabil E. , Guerrera Nicole , Alkhalil Imran , Lin Ben A. , Staib Lawrence H. , O’Donnell Matthew , Duncan James S. , Sinusas Albert J.
Published: January 2020

Background

Quantitative regional strain analysis by speckle tracking echocardiography (STE) may be particularly useful in the assessment of myocardial ischemia and viability, although reliable measurement of regional strain remains challenging, especially in the circumferential and radial directions. We present an acute canine model that integrates a complex sonomicrometer array with microsphere blood flow measurements to evaluate regional myocardial strain and flow in the setting of graded coronary stenoses and dobutamine stress. We apply this unique model to rigorously evaluate a commercial 2D STE software package and explore fundamental regional myocardial flow-function relationships.

Methods

Sonomicrometers (16 crystals) were implanted in epicardial and endocardial pairs across the anterior myocardium of anesthetized open chest dogs (n = 7) to form three adjacent cubes representing the ischemic, border, and remote regions, as defined by their relative locations to a hydraulic occluder on the mid-left anterior descending coronary artery (LAD). Additional cardiac (n = 3) and extra-cardiac (n = 3) reference crystals were placed to define the cardiac axes and aid image registration. 2D short axis echocardiograms, sonometric data, and microsphere blood flow data were acquired at baseline and in the presence of mild and moderate LAD stenoses, both before and during low-dose dobutamine stress (5 μg/kg/min). Regional end-systolic 2D STE radial and circumferential strains were calculated with commercial software (EchoInsight) and compared to those determined by sonomicrometry and to microsphere blood flow measurements. Post-systolic indices (PSIs) were also calculated for radial and circumferential strains.

Results

Low-dose dobutamine augmented both strain and flow in the presence of mild and moderate stenoses. Regional 2D STE strains correlated moderately with strains assessed by sonomicrometry (Rradial = 0.56, p < 0.0001; Rcirc = 0.55, p < 0.0001) and with regional flow quantities (Rradial = 0.61, Rcirc = 0.63). Overall, correspondence between 2D STE and sonomicrometry was better in the circumferential direction (Bias ± 1.96 SD: − 1.0 ± 8.2% strain, p = 0.06) than the radial direction (5.7 ± 18.3%, p < 0.0001). Mean PSI values were greatest in low flow conditions and normalized with low-dose dobutamine.

Conclusions

2D STE identifies changes in regional end-systolic circumferential and radial strain produced by mild and moderate coronary stenoses and low-dose dobutamine stress. Regional 2D STE end-systolic strain measurements correlate modestly with regional sonomicrometer strain and microsphere flow measurements.
Self-assembly of cholesterol end-capped polymer micelles for controlled drug delivery
Authors: Gao Ming , Yang Yifeng , Bergfel Andreas , Huang Lanli , Zheng Li , Bowden Tim Melander
Published: January 2020

Background

During the past few decades, drug delivery system (DDS) has attracted many interests because it could enhance the therapeutic effects of drugs and reduce their side effects. The advent of nanotechnology has promoted the development of nanosized DDSs, which could promote drug cellular uptake as well as prolong the half-life in blood circulation. Novel polymer micelles formed by self-assembly of amphiphilic polymers in aqueous solution have emerged as meaningful nanosystems for controlled drug release due to the reversible destabilization of hydrophobic domains under different conditions.

Results

The amphiphilic polymers presented here were composed of cholesterol groups end capped and poly (poly (ethylene glycol) methyl ether methacrylate) (poly (OEGMA)) as tailed segments by the synthesis of cholesterol-based initiator, followed by atom transfer radical polymerization (ATRP) with OEGMA monomer. FT-IR and NMR confirmed the successfully synthesis of products including initiator and polymers as well as the Mw of the polymers were from 33,233 to 89,088 g/mol and their corresponding PDI were from 1.25 to 1.55 by GPC. The average diameter of assembled polymer micelles was in hundreds nanometers demonstrated by DLS, AFM and SEM. The behavior of the amphiphilic polymers as micelles was investigated using pyrene probing to explore their critical micelle concentration (CMC) ranging from 2.53 × 10−4 to 4.33 × 10−4 mg/ml, decided by the balance between cholesterol and poly (OEGMA). Besides, the CMC of amphiphilic polymers, the quercetin (QC) feeding ratio and polarity of solvents determined the QC loading ratio maximized reaching 29.2% certified by UV spectrum, together with the corresponding size and stability changes by DLS and Zeta potential, and thermodynamic changes by TGA and DSC. More significantly, cholesterol end-capped polymer micelles were used as nanosized systems for controlled drug release, not only alleviated the cytotoxicity of QC from 8.6 to 49.9% live cells and also achieved the QC release in control under different conditions, such as the presence of cyclodextrin (CD) and change of pH in aqueous solution.

Conclusions

The results observed in this study offered a strong foundation for the design of favorable polymer micelles as nanosized systems for controlled drug release, and the molecular weight adjustable amphiphilic polymer micelles held potential for use as controlled drug release system in practical application.
Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics
Authors: Janßen Hilke Catherina , Angrisani Nina , Kalies Stefan , Hansmann Florian , Kietzmann Manfred , Warwas Dawid Peter , Behrens Peter , Reifenrath Janin
Published: January 2020

Background

In orthopedics, the treatment of implant-associated infections represents a high challenge. Especially, potent antibacterial effects at implant surfaces can only be achieved by the use of high doses of antibiotics, and still often fail. Drug-loaded magnetic nanoparticles are very promising for local selective therapy, enabling lower systemic antibiotic doses and reducing adverse side effects. The idea of the following study was the local accumulation of such nanoparticles by an externally applied magnetic field combined with a magnetizable implant. The examination of the biodistribution of the nanoparticles, their effective accumulation at the implant and possible adverse side effects were the focus. In a BALB/c mouse model (n = 50) ferritic steel 1.4521 and Ti90Al6V4 (control) implants were inserted subcutaneously at the hindlimbs. Afterwards, magnetic nanoporous silica nanoparticles (MNPSNPs), modified with rhodamine B isothiocyanate and polyethylene glycol-silane (PEG), were administered intravenously. Directly/1/7/21/42 day(s) after subsequent application of a magnetic field gradient produced by an electromagnet, the nanoparticle biodistribution was evaluated by smear samples, histology and multiphoton microscopy of organs. Additionally, a pathohistological examination was performed. Accumulation on and around implants was evaluated by droplet samples and histology.

Results

Clinical and histological examinations showed no MNPSNP-associated changes in mice at all investigated time points. Although PEGylated, MNPSNPs were mainly trapped in lung, liver, and spleen. Over time, they showed two distributional patterns: early significant drops in blood, lung, and kidney and slow decreases in liver and spleen. The accumulation of MNPSNPs on the magnetizable implant and in its area was very low with no significant differences towards the control.

Conclusion

Despite massive nanoparticle capture by the mononuclear phagocyte system, no significant pathomorphological alterations were found in affected organs. This shows good biocompatibility of MNPSNPs after intravenous administration. The organ uptake led to insufficient availability of MNPSNPs in the implant region. For that reason, among others, the nanoparticles did not achieve targeted accumulation in the desired way, manifesting future research need. However, with different conditions and dimensions in humans and further modifications of the nanoparticles, this principle should enable reaching magnetizable implant surfaces at any time in any body region for a therapeutic reason.
Does a novel exergame challenge balance and activate muscles more than existing off-the-shelf exergames?
Authors: Willaert Jente , De Vries Aijse Willem , Tavernier Julie , Van Dieen Jaap H. , Jonkers Ilse , Verschueren Sabine
Published: January 2020

Background

Novel balance-targeting exergames controlled with off-the-shelf hardware, were developed based on current recommendations for balance training in healthy older adults and documented shortcomings of existing games. The aim of this study was to explore the feasibility of these novel exergames as training tool for elderly and, more specifically whether these games can elicit more challenging weight shifts and higher levels of muscle activity compared to existing off-the-shelf exergames. Furthermore, the motivational pull in these new games was studied.

Methods

Sixteen healthy older adults were recruited to play the novel games and two reference games that were found to be the most challenging ones in terms of weight shifts or muscle activity in previous studies. Weight shifts were expressed relative to participants’ Functional Limits of Stability (FLOS). Muscular challenge of the games was quantified by dividing the signal into 200 ms blocks and determining the average muscle activity within these blocks. The muscle activity was normalized to maximal voluntary contractions (MVC) to categorize the blocks in zones of < 40, 40–60, 60–80 and > 80% MVC. Subsequently, the number of blocks per intensity level and the number of consecutive blocks above 40% were determined. Motivation to play the games was assessed using the Intrinsic Motivation Inventory (IMI) and scores between the games were analyzed using Generalized Estimated Equations (GEE).

Results

The novel exergames successfully elicited center of mass (COM) displacements with medians of around 80% of FLOS or higher for all directions. Furthermore, the COM displacements in the novel games were larger for each direction than in the reference games, although for one game the sideward left direction reached significance only at the third trial. Compared to the existing games, longer blocks of muscle activation above 40% MVC were found, but overall intensity remained low. IMI scores were high on all subscales, indicating that older adults experienced the games as motivating.

Conclusion

We conclude that affordable hardware can be used to create challenging and enjoyable balance training programs using exergames. The exergames that were successful in eliciting challenging weight shifts and muscle activity should now be further studied in longitudinal randomized controlled interventions, to assess effects on balance, muscle strength and eventually fall risk in healthy older adults.
Prevalence and clinical picture of premenstrual syndrome in females from Bulgaria
Authors: Chumpalova Petranka , Iakimova Rossitza , Stoimenova-Popova Maya , Aptalidis Daniil , Pandova Milena , Stoyanova Maria , Fountoulakis Konstantinos N.
Published: January 2020

Background

Premenstrual syndrome (PMS) and its more severe form premenstrual dysphoric disorder (PMDD) are highly prevalent conditions, but there seems to be ethnic and cultural variances in their distribution.

Aims

To explore the prevalence of PMS/PMDD and their typical clinical features in a Bulgarian population.

Materials and methods

This investigation was designed and executed as a cross-sectional descriptive study. Three hundred and five conveniently recruited females with no psychiatric history filled in a self-evaluation questionnaire based on DSM-IV tapping on different symptoms of PMS. The prevalence of the conditions was calculated.

Results

32.1% (N = 98) of the tested females (mean age 31.04 ± 6.31) suffered from PMS and 3.3% (N = 10) were diagnosed with PMDD. The leading symptoms in the sample were irritability, fatigue and changes in appetite, depressed mood, mood swings, and anxiety, and abdominal bloating, breast tension and tenderness. Most of the symptoms were moderately severe. Mild and moderate cases of PMS were near equally distributed and more frequent than severe ones.

Conclusion

PMS is a common condition which is usually mildly expressed, but severe cases are not an exception. The clinical picture is dominated by almost equally distributed psychological and somatic symptoms.