bluuebunny/crossref_metadata_2025 huggingface dataset:
Variations in biomarkers of dyslipidemia and dysbiosis during the menstrual cycle: a pilot study in healthy volunteers
Authors: Bergström Helena , Ekström Lena , Warnqvist Anna , Bergman Peter , Björkhem-Bergman Linda
Published: April 2021

Background

Dyslipidemia in metabolic syndrome may introduce an underestimation of the risk for cardiovascular disease (CVD) using Low-Density Lipoprotein-Cholesterol (LDL-C) as a surrogate marker. Recently, non-High-Density Lipoprotein-Cholesterol (non-HDL-C), Apolipoprotein B (ApoB) and remnant-Cholesterol (remnant-C) have been suggested as better biomarkers for dyslipidemia. In addition, the microbial metabolites trimethylamine-N-oxide (TMAO), betaine and choline have been associated with CVD and suggested as markers for dysbiosis. There is a lack of knowledge on potential alterations in these biomarkers during the menstrual cycle. The aim of this single center, prospective non-interventional study, was to investigate variations in biomarkers of dyslipidemia and dysbiosis in healthy volunteers during the menstrual cycle.

Method

Serum samples were collected from 17 healthy, regularly menstruating women during two menstrual cycles, including the follicular, ovulatory and luteal phases. Levels of lipoproteins, lipoprotein ratios and microbial metabolites were analyzed in a total of 90 samples (30 complete menstrual cycles).

Results

ApoB, ApoB/HDL and non-HDL-C/HDL ratios were significantly higher in the follicular phase compared to the ovulatory and luteal phases (p < 0.05). Remnant-C were higher during the luteal phase (p < 0.05). TMAO did not vary during the different phases and did not correlate with estrogen levels.

Conclusion

Our data support that biomarkers for dyslipidemia vary during the menstrual cycle. Thus, to avoid an underestimation of cardiovascular risk, sampling during the follicular phase, when levels of pro-atherogenic lipids are higher, may be considered.
Undertaking a high stakes virtual OSCE (“VOSCE”) during Covid-19
Authors: Blythe Jenny , Patel Nimesh S. A. , Spiring Will , Easton Graham , Evans Dason , Meskevicius-Sadler Egle , Noshib Hassan , Gordon Heather
Published: April 2021

Background

The Covid pandemic and associated lockdown forced medical schools globally not only to deliver emergency remote teaching, but to consider alternative methods of high stakes assessment. Here we outline our approach to the resit virtual OSCE (“VOSCE”) for final year medical students that we undertook during “lockdown” in the current pandemic.

Methods

The original ‘pre Covid’ examination blueprint was reviewed and modified for the virtual environment in both format and content. In anticipation of the new format delivery, a number of pre-training sessions took place for all parties, and standardised templates were developed.

Results

A total of 9 students undertook the VOSCE, which took the form of a two-part exam (a communication and clinical examination component, and a practical procedures component). The VOSCE was completed by all students, examiners, simulated patients and invigilators on an online digital platform with no issues with regards to technical problems.

Conclusions

A total of 6 students passed the VOSCE and as such progressed to graduation. The limitation of assessing some particular types of skills across the remote format (such as practical procedures) was recognised. The training and the templates developed were helpful in case the VOSCE format needs to be adopted in future at short notice and/or expanded in future.
Effectiveness of an escape room for undergraduate interprofessional learning: a mixed methods single group pre-post evaluation
Authors: Moore Leigh , Campbell Narelle
Published: April 2021

Background

Interprofessional practice (IPP) has been shown to contribute to quality service provision and improved health outcomes. This knowledge has led to the integration of interprofessional education into course curricula for many health-care disciplines. Offering interprofessional education in rural areas to students undertaking work integrated learning placements is challenging particularly because of the diversity of students and placement dates combined with the student focus on the assessable placement curriculum.

This research investigated and evaluated the utility of an escape room as an educational modality that facilitates learning whilst providing a supportive and motivating learning environment. Our project focused on the acquisition of interprofessional practice knowledge and experience by a health professional student cohort.

Methods

This study used the novel intervention of an escape room combined with an interactive teaching session to test student engagement and learning about interprofessional practice and teamwork. The research used a mixed methods single group pre-post design.

Results

Fifty students (78% female) from seventeen universities and seven professions participated in teams of three to six members. Most participants (66%) had not previously completed an escape room. The results showed that the intervention provided effective and engaging learning and was intrinsically appealing to students despite its non-assessable nature. Individual student reflection on their participation showed developing insight into the critical importance of clear communication and intentional team member collaboration in the provision of effective interprofessional practice.

Conclusions

The escape room intervention added value to the placement curriculum and proved flexible for a heterogeneous student cohort.
Exploring patient-provider interactions and the health system’s responsiveness to street-connected children and youth in Kenya: a qualitative study
Authors: Lonnie Embleton , Pooja Shah , Allison Gayapersad , Reuben Kiptui , David Ayuku , Juddy Wachira , Edith Apondi , Paula Braitstein
Published: April 2021

Background

In Kenya, street-connected children and youth (SCY) have poor health outcomes and die prematurely due to preventable causes. This suggests they are not accessing or receiving adequately responsive healthcare to prevent morbidity and mortality. We sought to gain insight into the health systems responsiveness to SCY in Kenya through an in-depth exploration of SCY’s and healthcare provider’s reflections on their interactions with each other.

Methods

This qualitative study was conducted across 5 counties in western Kenya between May 2017 and September 2018 using multiple methods to explore and describe the public perceptions of, and proposed and existing responses to, the phenomenon of SCY in Kenya. The present analysis focuses on a subset of data from focus group discussions and in-depth interviews concerning the delivery of healthcare to SCY, interactions between SCY and providers, and SCY’s experiences in the health system. We conducted a thematic analysis situated in a conceptual framework for health systems responsiveness.

Results

Through three themes, context, negative patient-provider interactions, and positive patient-provider interactions, we identified factors that shape health systems responsiveness to SCY in Kenya. Economic factors influenced and limited SCY’s interactions with the health system and shaped their experiences of dignity, quality of basic amenities, choice of provider, and prompt attention. The stigmatization and discrimination of SCY, a sociological process shaped by the social-cultural context in Kenya, resulted in experiences of indignity and a lack of prompt attention when interacting with the health system. Patient-provider interactions were highly influenced by healthcare providers’ adverse personal emotions and attitudes towards SCY, resulting in negative interactions and a lack of health systems responsiveness.

Conclusions

This study suggests that the health system in Kenya is inadequately responsive to SCY. Increasing public health expenditures and expanding universal health coverage may begin to address economic factors, such as the inability to pay for care, which influence SCY’s experiences of choice of provider, prompt attention, and dignity. The deeply embedded adverse emotional responses expressed by providers about SCY, associated with the socially constructed stigmatization of this population, need to be addressed to improve patient-provider interactions.
Glucose-6-phosphate dehydrogenase mutations in malaria endemic area of Thailand by multiplexed high‐resolution melting curve analysis
Authors: Boonyuen Usa , Songdej Duantida , Tanyaratsrisakul Sasipa , Phuanukoonnon Suparat , Chamchoy Kamonwan , Praoparotai Aun , Pakparnich Phonchanan , Sudsumrit Sirapapha , Edwards Thomas , Williams Christopher T. , Byrne Rachel L. , Adams Emily R. , Imwong Mallika
Published: April 2021

Background

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymopathy in humans, is prevalent in tropical and subtropical areas where malaria is endemic. Anti-malarial drugs, such as primaquine and tafenoquine, can cause haemolysis in G6PD-deficient individuals. Hence, G6PD testing is recommended before radical treatment against vivax malaria. Phenotypic assays have been widely used for screening G6PD deficiency, but in heterozygous females, the random lyonization causes difficulty in interpreting the results. Over 200 G6PD variants have been identified, which form genotypes associated with differences in the degree of G6PD deficiency and vulnerability to haemolysis. This study aimed to assess the frequency of G6PD mutations using a newly developed molecular genotyping test.

Methods

A multiplexed high-resolution melting (HRM) assay was developed to detect eight G6PD mutations, in which four mutations can be tested simultaneously. Validation of the method was performed using 70 G6PD-deficient samples. The test was then applied to screen 725 blood samples from people living along the Thai–Myanmar border. The enzyme activity of these samples was also determined using water-soluble tetrazolium salts (WST-8) assay. Then, the correlation between genotype and enzyme activity was analysed.

Results

The sensitivity of the multiplexed HRM assay for detecting G6PD mutations was 100 % [95 % confidence interval (CI): 94.87–100 %] with specificity of 100 % (95 % CI: 87.66–100 %). The overall prevalence of G6PD deficiency in the studied population as revealed by phenotypic WST-8 assay was 20.55 % (149/725). In contrast, by the multiplexed HRM assay, 27.17 % (197/725) of subjects were shown to have G6PD mutations. The mutations detected in this study included four single variants, G6PD Mahidol (187/197), G6PD Canton (4/197), G6PD Viangchan (3/197) and G6PD Chinese-5 (1/197), and two double mutations, G6PD Mahidol + Canton (1/197) and G6PD Chinese-4 + Viangchan (1/197). A broad range of G6PD enzyme activities were observed in individuals carrying G6PD Mahidol, especially in females.

Conclusions

The multiplexed HRM-based assay is sensitive and reliable for detecting G6PD mutations. This genotyping assay can facilitate the detection of heterozygotes, which could be useful as a supplementary approach for high-throughput screening of G6PD deficiency in malaria endemic areas before the administration of primaquine and tafenoquine.
A systematic review of factors influencing participation in two types of malaria prevention intervention in Southeast Asia
Authors: Cheng Breagh , Htoo Saw Nay , Mhote Naw Pue Pue , Davison Colleen M.
Published: April 2021

Background

Multi-pronged malaria elimination strategies are increasingly being considered for accelerating efforts against malaria transmission in Southeast Asia. Two malaria prevention interventions used in in the region are insecticide-treated bed-nets (ITNs) and mass drug administration (MDA). Universal access to ITNs is recommended and high population coverage (e.g. above 80%) is needed during MDA initiatives to maximize the impact of these interventions. However, variability in ITN use and individual MDA participation exists. This systematic review aims to provide a summary and overview of literature discussing factors influencing uptake of these two malaria control strategies in Southeast Asian countries.

Methods

A search of OVID Embase, OVID MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, OpenGrey, ProQuest, and Google Scholar was undertaken in February 2020. English-language publications with any study design using data from any of the ten member countries of the Association of Southeast Asian Nations were eligible for inclusion. In addition, reference lists of identified articles were manually searched. Websites for relevant international agencies were also searched to identify related grey literature.

Results

The review identified thirty publications that met the inclusion and exclusion criteria. Most discussed ITN use (n = 18) and were relevant to populations in Myanmar (n = 14). All MDA studies were published after 2016, whereas included ITN studies spanned from 1998 to 2020. Seven main themes emerged across the studies. Knowledge of malaria and attitudes towards ITNs were emphasized as key factors associated with ITN use. For MDA participation, key factors included the importance of positive attitudes towards the program, the influence of indirect costs and incentives, and the tendency for group decision-making.

Conclusions

As countries in Southeast Asia continue to work towards becoming malaria-free by 2030, the knowledge and attitudes of local population sub-groups should be assessed and incorporated into the planning and implementation of malaria prevention activities. The role of incentives and group decision making should also be considered particularly as they relate to MDA. There is need for ongoing involvement of health educators, the continuation of implementation research and the prioritization of community engagement efforts alongside malaria interventions in the region.
Antimicrobial resistance profile and multidrug resistance patterns of Streptococcus pneumoniae isolates from patients suspected of pneumococcal infections in Ethiopia
Authors: Sharew Bekele , Moges Feleke , Yismaw Gizachew , Abebe Wondwossen , Fentaw Surafal , Vestrheim Didrik , Tessema Belay
Published: April 2021

Background

Antimicrobial-resistant strains of Streptococcus pneumoniae have become one of the greatest challenges to global public health today and inappropriate use of antibiotics and high level of antibiotic use is probably the main factor driving the emergence of resistance worldwide. The aim of this study is, therefore, to assess the antimicrobial resistance profiles and multidrug resistance patterns of S. pneumoniae isolates from patients suspected of pneumococcal infections in Ethiopia.

Methods

A hospital-based prospective study was conducted from January 2018 to December 2019 at Addis Ababa city and Amhara National Region State Referral Hospitals. Antimicrobial resistance tests were performed from isolates of S. pneumoniae that were collected from pediatric and adult patients. Samples (cerebrospinal fluid, blood, sputum, eye discharge, ear discharge, and pleural and peritoneal fluids) from all collection sites were initially cultured on 5% sheep blood agar plates and incubated overnight at 37 °C in a 5% CO2 atmosphere. Streptococcus pneumoniae was identified and confirmed by typical colony morphology, alpha-hemolysis, Gram staining, optochin susceptibility, and bile solubility test. Drug resistance testing was performed using the E-test method according to recommendations of the Clinical and Laboratory Standards Institute.

Results

Of the 57 isolates, 17.5% were fully resistant to penicillin. The corresponding value for both cefotaxime and ceftriaxone was 1.8%. Resistance rates to erythromycin, clindamycin, tetracycline, chloramphenicol and trimethoprim-sulfamethoxazole were 59.6%, 17.5%, 38.6%, 17.5 and 24.6%, respectively. Multidrug resistance (MDR) was seen in 33.3% isolates. The most common pattern was co-resistance to penicillin, erythromycin, clindamycin, and tetracycline.

Conclusions

Most S. pneumoniae isolates were susceptible to ceftriaxone and cefotaxime. Penicillin has been used as a drug of choice for treating S. pneumoniae infection. However, antimicrobial resistance including multidrug resistance was observed to several commonly used antibiotics including penicillin. Hence, it is important to periodically monitor the antimicrobial resistance patterns to select empirical treatments for better management of pneumococcal infection.
Linkage to intensive adherence counselling among HIV-positive persons on ART with detectable viral load in Gomba district, rural Uganda
Authors: Nakalega Rita , Mukiza Nelson , Debem Henry , Kiwanuka George , Kakumba Ronald Makanga , Menge Robert , Kagimu Irene-Kinera , Nakaye Catherine , Babirye Juliet Allen , Kaganzi Hellen , Lukyamuzi Zubair , Kizito Samuel , Kuteesa Cynthia Ndikuno , Mujugira Andrew
Published: April 2021

Background

Antiretroviral therapy (ART) adherence is a primary determinant of sustained viral suppression, HIV transmission risk, disease progression and death. The World Health Organization recommends that adherence support interventions be provided to people on ART, but implementation is suboptimal. We evaluated linkage to intensive adherence counselling (IAC) for persons on ART with detectable viral load (VL).

Methods

Between January and December 2017, we conducted a retrospective chart review of HIV-positive persons on ART with detectable VL (> 1000 copies/ml), in Gomba district, rural Uganda. We abstracted records from eight HIV clinics; seven health center III’s (facilities which provide basic preventive and curative care and are headed by clinical officers) and a health center IV (mini-hospital headed by a medical doctor). Linkage to IAC was defined as provision of IAC to ART clients with detectable VL within three months of receipt of results at the health facility. Descriptive statistics and multivariable logistic regression analyses were used to evaluate factors associated with linkage to IAC.

Results

Of 4,100 HIV-positive persons on ART for at least 6 months, 411 (10%) had detectable VL. The median age was 32 years (interquartile range [IQR] 13–43) and 52% were female. The median duration on ART was 3.2 years (IQR 1.8–4.8). A total of 311 ART clients (81%) were linked to IAC. Receipt of ART at a Health Center level IV was associated with a two-fold higher odds of IAC linkage compared with Health Center level III (adjusted odds ratio [aOR] 1.78; 95% CI 1.00–3.16; p = 0.01). Age, gender, marital status and ART duration were not related to IAC linkage.

Conclusions

Linkage to IAC was high among persons with detectable VL in rural Uganda, with greater odds of linkage at a higher-level health facility. Strategies to optimize IAC linkage at lower-level health facilities for persons with suboptimal ART adherence are needed.
Getting into a “Flow” state: a systematic review of flow experience in neurological diseases
Authors: Ottiger Beatrice , Van Wegen Erwin , Keller Katja , Nef Tobias , Nyffeler Thomas , Kwakkel Gert , Vanbellingen Tim
Published: April 2021

Background

Flow is a subjective psychological state that people report when they are fully involved in an activity to the point of forgetting time and their surrounding except the activity itself. Being in flow during physical/cognitive rehabilitation may have a considerable impact on functional outcome, especially when patients with neurological diseases engage in exercises using robotics, virtual/augmented reality, or serious games on tablets/computer. When developing new therapy games, measuring flow experience can indicate whether the game motivates one to train. The purpose of this study was to identify and systematically review current literature on flow experience assessed in patients with stroke, traumatic brain injury, multiple sclerosis and Parkinson’s disease. Additionally, we critically appraised, compared and summarized the measurement properties of self-reported flow questionnaires used in neurorehabilitation setting.

Design

A systematic review using PRISMA and COSMIN guidelines.

Methods

MEDLINE Ovid, EMBASE Ovid, CINAHL EBSCO, SCOPUS were searched. Inclusion criteria were (1) peer-reviewed studies that (2) focused on the investigation of flow experience in (3) patients with neurological diseases (i.e., stroke, traumatic brain injury, multiple sclerosis and/or Parkinson’s disease). A qualitative data synthesis was performed to present the measurement properties of the used flow questionnaires.

Results

Ten studies out of 911 records met the inclusion criteria. Seven studies measured flow in the context of serious games in patients with stroke, traumatic brain injury, multiple sclerosis and Parkinson’s disease. Three studies assessed flow in other activities than gaming (song-writing intervention and activities of daily living). Six different flow questionnaires were used, all of which were originally validated in healthy people. None of the studies presented psychometric data in their respective research population.

Conclusion

The present review indicates that flow experience is increasingly measured in the physical/cognitive rehabilitation setting in patients with neurological diseases. However, psychometric properties of used flow questionnaires are lacking. For exergame developers working in the field of physical/cognitive rehabilitation in patients with neurological diseases, a valid flow questionnaire can help to further optimize the content of the games so that optimal engagement can occur during the gameplay. Whether flow experiences can ultimately have positive effects on physical/cognitive parameters needs further study.
VP39 of Spodoptera litura multicapsid nucleopolyhedrovirus cannot efficiently rescue the nucleocapsid assembly of vp39-null Autographa californica multiple nucleopolyhedrovirus
Authors: Li Sainan , Ou Bingming , Lv Yina , Gan Tian , Zhao Haizhou , Liu Wenhua
Published: April 2021

Background

Autographa californica multiple nucleopolyhedrovirus (AcMNPV) vp39 is conserved in all sequenced baculovirus genomes. In previous studies, VP39 has been identified as the major capsid structure protein of baculoviruses and found to be essential for nucleocapsid assembly. The nucleocapsid composition and structure of Group I and II NPVs of the Alphabaculovirus genus are very similar. It is not clear whether the major capsid structure protein VP39 of Group I NPVs is functionally identical to or substitutable with the Group II NPV VP39. In this study, the function of Group II Spodoptera litura MNPV (SpltMNPV) VP39 in Group I AcMNPV was characterized.

Methods

Sequence alignment of AcMNPV VP39 and SpltMNPV VP39 was performed using Clustal X and edited with GeneDoc. To determine whether VP39 of Group I NPVs can be functionally substituted by Group II NPV VP39, a vp39-null AcMNPV (vAcvp39KO) and a vp39-pseudotyped AcMNPV (vAcSpltvp39:FLAG), in which the Group I AcMNPV vp39 coding sequence was replaced with that of SpltMNPV from Group II NPVs, were constructed via homologous recombination in Escherichia coli. Using an anti-FLAG monoclonal antibody, immunoblot analysis was performed to examine SpltMNPV VP39 expression. Fluorescence and light microscopy were used to monitor viral replication and infection. Viral growth curve analysis was performed using a fifty percent tissue culture infective dose (TCID50) endpoint dilution assay. Viral morphogenesis was detected using an electron microscope.

Results

Sequence alignment indicated that the N-termini of AcMNPV VP39 and SpltMNPV VP39 are relatively conserved, whereas the C-terminus of SpltMNPV VP39 lacks the domain of amino acid residues 306–334 homologous to AcMNPV VP39. Immunoblot analysis showed that SpltMNPV VP39 was expressed in vAcSpltvp39:FLAG. Fluorescence and light microscopy showed that vAcSpltvp39:FLAG did not spread by infection. Viral growth curve analysis confirmed a defect in infectious budded virion production. Electron microscopy revealed that although masses of abnormally elongated empty capsid structures existed inside the nuclei of Sf9 cells transfected with vAcSpltvp39:FLAG, no nucleocapsids were observed.

Conclusion

Altogether, our results demonstrated that VP39 from SpltMNPV cannot efficiently substitute AcMNPV VP39 during nucleocapsid assembly in AcMNPV.
Variation of heart and lung radiation doses according to setup uncertainty in left breast cancer
Authors: Park Sunmin , Rim Chai Hong , Yoon Won Sup
Published: April 2021

Purpose

Breast radiotherapy set-up is often uncertain. Actual dose distribution to normal tissues could be different from planned dose distribution. The objective of this study was to investigate such difference in dose distribution according to the extent of set-up error in breast radiotherapy.

Materials and methods

A total of 50 Gy with fraction size of 2 Gy was given to 30 left breasts with different set-ups applying a deep inspiration breath holding (DIBH) or a free breathing (FB) technique. Under the assumption that errors might come from translational axes of deep or caudal directions, the isocenter was shifted from the original tangential alignment every 2.5 mm to simulate uncertainty of deep and caudal tangential set-up in DIBH and FB. Changes were evaluated for dosimetric parameters for the heart, the left ventricle (LV), the left anterior descending coronary artery (LAD), and the ipsilateral lung.

Results

On the original plan, mean doses of heart and ipsilateral lung were 2.0 ± 1.1 Gy and 3.7 ± 1.4 Gy in DIBH and 8.4 ± 1.3 Gy and 7.8 ± 1.5 Gy in FB, respectively. The change of dose distribution for the heart in DIBH was milder than that in FB. The deeper the tangential set-up, the worse the heart, LV, LAD, and ipsilateral lung doses, showing as much as 49.4%, 56.4%, 90.3%, and 26.1% shifts, respectively, in 5 mm DIBH setup. The caudal set-up did not show significant dose difference. In multiple comparison of DIBH, differences of mean dose occurred in all 7.5 mm deep set-ups for the heart (p = 0.025), the LV (p = 0.049), and LAD (p = 0.025) in DIBH.

Conclusions

To correct set-up error over indicated limitation for deep tangential set-up in DIBH at 5 mm action level, mean heart and ipsilateral lung doses are expected to increase approximately 50% and 25%, respectively.
Uniportal VATS pleural biopsy in the diagnosis of exudative pleural effusion: awake or intubated?
Authors: Gokce Mertol , Altinsoy Bulent , Piskin Ozcan , Bahadir Burak
Published: April 2021

Background

The aim of this study is to compare the diagnostic efficacy and safety of video-assisted thoracoscopic surgery (VATS) with awake VATS (AVATS) pleural biopsy in undiagnosed exudative pleural effusions.

Methods

The diagnostic efficacy of pleural biopsy by uniportal VATS under general anesthesia or AVATS under local anesthesia and sedation performed by the same surgeon in patients with undiagnosed exudative pleural effusion between 2007 and 2020 were retrospectively evaluated. Test sensitivity, specificity, positive predictive value and negative predictive value were compared as well as age, gender, comorbidities, procedure safety, additional pleural-based interventions, duration time of operation and length of hospital stay.

Results

Of 154 patients with undiagnosed exudative pleural effusion, 113 (73.37%) underwent pleural biopsy and drainage with VATS, while 41 (26.62%) underwent AVATS pleural biopsy. Sensitivity, specificity, positive predictive value and negative predictive value were 92, 100, 100, and 85.71% for VATS, and 83.3, 100, 100, and 78.9% for AVATS, respectively. There was no significant difference in diagnostic test performance between the groups, (p = 0.219). There was no difference in the rate of complications [15 VATS (13.3) versus 4 AVATS (9.8%),p = 0.557]. Considering additional pleural-based interventions, while pleural decortication was performed in 13 (11.5%) cases in the VATS group, no pleural decortication was performed in AVATS group, (p = 0.021). AVATS group was associated with shorter duration time of operation than VATS (22.17 + 6.57 min. Versus 51.93 + 8.85 min.,p < 0.001). Length of hospital stay was relatively shorter in AVATS but this was not statistically significant different (p = 0.063).

Conclusions

Our study revealed that uniportal AVATS pleural biopsy has a similar diagnostic efficacy and safety profile with VATS in the diagnosis and treatment of patients with undiagnosed pleural effusion who have a high risk of general anesthesia due to advanced age and comorbidities. Accordingly, uniportal AVATS pleural biopsy may be considered in the diagnosis and treatment of all exudative undiagnosed pleural effusions.
Long-term prognosis analysis of PARACHUTE device implantation in patients with ischemic heart failure: a single-center experience of Chinese patients
Authors: Li Jianghua , Liu Huadong , Liu Qiyun , Liu Cheng , Xiong Wei , Ma Wei , Zhang Baowei , Dong Shaohong , Li Tangzhiming
Published: April 2021

Background

Heart failure (HF) is one of the leading causes of mortality and morbidity. The PARACHUTE device is designed to partition for left ventricular (LV) apical aneurysm post extensive anterior myocardial infarction (MI). However, the long-term prognosis of the PARACHUTE device post-implantation is unclear.

Methods

From November 2015 to April 2017, six subjects with New York Heart Association Classes II, III and IV ischemic HF, LV ejection fraction between (LVEF) 15 and 40%; and LV anterior apical aneurysm were enrolled in our center. The cumulative event rates for MI, hospitalization, and mortality were documented. Further assessment of LVEF, LV end-diastolic diameter (LVEDD), and estimated pulmonary artery pressure were determined by echocardiography core laboratory. For quantitative data comparison, paired t-test was employed.

Results

Device implantation was successful in all six enrolled subjects, and acute device association adverse events were not observed. At 4.6 ± 1.7 years follow-up, major adverse cardiac events (MACEs) were found in 50% patients, and the survival rate was 86.7%. We observed that the LVEF was significantly elevated after deployment (46.00 ± 6.00% vs. 35.83 ± 1.47%, P = 0.009). Besides, the LVEDD elevated after MI (51.17 ± 3.71 vs. 62.83 ± 3.25, P < 0.001) was revealed, but the device sustained preserved LVEDD after implantation.

Conclusion

The PARACHUTE device is an alternative therapy for patients with severe LV maladaptive remodeling. However, the device seems to increase the HF ratio.

Trial registration

NCT02240940
Impact of tricuspid regurgitation on late right ventricular failure in left ventricular assist device patients ~can prophylactic tricuspid annuloplasty prevent late right ventricular failure? ~
Authors: Nakazato Taro , Yoshioka Daisuke , Toda Koichi , Miyagawa Shigeru , Kainuma Satoshi , Kawamura Takuji , Kawamura Ai , Kashiyama Noriyuki , Ueno Takayoshi , Kuratani Toru , Sakata Yasushi , Sawa Yoshiki
Published: April 2021

Background

In this study, we evaluated the prevalence of tricuspid regurgitation (TR) worsening in patients with left ventricular assist devices (LVADs) and its impact on late right ventricular (RV) failure.

Methods

We enrolled 147 patients of the 184 patients who underwent continuous-flow LVAD implantations from 2005 to March 2018. The prevalence of postoperative TR worsening and late RV failure were retrospectively evaluated.

Results

Concomitant tricuspid annuloplasty (TAP) was performed in 28 of 41 patients (68%) with preoperative TR greater than or equal to moderate (TR group) and in 23 of 106 patients (22%) with preoperative TR less than or equal to mild (non-TR group). Regarding the TR-free rates, despite receiving or not receiving concomitant TAP, there was no significant difference between the 2 groups (TR group: p = 0.37; non-TR group: p = 0.42). Of the 9 patients with postoperative TR greater than or equal to moderate, late RV failure developed in 3 patients, with TR worsening after RV failure in each case. During follow-up, 16 patients (11%) had late RV failure. As for the late RV failure-free rates, despite receiving or not receiving concomitant TAP, there was no significant difference between the 2 groups (TR group: p = 0.37; non-TR group: p = 0.96).

Conclusions

TR prognosis was preferable regardless of a patient receiving concomitant TAP; however, the presence of postoperative TR seemed to unrelated to late RV failure. Prophylactic TAP might not be necessary to prevent late RV failure.
Novel criteria to classify ARDS severity using a machine learning approach
Authors: Sayed Mohammed , Riaño David , Villar Jesús
Published: April 2021

Background

Usually, arterial oxygenation in patients with the acute respiratory distress syndrome (ARDS) improves substantially by increasing the level of positive end-expiratory pressure (PEEP). Herein, we are proposing a novel variable [PaO2/(FiO2xPEEP) or P/FPE] for PEEP ≥ 5 to address Berlin’s definition gap for ARDS severity by using machine learning (ML) approaches.

Methods

We examined P/FPE values delimiting the boundaries of mild, moderate, and severe ARDS. We applied ML to predict ARDS severity after onset over time by comparing current Berlin PaO2/FiO2 criteria with P/FPE under three different scenarios. We extracted clinical data from the first 3 ICU days after ARDS onset (N = 2738, 1519, and 1341 patients, respectively) from MIMIC-III database according to Berlin criteria for severity. Then, we used the multicenter database eICU (2014–2015) and extracted data from the first 3 ICU days after ARDS onset (N = 5153, 2981, and 2326 patients, respectively). Disease progression in each database was tracked along those 3 ICU days to assess ARDS severity. Three robust ML classification techniques were implemented using Python 3.7 (LightGBM, RF, and XGBoost) for predicting ARDS severity over time.

Results

P/FPE ratio outperformed PaO2/FiO2 ratio in all ML models for predicting ARDS severity after onset over time (MIMIC-III: AUC 0.711–0.788 and CORR 0.376–0.566; eICU: AUC 0.734–0.873 and CORR 0.511–0.745).

Conclusions

The novel P/FPE ratio to assess ARDS severity after onset over time is markedly better than current PaO2/FiO2 criteria. The use of P/FPE could help to manage ARDS patients with a more precise therapeutic regimen for each ARDS category of severity.
A double-blinded, placebo-controlled randomized trial evaluating the efficacy and safety of Zhigancao Tang granules for treating HFpEF: study protocol for a randomized controlled trial
Authors: Zhang Na , Zhao Yingli , Liu Yu , Tang Nuo , Zheng Wang , Mao Meijiao , Liu Qingcheng , Shen Lin , Deng Bing
Published: April 2021

Background

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by diastolic dysfunction. Despite the increasing incidence of HFpEF, there is no available therapy that reduces the mortality rate of HFpEF. Zhigancao Tang has been used traditionally for the treatment of cardiovascular diseases in China. The use of traditional Chinese medicine (TCM) is associated with improvements in clinical syndromes and quality of life of patients. A randomized clinical trial should be conducted to provide clear evidence regarding the efficacy and safety of Zhigancao Tang granules for the treatment of HFpEF.

Methods

A randomized, double-blinded, placebo-controlled clinical trial was proposed. A total of 122 patients with HFpEF will be randomly assigned to receive Zhigancao Tang granules or placebo for 12 weeks. The primary outcome measure is cardiac function. The secondary outcomes include measurement of the integral TCM syndrome score, echocardiography, 6-min walk test, N-terminal-pro hormone B-type natriuretic peptide level, atrial natriuretic peptide level, Minnesota Living with Heart Failure scale, and Lee’s scale. The outcome measures will be evaluated at baseline, 4 weeks, and 12 weeks. Adverse events will be evaluated from baseline till the 12-week follow-up period.

Discussion

The results of this trial will demonstrate whether Zhigancao Tang granules are effective and safe for treating HFpEF.

Trial registration

ClinicalTrials.gov NCT04317339. Registered on 23 March 2020.
Effect of acupotomy in knee osteoarthritis patients: study protocol for a randomized controlled trial
Authors: Xu Danghan , Lee Minghui , Huang Cihui , Wei Jia , Zhou Mengxue , Yao Taotao , Lu Jingjing , Zhao Wenjing , Xu Nuo , Huang Ruina , He Jun , Zheng Liang
Published: April 2021

Background

Symptomatic knee osteoarthritis (KOA) is common in China. Pharmacological therapy is not the first recommendation because of its safety issues. Nonpharmacological therapy, such as lifestyle adjustments, weight loss, muscle strengthening, and aerobic exercise programs, is strongly recommended for KOA. However, these approaches may fail due to poor patient compliance. There is a lack of high-quality randomized controlled trials of acupotomy, an effective treatment for KOA. This study was designed to investigate the efficacy of acupotomy in patients with KOA.

Methods

A total of 136 patients will be enrolled at the First Affiliated Hospital of Guangzhou University of Chinese Medicine and assigned to the acupotomy group or sham acupotomy group according to the block randomization scheme. Patients in the acupotomy group will receive 2 sessions of acupotomy for 2 weeks (once a week). Patients in the sham group will receive 2 sessions of sham stimulation for 2 weeks (once a week). All patients will use indomethacin cream externally. The primary outcome will be the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the secondary outcomes will be the visual analog scale (VAS) score, plantar pressure distribution test result, X-ray examination findings, musculoskeletal ultrasound findings, maximum knee circumference, joint mobility, and quality of life. Measurements will be taken at baseline, 1 week after the end of treatment, and at the 3- and 6-month follow-ups.

Discussion

To the best of our knowledge, this will be the first single-blind, sham-controlled study of acupotomy. The outcome assessors will also be blinded. The aim of this work is to demonstrate the efficacy of acupotomy in treating KOA.

Trial registration

Chinese Clinical Trial RegistryChiCTR2000033047. Registered on 18 May 2020.
ATP and NADPH engineering of Escherichia coli to improve the production of 4-hydroxyphenylacetic acid using CRISPRi
Authors: Shen Yu-Ping , Liao Yu-Ling , Lu Qian , He Xin , Yan Zhi-Bo , Liu Jian-Zhong
Published: April 2021

Background

4-Hydroxyphenylacetic acid (4HPAA) is an important raw material for the synthesis of drugs, pesticides and biochemicals. Microbial biotechnology would be an attractive approach for 4HPAA production, and cofactors play an important role in biosynthesis.

Results

We developed a novel strategy called cofactor engineering based on clustered regularly interspaced short palindromic repeat interference (CRISPRi) screening (CECRiS) for improving NADPH and/or ATP availability, enhancing the production of 4HPAA. All NADPH-consuming and ATP-consuming enzyme-encoding genes of E. coli were repressed through CRISPRi. After CRISPRi screening, 6 NADPH-consuming and 19 ATP-consuming enzyme-encoding genes were identified. The deletion of the NADPH-consuming enzyme-encoding gene yahK and the ATP-consuming enzyme-encoding gene fecE increased the production of 4HPAA from 6.32 to 7.76 g/L. Automatically downregulating the expression of the pabA gene using the Esa-PesaS quorum-sensing-repressing system further improved the production of 4HPAA. The final strain E. coli 4HPAA-∆yfp produced 28.57 g/L of 4HPAA with a yield of 27.64% (mol/mol) in 2-L bioreactor fed-batch fermentations. The titer and yield are the highest values to date.

Conclusion

This CECRiS strategy will be useful in engineering microorganisms for the high-level production of bioproducts.
Insecticide resistance status in Anopheles gambiae (s.l.) in coastal Kenya
Authors: Munywoki Daniel N. , Kokwaro Elizabeth D. , Mwangangi Joseph M. , Muturi Ephantus J. , Mbogo Charles M.
Published: April 2021

Background

The rapid and widespread evolution of insecticide resistance has emerged as one of the major challenges facing malaria control programs in sub-Saharan Africa. Understanding the insecticide resistance status of mosquito populations and the underlying mechanisms of insecticide resistance can inform the development of effective and site-specific strategies for resistance prevention and management. The aim of this study was to investigate the insecticide resistance status of Anopheles gambiae (s.l.) mosquitoes from coastal Kenya.

Methods

Anopheles gambiae (s.l.) larvae sampled from eight study sites were reared to adulthood in the insectary, and 3- to 5-day-old non-blood-fed females were tested for susceptibility to permethrin, deltamethrin, dichlorodiphenyltrichloroethane (DDT), fenitrothion and bendiocarb using the standard World Health Organization protocol. PCR amplification of rDNA intergenic spacers was used to identify sibling species of the An. gambiae complex. The An. gambiae (s.l.) females were further genotyped for the presence of the L1014S and L1014F knockdown resistance (kdr) mutations by real-time PCR.

Results

Anopheles arabiensis was the dominant species, accounting for 95.2% of the total collection, followed by An. gambiae (s.s.), accounting for 4.8%. Anopheles gambiae (s.l.) mosquitoes were resistant to deltamethrin, permethrin and fenitrothion but not to bendiocarb and DDT. The L1014S kdr point mutation was detected only in An. gambiae (s.s.), at a low allelic frequency of 3.33%, and the 1014F kdr mutation was not detected in either An. gambiae (s.s.) or An. arabiensis.

Conclusion

The findings of this study demonstrate phenotypic resistance to pyrethroids and organophosphates and a low level of the L1014S kdr point mutation that may partly be responsible for resistance to pyrethroids. This knowledge may inform the development of insecticide resistance management strategies along the Kenyan Coast.

Graphical Abstract
Urine proteomics for profiling of mouse toxoplasmosis using liquid chromatography tandem mass spectrometry analysis
Authors: Cui Lin-Lin , Zhou Chun-Xue , Han Bing , Wang Sha-Sha , Li Si-Ying , Xie Shi-Chen , Zhou Dong-Hui
Published: April 2021

Background

Toxoplasma gondii is an obligate intracellular parasite that causes toxoplasmosis. Urine is an easily obtained clinical sample that has been widely applied for diagnostic purposes. However, changes in the urinary proteome during T. gondii infection have never been investigated.

Methods

Twenty four-hour urine samples were obtained from BALB/c mice with acute infection [11 days post infection (DPI)], mice with chronic infection (35 DPI) and healthy controls, and were analyzed using a label-free liquid chromatography tandem mass spectrometry analysis.

Results

We identified a total of 13,414 peptides on 1802 proteins, of which 169 and 47 proteins were significantly differentially expressed at acute and chronic infection phases, respectively. Clustering analysis revealed obvious differences in proteome profiles among all groups. Gene ontology analysis showed that a large number of differentially expressed proteins (DEPs) detected in acute infection were associated with biological binding activity and single-organism processes. KEGG pathway enrichment analysis showed that the majority of these DEPs were involved in disease-related and metabolic pathways.

Conclusions

Our findings revealed global reprogramming of the urine proteome following T.gondii infection, and data obtained in this study will enhance our understanding of the host responses to T. gondii infection and lead to the identification of new diagnostic biomarkers.

Graphical Abstract
Impacts of ivermectin mass drug administration for onchocerciasis on mosquito populations of Ogun state, Nigeria
Authors: Omitola Olaitan Olamide , Umunnakwe Cynthia Uchechukwu , Bayegun Adedotun Ayodeji , Anifowose Samuel Akinjide , Mogaji Hammed Oladeji , Oluwole Akinola Stephen , Odoemene Simon Nnayere , Awolola Taiwo Sam , Osipitan Adebola Adedoyin , Sam-Wobo Sammy Olufemi , Ekpo Uwem Friday
Published: April 2021

Background

The impact of single-dose mass drug administration (MDA) of ivermectin for onchocerciasis on mosquito populations was investigated in Ogun State, Nigeria.

Methods

Indoor and outdoor collection of mosquitoes was carried out in two intervention (IC) and two control communities (CC) at three different periods: pre-MDA (baseline), 2–3 days after MDA and 13–14 days after MDA. The density and parity rate of female Anopheles and Culex mosquitoes were determined and compared. Environmental and climatic data of study locations were obtained to perform generalized linear model analysis.

Results

A total of 1399 female mosquitoes were collected, including 1227 Anopheles and 172 Culex mosquitoes. There was a similar magnitude of reduction in the indoor density of Anopheles by 29% in the IC and CC 2–3 days post-MDA but the reduction in indoor parity rate was significantly higher (p = 0.021) in the IC, reducing by more than 50%. In the IC, observation of a significant reduction at 2–3 days post-MDA was consistent for both the indoor density (1.43 to 1.02) and indoor parity rate (95.35% to 44.26%) of Anopheles mosquitoes. The indoor parity rate of Anopheles remained significantly reduced (75.86%) 13–14 post-MDA. On the other hand, the indoor density of Culex increased from 0.07 to 0.10 at 2–3 days post-MDA while the indoor parity rate of Culex did not change. The outdoor density of Anopheles in the IC increased (p = 0.394) from 0.58 to 0.90 at 2–3 days post-MDA; a similar observation was consistent for the outdoor density (2.83 to 3.90) and outdoor parity rate (70.59% to 97.44%) of Culex, while the outdoor parity rate of Anopheles reduced from 85.71 to 66.67% at 2–3 days post-MDA. A generalized linear model showed that ivermectin MDA significantly caused a reduction in both the indoor density (p < 0.001) and indoor parity rate (p = 0.003) of Anopheles in the IC.

Conclusion

Ivermectin MDA resulted in the reduction of both the survival and density of Anopheles mosquitoes. This has strong implications for malaria transmission, which depends strongly on vector survival.

Graphical abstract
Transcriptomic profiling of three-dimensional cholangiocyte spheroids long term exposed to repetitive Clonorchis sinensis excretory-secretory products
Authors: Kim Jung-Woong , Yi Junyeong , Park Jinhong , Jeong Ji Hoon , Kim Jinho , Won Jihee , Chung Seok , Kim Tong-Soo , Pak Jhang Ho
Published: April 2021

Background

Biliary tract infection with the carcinogenic human liver fluke, Clonorchis sinensis, provokes chronic inflammation, epithelial hyperplasia, periductal fibrosis, and even cholangiocarcinoma. Complications are proportional to the intensity and duration of the infection. In addition to mechanical irritation of the biliary epithelia from worms, their excretory-secretory products (ESPs) cause chemical irritation, which leads to inflammation, proliferation, and free radical generation.

Methods

A three-dimensional in vitro cholangiocyte spheroid culture model was established, followed by ESP treatment. This allowed us to examine the intrinsic pathological mechanisms of clonorchiasis via the imitation of prolonged and repetitive in vivo infection.

Results

Microarray and RNA-Seq analysis revealed that ESP-treated cholangiocyte H69 spheroids displayed global changes in gene expression compared to untreated spheroids. In ESP-treated H69 spheroids, 185 and 63 probes were found to be significantly upregulated and downregulated, respectively, corresponding to 209 genes (p < 0.01, fold change > 2). RNA-Seq was performed for the validation of the microarray results, and the gene expression patterns in both transcriptome platforms were well matched for 209 significant genes. Gene ontology analysis demonstrated that differentially expressed genes were mainly classified into immune system processes, the extracellular region, and the extracellular matrix. Among the upregulated genes, four genes (XAF1, TRIM22, CXCL10, and BST2) were selected for confirmation using quantitative RT-PCR, resulting in 100% similar expression patterns in microarray and RNA-Seq.

Conclusions

These findings broaden our understanding of the pathological pathways of liver fluke-associated hepatobiliary disorders and suggest a novel therapeutic strategy for this infectious cancer.

Graphical Abstract