bluuebunny/crossref_metadata_2025 huggingface dataset:
Cervical cancer screening – The challenges of complete pathways of care in low-income countries: Focus on Malawi
Authors: Cubie Heather A , Campbell Christine
Published: May 2020

Cervical cancer is the fourth most common cancer among women globally, with approximately 580,000 new diagnoses in 2018. Approximately, 90% of deaths from this disease occur in low- and middle-income countries, especially in areas of high HIV prevalence, and largely due to limited prevention and screening opportunities and scarce treatment options. In this overview, we describe the opportunities and challenges faced in many low- and middle-income countries in delivery of cervical cancer detection, treatment and complete pathways of care. In particular, drawing on our experience and that of colleagues, we describe cervical screening and pathways of care provision in Malawi, as a case study of a low-resource country with high incidence and mortality rates of cervical cancer. Screening methods such as cytology – although widely used in high-income countries – have limited relevance in many low-resource settings. The World Health Organization recommends screening using human papillomavirus testing wherever possible; however, although human papillomavirus primary testing is more sensitive and detects precancers and cancers earlier than cytology, there are currently costs, infrastructure considerations and specificity issues that limit its use in low- and middle-income countries. The World Health Organization accepts the alternative screening approach of visual inspection with acetic acid as part of ‘screen and treat’ programmes as a simple and inexpensive test that can be undertaken by trained health workers and hence give wider screening coverage; however, subjectivity and variability in interpretation of findings between providers raise issues of false positives and overtreatment. Cryotherapy using either nitrous oxide or carbon dioxide is an established treatment for precancerous lesions within ‘screen and treat’ programmes; more recently, thermal ablation has been recognized as suitable to low-resource settings due to lightweight equipment, short treatment times, and hand-held battery-operated and solar-powered models. For larger lesions and cancers, complete clinical pathways (including loop excision, surgery, radiotherapy, chemotherapy and palliative care) are required for optimal care of women. However, provision of each of these components of cancer control is often limited due to limited infrastructure and lack of trained personnel. Hence, global initiatives to reduce cervical mortality need to adopt a holistic approach to health systems strengthening.
A hybrid control strategy based on CSA and ELM for uncertain nonlinear chaotic system
Authors: Li Yan , He Yigang , Yu Wenxin
Published: May 2020

The study of nonlinear chaotic systems and their control is an important topic. In this paper, a hybrid control strategy based on cuckoo search algorithm and extreme learning machine is proposed. Cuckoo search algorithm is used in a hybrid control strategy in order to optimise the weights and biases in extreme learning machine leading to the improvement of its performance. Simulations indicate that the proposed method is able to fit nonlinear chaotic systems and control chaotic systems effectively. Data used in the nonlinear chaotic system are also tested for uncertainty and unknown systems. Simulation results confirm that the proposed method shows robustness for noisy data and perturbed parameters.
Use of non-sterile gloves in the ward environment: an evaluation of healthcare workers’ perception of risk and decision making
Authors: Flores Ashley , Wrigley Martha , Askew Peter , Craig Rachel , Egan Bernadette , Towey Linda , Shawe Jill
Published: May 2020

Background:

Studies have found that inappropriate use of non-sterile gloves (NSG) can affect hand hygiene compliance; the main risks are missing opportunities for hand hygiene and gloves being a vector for microbial transmission.

Aim:

The aims of this study were to explore the accuracy of healthcare worker (HCW) risk assessment and decision making regarding the use of NSG.

Methods:

The study was conducted in two acute NHS Trusts and a community social enterprise. A cross-sectional survey was carried out, followed by qualitative semi-structured interviews.

Findings:

There were highly significant differences at the 95% probability level between staff groups, unqualified staff being significantly more likely than qualified staff to report NSG use when not indicated ( P < 0.0001). The primary motivating factor for staff to wear NSG was for personal protection; the secondary factor being the protection of patients. Staff were also motivated by a desire to create an image of professionalism. Respondents were more likely to follow the lead of seniors in their own profession.

Discussion:

The results suggest a necessity for change interventions aimed at unqualified staff such as healthcare assistants (HCAs). It would be beneficial to review the indications for glove use and amend organisational policies accordingly. Leaders in each professional staff group would be required to influence practice across organisations, taking into account motivating factors, and in association with multi-modal interventions to improve practice.
Intra-articular Transcalcaneal Fracture-Dislocation Associated With Ipsilateral Transtalar Fracture: A Report of a Rare Combination
Authors: Nishikawa Danilo Ryuko Cândido , de Miranda Bruno Rodrigues , Duarte Fernando Aires , Saito Guilherme Honda , Bitar Rogério Carneiro , Monteiro Augusto César , Prado Marcelo Pires , de Cesar Netto Cesar
Published: May 2020

The association of ipsilateral talar and calcaneal fractures is an uncommon combination and is typically the result of a high-energy trauma. It is often associated with comminution, marked fracture displacement, and soft-tissue compromise. Obtaining satisfactory clinical and radiographic results is very challenging. Residual deformities, multiple procedures, and limitations are usually the norm. Therefore, studies have suggested that primary arthrodesis may represent the best option of surgical treatment. In this study, we report a case of a 30-year-old male patient with a rare combination of a highly comminuted transcalcaneal fracture-dislocation associated with a talar neck fracture successfully treated with open reduction and internal fixation (ORIF) with an 18-month follow-up. This case demonstrates that even when there are associated fractures of the talus and calcaneus with severe bone loss, ORIF may provide satisfactory outcomes in the short-term postoperative period.

Levels of Evidence: Level V: Case report
External validation of an emergency department triage algorithm for chest pain patients
Authors: Miró Òscar , Lopez-Ayala Pedro , Martínez-Nadal Gemma , Troester Valentina , Strebel Ivo , Coll-Vinent Blanca , Gil Víctor , Jiménez Sònia , García-Martínez Ana , Ortega Mar , Boeddinghaus Jasper , Nestelberger Thomas , Gualandro Danielle M , Bragulat Ernest , Sánchez Miquel , Peacock W Frank , Mueller Christian , López-Barbeito Beatriz
Published: May 2020

Background

We aimed to externally validate an emergency department triage algorithm including five hierarchical clinical variables developed to identify chest pain patients at low risk of having an acute coronary syndrome justifying delayed rather than immediate evaluation.

Methods

In a single-centre cohort enrolling 29,269 consecutive patients presenting with chest pain, the performance of the algorithm was compared against the emergency department discharge diagnosis. In an international multicentre study enrolling 4069 patients, central adjudication by two independent cardiologists using all data derived from cardiac work-up including follow-up served as the reference. Triage towards ‘low-risk’ required absence of all five clinical ‘high-risk’ variables: history of coronary artery disease, diabetes, pressure-like chest pain, retrosternal chest pain and age above 40 years. Safety (sensitivity and negative predictive value (NPV)) and efficacy (percentage of patients classified as low risk) was tested in this initial proposal (Model A) and in two additional models: omitting age criteria (Model B) and allowing up to one (any) of the five high-risk variables (Model C).

Results

The prevalence of acute coronary syndrome was 9.4% in the single-centre and 28.4% in the multicentre study. The triage algorithm had very high sensitivity/NPV in both cohorts (99.4%/99.1% and 99.9%/99.1%, respectively), but very low efficacy (6.2% and 2.7%, respectively). Model B resulted in sensitivity/NPV of 97.5%/98.3% and 96.1%/89.4%, while efficacy increased to 14.2% and 10.4%, respectively. Model C resulted in sensitivity/NPV of 96.7%/98.6% and 95.2%/91.3%, with a further increase in efficacy to 23.1% and 15.5%, respectively.

Conclusion

A triage algorithm for the identification of low-risk chest pain patients exclusively based on simple clinical variables provided reasonable performance characteristics possibly justifying delayed rather than immediate evaluation in the emergency department.
An innovative lipid-lowering approach to enhance attainment of low-density lipoprotein cholesterol goals
Authors: Buonvino Camille , Chopard Romain , Guillon Benoît , Puymirat Etienne , Farnier Michel , Ferrières Jean , Krempf Michel , Bruckert Eric , Meneveau Nicolas , Schiele François
Published: May 2020

Aims

To improve attainment of LDL-cholesterol (LDL-c) targets, an expert group proposed an algorithm for lipid-lowering therapy during hospitalization for acute coronary syndrome and during follow-up. We aimed to assess adherence to this algorithm, and evaluate its impact on LDL-c levels and on attainment of therapeutic LDL-c targets in a population of post-acute coronary syndrome patients.

Methods and results

Prospective, observational study including patients admitted for acute coronary syndrome between February 2017 and September 2018. Patients admitted without statins or ezetimibe were considered ‘naïve’. Baseline LDL-c was admission LDL-c in naïve patients, and for those taking lipid-lowering therapy at admission, baseline LDL-c was back-calculated. In line with the most recent guidelines, the target was a >50% reduction in naïve LDL-c and <55 mg/dL. In total, 270 patients were analysed, mean age 67 ± 12 years, 78% men, 26% diabetic. At admission, 175 (65%) were naïve, 95 (35%) had previous lipid-lowering therapy, of which 13 (5%) statin+ezetimibe. Average LDL-c at admission was 120 ± 47 mg/dL (136 ± 44 mg/dL in naïve, 91 ± 39 mg/dL in pretreated patients). Discharge prescription was in compliance with the algorithm in 204 (76%) patients. Average LDL-c at two months was 57 ± 28 mg/dL; it was <55 mg/dL in 135 (50%), and 178 (66%) achieved a >50% reduction. Overall, 125/270 (46%) achieved the LDL-c goal. The reduction in LDL-c observed at two months persisted at five months.

Conclusion

Prescription of high-intensity statins, associated with ezetimibe where applicable, achieves LDL-c levels <55 mg/dL in 50% of patients at two months, and attains therapeutic goals defined by the European Society of Cardiology in 46% of cases.
Clinical Outcomes After Medial Patellofemoral Ligament Reconstruction Using Transosseous Sutures Versus Suture Anchors: A Prospective Nonrandomized Controlled Trial
Authors: Ye Mao , Zhang Hangzhou , Liang Qingwei
Published: May 2020

Background:

Patellar instability remains a challenging problem for orthopaedic surgeons. Recurrent patellar instability is traditionally treated with medial patellofemoral ligament (MPFL) reconstruction using a suture anchor or bone tunnel technique. Although the use of transosseous sutures was recently described for MPFL reconstruction, relevant clinical data have not been reported.

Purpose/Hypothesis:

The purpose of this study was to compare a new transosseous suture fixation technique with the suture anchor technique for MPFL reconstruction. The hypothesis was that reconstruction with transosseous sutures would show similar clinical results to reconstruction with suture anchors.

Study Design:

Cohort study; Level of evidence, 2.

Methods:

There were 65 patients with recurrent lateral patellar dislocations from January 2014 to December 2016 who were included in this prospective nonrandomized controlled trial. In total, 31 patients underwent MPFL reconstruction with suture anchors at the patella site (suture anchor group), while the other 34 patients underwent MPFL reconstruction with transosseous sutures (transosseous suture group). The main outcome variable (patellar redislocation) was recorded at follow-up (range, 25-60 months). The International Knee Documentation Committee (IKDC) score, Kujala score, range of motion, congruence angle, patellar tilt, redislocation rate, and complications were collected preoperatively and/or postoperatively.

Results:

No recurrent dislocations or other complications were observed in any of the patients. No significant differences were found at follow-up between the suture anchor and transosseous suture groups for subjective IKDC score, Kujala score, congruence angle, patellar tilt, redislocation rate, or range of motion.

Conclusion:

This short-term study showed that after MPFL reconstruction (suture anchors or transosseous sutures), patellar stability could be restored. With the numbers available, no significant differences in outcome scores were observed between patients in the transosseous suture and suture anchor groups.
Pentecost and the World: Roland Allen, the Spirit, and Remodeling Twenty-First-Century Mission
Authors: Oxbrow Mark
Published: May 2020

A century after his major publications, Roland Allen continues to attract attention within the mission community. He has much to say to contemporary perceptions that new models in mission are urgently required. Allen is less concerned with methods than with the spiritual impulse for mission and the biblical principles by which it is lived. The missionary Spirit of Christ is at the heart of all mission, and the Pauline principles that Allen advances derive from our response to that Spirit. Following Allen, this article challenges a number of accepted contemporary practices in mission, asking “Is Christ here being revealed?”
Mineralogical and hydraulic characteristics of mudstone in the Tamusu candidate area in northwest China for high-level radioactive waste geological disposal
Authors: Xiang Long , Liu Xiaodong , Liu Pinghui , Jiang Xingfu , Dai Chaocheng
Published: May 2020

The Tamusu region in northwest China is a key candidate area for China's clay rock deep geological repositories (DGRs) for high-level radioactive waste (HLRW) as it is composed of a continuous layer of thick lacustrine mudstone. To evaluate this mudstone as a host rock, two special test boreholes were drilled to investigate its spatial distribution and mineralogical and hydraulic characteristics. The southwest boundary and depositional centre of the lake basin were well delineated by boreholes TZK-1 and TZK-2. The continuous single-layer thickness of the target mudstone formation was up to 300 m at a depth of 500–800 m. Three main mineral types were determined, namely carbonates (mainly dolomite and ankerite), analcime and albite, and their abundance was used to distinguish three different facies. Other mineral phases, such as clay minerals (mainly illite and kaolinite), pyrite, hematite, quartz and calcite, were present as admixtures. The presence of carbonates may increase the mechanical strength and analcime may enhance the radionuclide adsorption properties of the mudstone. The self-sealing properties, which may be affected by the small amount of clay minerals, remain to be investigated. The hydraulic conductivity of the mudstone determined via in situ pulse tests ranged from 10–13 to 10–10 m s–1, suggesting that the Tamusu mudstone has ultra-low permeability. The transmissivity of the Tamusu mudstone fluctuated in regions with varying lithologies, but remained relatively constant for consistent lithologies. In summary, these preliminarily results confirm the possible suitability of the target formation as a host rock for DGRs of China's HLRW.
Mobilising community networks for early identification of tuberculosis and treatment initiation in Cambodia: an evaluation of a seed-and-recruit model
Authors: Teo Alvin Kuo Jing , Prem Kiesha , Tuot Sovannary , Ork Chetra , Eng Sothearith , Pande Tripti , Chry Monyrath , Hsu Li Yang , Yi Siyan
Published: May 2020

Background and objectives

The effects of active case finding (ACF) models that mobilise community networks for early identification and treatment of tuberculosis (TB) remain unknown. We investigated and compared the effect of community-based ACF using a seed-and-recruit model with one-off roving ACF and passive case finding (PCF) on the time to treatment initiation and identification of bacteriologically confirmed TB.

Methods

In this retrospective cohort study conducted in 12 operational districts in Cambodia, we assessed relationships between ACF models and: 1) the time to treatment initiation using Cox proportional hazards regression; and 2) the identification of bacteriologically confirmed TB using modified Poisson regression with robust sandwich variance.

Results

We included 728 adults with TB, of whom 36% were identifiedviathe community-based ACF using a seed-and-recruit model. We found community-based ACF using a seed-and-recruit model was associated with shorter delay to treatment initiation compared to one-off roving ACF (hazard ratio 0.81, 95% CI 0.68–0.96). Compared to one-off roving ACF and PCF, community-based ACF using a seed-and-recruit model was 45% (prevalence ratio (PR) 1.45, 95% CI 1.19–1.78) and 39% (PR 1.39, 95% CI 0.99–1.94) more likely to find and detect bacteriologically confirmed TB, respectively.

Conclusion

Mobilising community networks to find TB cases was associated with early initiation of TB treatment in Cambodia. This approach was more likely to find bacteriologically confirmed TB cases, contributing to the reduction of risk of transmission within the community.
Development of a novel method for the quantification of tyrosine 39 phosphorylated α- and β-synuclein in human cerebrospinal fluid
Authors: Na Chan Hyun , Sathe Gajanan , Rosenthal Liana S. , Moghekar Abhay R. , Dawson Valina L. , Dawson Ted M. , Pandey Akhilesh
Published: May 2020

Background

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder. Biomarkers that can help monitor the progression of PD or response to disease-modifying agents will be invaluable in making appropriate therapeutic decisions. Further, biomarkers that could be used to distinguish PD from other related disorders with PD-like symptoms will be useful for accurate diagnosis and treatment. C-Abl tyrosine kinase is activated in PD resulting in increased phosphorylation of the tyrosine residue at position 39 (Y39) of α-synuclein (α-syn) (pY39 α-syn), which contributes to the death of dopaminergic neurons. Because pY39 α-syn may be pathogenic, monitoring pY39 α-syn could allow us to diagnose presymptomatic PD and help monitor disease progression and response to treatment. We sought to investigate if increased phosphorylation of pY39 α-syn can be detected in the cerebrospinal fluid (CSF) of PD patients by targeted mass spectrometry.

Methods

Here, we report a two-step enrichment method in which phosphotyrosine peptides were first enriched with an anti-phosphotyrosine antibody followed by a second round of enrichment by titanium dioxide (TiO2) beads to detect EGVLpYVGSK sequence derived from tyrosine 39 region of α- and β-synuclein (αβ-syn). Accurate quantification was achieved by adding a synthetic heavy version of pY39 αβ-syn peptide before enzymatic digestion.

Results

Using the developed enrichment methods and optimized parallel reaction monitoring (PRM) assays, we detected pY39 αβ-syn peptide in human CSF and demonstrated that the ratio of pY39 αβ-syn to Y39 αβ-syn was significantly increased in the CSF of patients with PD.

Conclusions

We anticipate that this optimized two-step enrichment-based PRM detection method will help monitor c-Abl activation in PD patients and can also be used to quantify other phosphotyrosine peptides of low abundance in biological samples.
Individualized intervention for frail non-dialysis elderly patients with chronic kidney disease: protocol for a randomized controlled trial
Authors: Chang Jing , Gao Yun , Fang Xiang-Yang , Zhao Su-Mei , Hou Yuan-Ping , Sun Qian-Mei
Published: May 2020

Background

Frailty describes an age-related clinical state and can be regarded as a predictive factor for fall, disability, hospitalization, and death in the elderly. Previous studies proved that frailty could be reversed or attenuated by multi-disciplinary intervention. However, only a few studies have been performed in non-dialysis patients with chronic kidney disease.

Methods

A randomized parallel controlled trial will be conducted to compare an individualized intervention according to the consequence of the comprehensive geriatric assessment with routine treatment. A total of 242 individuals aged ≥65 years, who fulfill the Fried Phenotype of frailty and have chronic kidney disease stage 3–5 without dialysis will be recruited from the Department of Nephrology and Department of Internal Medicine, Beijing Chaoyang Hospital, Capital Medical University. The participants will be followed-up for 30 days and 12 months.

Discussion

This protocol would be established to examine the efficiency of targeted intervention for frailty. If a positive consequence could be obtained, a novel treatment for frail elderly patients with chronic kidney disease who have never undergone dialysis can be carried out in routine clinical practice.

Trial registration

The trial was prospectively registered at the Chinese Clinical Trials Registry with the registration numberChiCTR-IOR-17013429on November 17, 2017.
Continuous quality monitoring in the field: an evaluation of the performance of the Fio Deki Reader™ for rapid HIV testing in South Africa
Authors: Noble Lara , Scott Lesley , Stewart-Isherwood Lynsey , Molifi Seponono John , Sanne Ian , Da Silva Pedro , Stevens Wendy
Published: May 2020

Background

Rapid diagnostic tests (RDTs) are a cornerstone of HIV diagnosis and rely on good quality processing and interpretation, particularly in the era of test and treat. The Deki Reader (Fio Corporation®, Toronto, Ontario, Canada) is a portable device designed specifically for analysing RDTs and was selected for evaluation in South Africa in the context of HIV RDT analysis.

Methods

This study consisted of a laboratory evaluation and two-part field evaluation of the Deki Reader v100, covering two RDT testing algorithms, and an evaluation of the continuous quality monitoring through the Fionet™ web portal. Based on user feedback from the field evaluation, the device underwent hardware and software redesign, and the Deki Reader v200 was evaluated in the laboratory. Ethics approval for this evaluation was obtained from the University of the Witwatersrand Human Research Ethics Committee: M150160.

Results

The intra- and inter-device laboratory precision of the Deki Reader v100 were 98.3 and 99.2% respectively, and 99.3 and 100% for the Deki Reader v200. The laboratory concordances compared to standard-of-care reporting were 99.5 and 98.0% for the two respective models, while sensitivity and specificity were 99.5 and 99.4% for the Deki Reader V100 and 100 and 93.1% for the Deki Reader V200 respectively. Screening and confirmatory concordances in the field were 99.3 and 96.5% under algorithm 1 and 99.7 and 100% under algorithm 2. Sensitivity and specificity for the field evaluation were 99.8 and 97.7%. Overall robustness of the device was acceptable and continuous quality monitoring through Fionet™ was feasible.

Conclusions

The Deki Reader provides an option for improved and reliable quality assessment for rapid diagnosis of HIV using RDTs to enhance the quality of healthcare at the point-of-care. However, the introduction of new RDTs and modification of current algorithms necessitates ongoing and agile RDT reader adjustments, which will require cost modelling to ensure sustainability of devices implemented into national HIV programs.
Dehydration-associated chronic kidney disease: a novel case of kidney failure in China
Authors: Yang Xinglin , Wu Haiting , Li Hang
Published: May 2020

Background

Mesoamerican nephropathy (MeN) is a pattern of chronic kidney disease (CKD) prevalent among Central American men who work in agriculture, and its underlying cause has not been elucidated. Currently, experts hypothesize that MeN is related to repeated episodes of occupational heat stress leading to water loss and hence it is also called dehydration-associated CKD.

Case presentation

We report a case of a 40-year-old man, whose first admission to Peking Union Medical College Hospital was due to acute kidney injury (AKI). The clinical and pathological processes were consistent with acute tubular necrosis (ATN). However, after full recovery, CKD developed 1 year later. The second renal biopsy showed characteristics of ischemic renal disease but there was no evidence of vascular disease. It is worth noting that the patient had been taking part in long-distance running without drinking adequate water for years, which would have markedly decrease his renal blood flow. Thus, this patient may have developed chronic dehydration-associated kidney disease sharing the similar etiology of MeN.

Conclusions

We report here a case of dehydration-associated CKD in a Chinese patient which shared similar etiology to MeN. Even in non-agricultural areas, this etiology of CKD should be noted to obtain a relevant history and prompt diagnosis.
FAT4 silencing promotes epithelial-to-mesenchymal transition and invasion via regulation of YAP and β-catenin activity in ovarian cancer
Authors: Malgundkar Shika Hanif , Burney Ikram , Al Moundhri Mansour , Al Kalbani Moza , Lakhtakia Ritu , Okamoto Aikou , Tamimi Yahya
Published: May 2020

Background

The adhesion molecule, FAT4, has a tumor suppressor function with a critical role in the epithelial-to-mesenchymal-transition (EMT) and anti-malignant growth in several cancers. No study has investigated yet its role in epithelial ovarian cancer (EOC) progression. In the present study, we examined the role of FAT4 in proliferation and metastasis, and its mechanisms of interaction in these processes.

Methods

We have performed cell viability, colony formation, and invasion assays in ovarian cancer cells treated with siRNA to knockdown FAT4 gene expression. The regulatory effects of FAT4 on proteins involved in apoptotic, Wnt, Hippo, and retinoblastoma signaling pathways were evaluated by Western blotting following FAT4 repression. Also, 426 ovarian tumor samples and 88 non-tumor samples from the Gene Expression Profiling Interactive Analysis (GEPIA) database were analyzed for the expression of FAT4. Pearson’s correlation was performed to determine the correlation between FAT4 and the E2F5, cyclin D1, cdk4, and caspase 9 expressions.

Results

Lower expression of FAT4 was observed in ovarian cancer cell lines and human samples as compared to non-malignant tissues. This down-regulation seems to enhance cell viability, invasion, and colony formation. Silencing FAT4 resulted in the upregulation of E2F5, vimentin, YAP, β-catenin, cyclin D1, cdk4, and Bcl2, and in the downregulation of GSK-3-β, and caspase 9 when compared to control. Furthermore, regulatory effects of FAT4 on the EMT and aggressive phenotype seem to occur through Hippo, Wnt, and cell cycle pathways.

Conclusion

FAT4 downregulation promotes increased growth and invasion through the activation of Hippo and Wnt-β-catenin pathways.
Vaping induced pneumonitis: a small community hospital’s case series and analysis
Authors: Silverman Andrew L. , Siddique Haseeb , Kumar Vikas , Le Thuy-Hong , Ng Joseph
Published: May 2020

Background

Electronic cigarettes/e-cigarettes (ECs), or vaping, is currently the most popular form of smoking amongst youth in the United States. ECs are battery-powered devices that vaporize a liquid that comes in small cartridges, or pods, that contain various chemicals, nicotine, and an array of flavors that can be modified to include cannabinoids (THC). With increasing popularity, however, there is an epidemic of pulmonary and gastrointestinal illnesses associated with vaping in the continental U.S.A.

Methods

We analyzed medical charts of three patients who were active users of ECs and presented with pneumonitis to our community medical center between January and August 2019.

Results

We report three cases of vaping pneumonitis in young adults, ages 18 to 21, who presented with similar symptoms, profiles, imaging studies, and disease progression. The average length of stay was approximately one week, and all patients had an extensive work-up in addition to a relapsing and remitting course of their condition.

Conclusions

Early recognition and diagnosis of vaping pneumonitis are essential in the treatment of the ongoing epidemic. Extensive unnecessary work up may lead to increased healthcare costs. Our case series echoes the concerns of the CDC such that ECs should be avoided, and those with any pulmonary or gastrointestinal symptoms should seek medical attention promptly.
Novel enterocin E20c purified from Enterococcus hirae 20c synergised with ß-lactams and ciprofloxacin against Salmonella enterica
Authors: Sharma Preeti , Rashid Muzamil , Kaur Sukhraj
Published: May 2020

Background

An increasing rate of antibiotic resistance among Gram-negative bacterial pathogens has created an urgent need to discover novel therapeutic agents to combat infectious diseases. Use of bacteriocins as therapeutic agents has immense potential due to their high potency and mode of action different from that of conventional antibiotics.

Results

In this study, a novel bacteriocin E20c of molecular weight 6.5 kDa was purified and characterized from the probiotic strain of Enterococcus hirae. E20c had bactericidal activities against several multidrug resistant (MDR) Gram-negative bacterial pathogens. Flow cytometry and scanning electron microscopy studies showed that it killed the Salmonella enterica cells by forming ion-permeable channels in the cell membrane leading to enhanced cell membrane permeability. Further, checkerboard titrations showed that E20c had synergistic interaction with antibiotics such as ampicillin, penicillin, ceftriaxone, and ciprofloxacin against a ciprofloxacin- and penicillin-resistant strain of S. enterica.

Conclusion

Thus, this study shows the broad spectrum antimicrobial activity of novel enterocin E20c against various MDR pathogens. Further, it highlights the importance of bacteriocins in lowering the minimum inhibitory concentrations of conventional antibiotics when used in combination.
circNFIB1 inhibits lymphangiogenesis and lymphatic metastasis via the miR-486-5p/PIK3R1/VEGF-C axis in pancreatic cancer
Authors: Kong Yao , Li Yuting , Luo Yuming , Zhu Jiang , Zheng Hanhao , Gao Bowen , Guo Xiaofeng , Li Zhihua , Chen Rufu , Chen Changhao
Published: May 2020

Background

Patients with lymph node (LN)-positive pancreatic ductal adenocarcinoma (PDAC) have extremely poor survival rates. Circular RNAs (circRNAs), a newly discovered type of endogenous noncoding RNAs, have been proposed to mediate the progression of diverse types of tumors. However, the role and underlying regulatory mechanisms of circRNAs in the LN metastasis of PDAC remain unknown.

Methods

Next-generation sequencing was used to identify differentially expressed circRNAs between PDAC and normal adjacent tissues. In vitro and in vivo experiments were conducted to evaluate the functional role of circNFIB1. RNA pulldown and luciferase assays were performed to examine the binding of circNFIB1 and miR-486-5p.

Results

In the present study, we identified that a novel circRNA (circNFIB1, hsa_circ_0086375) was downregulated in PDAC and negatively associated with LN metastasis in PDAC patients. Functionally, circNFIB1 knockdown promoted lymphangiogenesis and LN metastasis of PDAC both in vitro and in vivo. Mechanistically, circNFIB1 functioned as a sponge of miR-486-5p, and partially reversed the effect of miR-486-5p. Moreover, circNFIB1 attenuated the oncogenic effect of miR-486-5p and consequently upregulated PIK3R1 expression, which further downregulated VEGF-C expression through inhibition of the PI3K/Akt pathway, and ultimately suppressed lymphangiogenesis and LN metastasis in PDAC.

Conclusions

Our findings provide novel insight into the underlying mechanism of circRNA-mediated LN metastasis of PDAC and suggest that circNFIB1 may serve as a potential therapeutic target for LN metastasis in PDAC.

Graphical abstract
GlucoTRIG: a novel tool to determine the nutritional quality of foods and meals in general population
Authors: Thota Rohith N. , Moughan Paul J. , Singh Harjinder , Garg Manohar L.
Published: May 2020

Background

This study aimed to develop a novel criterion, GlucoTRIG, to rank meals for healthiness, that considers both glycaemic (serum insulin) and lipaemic (serum triglycerides) responses.

Methods

Healthy volunteers (n = 10) were recruited with the aim of deriving a standard GlucoTRIG value for a reference meal. Volunteers consumed the reference meal (2 regular slices of wholemeal bread; 250 mL chocolate flavoured milk; 7 g butter and 11 g peanut butter) comprising of carbohydrate, fat and protein (41, 40 and 16% energy respectively) on three different occasions with a minimum washout period of 3 days. The GlucoTRIG value was determined as the difference between the product of insulin and triglyceride obtained from venous blood samples at baseline and the product of insulin and triglyceride at 180 min.

Results

There were no significant differences in the participants’ dietary intakes and their metabolic parameters between three visits (P > 0.005). The GlucoTRIG value obtained from three mean values of the reference meal was found to be 19 ± 3.5. There were no significant (P = 0.2303) differences observed between the GlucoTRIG values for the three visits.

Conclusion

GlucoTRIG, consisting of both glycaemic and lipaemic responses, may be a physiologically relevant tool to rank foods and meals for reducing the risk of metabolic diseases.

Trial registration

ACTRN12619000973112.
Quality of life and influencing factors of patients with rheumatoid arthritis in Northeast China
Authors: Bai Bingqing , Chen Meng , Fu Lingyu , Liu Haina , Jin Lei , Wei Tingting , Xin Fangran
Published: May 2020

Purpose

Rheumatoid arthritis (RA) is a disease with a high disability rate, resulting in severe family and social burden. The aim of treatment is to improve the health-related quality of life (QoL) of patients. The purpose of this study was to evaluate the QoL of patients with RA in Northeast China and analyze its influencing factors.

Methods

The study group consisted of 200 patients diagnosed with RA. The control group consisted of 200 healthy subjects. All subjects were residents in Northeast China. The investigation was conducted by questionnaire survey and electronic medical record. The WHOQOL-BREF, The Short-Form 36 Health Survey (SF-36) and Quality of Life Instruments for Chronic Diseases-RA (QLICD-RA) were used as questionnaires.

Results

The QoL scores acquired by SF-36, WHOQOL-BREF and QLICD-RA scales showed significant differences between RA and control groups (P < 0.001). Multiple regression analysis showed that sleep duration (P = 0.001), psychological counseling (P < 0.001) and C4 level (P = 0.001) influenced the SF-36 scale evaluation model. IgA levels (P < 0.001) and being overweight (P = 0.030) were included in the WHOQOL-BREF evaluation model. Adequate sleep (P = 0.001) and psychological counseling(P = 0.050) entered the QLICD-RA scale evaluation model (P = 0.050), in which psychological counseling, normal C4 levels and being overweight were protective factors for RA, insufficient sleep and IgA levels were risk factors for RA.

Conclusions

The QoL of RA patients is generally lower than those of healthy subjects in the Northeast China, Northeast China. Sleep duration, BMI (Body mass index), psychological counseling, C4 and IgA levels are factors that influence the QoL scores of RA patients.
Molecular analysis of lipid uptake- and necroptosis-associated factor expression in vitrified-warmed mouse oocytes
Authors: Um Da-Eun , Shin Hyejin , Park Dayoung , Ahn Jeong Min , Kim Jayeon , Song Haengseok , Lim Hyunjung Jade
Published: May 2020

Background

We had previously demonstrated that vitrification reduces the levels of certain phospholipid classes, and that oocytes from aged mice show a similar lipidome alteration, even without vitrification. In the current investigation, we examined if vitrification-warming of mouse oocytes from young and aged mice causes any changes in molecular aspects of lipid-associated features.

Methods

Metaphase II (MII) stage oocytes were harvested from young (10–14-week-old) and aged (45–54-week-old) mice by a superovulation regime with PMSG followed by hCG. We examined the status of the intracellular lipid pool and the integrity of the plasma membrane by staining oocytes with BODIPY 500/510 and CellMask live dyes. Expression of lipid uptake- and necroptosis-associated genes was assessed by quantitative PCR analyses, in oocytes from young and old mice, before and after vitrification. Localization patterns of two crucial necroptosis proteins, phosphorylated MLKL (pMLKL) and phosphorylated RIPK1 (pRIPK1) were examined in mouse oocytes by immunofluorescence staining. Necrostain-1 (Nec1), an inhibitor of RIPK1, was used to examine if RIPK1 activity is required to maintain oocyte quality during vitrification.

Results

We confirmed that vitrified-warmed oocytes from aged mice showed noticeable decrease in both CellMask and BODIPY 500/510 dyes. Among the lipid uptake-associated genes,Cd36expression was higher in oocytes from aged mice. Necroptosis is a type of programmed cell death that involves damage to the plasma membrane, eventually resulting in cell rupture. The expression of necroptosis-associated genes did not significantly differ among groups. We observed that localization patterns of pMLKL and pRIPK1 were unique in mouse oocytes, showing association with microtubule organizing centers (MTOCs) and spindle poles. pMLKL was also localized on kinetochores of MII chromosomes. Oocytes treated with Nec1 during vitrification showed a decreased survival rate, indicating the importance of RIPK1 activity in oocyte vitrification.

Conclusions

We report that oocytes from aged mice show differential expression of CD36, which suggests that CD36-mediated lipid uptake may be influenced by age. We also show for the first time that pMLKL and pRIPK1 exhibit unique localization pattern in mouse oocytes and this may suggest role(s) for these factors in non-necroptosis-associated cellular processes.
Increased risk of maternal and neonatal complications in hormone replacement therapy cycles in frozen embryo transfer
Authors: Zong Liping , Liu Peihao , Zhou Liguang , Wei Daimin , Ding Lingling , Qin Yingying
Published: May 2020

Background

The endometrial preparation during frozen embryo transfer (FET) can be performed by natural cycle (NC), hormone replacement therapy (HRT) cycle and cycle with ovulation induction (OI). Whether different FET preparation protocols can affect maternal and neonatal outcomes is still inconclusive.

Methods

This was a retrospective cohort study that included 6886 women who delivered singleton live birth babies after 28 weeks of pregnancy underwent FET from January, 2015 to July, 2018. Women were divided into three groups according to the protocols used for endometrial preparation during FET: NC group (N = 4727), HRT group (N = 1642) and OI group (N = 517).

Results

After adjusting for the effect of age, body mass index (BMI), irregular menstruation, antral follicle count (AFC), endometrial thickness, the levels of testosterone, anti-Müllerian hormone (AMH), preconceptional fasting glucose (PFG), systolic and diastolic pressure et al., the HRT group had higher risk of hypertensive disorders of pregnancy (HDP) compared with the NC group (adjusted odds ratio (aOR) 2.00, 95% confidence interval (CI) 1.54–2.60). Singletons born after HRT FET were at increased risk of low birth weight (LBW) compared to NC group (aOR 1.49, 95%CI 1.09–2.06). The risks of preterm birth (PTB) in the HRT and OI group were elevated compared with the NC group (aOR 1.78, 95%CI 1.39–2.28 and aOR 1.51, 95%CI 1.02–2.23, respectively).

Conclusions

The HRT protocol for endometrial preparation during frozen embryo transfer of blastocysts was associated with increased risk of maternal and neonatal complications, compared to the NC and OI protocol.
Inhibition of mast cell tryptase attenuates neuroinflammation via PAR-2/p38/NFκB pathway following asphyxial cardiac arrest in rats
Authors: Ocak Umut , Eser Ocak Pinar , Huang Lei , Xu Weilin , Zuo Yuchun , Li Peng , Gamdzyk Marcin , Zuo Gang , Mo Jun , Zhang Guangyu , Zhang John H.
Published: May 2020

Background

Cardiac arrest survivors suffer from neurological dysfunction including cognitive impairment. Cerebral mast cells, the key regulators of neuroinflammation contribute to neuroinflammation-associated cognitive dysfunction. Mast cell tryptase was demonstrated to have a proinflammatory effect on microglia via the activation of microglial protease-activated receptor-2 (PAR-2). This study investigated the potential anti-neuroinflammatory effect of mast cell tryptase inhibition and the underlying mechanism of PAR-2/p-p38/NFκB signaling following asphyxia-induced cardiac arrest in rats.

Methods

Adult male Sprague-Dawley rats resuscitated from 10 min of asphyxia-induced cardiac arrest were randomized to four separate experiments including time-course, short-term outcomes, long-term outcomes and mechanism studies. The effect of mast cell tryptase inhibition on asphyxial cardiac arrest outcomes was examined after intranasal administration of selective mast cell tryptase inhibitor (APC366; 50 μg/rat or 150 μg/rat). AC55541 (selective PAR-2 activator; 30 μg/rat) and SB203580 (selective p38 inhibitor; 300 μg/rat) were used for intervention. Short-term neurocognitive functions were evaluated using the neurological deficit score, number of seizures, adhesive tape removal test, and T-maze test, while long-term cognitive functions were evaluated using the Morris water maze test. Hippocampal neuronal degeneration was evaluated by Fluoro-Jade C staining.

Results

Mast cell tryptase and PAR-2 were dramatically increased in the brain following asphyxia-induced cardiac arrest. The inhibition of mast cell tryptase by APC366 improved both short- and long-term neurological outcomes in resuscitated rats. Such behavioral benefits were associated with reduced expressions of PAR-2, p-p38, NFκB, TNF-α, and IL-6 in the brain as well as less hippocampal neuronal degeneration. The anti-neuroinflammatory effect of APC366 was abolished by AC55541, which when used alone, indeed further exacerbated neuroinflammation, hippocampal neuronal degeneration, and neurologic deficits following cardiac arrest. The deleterious effects aggregated by AC55541 were minimized by p38 inhibitor.

Conclusions

The inhibition of mast cell tryptase attenuated neuroinflammation, led to less hippocampal neuronal death and improved neurological deficits following cardiac arrest. This effect was at least partly mediated via inhibiting the PAR-2/p-p38/NFκB signaling pathway. Thus, mast cell tryptase might be a novel therapeutic target in the management of neurological impairment following cardiac arrest.
IC100: a novel anti-ASC monoclonal antibody improves functional outcomes in an animal model of multiple sclerosis
Authors: Desu Haritha L. , Plastini Melanie , Illiano Placido , Bramlett Helen M. , Dietrich W. Dalton , de Rivero Vaccari Juan Pablo , Brambilla Roberta , Keane Robert W.
Published: May 2020

Background

The inflammasome adaptor apoptosis-associated speck-like protein containing a CARD (ASC) is involved in immune signaling by bridging the interactions between inflammasome sensors and caspase-1. Strong experimental evidence has shown that ASC−/−mice are protected from disease progression in animal models of multiple sclerosis (MS), suggesting that targeting inflammasome activation via ASC inhibition may be a promising therapeutic strategy in MS. Thus, the goal of our study is to test the efficacy of IC100, a novel humanized antibody targeting ASC, in preventing and/or suppressing disease in the experimental autoimmune encephalomyelitis (EAE) model of MS.

Methods

We employed the EAE model of MS where disease was induced by immunization of C57BL/6 mice with myelin oligodendrocyte glycoprotein peptide 35–55 (MOG35–55). Mice were treated with vehicle or increasing doses of IC100 (10, 30, and 45 mg/kg) and clinical disease course was evaluated up to 35 days post EAE induction. Immune cell infiltration into the spinal cord and microglia responses were assessed.

Results

We show that IC100 treatment reduced the severity of EAE when compared to vehicle-treated controls. At a dose of 30 mg/kg, IC100 significantly reduced the number of CD4+and CD8+T cells and CD11b+MHCII+activated myeloid cells entering the spinal cord from the periphery, and reduced the number of total and activated microglia.

Conclusions

These data indicate that IC100 suppresses the immune-inflammatory response that drives EAE development and progression, thereby identifying ASC as a promising target for the treatment of MS as well as other neurological diseases with a neuroinflammatory component.
A united statement of the global chiropractic research community against the pseudoscientific claim that chiropractic care boosts immunity
Authors:   and more than 140 signatories# call for an end to pseudoscientific claims on the effect of chiropractic care on immune function, Côté Pierre , Bussières André , Cassidy J. David , Hartvigsen Jan , Kawchuk Greg N. , Leboeuf-Yde Charlotte , Mior Silvano , Schneider Michael
Published: May 2020

Background

In the midst of the coronavirus pandemic, the International Chiropractors Association (ICA) posted reports claiming that chiropractic care can impact the immune system. These claims clash with recommendations from the World Health Organization and World Federation of Chiropractic. We discuss the scientific validity of the claims made in these ICA reports.

Main body

We reviewed the two reports posted by the ICA on their website on March 20 and March 28, 2020. We explored the method used to develop the claim that chiropractic adjustments impact the immune system and discuss the scientific merit of that claim. We provide a response to the ICA reports and explain why this claim lacks scientific credibility and is dangerous to the public. More than 150 researchers from 11 countries reviewed and endorsed our response.

Conclusion

In their reports, the ICA provided no valid clinical scientific evidence that chiropractic care can impact the immune system. We call on regulatory authorities and professional leaders to take robust political and regulatory action against those claiming that chiropractic adjustments have a clinical impact on the immune system.