bluuebunny/crossref_metadata_2025 huggingface dataset:
How views of oncologists and haematologists impacts palliative care referral: a systematic review
Authors: Salins Naveen , Ghoshal Arunangshu , Hughes Sean , Preston Nancy
Published: November 2020

Background

Worldwide, many patients with cancer, are infrequently referred to palliative care or are referred late. Oncologists and haematologists may act as gatekeepers, and their views may facilitate or hinder referrals to palliative care. This review aimed to identify, explore and synthesise their views on referrals systematically.

Methods

Databases of MEDLINE, CINAHL, PsycINFO, EMBASE, Scopus, Web of Science and Cochrane were searched for articles from 01/01/1990 to 31/12/2019. All studies were scored for their methodological rigour using Hawker’s tool. Findings were synthesised using Popay’s narrative synthesis method and interpreted using a critical realist lens and social exchange theory.

Results

Out of 9336 initial database citations, 23 studies were included for synthesis. Five themes were developed during synthesis.

1. Presuppositions of oncologists and haematologists about palliative care referral: Role conflict, abandonment, rupture of therapeutic alliance and loss of hope were some of the presuppositions that hindered palliative care referral. Negative emotions and perception of self-efficacy to manage palliative care need also hindered referral.

2. Power relationships and trust issues: Oncologists and haematologists preferred to gatekeep the referral process and wished to control and coordinate the care process. They had diminished trust in the competency of palliative care providers.

3. Making a palliative care referral: A daunting task: The stigma associated with palliative care, navigating illness and treatment associated factors, addressing patient and family attitudes, and overcoming organisational challenges made referral a daunting task. Lack of referral criteria and limited palliative care resources made the referral process challenging.

4. Cost-benefit of palliative care referral: Pain and symptom management and psychosocial support were the perceived benefits, whereas inconsistencies in communication and curtailment of care were some of the costs associated with palliative care referral.

5. Strategies to facilitate palliative care referral: Developing an integrated model of care, renaming and augmenting palliative care resources were some of the strategies that could facilitate a referral.

Conclusion

Presuppositions, power relationships, trust issues and the challenges associated with the task of referrals hindered palliative care referral. Oncologists and haematologists appraised the cost-benefit of making a palliative care referral. They felt that an integrated model of care, changing the name of palliative care and augmenting palliative care resources might facilitate a referral.
Is early integration of palliative home care in oncology treatment feasible and acceptable for advanced cancer patients and their health care providers? A phase 2 mixed-methods study
Authors: Dhollander Naomi , Smets Tinne , De Vleminck Aline , Lapeire Lore , Pardon Koen , Deliens Luc
Published: November 2020

Background

To support the early integration of palliative home care (PHC) in cancer treatment, we developed the EPHECT intervention and pilot tested it with 30 advanced cancer patients in Belgium using a pre post design with no control group. We aim to determine the feasibility, acceptability and perceived effectiveness of the EPHECT intervention.

Methods

Interviews with patients (n = 16 of which 11 dyadic with family caregivers), oncologists and GPs (n = 11) and a focus group with the PHC team. We further analyzed the study materials and logbooks of the PHC team (n = 8). Preliminary effectiveness was assessed with questionnaires EORTC QLQ C-30, HADS and FAMCARE and were filled in at baseline and 12, 18 and 24 weeks.

Results

In the interviews after the intervention period, patients reported feelings of safety and control and an optimized quality of life. The PHC team could focus on more than symptom management because they were introduced earlier in the trajectory of the patient. Telephone-based contact appeared to be insufficient to support interprofessional collaboration. Furthermore, some family caregivers reported that the nurse of the PHC team was focused little on them.

Conclusion

Nurses of PHC teams are able to deliver early palliative care to advanced cancer patients. However, more attention needs to be given to family caregivers as caregiver and client. Furthermore, the home visits by the PHC team have to be further evaluated and adapted. Lastly, professionals have to find a more efficient way to discuss future care.
In vitro activities of Acacia nilotica (L.) Delile bark fractions against Oral Bacteria, Glucosyltransferase and as antioxidant
Authors: Muddathir Ali Mahmoud , Mohieldin Ebtihal Abdalla M. , Mitsunaga Tohru
Published: November 2020

Background

Dental caries and periodontal disease are the most common chronic infectious oral diseases in the world. Acacia nilotica was commonly known in Sudan as Garad or Sunt has a wide range of medicinal uses. In the present study, antibacterial activity of oral bacteria (Streptococcus sobrinus and Porphyromonas gingivalis), inhibitory activity against glucosyltransferase (GTF) enzyme and antioxidant activity were assayed for methanolic crude extract of A. nilotica bark and its fractions.

Methods

Methanoilc crude extract of A. nilotica bark was applied to a Sephadex LH-20 column and eluted with methanol, aqueous methanol, and finally aqueous acetone to obtain four fractions (Fr1- Fr4). Furthermore, the crude extract and fractions were subjected to analytical high performance liquid chromatography (HPLC). The crude extract and its fractions were assayed for antibacterial activity against S. sobrinus and P. gingivalis using a microplate dilution assay method to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), as well as GTF inhibition and antioxidant activity using ABTS radical scavenging method.

Results

Fractions (Fr1 and Fr2) exhibited MIC values of 0.3 mg/ml against the P. gingivalis. Additionally, Fr2 displayed MBC value of 1 mg/ml against two types of bacteria. Fr4 showed an especially potent GTF inhibitory activity with IC50 value of 3.9 μg/ml. Fr1 displayed the best antioxidant activity with IC50 value of 1.8 μg/ml. The main compound in Fr1 was identified as gallic acid, and Fr2 was mostly a mixture of gallic acid and methyl gallate.

Conclusions

The results obtained in this study provide some scientific rationale and justify the use of this plant for the treatment of dental diseases in traditional medicine. A. nilotica bark, besides their antibacterial potentiality and GTF inhibitory activity, it may be used as adjuvant antioxidants in mouthwashes. Further studies in the future are required to identify the rest of the active compounds.
The impacts and unintended consequences of the nationwide pricing reform for drugs and medical services in the urban public hospitals in China
Authors: Zhang Xiaoxi , Lai Hongyu , Zhang Lidan , He Jiangjiang , Fu Bo , Jin Chunlin
Published: November 2020

Background

Since 2015, China has been rolling out the pricing reform for drugs and medical services (PRDMS) in the urban public hospitals in order to reduce drug expenditures and to relieve financial burdens of patients. This study aims at evaluating the effectiveness of the reform and investigating its positive impacts and unintended consequences to provide evidence basis for further policy making.

Methods

The Difference-in-difference (DID) approach was employed to analyze the reform impacts on the 31 provincial administrative areas in China based on data abstracted from China Statistics Yearbooks and China Health Statistics Yearbooks from 2012 to 2018.

Results

The reform resulted in a decrease of 7.59% in drug cost per outpatient visit, a decrease of 5.73% in drug cost per inpatient admission, a decrease of 3.63% in total cost per outpatient visit and an increase of 9.10% in surgery cost per inpatient admission in the intervention group. However, no significant change in examination cost was found. The reduction in the medical cost per inpatient admission was not yet demonstrated, nor was that in the total outpatient/ inpatient expenses. The nationwide pricing reform for drugs and medical services in urban public hospitals (PRDMS-U) in China is demonstrated to be effective in cutting down the drug expenditures. However, the revealed unintended consequences indicate that there are still significant challenges for the reform to reach its ultimate goal of curbing the medical expenditures.

Conclusion

We conclude that the pricing reform alone may not be enough to change the profit-driven behavior of medical service providers as the root cause lies in the unchanged incentive scheme for providers in the service delivery. This holds lessons for policy making of other low- and middle-income countries (LMICs) with similar health systems set up in the achievement of Universal Health Coverage (UHC).
Translation, cultural adaptation and psychometric properties of the Ghanaian language (Akan; Asante Twi) version of the Health Literacy Questionnaire
Authors: Boateng Millicent Addai , Agyei-Baffour Peter , Angel Sanne , Enemark Ulrika
Published: November 2020

Background

Patients’ competencies and resources to manage their own health, which is termed health literacy, is a necessity for better health outcomes. Thus, it is relevant to have a comprehensive health literacy measurement tool suitable for populations of interest. The Health Literacy Questionnaire (HLQ) is a tool useful for health literacy assessment covering nine dimensions/scales of health literacy. The HLQ has been translated and validated in diverse contexts but has so far not been assessed in any country in sub-Saharan Africa. We sought to translate this tool into the most common language used in Ghana and assess its validity.

Methods

We carried out a cross-sectional study using the HLQ concurrently with an assessment of a malaria programme for caregivers with children under 5 years. The HLQ was translated using a systematic translation procedure. We analysed the psychometric properties of the HLQ based on data collected by face-to-face interview of 1234 caregivers. The analysis covered tests on difficulty level of scales, composite reliability, Cronbach’s alpha and confirmatory factor analysis (CFA).

Results

Cognitive testing showed that some words were ambiguous, which led to minor rewording of the questionnaire. A nine-factor CFA model was fitted to the 44 question items with no cross-loadings or correlated residuals allowed. Given the very restricted nature of the model, the fit was quite satisfactory: χ2 DWLS (866 df) = 17,177.58,p < 0.000, CFI = 0.971, TLI = 0.969, RMSEA = 0.126 and SRMR = 0.107. Composite reliability and Cronbach’s alpha were > 0.65 for all scales except Cronbach’s alpha for scale 9, ‘Understanding health information well enough to know what to do’ (0.57). The mean differences between most demographic groups among health literacy scales were statistically significant.

Conclusion

The Akan-Twi version of HLQ proved relevant in our description of the health literacy levels among the caregivers in our study. This validated tool will be useful to conduct health literacy needs assessments to guide policies addressing such needs. Further work is needed to validate this tool for use in Ghana and similar contexts.
Identifying and understanding determinants of high healthcare costs for breast cancer: a quantile regression machine learning approach
Authors: Hu Liangyuan , Li Lihua , Ji Jiayi , Sanderson Mark
Published: November 2020

Background

To identify and rank the importance of key determinants of high medical expenses among breast cancer patients and to understand the underlying effects of these determinants.

Methods

The Oncology Care Model (OCM) developed by the Center for Medicare & Medicaid Innovation were used. The OCM data provided to Mount Sinai on 2938 breast-cancer episodes included both baseline periods and three performance periods between Jan 1, 2012 and Jan 1, 2018. We included 11 variables representing information on treatment, demography and socio-economics status, in addition to episode expenditures. OCM data were collected from participating practices and payers. We applied a principled variable selection algorithm using a flexible tree-based machine learning technique, Quantile Regression Forests.

Results

We found that the use of chemotherapy drugs (versus hormonal therapy) and interval of days without chemotherapy predominantly affected medical expenses among high-cost breast cancer patients. The second-tier major determinants were comorbidities and age. Receipt of surgery or radiation, geographically adjusted relative cost and insurance type were also identified as important high-cost drivers. These factors had disproportionally larger effects upon the high-cost patients.

Conclusions

Data-driven machine learning methods provide insights into the underlying web of factors driving up the costs for breast cancer care management. Results from our study may help inform population health management initiatives and allow policymakers to develop tailored interventions to meet the needs of those high-cost patients and to avoid waste of scarce resource.
Using person-specific networks in psychotherapy: challenges, limitations, and how we could use them anyway
Authors: von Klipstein Lino , Riese Harriëtte , van der Veen Date C. , Servaas Michelle N. , Schoevers Robert A.
Published: November 2020

Background

The complexity of psychopathology is evident from its multifactorial etiology and diversity of symptom profiles and hampers effective treatment. In psychotherapy, therapists approach this complexity by using case conceptualization. During this process, patients and therapists closely collaborate on a personalized working theory of the patient’s psychopathology. This is a challenging process and shows low reliability between therapists. With the experience sampling method (ESM), time-series data—valuable for case conceptualization—can be systematically gathered in a patient’s normal daily life. These data can be analyzed and visualized in person-specific networks (PSNs). PSNs may support case conceptualization by providing a schematic representation of association patterns between affective, cognitive, behavioral, and context variables.

Main text

We adopt a clinical perspective in considering how PSNs might be implemented to serve case conceptualization and what their role could be in psychotherapy. We suggest PSNs to be based on personalized ESM assessment to capture the unique constellation of variables in each patient. We reflect on the lack of a gold standard for creating PSNs, which may result in substantially different PSNs and thereby disparate information for case conceptualization. Moreover, even if PSNs are created in a consistent manner, results remain ambiguous as they are subject to multiple interpretations. Therefore, associations in PSNs do not allow for firm conclusions about a patient’s psychopathology, but they may nevertheless be valuable in the process of case conceptualization. PSNs are based on systematically gathered, ecologically valid ESM data and provide a unique personalized perspective. When used responsibly, PSNs may be able to support case conceptualization by generating questions that serve as a starting point for a dialog between therapists and patients. Well-targeted questions are an essential tool for therapists to gain insight into the patients’ psychopathology patterns and improve the quality of case conceptualization.

Conclusions

PSNs have limitations in terms of the reliability of the insights they provide directly. However, taking these challenges into account, we believe they have potential as a tool to help therapists and patients in their collaborative exploration of a patient’s psychopathology. Clearly, this would need to be validated in future clinical research.
The effect of long-term dehydration and subsequent rehydration on markers of inflammation, oxidative stress and apoptosis in the camel kidney
Authors: Ali Mahmoud A. , Abu Damir Hassan , Ali Osman M. , Amir Naheed , Tariq Saeed , Greenwood Michael P. , Lin Panjiao , Gillard Benjamin , Murphy David , Adem Abdu
Published: November 2020

Background

Dehydration has deleterious effects in many species, but camels tolerate long periods of water deprivation without serious health compromise. The kidney plays crucial role in water conservation, however, some reports point to elevated kidney function tests in dehydrated camels. In this work, we investigated the effects of dehydration and rehydration on kidney cortex and medulla with respect to pro-inflammatory markers, oxidative stress and apoptosis along with corresponding gene expression.

Results

The cytokines IL-1β and IL-18 levels were significantly elevated in the kidney cortex of dehydrated camel, possibly expressed by tubular epithelium, podocytes and/or mesangial cells. Elevation of IL-18 persisted after rehydration. Dehydration induced oxidative stress in kidney cortex evident by significant increases in MDA and GSH, but significant decreases in SOD and CAT. In the medulla, CAT decreased significantly, but MDA, GSH and SOD levels were not affected. Rehydration abolished the oxidative stress. In parallel with the increased levels of MDA, we observed increased levels of PTGS1 mRNA, in MDA synthesis pathway. GCLC mRNA expression level, involved in GSH synthesis, was upregulated in kidney cortex by rehydration. However, both SOD1 and SOD3 mRNA levels dropped, in parallel with SOD activity, in the cortex by dehydration. There were significant increases in caspases 3 and 9, p53 and PARP1, indicating apoptosis was triggered by intrinsic pathway. Expression of BCL2l1 mRNA levels, encoding for BCL-xL, was down regulated by dehydration in cortex. CASP3 expression level increased significantly in medulla by dehydration and continued after rehydration whereas TP53 expression increased in cortex by rehydration. Changes in caspase 8 and TNF-α were negligible to instigate extrinsic apoptotic trail. Generally, apoptotic markers were extremely variable after rehydration indicating that animals did not fully recover within three days.

Conclusions

Dehydration causes oxidative stress in kidney cortex and apoptosis in cortex and medulla. Kidney cortex and medulla were not homogeneous in all parameters investigated indicating different response to dehydration/rehydration. Some changes in tested parameters directly correlate with alteration in steady-state mRNA levels.
Multi-locus sequence typing of Mycoplasma bovis to assess its genetic diversity from 2009 to 2018 in Ningxia Hui Autonomous Region, China
Authors: Guo Yanan , Luo Haifeng , Guo Shuqiang , Lei Yuanyuan , Li Yong , He Shenghu
Published: November 2020

Background

Mycoplasma bovis (M. bovis) is a highly contagious cattle pathogen spreading worldwide and especially in Ningxia Hui Autonomous Region in China.

Results

Two types of ST, ST10and ST134, were identified in Ningxia Hui Autonomous Region. Thirty-seven strains belonged to ST10 and 28 strains belonged to ST134. ST134 was a new ST and first found in 2009 and was only widely distributed in Ningxia Hui Autonomous Region at present. The M. bovis ST10 was widely spread in many provinces in China and was widespread in Ningxia Hui Autonomous Region since 2010. It is speculated that the prevalence of M. bovis ST10 in Ningxia Hui Autonomous Region began in 2010.

Conclusions

This study is the first report on the genetic diversity of M. bovis from 2009 to 2018 in Ningxia Hui Autonomous Region and provides the epidemiological information. These results may help further our understanding of the evolution of M. bovis and provide information that may be useful for the development of novel vaccines.
Generation and molecular characteristics of a highly attenuated GPV strain through adaptation in GEF cells
Authors: Shao Hongxia , Jiang Yuchen , Yuan Huisha , Ji Lifei , Jin Wenjie , Qian Kun , Ye Jianqiang , Qin Aijian
Published: November 2020

Background

Goose parvoviruses (GPVs) spread globally and cause a huge economic loss to the poultry industry. Although the attenuated GPV vaccines play a key role in preventing the disease caused by GPV, the molecular basis for the attenuation of GPV is barely known.

Results

A highly attenuated GPV strain, GPV-CZM-142, was generated through blindly passaging of the highly pathogenic strain, GPV-CZM, in goose embryonic fibroblasts (GEF) for 142 generations. The GEF-adapted GPV strain’s virulence was 10,000 times weaker than its wild type counterpart, GPV-CZM, based on the ELD50 (50% Embryo Lethal Dose). By comparing with the wild type strain, genome sequencing analysis identified adapted mutations either in ITR or in NS and VP1 of GPV-CZM-142.

Conclusions

The highly attenuated GPV strain, GPV-CZM-142, provides a GPV vaccine candidate, and the identified virulence-related mutations give a novel insight into the molecular determinants of GPV virulence.
Metabolite secretions of Lactobacillus plantarum YYC-3 may inhibit colon cancer cell metastasis by suppressing the VEGF-MMP2/9 signaling pathway
Authors: Yue Yuan-Chun , Yang Bao-Yu , Lu Jing , Zhang Shu-Wen , Liu Liu , Nassar Khaled , Xu Xiao-Xi , Pang Xiao-Yang , Lv Jia-Ping
Published: November 2020

Background

Colorectal cancer (CRC) is a major clinical challenge, and the gut microbiome plays important roles in the occurrence and metastasis of CRC. Lactobacillus and their metabolites are thought to be able to suppress the growth of CRC cells. However, the antimetastatic mechanism of Lactobacillus or their metabolites toward CRC cells is not clear. Therefore, the aim of this study was to assess the inhibitory mechanism of cell-free supernatants (CFSs) of L. rhamnosus GG, L. casei M3, and L. plantarum YYC-3 on metastasis of CRC cells.

Results

YYC-3 CFS showed the highest inhibitory effect on CRC cell growth, invasion and migration, and inhibited MMP2, MMP9, and VEGFA gene and protein expression, and protein secretion. Furthermore, it suppressed the activities of MMPs by gelatin zymography. Moreover, the effective compounds in these CFSs were analyzed by Q Exactive Focus liquid chromatography–mass spectrometry.

Conclusions

Our results showed that metabolite secretions of YYC-3 may inhibited cell metastasis by downregulating the VEGF/MMPs signaling pathway. These data suggest that treatment of CRC cells with metabolites from L. plantarum YYC-3 may reduce colon cancer metastasis.
Parthenolide inhibits the growth of non-small cell lung cancer by targeting epidermal growth factor receptor
Authors: Li Xiaoling , Huang Riming , Li Mingyue , Zhu Zheng , Chen Zhiyan , Cui Liao , Luo Hui , Luo Lianxiang
Published: November 2020

Background

EGFR tyrosine kinase inhibitors (TKIs) have been developed for the treatment of EGFR mutated NSCLC. Parthenolide, a natural product of parthenolide, which belongs to the sesquiterpene lactone family and has a variety of biological and therapeutic activities, including anti-cancer effects. However, its effect on non-small cell lung cancer is little known.

Methods

The CCK8 assay and colony formation assays were used to assess cell viability. Flow cytometry was used to measure the cell apoptosis. In silico molecular docking was used to evaluate the binding of parthenolide to EGFR. Network pharmacology analysis was was used to evaluate the key gene of parthenolide target NSCLC. Western blotting was used to evaluate the key proteins involved apoptosis and EGFR signalling. The effect of parthenolide treatment in vivo was determined by using a xenograft mouse model.

Results

In this study, parthenolide could induce apoptosis and growth inhibition in the EGFR mutated lung cancer cells. Parthenolide also reduces the phosphorylation of EGFR as well as its downstream signaling pathways MAPK/ERK and PI3K/Akt. Molecular docking analysis of EGFR binding site with parthenolide show that the anti-cancer effect of parthenolide against NSCLC is mediated by a strong binding to EGFR. Network pharmacology analysis show parthenolide suppresses NSCLC via inhibition of EGFR expression. In addition, parthenolide inhibits the growth of H1975 xenografts in nude mice, which is associated with the inhibition of the EGFR signaling pathway.

Conclusions

Taken together, these results demonstrate effective inhibition of parthenolide in NSCLC cell growth by targeting EGFR through downregulation of ERK and AKT expression, which could be promisingly used for patients carrying the EGFR mutation.
Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer
Authors: Khan Khushbukhat , Quispe Cristina , Javed Zeeshan , Iqbal Muhammad Javed , Sadia Haleema , Raza Shahid , Irshad Asma , Salehi Bahare , Reiner Željko , Sharifi-Rad Javad
Published: November 2020

Bladder cancer (BC) is a leading cause of death among urothelial malignancies that more commonly affect male population. Poor prognosis and resistance to chemotherapy are the two most important characteristics of this disease. PI3K/Akt/mTOR signaling pathway has been considered pivotal in the regulation of proliferation, migration, invasiveness, and metastasis. Deregulation of PI3K/Akt/mTOR signaling has been found in 40% of bladder cancers. Several microRNAs (miRNAs) have been reported to interact with the PI3K/Akt/mTOR signaling pathway with a different possible role in proliferation and apoptosis in bladder cancer. Thus, miRNAs can be used as potential biomarkers for BC. Natural compounds have been in the spotlight for the past decade due to their effective anti-proliferative capabilities. However, little is known of its possible effects in bladder cancer. The aim of this review is to discuss the interplay between PI3K/Akt/mTOR, miRNAs, and natural compounds and emphasize the importance of miRNAs as biomarkers and resveratrol, curcumin and paclitaxel as a possible therapeutic approach against bladder cancer.
Clinical presentation and immunological features of Post-Malaria Neurologic Syndrome: a case report and review of literature
Authors: Castaldo Nadia , Tascini Carlo , Della Siega Paola , Peghin Maddalena , Pecori Davide
Published: November 2020

Background

Malaria still represents a major health threat, in terms of both morbidity and mortality. Complications of malaria present a diversified clinical spectrum, with neurological involvement leading to the most serious related-conditions. The authors recently encountered a case of a 60-year old Italian man presenting with confusion, language disturbances and Parkinson-like syndrome 3 weeks after complete remission from severePlasmodium falciparumcerebral malaria. Chemical and microbiological analysis revealed aseptic meningitis, diffuse encephalitis and abnormal immune-activation. Re-infection and recrudescence of infection were excluded. Further analysis excluded paraneoplastic and autoimmune causes of encephalitis. A diagnosis of Post-Malaria Neurological Syndrome (PMNS) was finally formulated and successfully treated with high dose of steroids.

Methods

A systematic research of current literature related to PMNS was performed.

Results

151 cases of PMNS were included, the majority of which occurred after severeP. falciparuminfections. Four main clinical pattern were identified: 37% of the cases presented as “classical” PMNS, 36% presented as delayed cerebellar ataxia (DCA), 18% resembled acute inflammatory demyelinating polyneuropathy (AIDP), and 8% presented as acute disseminated encephalomyelitis (ADEM)-like form. Differentiation between different forms was not always simple, as clinical and radiological findings frequently overlap. Overall, in almost all of the tested cases, cerebrospinal fluid was found pathological; EEG revealed nonspecific encephalopathy in 30% of classical PMNS and 67% ADEM; imaging tests were found abnormal in 92% of ADEM-like forms. Pathogenesis remains unclear. An autoimmune mechanism is the most corroborated pathogenic hypothesis. Overall, the majority of PMNS cases revert without specific treatment. In most severe forms, high dose steroids, intravenous immunoglobulins, and plasmapheresis have been shown to improve symptoms.

Conclusions

PMNS is a disabling complication of malaria. The overall incidence is not known, due to frequent misdiagnosis and under-reporting. Pathogenesis is not also fully understood, but rapid response to immune-modulating treatment along with similarities to auto-immune neurological disease, strongly support a dysregulated immunological genesis of this condition. The lack of randomized controlled studies regarding therapeutic approaches is a major unmet need in this setting. A systematic collection of all the PMNS cases would be desirable, in order to increase awareness of this rare condition and to prospectively investigate the most appropriate management.
Capacity of National Malaria Control Programmes to implement vector surveillance: a global analysis
Authors: Russell Tanya L. , Farlow Robert , Min Myo , Espino Effie , Mnzava Abraham , Burkot Thomas R.
Published: November 2020

Background

Solving the problem of malaria requires a highly skilled workforce with robust infrastructure, financial backing and sound programme management coordinated by a strategic plan. Here, the capacity of National Malaria Control Programmes (NMCPs) was analysed to identify the strengths and weaknesses underpinning the implementation of vector surveillance and control activities by the core elements of programme capacity, being strategic frameworks, financing, human resources, logistics and infrastructure, and information systems.

Results

Across nearly every country surveyed, the vector surveillance programmes were hampered by a lack of capacity and capability. Only 8% of NMCPs reported having sufficient capacity to implement vector surveillance. In contrast, 57%, 56% and 28% of NMCPs had the capacity to implement long-lasting insecticidal nets (LLINs), indoor residual spraying (IRS) and larval source management (LSM) activities, respectively. Largely underlying this was a lack of up-to-date strategic plans that prioritize vector surveillance and include frameworks for decision-making and action.

Conclusions

Strategic planning and a lack of well-trained entomologists heavily hamper vector surveillance. Countries on the path to elimination generally had more operational/field staff compared to countries at the stage of control, and also were more likely to have an established system for staff training and capacity building. It is unlikely that controlling countries will make significant progress unless huge investments also go towards increasing the number and capacity of programmatic staff.
From Plasmodium vivax outbreak to elimination: lessons learnt from a retrospective analysis of data from Guantang
Authors: Yang Guo-Jing , Liu Ying , Shang Le-Yuan , Zhang Hong-Wei , Zhou Xiao-Nong , Penny Melissa A. , Smith Thomas A.
Published: November 2020

Background

Malaria was once a serious public health problem in China, with Plasmodium vivax the major species responsible for more than 90% of local transmission. Following significant integrated malaria control and elimination programmes, malaria burden declined, and since 2017 China has not recorded any indigenous case. To understand the historical malaria transmission patterns and epidemic characteristics in China and insights useful to guide P. vivax malaria control and elimination elsewhere, a retrospective study was carried out.

Methods

Historical data from a pilot study conducted in Guantang, Luyi in central China from 1971–1995, were digitized. The data included monthly numbers of reported cases, febrile cases, parasite carriage rates, the neonatal infection rate, and entomological data regarding Anopheles sinensis.

Results

Following 25 years of continuous integrated malaria control activities, malaria incidence in Guantang decreased from 4,333 cases per 10,000 in 1970 before integrated implementation to 0.23 cases per 10,000 in 1991, and no cases in 1992–1995. Some fluctuations in incidence were observed between 1977 and 1981. During the period parasite rates, antibody levels and the neonatal infection rate also decreased. The pattern of seasonality confirmed that P. vivax in Henan Province was primarily of the long incubation type (temperate) during non-transmission period. The findings retrospectively provide a scientific basis for the implementation of mass campaigns of liver stage hypnozoite clearance. Entomological studies indicated that An. sinensis was the only vector, and it preferred bovine to human hosts, predominantly biting and resting outdoors. Mosquito densities declined between 1971 and 1984.

Conclusion

The integrated malaria control approach in Guantang effectively controlled malaria and achieved elimination. Analysis of the effectiveness of the programme can provide guidance to other regions or countries with similar ecological settings aiming to move from malaria control to elimination. There is a potential challenge in the maintenance of non-transmission status owing to imported cases and the long dormancy of liver stage hypnozoites.
The circular RNA circ-ERBIN promotes growth and metastasis of colorectal cancer by miR-125a-5p and miR-138-5p/4EBP-1 mediated cap-independent HIF-1α translation
Authors: Chen Liang-Yan , Wang Lian , Ren Yue-Xiang , Pang Zheng , Liu Yao , Sun Xiao-Dong , Tu Jian , Zhi Zheng , Qin Yan , Sun Li-Na , Li Jian-Ming
Published: November 2020

Background

Circular RNA (circRNAs) and hypoxia have been found to play the key roles in the pathogenesis and progression of cancer including colorectal cancer (CRC). However, the expressions and functions of the specific circRNAs in regulating hypoxia-involved CRC metastasis, and the circRNAs that are relevant to regulate HIF-1α levels in CRC remain elusive.

Methods

qRT-PCR was used to detect the expression of circRNAs and mRNA in CRC cells and tissues. Fluorescence in situ hybridization (FISH) was used to analyze the location of circ-ERBIN. Function-based experiments were performed using circ-ERBIN overexpression and knockdown cell lines in vitro and in vivo, including CCK8, colony formation, EdU assay, transwell, tumor growth and metastasis models. Mechanistically, luciferase reporter assay, western blots and immunohistochemical stainings were performed.

Results

Circ-Erbin was highly expressed in the CRC cells and Circ-Erbin overexpression facilitated the proliferation, migration and metastasis of CRC in vitro and in vivo. Notably, circ-Erbin overexpression significantly promoted angiogenesis by increasing the expression of hypoxia induced factor (HIF-1α) in CRC. Mechanistically, circ-Erbin accelerated a cap-independent protein translation of HIF-1α in CRC cells as the sponges of miR-125a-5p and miR-138-5p, which synergistically targeted eukaryotic translation initiation factor 4E binding protein 1(4EBP-1).

Conclusions

Our findings uncover a key mechanism for circ-Erbin mediated HIF-1α activation by miR-125a-5p-5p/miR-138-5p/4EBP-1 axis and circ-ERBIN is a potential target for CRC treatment.
Nanoparticle-complexed antimiRs for inhibiting tumor growth and metastasis in prostate carcinoma and melanoma
Authors: Kunz Manfred , Brandl Madeleine , Bhattacharya Animesh , Nobereit-Siegel Lars , Ewe Alexander , Weirauch Ulrike , Hering Doreen , Reinert Anja , Kalwa Hermann , Guzman Juan , Weigelt Katrin , Wach Sven , Taubert Helge , Aigner Achim
Published: November 2020

Background

MiRNAs act as negative regulators of gene expression through target mRNA degradation or inhibition of its translation. In cancer, several miRNAs are upregulated and play crucial roles in tumorigenesis, making the inhibition of these oncomiRs an interesting therapeutic approach. This can be achieved by directly complementary single-stranded anti-miRNA oligonucleotides (antimiRs). A major bottleneck in antimiR therapy, however, is their efficient delivery. The nanoparticle formation with polyethylenimine (PEI) may be particularly promising, based on the PEI’s ability to electrostatically interact with oligonucleotides. This leads to their protection and supports delivery. In the present study, we explore for the first time PEI for antimiR formulation and delivery. We use the branched low molecular weight PEI F25-LMW for the complexation of different antimiRs, and analyse tumor- and metastasis-inhibitory effects of PEI/antimiR complexes in different tumor models.

Results

In prostate carcinoma, transfection of antimiRs against miR-375 and miR-141 leads to tumor cell inhibition in 2D- and 3D-models. More importantly, an in vivo tumor therapy study in prostate carcinoma xenografts reveals anti-tumor effects of the PEI/antimiR complexes. In advanced melanoma and metastasis, we identify by a microRNA screen miR-150 as a particularly relevant oncomiR candidate, and validate this result in vitro and in vivo. Again, the systemic application of PEI/antimiR complexes inhibiting this miRNA, or the previously described antimiR-638, leads to profound tumor growth inhibition. These effects are associated with the upregulation of direct miRNA target genes. In a melanoma metastasis mouse model, anti-metastatic effects of PEI/antimiR treatment are observed as well.

Conclusions

We thus describe PEI-based complexes as efficient platform for antimiR therapy, as determined in two different tumor entities using in vivo models of tumor growth or metastasis. Our study also highlights the therapeutic relevance of miR-375, miR-141, miR-150 and miR-638 as target miRNAs for antimiR-mediated inhibition.
Generation of a novel human dermal substitute functionalized with antibiotic-loaded nanostructured lipid carriers (NLCs) with antimicrobial properties for tissue engineering
Authors: Chato-Astrain Jesús , Chato-Astrain Isabel , Sánchez-Porras David , García-García Óscar-Darío , Bermejo-Casares Fabiola , Vairo Claudia , Villar-Vidal María , Gainza Garazi , Villullas Silvia , Oruezabal Roke-Iñaki , Ponce-Polo Ángela , Garzón Ingrid , Carriel Víctor , Campos Fernando , Alaminos Miguel
Published: November 2020

Background

Treatment of patients affected by severe burns is challenging, especially due to the high risk ofPseudomonasinfection. In the present work, we have generated a novel model of bioartificial human dermis substitute by tissue engineering to treat infected wounds using fibrin-agarose biomaterials functionalized with nanostructured lipid carriers (NLCs) loaded with two anti-Pseudomonasantibiotics: sodium colistimethate (SCM) and amikacin (AMK).

Results

Results show that the novel tissue-like substitutes have strong antibacterial effect onPseudomonascultures, directly proportional to the NLC concentration. Free DNA quantification, WST-1 and Caspase 7 immunohistochemical assays in the functionalized dermis substitute demonstrated that neither cell viability nor cell proliferation were affected by functionalization in most study groups. Furthermore, immunohistochemistry for PCNA and KI67 and histochemistry for collagen and proteoglycans revealed that cells proliferated and were metabolically active in the functionalized tissue with no differences with controls. When functionalized tissues were biomechanically characterized, we found that NLCs were able to improve some of the major biomechanical properties of these artificial tissues, although this strongly depended on the type and concentration of NLCs.

Conclusions

These results suggest that functionalization of fibrin-agarose human dermal substitutes with antibiotic-loaded NLCs is able to improve the antibacterial and biomechanical properties of these substitutes with no detectable side effects. This opens the door to future clinical use of functionalized tissues.
How effective are electronic cigarettes for reducing respiratory and cardiovascular risk in smokers? A systematic review
Authors: Goniewicz Maciej L. , Miller Connor R. , Sutanto Edward , Li Dongmei
Published: November 2020

Background

Electronic cigarettes (e-cigarettes) are widely promoted as harm-reduction products for smokers, and smokers commonly perceive them as less harmful than combustible cigarettes. One of the key questions regarding public health consequences of e-cigarettes is the magnitude of harm reduction achievable by smokers who switch from combustible cigarettes to e-cigarettes. We conducted a systematic literature review of epidemiological studies that estimated odds of respiratory and cardiovascular outcomes among former smokers who use e-cigarettes compared to current smokers.

Methods

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. We searched the PubMed and Embase databases in September 2020 to identify epidemiological studies that compared odds of cardiovascular and respiratory outcomes among former smokers who transitioned to e-cigarettes relative to odds among current smokers not using e-cigarettes (current exclusive smokers). We included studies that provided direct estimates of relevant odds ratios (ORs). We also included studies where indirect estimates of relevant ORs could be calculated based on published results. Two reviewers independently extracted data and conducted quality appraisals.

Results

Six population-based studies with sample sizes ranging from 19,475 to 161,529 respondents met review inclusion criteria, five of which were cross-sectional and one longitudinal. Three studies reported respiratory outcomes and three reported cardiovascular outcomes. ORs of respiratory outcomes (including chronic obstructive pulmonary disease, chronic bronchitis, emphysema, asthma, and wheezing) in former smokers who transitioned to e-cigarettes versus current exclusive smokers were below 1.0, ranging from 0.58 (95%CI 0.36–0.94) to 0.66 (95%CI 0.50–0.87; all p < 0.05). All ORs for cardiovascular outcomes (including stroke, myocardial infarction, and coronary heart disease) did not differ significantly from 1.0.

Conclusion

Though our review included a small number of studies, it provided consistent results. Former smokers who transitioned to e-cigarettes showed ~ 40% lower odds of respiratory outcomes compared to current exclusive smokers. Switching from smoking to e-cigarette does not appear to significantly lower odds of cardiovascular outcomes. Since the utility of cross-sectional studies for causal inference remains limited, both randomized controlled trials and prospective cohort studies are needed to better evaluate contributions of e-cigarettes as harm reduction tools for smokers.
Individual quality of life in spousal ALS patient-caregiver dyads
Authors: Galvin Miriam , Gavin Tommy , Mays Iain , Heverin Mark , Hardiman Orla
Published: November 2020

Background

Quality of life is a basic goal of health and social care. The majority of people with Amyotrophic Lateral Sclerosis (ALS) are cared for at home by family caregivers. It is important to recognize the factors that contribute to quality of life for individuals to better understand the lived experiences in a condition for which there is currently no curative treatment.

Aim

To explore individual quality of life of people with ALS and their informal caregivers over time.

Methods

Over three semi-structured home interviews, 28 patient-caregiver dyads provided information on a range of demographic and clinical features, psychological distress, caregiver burden, and individual quality of life. Quality of life data were analysed using quantitative and qualitative methods with integration at the analysis and interpretation phases.

Results

Individual Quality of Life was high for patients and caregivers across the interviews series, and higher among patients than their care partners at each time point. Family, hobbies and social activities were the main self-defined contributors to quality of life. The importance of health declined relative to other areas over time. Friends and finances became less important for patients, but were assigned greater importance by caregivers across the illness trajectory. Psychological distress was higher among caregivers. Caregiver burden consistently increased.

Conclusion

The findings from this study point to the importance of exploring and monitoring quality of life at an individual level. Self-defined contributory factors are relevant to the individual within his/her context. As an integrated outcome measure individual quality of life should be assessed and monitored as part of routine clinical care during the clinical encounter. This can facilitate conversations between health care providers, patients and families, and inform interventions and contribute to decision support mechanisms. The ascertainment of self-defined life quality, especially in progressive neurodegenerative conditions, mean health care professionals are in a better position to provide person-centred care.
Establishment of an immortalized stromal cell line derived from human Endometriotic lesion
Authors: Huang Zhi-Xiong , Wu Rong-Feng , Mao Xiao-Mei , Huang Shao-Min , Liu Tian-Tian , Chen Qiong-Hua , Chen Qing-Xi
Published: November 2020

Background

Endometriosis is a benign gynecological disease with obviously feature of estrogen-dependence and inflammatory response. The applications of primary endometriotic stromal cells in research of endometriosis are restricted for short life span, dedifferentiation of hormone and cytokine responsiveness. The objective of this study was to establish and characterize immortalized human endometriotic stromal cells (ihESCs).

Methods

The endometriotic samples were from a patient with ovarian endometriosis and the primary endometriotic stromal cells were isolated from the endometriotic tissues. The primary cells were infected by lentivirus to establish telomerase reverse transcriptase (hTERT)-induced immortalized cells. Quantification of mRNA and proteins was examined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot. CCK-8 assay and EdU labeling assay were assigned to assess the growth of ihESCs. Karyotype assay was performed to detect the chromosomes of ihESCs. Colony formation assay and nude mouse tumorigenicity assay were used to evaluate colony-formation and tumorigenesis abilities.

Results

ihESCs continuously overexpressed hTERT via infection of lentivirus and significant extended the life span reaching 31 passages. The morphology, proliferation and karyotype of ihESCs remained unchanged. The expression of epithelial-mesenchymal transition (EMT) markers, estrogen-metabolizing proteins and estrogen/progesterone receptors (ERs and PRs) were unaltered. Furthermore, the treatment of estrogen increased the proliferation and EMT of ihESCs. Lipopolysaccharides (LPS) and IL-1β remarkably induced inflammatory response. The clonogenesis ability of ihESCs was consistent with primary cells, which were much lower than Ishikawa cells. In addition, nude mouse tumorigenicity assay demonstrated that ihESCs were unable to trigger tumor formation.

Conclusion

This study established and characterized an immortalized endometriotic stromal cell line that exhibited longer life span and kept the cellular morphology and physiological function as the primary cells. The immortalized cells remained normal feedback to estrogen and inflammatory response. Moreover, the immortalized cells were not available with tumorigenic ability. Therefore, ihESCs would be serviceable as in vitro cell tool to investigate the pathogenesis of endometriosis.