bluuebunny/crossref_metadata_2025 huggingface dataset:
Gas chromatography-mass spectrometry analysis, phytochemical screening and antiprotozoal effects of the methanolic Viola tricolor and acetonic Laurus nobilis extracts
Authors: Batiha Gaber El-Saber , Beshbishy Amany Magdy , Alkazmi Luay , Adeyemi Oluyomi Stephen , Nadwa Eman , Rashwan Eman , El-Mleeh Amany , Igarashi Ikuo
Published: March 2020

Background

The antiprotozoal and antioxidant activities of Viola tricolor and Laurus nobilis have been reported recently. Thus, the existing study pursued to assess the growth inhibition effect of methanolic extract of V. tricolor (MEVT) and acetonic extract of L. nobilis (AELN) against five Babesia parasites and Theileria equi in vitro and in vivo.

Results

MEVT and AELN suppressed Babesia bovis, B. bigemina, B. divergens, B. caballi, and T. equi growth at half-maximal inhibitory concentration (IC50) values of 75.7 ± 2.6, 43.3 ± 1.8, 67.6 ± 2.8, 48 ± 3.8, 54 ± 2.1 μg/mL, and 86.6 ± 8.2, 33.3 ± 5.1, 62.2 ± 3.3, 34.5 ± 7.5 and 82.2 ± 9.3 μg/mL, respectively. Qualitative phytochemical estimation revealed that both extracts containing multiple bioactive constituents and significant amounts of flavonoids and phenols. The toxicity assay revealed that MEVT and AELN affected the mouse embryonic fibroblast (NIH/3 T3) and Madin–Darby bovine kidney (MDBK) cell viability with half-maximum effective concentrations (EC50) of 930 ± 29.9, 1260 ± 18.9 μg/mL, and 573.7 ± 12.4, 831 ± 19.9 μg/mL, respectively, while human foreskin fibroblasts (HFF) cell viability was not influenced even at 1500 μg/mL. The in vivo experiment revealed that the oral administration of MEVT and AELN prohibited B. microti multiplication in mice by 35.1 and 56.1%, respectively.

Conclusions

These analyses indicate the prospects of MEVT and AELN as good candidates for isolating new anti-protozoal compounds which could assist in the development of new drug molecules with new drug targets.
RETRACTED ARTICLE: Sedum sarmentosum Bunge extract ameliorates lipopolysaccharide- and D-galactosamine-induced acute liver injury by attenuating the hedgehog signaling pathway via regulation of miR-124 expression
Authors: Hao Li , Liu Ming-wei , Gu Song-tao , Huang Xue , Deng Hong , Wang Xu
Published: March 2020

Background

Sedum sarmentosum is traditionally used to treat various inflammatory diseases in China. It has protective effects against acute liver injury, but the exact mechanism of such effects remains unclear. This study investigated the protective effects of S. sarmentosum extract on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute liver injury in mice and the mechanism of such effects.

Methods

Mice were randomly divided into control, treatment, model, and model treatment groups. Acute liver injury was induced in model mice via intraperitoneal injection of LPS and D-GalN with doses of 10 μg/kg of LPS and 500 mg/kg, respectively. The mRNA expression levels of miR-124, Hedgehog, Patched (Ptch), Smoothened (Smo), and glioma-associated oncogene homolog (Gli) in liver tissues were determined through RT-PCR, and the protein levels of Hedgehog, Ptch, Smo, Gli, P13k, Akt, HMGB1, TLR4, IkB-α, p-IkB-α, and NF-kB65 were evaluated via Western blot analysis. The serum levels of IL-6, TNF-α, CRP, IL-12, and ICAM-1 were determined via ELISA. TLR4 and NF-κBp65 activity and the levels of DNA-bound NF-KB65 and TLR4 in LPS/D-GalN-induced liver tissues were also determined. We recorded the time of death, plotted the survival curve, and calculated the liver index. We then observed the pathological changes in liver tissue and detected the levels of liver enzymes (alanine aminotransferase [ALT] and aspartate transaminase [AST]) in the serum and myeloperoxidase (MPO) and plasma inflammatory factors in the liver homogenate. Afterward, we evaluated the protective effects of S. sarmentosum extracts on acute liver injury in mice.

Results

Results showed that after S. sarmentosum extract was administered, the expression level of miR-124 increased in liver tissues. However, the protein expression levels of Hedgehog, Ptch, Smo, Gli, P13k, p-Akt, HMGB1, TLR4, p-IκB-α, and NF-κB65 and the mRNA expression levels of Hedgehog, Ptch, Smo, and Gli decreased. The MPO level in the liver, the IL-6, TNF-α, CRP, IL-12, and MMP-9 levels in the plasma, and the serum ALT and AST levels also decreased, thereby reducing LPS/D-GalN-induced liver injury and improving the survival rate of liver-damaged animals within 24 h.

Conclusions

S. sarmentosum extract can alleviate LPS/D-GalN-induced acute liver injury in mice and improve the survival rate of mice. The mechanism may be related to the increase in miR-124 expression, decrease in Hedgehog and HMGB1 signaling pathway activities, and reduction in inflammatory responses in the liver. Hedgehog is a regulatory target for miR-124.
Evaluation of antimicrobial activity of the hydrolate of Coridothymus capitatus (L.) Reichenb. fil. (Lamiaceae) alone and in combination with antimicrobial agents
Authors: Marino Andreana , Nostro Antonia , Mandras Narcisa , Roana Janira , Ginestra Giovanna , Miceli Natalizia , Taviano Maria Fernanda , Gelmini Fabrizio , Beretta Giangiacomo , Tullio Vivian
Published: March 2020

Background

Hydrolates, complex mixtures containing traces of essential oils (EOs), are inexpensive, easy to make and less toxic than their corresponding EOs. The antibacterial and antifungal activity of the hydrolate of Coridothymus capitatus (L.) Reichenb. fil. (Lamiaceae) alone and in combination with antimicrobial drugs, such as tetracycline and itraconazole, were evaluated.

Methods

The chemical composition was analysed by gas-chromatography-mass spectrometry (GC-MS). Standard methods were performed to evaluate the susceptibility of some Gram-positive and Gram-negative bacteria, and Candida spp. to the hydrolate, in comparison with its EO. The hydrolate mechanism of action was assayed by propidium iodide and MitoTracker staining. Checkerboard tests were carried out for combinations studies.

Results

GC-MS identified 0.14% (v/v) of total EO content into hydrolate and carvacrol as a dominant component. The hydrolate showed a good antimicrobial activity against bacteria and yeasts. It exhibited a synergistic effect with itraconazole against Candida krusei, and an additive effect with tetracycline against methicillin-resistant Staphylococcus aureus strains. Hydrolate changed the membranes permeability of bacteria and yeasts and altered mitochondrial function of yeasts.

Conclusions

Our study extends the knowledge by exploiting non-conventional antimicrobial agents to fight the emergence of antibiotic resistance.
Teaching medical professionalism: a qualitative exploration of persuasive communication as an educational strategy
Authors: Page Michael , Crampton Paul , Viney Rowena , Rich Antonia , Griffin Ann
Published: March 2020

Background

Across the world, local standards provide doctors with a backbone of professional attitudes that must be embodied across their practice. However, educational approaches to develop attitudes are undermined by the lack of a theoretical framework. Our research explored the ways in which the General Medical Council’s (GMC) programme of preventative educational workshops (the Duties of a Doctor programme) attempted to influence doctors’ professional attitudes and examined how persuasive communication theory can advance understandings of professionalism education.

Methods

This qualitative study comprised 15 ethnographic observations of the GMC’s programme of preventative educational workshops at seven locations across England, as well as qualitative interviews with 55 postgraduate doctors ranging in experience from junior trainees to senior consultants. The sample was purposefully chosen to include various geographic locations, different programme facilitators and doctors, who varied by seniority. Data collection occurred between March to December 2017. Thematic analysis was undertaken inductively, with meaning flowing from the data, and deductively, guided by persuasive communication theory.

Results

The source (educator); the message (content); and the audience (participants) were revealed as key influences on the persuasiveness of the intervention. Educators established a high degree of credibility amongst doctors and worked to build rapport. Their message was persuasive, in that it drew on rational and emotional communicative techniques and made use of both statistical and narrative evidence. Importantly, the workshops were interactive, which allowed doctors to engage with the message and thus increased its persuasiveness.

Conclusions

This study extends the literature by providing a theoretically-informed understanding of an educational intervention aimed at promoting professionalism, examining it through the lens of persuasive communication. Within the context of interactive programmes that allow doctors to discuss real life examples of professional dilemmas, educators can impact on doctors’ professional attitudes by drawing on persuasive communication techniques to enhance their credibility to demonstrate expertise, by building rapport and by making use of rational and emotional appeals.
Testing the validity and feasibility of using a mobile phone-based method to assess the strength of implementation of family planning programs in Malawi
Authors: Pattnaik Anooj , Mohan Diwakar , Chipokosa Sam , Wachepa Sautso , Katengeza Hans , Misomali Amos , Marx Melissa A.
Published: March 2020

Background

To effectively deliver on proposed objectives, it is vital that practitioners, policymakers, and other stakeholders are able to clearly understand how strongly their large-scale program is being implemented. This study sought to test the feasibility, cost-effectiveness, and validity of a phone-based method as an innovative and cost-efficient approach to assessing program implementation strength (through an Implementation Strength Assessment - ISA), alternative to the traditional in-person field methods.

Methods

We conducted 701 mobile phone and 356 in-person interviews with facility in-Charges and two types of community health workers who provide family planning services in the Dowa and Ntcheu districts in Malawi. Responses received via the phone interview were validated through in-person review of records and inspections. Sensitivity and specificity were calculated to determine validity.

Results

Most indicators at the health facility and community health worker levels were above a 70% threshold for sensitivity. However, there were fewer indicators that met this threshold for specificity. The primary reason for lower specificity was due to poor recordkeeping. Collecting data via mobile phone was found to be feasible and twice as cost-efficient as collecting the same data via in-person inspections.

Conclusions

The rapid increase in mobile phone ownership and network availability in lower income countries could offer an alternative, cost-effective avenue to collect data for a better understanding of program implementation. Through rigorous assessment, this study found that using mobile phones could be a low-cost alternative to collect data on health system delivery of services, especially in places where routine data quality is poor and traditional, in-person methods are costly.
Understanding implementation barriers in the national scale-up of differentiated ART delivery in Uganda
Authors: Zakumumpa Henry , Rujumba Joseph , Kwiringira Japheth , Katureebe Cordelia , Spicer Neil
Published: March 2020

Background

Although Differentiated Service Delivery (DSD) for anti-retroviral therapy (ART) has been rolled-out nationally in several countries since World Health Organization (WHO)‘s landmark 2016 guidelines, there is little research evaluating post-implementation outcomes. The objective of this study was to explore patients’ and HIV service managers’ perspectives on barriers to implementation of Differentiated ART service delivery in Uganda.

Methods

We employed a qualitative descriptive design involving 124 participants. Between April and June 2019 we conducted 76 qualitative interviews with national-level HIV program managers (n = 18), District Health Team leaders (n = 24), representatives of PEPFAR implementing organizations (11), ART clinic in-charges (23) in six purposively selected Uganda districts with a high HIV burden (Kampala, Luwero, Wakiso, Mbale, Budadiri, Bulambuli). Six focus group discussions (48 participants) were held with patients enrolled in DSD models in case-study districts. Data were analyzed by thematic approach as guided by a multi-level analytical framework: Individual-level factors; Health-system factors; Community factors; and Context.

Results

Our data shows that multiple barriers have been encountered in DSD implementation. Individual-level: Individualized stigma and a fear of detachment from health facilities by stable patients enrolled in community-based models were reported as bottlenecks. Socio-economic status was reported to have an influence on patient selection of DSD models. Health-system: Insufficient training of health workers in DSD delivery and supply chain barriers to multi-month ART dispensing were identified as constraints. Patients perceived current selection of DSD models to be provider-intensive and not sufficiently patient-centred. Community: Community-level stigma and insufficient funding to providers to fully operationalize community drug pick-up points were identified as limitations. Context: Frequent changes in physical addresses among urban clients were reported to impede the running of patient groups of rotating ART refill pick-ups.

Conclusion

This is one of the first multi-stakeholder evaluations of national DSD implementation in Uganda since initial roll-out in 2017. Multi-level interventions are needed to accelerate further DSD implementation in Uganda from demand-side (addressing HIV-related stigma, community engagement) and supply-side dimensions (strengthening ART supply chain capacities, increasing funding for community models and further DSD program design to improve patient-centeredness).
Towards universal access to healthcare for older adults: an assessment of the old-age exemption policy under Ghana’s National Health Insurance Scheme
Authors: Dake Fidelia A. A. , van der Wielen Nele
Published: March 2020

Background

Despite calls for governments to provide universal health coverage for all, social health insurance programmes (SHI) that specifically target older adults continue to be largely absent in many African countries. Only a few African countries have implemented SHI programmes that include specific provisions for older adults. Ghana’s National Health Insurance Scheme (NHIS) is one of the few programmes in Africa that exempts older adults from paying premiums for health insurance. This study examined socio-demographic factors associated with old-age premium exemption under Ghana’s NHIS.

Methods

The study used data from the seventh round of the Ghana Living Standards Survey (GLSS 7) conducted in 2017. Descriptive statistics and binary logistic regression were used in analysing data from a sample of 1532 older adults aged 70 years and older.

Results

The results reveal that only about 43% of older adults who were enrolled on the NHIS at the time of the survey acquired their membership through the old-age exemption policy. Additionally, increasing age was associated with higher odds of reporting exemption from paying premiums for health insurance. Also, older adults who are living in rural areas were more likely to pay premiums rather than being exempt as compared to their counterparts living in urban areas.

Conclusions

These findings indicate that the old-age exemption policy is not achieving the intended goal of providing financial risk protection for some older adults. Additionally, the policy is not reaching those who need it most, particularly those living in rural areas. Specific targeting is required for older adults living in rural areas who are less likely to benefit from the old-age exemption policy in spite of being eligible.
Matrix metalloprotein-triggered, cell penetrating peptide-modified star-shaped nanoparticles for tumor targeting and cancer therapy
Authors: Guo Fangyuan , Fu Qiafan , Zhou Kang , Jin Chenghao , Wu Wenchao , Ji Xugang , Yan Qinying , Yang Qingliang , Wu Danjun , Li Aiqin , Yang Gensheng
Published: March 2020

Background

Specific targeting ability and good cell penetration are two critical requirements of tumor-targeted delivery systems. In the present work, we developed a novel matrix metalloprotein-triggered, cell-penetrating, peptide-modified, star-shaped nanoparticle (NP) based on a functionalized copolymer (MePEG-Peptide-Tri-CL), with the peptide composed of GPLGIAG (matrix metalloprotein-triggered peptide for targeted delivery) and r9 (cell-penetrating peptide for penetration improvement) to enhance its biological specificity and therapeutic effect.

Results

Based on the in vitro release study, a sustained release profile was achieved for curcumin (Cur) release from the Cur-P-NPs at pH 7.4. Furthermore, the release rate of Cur was accelerated in the enzymatic reaction. MTT assay results indicated that the biocompatibility of polymer NPs (P-NPs) was inversely related to the NP concentration, while the efficiency toward tumor cell inhibition was positively related to the Cur-P-NP concentration. In addition, Cur-P-NPs showed higher fluorescence intensity than Cur-NPs in tumor cells, indicating improved penetration of tumor cells. An in vivo biodistribution study further demonstrated that Cur-P-NPs exhibited stronger targeting to A549 xenografts than to normal tissue. Furthermore, the strongest tumor growth inhibition (76.95%) was observed in Cur-P-NP-treated A549 tumor xenograft nude mice, with slight pulmonary toxicity.

Conclusion

All results demonstrated that Cur-P-NP is a promising drug delivery system that possesses specific enzyme responsiveness for use in anti-tumor therapy.
Circ-FOXM1 contributes to cell proliferation, invasion, and glycolysis and represses apoptosis in melanoma by regulating miR-143-3p/FLOT2 axis
Authors: Tian Shan , Han Gangwen , Lu Lulu , Meng Xiangyu
Published: March 2020

Background

Numerous literatures have demonstrated that circular RNAs (circRNAs) are involved in multiple types of tumors. However, the effects of circRNAs in melanoma are not very clear. In this study, we aimed to investigate the roles and mechanisms of circ-FOXM1 in melanoma.

Methods

Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to determine the expression of circ-FOXM1, microRNA-143-3p (miR-143-3p), and Flotillin 2 (FLOT2) mRNA. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, flow cytometry analysis, and transwell assay were employed to test cell proliferation, apoptosis, and invasion, respectively. The glucose consumption and lactate production were examined by specific kits. Western blot assay was utilized for the detection of hexokinase2 (HK2), pyruvate kinase isozyme type M2 (PKM2), and FLOT2. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were employed to verify the targeting association between miR-143-3p and circ-FOXM1 or FLOT2. A murine xenograft model was established to explore the effect of circ-FOXM1 in vivo.

Results

Circ-FOXM1 was elevated and miR-143-3p was reduced in melanoma tissues and cells. Circ-FOXM1 deficiency impeded cell proliferation, invasion, and glycolysis and facilitated cell apoptosis in melanoma in vitro and tumorigenesis in vivo. Circ-FOXM1 acted as a sponge of miR-143-3p and the impacts of circ-FOXM1 silencing on cell proliferation, apoptosis, invasion, and glycolysis were overturned by miR-143-3p deletion. Moreover, FLOT2 was a target gene of miR-143-3p and FLOT2 overexpression rescued the inhibitory effect of miR-143-3p on melanoma progression.

Conclusion

Circ-FOXM1 facilitated the development of melanoma by upregulating FLOT2 through miR-143-3p.
Attitudes of anesthetists towards an anesthesia-led nurse practitioner model for low-risk colonoscopy procedures: a cross-sectional survey
Authors: Weinberg L. , Grover H. , Cowie D. , Langley E. , Heland M. , Story D. A.
Published: March 2020

Background

The mounting pressure on the Australian healthcare system is driving a continual exploration of areas to improve patient care and access and to maximize utilization of our workforce. We hypothesized that there would be support by anesthetists employed at our hospital for the design, development, and potential implementation of an anesthesia-led nurse practitioner (NP) model for low-risk colonoscopy patients.

Methods

We conducted a cross-sectional, mixed methods study to ascertain the attitudes and acceptability of anesthetists towards a proposed anesthesia-led NP model for low-risk colonoscopy patients. An online survey using commercial software and theoretical questions pertaining to participants’ attitudes towards an anesthesia-led NP model was e-mailed to consultant anesthetists. Participants were also invited to participate in a voluntary 20-min face-to-face interview.

Results

A total of 60 survey responses were received from a pool of 100 anesthetists (response rate = 60%, accounting for 8.04% margin of error). Despite the theoretical benefits of improved patient access to colonoscopy services, most anesthetists were not willing to participate in the supervision and training of NPs. The predominant themes underlying their lack of support for the program were a perception that patient safety would be compromised compared to the current model of anesthesia-led care, the model does not meet the Australian and New Zealand College of Anesthetists guidelines for procedural sedation and analgesia, and the program may be a public liability prone to litigation in the event of an adverse outcome. Concerns about consumer acceptance and cost-effectiveness were also raised. Finally, participants thought the model should be pilot tested to better understand consumer attitudes, logistical feasibility, patient and proceduralist attitudes, clinical governance, and, importantly, patient safety.

Conclusions

Most anesthetists working in a single-center university hospital did not support an anesthesia-led NP model for low-risk colonoscopy patients. Patient safety, violations of the current Australian and New Zealand College of Anesthetists guidelines on procedural sedation, and logistical feasibility were significant barriers to the acceptance of the model.

Trial registration

Australian and New Zealand Clinical Trials Registry,12619001036101
Increased serum neurofilament light chain concentration indicates poor outcome in Guillain-Barré syndrome
Authors: Altmann Patrick , De Simoni Desiree , Kaider Alexandra , Ludwig Birgit , Rath Jakob , Leutmezer Fritz , Zimprich Fritz , Hoeftberger Romana , Lunn Michael P. , Heslegrave Amanda , Berger Thomas , Zetterberg Henrik , Rommer Paulus Stefan
Published: March 2020

Background

Guillain-Barré syndrome (GBS) is an autoimmune disease that results in demyelination and axonal damage. Five percent of patients die and 20% remain significantly disabled on recovery. Recovery is slow in most cases and eventual disability is difficult to predict, especially early in the disease. Blood or cerebrospinal fluid (CSF) biomarkers that could help identify patients at risk of poor outcome are required. We measured serum neurofilament light chain (sNfL) concentrations from blood taken upon admission and investigated a correlation between sNfL and clinical outcome.

Methods

Baseline sNfL levels in 27 GBS patients were compared with a control group of 22 patients with diagnoses not suggestive of any axonal damage. Clinical outcome parameters for GBS patients included (i) the Hughes Functional Score (HFS) at admission, nadir, and discharge; (ii) the number of days hospitalised; and (iii) whether intensive care was necessary.

Results

The median sNfL concentration in our GBS sample on admission was 85.5 pg/ml versus 9.1 pg/ml in controls. A twofold increase in sNfL concentration at baseline was associated with an HFS increase of 0.6 at nadir and reduced the likelihood of discharge with favourable outcome by a factor of almost three. Higher sNfL levels upon admission correlated well with hospitalisation time (rs = 0.69, p < 0.0001), during which transfer to intensive care occurred more frequently at an odds ratio of 2.4. Patients with baseline sNfL levels below 85.5 pg/ml had a 93% chance of being discharged with an unimpaired walking ability.

Conclusions

sNfL levels measured at hospital admission correlated with clinical outcome in GBS patients. These results represent amounts of acute axonal damage and reflect mechanisms resulting in disability in GBS. Thus, sNfL may serve as a convenient blood-borne biomarker to personalise patient care by identifying those at higher risk of poor outcome.
Adverse pregnancy outcomes among women presenting at antenatal clinics in Ouélessébougou, Mali
Authors: Andemel Naissem , Gaoussou Santara , Barry Amadou , Issiaka Djibrilla , Mahamar Almahamoudou , Traore Moussa , Duffy Patrick E. , Dicko Alassane , Fried Michal
Published: March 2020

Background

In sub-Saharan Africa, malaria continues to scourge the population and is the primary cause of morbidity and mortality in young children and pregnant women. As current preventative measures such as intermittent preventive treatment and use of insecticide-treated nets provide incomplete protection, several malaria vaccines are currently under development, including one to specifically prevent pregnancy malaria. Prior to conducting vaccine trials, it is important to obtain background information on poor pregnancy outcomes in the target population to establish a baseline.

Methods

Pregnant women presenting at community health care centers for antenatal care were recruited to the study. Gestational age was determined by ultrasound examination following recruitment. Antenatal care and pregnancy outcome information were collected during a visit 4–8 weeks post-delivery.

Results

One thousand eight hundred fifty women completed the study, and analysis included 1814 women after excluding multiple gestations (n = 26) and missing/incomplete data (n = 10). The percentage (95% CI) of adverse pregnancy outcomes is as follows: miscarriage, 0.28% (0.04–0.52); stillbirth, 1.93% (1.30–2.56); early neonatal death, 1.65% (1.03–2.24); late neonatal death, 0.39%, (0.10–0.68); and preterm delivery (PTD), 4.74% (3.76–5.73). The percentages of early and late neonatal deaths and PTD were significantly higher (p < 0.01) in primigravid compared to multigravid women. In primigravidae, 3.1, 1.1 and 7.1% of pregnancies resulted in early neonatal death, late neonatal death and PTD, respectively, while these outcomes in multigravidae were 1.0, 0.1 and 2.7%, respectively. Major malformations were identified in 4 newborns.

Conclusions

Low gravidity and young age predict perinatal death and PTD. The information collected here can be used as a baseline for adverse pregnancy outcomes in future vaccine trials in pregnant women.
Abnormally increased carotid intima media-thickness and elasticity in patients with Morquio A disease
Authors: Wang Raymond Y. , Rudser Kyle D. , Dengel Donald R. , Evanoff Nicholas , Steinberger Julia , Movsesyan Nina , Garrett Robert , Christensen Katherine , Boylan Deborah , Braddock Stephen R. , Shinawi Marwan , Gan Qi , Montaño Adriana M.
Published: March 2020

Background

Cardiovascular disease frequently causes morbidity and mortality in mucopolysaccharidoses (MPS); however, cardiovascular anatomy and dysfunction in MPS IVA (Morquio A disease) is not well described. Consequently, the study aimed to compare carotid artery structure and elasticity of MPS IVA patients with other MPS patients and healthy control subjects, and quantitate frequency of MPS IVA cardiac structural and functional abnormalities.

Methods

Prospective, multi-center echocardiogram and carotid ultrasound evaluations of 12 Morquio A patients were compared with other MPS and healthy control subjects. Average differences between groups were adjusted for age, sex, and height with robust variance estimation for confidence intervals and P-values.

Results

Morquio A patients demonstrated significantly higher (P < 0.001) adjusted carotid intima-media thickness (cIMT), mean (SD) of 0.56 mm (0.03) compared to control subjects, 0.44 mm (0.04). The Morquio A cohort had significantly greater adjusted carotid elasticity (carotid cross-sectional compliance + 43%, P < 0.001; carotid incremental elastic modulus − 33%, P = 0.003) than control subjects and other MPS patients. Aortic root dilatation was noted in 56% of the Morquio A cohort, which also had highly prevalent mitral (73%) and aortic (82%) valve thickening, though hemodynamically significant valve dysfunction was less frequent (9%).

Conclusions

Increased carotid elasticity in Morquio A patients is an unexpected contrast to the reduced elasticity observed in other MPS. These Morquio A cIMT findings corroborate MPS IVA arterial post-mortem reports and are consistent with cIMT of other MPS. Aortic root dilatation in Morquio A indicates arterial elastin dysfunction, but their carotid hyperelasticity indicates other vascular intima/media components, such as proteoglycans, may also influence artery function. Studying MPS I and IVA model systems may uniquely illuminate the function of glycosaminoglycan-bearing proteoglycans in arterial health.
Treatment of mantle cell lymphoma in Asia: a consensus paper from the Asian Lymphoma Study Group
Authors: Yoon Dok Hyun , Cao Junning , Chen Tsai-Yun , Izutsu Koji , Kim Seok Jin , Kwong Yok Lam , Lin Tong Yu , Thye Lim Soon , Xu Bing , Yang Deok Hwan , Kim Won Seog
Published: March 2020

Background

Mantle cell lymphoma (MCL) is a B cell malignancy that can be aggressive and with a poor prognosis; the clinical course is heterogeneous. The epidemiology of MCL in Asia is not well documented but appears to comprise 2–6% of all lymphoma cases based on available data, with variation observed between countries. Although international guidelines are available for the treatment of MCL, there is a lack of published data or guidance on the clinical characteristics and management of MCL in patient populations from Asia. This paper aims to review the available treatment and, where clinical gaps exist, provide expert consensus from the Asian Lymphoma Study Group (ALSG) on appropriate MCL management in Asia.

Body

Management strategies for MCL are patient- and disease stage-specific and aim to achieve balance between efficacy outcomes and toxicity. For asymptomatic patients with clearly indolent disease, observation may be an appropriate strategy. For stage I/II disease, following international guidelines is appropriate, which include either a short course of conventional chemotherapy followed by consolidated radiotherapy, less aggressive chemotherapy regimens, or a combination of these approaches. For advanced disease, the approach is based on the age and fitness of the patient. For young, fit patients, the current practice for induction therapy differs across Asia, with cytarabine having an important role in this setting. Hematopoietic stem cell transplantation (HSCT) may be justified in selected patients because of the high relapse risk. In elderly patients, specific chemoimmunotherapy regimens available in each country/region are a treatment option. For maintenance therapy after first-line treatment, the choice of approach should be individualized, with cost being an important consideration within Asia. For relapsed/refractory disease, ibrutinib should be considered as well as other follow-on compounds, if available.

Conclusion

Asian patient-specific data for the treatment of MCL are lacking, and the availability of treatment options differs between country/region within Asia. Therefore, there is no clear one-size-fits-all approach and further investigation on the most appropriate sequence of treatment that should be considered for this heterogeneous disease.
Effects of Astragalus injection and Salvia Miltiorrhiza injection on serum inflammatory markers in patients with stable coronary heart disease: a randomized controlled trial protocol
Authors: Luo Zhihao , Liu Yuntao , Zhao Zhen , Yan Xia , Wang Dawei , Liu Qing
Published: March 2020

Background

Coronary heart disease (CHD) is a clinical syndrome caused by coronary atherosclerosis (AS) or functional changes in coronary arteries. We have previously reported that astragaloside IV (in astragalus) and tanshinone IIA (in Salvia miltiorrhiza) improve myocardial ischemic injury.

Methods

This study will employ the randomized, blinded, prospective, single-center experiments approach. Briefly, a total of 160 eligible patients will be equally randomized into three treatment groups and placebo control groups. Patients will receive appropriate treatments every 24 h for seven days after enrollment and followed up for 28 days. The main evaluation indicators will be cell count, serum high-sensitivity C-reactive protein (hs-CRP) level, monocyte chemoattractant protein 1 (MCP-1), interleukin-6 (IL-6), interleukin-1β (IL-1β), interleukin-8 (IL-8), interleukin-18 (IL-18), interleukin-10 (IL-10), tumor necrosis factor (TNF)-α, oxidized low density lipoprotein (OX-LDL), angina grade, and Traditional Chinese Medicine (TCM) symptom changes scale. Secondary indicators to be evaluated will include B-type natriuretic peptide (BNP) levels, troponin (cTn), muscle enzyme isoenzyme (CK-MB), heart-type fatty acid binding protein (H-FABP), liver and renal functions, as well as blood coagulation. Close monitoring of adverse events during the trial will also be conducted.

Discussion

This randomized controlled trial of Chinese herbal extracts for the treatment of coronary heart disease will generate results that are expected to provide valuable clinical evidence to inform future development of therapies towards management of CHD.

Trial registration

China Clinical Trial Registration Center, ChiCTR1900021590. Registered on 28 February 2019.
Evaluating the feasibility and preliminary efficacy of a Cognitive Occupation-Based programme for people with Multiple Sclerosis (COB-MS): protocol for a feasibility cluster-randomised controlled trial
Authors: Dwyer Christopher P. , Alvarez-Iglesias Alberto , Joyce Robert , Counihan Timothy J. , Casey Dympna , Hynes Sinéad M.
Published: March 2020

Background

Cognitive difficulties experienced by people with multiple sclerosis (MS) impact their quality of life and daily functioning, from childcare and work, to social and self-care activities. Despite the high prevalence of cognitive difficulties seen in MS, there is a lack of developed programmes that target cognition, while also supporting patients by helping them to function well in everyday life. The Cognitive Occupation-Based programme for people with MS (COB-MS) was developed as a holistic, individualised cognitive rehabilitation intervention. It addresses the wide-ranging symptoms and functional difficulties that present in MS, including the ability to maintain employment, social activities, home management and self-care. The aim of the current research is to evaluate the feasibility and preliminary efficacy of COB-MS for people with MS. The focus is on feasibility outcomes as well as functioning associated with cognitive difficulty and secondary outcomes related to cognition, fatigue and quality of life.

Methods

One hundred and twenty people with MS will be assigned to participate in either the COB-MS programme or a treatment as usual, wait-list control group as part of this single-blind, cluster-randomised controlled feasibility and preliminary efficacy trial of the COB-MS programme. The COB-MS group will participate in an eight-session occupational-based cognitive rehabilitation programme over 9 weeks. The primary outcome measure is the goal attainment scaling at 12 weeks. Participants will be assessed pre-intervention, post-intervention and at 12 weeks post-intervention and 6 months post-intervention. Qualitative evaluations of participants’ perspectives will also be examined as part of the feasibility study.

Discussion

Results will provide recommendations for a future definitive trial of COB-MS, with respect to both feasibility and preliminary, clinical efficacy. In the event that results indicate efficacy, study findings will suggest that COB-MS requires consideration as a means of enhancing cognitive and daily functioning in people living with MS.

Trial registration

ISRCTN: ISRCTN11462710. Registered on 9 September 2019.
Protocol for a mixed methods process evaluation of a hybrid implementation-effectiveness trial of a scaled-up whole-school physical activity program for adolescents: Physical Activity 4 Everyone (PA4E1)
Authors: Mclaughlin Matthew , Duff Jed , Sutherland Rachel , Campbell Elizabeth , Wolfenden Luke , Wiggers John
Published: March 2020

Background

Physical Activity 4 Everyone (PA4E1) is a physical activity program for secondary schools located in low-socioeconomic areas. Over a 24-month period, schools in the program arm of a cluster randomised controlled trial (n = up to 38 schools) will receive a multi-component implementation support strategy to embed the seven school physical activity practices of the PA4E1 program. This article describes the process evaluation of the PA4E1 hybrid implementation-effectiveness trial. The process evaluation aims to describe the fidelity and reach of the implementation support strategies using quantitative data; and to describe the acceptability, appropriateness and feasibility of the implementation support strategies and physical activity practices to school stakeholders using mixed methods.

Methods

Quantitative and qualitative data will be collected from participants (Physical Education teachers, in-School Champions, students) in the program arm. Data collection will involve semi-structured interviews, focus groups, a fidelity monitoring log, a fidelity checklist, surveys, and routinely collected administrative and website data. Quantitative data will be analysed descriptively and qualitative data will be analysed thematically within and across data sets. Triangulation between data sources will be used to synthesise findings regarding the implementation and potential mechanisms of impact of PA4E1 on school physical activity practice adoption, with respect to context.

Discussion

Results of the process evaluation will facilitate the interpretation of the findings of the trial outcomes. It will comprehensively describe what was actually implemented and identify the potential contribution of the various components of the implementation support strategy to the school physical activity practice adoption outcomes. Findings will inform future improvement and scale-up of PA4E1 and approaches to implementing secondary school-based physical activity programs more broadly.

Trial registration

Australian New Zealand Clinical Trials Registry ACTRN12617000681358 registered 12 May 2017.
Lrig1 expression prospectively identifies stem cells in the ventricular-subventricular zone that are neurogenic throughout adult life
Authors: Nam Hyung-song , Capecchi Mario R.
Published: March 2020

Background

Leucine-rich repeats and immunoglobulin-like domains 1 (Lrig1) regulates stem cell quiescence. As a marker, it identifies stem cells in multiple organs of the mouse. We had detected Lrig1 expression in cultured Id1high neural stem cells obtained from the lateral walls lining the lateral ventricles of the adult mouse brain. Thus, we investigated whether Lrig1 expression also identifies stem cells in that region in vivo.

Methods

Publicly available single cell RNA sequencing datasets were analyzed with Seurat and Monocle. The Lrig1+ cells were lineage traced in vivo with a novel non-disruptive co-translational Lrig1T2A-iCreERT2 reporter mouse line.

Results

Analysis of single cell RNA sequencing datasets suggested Lrig1 was highly expressed in the most primitive stem cells of the neurogenic lineage in the lateral wall of the adult mouse brain. In support of their neurogenic stem cell identity, cell cycle entry was only observed in two morphologically distinguishable Lrig1+ cells that could also be induced into activation by Ara-C infusion. The Lrig1+ neurogenic stem cells were observed throughout the lateral wall. Neuroblasts and neurons were lineage traced from Lrig1+ neurogenic stem cells at 1 year after labeling.

Conclusions

We identified Lrig1 as a marker of long-term neurogenic stem cells in the lateral wall of the mouse brain. Lrig1 expression revealed two morphotypes of the Lrig1+ cells that function as long-term neurogenic stem cells. The spatial distribution of the Lrig1+ neurogenic stem cells suggested all subtypes of the adult neurogenic stem cells were labeled.
Variation in the response of bovine alveolar lavage cells to diverse species of probiotic bacteria
Authors: Eicher Susan D. , Chitko-McKown Carol G. , Bryan Keith A.
Published: March 2020

Objective

Probiotics are fed to improve enteric health, and they may also affect respiratory immunity through their exposure to the upper respiratory tract upon ingestion. However, their effect on the respiratory system is not known. Our aim was to determine how probiotics affect functions and markers of bronchoalveolar lung lavage cells (BAL) isolated from lungs of calves at slaughter.

Results

Treatments consisted of ten probiotic species and one control treatment. Probiotics and BAL were incubated 1:1 for 2 h at 37 °C and 5% CO2. The cell surface markers measured included CD14, CD205, and CD18, and E. coli bioparticles were used to measure phagocytosis and oxidative burst. Differences were considered significant at P ≤ 0.05 and were noted for percent cells fluorescing and mean fluorescence intensity for CD14 and CD205. Additionally, oxidative burst was different as measured by both percentage of cells fluorescing and mean fluorescence intensity, and phagocytosis differed among species as measured by mean fluorescence intensity. Overall, probiotic species differed in their ability to suppress or increase leukocyte function showing that probiotic bacteria differentially modulate BAL.
Crosstalk between DNA methylation and histone acetylation triggers GDNF high transcription in glioblastoma cells
Authors: Zhang Baole , Gu Xiaohe , Han Xiao , Gao Qing , Liu Jie , Guo Tingwen , Gao Dianshuai
Published: March 2020

Background

Glial cell line-derived neurotrophic factor (GDNF) is highly expressed in glioblastoma (GBM) and blocking its expression can inhibit the initiation and development of GBM. GDNF is a dual promoter gene, and the promoter II with two enhancers and two silencers plays a major role in transcription initiation. We had previously reported that histone hyperacetylation and DNA hypermethylation in GDNF promoter II region result in high transcription of GDNF in GBM cells, but the mechanism remains unclear. In this study, we investigated whether these modifications synergistically regulate high GDNF transcription in GBM.

Results

Cyclic AMP response element binding protein (CREB) expression and phosphorylation at S133 were significantly increased in human GBM tissues and GBM cell lines (U251 and U343). In U251 GBM cells, high expressed CREB significantly enhanced GDNF transcription and promoter II activity. CREB regulated GDNF transcription via the cyclic AMP response elements (CREs) in enhancer II and silencer II of GDNF promoter II. However, the two CREs played opposite regulatory roles. Interestingly, hypermethylation of CRE in silencer II occurred in GBM tissues and cells which led to decreased and increased phosphorylated CREB (pCREB) binding to silencer II and enhancer II, respectively. Moreover, pCREB recruited CREB binding protein (CBP) with histone acetylase activity to the CRE of GDNF enhancer II, thereby increasing histone H3 acetylation and RNA polymerase II recruitment there and at the transcription start site (TSS), and promoted GDNF high transcription in U251 cells. The results indicated that high GDNF transcription was attributable to DNA hypermethylation in CRE of GDNF silencer II increasing pCREB binding to CRE in enhancer II, which enhanced CBP recruitment, histone H3 acetylation, and RNA polymerase II recruitment there and at the TSS.

Conclusions

Our results demonstrate that pCREB-induced crosstalk between DNA methylation and histone acetylation at the GDNF promoter II enhanced GDNF high transcription, providing a new perspective for GBM treatment.
CT imaging findings of abdominopelvic vascular compression syndromes: what the radiologist needs to know
Authors: Gozzo Cecilia , Giambelluca Dario , Cannella Roberto , Caruana Giovanni , Jukna Agita , Picone Dario , Midiri Massimo , Salvaggio Giuseppe
Published: March 2020

Abdominopelvic vascular compression syndromes include a variety of uncommon conditions characterized by either extrinsic compression of blood vessels by adjacent anatomical structures (i.e., median arcuate ligament syndrome, nutcracker syndrome, May-Thurner syndrome) or compression of hollow viscera by adjacent vessels (i.e., superior mesenteric artery syndrome, ureteropelvic junction obstruction, ureteral vascular compression syndromes, portal biliopathy). These syndromes can be unexpectedly diagnosed even in asymptomatic patients and the predisposing anatomic conditions can be incidentally discovered on imaging examinations performed for other indications, or they can manifest with atypical abdominal symptoms and acute complications, which may lead to significant morbidity if unrecognized. Although computed tomography (CT) is an accurate noninvasive technique for their detection, the diagnosis remains challenging due to the uncommon clinical presentation and often overlooked imaging features. Dynamic imaging may be performed in order to evaluate patients with inconstant symptoms manifesting in a specific position. The purposes of this paper are to review the CT imaging findings of abdominopelvic vascular compression syndromes, correlating with anatomical variants and to provide key features for the noninvasive imaging diagnosis.
CD59 receptor targeted delivery of miRNA-1284 and cisplatin-loaded liposomes for effective therapeutic efficacy against cervical cancer cells
Authors: Wang Li , Liang Ting-Ting
Published: March 2020

Co-delivery of two different therapeutics (miRNA-1284 and cisplatin (CDDP)) into the cancer cells in a single nanocarrier provides new dimension to the cancer treatment. In this study, we have designed the CD59sp-conjugated miRNA-1284/cisplatin(CDDP)-loaded liposomes for the enhanced therapeutic effect against cervical cancers. Compared with miRNA-1284/CDDP-loaded liposomes (LP-miCDDP), CD59 antibody-conjugated LP-miCDDP (CD/LP-miCDDP) showed a significantly higher cytotoxicity in HeLa cells. Notably, MiR-1284 showed a typical concentration-dependent cell killing effect in the cervical cancer cells owing to the downregulation of HMGB1. Flow cytometer analysis showed that CD/LP-miCDDP resulted in maximum apoptosis effect (~ 60%) compared to CDDP (~ 20%) or miR-1284 (~ 12%) treated cells indicating the superior anticancer effect in the cancer cells. Importantly, CD/LP-miCDDP significantly prolonged the blood circulation of encapsulated drug in rats with AUC(o-t) of CD/LP-miCDDP showed a 6.9 fold higher value than that of free CDDP. Similarly, CD/LP-miCDDP showed an eightfold decrease in the clearance (CL) and 3.6-fold higher t1/2 compared to that of free CDDP. Overall, results demonstrated that targeted and synergistic co-delivery of therapeutic components could be promising in cervical cancer therapy.