bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental and computational evidence for C=O π-bonding in [CH2OH]+ and related oxonium ions
Authors: Bowen Richard D , Martin William HC , Hudson Charles E , McAdoo David J
Published: January 2020

The question of whether [CH2OH]+ should be described as the hydroxymethyl cation, +CH2OH, or protonated formaldehyde, CH2=OH+, is reconsidered in the light of experimental information and new computational evidence. Previous arguments that the charge distribution in [CH2OH]+ may be probed by considering the incremental stabilisation of [CH2OH]+ induced by homologation on carbon (to give [CH3CHOH]+) or oxygen (to produce [CH2OCH3]+) are critically examined. Cation stabilisation energies are shown to be better indicators of the nature of these oxonium ions. Further insight into the structure of larger CnH2n+1O+ oxonium ions is obtained by considering the site of protonation of enol ethers and related species. Computational information, including AIM (Atoms and Molecules) and NBA (Natural Bond Analysis) charges on the carbon and oxygen atoms in [CH2OH]+ and related species, is considered critically. Particular attention is focused on the calculated bond lengths and barriers to rotation about the C–O bond(s) in [CH2OH]+, [CH3CHOH]+, [(CH3)2COH]+, CH3OH and [CH2OCH3]+ and the C–N bond in [CH2NH2]+. Trends in these data are consistent with appreciable π-bonding only in the C–O connections which correspond to the C=O bond in the parent aldehyde or ketone from which the oxonium ion may be considered to be derived by protonation or alkyl cationation.
Reversing the Tide of Suburban Families? The Design, Marketing, and Occupancy of Urban Renewal’s High-rise Housing
Authors: Ammon Francesca Russello
Published: January 2020

During the postwar urban renewal era, many US cities constructed high-rise downtown apartment buildings to lure families back from the suburbs. These projects met demand for high-end downtown housing. They often remain occupied today—in stark contrast to the more rapid demise of many other redevelopment projects designed for shopping, entertainment, or public housing use. Yet, they also often fell short of their larger demographic goals. This occupational history of New Haven, Connecticut’s first downtown high-rises shows that the projects’ architecture, site planning, public realm, and rental structures never lived up to either suburban alternatives or their own marketing promises.
Brain Metabolism but Not Gray Matter Volume Underlies the Presence of Language Function in the Minimally Conscious State (MCS): MCS+ Versus MCS− Neuroimaging Differences
Authors: Aubinet Charlène , Cassol Helena , Gosseries Olivia , Bahri Mohamed Ali , Larroque Stephen Karl , Majerus Steve , Martial Charlotte , Martens Géraldine , Carrière Manon , Chatelle Camille , Laureys Steven , Thibaut Aurore
Published: January 2020

Background. The minimally conscious state (MCS) is subcategorized into MCS− and MCS+, depending on the absence or presence, respectively, of high-level behavioral responses such as command-following. Objective. We aim to investigate the functional and structural neuroanatomy underlying the presence of these responses in MCS− and MCS+ patients. Methods. In this cross-sectional retrospective study, chronic MCS patients were diagnosed using repeated Coma Recovery Scale–Revised assessments. Fluorodeoxyglucose-positron emission tomography data were acquired on 57 patients (16 MCS−; 41 MCS+) and magnetic resonance imaging with voxel-based morphometry analysis was performed on 66 patients (17 MCS−; 49 MCS+). Brain glucose metabolism and gray matter integrity were compared between patient groups and control groups. A metabolic functional connectivity analysis testing the hypothesis of preserved language network in MCS+ compared with MCS− was also done. Results. Patients in MCS+ presented higher metabolism mainly in the left middle temporal cortex, known to be important for semantic processing, compared with the MCS− group. The left angular gyrus was also functionally disconnected from the left prefrontal cortex in MCS− compared with MCS+ group. No significant differences were found in gray matter volume between patient groups. Conclusions. The clinical subcategorization of MCS is supported by differences in brain metabolism but not in gray matter structure, suggesting that brain function in the language network is the main support for recovery of command-following, intelligible verbalization and/or intentional communication in the MCS. Better characterizing the neural correlates of residual cognitive abilities of MCS patients contributes to reduce their misdiagnosis and to adapt therapeutic approaches.
Dorsal Subluxation of the Proximal Interphalangeal Joint After Volar Base Fracture of the Middle Phalanx
Authors: Oflazoglu Kamilcan , de Planque Catherine A. , Guitton Thierry G. , Rakhorst Hinne , Chen Neal C.
Published: January 2020

Background: Treatment decisions regarding volar base fractures of the middle phalanx depend on whether the proximal interphalangeal (PIP) joint is reduced. Our aim was to study the agreement among hand surgeons in determining whether the PIP joint fractures are subluxated and to study the factors associated with subluxation of these fractures. Methods: In this retrospective chart review, 413 volar base fractures of the middle phalanx were included. Demographic and injury-related factors were gathered from medical records and radiographs. Using a Web-based survey, interobserver agreement was determined among 105 hand surgeons on the assessment of PIP joint subluxation of a series of 26 cases. Using the cohort of 413 fractures, a threshold for percent articular involvement and relative fracture displacement that corresponds with subluxation of the PIP joint was analyzed. Results: We found moderate to substantial agreement between hand surgeons on subluxation (κ = 0.59, P < .0001) and an overall percent agreement of 85%. Percent articular involvement and relative fracture displacement were independently associated with subluxation of the PIP joint ( P < .001). Percent articular involvement of 35% had a specificity of 90% and a negative predicting value (NPV) of 92% for joint subluxation. Relative fracture displacement of 35% had a specificity of 92% and an NPV of 94% for joint subluxation. Conclusions: Surgeons generally agree on whether a PIP joint is subluxated. Percent articular involvement and relative fragment displacement are objective measurements that can help characterize joint stability and assist with decision-making.
Isolated superior striate vein thrombosis in adults
Authors: Mazini Bianca , Bonvin Christophe , Gailloud Philippe , San Millán Diego
Published: January 2020

Background

Isolated cerebral deep medullary vein thrombosis has been described in the setting of hemorrhagic periventricular white matter lesions in preterm and full-term neonates, but to the best of our knowledge, has never been reported in adults. We present two cases of isolated thrombosis of the superior striate vein occurring in adults that could be analogous to deep medullary vein thrombosis in that they involve deep cerebral veins only without thrombosis of the subependymal or internal cerebral veins.

Case description

Two women aged 20 and 39, presented with transient neurological deficits and headache. Diagnosis of isolated superior striate vein thrombosis was based on CT and MRI findings with long term imaging follow-up. Both patients evolved favorably under conservative treatment without anticoagulation. Thrombophilia workup was negative and both patients were active smokers under oral contraception.

Conclusion

Isolated superior striate vein thrombosis is a rare form of intracranial venous thrombosis and should be considered in the differential diagnosis of stroke-like episodes with headache in adults. Isolated superior striate vein thrombosis presents with characteristic imaging features on CT and MRI.
Safety of carotid artery stenting for elderly patients with cervical carotid artery stenosis
Authors: Taguchi Akira , Sakamoto Shigeyuki , Okazaki Takahito , Oshita Jumpei , Kuwabara Masashi , Kurisu Kaoru
Published: January 2020

Background

Several recent randomized controlled trials have reported that perioperative complications of carotid artery stenting increase with age, and Japan has the highest proportion of elderly in the world. We retrospectively compared clinical factors, treatment outcomes, and adverse events between younger and elderly carotid artery stenting patients at a single institution in Japan to assess carotid artery stenting safety for the aged population.

Methods

A total of 150 consecutive patients treated with carotid artery stenting using the dual protection (simultaneous flow reversal and distal filter) and blood aspiration method were enrolled. Patients were classified into an elderly (O) group ≥75 years (54/150, 36.0%) and a younger (Y) group <75 years (96/150, 64%) for comparison of demographics, clinical background, incidence of captured debris during the procedure, outcome, minor stroke, major adverse events (major stroke, myocardial infarction, or death) within 30 days, hyperintense spots on diffusion-weighted images after carotid artery stenting, and postoperative hospitalization days.

Results

The carotid artery stenting procedure was successful in all cases. No major adverse events occurred within 30 days in the Y group, and only one occurred in the O group ( P = 0.348). Visible debris was captured in a significantly greater proportion of O group patients than in Y group patients (33/54 (63.5%) vs. 40/96 (42.1%), P = 0.016), but there was no significant difference in the frequency of hyperintense spots on diffusion-weighted images between Y and O groups (23/96 (24.0%) vs. 16/52 (30.8%), P = 0.435).

Conclusions

Carotid artery stenting using dual protection and blood aspiration is equally safe for younger and elderly patients.
The impact of body mass index and sociodemographic factors on moderate-to-vigorous physical activity and sedentary behaviors of women with young children: A cross-sectional examination
Authors: Dinkel Danae M , Hein Nicholas , Snyder Kailey , Siahpush Mohammad , Maloney Shannon , Smith Lynette , Farazi Paraskevi A , Hanson Corrine
Published: January 2020

Objectives:

Moderate-to-vigorous physical activity provides multiple benefits to women after childbirth. To achieve these benefits, the recommendation that adults obtain, 150 min of moderate-to-vigorous physical activity per week and reduce sedentary behaviors, also applies to women in the post-partum phase of the life span. However, research examining the moderate-to-vigorous physical activity and sedentary behaviors of women with young children (0–2 years) is limited. A greater understanding of these behaviors from a nationally representative sample is needed. Therefore, the primary objective of this study was to determine the levels of moderate-to-vigorous physical activity and sedentary behaviors of a nationally representative sample of women with young children within the United States. A secondary objective was to examine the influence of body mass index and sociodemographic factors on these behaviors.

Methods:

Cross-sectional data from four cycles of the National Health and Nutrition Examination Survey (2007–2008, 2009–2010, 2011–2012, and 2013–2014) were used for analysis. Descriptive statistics were calculated and a generalized linear model was used to investigate associations between mean minutes of moderate-to-vigorous physical activity, sedentary activity, body mass index, and sociodemographic variables.

Discussion:

Women with young children (n = 477) obtained 634 min in moderate-to-vigorous physical activity per week and this was positively associated with having a higher income (p < 0.001) and the number of children in the home (p < 0.001). In total, 62% of women were meeting the World Health Organization guidelines for aerobic activity. Lower odds of achieving guidelines was associated with being Black (p = 0.004), Mexican American (p = 0.009), or married (p = 0.042) compared with being White or not married. Finally, women accumulated ~5 h of sedentary activity per day, with higher levels associated with race (p = 0.005), education (p = 0.022), and number of children within the home (p < 0.001). Research efforts should continue to focus on strategies to help non-adhering women with young children achieve the physical activity recommendations and reduce time spent in sedentary behaviors.
Operation of the Basketball Jump Shooting Accuracy Test: Intra- and inter-rater reliability of scoring procedures and floor and ceiling effects for test performance
Authors: Boddington Brenton J , Cripps Ashley J , Scanlan Aaron T , Spiteri Tania
Published: January 2020

The purpose of this study was to determine the intra- and inter-rater reliability of scoring procedures used in the newly developed Basketball Jump Shooting Accuracy Test (BJSAT) and assess for floor and ceiling effects in test performance. Thirty-one semi-professional basketball athletes completed four trials of the BJSAT. The BJSAT contains one jump shot at eight different locations, equally distributed across two- and three-point shots. Intra-rater reliability was determined by assessing the level of agreement between scores live in-person and watching captured video by the same assessor. Inter-rater reliability was determined by examining the level of agreement between two assessors who separately scored the BJSAT while watching captured video. Descriptive statistics and Cohen’s kappa (κ) were calculated to quantify the intra- and inter-rater reliability of the BJSAT. Floor and ceiling effects in scoring outcomes were analyzed to evaluate the suitability of the BJSAT. Significance for the study was set at p <0.05. Intra-rater reliability demonstrated an almost perfect (κ = 0.85, p <0.01) agreement between scores (12.6 ± 2.5 vs. 13.1 ± 2.8). The agreement for inter-rater reliability was rated as substantial (12.3 ± 2.5 vs. 13.5 ± 2.9, κ = 0.70, p <0.01). Floor and ceiling effects were absent in the BJSAT indicating the assessment is suitable for semi-professional basketball athletes. The BJSAT is an assessment where one or multiple assessors can reliably score shooting performance for functions including player monitoring, to assess the efficacy of interventions aimed at improving skills and to assist with team selection across the season.
Accuracy of aortic dissection detection risk score alone or with D-dimer: A systematic review and meta-analysis
Authors: Tsutsumi Yusuke , Tsujimoto Yasushi , Takahashi Sei , Tsuchiya Asuka , Fukuma Shingo , Yamamoto Yosuke , Fukuhara Shunichi
Published: January 2020

Background:

To evaluate the diagnostic accuracy and clinical utility of the acute aortic dissection detection risk score (ADD-RS) alone or with D-dimer as a screening test to exclude acute aortic syndrome.

Methods:

We conducted a systematic review and meta-analysis of studies examining the diagnostic accuracy of ADD-RS. We searched MEDLINE, Embase and Cochrane Controlled Register of Trials up to 12 December 2018.

Results:

We identified nine studies involving 26,598 patients for ADD-RS alone and 3421 patients with D-dimer. Overall, the methodological quality based on the Quality Assessment of Diagnostic Accuracy Studies 2 was moderate to high. Bivariate meta-analyses showed that the pooled sensitivities were 0.94 (95% confidence interval (CI) 0.90, 0.96) at the threshold of ADD-RS ≥1, 0.46 (95% CI, 0.34, 0.59) at ADD-RS ≥2, 1.00 (95% CI 0.99, 1.00) at ADD-RS ≥1 with D-dimer and 0.99 (95% CI 0.97, 1.00) at ADD-RS ≥2 with D-dimer. For the low prevalence population, failure rate and efficiency were 0.8% and 38.3% at ADD-RS ≥1, 0.03% and 14.5% at ADD-RS ≥1 with D-dimer, and 0.1% and 33.6% at ADD-RS ≥2 with D-dimer, respectively. For the high prevalence population, failure rate and efficiency were 3.8% and 33.3% at ADD-RS ≥1, 0.2% and 12.3% at ADD-RS ≥1 with D-dimer and 0.6% and 28.4% at ADD-RS ≥2 with D-dimer, respectively.

Conclusions:

ADD-RS alone or with D-dimer was a useful screening test with high sensitivity to exclude acute aortic syndrome. However, the optimal threshold of ADD-RS alone or with D-dimer may depend on the clinical setting.
The Current Status, Trend, and Development Strategies of Chinese Biopharmaceutical Industry With a Challenging Perspective
Authors: Zhang Kerong , Liu Wuyi
Published: January 2020

Biopharmaceutical technology is one of the most promising biotechnologies in the world. With the development of modern biotechnology, biopharmaceuticals are thriving and developing rapidly as a global high-tech biotechnology industry, bringing the unprecedented market prospects to biopharmaceuticals in China and the world. Today, world is witnessing that Chinese biopharmaceutical industry is booming and growing up. The national biopharmaceutical industry of China, especially the development and industrialization of biological medicines with genetic engineering drugs as its core fields, has already reached a certain market scale after over 20 years of development. The biopharmaceutical industry will be one of the most active economic sectors in China, whereas the biotechnological revolution with modern biopharmaceutical technology has become the lifeblood of maintaining human health and food safety in the future. The article systematically analyzed and evaluated the current status and trend and explored the main existing problems of Chinese biopharmaceutical industry with some development strategies in a challenging perspective. It probes into Chinese biopharmaceutical industry and its bases too. The future development prospects of Chinese national biopharmaceutical industry are much optimistic but challenging.
Why Does the Importance of Education for Health Differ across the United States?
Authors: Kemp Blakelee R. , Montez Jennifer Karas
Published: January 2020

The positive association between educational attainment and adult health (“the gradient”) is stronger in some areas of the United States than in others. Explanations for the geographic pattern have not been rigorously investigated. Grounded in a contextual and life-course perspective, the aim of this study is to assess childhood circumstances (e.g., childhood health, compulsory schooling laws) and adult circumstances (e.g., wealth, lifestyles, economic policies) as potential explanations. Using data on U.S.-born adults aged 50 to 59 years at baseline ( n = 13,095) and followed for up to 16 years across the 1998 to 2014 waves of the Health and Retirement Study, the authors examined how and why educational gradients in morbidity, functioning, and mortality vary across nine U.S. regions. The findings indicate that the gradient is stronger in some areas than others partly because of geographic differences in childhood socioeconomic conditions and health, but mostly because of geographic differences in adult circumstances such as wealth, lifestyles, and economic and tobacco policies.
Subclonal NT5C2 mutations are associated with poor outcomes after relapse of pediatric acute lymphoblastic leukemia
Authors: Barz Malwine J. , Hof Jana , Groeneveld-Krentz Stefanie , Loh Jui Wan , Szymansky Annabell , Astrahantseff Kathy , von Stackelberg Arend , Khiabanian Hossein , Ferrando Adolfo A. , Eckert Cornelia , Kirschner-Schwabe Renate
Published: January 2020

Activating mutations in cytosolic 5′-nucleotidase II (NT5C2) are considered to drive relapse formation in acute lymphoblastic leukemia (ALL) by conferring purine analog resistance. To examine the clinical effects of NT5C2 mutations in relapsed ALL, we analyzed NT5C2 in 455 relapsed B-cell precursor ALL patients treated within the ALL-REZ BFM 2002 relapse trial using sequencing and sensitive allele-specific real-time polymerase chain reaction. We detected 110 NT5C2 mutations in 75 (16.5%) of 455 B-cell precursor ALL relapses. Two-thirds of relapses harbored subclonal mutations and only one-third harbored clonal mutations. Event-free survival after relapse was inferior in patients with relapses with clonal and subclonal NT5C2 mutations compared with those without (19% and 25% vs 53%, P < .001). However, subclonal, but not clonal, NT5C2 mutations were associated with reduced event-free survival in multivariable analysis (hazard ratio, 1.89; 95% confidence interval, 1.28-2.69; P = .001) and with an increased rate of nonresponse to relapse treatment (subclonal 32%, clonal 12%, wild type 9%, P < .001). Nevertheless, 27 (82%) of 33 subclonal NT5C2 mutations became undetectable at the time of nonresponse or second relapse, and in 10 (71%) of 14 patients subclonal NT5C2 mutations were undetectable already after relapse induction treatment. These results show that subclonal NT5C2 mutations define relapses associated with high risk of treatment failure in patients and at the same time emphasize that their role in outcome is complex and goes beyond mutant NT5C2 acting as a targetable driver during relapse progression. Sensitive, prospective identification of NT5C2 mutations is warranted to improve the understanding and treatment of this aggressive ALL relapse subtype.
Feed-forward regulatory loop driven by IRF4 and NF-κB in adult T-cell leukemia/lymphoma
Authors: Wong Regina Wan Ju , Tan Tze King , Amanda Stella , Ngoc Phuong Cao Thi , Leong Wei Zhong , Tan Shi Hao , Asamitsu Kaori , Hibi Yurina , Ueda Ryuzo , Okamoto Takashi , Ishida Takashi , Iida Shinsuke , Sanda Takaomi
Published: January 2020

Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive hematological malignancy derived from mature CD4+ T-lymphocytes. Here, we demonstrate the transcriptional regulatory network driven by 2 oncogenic transcription factors, IRF4 and NF-κB, in ATL cells. Gene expression profiling of primary ATL samples demonstrated that the IRF4 gene was more highly expressed in ATL cells than in normal T cells. Chromatin immunoprecipitation sequencing analysis revealed that IRF4-bound regions were more frequently found in super-enhancers than in typical enhancers. NF-κB was found to co-occupy IRF4-bound regulatory elements and formed a coherent feed-forward loop to coordinately regulate genes involved in T-cell functions and development. Importantly, IRF4 and NF-κB regulated several cancer genes associated with super-enhancers in ATL cells, including MYC, CCR4, and BIRC3. Genetic inhibition of BIRC3 induced growth inhibition in ATL cells, implicating its role as a critical effector molecule downstream of the IRF4-NF-κB transcriptional network.
The value of monitoring data in a process evaluation of hygiene behaviour change in Community Health Clubs to explain findings from a cluster-randomised controlled trial in Rwanda
Authors: Waterkeyn Juliet , Waterkeyn Anthony , Uwingabire Fausca , Pantoglou Julia , Ntakarutimana Amans , Mbirira Marcie , Katabarwa Joseph , Bigirimana Zachary , Cairncross Sandy , Carter Richard
Published: January 2020

Background

A cluster-Randomised Controlled Trial evaluation of the impact of the Community Health Clubs (CHCs) in the Community Based Environmental Health Promotion Programme in Rwanda in 2015 appeared to find little uptake of 7 hygiene indicators 1 year after the end of the intervention, and low impact on prevention of diarrhoea and stunting.

Methods

Monitoring data was revisited through detailed community records with all the expected inputs, outputs and external determinants analysed for fidelity to the research protocol. Five household inventory observations were taken over a 40-month period including 2 years after the end of the cRCT in a random selection of the 50 intervention CHCs and data compared to that of the trial. Focus Group Discussion with all Environmental Health Officers of the Ministry of Health provided context to understand the long-term community dynamics of hygiene behaviour change.

Results

It was found that the intervention had been jeopardised by external determinants with only 54% fidelity to protocol. By the end of the designated intervention period in June 2014, the treatment had reached only 58% of households with 41% average attendance at training sessions by the 4056 registered members and 51% mean completion rate of 20+ sessions. Therefore only 10% of 50 CHCs provided the full so-called ‘Classic’ training as per-protocol. However, sustainability of the CHCs was high, with all 50 being active 2 years after the end of the cRCT and over 80% uptake of recommended practices of the same 7 key indicators as the trial was achieved by 2017.

Conclusions

The cRCT conclusion that the case study of Rusizi District does not encourage the use of the CHC model for scaling up, raises concerns over the possible misrepresentation of the potential of the holistic CHC model to achieve health impact in a more realistic time frame. It also questions the appropriateness of apparently rigorous quantitative research, such as the cluster-Randomised Controlled Trial as conducted in Rusizi District, to adequately assess community dynamics in complex interventions.
Technical note on introducing a digital workflow for newborns with craniofacial anomalies based on intraoral scans - part I: 3D printed and milled palatal stimulation plate for trisomy 21
Authors: Xepapadeas Alexander B. , Weise Christina , Frank K. , Spintzyk S. , Poets C. F. , Wiechers C. , Arand J. , Koos B.
Published: January 2020

Background

Advanced digital workflows in orthodontics and dentistry often require a combination of different software solutions to create patient appliances, which may be a complex and time-consuming process. The main objective of this technical note is to discuss treatment of craniofacial anomalies using digital technologies. We present a fully digital, linear workflow for manufacturing palatal plates for infants with craniofacial anomalies based on intraoral scanning. Switching to intraoral scanning in infant care is advantageous as taking conventional impressions carries the risk of impression material aspiration and/or infections caused by material remaining in the oronasal cavity.

Material and methods

The fully digital linear workflow presented in this technical note can be used to design and manufacture palatal plates for cleft palate patients as well as infants with functional disorders. We describe the workflow implemented in an infant with trisomy 21. The maxilla was registered using a digital scanner and a stimulation plate was created using dental CAD software and an individual impression tray module on a virtual model. Plates were manufactured using both additive and subtractive methods. Methacrylate based light curing resin and Poly-Ether-Ether-Ketone were the materials used.

Results

The palatal area was successfully scanned to create a virtual model. The plates fitted well onto the palatal area. Manual post-processing was necessary to optimize a functional ridge along the vestibular fold and remove support structures from the additively manufactured plate as well as the milled plate produced from a blank. The additively manufactured plate fitted better than the milled one.

Conclusion

Implementing a fully digital linear workflow into clinical routine for treatment of neonates and infants with craniofacial disorders is feasible. The software solution presented here is suitable for this purpose and does not require additional software for the design. This is the key advantage of this workflow, which makes digital treatment accessible to all clinicians who want to deal with digital technology. Whether additive or subtractive manufacturing is preferred depends on the appliance material of choice and influences the fit of the appliance.
Correction to: Health-related quality of life and its socio-economic and cultural predictors among advanced cancer patients: evidence from the APPROACH cross-sectional survey in Hyderabad-India
Authors: Jacob Jean , Palat Gayatri , Verghese Naina , Kumari Priya , Rapelli Vineela , Kumari Sanjeeva , Malhotra Chetna , Teo Irene , Finkelstein Eric , Ozdemir Semra
Published: January 2020

Following publication of the original article [1], the corresponding author reported an error on the name of the fourth author.
Microbial contamination in herbal medicines: a serious health hazard to elderly consumers
Authors: de Sousa Lima Carolina Miranda , Fujishima Mayara Amoras Teles , de Paula Lima Bruno , Mastroianni Patrícia Carvalho , de Sousa Francisco Fábio Oliveira , da Silva Jocivânia Oliveira
Published: January 2020

Introduction

The use of herbal medicine is on the rise worldwide, and safety issues associated with herbal medicines may have an exacerbated impact in elderly because this population has an increased susceptibility and sensitivity to health complications due to the aging process.

Methods

This cross-sectional study was carried out at a primary health care unit in the city of Macapa, Brazil. The herbal medicines used and the sociodemographic characteristics of 123 voluntarily consenting participants were collected using a structured questionnaire. A total of 132 herbal medicines with oral or topical administration were donated by the elderly for microbial analysis before consumption, and 18 water samples used in the preparation of homemade herbal medicines were collected. Bacterial and fungal counts and identification of bacterial pathogens (Escherichia coli, Salmonella spp., Pseudomonas aeruginosa and Staphylococcus aureus) were performed according to the regulations of the Brazilian Pharmacopoeia and World Health Organization. Water analysis for the detection of coliforms and E. coli was carried out using Colilert® according to the manufacturer’s instructions and the techniques established by Standard Methods.

Results

Of the study participants, 78.8% were women. Bacterial growth was observed in samples from 51.5% of study and 35.6% had fungal growth. A total of 31.8% of the herbal medicine samples exceeded the safety limits (CFU/g ≤ 105), including 16.7% of the homemade herbal medicines and 15.1% of the commercial herbal medicines. It was also found that 31.0% of the samples exceeded the safety limit for fungal growth. The microorganisms most commonly isolated from the herbal medicines were S. aureus (49.2%), followed by Salmonella spp. (34.8%), E. coli (25.8%), and P. aeruginosa (14.4%). Of water samples analyzed, 77.8% were positive for total coliforms (1 ml) and in 66.7% water samples E. coli was detected (1 ml), making them unfit for consumption.

Conclusions

The use of homemade and commercial herbal medicines is a major risk to the health of elderly who use these therapies due to the lack of microbial quality standards. We observed levels of viable bacteria and fungi that were above safety limits; in addition, we were able to isolate pathogenic bacteria from these herbal medicines.
Gold nanoparticle based double-labeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors
Authors: Lara Pablo , Palma-Florez Sujey , Salas-Huenuleo Edison , Polakovicova Iva , Guerrero Simón , Lobos-Gonzalez Lorena , Campos America , Muñoz Luis , Jorquera-Cordero Carla , Varas-Godoy Manuel , Cancino Jorge , Arias Eloísa , Villegas Jaime , Cruz Luis J. , Albericio Fernando , Araya Eyleen , Corvalan Alejandro H. , Quest Andrew F. G. , Kogan Marcelo J.
Published: January 2020

Background

Extracellular vesicles (EVs) have shown great potential for targeted therapy, as they have a natural ability to pass through biological barriers and, depending on their origin, can preferentially accumulate at defined sites, including tumors. Analyzing the potential of EVs to target specific cells remains challenging, considering the unspecific binding of lipophilic tracers to other proteins, the limitations of fluorescence for deep tissue imaging and the effect of external labeling strategies on their natural tropism. In this work, we determined the cell-type specific tropism of B16F10-EVs towards cancer cell and metastatic tumors by using fluorescence analysis and quantitative gold labeling measurements. Surface functionalization of plasmonic gold nanoparticles was used to promote indirect labeling of EVs without affecting size distribution, polydispersity, surface charge, protein markers, cell uptake or in vivo biodistribution. Double-labeled EVs with gold and fluorescent dyes were injected into animals developing metastatic lung nodules and analyzed by fluorescence/computer tomography imaging, quantitative neutron activation analysis and gold-enhanced optical microscopy.

Results

We determined that B16F10 cells preferentially take up their own EVs, when compared with colon adenocarcinoma, macrophage and kidney cell-derived EVs. In addition, we were able to detect the preferential accumulation of B16F10 EVs in small metastatic tumors located in lungs when compared with the rest of the organs, as well as their precise distribution between tumor vessels, alveolus and tumor nodules by histological analysis. Finally, we observed that tumor EVs can be used as effective vectors to increase gold nanoparticle delivery towards metastatic nodules.

Conclusions

Our findings provide a valuable tool to study the distribution and interaction of EVs in mice and a novel strategy to improve the targeting of gold nanoparticles to cancer cells and metastatic nodules by using the natural properties of malignant EVs.
Time trends for pulmonary embolism incidence in Greece
Authors: Raptis Dimitrios G. , Gourgoulianis Konstantinos I. , Daniil Zoe , Malli Foteini
Published: January 2020

Background

Pulmonary embolism (PE) is a disease with a significant impact on public health. However, international epidemiological data are unclear and show considerable heterogeneity. The present study aims to investigate the incidence of PE at the Greek population and the associated demographic characteristics of patients with PE.

Methods

Data on hospital admissions for PE between 1999 and 2012 were provided by the Hellenic Statistical Authority of Greece. Data on age, gender and days of hospitalization from 1999 to 2007 were provided as well. The total population in each region was derived from the 1991, 2001, 2011 Census of the national statistical service of Greece.

Results

The mean annual incidence of PE during the study period was 18.5 per 100.000 population. The annual incidence of PE showed an upward trend ranging from 14 (1999) to 30 (2012) per 100.000 population. In the years before and after the economic crisis faced by Greece we observed statistically significant differences of PE incidence for the two different periods (1999–2008 versus 2009–2012, 14.49 versus 23.06 respectively, p = 0.002). The available data revealed a female predominance (16.48 cases for females per 100.000 population versus 13.69 cases for males per 100.000 population, p = 0.031). Incidence rate increased with age with a higher incidence in the “80–89” age group.

Conclusions

The incidence of PE appeared to increase in Greece, while it remains below the expected trend in an international context that may be attributed to Computed Tomography Pulmonary Angiography availability and/or PE awareness among clinicians.
Immunological effects of adjuvants in subsets of antigen presenting cells of cancer patients undergoing chemotherapy
Authors: Mauriello Angela , Manolio Carmen , Cavalluzzo Beatrice , Avallone Antonio , Borrelli Marco , Morabito Alessandro , Iovine Emanuele , Chambery Angela , Russo Rosita , Tornesello Maria Lina , Buonaguro Franco M. , Tagliamonte Maria , Buonaguro Luigi
Published: January 2020

Background

We have previously shown that HCC patients and healthy subjects are equally responsive to a RNAdjuvant®, a novel TLR-7/8/RIG-I agonist based on noncoding RNA developed by CureVac, by an ex vivo evaluation. However, the immunological effect of adjuvants on immune cells from cancer patients undergoing chemotherapy remains to be demonstrated. Different adjuvants currently used in cancer vaccine clinical trials were evaluated in the present study on immune cells from cancer patients before and after chemotherapy in an ex vivo setting.

Methods

PBMCs were obtained from 4 healthy volunteers and 23 patients affected by either colon (OMA) or lung cancer (OT). The effect of CpG, Poly I:C, Imiquimod and RNA-based adjuvant (RNAdjuvant®) was assessed using a multiparametric approach to analyze network dynamics of early immune responses. Evaluation of CD80, CD86 and HLA-DR expression as well as the downstream effect on CD4+ T cell phenotyping was performed by flow cytometry; cytokine and chemokine production was evaluated by Bio-Plex ProTM.

Results

Treatment with RNAdjuvant® induced the strongest response in cancer patients in terms of activation of innate and adoptive immunity. Indeed, CD80, CD86 and HLA-DR expression was found upregulated in circulating dendritic cells, which promoted a CD4+ T cell differentiation towards an effector phenotype. RNAdjuvant® was the only one to induce most of the cytokines/chemokines tested with a pronounced Th1 cytokine pattern. According to the different parameters evaluated in the study, no clear cut difference in immune response to adjuvants was observed between healthy subjects and cancer patients. Moreover, in the latter group, the chemotherapy treatment did not consistently correlate to a significant altered response in the different parameters.

Conclusions

The present study is the first analysis of immunological effects induced by adjuvants in cancer patients who undergo chemotherapy, who are enrolled in the currently ongoing cancer vaccine clinical trials. The results show that the RNAdjuvant® is a potent and Th1 driving adjuvant, compared to those tested in the present study. Most importantly, it is demonstrated that chemotherapy does not significantly impair the immune system, implying that cancer patients are likely to respond to a cancer vaccine even after a chemotherapy treatment.
Neuroprotective effect of microglia against impairments of auditory steady-state response induced by anti-P IgG from SLE patients in naïve mice
Authors: Wang Xuejiao , Li Yingzhuo , Li Zijie , Li Jinhong , Xu Jingyi , Yang Pingting , Qin Ling
Published: January 2020

Objective

Autoantibodies against ribosomal P proteins (anti-P antibodies) are strongly associated with the neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE). The present study was designed to assess whether anti-P antibodies can induce abnormal brain electrical activities in mice and investigate the potential cytopathological mechanism.

Methods

Affinity-purified human anti-ribosomal P antibodies were injected intravenously into mice after blood–brain barrier (BBB) disruption. The auditory steady-state response (ASSR) was evaluated based on electroencephalography (EEG) signals in response to 40-Hz click-train stimuli, which were recorded from electrodes implanted in the skull of mice. Immunofluorescence staining was used to examine the morphology and density of neurons and glia in the hippocampus and cortex. The presence of apoptosis in the brain tissues was studied using the TUNEL assay. A PLX3397 diet was used to selectively eliminate microglia from the brains of mice.

Results

Circulating anti-P antibodies caused an enhancement of the ASSR and the activation of microglia through the disrupted BBB, while no obvious neural apoptosis was observed. In contrast, when microglia were depleted, anti-P antibodies induced a serious reduction in the ASSR and neural apoptosis.

Conclusion

Our study indicates that anti-P antibodies can directly induce the dysfunction of auditory-evoked potentials in the brain and that microglia are involved in the protection of neural activity after the invasion of anti-P antibodies, which could have important implications for NPSLE.
A comprehensive reproductive health program for vulnerable adolescent girls
Authors: Pourkazemi Razieh , Janighorban Mojgan , Boroumandfar Zahra , Mostafavi Firoozeh
Published: January 2020

Background

Reproductive health of vulnerable adolescent girls is a top priority in global programs. Alcohol consumption, drug abuse, high risk sexual behaviors, sexually transmitted diseases, sexual assault, escape from home, unrestrained sex in the family, history of robbery, imprisonment and living in drug hangouts expose adolescents to different sorts of damage and injury. These adolescent girls are at risk of AIDS and other STDs, unwanted pregnancies, illegal and unsafe abortions, unplanned pregnancy and childbirth, and unsafe motherhood. Therefore, assessing these girls’ reproductive health needs and designing programs to improve their sexual and reproductive health seem to be essential. This study will be conducted to design a comprehensive program for improving the reproductive health of vulnerable adolescent girls.

Methods

The present study is an exploratory sequential mixed methods study (Qual-Quan) designed in three phases. In the first phase, a qualitative study will be used to describe the reproductive health needs of vulnerable adolescent girls, identify facilitating and inhibiting factors, and explain the strategies of reproductive health programs for these girls. Participants will be selected in this phase using purposive sampling method, and the data will be collected through semi-structured interviews. The obtained data will be analyzed using conventional qualitative content analysis. In the second phase, through a quantitative study, the strategies obtained from the qualitative study and review of the literature will be provided to reproductive health care providers, experts, policymakers, and planners to prioritize and select the best strategies. In the third phase, the initial draft of the program will be formulated based on prioritized strategies and will be proposed in a panel comprised of specialists in the areas of reproductive and sexual health, health promotion, social injuries and a psychiatrist. Finally, the final program will be developed and presented after obtaining the agreement and approval of the panel members.

Discussion

Designing a program based on a qualitative study, review of the existing evidence and programs, and using the opinions of experts in different areas can lead to different aspects of reproductive and sexual health of vulnerable adolescent girls. On the other hand, taking into account all cultural sensitivities and taboos as well as political, economic and social barriers, the development of such a program can provide the appropriate possibility of presenting comprehensive reproductive and sexual health services to vulnerable adolescent girls and achieve the goals agreed universally.
Joining forces: the need to combine science and ethics to address problems of validity and translation in neuropsychiatry research using animal models
Authors: Meijboom Franck L. B. , Kostrzewa Elzbieta , Leenaars Cathalijn H. C.
Published: January 2020

Background

Current policies regulating the use of animals for scientific purposes are based on balancing between potential gain of knowledge and suffering of animals used in experimentation. The balancing process is complicated, on the one hand by plurality of views on our duties towards animals, and on the other hand by more recent discussions on uncertainty in the probability of reaching the final aim of the research and problems of translational failure.

Methods

The study combines ethical analysis based on a literature review with neuropsychiatry-related preclinical research as a case study.

Results

Based on the analysis and the case study we show that neuropsychiatry-related preclinical research is an especially interesting case from an ethical perspective. The 3R principles (Replacement, Reduction and Refinement) are used to minimize the negative consequences for the animals used in research. However, neuropsychiatric research is characterized by specific challenges in assessing the probability of success of reaching the final aim, due to our limited mechanistic knowledge of human neuropsychiatric illness. Consequently, the translational value of the currently used animal models may be difficult to prove, which undermines the validity of these models and complicated the ethical assessment.

Conclusions

We conclude that a combined approach that deals with both science and the ethical dimensions is necessary to address the problems of validity and translation in neuropsychiatry-related preclinical research. We suggest this approach to comprise first, improved experimental methods, e.g. by using systematic reviews, second, a more patients-based approach that leads to models that reflect interindividual variation better, and third, more interdisciplinary cooperation.
“Becoming myself”: how participants in a longitudinal substance use disorder recovery study experienced receiving continuous feedback on their results
Authors: Svendsen Thomas Solgaard , Bjornestad Jone , Slyngstad Tale Ekeroth , McKay James R. , Skaalevik Aleksander Waagan , Veseth Marius , Moltu Christian , Nesvaag Sverre
Published: January 2020

Background

Being a participant in longitudinal follow-up studies is not commonly a factor considered when investigating useful self-change aspects for individuals attempting recovery from substance use disorder (SUD). This study reports on how ongoing monitoring, and feedback on data results in a longitudinal follow-up study of SUD recovery were perceived by individuals who had achieved long-term abstinence and social recovery.

Methods

Interviewers with first-hand experience with the topic conducted interviews with 30 participants and analysed the data using a thematic analytic approach within an interpretative–phenomenological framework.

Results

Analyses resulted in the following themes. 1) Ongoing short text messaging (SMS) monitoring: helped participants by offering recovery milestones and reminders of the past. 2) Feedback on data results helped participants track physical and cognitive recovery: “I am more like myself”. 3) Using feedback in treatment: understanding the importance of a functional brain to participants may help with long-term retention in treatment.

Conclusions

Self-changes that were challenging to detect on a day-to-day basis were available for reflection through longitudinal study participation, including ongoing monitoring and feedback on the results, allowing personal consolidation of change processes. Clinical services could benefit from continuing development and implementation of such technology for ongoing monitoring and feedback on assessments to motivate self-change in SUD recovery. The development of guidelines for providing the results of research assessments to individuals could help reduce attrition in research projects and support recovery and healthy choices for study participants.