bluuebunny/crossref_metadata_2025 huggingface dataset:
HLA-E expression in diffuse glioma: relationship with clinicopathological features and patient survival
Authors: Wu Zhifeng , Liang Jingshan , Wang Zheng , Li Aimin , Fan Xing , Jiang Tao
Published: February 2020

Background

Human leukocyte antigen-E (HLA-E) has been extensively investigated in various human cancers including glioma. However, the clinical significance of HLA-E expression in glioma patients has not been elucidated. The current study aimed to investigate the association of HLA-E expression with clinicopathological features and survival in patients with diffuse glioma.

Methods

A total of 261 glioma patients were enrolled, subsequently, mRNA microarray analysis was conducted to identify the relationship of HLA-E with clinicopathological features and patient survival.

Results

HLA-E was significantly overexpressed in high-grade gliomas compared to low-grade gliomas (LGGs). Moreover, HLA-E expression was significantly higher in diffuse astrocytomas than oligodendrogliomas (p = 0.032, t-test). Kaplan-Meier analysis showed that progression-free survival (PFS) and overall survival (OS) were significantly better in LGG patients with low HLA-E expression (p = 0.018 for PFS and p = 0.020 for OS, Log-rank test). Furthermore, HLA-E expression was identified to be an independent prognostic factor by Cox analysis (p = 0.020 for PFS and p = 0.024 for OS).

Conclusions

This is the first study which identified the clinical significance of HLA-E in diffuse glioma. HLA-E expression was correlated with more aggressive tumor grade and histological type and was identified as an independent prognostic biomarker in LGG patients.
Introducing an efficient model for the prediction of placenta accreta spectrum using the MCP regression approach based on sonography indexes: how efficient is sonography in diagnosing accreta?
Authors: Boroomand fard Mahboobeh , Kasraeian Maryam , Vafaei Homeira , Jahromi Mojgan Akbarzadeh , Arasteh Payam , Shahraki Hadi Raeisi , Arasteh Peyman
Published: February 2020

Background

For the first time, we aimed to introduce a model for prediction of placenta accreta spectrum (PAS), using existing sonography indices.

Methods

Women with a history of Cesarean sections were included. Participants were categorized “high risk” for PAS if the placenta was previa or low-lying.

Sonography indices including abnormal placental lacuna, loss of clear zone, bladder wall interruption, myometrial thinning, placental bulging, exophytic mass, utero-vesical hypervascularity, subplacental hypervascularity, existence of bridging vessels, and lacunar flow, were registered.

To investigate simultaneous effects of 15 variables on PAS, Minimax Concave Penalty (MCP) was used.

Results

Among 259 participants, 74 (28.5%) were high risk and 43 individuals had PASs.

All sonography indices were higher among patient with PAS (p < 0.001) in the high risk group.

Our model showed that utero-vesical hypervascularity, bladder interruption and new lacunae have significant contribution in PAS. Optimal cut off point was p = 0.51 in ROC analysis. Probability of PAS for women with lacunae was between 96 and 100% and probability of PAS for women without lacunae was between 0 to 7%, therefore accuracy of the proposed model was equal to 100%.

Conclusions

Using the introduced model based on three factors of abnormal lacuna structures (grades 2 and 3), bladder wall interruption and utero-vesical vascularity, 100% of all cases of PASs are diagnosable. If supported by future studies our model eliminates the need for other imaging assessments for diagnosis of invasive placentation among high risk women with previous history of Cesarean sections.
Descending necrotizing mediastinitis caused by Streptococcus constellatus in an immunocompetent patient: case report and review of the literature
Authors: Ye Rui-hai , Yang Jun-chao , Hong Hui-hua , Mao Yu-ping , Zhu Yuan-hong , Cao Yu , Wang Zhen
Published: February 2020

Descending necrotizing mediastinitis is a severe infection of the mediastinum. This syndrome manifests as fever and chest pain following cough and sputum production. A 49-year-old woman presented with fever and a 14-day history of pneumonia. CT showed mediastinal abscesses with a giant calcified mediastinal lymph node (21 × 18 mm) and pneumonia. Bronchoscopy by EBUS-TBNA under general anesthesia was performed. The pathogen found in the puncture culture was Streptococcus constellatus, and antibiotics (mezlocillin/sulbactam 3.375 IVGTT q8h) was administered. A proximal right main bronchial neoplasm, suspected lung cancer, was found and conformed to inflammatory granuloma. A total of 22 months post-discharge the patient was clinically stable. We also conducted a review of the literature for all Streptococcus constellatus descending necrotizing mediastinitis infections between 2011 and 2017.
Influence of the implant-abutment connection on the ratio between height and thickness of tissues at the buccal zenith: a randomized controlled trial on 188 implants placed in 104 patients
Authors: Farronato Davide , Pasini Pietro Mario , Manfredini Mattia , Scognamiglio Cristian , Orsina Andrea Alain , Farronato Marco
Published: February 2020

Background

To compare tissue response to two implant systems, featuring internal hexed connections with different designs.

Methods

Patients enrolled in this randomized controlled trial were assigned to two groups. In Group 1, patients were treated with implants with a 5° conical internal hexed connection (Anyridge®, MegaGen, South Korea). In Group 2, patients were treated with implants with an internal hexed connection (Core®, Kristal, Italy). After implant placement and a provisionalisation period of 12 months, impressions were taken, stone casts were poured and digitised with a desktop scanner (D700®, 3Shape, Copenhagen, Denmark). In a digital environment, for each fixture, two values were collected at the buccal zenith: the height of the peri-implant mucosa (mucosal height; MH), calculated from the vestibular shoulder of the implant analogue to the upper gingival margin of the supra-implant tissue; and the width of the peri-implant mucosa (mucosal thickness; MT), calculated from the vestibular shoulder of the analogue to the external mucosa point perpendicular to the implant major axis. The mean and standard deviation for MH and MT, as well as their ratios, were calculated for each group; the sectors in which the implants were placed were also considered. Finally, correlation between MH, MT, connection type and sector was assessed by Pearson’s correlation coefficient, with significance level set at 0.05, and a confidence interval (CI) set at 95%.

Results

Data deriving from 188 implants placed in 104 patients were evaluated. The mean MH values were 3.32 (± 0.12) and 2.70 (± 0.16) mm for Groups 1 and 2, respectively. The mean MT values were 4.37 (± 0.16) and 3.93 (± 0.18) mm for Groups 1 and 2, respectively. Group 1 showed higher MH and MT values and a better ratio (1.50 ± 0.88) than Group 2 (1.81 ± 1.20). The MH, MT and MH/MT ratio were significantly influenced both by sector (p = 0.015) and group (p = 0.047).

Conclusions

Within the limits of this study, the 5° connection implants supported a more extended tissue height and thickness at the buccal zenith, and a better ratio between them.

Trial registration

This study was retrospectively registered in Clinicaltrials.gov, with number NCT04160689, dated 13/11/2019.
Women’s economic empowerment, participation in decision-making and exposure to violence as risk indicators for early childhood caries
Authors:   Early Childhood Caries Advocacy Group, Folayan Morenike Oluwatoyin , El Tantawi Maha , Vukovic Ana , Schroth Robert , Gaffar Balgis , Al-Batayneh Ola B. , Amalia Rosa , Arheiam Arheiam , Obiyan Mary , Daryanavard Hamideh
Published: February 2020

Objectives

In view of the association between early childhood caries (ECC])and maternal social risk factors, this study tried to determine if there were associations between indicators of processes, outputs and outcomes of women’s empowerment, and the prevalence of ECC.

Methods

In this ecological study, indicators measuring the explanatory variables - economic empowerment, decision-making and violence against women - were selected from the Integrated Results and Resources Framework of the UN-Women Strategic Plan 2018–2021 and WHO database. Indicators measuring the outcome variables - the prevalence of ECC for children aged 0 to 2 years, and 3 to 5 years - were extracted from a published literature. The general linear models used to determine the association between the outcome and explanatory variables were adjusted for economic level of countries. Regression estimates (B), 95% confidence intervals and partial eta squared (η2) were calculated.

Results

Countries with more females living under 50% of median income had higher prevalence of ECC for 3 to 5-year olds (B = 1.82, 95% CI = 0.12, 3.52). Countries with higher percentage of women participating in their own health care decisions had higher prevalence of ECC for 0 to 2-year-olds (B = 0.85, 95% CI = 0.03, 1.67). Countries with higher percentage of women participating in decisions related to visiting family, relatives and friends had higher prevalence of ECC for 3 to 5-year-olds (B = 0.67, 95% CI = 0.03, 1.32). None of the indicators for violence against women was significantly associated with the prevalence of ECC.

Conclusion

Empowerment of women is a welcome social development that may have some negative impact on children’s oral health. Changes in policies and norms are needed to protect children’s oral health while empowering women.
Process evaluation of the response of nursing homes to the implementation of the dementia-specific case conference concept WELCOME-IdA: A qualitative study
Authors: Holle Daniela , Teupen Sonja , Graf Rabea , Müller-Widmer Rene , Reuther Sven , Halek Margareta , Roes Martina
Published: February 2020

Background

The implementation of clearly structured dementia-specific case conferences could be an important tool to enable nursing staff to properly analyse and manage challenging behaviour in nursing home residents with dementia. A process evaluation of the responses of nursing homes to the implementation of WELCOME-IdA (Wittener model of case conferences for people with dementia – the Innovative dementia-oriented Assessment tool) was carried out to gain insight into which key elements of the intervention were adopted by the nursing homes and which elements were adapted.

Methods

This study was part of a larger process evaluation using a qualitative design. Thirty-four semi-structured telephone interviews and 15 focus group interviews were conducted in four nursing homes. The interviews were analysed using deductive content analysis, although inductive categories have been developed.

Results

Nursing home staff adopted the roles of moderator, case reporter, keeper of the minutes and reflection partner in WELCOME-IdA, but the selection of the staff members who filled these roles differed across nursing homes. The recommended group size of 5–8 participants per case conference was sometimes adopted. The key element of having core nursing teams who participated continuously in all case conferences was not adopted at all. Instead, there was a high level of rotation among staff members. The pre-defined process structure of WELCOME-IdA was adapted in such a way that the assessment of the residents’ behaviour and the selection of the relevant domain for the behaviour analysis were conducted in advance of the case conference. The evaluation of the interventions was also organized differently.

Conclusion

The scope of the response implies that WELCOME-IdA requires further adaptation to the requirements of nursing processes in nursing homes. The results provide important information on the selection of role keepers and offer insights into a) how knowledge of the structured training was circulated and transformed into self-organized case conferences and b) how knowledge was circulated throughout the entire processing of one case. Thus, these results can be used to optimize intervention and implementation. Overall, the intervention should allow more possibilities for tailored adaptation than it currently does.
Improving post-partum family planning services provided by female community health volunteers in Nepal: a mixed methods study
Authors: Thapa Kusum , Dhital Rolina , Rajbhandari Sameena , Mishra Sangeeta , Subedi Shanti , Dotel Bhogendra Raj , Vaidya Sapana , Pande Saroja , Tunnacliffe Emily-Anne , Makins Anita , Arulkumaran Sabaratnam
Published: February 2020

Background

Family planning services in the post-partum period, termed post-partum family planning (PPFP) is critical to cover the unmet need for contraception, especially when institutional delivery rates have increased. However, the intention to choose PPFP methods such as post-partum intrauterine devices (PPIUD) remains low in countries such as Nepal. Community health workers such as Female Community Health Volunteers (FCHVs) could play an important role in improving the service coverage of PPFP in Nepal. However, their knowledge of PPFP and community-based services related to PPFP remain unclear. This study aims to assess the effect on community-based PPFP services by improving FCHV’s knowledge through orientation on PPFP.

Methods

We conducted this mixed-methods study in Morang District in Nepal. The intervention involved orientation of FCHVs on PPFP methods. We collected quantitative data from three sources; via a survey of FCHVs that assessed their knowledge before and after the intervention, from their monthly reporting forms on counseling coverage of women at different stages of pregnancy from the communities, and by interviewing mothers in their immediate post-partum period in two selected hospitals. We also conducted six focus group discussions with the FCHVs to understand their perception of PPFP and the intervention. We performed descriptive and multivariable analyses for quantitative results and thematic analysis for qualitative data.

Results

In total, 230 FCHVs participated in the intervention and their knowledge of PPFP improved significantly after it. The intervention was the only factor significantly associated with their improved knowledge (adjusted odds ratio = 24, P < 0.001) in the multivariable analysis. FCHVs were able to counsel 83.3% of 1872 mothers at different stages of pregnancy in the communities. In the two hospitals, the proportion of mothers in their immediate post-partum period whom reported they were counseled by FCHVs during their pregnancy increased. It improved from 7% before the intervention to 18.1% (P < 0.001) after the intervention. The qualitative findings suggested that the intervention improved their knowledge in providing PPFP counseling.

Conclusion

The orientation improved the FCHV’s knowledge of PPFP and their community-based counseling. Follow-up studies are needed to assess the longer term effect of the FCHV’s role in improving community-based PPFP services.
TeamMate: a longitudinal study of New Zealand working farm dogs. I. Methods, population characteristics and health on enrolment
Authors: Isaksen Katja E. , Linney Lori , Williamson Helen , Cave Nick J. , Beausoleil Ngaio J. , Norman Elizabeth J. , Cogger Naomi
Published: February 2020

Background

Working farm dogs are invaluable on New Zealand sheep and beef farms. To date no study describing farm dog population and health has included information about incidence of illness and injury, or risk factors affecting health and career duration. This paper describes the methodology and initial results from TeamMate, a longitudinal study that was designed to address this gap. We describe the study population, husbandry practices, and prevalence of clinical abnormalities on enrolment.

Methods

Data about the farms, owners, husbandry practices and dogs were collected on farm at approximately 6-month intervals. All dogs over 18 months old and in full work were enrolled. Dogs were given physical examinations by veterinarians. On examination all abnormalities were noted, regardless of clinical significance.

Results

Six hundred forty-one working farm dogs and 126 owners were enrolled from the South Island of New Zealand. Forty-nine percent of dogs were Heading dogs (314 of 641) and 48% Huntaways (308 of 641). Median age of dogs was 4 years (range 1.5–14) and median body condition score (BCS) was four on a 9-point scale (interquartile range (IQR) 3–5). Fifty-four percent of dogs were male (345 of 641), and 6% (41 of 641) were neutered.

Eighty-one percent of owners (102 of 126) fed dogs commercial biscuits and meat sourced on farm. Forty-four percent of dogs (279 of 641) had bedding in their kennel, 14% (55 of 393) had insulated kennels, 69% (442 of 641) had been vaccinated and 33% (213 of 641) were insured.

Clinical abnormalities were found in 74% of dogs (475 of 641). Common abnormalities involved the musculoskeletal system (43%, 273 of 641), skin (including scars and callouses; 42%, 272 of 641), and oral cavity (including worn and broken teeth; 35%, 227 of 641).

Conclusions

Our results expand on those from previous surveys and indicate that musculoskeletal illness and injury, and skin trauma are the most commonly seen clinical abnormalities in working farm dogs. These results will provide a baseline for investigation of incidence and risk factors for illness, injury, retirement and death in New Zealand working farm dogs.
Pathway mapping of leukocyte transcriptome in influenza patients reveals distinct pathogenic mechanisms associated with progression to severe infection
Authors:   on behalf of the Nepean Genomic Research Group, Zerbib Yoann , Jenkins Emily K. , Shojaei Maryam , Meyers Adrienne F. A. , Ho John , Ball T. Blake , Keynan Yoav , Pisipati Amarnath , Kumar Aseem , Kumar Anand , Nalos Marek , Tang Benjamin M. , Schughart Klaus , McLean Anthony
Published: February 2020

Background

Influenza infections produce a spectrum of disease severity, ranging from a mild respiratory illness to respiratory failure and death. The host-response pathways associated with the progression to severe influenza disease are not well understood.

Methods

To gain insight into the disease mechanisms associated with progression to severe infection, we analyzed the leukocyte transcriptome in severe and moderate influenza patients and healthy control subjects. Pathway analysis on differentially expressed genes was performed using a topology-based pathway analysis tool that takes into account the interaction between multiple cellular pathways. The pathway profiles between moderate and severe influenza were then compared to delineate the biological mechanisms underpinning the progression from moderate to severe influenza.

Results

107 patients (44 severe and 63 moderate influenza patients) and 52 healthy control subjects were included in the study. Severe influenza was associated with upregulation in several neutrophil-related pathways, including pathways involved in neutrophil differentiation, migration, degranulation and neutrophil extracellular trap (NET) formation. The degree of upregulation in neutrophil-related pathways were significantly higher in severely infected patients compared to moderately infected patients. Severe influenza was also associated with downregulation in immune response pathways, including pathways involved in antigen presentation such as CD4+ T-cell co-stimulation, CD8+ T cell and Natural Killer (NK) cells effector functions. Apoptosis pathways were also downregulated in severe influenza patients compare to moderate and healthy controls.

Conclusions

These findings showed that there are changes in gene expression profile that may highlight distinct pathogenic mechanisms associated with progression from moderate to severe influenza infection.
New 6,19-oxidoandrostan derivatives obtained by biotransformation in environmental filamentous fungi cultures
Authors: Kozłowska Ewa , Matera Agata , Sycz Jordan , Kancelista Anna , Kostrzewa-Susłow Edyta , Janeczko Tomasz
Published: February 2020

Background

Steroid compounds with a 6,19-oxirane bridge possess interesting biological activities including anticonvulsant and analgesic properties, bacteriostatic activity against Gram-positive bacteria and selective anti-glucocorticoid action, while lacking mineralocorticoid and progestagen activity.

Results

The study aimed to obtain new derivatives of 3β-acetyloxy-5α-chloro-6,19-oxidoandrostan-17-one by microbial transformation. Twelve filamentous fungal strains were used as catalysts, including entomopathogenic strains with specific activity in the transformation of steroid compounds. All selected strains were characterised by high biotransformation capacity for steroid compounds. However, high substrate conversions were obtained in the cultures of 8 strains: Beauveria bassiana KCh BBT, Beauveria caledonica KCh J3.4, Penicillium commune KCh W7, Penicillium chrysogenum KCh S4, Mucor hiemalis KCh W2, Fusarium acuminatum KCh S1, Trichoderma atroviride KCh TRW and Isaria farinosa KCh KW1.1. Based on gas chromatography (GC) and nuclear magnetic resonance (NMR) analyses, it was found that almost all strains hydrolysed the ester bond of the acetyl group. The strain M. hiemalis KCh W2 reduced the carbonyl group additionally. From the P. commune KCh W7 and P. chrysogenum KCh S4 strain cultures a product of D-ring Baeyer–Villiger oxidation was isolated, whereas from the culture of B. bassiana KCh BBT a product of hydroxylation at the 11α position and oxidation of the D ring was obtained. Three 11α-hydroxy derivatives were obtained in the culture of I. farinosa KCh KW1.1: 3β,11α-dihydroxy-5α-chloro-6,19-oxidoandrostan-17-one, 3β,11α,19-trihydroxy-5α-chloro-6,19-oxidoandrostan-17-one and 3β,11α-dihydroxy-5α-chloro-6,19-oxidoandrostan-17,19-dione. They are a result of consecutive reactions of hydrolysis of the acetyl group at C-3, 11α- hydroxylation, then hydroxylation at C-19 and its further oxidation to lactone.

Conclusions

As a result of the biotransformations, seven steroid derivatives, not previously described in the literature, were obtained: 3β-hydroxy-5α-chloro-6,19-oxidoandrostan-17-one, 3β,17α-dihydroxy-5α-chloro-6,19-oxidoandrostane, 3β-hydroxy-5α-chloro-17α-oxa-D-homo-6,19-oxidoandrostan-17-one, 3β,11α-dihydroxy-5α-chloro-17α-oxa-D-homo-6,19-oxidoandrostan-17-one and the three above–mentioned 11α-hydroxy derivatives. This study will allow a better understanding and characterisation of the catalytic abilities of individual microorganisms, which is crucial for more accurate planning of experiments and achieving more predictable results.
The impact of long-term PM2.5 exposure on specific causes of death: exposure-response curves and effect modification among 53 million U.S. Medicare beneficiaries
Authors: Wang Bingyu , Eum Ki-Do , Kazemiparkouhi Fatemeh , Li Cheng , Manjourides Justin , Pavlu Virgil , Suh Helen
Published: February 2020

Background

The shape of the exposure-response curve for long-term ambient fine particulate (PM2.5) exposure and cause-specific mortality is poorly understood, especially for rural populations and underrepresented minorities.

Methods

We used hybrid machine learning and Cox proportional hazard models to assess the association of long-term PM2.5 exposures on specific causes of death for 53 million U.S. Medicare beneficiaries (aged ≥65) from 2000 to 2008. Models included strata for age, sex, race, and ZIP code and controlled for neighborhood socio-economic status (SES) in our main analyses, with approximately 4 billion person-months of follow-up, and additionally for warm season average of 1-h daily maximum ozone exposures in a sensitivity analysis. The impact of non-traffic PM2.5 on mortality was examined using two stage models of PM2.5 and nitrogen dioxide (NO2).

Results

A 10 μg /m3 increase in 12-month average PM2.5 prior to death was associated with a 5% increase in all-cause mortality, as well as an 8.8, 5.6, and 2.5% increase in all cardiovascular disease (CVD)-, all respiratory-, and all cancer deaths, respectively, in age, gender, race, ZIP code, and SES-adjusted models. PM2.5 exposures, however, were not associated with lung cancer mortality. Results were not sensitive to control for ozone exposures. PM2.5-mortality associations for CVD- and respiratory-related causes were positive and significant for beneficiaries irrespective of their sex, race, age, SES and urbanicity, with no evidence of a lower threshold for response or of lower Risk Ratios (RRs) at low PM2.5 levels. Associations between PM2.5 and CVD and respiratory mortality were linear and were higher for younger, Black and urban beneficiaries, but were largely similar by SES. Risks associated with non-traffic PM2.5 were lower than that for all PM2.5 and were null for respiratory and lung cancer-related deaths.

Conclusions

PM2.5 was associated with mortality from CVD, respiratory, and all cancer, but not lung cancer. PM2.5-associated risks of CVD and respiratory mortality were similar across PM2.5 levels, with no evidence of a threshold. Blacks, urban, and younger beneficiaries were most vulnerable to the long-term impacts of PM2.5 on mortality.
Antimicrobial utilization and antimicrobial resistance in patients with haematological malignancies in Japan: a multi-centre cross-sectional study
Authors: Mimura Wataru , Fukuda Haruhisa , Akazawa Manabu
Published: February 2020

Background

Infection is a major complication for patients with haematological malignancies. It is important to better understand the use of antimicrobial agents and antibiotic resistance for appropriate treatment and prevention of drug resistance. However, very few multi-centre analyses have focused on the use of antimicrobial agents and antibiotic resistance have been carried out in Japan. This study aimed to describe the characteristics of the use of antimicrobial agents and antibiotic resistance in patients with haematological malignancies.

Methods

We conducted a cross-sectional study using administrative claims data and antimicrobial susceptibility data in Japan. We included patients diagnosed with haematological malignancies, who were hospitalized in a haematology ward between 1 April 2015 and 30 September 2017 in 37 hospitals. Descriptive statistics were used to summarize patient characteristics, antimicrobial utilization, bacterial infections, and antibiotic resistance.

Results

In total, 8064 patients were included. Non-Hodgkin lymphoma (50.0%) was the most common malignancy. The broad-spectrum antibiotics displayed a following antimicrobial use density (AUD): cefepime (156.7), carbapenems (104.8), and piperacillin/tazobactam (28.4). In particular, patients with lymphoid leukaemia, myeloid leukaemia, or myelodysplastic syndromes presented a higher AUD than those with Hodgkin lymphoma, non-Hodgkin lymphoma, or multiple myeloma. The most frequent bacterial species in our study cohort was Escherichia coli (9.4%), and this trend was also observed in blood specimens. Fluoroquinolone-resistant E. coli (3.6%) was the most frequently observed antibiotic-resistant strain, while other antibiotic-resistant strains were rare.

Conclusions

Broad-spectrum antibiotics were common in patients with haematological malignancies in Japan; however, antibiotic-resistant bacteria including carbapenem-resistant or multidrug-resistant bacteria were infrequent. Our results provide nationwide, cross-sectional insight into the use of antimicrobial agents, prevalence of bacteria, and antibiotic resistance, demonstrating differences in antimicrobial utilization among different haematological diseases.
Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules
Authors: Pinton Laura , Magri Sara , Masetto Elena , Vettore Marina , Schibuola Ilaria , Ingangi Vincenzo , Marigo Ilaria , Matha Kevin , Benoit Jean-Pierre , Della Puppa Alessandro , Bronte Vincenzo , Lollo Giovanna , Mandruzzato Susanna
Published: February 2020

Background

Myeloid derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are two of the major players involved in the inhibition of anti-tumor immune response in cancer patients, leading to poor prognosis. Selective targeting of myeloid cells has therefore become an attractive therapeutic strategy to relieve immunosuppression and, in this frame, we previously demonstrated that lipid nanocapsules (LNCs) loaded with lauroyl-modified gemcitabine efficiently target monocytic MDSCs in melanoma patients. In this study, we investigated the impact of the physico-chemical characteristics of LNCs, namely size and surface potential, towards immunosuppressive cell targeting. We exploited myeloid cells isolated from glioblastoma patients, which play a relevant role in the immunosuppression, to demonstrate that tailored nanosystems can target not only tumor cells but also tumor-promoting cells, thus constituting an efficient system that could be used to inhibit their function.

Results

The incorporation of different LNC formulations with a size of 100 nm, carrying overall positive, neutral or negative charge, was evaluated on leukocytes and tumor-infiltrating cells freshly isolated from glioblastoma patients. We observed that the maximum LNC uptake was obtained in monocytes with neutral 100 nm LNCs, while positively charged 100 nm LNCs were more effective on macrophages and tumor cells, maintaining at low level the incorporation by T cells. The mechanism of uptake was elucidated, demonstrating that LNCs are incorporated mainly by caveolae-mediated endocytosis.

Conclusions

We demonstrated that LNCs can be directed towards immunosuppressive cells by simply modulating their size and charge thus providing a novel approach to exploit nanosystems for anticancer treatment in the frame of immunotherapy.
Defining the content of a minimal dataset for acquired brain injury using a Delphi procedure
Authors: Domensino Anne-Fleur , Winkens Ieke , van Haastregt Jolanda C. M. , van Bennekom Coen A. M. , van Heugten Caroline M.
Published: February 2020

Background

The lack of consistency in outcome measurement within the field of acquired brain injury (ABI) leads to incomparability of collected data and, consequently, reduced generalisation of findings. We aim to develop a set of standardised measures which can be used to obtain the minimum amount of data necessary to characterise ABI-patients across all healthcare sectors and disciplines and in every stage of recovery; i.e., an ABI-specific minimal dataset (MDS-ABI). The current study was conducted to identify the core outcome domains for adults with ABI (what to measure?) and to select the most suitable measurements within these domains (how to measure it?).

Methods

An initial comprehensive set of outcome domains and measurement instruments relevant for measuring the consequences of ABI was identified by a literature study. The selection of relevant domains was based on the International Classification of Functioning, Disability and Health framework. Measurement instruments were included in the Delphi procedure when they met pre-set requirements. A three-round Delphi study was conducted among Dutch experts (n = 48) using iterative web-based surveys to prioritise the proposed domains and instruments for the MDS-ABI. Throughout all rounds, participants could recommend additional or alternative domains and measurement instruments, and were fed back the collated group responses of the previous round.

Results

Response rates ranged from 89 to 100%. After three rounds, the expert panel reached consensus (≥51%) on the inclusion of 12 outcome domains (demographics, injury characteristics, comorbidity, cognitive functioning, emotional functioning, energy, mobility, self-care, communication, participation, social support and quality of life), measured with six measurement instruments, two screening questions and a registry of demographic- and injury information. No consensus was reached on how to measure quality of life.

Conclusions

The current study achieved consensus on the content of a minimal dataset for patients with ABI. The current version of the MDS-ABI will be evaluated and optimised if necessary in the near future.
Measurement invariance across gender and age groups, validity and reliability of the Chinese version of the short-form supportive care needs survey questionnaire (SCNS-SF34)
Authors: Choi Edmond Pui Hang , Liao Qiuyan , Soong Inda , Chan Karen Kar Loen , Lee Conrad C. Y. , Ng Alice , Sze Wing Kin , Tsang Janice Wing Hang , Lee Victor Ho Fun , Lam Wendy Wing Tak
Published: February 2020

Background

Despite the wide use of the Short-Form Supportive Care Needs Survey Questionnaire (SCNS-SF34), the measurement invariance of the SCNS-SF34 across the main groups—gender and age—which might be of interest in the application of the instrument has never been confirmed. To provide an accurate assessment tool to evaluate the unmet needs of Chinese cancer patients, the present study aimed to assess the measurement invariance of the SCNS-SF34 across gender and age groups and to assess the validity and reliability of the Chinese version of the SCNS-SF34.

Methods

The SCNS-SF34 was administrated to 1106 Chinese cancer patients. Other instruments included the Memorial Symptom Assessment Scale-Short Form (MSAS-SF), the Short-Form-12 Health Survey version 2 (SF-12 v2) and the Hospital Anxiety and Depression Scale (HADS). Factor structure, internal construct validity, convergent validity, known-group validity and internal consistency were assessed.

Results

Our data fit the original five-factor model. Multi-group confirmatory factor analysis indicated measurement invariance across age and gender groups. The domains of the SCNS-SF34 had moderate correlations with the corresponding domains of the MSAS-SF, the SF-12 v2 and the HADS, which supported convergent validity. Of the 34 items, 33 had an item-total correlation that was corrected for an overlap of > 0.4 to support the internal construct validity. The SCNS-SF34 aptly differentiated patients by age and gender. The Cronbach’s alpha coefficient ranged from 0.64 to 0.87.

Conclusions

We confirm the measurement invariance of the Chinese version of the SCNS-SF34 across gender and age group. It is a valid and reliable tool for evaluating the needs of Chinese patients with cancer.
Staging laparoscopy and peritoneal cytology in patients with early stage gastric adenocarcinoma
Authors: Allen Casey J. , Blumenthaler Alisa N. , Das Prajnan , Minsky Bruce D. , Blum Mariela , Roy-Chowdhuri Sinchita , Ajani Jaffer A. , Ikoma Naruhiko , Mansfield Paul F. , Badgwell Brian D.
Published: February 2020

Background

Staging laparoscopy and peritoneal cytology can detect occult metastatic disease prior to treatment of gastric cancer. The yield of peritoneal staging in patients with early stage disease is lacking. We assess the yield of peritoneal staging in early stage gastric cancer and its impact on survival.

Methods

Data were obtained from a prospective database of patients who underwent staging laparoscopy and peritoneal cytology for gastric cancer at our institution between July 1995 and July 2018. Clinical stage was determined by endoscopic ultrasound, and early stage was defined as cT1-2 and cN0. Rates of positive cytology and carcinomatosis at time of laparoscopy were obtained. Univariate analyses were used to compare groups, and Kaplan-Meier survival analyses were used to assess survival outcomes.

Results

Eight hundred sixty-seven patients underwent staging laparoscopy and peritoneal cytology; 56 were defined as early stage. Age was 61 ± 12 years, 66.4% were male, and 62.3% were white. Of the patients with early stage disease, 17.9% had either gross carcinomatosis (10.7%) and/or positive peritoneal cytology (10.9%). All cases of peritoneal disease were in patients with cT2 disease. There were no differences in age, gender, or race based on peritoneal disease (all p > 0.05). The presence of carcinomatosis or positive cytology significantly affected overall survival (p < 0.001), regardless of clinical T or N stage.

Conclusions

Peritoneal staging identifies metastatic disease in a significant number of patients with early stage disease. Given its poor prognosis and alternate therapy options, independent staging laparoscopy and peritoneal cytology should be considered in patients with early stage gastric adenocarcinoma.
Suppression of p66Shc prevents hyperandrogenism-induced ovarian oxidative stress and fibrosis
Authors: Wang Daojuan , Wang Tingyu , Wang Rong , Zhang Xinlin , Wang Lei , Xiang Zou , Zhuang Lingjia , Shen Shanmei , Wang Hongwei , Gao Qian , Wang Yong
Published: February 2020

Background

Rats with hyperandrogen-induced polycystic ovary syndrome (PCOS) have been shown to develop ovarian oxidative stress (OS) and fibrosis. The Sirt1 agonist, resveratrol, can reduce OS through inhibiting p66Shc in other models of OS.

Methods

We created a rat PCOS model with increased OS levels following treatment with one of the two androgens, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT). The PCOS related features were determined by measurement of malondialdehyde (MDA) and superoxide dismutase (SOD) levels or by examining the reactive oxygen species (ROS) levels using the DCF-DA probe. The potential mechanisms by which p66Shc/Sirt1 mediates ovarian fibrosis were explored by western blotting, quantitative reverse transcription-PCR, immunofluorescence staining, and immunohistochemistry.

Results

Hyperandrogen dramatically augmented OS and activation of fibrotic factors in the ovary. Our data demonstrated that treatment with resveratrol enhanced Sirt1 and decreased ovarian OS as well as inhibited phosphorylation of p66Shc both in vivo and in vitro. The treatment suppressed fibrotic factor activation and improved ovarian morphology. Lentivirus- or siRNA-mediated p66Shc knockdown resulted in a dramatic enhancement of Sirt1 expression, down-regulation of ROS and suppression of fibrotic factors in granulosa cells. Moreover, p66Shc overexpression markedly increased the expression of fibrotic factors. Additionally, silencing Sirt1 induced a dramatic increase in p66Shc and enhanced activation of fibrotic factors.

Conclusions

p66Shc may be a direct target of Sirt1 for inducing ROS and thus promoting fibrosis. Further exploration of the mechanisms of p66Shc in both fibrosis and OS may provide novel therapeutic strategies that will facilitate the improvement in PCOS symptoms and reproductive functions.
Assessment of scalability and performance of the record linkage tool E-PIX® in managing multi-million patients in research projects at a large university hospital in Germany
Authors: Hampf Christopher , Geidel Lars , Zerbe Norman , Bialke Martin , Stahl Dana , Blumentritt Arne , Bahls Thomas , Hufnagl Peter , Hoffmann Wolfgang
Published: February 2020

Background

The identity management is a central component in medical research. Patients are recruited from various sites, which requires an error tolerant record linkage method, to ensure that patients are registered only once. In large research projects or institutions, the identity management has to deal with several thousands or millions of patients. In environments with large numbers of patients the register process could lead to high runtimes caused by record linkage. The Central Biomaterial Bank of the Charité (ZeBanC) searched for an identity management solution, which can handle millions of patients in large research projects with an acceptable performance. The goal of this paper was to simulate the registration of several million patients using the E-PIX service at Charité – Universitätsmedizin Berlin. The E-PIX service was evaluated in terms of needed runtimes, memory requirements, and processor utilization. A total of at least 20 million patients had to be registered. The runtimes to register patients into databases with various sizes should be examined, and the maximum number of patients, which the E-PIX service could handle, should be determined.

Methods

Tools were set up or developed to measure the needed runtimes, the memory used and the processor usage to register patients into various sizes of databases. To generate runtimes close to reality, modified patient data based on transposed real patient data were used for the simulation. The transposed patient data were sent to E-PIX to measure the runtimes of the registration process. This measurement was repeated for various database sizes.

Results

E-PIX is suitable to manage multi-million patients within a dataset. With the given hardware, it was possible to register a total of more than 30 million patients. It was possible to register more than 16 thousand patients per day into this database.

Conclusions

The E-PIX tool fulfills the requirements of the Charité to be used for large research projects. The use of E-PIX is intended for the research context in the Charité.
Cannabis use during pregnancy and its relationship with fetal developmental outcomes and psychiatric disorders. A systematic review
Authors: Roncero Carlos , Valriberas-Herrero Isabel , Mezzatesta-Gava Marcela , Villegas José L. , Aguilar Lourdes , Grau-López Lara
Published: February 2020

Introduction

This study analyze factors associated to cannabis use in pregnant women, its perceived availability, its risk perception and the relationship between prenatal exposure to cannabis and developmental and mental disorders.

Objectives

We present a review of the literature on cannabis use among pregnant women. The objective is to analyze factors associated to cannabis use during pregnancy and assess the potential effects of prenatal exposure to cannabis on the development of the fetus and the mental health of those exposed.

Methods

Systematic review of studies on the maternal use of cannabis and the relationship between early exposure and the development of psychiatric disorders in the PubMed database until July 2018 in English and Spanish with the following keywords: Marijuana, Cannabinoids, Mental disorders, Pregnancy, Prenatal Cannabis Exposure, Risk factors.

Results

The use of cannabis among pregnant women is frequent but it has not been extensively researched. Prenatal exposure to cannabis may be associated with affective symptoms and ADHD.

Conclusions

Mental healthcare professionals who treat women during their fertile life need to be able to explain the relationship between prenatal exposure to cannabis and the presence of developmental and mental disorders.
Epidemiologic and viral predictors of antiretroviral drug resistance among persons living with HIV in a large treatment program in Nigeria
Authors: Ekong Ernest , Ndembi Nicaise , Okonkwo Prosper , Dakum Patrick , Idoko John , Banigbe Bolanle , Okuma James , Agaba Patricia , Blattner William , Adebamowo Clement , Charurat Manhattan
Published: February 2020

Background

Expanded access to combination antiretroviral therapy (cART) throughout sub-Saharan Africa over the last decade has remarkably improved the prognosis of persons living with HIV (PLWH). However, some PLWH experience virologic rebound after a period of viral suppression, usually followed by selection of drug resistant virus. Determining factors associated with drug resistance can inform patient management and healthcare policies, particularly in resource-limited settings where drug resistance testing is not routine.

Methods

A case–control study was conducted using data captured from an electronic medical record in a large treatment program in Nigeria. Cases PLWH receiving cART who developed acquired drug resistance (ADR) and controls were those without ADR between 2004 and 2011. Each case was matched to up to 2 controls by sex, age, and education. Logistic regression was used estimate odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with ADR.

Results

We evaluated 159 cases with ADR and 299 controls without ADR. In a multivariate model, factors associated with ADR included older age (OR = 2.35 [age 30–40 years 95% CI 1.29, 4.27], age 41 + years OR = 2.31 [95% CI 1.11, 4.84], compared to age 17–30), higher education level (secondary OR 2.14 [95% CI 1.1.11–4.13]), compared to primary and tertiary), non-adherence to care (OR = 2.48 [95% CI 1.50–4.00]), longer treatment duration (OR = 1.80 [95% CI 1.37–2.35]), lower CD4 count((OR = 0.95 [95% CI 0.95–0.97]) and higher viral load (OR = 1.97 [95% CI 1.44–2.54]).

Conclusions

Understanding these predictors may guide programs in developing interventions to identify patients at risk of developing ADR and implementing prevention strategies.
Development and evaluation of a high-fidelity lactation simulation model for health professional breastfeeding education
Authors: Sadovnikova Anna , Chuisano Samantha A. , Ma Kaoer , Grabowski Aria , Stanley Kate P. , Mitchell Katrina B. , Eglash Anne , Plott Jeffrey S. , Zielinski Ruth E. , Anderson Olivia S.
Published: February 2020

Background

A key reason for premature cessation of breastfeeding is inadequate support from healthcare providers. Most physicians and nurses do not feel confident in their ability to support families with breastfeeding initiation or maintenance. Increasing health professional confidence in clinical lactation skills is key to improving maternal and child health outcomes. High-fidelity (realistic) simulators encourage learner engagement, resulting in increased clinical skills competency, confidence, and transfer to patient care. Lactation educators teach with low-fidelity cloth and single breast models. There are no high-fidelity breast simulators for health professional education in clinical lactation.

Development and evaluation of a high-fidelity lactation simulation model

In this commentary we describe the development of a high-fidelity Lactation Simulation Model (LSM) and how physician residents, nurse-midwifery students, and clinical lactation experts provided feedback on LSM prototypes.

Limitations

The user-testing described in this commentary does not represent comprehensive validation of the LSM due to small sample sizes and the significant conflict of interest.

Conclusion

For breastfeeding rates to improve, mothers need support from their nurses, midwives, pediatricians, obstetricians and gynecologists, and all healthcare staff who interact with pregnant and lactating women. Clinical education with high-fidelity breastfeeding simulators could be the ideal learning modality for trainees and hospital staff to build confidence in clinical lactation skills. The ability of a high-fidelity breastfeeding simulator to increase a learner’s lactation knowledge and psychomotor skills acquisition, retention, and transfer to patient care still needs to be tested.