bluuebunny/crossref_metadata_2025 huggingface dataset:
“There is a Place”: impacts of managed alcohol programs for people experiencing severe alcohol dependence and homelessness
Authors: Pauly B. , Brown M. , Evans J. , Gray E. , Schiff R. , Ivsins A. , Krysowaty B. , Vallance K. , Stockwell T.
Published: December 2019

Background

The twin problems of severe alcohol dependence and homelessness are associated with precarious living and multiple acute, social and chronic harms. While much attention has been focused on harm reduction services for illicit drug use, there has been less attention to harm reduction for this group. Managed alcohol programs (MAPs) are harm reduction interventions that aim to reduce the harms of severe alcohol use, poverty and homelessness. MAPs typically provide accommodation, health and social supports alongside regularly administered sources of beverage alcohol to stabilize drinking patterns and replace use of non-beverage alcohol (NBA).

Methods

We examined impacts of MAPs in reducing harms and risks associated with substance use and homelessness. Using case study methodology, data were collected from five MAPs in five Canadian cities with each program constituting a case. In total, 53 program participants, 4 past participants and 50 program staff were interviewed. We used situational analysis to produce a series of “messy”, “ordered” and “social arenas” maps that provide insight into the social worlds of participants and the impact of MAPs.

Results

Prior to entering a MAP, participants were often in a revolving world of cycling through multiple arenas (health, justice, housing and shelters) where abstinence from alcohol is often required in order to receive assistance. Residents described living in a street-based survival world characterized by criminalization, unmet health needs, stigma and unsafe spaces for drinking and a world punctuated by multiple losses and disconnections. MAPs disrupt these patterns by providing a harm reduction world in which obtaining accommodation and supports are not contingent on sobriety. MAPs represent a new arena that focuses on reducing harms through provision of safer spaces and supply of alcohol, with opportunities for reconnection with family and friends and for Indigenous participants, Indigenous traditions and cultures. Thus, MAPs are safer spaces but also potentially spaces for healing.

Conclusions

In a landscape of limited alcohol harm reduction options, MAPs create a new arena for people experiencing severe alcohol dependence and homelessness. While MAPs reduce precarity for participants, programs themselves remain precarious due to ongoing challenges related to lack of understanding of alcohol harm reduction and insecure program funding.
HTLV-1 contains a high CG dinucleotide content and is susceptible to the host antiviral protein ZAP
Authors: Miyazato Paola , Matsuo Misaki , Tan Benjy J. Y. , Tokunaga Michiyo , Katsuya Hiroo , Islam Saiful , Ito Jumpei , Murakawa Yasuhiro , Satou Yorifumi
Published: December 2019

Background

Human T cell leukaemia virus type 1 (HTLV-1) is a retrovirus associated with human diseases such as adult T-cell leukaemia/lymphoma and HTLV-1 associated myelopathy/tropical spastic paraparesis. In contrast to another human retrovirus, human immunodeficiency virus type 1 (HIV-1), HTLV-1 persists in the host not via vigorous virus production but mainly via proliferation and/or long-term survival in the form of silent proviruses in infected host cells. As a result, HTLV-1-infected cells rarely produce virus particles in vivo even without anti-retroviral treatment. That should be an advantage for the virus to escape from the host immune surveillance by minimizing the expression of viral antigens in host cells. However, why HIV-1 and HTLV-1 behave so differently during natural infection is not fully understood.

Results

We performed cap analysis of gene expression (CAGE) using total RNAs and nascent, chromatin-associated, RNAs in the nucleus and found that HTLV-1 RNAs were processed post-transcriptionally in infected cells. RNA processing was evident for the sense viral transcripts but not the anti-sense ones. We also found a higher proportion of CG di-nucleotides in proviral sequences of HTLV-1-infected cells, when compared to the HIV-1 genomic sequence. It has been reported recently that CG dinucleotide content of viral sequence is associated with susceptibility to the antiviral ZC3HAV1 (ZAP), suggesting the involvement of this protein in the regulation of HTLV-1 transcripts. To analyse the effect of ZAP on HTLV-1 transcripts, we over-expressed it in HTLV-1-infected cells. We found there was a dose-dependent reduction in virus production with ZAP expression. We further knocked down endogenous ZAP with two independent targeting siRNAs and observed a significant increase in virus production in the culture supernatant. Other delta-type retroviruses such as simian T-cell leukaemia virus and bovine leukaemia virus, also contain high CG-dinucleotide contents in their viral genomes, suggesting that ZAP-mediated suppression of viral transcripts might be a common feature of delta-type retroviruses, which cause minimal viremia in their natural hosts.

Conclusions

The post-transcriptional regulatory mechanism involving ZAP might allow HTLV-1 to maintain a delicate balance required for prolonged survival in infected individuals.
Evaluation of novel inactivated vaccines for the SAT 1, SAT 2 and SAT 3 serotypes of foot-and-mouth disease in pigs
Authors: Jo Hye-Eun , You Su-Hwa , Choi Joo-Hyung , Ko Mi-Kyeong , Shin Sung Ho , Song Jisoo , Jo Hyundong , Lee Min Ja , Kim Su-Mi , Kim Byounghan , Park Jong-Hyeon
Published: December 2019

Background

The foot-and-mouth disease (FMD) virus is classified into seven serotypes, of which the South African types have South African Territories (SAT)1, SAT2, and SAT3 that are prevalent in Africa. Especially SAT2 have spread to Arabian Peninsula and the Palestinian Autonomous Territories. Of these viruses, the incidence of SAT2 is the highest. It is important to prepare for the spread of the virus to other continents, even though most FMD viruses are bovine-derived. In particular, due to the high breeding density of pigs in Asia, more attention is usually paid to the immunity and protection of pigs than cattle. For this reason, this study investigated the immunity and protection of pigs against the SAT viruses.

Methods

Specific vaccines were developed for SAT1, SAT2, and SAT3 serotypes. These vaccine viruses were designed to be distinguished from the wild-type strain. An immunogenicity test was conducted using these vaccines in both cattle (n = 5/group) and pigs (n = 20/group).

Results

High virus-neutralizing titer of antibodies (> 1:100) was induced in only 2 weeks after the immunization of cattle with the individual vaccine for SAT1, SAT2 or SAT3, and a clear immune response was induced after the second immunization in pigs. When the vaccinated pigs (n = 4–5/group) were challenged by the homologous wild-type virus strain 4 weeks after immunization, all the pigs were protected from the challenge.

Conclusions

This study confirmed that these vaccines can be used against SAT1, SAT2, and SAT3 viruses in cattle and pigs. The vaccine strains developed in this study are expected to be used as vaccines that can protect against FMD in the event of a future FMD outbreak in pigs in consideration of the situation in Asia.
Fucoidan prevent murine autoimmune diabetes via suppression TLR4-signaling pathways, regulation DC/Treg induced immune tolerance and improving gut microecology
Authors: Xue Meilan , Liang Hui , Ji Xinqiang , Liu Ying , Ge Yinlin , Hou Lin , Sun Ting
Published: December 2019

Background

This study was to investigate the effect and its possible mechanism of fucoidan on the development of spontaneous autoimmune diabetes in non-obese diabetic (NOD) mice.

Methods

7-week-old NOD mice were randomly divided into three groups: control group, low-dose (300 mg/kg) and high-dose (600 mg/kg) fucoidan-treatment groups. After 5 weeks of treatment, 10 mice per group were randomly selected to be sacrificed after feces collection. The remaining 12 mice per group were fed until 26 weeks of age to assess the incidence of diabetes.

Results

Treatment with fucoidan increased serum insulin level, delayed the onset and decreased the development of diabetes in NOD mice. Fucoidan reduced the levels of strong Th1 proinflammatory cytokines, but induced Th2-bias ed. cytokine response. And dentridic cells (DCs) in fucoidan treatment group were characterized as low expression of MHC class II and CD86 molecules. TLR4 expressions and the downstream molecules in pancreas were down-regulated in fucoidan-treated groups. There were significant differences in the composition of gut flora between NOD control group and fucoidan group. Lactobacillus and Akkermansia were significantly enriched in fucoidan group.

Conclusions

Fucoidan could prevent the development of autoimmune diabetes in NOD mice via regulating DC/Treg induced immune tolerance, improving gut microecology, down-regulating TLR4 signaling pathway, and maintaining pancreatic internal environment.
Splenic cord capillary hemangioma with non-islet cell tumor hypoglycemia: a case report
Authors: Daimon Tatsuaki , Kosaka Takeo , Horinaga Minoru , Saito Junichi , Ueyama Yoshito , Matsuzaki Shoji , Oya Mototsugu
Published: December 2019

Background

Splenic cord capillary hemangioma is a rare benign vascular lesion classified as a splenic hamartoma. On the other hand, non-islet cell tumor hypoglycemia (NICTH) is one of the rare causes of spontaneous hypoglycemia and is considered to be one of the paraneoplastic syndromes. To the best of our knowledge, this is the first reported case of a splenic cord capillary hemangioma with NICTH.

Case presentation

A 25-year-old male was referred to our hospital with hypoglycemia. Except for his low blood sugar, there were no abnormal findings from laboratory tests, which included an endocrinological examination. Enhanced computed tomography confirmed the presence of a solid mass measuring about 6 cm in the retroperitoneum, and a tumorectomy was performed. During this operation, it became clear that the tumor turned out to be a splenic parenchyma, and as a result, a total splenectomy was performed. Microscopically, we diagnosed this as a cord capillary hemangioma, and through immunohistochemistry, we found that some tumor cells were positive for insulin-like growth factor -II. Fortunately, the hypoglycemia-related symptoms disappeared after surgical resection was performed. The patient is still alive and well without evidence of local tumor recurrence 15 years after the operation.

Conclusions

Splenic cord capillary hemangioma, one of the types of splenic hamartomas, is a very rare benign vascular lesion and might be associated with hypoglycemia thought to be NICTH.
Local perceptions and factors determining ecosystem services identification around two forest reserves in Northern Benin
Authors: Gouwakinnou Gerard N. , Biaou Séverin , Vodouhe Fifanou G. , Tovihessi Marc S. , Awessou Beranger K. , Biaou Honoré S. S.
Published: December 2019

Background

Ecosystems provide humanity with goods and services known as ecosystem services. The value of these services represents a basis for political decision-making. To be sure that these decisions are made on a valid basis, policymakers require an understanding of the biophysical processes involved. This study was carried out around two forest reserves (Alibori-Supérieur and Ouénou-Bénou) in Northern Benin. It aimed to highlight the knowledge of the surrounding communities and their perceptions about the importance of the ecosystem services provided by these forest reserves as well as the factors that influence their knowledge and perceptions.

Methods

Primary data were collected from 25 group discussions in 25 villages surrounding the forest reserves based on predefined ecosystems services of the Millennium Ecosystems Assessment (MA). Multiple linear regression models were used to examine how socio-economic characteristics of the communities influenced the ecosystem services identification rate. Perceptions of importance, levels of satisfaction, and trends of services provided were analyzed using descriptive statistics.

Results

Our results showed that education level, poverty index, household size, and proximity to forests played an important role in the variation in knowledge of ecosystem services (P < 0.05). Provisioning services (such as crops supply, fuelwood, lumber, wild food, and medicinal plants) were mostly identified by the poorest villages located very close to the forests (P < 0.05). The importance of the provided services for well-being has been unanimously recognized. The most recognized cultural services were education and knowledge facilitation (84%) and spiritual value (76%). Climate regulation (84%) and pollination (84%) were the best-known regulating services. However, supporting services (soil formation and pest regulation) that are important for improving production systems were unknown to the communities.

Conclusion

Education level, poverty index, and village proximity to the forest were important predictors of regulating and supporting services identification. But use of non-tangible services by local rural communities will require more emphasis on targeted environmental education specifically designed according to the needs of each group.
Traditional knowledge of invertebrates used for medicine and magical–religious purposes by traditional healers and indigenous populations in the Plateau Department, Republic of Benin
Authors: Loko Laura Estelle Yêyinou , Medegan Fagla Sédami , Orobiyi Azize , Glinma Bienvenu , Toffa Joelle , Koukoui Omédine , Djogbenou Luc , Gbaguidi Fernand
Published: December 2019

Background

Since ancient times, invertebrates have played an important role in the traditional medicine in many parts of the world. In south-eastern Benin, more specifically in the Plateau Department, invertebrates are widely used in folk medicine. However, studies on their therapeutic use has been neglected and their magical–religious purposes are poorly understood. The present study aims to document traditional knowledge related to the use of invertebrates for medicinal and magical–religious purposes by traditional healers and indigenous people of Plateau Department.

Methods

An ethno-sociological survey was conducted with 145 informants (80 traditional healers, 12 merchants of medicinal animals and 53 households) belonging to six ethnic groups, in 20 villages located in Plateau of Benin. Data were collected through the participatory rural appraisal method involving individual interviews and direct observations with semi-structured questionnaires. The collected data regarding various medicinal and magical–religious uses of invertebrates were analysed through informant consensus factor (ICF), use value (UV) and, fidelity level (FL).

Results

A total of 20 families and 38 species of invertebrates, distributed among 6 taxonomic categories, were found to be used to treat 50 different ailments. Insects occupied 64.7% of the total invertebrates listed. The African earthworm Eudrilus eugeniae K. and African giant snail Achatina achatina L. had the highest use values. The highest ICF value (1.0) was cited for diseases of the blood or blood-forming organs. A principal component analysis (PCA) revealed the influence of ethnic groups in the diseases treated with invertebrates. The highest FL (100%) was recorded for 12 invertebrate species treating various ailments. Most of invertebrate-based remedies were associated with plant species. The mode of administration was mainly oral and topical. Most of the invertebrate drugs were traditionally collected in nature or imported, mainly from Nigeria. In addition, 7 magical–religious practices are documented.

Conclusions

Our results reveal that several invertebrate species play an important role in healing practices and magical–religious rituals in the Plateau Department. We suggest further studies to confirm the presence of any bioactive compounds on invertebrate species use in traditional medicine. In addition, this study highlights the need for ecological investigations of these species, in order to develop strategies for their conservation and sustainable use.
Plant-derived utility products: knowledge comparison across gender, age and education from a tribal landscape of western Himalaya
Authors: Sharma Alpy , Thakur Deepika , Uniyal Sanjay Kr.
Published: December 2019

Background

Plant-derived utility products (PDPs) play an important role in sustaining humans, especially tribal communities. Despite this, knowledge on PDPs is declining.

Methods

The present study was therefore carried to document the PDPs used by Bhangalis, a tribal community of western Himalaya, through door-to-door surveys (n=420) and detailed questionnaire recordings (n=240). In addition to taxonomic richness, frequency of species used; use value (UV), use diversity (UD), and cultural importance index (CI) were also analysed. Knowledge comparison between genders, four identified age groups (group 1: 16-32 years, group 2: 33–49 years, group 3: 50–66 years, group 4: >66 years), and level of education of the respondents was also carried out using multiple regression in SPSS.

Results

Bhangalis reported 55 PDPs under five use categories namely tools (34), artefacts (7), construction and storage (6 each), and miscellaneous (2). For making these PDPs, 20 plant species representing 12 families were used. Picea smithiana (16.54%), Cedrus deodara (14.96%), Cotoneaster bacillaris (12.60%) and Quercus semecarpifolia (11.02%) reported the highest use frequency. On an average 15.13±0.25 PDPs per respondent was noted. Similarly, Picea smithiana (UV=0.088) and Cedrus deodara (UV= 0.079) reported the highest UV when compared to other species. Amongst all the species, maximum UD was revealed for Juglans regia in the tool category (0.91). On the other hand, maximum CI was also recorded for Picea smithiana (CITotal=2.91). With respect to gender, males were found to be more knowledgeable than females (B=6.370, p=0.001). Amongst the four age groups, respondents in group 1 (B=-13.302, p=0.001) and group 2 (B=-5.867, p=0.001) were less knowledgeable in comparison to respondents in the third and fourth age groups. Similarly, education also had a significant negative coefficient (B=-0.275, p=0.037), with educated respondents having lesser knowledge. It was observed that alternates available in the market seem to be limiting the use of PDPs.

Conclusions

Bhangalis still use PDPs that have a crucial role in their lifestyle. However, their use is declining. A multipronged strategy that not only focusses on socio-economic characteristics but also on awareness especially at school levels is desired.
Perspectives of cellular communication through tunneling nanotubes in cancer cells and the connection to radiation effects
Authors: Matejka Nicole , Reindl Judith
Published: December 2019

Direct cell-to-cell communication is crucial for the survival of cells in stressful situations such as during or after radiation exposure. This communication can lead to non-targeted effects, where non-treated or non-infected cells show effects induced by signal transduction from non-healthy cells or vice versa. In the last 15 years, tunneling nanotubes (TNTs) were identified as membrane connections between cells which facilitate the transfer of several cargoes and signals. TNTs were identified in various cell types and serve as promoter of treatment resistance e.g. in chemotherapy treatment of cancer. Here, we discuss our current understanding of how to differentiate tunneling nanotubes from other direct cellular connections and their role in the stress reaction of cellular networks. We also provide a perspective on how the capability of cells to form such networks is related to the ability to surpass stress and how this can be used to study radioresistance of cancer cells.
Prognostic impact of pathological complete remission after preoperative irradiation in patients with locally advanced head and neck squamous cell carcinoma: re-analysis of a phase 3 clinical study
Authors: Wang Kai , Yi Junlin , Huang Xiaodong , Qu Yuan , Luo Jingwei , Xiao Jianping , Zhang Shiping , Tang Yuan , Liu Weixin , Xu Guozhen , Gao Li , Xu Zhengang , Liu Shaoyan , Wang Xiaolei
Published: December 2019

Purpose

The purpose of this study was to determine the associations between pathological complete remission (pCR) and clinical outcomes in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who received preoperative radiotherapy or chemoradiotherapy in a phase 3 clinical study.

Methods

A total of 222 newly diagnostic stage III/IVM0 HNSCC patients were randomly assigned to a preoperative concurrent chemoradiotherapy group (n = 104) or preoperative radiotherapy alone group (n = 118). Over a mean follow-up of 59 months, 72 patients were defined as non-responders to preoperative therapy and subsequently underwent resection of the primary lesion with or without neck dissection. The relationship between the pathological tumor response of the primary lesion and treatment prognosis was analyzed. Kaplan–Meier and Cox regression multivariate analyses were performed to evaluate the impact of pCR on local control (LC), overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS).

Results

Among the 72 non-responders, 25 patients, 10 in the chemotherapy group and 15 in the radiotherapy group, achieved pCR. The 5-year LC, OS, PFS, and DMFS of pCR patients and non-pCR patients were 93.2% vs. 67.7% (p = 0.007), 83.3% vs. 39.7% (p = 0.0006), 76.1% vs. 44.0% (p = 0.009), and 90.4% vs. 56.3% (p = 0.005), respectively. In multivariate analysis, pCR is also an independent prognostic factor in prognosis, with statistically significant differences.

Conclusion

pCR after preoperative radiotherapy or concurrent chemoradiotherapy is a good prognostic factor in locally advanced HNSCC.

Trial registration

Number:ChiCTR-TRC-114004322

Date:05 Mar, 2014
Adjacency-constrained hierarchical clustering of a band similarity matrix with application to genomics
Authors: Ambroise Christophe , Dehman Alia , Neuvial Pierre , Rigaill Guillem , Vialaneix Nathalie
Published: December 2019

Background

Genomic data analyses such as Genome-Wide Association Studies (GWAS) or Hi-C studies are often faced with the problem of partitioning chromosomes into successive regions based on a similarity matrix of high-resolution, locus-level measurements. An intuitive way of doing this is to perform a modified Hierarchical Agglomerative Clustering (HAC), where only adjacent clusters (according to the ordering of positions within a chromosome) are allowed to be merged. But a major practical drawback of this method is its quadratic time and space complexity in the number of loci, which is typically of the order of $$10^4$$104 to $$10^5$$105 for each chromosome.

Results

By assuming that the similarity between physically distant objects is negligible, we are able to propose an implementation of adjacency-constrained HAC with quasi-linear complexity. This is achieved by pre-calculating specific sums of similarities, and storing candidate fusions in a min-heap. Our illustrations on GWAS and Hi-C datasets demonstrate the relevance of this assumption, and show that this method highlights biologically meaningful signals. Thanks to its small time and memory footprint, the method can be run on a standard laptop in minutes or even seconds.

Availability and implementation

Software and sample data are available as an package, adjclust, that can be downloaded from the Comprehensive R Archive Network (CRAN).
Is I-FABP not only a marker for the detection abdominal injury but also of hemorrhagic shock in severely injured trauma patients?
Authors: Voth Maika , Lustenberger Thomas , Relja Borna , Marzi Ingo
Published: December 2019

Background

Hemorrhagic shock can lead to intestinal damage with subsequent hyperinflammation and multiple organ dysfunction syndrome (MODS). The intestinal fatty acid-binding protein (I-FABP) is solely expressed in the intestine and is released extracellulary after tissue damage. This study evaluates the validity of I-FABP as an early biomarker to detect hemorrhagic shock and abdominal injury.

Patients and methods

Severely injured patients with an Injury Severity Score (ISS) ≥ 16 points and an age ≥ 18 years, admitted from January 2010 to December 2016, were included. Overall, 26 patients retrospectively presented with hemorrhagic shock to the emergency room (ER): 8 patients without abdominal injury (“HS noAbd”) and 18 patients with abdominal injury (“HS Abd”). Furthermore, 16 severely injured patients without hemorrhagic shock and without abdominal injury (“noHS noAbd”) were retrospectively selected as controls. Plasma I-FABP levels were measured at admission to the ER and up to 3 days posttraumatic (d1-d3).

Results

Median I-FABP levels were significantly higher in the “HS Abd” group compared with the “HS noAbd” group (28,637.0 pg/ml [IQR = 6372.4–55,550.0] vs. 7292.3 pg/ml [IQR = 1282.5–11,159.5],p < 0.05). Furthermore, I-FABP levels of both hemorrhagic shock groups were significantly higher compared with the “noHS noAbd” group (844.4 pg/ml [IQR = 530.0–1432.9],p < 0.05). The time course of I-FABP levels showed a peak on the day of admission with a subsequent decline in the post-traumatic course. Furthermore, significant correlations between I-FABP levels and clinical parameters of hemorrhagic shock, such as hemoglobin, lactate value, systolic blood pressure (SBP), and shock index, were found.

The optimal cut-off level of I-FABP for detection of hemorrhagic shock was 1761.9 pg/ml with a sensitivity of 85% and a specificity of 81%.

Conclusion

This study confirmed our previous observation that I-FABP might be used as a suitable early biomarker for the detection of abdominal injuries in general. In addition, I-FABP may also be a useful and a promising parameter in the diagnosis of hemorrhagic shock, because of reflecting low intestinal perfusion.
Gamma 3 U-Blade lag screws in patients with trochanteric femur fractures: are rotation control lag screws better than others?
Authors: Yoo Jehyun , Kim Sangmin , Choi Junyoung , Hwang Jihyo
Published: December 2019

Background

Intramedullary hip nails may be classified as blades or screws depending on the type of lag screw used. Recently, a combination of lag screw types with a U-clip insertion has also been used. The purpose of this study was to evaluate the clinical and radiological outcomes of these new screw types.

Methods

A total of 185 patients with trochanteric femoral fractures (age ≥ 65 years) who underwent surgery with intramedullary nails were selected. Surgeries with InterTrochanteric/SubTrochanteric (ITST), Proximal Femoral Nail Antirotation (PFNA), and Gamma 3 U-Blade lag screws were performed between January 2011 and June 2016. The AO/OTA classification, presence of a basicervical fracture type on 3D-CT, BMI, BMD, reduction quality, position of the lag screw, TAD (tip apex distance) of the lag screw, sliding distance of the lag screw, varus change (neck shaft angle), radiological union period, fixation failure and functional outcome as determined by walking ability were analyzed.

Results

There were 3/60 (5.0%) cases of fixation failure in the ITST group, all caused by cut-out; 4/57 (7.0%) in the PFNA II group: 3 caused by cut-through and 1 by metal fracture; 1/68 (1.5%) in the Gamma 3 U-Blade lag screw group (P= 0.301). In each group, the sliding distance of the lag screw showed a significant difference (P= 0.017), whereas significant sliding over 10 mm showed no statistically significant results.

Conclusion

There was only one (1.5%) case of fixation failure in the Gamma 3 U-Blade lag screw group. The sliding distance of the U-Blade was found to be in the middle, between the PFNA II (shorter) and ITST (longer) implants. The new rotational control lag screw seems to be comparable to other screw types.
Three-dimensional technology assisted trabecular metal cup and augments positioning in revision total hip arthroplasty with complex acetabular defects
Authors: Li Qingtian , Chen Xuepan , Lin Bofu , Ma Yuanchen , Liao Jun Xing , Zheng Qiujian
Published: December 2019

Background

Revision total hip arthroplasty (THA) with large acetabular defect remains a challenge. Though trabecular metal (TM) cup and augments have been introduced in defect reconstruction with good result, the accurate positioning of implant is important to avoid complications. Therefore, we aimed to evaluate the usefulness of three-dimensional (3D) simulation and 3D model in assisting implant positioning during complex revision THA.

Methods

Sixteen patients (18 hips) who underwent revision THA with a Paprosky type III acetabular defect were analyzed retrospectively. Placement of acetabular cup and TM augments was simulated with 3D simulation software and 3D model preoperatively. Cup anteversion, abduction angle, and hip center were measured in each case preoperatively and postoperatively. Primary outcome was the percentage of outliers according to Lewinnek safe zone and Harris hip score (HHS). Secondary outcome was the correlation between the 3D planned and the postoperative value.

Results

The percentage of outliers was significantly corrected from 77.78% (14/18) preoperatively to 38.88% (7/18) postoperatively (p = 0.04). There was a significant correlation between mean planned cup anteversion and postoperative value (13.39 vs 11.99, r = 0.894; p < 0.001). There was a significant correlation between mean planned abduction and postoperative value (42.67 vs 44.91, r = 0.921, p < 0.001). The number of planned and used augments was the same in all the cases. In 15 cases (83.33%), the size of planned and used TM augments was the same. The HHS was significantly improved at final follow-up (80.94 vs 27.50, p < 0.001). No cases presented dislocation or radiological signs of loosening.

Conclusion

Preoperative 3D simulation and model were considered the useful method to assist implant positioning in revision THA with complex acetabular defect, with moderate to high accuracy and satisfied clinical outcome.
Osteogenic differentiation of follicular stem cells on nano-Saghez scaffold containing BMP2
Authors: Bayat Hananeh , Shahabinejad Hassan , Bayat Mohammad , Shirian Sadegh , Mohamadnia Abdolreza , Alijani Mohammadreza , Godarzi Arash , Shojaei Pegah , Shojaei Sahar , Shevidi Abolfazl , Bahrami Naghmeh
Published: December 2019

Background

Bone tissue is one of the tissues that are capable of self-regeneration. However, bone self-regeneration is defeated in the case of broad lesion of bone structure. Isolated stem cells from wisdom tooth follicles can potentially differentiate into ectodermal and mesodermal cells. Saghez is a natural substance that has been extracted from Pistacia terebinthus with unique features, such as high temperature and mechanical stability, adhesive structure, biocompatibility, and anti-neoplastic properties.

Methods

In this study, Saghez-encapsulated BMP2 was applied as a scaffold for wisdom tooth follicle stem cell differentiation into the osteocyte. A total of three wisdom tooth follicles were obtained for stem cell isolation. For verification of differentiation of the isolated stem cells into osteocyte and adipocyte, Oil Red and Alizarin staining were applied, respectively. Moreover, mesenchymal stem cells were distinguished by profiling their cell surface markers, includingCD73, CD90, CD44, and CD105, by flow cytometry. Saghez scaffold loaded with BMP2 factor was prepared using sol-gel method. Four experimental groups were considered in this study: cells seeded on BMP2 encapsulated in Saghez scaffold, Saghez scaffold, osteogenic medium, and DMEM medium.

Results

Mechanical properties of Saghez scaffold, including tensile Young’s modulus, ultimate tensile stress, compression Young’s modulus, and complex shear modulus, were 19 MPa, 32 MPa, 0.42 MPa, and 0.9 MPa, respectively. The porosity of the scaffold was 70–140 μm, and the percentage of porosity was 75–98%. The results of flow cytometry studies indicated that CD44, CD73, CD90, and CD105 were positively expressed on the membrane of the tooth follicles’ stem cell. The results indicated that the rate of differentiation of the follicle stem cells into osteocyte was the highest in the Saghez-BMP2 scaffold containing differentiation medium groups. These findings were verified by morphological studies, osteoblast and osteocalcin gene and protein expression investigations, and alkaline phosphatase activity measurement. The highest osteopontin and osteocalcin genes expression levels (1.7 and 1.9) were seen in positive control, followed by DMEM + differentiation factor (1.5 and 1.6), scaffold + BMP2 (1.2 and 1.4), DMEM + stem cell (1 and 1) and scaffold (0.4 and 0.5), and negative control respectively.

Conclusion

This study provides a novel system for differentiation of the stem cell into osteocytes. The results of this study suggest that loaded BMP2 in Saghez scaffold possibly acts as an osteocyte differentiator factor.
Health-related quality of life in children and adolescents undergoing intraoperative device closure of isolated perimembranous ventricular septal defects in southeastern China
Authors: Huang Jiang-Shan , Huang Shu-Ting , Sun Kai-Peng , Hong Zhi-Nuan , Chen Liang-Wan , Kuo Yur-Ren , Chen Qiang
Published: December 2019

Objectives

To investigate the health-related quality of life (HRQOL) in children and adolescents who underwent intraoperative device closure of perimembranous ventricular septal defects (pmVSDs).

Methods

From October 2017 to January 2018, a total of 126 children and adolescents with isolated pmVSDs who underwent intraoperative device closure were enrolled in this study. We used the Pediatric Quality of Life Inventory Measurement Models 4.0 generic core scales to measure HRQOL 24 h before the operation and three months and one year after surgery.

Results

A total of 126 patients were successfully occluded. No severe complications occurred during the operative time, and 1 case of Mobitz type I atrioventricular block (AVB) and 1 case of complete cAVB occurred during the postoperative period. Compared with the data before the operation, the total score and five domain scores, including physical, psychosocial, emotional, social and psychological functioning, were significantly higher at three months after the operation. In addition, the total score, physical functioning score, and the psychosocial functioning score at the 1-year follow-up were even higher than those at 3 months after the operation.

Conclusions

The present study suggests that intraoperative device closure of pmVSD could improve health-related quality of life in children/adolescents and that the improvement may progress as the time after the operation increases. Further studies should concentrate on comparisons with other medical methods, larger samples, and longer follow-up periods.
Inhibition of human carboxylesterases by ginsenosides: structure–activity relationships and inhibitory mechanism
Authors: Sun Zhao-Hui , Chen Jing , Song Yun-Qing , Dou Tong-Yi , Zou Li-Wei , Hao Da-Cheng , Liu Hai-Bin , Ge Guang-Bo , Yang Ling
Published: December 2019

Background

Human carboxylesterases (hCES) are key serine hydrolases responsible for the hydrolysis of a wide range of endogenous and xenobiotic esters. Although it has been reported that some ginsenosides can modulate the activities of various enzymes, the inhibitory effects of ginsenosides on hCES have not been well-investigated.

Methods

In this study, more than 20 ginsenosides were collected and their inhibitory effects on hCES1A and hCES2A were assayed using the highly specific fluorescent probe substrates for each isoenzyme. Molecular docking simulations were also performed to investigate the interactions between ginsenosides and hCES.

Results

Among all tested ginsenosides, Dammarenediol II (DM) and 20S-O-β-(d-glucosyl)-dammarenediol II (DMG) displayed potent inhibition against both hCES1A and hCES2A, while protopanaxadiol (PPD) and protopanaxatriol (PPT) exhibited strong inhibition on hCES2A and high selectivity over hCES1A. Introduction of O-glycosyl groups at the core skeleton decreased hCES inhibition activity, while the hydroxyl groups at different sites might also effect hCES inhibition. Inhibition kinetic analyses demonstrated that DM and DMG functioned as competitive inhibitors against hCES1A-mediated d-luciferin methyl ester (DME) hydrolysis. In contrast, DM, DMG, PPD and PPT inhibit hCES2A-mediated fluorescein diacetate (FD) hydrolysis via a mixed manner.

Conclusion

The structure–inhibition relationships of ginsenosides as hCES inhibitors was investigated for the first time. Our results revealed that DM and DMG were potent inhibitors against both hCES1A and hCES2A, while PPD and PPT were selective and strong inhibitors against hCES2A.
Methylmalonic and propionic acidemia among hospitalized pediatric patients: a nationwide report
Authors: Jiang Yi-Zhou , Shi Yu , Shi Ying , Gan Lan-Xia , Kong Yuan-Yuan , Zhu Zhi-Jun , Wang Hai-Bo , Sun Li-Ying
Published: December 2019

Background

Methylmalonic acidemia (MMA) and propionic acidemia (PA) are two kinds of diseases caused by inborn errors of metabolism. So far, the epidemiological data on them are limited in China. The aim of our study is to investigate the proportion and characteristics of hospitalized pediatric patients with MMA and PA in China.

Methods

The data in this study were obtained from the Hospital Quality Monitoring System, a national inpatient database in China, with information on the patients hospitalized during the period from 2013 to 2017. We identified the data related to the patients who were under 18 years old and were diagnosed with MMA/PA, and extracted the information on demographic characteristics, hospital location, total cost and other related clinical presentations from the data.

Results

Among all hospitalized pediatric patients with liver diseases, there were increasing trends in the proportion of individuals diagnosed with MMA or PA during the period from 2013 (0.76% for MMA; 0.13% for PA) to 2017 (1.61% for MMA; 0.32% for PA). For both MMA and PA, children under 2-year-old accounted for the highest proportion. The median of total cost per hospitalization was relatively high (RMB 7388.53 for MMA; RMB 4999.66 for PA). Moreover, most patients hospitalized in tertiary class A hospitals (MMA: 80.96%, PA: 76.21%); and a majority of pediatric patients admitted in the hospitals in Shanghai and Beijing are from outside districts. Manifestations of nervous system-related symptoms, and metabolic acidosis or anemia in laboratory findings were more common during hospitalization.

Conclusions

The study is the first nationwide one in providing epidemiological and clinical information on hospitalized pediatric patients with MMA/PA. An increasing hospitalization with various presentations and a heavy financial burden were observed. In addition, geographically, the medical resources in China have been unevenly distributed.
Dua Ti Dawa Ti: understanding psychological distress in the ten districts of the Kashmir Valley and community mental health service needs
Authors: Housen Tambri , Ara Shabnum , Shah Akmal , Shah Showkat , Lenglet Annick , Pintaldi Giovanni
Published: December 2019

Background

An extensive body of research exists looking at the level of psychological distress in populations affected by political conflict. Recommended response to psychological distress in humanitarian crises is still based on frameworks for interventions developed in western/European contexts including psychological first aid, counselling and group therapy. While there is growing, but limited, evidence that culturally modified interventions can lead to reduction in symptoms of psychological distress in conflict affected populations, there is a need to understand mental health help-seeking behaviour and mental health service needs from the perspective of affected communities.

Methods

This study employed a qualitative exploratory research design based on principles of grounded theory. A combination of convenience and snowball sampling was used to recruit 186 adults from the general population to 20 focus group discussions; 95 men, median age 40 years, interquartile range (IQR): 27–48 years and 91 women, median age 40 years IQR: 32–50 years. Trained Kashmiri facilitators used a semi-structured interview guide to ascertain community perceptions on mental illness, help-seeking and service needs from the perspective of communities in the Kashmir Valley. Content analysis of transcripts resulted in the identification of seven overarching themes.

Results

Common locally recognized symptoms of psychological distress were synonymous with symptoms listed in the Hopkins Symptoms Checklist (HSCL-25) and the Harvard Trauma Questionnaire (HTQ). Protracted political insecurity was highlighted as a major perceived cause of psychological distress in communities. Mental health help-seeking included traditional/spiritual healers in combination with practitioners of western medicine, with access highlighted as the main barrier. Divergent views were expressed on the effectiveness of treatment received. Participants’ expressed the need for investment in mental health literacy to improve the community’s capacity to recognize and support those suffering from psychological distress.

Conclusions

Our findings demonstrate the universality of symptoms of psychological distress whilst simultaneously highlighting the importance of recognizing the cultural, spiritual and contextual framework within which psychological distress is understood and manifest. Co-constructed models of community based mental health services are needed.
Recommended care and care adherence following a diagnosis of Lynch syndrome: a mixed-methods study
Authors: Mittendorf Kathleen F. , Hunter Jessica Ezzell , Schneider Jennifer L. , Shuster Elizabeth , Rope Alan F. , Zepp Jamilyn , Gilmore Marian J. , Muessig Kristin R. , Davis James V. , Kauffman Tia L. , Bergen Kellene M. , Wiesner Georgia L. , Acheson Louise S. , Peterson Susan K. , Syngal Sapna , Reiss Jacob A. , Goddard Katrina A. B.
Published: December 2019

Background

Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome. This study assesses trends in diagnosis of LS and adherence to recommended LS-related care in a large integrated healthcare organization (~ 575,000 members).

Methods

Electronic medical record (EMR) data (1999–2015) were examined to identify patients with a diagnosis of LS. We examined their LS-associated care recommendations and adherence to these recommendations. Qualitative patient and provider interviews were conducted with the aim of identifying opportunities for improved care delivery.

Results

We identified 74 patients with a diagnosis of LS; 64% were diagnosed with a LS-related malignancy prior to their diagnosis of LS. The time to LS diagnosis following development of a LS-related cancer decreased over time: before 2009 11% of individuals received a diagnosis of LS within 1 year of developing a LS-related cancer compared to 83% after 2009 (p < 0.0001). Colonoscopy recommendations were documented in the EMR for almost all patients with LS (96%). Documentation of other recommendations for cancer surveillance was less commonly found. Overall, patient adherence to colonoscopy was high (M = 81.5%; SD = 32.7%), and adherence to other recommendations varied. To improve care coordination, patients and providers suggested providing automated reminder prompts for LS-related surveillance, adding a LS-specific diagnosis code, and providing guidelines for LS-related surveillance in the EMR.

Conclusions

We identified fewer than expected patients with LS in our large care system, indicating that there is still a diagnostic care gap. However, patients with LS were likely to receive and follow CRC surveillance recommendations. Recommendations for and adherence to extracolonic surveillance were variable. Improved care coordination and clearer documentation of the LS diagnosis is needed.
Current treatment landscape for patients with locally recurrent inoperable or metastatic triple-negative breast cancer: a systematic literature review
Authors: Li Claire H. , Karantza Vassiliki , Aktan Gursel , Lala Mallika
Published: December 2019

Background

Metastatic triple-negative breast cancer (mTNBC), an aggressive histological subtype, has poor prognosis. Chemotherapy remains standard of care for mTNBC, although no agent has been specifically approved for this breast cancer subtype. Instead, chemotherapies approved for metastatic breast cancer (MBC) are used for mTNBC (National Comprehensive Cancer Network Guidelines [NCCN] v1.2019). Atezolizumab in combination with nab-paclitaxel was recently approved for programmed death-ligand 1 (PD-L1)–positive locally advanced or metastatic TNBC. Published historical data were reviewed to characterize the efficacy of NCCN-recommended (v1.2016) agents as first-line (1L) and second-line or later (2L+) treatment for patients with locally recurrent inoperable or metastatic TNBC (collectively termed mTNBC herein).

Methods

A systematic literature review was performed, examining clinical efficacy of therapies for mTNBC based on NCCN v1.2016 guideline recommendations. Data from 13 studies, either published retrospective mTNBC subgroup analyses based on phase III trials in MBC or phase II trials in mTNBC, were included.

Results

A meta-analysis of mTNBC subgroups from three phase III trials in 1L MBC reported pooled objective response rate (ORR) of 23%, median overall survival (OS) of 17.5 months, and median progression-free survival (PFS) of 5.4 months with single-agent chemotherapy. In two subgroup analyses from a phase III study and a phase II trial (n = 40 each), median duration of response (DOR) to 1L chemotherapy for mTNBC was 4.4–6.6 months; therefore, responses were not durable. A meta-analysis of seven cohorts showed the pooled ORR for 2L+ chemotherapy was 11% (95% CI, 9–14%). Median DOR to 2L+ chemotherapy in mTNBC was also limited (4.2–5.9 months) per two subgroup analyses from a phase III study. No combination chemotherapy regimens recommended by NCCN v1.2016 for treatment of MBC showed superior OS to single agents.

Conclusions

Chemotherapies have limited effectiveness and are associated with unfavorable toxicity profiles, highlighting a considerable unmet medical need for improved therapeutic options in mTNBC. In addition to the recently approved combination of atezolizumab and nab-paclitaxel for PD-L1–positive mTNBC, new treatments resulting in durable clinical responses, prolonged survival, and manageable safety profile would greatly benefit patients with mTNBC.
Guidelines for benchmarking of optimization-based approaches for fitting mathematical models
Authors: Kreutz Clemens
Published: December 2019

Insufficient performance of optimization-based approaches for the fitting of mathematical models is still a major bottleneck in systems biology. In this article, the reasons and methodological challenges are summarized as well as their impact in benchmark studies. Important aspects for achieving an increased level of evidence for benchmark results are discussed. Based on general guidelines for benchmarking in computational biology, a collection of tailored guidelines is presented for performing informative and unbiased benchmarking of optimization-based fitting approaches. Comprehensive benchmark studies based on these recommendations are urgently required for the establishment of a robust and reliable methodology for the systems biology community.