bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiographic characteristics of wrists in idiopathic carpal tunnel syndrome patients
Authors: Ikeda Kazuhiro , Yoshii Yuichi , Ogawa Takeshi , Ishii Tomoo
Published: April 2020

Background

To determine the radiographic characteristics of wrists in idiopathic carpal tunnel syndrome patients, we compared the radiographic parameters of the wrists between carpal tunnel syndrome patients and non-symptomatic controls.

Methods

We evaluated radiographic parameters of 94 wrists of 62 idiopathic carpal tunnel syndrome patients and 94 asymptomatic wrists of 94 controls. Carpal tunnel syndrome was diagnosed by clinical findings and nerve conduction studies. The lack of symptoms was confirmed with the medical records and interviews for the controls. X-ray images of the postero-anterior and lateral views of the wrist were taken. Using the obtained X-ray images, the indices of radial inclination, volar tilt, ulnar variance, and transverse and antero-posterior diameters of the wrists were measured. Two raters independently performed the measurement. One rater measured without information of clinical symptoms. Inter-rater reliabilities for each parameter were evaluated by the intra-class correlation coefficients. The averages of the measurements of two raters were compared between the carpal tunnel syndrome patients and the controls.

Results

The intra-class correlation coefficients were 0.58 for radial inclination, 0.77 for ulnar variance, 0.99 for transverse diameter, 0.60 for volar tilt, and 0.91 for antero-posterior diameter. Statistically significant correlations were found for all parameters (P < 0.01). The ulnar variance was significantly larger in the carpal tunnel syndrome patients compared to the controls (1.7 +/− 1.8 mm and 0.8 +/− 1.5 mm for the patients and controls, respectivelyP < 0.01). There were no significant differences in the other parameters.

Conclusions

Significant differences in the ulnar variance were observed between carpal tunnel syndrome patients and controls. This suggests that the imbalance of radioulnar bone length is one of the risk factors to develop carpal tunnel syndrome. The positive ulnar variance may be an index that needs attention to the development of carpal tunnel syndrome.

Level of evidence

level III, a case control study.
Simultaneous bilateral femoral neck fractures in a dialysis-dependent patient: case report and literature review
Authors: Zhu Yunyun , Hu Jingtao , Han Wenlun , Lu Jianwei , Zeng Yuqing
Published: April 2020

Background

Simultaneous bilateral femoral neck fractures are extremely rare without obvious injury. Herein, we report the case of a patient on dialysis presenting with bilateral femoral neck fractures, which is a condition with high complication and mortality rates according to a review of the pertinent literature.

Case presentation

We report the case a 47-year-old female with a history of 8 years of haemodialysis due to polycystic kidney disease who presented with bilateral hip pain during walking. The clinical history and results of physical and radiographic examinations of this patient are shown. Single-stage bilateral hemiarthroplasty was performed after a multidisciplinary team consultation. Three days after the operation, she could ambulate with a walker. The woman gradually regained her previous ability to walk over 6 months after surgery.

Conclusions

A multidisciplinary team consultation for perioperative management is necessary and effective in patients on dialysis. Early diagnosis with prompt surgical treatment could lead to favourable recovery.
Simultaneous dislocation of the radial head and distal radio-ulnar joint without fracture in an adult patient: a case report and review of literature
Authors: Jin Xiang-Yun , Zhao Wen-Bo , Dong Yu-Qi , Huang Yi-Gang
Published: April 2020

Background

Simultaneous dislocation of the radial head and distal radio-ulnar joint without fracture (Criss-Cross Injury) in an adult patient is rarely reported in previous studies. The pathological changes and injury patterns have not been clearly demonstrated.

Case presentation

A 26-year-old woman presented with acute pain of the right wrist and elbow after a fall from cycling. Physical examination revealed an unstable elbow and wrist joint. Plain radiographs showed volar dislocation of the radial head and dorsal dislocation of the distal radius without associated fracture, forming a criss-cross appearance of the ulna and radius on the lateral radiograph. MRI images confirmed partial rupture of the proximal interosseous membrane from its dorsal attachment on the radius, as well as partial rupture of the medial collateral ligament. Conservative treatment failed because the radiocapitellar joint and distal radio-ulnar joint could not be simultaneously reduced. Surgical exploration revealed a highly unstable radial head, but the annular ligament was found to be intact. Manual force was applied to reduce the radial head and a percutaneous K-wire was used to stabilize the proximal radioulnar joint with the forearm in full supination. After surgery, the elbow was immobilized in 90° flexion by a long arm cast for 4 weeks. The K-wire was removed at 6 weeks postoperatively. At 18 months postoperatively, the patient had regained a full range of flexion and extension, with normal supination and a slight limitation in pronation.

Conclusions

The proximal IOM, especially the dorsal band, was injured in Criss-Cross injuries, while the central part of the IOM remained intact. This injury pattern distinguished itself from Essex-Lopresti injury, which mainly involves rupture of the central band of the IOM.
Genetic diversity and differentiation of populations of Chlorops oryzae (Diptera, Chloropidae)
Authors: Zhou Ailin , Tian Ping , Li Zhongcai , Li Xinwen , Tan Xiaoping , Zhang Zhengbing , Qiu Lin , He Hualiang , Ding Wenbing , Li Youzhi
Published: April 2020

Background

Chlorops oryzae is an important pest of rice crops. There have been frequent outbreaks of this pest in recent years and it has become the main rice pest in some regions. To elucidate the molecular mechanism of frequent C. oryzae outbreaks, we estimated the genetic diversity and genetic differentiation of 20 geographical populations based on a dataset of ISSR markers and COI sequences.

Results

ISSR data revealed a high level of genetic diversity among the 20 populations as measured by Shannon’s information index (I), Nei’s gene diversity (H), and the percentage of polymorphic bands (PPB). The mean coefficient of gene differentiation (Gst) was 0.0997, which indicates that only 9.97% genetic variation is between populations. The estimated gene flow (Nm) value was 4.5165, indicating a high level of gene flow and low, or medium, genetic differentiation among some populations. The results of a Mantel test revealed no significant correlation between genetic and geographic distance among populations, which means there is no evidence of significant genetic isolation by distance. An UPGMA (unweighted pair-group method with arithmetic averages) dendrogram based on genetic identity, did not indicate any major geographic structure for the 20 populations examined. mtDNA COI data indicates low nucleotide (0.0007) and haplotype diversity (0.36) in all populations. Fst values suggest that the 20 populations have low, or medium, levels of genetic differentiation. And the topology of a Neighbor-Joining tree suggests that there are no independent groups among the populations examined.

Conclusions

Our results suggest that C. oryzae populations have high genetic diversity at the species level. There is evidence of frequent gene flow and low, or medium, levels of genetic differentiation among some populations. There is no significant correlation between genetic and geographic distance among C. oryzae populations, and therefore no significant isolation by distance. All results are consistent with frequent gene exchange between populations, which could increase the genetic diversity, and hence, adaptability of C. oryzae, thereby promoting frequent outbreaks of this pest. Such knowledge may provide a scientific basis for predicting future outbreaks.
A review of water fluoridation implementation strategy in England 2002–2005
Authors: Wordley V. , Bedi R.
Published: April 2020

Before 2002, there had been a long-term stalemate between private water companies and District Health Authorities across England. Between 2002 and 2005 the team in the Office of the Chief Dental Officer used leadership and advocacy skills to overcome political barriers, introducing the Water Act 2003 and a Statutory Instrument in 2005 providing indemnity for water companies. This legislation was key in removing obstacles towards the expansion water fluoridation across England.
DLI-IT: a deep learning approach to drug label identification through image and text embedding
Authors: Liu Xiangwen , Meehan Joe , Tong Weida , Wu Leihong , Xu Xiaowei , Xu Joshua
Published: April 2020

Background

Drug label, or packaging insert play a significant role in all the operations from production through drug distribution channels to the end consumer. Image of the label also called Display Panel or label could be used to identify illegal, illicit, unapproved and potentially dangerous drugs. Due to the time-consuming process and high labor cost of investigation, an artificial intelligence-based deep learning model is necessary for fast and accurate identification of the drugs.

Methods

In addition to image-based identification technology, we take advantages of rich text information on the pharmaceutical package insert of drug label images. In this study, we developed the Drug Label Identification through Image and Text embedding model (DLI-IT) to model text-based patterns of historical data for detection of suspicious drugs. In DLI-IT, we first trained a Connectionist Text Proposal Network (CTPN) to crop the raw image into sub-images based on the text. The texts from the cropped sub-images are recognized independently through the Tesseract OCR Engine and combined as one document for each raw image. Finally, we applied universal sentence embedding to transform these documents into vectors and find the most similar reference images to the test image through the cosine similarity.

Results

We trained the DLI-IT model on 1749 opioid and 2365 non-opioid drug label images. The model was then tested on 300 external opioid drug label images, the result demonstrated our model achieves up-to 88% of the precision in drug label identification, which outperforms previous image-based or text-based identification method by up-to 35% improvement.

Conclusion

To conclude, by combining Image and Text embedding analysis under deep learning framework, our DLI-IT approach achieved a competitive performance in advancing drug label identification.
Current state of fall prevention and management policies and procedures in Canadian spinal cord injury rehabilitation
Authors: Singh Hardeep , Flett Heather M. , Silver Michelle P. , Craven B. Catharine , Jaglal Susan B. , Musselman Kristin E.
Published: April 2020

Background

Preventing patient falls is a priority in tertiary spinal cord injury (SCI) rehabilitation. Falls can result in patient or staff injury, delayed rehabilitation, and hospital liability. A comprehensive overview of fall prevention/management policies and procedures in Canadian SCI rehabilitation is currently lacking. We describe and compare the fall prevention/management policies and procedures implemented in Canadian tertiary hospitals that provide SCI rehabilitation.

Methods

Fall prevention/management documents implemented in SCI rehabilitation at six Canadian tertiary rehabilitation hospitals across five provinces were analyzed using a document analysis. Analysis involved multiple readings of the documents followed by a content and thematic document analysis.

Results

Fall prevention/management policies and procedures in SCI rehabilitation were organized into three main categories: 1) pre-fall policies and procedures; 2) post-fall policies and procedures; and, 3) communication between and amongst staff, patients, and families. Pre-fall policies and procedures encompassed: a) the definition of a fall; b) fall risk assessments in SCI rehabilitation; and, c) fall prevention strategies. The post-fall policies and procedures included: a) recovery from a fall; b) incident reporting process; and, c) fall classification. Components of fall prevention/management policies and practices that differed between hospitals included the fall risk assessments, post-fall huddles, and fall classifications.

Conclusions

Fall prevention/management is a required organizational practice for all hospitals. Although Canadian tertiary hospitals that provide SCI rehabilitation have similar components of fall prevention/management policies and procedures, the specific requirements differ at each site. There is a need for evidence-informed, consensus-driven implementation of SCI-specific fall prevention and management procedures across Canadian SCI rehabilitation settings.
Bacterial fecal microbiota is only minimally affected by a standardized weight loss plan in obese cats
Authors: Tal Moran , Weese J. Scott , Gomez Diego E. , Hesta Myriam , Steiner Joerg M. , Verbrugghe Adronie
Published: April 2020

Background

Research in humans and mice suggests that obesity influences the abundance and diversity of gastrointestinal (GI) microbiota, and that an “obese microbiome” influences energy metabolism and fat storage in the host. Microbiota membership and composition have been previously assessed in healthy cats. However, research investigating the effects of obesity and weight loss on the cat’s fecal microbiota is limited. Therefore, this study’s objective was to evaluate differences in fecal microbial abundance and biodiversity, as well as serum cobalamin and folate concentrations in obese cats, before and after weight loss, and compare to lean cats.

Fourteen lean and 17 obese healthy client-owned cats were fed a veterinary therapeutic weight loss food at maintenance energy requirement for 4 weeks. At the end of week 4, lean cats finished the study, whereas obese cats continued with a 10-week weight loss period on the same food, fed at individually-tailored weight loss energy requirements. Body weight and body condition score were recorded every 2 weeks throughout the study. At the end of each period, a fecal sample and food-consumption records were obtained from the owners, and serum cobalamin and folate concentrations were analysed. DNA was extracted from fecal samples, polymerase chain reaction (PCR) was performed, and products were sequenced using next-generation sequencing (Illumina MiSeq).

Results

No significant differences in the relative abundance of taxa and in biodiversity indices were observed between cats in either group (P > 0.05 for all tests). Nevertheless, some significantly enriched taxa, mainly belonging to Firmicutes, were noted in linear discriminant analysis effect size test in obese cats before weight loss compared to lean cats. Serum cobalamin concentrations were significantly higher in lean compared to obese cats both before and after weight loss. Serum folate concentrations were higher in obese cats before weight loss compared to after.

Conclusions

The association between feline obesity and the fecal bacterial microbiota was demonstrated in enriched taxa in obese cats compared to lean cats, which may be related to enhanced efficiency of energy-harvesting. However, in obese cats, the fecal microbial abundance and biodiversity were only minimally affected during the early phase of a standardized weight loss plan.
Antimicrobial resistance and novel mutations detected in the gyrA and parC genes of Pseudomonas aeruginosa strains isolated from companion dogs
Authors: Park Youjin , Oh Jaeyoung , Park Sowon , Sum Samuth , Song Wonkeun , Chae Jongchan , Park Heemyung
Published: April 2020

Background

Fluoroquinolone agents, such as enrofloxacin and marbofloxacin, are commonly used for pseudomonal infection in veterinary medicine. However, the rate of resistance to fluoroquinolones is rapidly increasing, according to multiple studies in various countries. Point mutations in the quinolone resistance-determining region (QRDR) are closely related to the increased fluoroquinolone resistance of Pseudomonas aeruginosa. The aim of this study was to investigate current antimicrobial susceptibility and fluoroquinolone resistance in P. aeruginosa strains isolated from dogs. The presence of point mutations in the QRDR was confirmed by gyrA and parC polymerase chain reaction and nucleotide sequencing analysis.

Results

A total of 84 nonduplicated P. aeruginosa strains were obtained from 228 healthy dogs (healthy group) and 260 dogs with clinical signs (infected group). Among these isolates, 38 strains from the healthy group were detected in several sample types, whereas 46 strains from the infected group were obtained mostly from dogs’ ears with otitis externa (41/260, 15.8%). All strains were resistant to nalidixic acid, while some were also resistant to enrofloxacin (23/84, 27.4%), marbofloxacin (17/84, 20.2%), levofloxacin (12/84, 14.3%), or ciprofloxacin (11/84, 13.1%). Enrofloxacin resistance was significantly higher in strains from the infected group than in those from the healthy group (p < 0.05). Among the 23 fluoroquinolone-resistant strains, 8 and 4 different mutations were detected in the gyrA and parC genes, respectively. Mutations in gyrA were significantly common in the infected group (p < 0.05). Hotspots for the gyrA and parC mutations were Thr83 (34.8%, 8/23) and Pro116 (91.3%, 21/23), respectively. Double and triple mutations were also found in 5 of the strains.

Conclusion

Novel mutations in the gyrA and parC genes were first found in P. aeruginosa isolated from companion dogs in South Korea. These findings suggest that it is important to encourage prudent use of fluoroquinolone antibiotics in canine pseudomonal infection treatment.
KIF15 facilitates gastric cancer via enhancing proliferation, inhibiting apoptosis, and predict poor prognosis
Authors: Ding Lixian , Li Bin , Yu Xiaotong , Li Zhongsheng , Li Xinglong , Dang Shuwei , Lv Qiang , Wei Jiufeng , Sun Haixia , Chen Hongsheng , Liu Ming , Li Guodong
Published: April 2020

Background

Kinesin superfamily proteins (KIFs) can transport membranous organelles and protein complexes in an ATP-dependent manner. Kinesin family member 15 (KIF15) is overexpressed in various cancers. However, the function of KIF15 in gastric cancer (GC) is still unclear.

Methods

GC patients’ data from The Cancer Genome Atlas (TCGA) were analyzed by bioinformatics methods. The expression of KIF15 was examined in GC and paracarcinoma tissues from 41 patients to verify the analysis results. The relationship between KIF15 expression and clinical characteristics were also observed by bioinformatics methods. Kaplan–Meier survival analysis of 122 GC patients in our hospital was performed to explore the relationship between KIF15 expression levels and GC patients’ prognosis. KIF15 was downregulated in GC cell lines AGS and SGC-7901 by transfecting a lentivirus-mediated shRNA plasmid targeting KIF15. In vitro, GC cell proliferation and apoptosis were detected by MTT assay, colony formation assay, and Annexin V-APC staining. In vivo, xenograft experiments were used to verify the in vitro results. Furthermore, Human Apoptosis Antibody Array kit was used to screen possible targets of KIF15 in GC cell lines.

Results

The bioinformatics results showed that KIF15 expression levels were higher in GC tissues than in normal tissues. IHC showed same results. High expression of KIF15 was statistical correlated with high age and early histologic stage. Kaplan–Meier curves indicated that high KIF15 expression predict poor prognosis in patients with GC. MTT assay and colony formation assay showed that KIF15 promote GC cell proliferation. Annexin V-APC staining found that KIF15 can inhibit GC cell apoptosis. Xenograft experiments reveal that downregulating KIF15 can inhibit GC tumor growth and promote GC apoptosis. Through detection of 43 anti-apoptotic proteins by the Human Apoptosis Antibody Array kit, it was confirmed that knocking down KIF15 can reduce seven anti-apoptotic proteins expression.

Conclusions

Taken together, our study revealed a critical role for KIF15 to inhibit GC cell apoptosis and promote GC cell proliferation. KIF15 may decrease anti-apoptotic proteins expression by regulating apoptosis pathways. High expression of KIF15 predicts a poor prognosis in patients with GC. KIF15 might be a novel prognostic biomarker and a therapeutic target for GC.
Barriers and facilitators to implementation of menu labelling interventions from a food service industry perspective: a mixed methods systematic review
Authors: Kerins Claire , McHugh Sheena , McSharry Jenny , Reardon Caitlin M. , Hayes Catherine , Perry Ivan J. , Geaney Fiona , Seery Suzanne , Kelly Colette
Published: April 2020

Background

Eating outside the home contributes to poor dietary habits worldwide and is associated with increased body fat and weight gain. Evidence shows menu labelling is effective in promoting healthier food choices; however, implementation issues have arisen. The purpose of this systematic review was to synthesise the evidence on the perceived barriers and facilitators to implementation of menu labelling interventions from the perspective of the food service industry.

Methods

Peer-reviewed and grey literature were searched using databases, specialised search engines and public health organisation websites. Screening reference lists, citation chaining and contacting authors of all included studies were undertaken. Primary research studies relevant to direct supply-side stakeholders were eligible for inclusion. There were no restrictions on menu labelling scheme or format, study methods, publication year or language. At least two independent reviewers performed study selection, data extraction and quality appraisal. The results were synthesised using the ‘best fit’ framework synthesis approach, with reference to the Consolidated Framework for Implementation Research (CFIR).

Results

Seventeen studies met the eligibility criteria, with the majority rated as average quality (n = 10). The most frequently cited barriers were coded to the CFIR constructs ‘Consumer Needs & Resources’ (e.g. lack of customer demand for/interest in menu labelling, risk of overwhelmed/confused customers) and ‘Compatibility’ with organisation work processes (e.g. lack of standardised recipes, limited space on menus). Frequently cited facilitators were coded to the CFIR constructs ‘Relative Advantage’ of menu labelling (e.g. improved business image/reputation) and ‘Consumer Needs & Resources’ (e.g. customer demand for/interest in menu labelling, providing nutrition information to customers). An adapted framework consisting of a priori and new constructs was developed, which illustrates the relationships between domains.

Conclusion

This review generates an adapted CFIR framework for understanding implementation of menu labelling interventions. It highlights that implementation is influenced by multiple interdependent factors, particularly related to the external and internal context of food businesses, and features of the menu labelling intervention. The findings can be used by researchers and practitioners to develop or select strategies to address barriers that impede implementation and to leverage facilitators that assist with implementation effort.

Trial registration

Systematic review registration: PROSPERO CRD42017083306.
Increasing translation of research evidence for optimal park design: a qualitative study with stakeholders
Authors: Veitch Jenny , Denniss Emily , Ball Kylie , Koorts Harriet , Deforche Benedicte , Timperio Anna
Published: April 2020

Background

The design of parks is critical to ensure they are appealing, meet the needs of the community and optimise opportunities for physical activity, relaxation, exposure to nature and social interaction. There is currently a lack of understanding on how research evidence is informing park design and how to reduce the many challenges associated with research-practice-policy translation. Understanding how organisations use evidence for decision-making regarding park design is critical for reducing the research-practice-policy gap and ensuring evidence based strategies inform park design to support healthy active living. This study explored stakeholder perceptions regarding factors that influence the use of research evidence to inform park planning and design, and potential strategies to enhance effective translation of research evidence for optimal park design into policy and practice.

Methods

One-on-one in-depth interviews were conducted with 23 stakeholders within the park design, planning and management sector. Participants shared experiences regarding: influences on park development and design; current park development policies; ways to facilitate use of evidence; and priorities for future research. Interviews were recorded and transcribed verbatim and content analysis performed using NVivo 12.

Results

Research evidence is used and considered important for park planning; however, several barriers were highlighted: time and cost constraints; difficulties accessing research; and limited research relevant to specific needs. Developing partnerships between researchers and park developers and providing evidence in a more accessible format such as short summaries/reports, infographics, presentations, research updates and dedicated research databases emerged as key enablers. The main research gaps identified included research into park features to encourage visitation and cost-benefit analyses studies.

Conclusions

This research is a first step to better understand strategies to promote more effective uptake and use of evidence to inform park planning. Researchers must develop multi-sectoral collaborations and generate policy-relevant research in a readily accessible, timely and user-friendly format to ensure evidence is used to enhance park design and ultimately public health.
Familial chilblain lupus due to a novel mutation in TREX1 associated with Aicardi–Goutie’res syndrome
Authors: Yi Cuili , Li Qiyuan , Xiao Jihong
Published: April 2020

Background

Familial chilblain lupus (FCL) is a rare, chronic form of cutaneous lupus erythematosus, which is characterized by painful bluish-red inflammatory cutaneous lesions in acral locations. Mutations in TREX1, SAMHD1 and STING have been described in FCL patients. Less than 10 TREX1 mutation positive FCL families have been described in the literature.

Case presentation

Genetic study was performed in a large, nonconsanguineous Chinese family with 13 members over 4 generations affected by chilblain lupus. Whole exome sequencing was performed for the index patient. Significant variant detection was subsequently validated by resequencing using Sanger sequencing in the index patient and other family members. A novel pathogenic mutation TREX1 p.Asp18His was iditified in the index patient. The mutation was present in affected individuals and was absent in non-affected individuals in the familiy.

Conclusions

We present a four-generation Chinese family with FCL caused by a novel heterozygous mutation TREX1 p.Asp18His, which had been reported in a patient with Aicardi–Goutie’res syndrome. This is the first reported Chinese family with FCL based on mutation in TREX1.
Experiences, perspectives and expectations of adolescents with juvenile idiopathic arthritis regarding future work participation; a qualitative study
Authors: van Gulik E. Charlotte , Verkuil Floris , Barendregt Anouk M. , Schonenberg-Meinema Dieneke , Nassar-Sheikh Rashid Amara , Kuijpers Taco W. , van den Berg J. Merlijn , Hoving Jan L.
Published: April 2020

Background

Having Juvenile idiopathic Arthritis (JIA) has widespread implications for a person’s life. Patients have to deal with recurring arthritis, characterized by pain often accompanied by a loss of energy. Since JIA often persists into adulthood, patients with JIA are likely to encounter difficulties in their working life. We expect that the experiences in school life may be comparable to the barriers and opportunities which patients affected by JIA encounter in adult working life. Therefore, the aim of this study was to elicit the experiences during school life and the perspectives and expectations regarding future work participation of adolescents with JIA.

Methods

This study used individual, semi-structured interviews and followed a predefined interview guide. Participants between 14 and 18 years of age (n = 22) were purposively selected to achieve a broad range of participant characteristics. Open coding was performed, followed by axial coding and selective coding.

Results

Great differences were seen in the support and understanding that adolescents received in dealing with JIA at school, leisure activities and work. Varying approaches were mentioned on how to pursue a desired vocation. Perspectives regarding disclosure varied. Participants wished to be approached like any other healthy adolescent. Expectations regarding work participation were positively expressed.

Conclusion

This study showed that participants often disregarded having JIA when making plans for their future career. Facilitating an open discussion about the possible limitations accompanying JIA with educators and employers might prevent overburden and increase the chance of starting a career which would accommodate the patient with JIA in the near and distant future.
Maternal high-fat diet induces sex-specific changes to glucocorticoid and inflammatory signaling in response to corticosterone and lipopolysaccharide challenge in adult rat offspring
Authors: Wijenayake Sanoji , Rahman Mouly F. , Lum Christine M. W. , De Vega Wilfred C. , Sasaki Aya , McGowan Patrick O.
Published: April 2020

Background

Maternal obesity as a result of high levels of saturated fat (HFD) consumption leads to significant negative health outcomes in both mother and exposed offspring. Offspring exposed to maternal HFD show sex-specific alterations in metabolic, behavioral, and endocrine function, as well as increased levels of basal neuroinflammation that persists into adulthood. There is evidence that psychosocial stress or exogenous administration of corticosterone (CORT) potentiate inflammatory gene expression; however, the response to acute CORT or immune challenge in adult offspring exposed to maternal HFD during perinatal life is unknown. We hypothesize that adult rat offspring exposed to maternal HFD would show enhanced pro-inflammatory gene expression in response to acute administration of CORT and lipopolysaccharide (LPS) compared to control animals, as a result of elevated basal pro-inflammatory gene expression. To test this, we examined the effects of acute CORT and/or LPS exposure on pro and anti-inflammatory neural gene expression in adult offspring (male and female) with perinatal exposure to a HFD or a control house-chow diet (CHD).

Methods

Rat dams consumed HFD or CHD for four weeks prior to mating, during gestation, and throughout lactation. All male and female offspring were weaned on to CHD. In adulthood, offspring were ‘challenged’ with administration of exogenous CORT and/or LPS, and quantitative PCR was used to measure transcript abundance of glucocorticoid receptors and downstream inflammatory markers in the amygdala, hippocampus, and prefrontal cortex.

Results

In response to CORT alone, male HFD offspring showed increased levels of anti-inflammatory transcripts, whereas in response to LPS alone, female HFD offspring showed increased levels of pro-inflammatory transcripts. In addition, male HFD offspring showed greater pro-inflammatory gene expression and female HFD offspring exhibited increased anti-inflammatory gene expression in response to simultaneous CORT and LPS administration.

Conclusions

These findings suggest that exposure to maternal HFD leads to sex-specific changes that may alter inflammatory responses in the brain, possibly as an adaptive response to basal neuroinflammation.
Tumor sequencing is useful to refine the analysis of germline variants in unexplained high-risk breast cancer families
Authors: Van Marcke Cédric , Helaers Raphaël , De Leener Anne , Merhi Ahmad , Schoonjans Céline A. , Ambroise Jérôme , Galant Christine , Delrée Paul , Rothé Françoise , Bar Isabelle , Khoury Elsa , Brouillard Pascal , Canon Jean-Luc , Vuylsteke Peter , Machiels Jean-Pascal , Berlière Martine , Limaye Nisha , Vikkula Miikka , Duhoux François P.
Published: April 2020

Background

Multigene panels are routinely used to assess for predisposing germline mutations in families at high breast cancer risk. The number of variants of unknown significance thereby identified increases with the number of sequenced genes. We aimed to determine whether tumor sequencing can help refine the analysis of germline variants based on second somatic genetic events in the same gene.

Methods

Whole-exome sequencing (WES) was performed on whole blood DNA from 70 unrelated breast cancer patients referred for genetic testing and without a BRCA1, BRCA2, TP53, or CHEK2 mutation. Rare variants were retained in a list of 735 genes. WES was performed on matched tumor DNA to identify somatic second hits (copy number alterations (CNAs) or mutations) in the same genes. Distinct methods (among which immunohistochemistry, mutational signatures, homologous recombination deficiency, and tumor mutation burden analyses) were used to further study the role of the variants in tumor development, as appropriate.

Results

Sixty-eight patients (97%) carried at least one germline variant (4.7 ± 2.0 variants per patient). Of the 329 variants, 55 (17%) presented a second hit in paired tumor tissue. Of these, 53 were CNAs, resulting in tumor enrichment (28 variants) or depletion (25 variants) of the germline variant. Eleven patients received variant disclosure, with clinical measures for five of them. Seven variants in breast cancer-predisposing genes were considered not implicated in oncogenesis. One patient presented significant tumor enrichment of a germline variant in the oncogene ERBB2, in vitro expression of which caused downstream signaling pathway activation.

Conclusion

Tumor sequencing is a powerful approach to refine variant interpretation in cancer-predisposing genes in high-risk breast cancer patients. In this series, the strategy provided clinically relevant information for 11 out of 70 patients (16%), adapted to the considered gene and the familial clinical phenotype.
Ethical issues in cluster randomized trials conducted in low- and middle-income countries: an analysis of two case studies
Authors: Choko Augustine T. , Roshandel Gholamreza , Conserve Donaldson F. , Corbett Elizabeth L. , Fielding Katherine , Hemming Karla , Malekzadeh Reza , Weijer Charles
Published: April 2020

Background

Cluster randomized trials are common in health research in low- and middle-income countries raising issues that challenge interpretation of standard ethical guidelines. While the Ottawa Statement on the ethical design and conduct of cluster randomized trials provides guidance for researchers and research ethics committees, it does not explicitly focus on low- and middle-income settings.

Main body

In this paper, we use the lens of the Ottawa Statement to analyze two cluster randomized trials conducted in low- and middle-income settings in order to identify gaps or ethical issues requiring further analysis and guidance. The PolyIran trial was a parallel-arm, cluster trial examining the effectiveness of a polypill for prevention of cardiovascular disease in Golestan province, Iran. The PASTAL trial was an adaptive, multistage, parallel-arm, cluster trial evaluating the effect of incentives for human immunodeficiency virus self-testing and follow-up on male partners of pregnant women in Malawi. Through an in-depth case analysis of these two studies we highlight several issues in need of further exploration. First, standards for verbal consent and waivers of consent require methods for operationalization if they are to be employed consistently. Second, the appropriate choice of a control arm remains contentious. Particularly in the case of implementation interventions, locally available care is required as the comparator to address questions of comparative effectiveness. However, locally available care might be lower than standards set out in national guidelines. Third, while the need for access to effective interventions post-trial is widely recognized, it is often not possible to guarantee this upfront. Clarity on what is required of researchers and sponsors is needed. Fourth, there is a pressing need for ethics education and capacity building regarding cluster randomized trials in these settings.

Conclusion

We identify four issues in cluster randomized trials conducted in low- and middle-income countries for which further ethical analysis and guidance is required.
Disease features associated with a low disease impact in patients with psoriatic arthritis: results of a cross-sectional multicenter study
Authors:   on behalf of the MAAPS study group, Queiro Ruben , Cañete Juan D. , Montoro María , Gómez Susana , Cábez Ana
Published: April 2020

Background

Patient-reported outcomes measures, such as those provided by the Psoriatic Arthritis Impact of Disease (PsAID) questionnaire, have been found to be a reliable indicator of change during treatment, predictive of long-term outcomes, and the impact of psoriatic arthritis (PsA) on patients’ lives. The objective of the study was to describe the demographic and clinical characteristics of PsA patients with a low disease impact and to analyze predictive factors for that state.

Methods

Post hoc analysis of a cross-sectional multicenter study that included 223 consecutive patients. PsAID questionnaire was used to estimate disease impact. Patients with a PsAID < 4 were considered in low disease impact. Minimal disease activity (MDA) response and the Health Assessment Questionnaire (HAQ) were also assessed. The degree of agreement between the different outcomes was addressed by Cohen’s kappa index.

Results

One hundred and twenty-two (54.7%) patients reached a PsAID < 4. Among them, 52.0% and 68.0% presented articular or skin remission, respectively. Almost 75% of patients were in MDA state and 85.2% presented a low disability state according to the HAQ. A moderate concordance between HAQ ≤ 0.5 and PsAID < 4 (k = 0.53), fair between MDA and PsAID < 4 (k = 0.36), and moderate between DAPSA remission and PsAID < 4 (k = 0.46) was observed. Multivariate logistic regression analysis showed that patients with distal interphalangeal joint (DIP) disease (OR 0.40, 95%CI, 0.20–0.79, p = 0.009), family history of PsA (OR 0.25, 95%CI, 0.09–0.72, p = 0.010), and higher C-reactive protein (OR 0.92, 95%CI, 0.85–0.99, p = 0.036) were significantly less likely to reach a PsAID < 4.

Conclusions

There is certain discrepancy between disease activity measures and a low impact of disease in PsA. Clinical features (DIP joint involvement), biologic activity, and genetic factors (familial history) seem to be associated with lower odds of reaching a low disease impact.
Knockdown of lncRNA PVT1 alleviates high glucose-induced proliferation and fibrosis in human mesangial cells by miR-23b-3p/WT1 axis
Authors: Zhong Wen , Zeng Jiaoe , Xue Junli , Du Aimin , Xu Yancheng
Published: April 2020

Background

Diabetic nephropathy (DN) is a severe complication of diabetes with type 1 and 2. Long non-coding RNAs (lncRNAs) are being found to be involved in the DN pathogenesis. In this study, we aimed to further explore the effect and underlying mechanism of plasmacytoma variant translocation 1 (PVT1) in DN pathogenesis.

Methods

The expression levels of PVT1, miR-23b-3p, and Wilms tumor protein 1 (WT1) mRNA were assessed by quantitative real-time polymerase chain reaction (qRT-PCR). Western blot analysis was performed to determine protein expression. Cell proliferation was detected using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetr-azolium (MTS) assay. The targeted correlation between miR-23b-3p and PVT1 or WT1 was verified by dual-luciferase reporter assay.

Results

PVT1 and WT1 were highly expressed in the serum of DN patients and high glucose (HG)-induced mesangial cells (MCs). The knockdown of PVT1 or WT1 ameliorated HG-induced proliferation and fibrosis in MCs. Mechanistically, PVT1 modulated WT1 expression through acting as a molecular sponge of miR-23b-3p. The miR-23b-3p/WT1 axis mediated the protective effect of PVT1 knockdown on HG-induced proliferation and fibrosis in MCs. The NF-κB pathway was involved in the regulatory network of the PVT1/miR-23b-3p/WT1 axis in HG-induced MCs.

Conclusion

Our study suggested that PVT1 knockdown ameliorated HG-induced proliferation and fibrosis in MCs at least partially by regulating the miR-23b-3p/WT1/NF-κB pathway. Targeting PVT1 might be a potential therapeutic strategy for DN treatment.
Effect of circulating exosomes derived from normal-weight and obese women on gluconeogenesis, glycogenesis, lipogenesis and secretion of FGF21 and fetuin A in HepG2 cells
Authors: Afrisham Reza , Sadegh-Nejadi Sahar , Meshkani Reza , Emamgholipour Solaleh , Paknejad Maliheh
Published: April 2020

Background

It is generally accepted that obesity can lead to metabolic disorders such as NAFLD and insulin resistance. However, the underlying mechanism has been poorly understood. Moreover, there is evidence to support the possible role of exosomes in the metabolic homeostasis regulation. Accordingly, we aimed to determine the effect of plasma circulating exosomes derived from obese and normal-weight women on insulin signaling and the secretion of hepatokines in human liver cells.

Methods

Plasma exosomes isolated from four obese (O-Exo) women and four normal-weight (N-Exo) female candidates were characterized for size, zeta potential, and CD63 protein expression and were used for stimulation of HepG2 cells. Then, cell viability, as well as levels of glycogen and triglyceride (TG), were evaluated. Levels of fetuin-A and FGF21 were measured using the ELISA kit. Expression of glucose 6-phosphatase (G6pase) and phosphoenolpyruvate carboxykinase (PEPCK) genes were determined using qRT-PCR. Western blot analysis was carried out to evaluating the phosphorylation of GSK3β.

Results

The TG levels increased significantly in the cells treated with O-Exo than the control (vehicle) group (P = 0.005) and normal-weight group (P = 0.018). Levels of p-GSK3β and glycogen were significantly reduced by O-Exo in comparison with control (P = 0.002, P = 0.018, respectively). The mRNA expression of G6pase and PEPCK enzymes increased in the cells treated with O-Exo in comparison with the vehicle group (P = 0.017, P = 0.010, respectively). The levels of FGF21 in the supernatant of cells treated with O-Exo and N-Exo were significantly lower than the control group (P = 0.007).

Conclusion

It appears that obesity-related circulating exosomes can impair insulin signaling pathways and associated components, increase intracellular TG content, and decrease FGF21 secretion in the hepatocytes.
Epinephrine auto-injector needle length
Authors: Dreborg Sten , Tsai Gina , Kim Harold
Published: April 2020

Background

Epinephrine auto-injectors are expected to deliver the drug intramuscularly.

Objective

To study whether injection through clothing influences the frequency of subcutaneous and intraosseous/periosteal deposition of epinephrine.

Methods

Skin to muscle and skin to bone distances were measured for 303 children and adolescents and 99 adults. Distance was determined by ultrasound, with high or low pressure on the ultrasound probe. The risk/percentage of subcutaneous and intraosseous/periosteal injections was calculated using the lower and upper limits for the authority-approved length of EAI needles as provided by two high pressure EAI manufacturers and one low pressure EAI manufacturer. The addition winter clothing on the delivery of epinephrine was illustrated by comparing drug delivery fissue depth with no clothes. Furthermore, the riof non-intramuscular delivery for the shortest and longest approved needle length was calculated.

Results

When using EpipenJr® in children < 15 kg the risk of intraosseous/periostal injection was reduced from 1% and 59% for the shortest and longest approved needle length to 0 and 15% with winter clothes. The Auvi-Q® 0.1 mg had no risk of intraosseous/periosteal injection. However, the subcutaneous deposition risk increased from 94% and 28% to 100% and 99% with winter clothes. The risk of subcutaneous injection using EpipenJr® in the youngest children increased from 13% and 0% to 81% and 1% with winter clothes, and with Epipen® in adults from 45% and 17% to 60% and 38%. Emerade®, had a risk of subcutaneous injection in adults increasing from 14% and 10% to 28% and 21% adding winter clothes.

Conclusion

The risk of intraosseous/periosteal injections decreases and the risk of subcutaneous injection increases when injecting through winter clothes for all EAIs.
Sex differences in cancer mechanisms
Authors: Rubin Joshua B. , Lagas Joseph S. , Broestl Lauren , Sponagel Jasmin , Rockwell Nathan , Rhee Gina , Rosen Sarah F. , Chen Si , Klein Robyn S. , Imoukhuede Princess , Luo Jingqin
Published: April 2020

We now know that cancer is many different diseases, with great variation even within a single histological subtype. With the current emphasis on developing personalized approaches to cancer treatment, it is astonishing that we have not yet systematically incorporated the biology of sex differences into our paradigms for laboratory and clinical cancer research. While some sex differences in cancer arise through the actions of circulating sex hormones, other sex differences are independent of estrogen, testosterone, or progesterone levels. Instead, these differences are the result of sexual differentiation, a process that involves genetic and epigenetic mechanisms, in addition to acute sex hormone actions. Sexual differentiation begins with fertilization and continues beyond menopause. It affects virtually every body system, resulting in marked sex differences in such areas as growth, lifespan, metabolism, and immunity, all of which can impact on cancer progression, treatment response, and survival. These organismal level differences have correlates at the cellular level, and thus, males and females can fundamentally differ in their protections and vulnerabilities to cancer, from cellular transformation through all stages of progression, spread, and response to treatment. Our goal in this review is to cover some of the robust sex differences that exist in core cancer pathways and to make the case for inclusion of sex as a biological variable in all laboratory and clinical cancer research. We finish with a discussion of lab- and clinic-based experimental design that should be used when testing whether sex matters and the appropriate statistical models to apply in data analysis for rigorous evaluations of potential sex effects. It is our goal to facilitate the evaluation of sex differences in cancer in order to improve outcomes for all patients.