bluuebunny/crossref_metadata_2025 huggingface dataset:
Deciphering the activation and recognition mechanisms of Staphylococcus aureus response regulator ArlR
Authors: Ouyang Zhenlin , Zheng Fang , Chew Jared Y , Pei Yingmei , Zhou Jinhong , Wen Keqing , Han Miao , Lemieux M Joanne , Hwang Peter M , Wen Yurong
Published: October 2019

Staphylococcus aureus ArlRS is a key two-component regulatory system necessary for adhesion, biofilm formation, and virulence. The response regulator ArlR consists of a C-terminal DNA-binding effector domain and an N-terminal receiver domain that is phosphorylated by ArlS, the cognate transmembrane sensor histidine kinase. We demonstrate that the receiver domain of ArlR adopts the canonical α5β5 response regulator assembly, which dimerizes upon activation, using beryllium trifluoride as an aspartate phosphorylation mimic. Activated ArlR recognizes a 20-bp imperfect inverted repeat sequence in the ica operon, which is involved in intercellular adhesion polysaccharide production. Crystal structures of the inactive and activated forms reveal that activation induces a significant conformational change in the β4-α4 and β5-α5-connecting loops, in which the α4 and α5 helices constitute the homodimerization interface. Crystal structures of the DNA-binding ArlR effector domain indicate that it is able to dimerize via a non-canonical β1–β2 hairpin domain swapping, raising the possibility of a new mechanism for signal transduction from the receiver domain to effector domain. Taken together, the current study provides structural insights into the activation of ArlR and its recognition, adding to the diversity of response regulation mechanisms that may inspire novel antimicrobial strategies specifically targeting Staphylococcus.
Analysis of the structural variability of topologically associated domains as revealed by Hi-C
Authors: Sauerwald Natalie , Singhal Akshat , Kingsford Carl
Published: October 2019

Three-dimensional chromosome structure plays an integral role in gene expression and regulation, replication timing, and other cellular processes. Topologically associated domains (TADs), building blocks of chromosome structure, are genomic regions with higher contact frequencies within the region than outside the region. A central question is the degree to which TADs are conserved or vary between conditions. We analyze 137 Hi-C samples from 9 studies under 3 measures to quantify the effects of various sources of biological and experimental variation. We observe significant variation in TAD sets between both non-replicate and replicate samples, and provide initial evidence that this variability does not come from genetic sequence differences. The effects of experimental protocol differences are also measured, demonstrating that samples can have protocol-specific structural changes, but that TADs are generally robust to lab-specific differences. This study represents a systematic quantification of key factors influencing comparisons of chromosome structure, suggesting significant variability and the potential for cell-type-specific structural features, which has previously not been systematically explored. The lack of observed influence of heredity and genetic differences on chromosome structure suggests that factors other than the genetic sequence are driving this structure, which plays an important role in human disease and cellular functioning.
Renal outcomes in adult patients with horseshoe kidney
Authors: Kang Minjung , Kim Yong Chul , Lee Hajeong , Kim Dong Ki , Oh Kook-Hwan , Joo Kwon Wook , Kim Yon Su , Chin Ho Jun , Han Seung Seok
Published: October 2019

Background

  Horseshoe kidney (HSK) is a congenital disorder that is usually asymptomatic, but that increases the risks of kidney stones and infectious disease. However, renal outcomes such as end-stage renal disease (ESRD) in patients with HSK remain unclear.

Methods

In total, 146 patients with HSK (age of ≥20 years) from two tertiary hospitals were included in this study. Control individuals who underwent medical check-ups were selected by matching for age, sex, serum creatinine level, hypertension and diabetes. The hazard ratios (HRs) for the risks of ESRD and all-cause mortality were calculated after adjustment for multiple variables.

Results

The proportions of HSK-related complications for obstruction, kidney stones, urinary tract infection and urogenital cancer were 26, 25, 19 and 4%, respectively. During the median follow-up period of 9 years (maximum 32 years), the incidence of ESRD was 2.6/10 000 person-years. The risk of ESRD in patients with HSK was higher than in control individuals [adjusted HR = 7.6; 95% confidence interval (CI) 1.14–50.47]. All-cause mortality did not differ between the two groups (adjusted HR = 0.6; 95% CI 0.08–4.29).

Conclusions

Patients with HSK are at risk of ESRD, which may be attributable to the high prevalence of complications. Accordingly, these patients should be regarded as having chronic kidney disease and require regular monitoring of both kidney function and potential complications.
Interrelationships between molecular subtype, anatomical location, and extent of resection in diffuse glioma: a systematic review and meta-analysis
Authors: De Leeuw Beverly I , Van Baarsen Kirsten M , Snijders Tom J , Robe Pierre A J T
Published: October 2019

Background

The introduction of the 2016 WHO Classification of Tumors of the Central Nervous System has resulted in tumor groupings with improved prognostic value for diffuse glioma patients. Molecular subtype, primarily based on IDH-mutational status and 1p/19q-status, is a strong predictor of survival. It is unclear to what extent this finding may be mediated by differences in anatomical location and surgical resectability among molecular subgroups. Our aim was to elucidate possible correlations between (1) molecular subtype and anatomical location and (2) molecular subtype and extent of resection.

Methods

We performed a systematic review of literature searching for studies on molecular subtype in relation to anatomical location and extent of resection. Only original data concerning adult participants suffering from cerebral diffuse glioma were included. Studies adopting similar outcomes measures were included in our meta-analysis.

Results

In the systematic analysis for research questions 1 and 2, totals of 20 and 9 studies were included, respectively. Study findings demonstrated that IDH-mutant tumors were significantly more frequently located in the frontal lobe and less often in the temporal lobe compared with IDH-wildtype gliomas. Within the IDH-mutant group, 1p/19q-codeleted tumors were associated with more frequent frontal and less frequent temporal localization compared with 1p/19q-intact tumors. In IDH-mutant gliomas, greater extent of resection was achieved than in IDH-wildtype tumors.

Conclusions

Genetic profile of diffuse cerebral glioma influences their anatomical location and seems to affect tumor resectability.
Long-term trends in glioblastoma survival: implications for historical control groups in clinical trials
Authors: Sheikh Shehryar , Radivoyevitch Tom , Barnholtz-Sloan Jill S , Vogelbaum Michael
Published: October 2019

Background

Historical controls continue to be used in early-phase brain tumor trials. We aim to show that historical changes in survival trends for glioblastoma (GBM) call into question the use of noncontemporary controls.

Methods

We analyzed data from 46 106 primary GBM cases from the SEER database (1998-2016). We performed trend analysis on survival outcomes (2-year survival probability, median survival, and hazard ratios) and patient characteristics (age, sex, resection extent, and treatment type).

Results

In 2005-2016 (ie, the post–Stupp protocol era), fitting a parameter independently to each year, there was a demonstrable increase in median survival (R2 = 0.81, P < .001) and 2-year survival probability (R2 = 0.55, P = .006) for GBM. Trend analysis of the hazard ratio showed a significant time-dependent downward trend (R2 = 0.62, P = .002). When controlling, via multivariable Cox regression modeling, for age, sex, resection extent, and treatment type, there was a persistent downward trend in hazard ratios with increases in calendar time, especially in the most recent data.

Conclusion

Contemporary GBM patients face a different overall hazard profile from their historical counterparts, which is evident in changes in measures of patient survival and parametric hazard modeling. Though there was a plateau in these measures before 2005 (pre–Stupp protocol), there is no evidence of a new plateau in recent years even when controlling for known prognostic factors (age, sex, resection extent, and treatment type), suggesting that it may be insufficient to match contemporary patients and noncontemporary controls on the basis of these factors.
Social media partnerships with patient organizations for neuro-oncology patient recruitment
Authors: Claus Elizabeth B , Feliciano Josemari , Benz Luke S , Calvocoressi Lisa
Published: October 2019

Background

In neuro-oncology, traditional methods of enrolling the large numbers of participants required for studies of disease etiology and treatment response are costly, labor intensive, and may not include patients in regions without tumor registries.

Methods

In the Yale Acoustic Neuroma (AN) Study and International Low-Grade Glioma (LGG) Registry, we partnered with several brain tumor patient organizations to develop social media enrollment campaigns and use web-based data collection resources at the Yale University School of Public Health to test alternative methods to enroll neuro-oncology patients for epidemiologic study.

Results

In the AN study, we enrolled 1024 patients over 2 years. Of these, 865 patients completed the online questionnaire, 697 returned written consent, 583 sent a pathology report, and 569 returned a saliva specimen. The completed 569 participants did not differ by age or treatment from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) data but were more likely to be female (67% vs 52%) and white (94.8% vs 84%). Patients learned of the study through the Acoustic Neuroma Association (ANA) website (61.3%), ANA support group members (18%), and social media (primarily Facebook). Costs per patient enrolled were approximately 10% to 20% that of traditional registry-based enrollment methods. Results for the LGG study were similar.

Conclusions

Although additional effort will be required to ensure a diverse participant population, partnership with established patient organizations along with use of web-based technology and social media allowed for the successful enrollment of neuro-oncology patients at a fraction of the cost relative to traditional methods.
A chemical perspective on high pressure crystal structures and properties
Authors: Tse John S
Published: October 2019

The general availability of third generation synchrotron sources has ushered in a new era of high pressure research. The crystal structure of materials under compression can now be determined by X-ray diffraction using powder samples and, more recently, from multi-nano single crystal diffraction. Concurrently, these experimental advancements are accompanied by a rapid increase in computational capacity and capability, enabling the application of sophisticated quantum calculations to explore a variety of material properties. One of the early surprises is the finding that simple metallic elements do not conform to the general expectation of adopting 3D close-pack structures at high pressure. Instead, many novel open structures have been identified with no known analogues at ambient pressure. The occurrence of these structural types appears to be random with no rules governing their formation. The adoption of an open structure at high pressure suggested the presence of directional bonds. Therefore, a localized atomic hybrid orbital description of the chemical bonding may be appropriate. Here, the theoretical foundation and experimental evidence supporting this approach to the elucidation of the high pressure crystal structures of group I and II elements and polyhydrides are reviewed. It is desirable and advantageous to extend and apply established chemical principles to the study of the chemistry and chemical bonding of materials at high pressure.
Targeting cancer stem cells in squamous cell carcinoma
Authors: Chen Demeng , Wang Cun-Yu
Published: October 2019

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive tumor and the sixth most common cancer worldwide. Current treatment strategies for HNSCC are surgery, radiotherapy, chemotherapy, immunotherapy or combinatorial therapies. However, the overall 5-year survival rate of HNSCC patients remains at about 50%. Cancer stem cells (CSCs), a small population among tumor cells, are able to self-renew and differentiate into different tumor cell types in a hierarchical manner, similar to normal tissue. In HNSCC, CSCs are proposed to be responsible for tumor initiation, progression, metastasis, drug resistance, and recurrence. In this review, we discuss the molecular and cellular characteristics of CSCs in HNSCC. We summarize current approaches used in the literature for identification of HNSCC CSCs, and mechanisms required for CSC regulation. We also highlight the role of CSCs in treatment failure and therapeutic targeting options for eliminating CSCs in HNSCC.
Increasing uptake of National Health Service Health Checks in primary care: a pragmatic randomized controlled trial of enhanced invitation letters in Northamptonshire, England
Authors: Sallis A , Gold N , Agbebiyi A , James R J E , Berry D , Bonus A , Vlaev I , Chadborn T
Published: October 2019

Background

Uptake of NHS Health Checks (NHSHCs) is sub-optimal. This study aimed to increase their uptake using behaviourally informed invitation letters.

Method

Patients registered with 6 general practices in Northamptonshire, England who were eligible for an NHSHC between 10 February 2014 and 31 January 2015 were randomized monthly, using a random number generator, to three trial arms: control (standard invitation), sunk costs (resources already allocated) and counterargument (against common barriers to attendance). The outcome measure was uptake of NHSHC by 12 weeks after 31 January.

Results

In total, 6331 patients were randomized. After exclusions, due to ineligibility for the NHSHC, data were analysed for N = 6313 patients: N = 2123 control; N = 2085 counterargument; N = 2105 sunk costs. Overall, 2364 (37.45%) patients attended an NHSHC. Both intervention letters increased uptake compared to control, by 5.46% using counterargument (adjusted odds ratio (AOR) 1.32, CI 1.162–1.51, p < 0.001) and 4.33% using sunk costs (AOR 1.246, CI 1.10–1.42, p < 0.001), with no significant difference between the two.

Conclusion

Behaviourally informed invitation letters, containing sunk costs or counterargument messages, can improve the uptake of NHSHCs. The trial was registered with the International Standard Randomised Controlled Trial Registration Number Scheme (ISRCTN57110614).
Engineered chitosan for improved 3D tissue growth through Paxillin-FAK-ERK activation
Authors: Kafi Md Abdul , Aktar Khudishta , Todo Mitsugu , Dahiya Ravinder
Published: October 2019

Scaffold engineering has attracted significant attention for three-dimensional (3D) growth, proliferation and differentiation of stem cells in vitro. Currently available scaffolds suffer from issues such as poor ability for cell adhesion, migration and proliferation. This paper addresses these issues with 3D porous chitosan scaffold, fabricated and functionalized with cysteine-terminated Arg-Gly-Asp (Cys-RGD) tri-peptide on their walls. The study reveals that the compressive moduli of the scaffold is independent to RGD functionalization but shows dependence on the applied freezing temperature (TM) during the fabrication process. The low freezing TM (−80°C) produces scaffold with high compressive moduli (14.64 ± 1.38 kPa) and high TM (−30°C) produces scaffold with low compressive moduli (5.6 ± 0.38 kPa). The Cys-RGD functionalized scaffolds lead to significant improvements in adhesion (150%) and proliferation (300%) of human mesenchymal stem cell (hMSC). The RGD-integrin coupling activates the focal adhesion signaling (Paxillin-FAK-ERK) pathways, as confirmed by the expression of p-Paxillin, p-FAK and p-ERK protein, and results in the observed improvement of cell adhesion and proliferation. The proliferation of hMSC on RGD functionalized surface was evaluated with scanning electron microscopy imaging and distribution though pore was confirmed by histochemistry of transversely sectioned scaffold. The hMSC adhesion and proliferation in scaffold with high compressive moduli showed a constant enhancement (with a slope value 9.97) of compressive strength throughout the experimental period of 28 days. The improved cell adhesion and proliferation with RGD functionalized chitosan scaffold, together with their mechanical stability, will enable new interesting avenues for 3D cell growth and differentiation in numerous applications including regenerative tissue implants.
Does Advertising Serve as a Signal? Evidence from a Field Experiment in Mobile Search
Authors: Sahni Navdeep S , Nair Harikesh S
Published: October 2019

We develop a field experiment that assesses whether advertising can serve as a signal that enhances consumers’ evaluations of advertised goods. We implement the experiment on a mobile search platform that provides listings and reviews for an archetypal experience good, restaurants. In collaboration with the platform, we randomize about 200,000 users in 13 Asian cities into exposure of ads for about 600+ local restaurants. Within the exposure group, we randomly vary the disclosure to the consumer of whether a restaurant’s listing is a paid-ad. This enables isolating the effect on outcomes of a user knowing that a listing is sponsored—a pure signalling effect. We find that this disclosure increases calls to the restaurant by 77%, holding fixed all other attributes of the ad. The disclosure effect is higher when the consumer uses the platform away from his typical city of search, when the uncertainty about restaurant quality is larger, and for restaurants that have received fewer ratings in the past. On the supply side, newer, higher rated and more popular restaurants are found to advertise more on the platform; and ratings of those that advertised during the experiment are found to be higher two years later. Taken together, we interpret these results as consistent with a signalling equilibrium in which ads serve as implicit signals that enhance the appeal of the advertised restaurants to consumers. Both consumers and advertisers seem to benefit from the signalling. Consumers shift choices towards restaurants that are better rated (at baseline) in the disclosure group compared to the no disclosure group, and advertisers gain from the improved outcomes induced by disclosure.
The Equity Premium and the One Percent
Authors: Toda Alexis Akira , Walsh Kieran James
Published: October 2019

We show that in a general equilibrium model with heterogeneity in risk aversion or belief, shifting wealth from an agent who holds comparatively fewer stocks to one who holds more reduces the equity premium. From an empirical view, the rich hold more stocks, so inequality should predict excess stock market returns. Consistent with our theory, we find that when the U.S. top ($\textrm{e.g.}$, 1%) income share rises, subsequent 1-year excess market returns significantly decline. This negative relation is robust to controlling for classic return predictors, predicting out-of-sample, and instrumenting inequality with estate tax rate changes. It also holds in international markets.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
P41 Art therapy and rheumatology: using a collaborative approach to address the emotional needs of a child with Marfan syndrome
Authors: Watts Patricia , Walsh Jo
Published: October 2019

Background

1:1 art therapy sessions have been offered to rheumatology patients at the Royal Hospital for Children, Glasgow since 2012, supported by the Teapot Trust. A relationship is established between child and Therapist, allowing safe exploration of difficult issues. We describe a new way of collaborative working to include input from other professionals within therapy sessions.

Methods

A 10 year-old girl was referred to art therapy by the consultant rheumatologist to help her process an existing diagnosis of Marfan syndrome. She displayed intense anger towards her family, lost all confidence socialising and became extremely distressed when having medical examinations.

The child identified anger towards her family was because she perceived a lack of honesty about her condition making her feel worried she would die, which in turn prevented her from socialising. The child noticed she became distressed when clinicians didn’t ask permission to examine her.

It was apparent that the child needed a joined up approach with the art therapist and consultant rheumatologist collaborating to communicate the child’s views to all professionals involved, which at times involved the consultant rheumatologist joining art therapy sessions.

The child identified her own goals for art therapy: Not saying mean things when I’m angry and think of other ways to express my anger Get my confidence back

Progress in therapy was measured using Goal Based Outcomes and Psychlops Outcome Measurement Tools allowing the child to report on her own progress.

Results

Through Goal Based Outcomes, she communicated her anger ‘was getting better’ and she felt confident enough ‘to go on a trampoline’. Family sessions were used to help the child speak honestly with her parents about her diagnosis and prognosis. Having her consultant rheumatologist at sessions enabled her to ask questions like ‘why do I have this,’ ‘will I die’ and ‘can I go on roller coasters.’

Through Psychlops, she communicated her anger was related to feeling embarrassed and exposed during examinations. The art therapist supported the child to explore her body boundaries and to create rules clinicians should follow when examining her. The consultant rheumatologist shared these rules with the rheumatology MDT. The MDT encouraged the child to create a poster to be displayed in the paediatric outpatient clinic, which raised her confidence.

At subsequent medical examinations she has been able to communicate her wishes to clinicians instead of becoming distressed. The child is also socialising more and can communicate her feelings at home without becoming angry.

Conclusion

This collaborative approach supported the child to process her diagnosis by creating a safe and honest space for her feelings to be explored whilst reducing barriers to engaging with clinicians. We have since used this methodology with other members of the rheumatology MDT.

Conflicts of Interest

The authors declare no conflicts of interest.
Treatment with cyclophosphamide i.v. pulse therapy is an option for effective treatment of skin fibrosis in patients with early systemic sclerosis
Authors: Kersten Brigit E , den Broeder Nathan , van den Hoogen Frank H J , Knaapen-Hans Hanneke A K , van den Ende Cornelia H M , Vonk Madelon C
Published: October 2019

Objectives

SSc is a autoimmune disease characterized by fibrosis of the skin and internal organs. There is a lack of evidence for the efficacy of i.v. CYC pulse therapy on skin thickening. We aimed to examine the response of i.v. CYC pulse therapy on skin thickening in our cohort of SSc patients and analysed factors that predict this response.

Methods

We retrospectively evaluated the data for 143 patients with SSc from baseline to 12, 24 and 36 months. All patients were treated with at least 6 i.v. CYC pulses (750 mg/m2/month). We applied the modified Rodnan Skin Score (mRSS) to assess skin thickening. A clinically relevant response was defined as a decrease in mRSS of 5 points and 25% from baseline. Different baseline variables for predicting response on month 12 were tested in logistic regression analyses.

Results

Baseline characteristics of the patients with dcSSc and lcSSc were collected. Forty-three percent (n = 42) of dcSSc patients had a clinically relevant response on month 12. Non-responding on month 6 predicts non-response on month 12 (odds ratio 37.1; 95% CI 4.5, 306.4).

Conclusion

We concluded that i.v. CYC pulse therapy should be considered as an effective treatment option for skin thickening in dcSSc patients, because 43% of this group of patients were found to have a clinically relevant response. Of the dcSSC patients who did not respond by month 6, only 29% had a response by month 12. This finding can help the physician and patient in shared decision making about whether or not to continue therapy.
The effect of emotion regulation on risk-taking and decision-related activity in prefrontal cortex
Authors: Morawetz Carmen , Mohr Peter N C , Heekeren Hauke R , Bode Stefan
Published: October 2019

Emotion regulation impacts the expected emotional responses to the outcomes of risky decisions via activation of cognitive control strategies. However, whether the regulation of emotional responses to preceding, incidental stimuli also impacts risk-taking in subsequent decisions is still poorly understood. In this study, we investigated the interplay between the regulation of incidentally induced emotional responses and subsequent choice behavior using a risky decision-making task in two independent samples (behavioral and functional magnetic resonance imaging experiment). We found that overall, emotion regulation was followed by less risky decisions, which was further reflected in an increase in activation in brain regions in dorsolateral and ventrolateral prefrontal cortex and cingulate cortex. These findings suggest that altering incidental emotions using reappraisal strategies impacts on subsequent risk-taking in decision-making.
Knowledge production at the science–policy interface: Lessons from fisheries scientists
Authors: Olson Julia , Pinto da Silva Patricia
Published: October 2019

While fisheries science in the USA has in the past been dominated by mode 1 knowledge production that is discipline-specific and focused on basic research, it has increasingly opened up to concerns with relevance, participation, and interdisciplinary inquiry. We consider how this transition has been experienced through the analysis of oral histories conducted with marine scientists, looking at the changes they have seen to their role as scientists and to the practice of doing science at the interface of knowledge production and policy. In particular, we examine scientists’ ideas about and experiences of collaboration, public responsibility, freedom and politics in science, diversity and outreach, involvement, and relevance to society. In so doing, we explore the implications of the co-production of science and policy as traditional domain boundaries are increasingly problematized.
Prevalence and risk factors for HIV-1 infection in people who use illicit drugs in northern Brazil
Authors: Oliveira-Filho Aldemir B , Silva Fabricio Quaresma , Santos Francisco Junior A , Cardoso Yasmin Maria N , Di Miceli Jeruza Ferraz F , Resque Rafael Lima , Silva-Oliveira Gláucia C , Martins Luisa Caricio , Pinheiro Luiz Marcelo L , Machado Luiz Fernando A , Pinto Aguinaldo Roberto , Lemos José Alexandre R , Fischer Benedikt , Kupek Emil
Published: October 2019

Background

People who use illicit drugs (PWUDs) have a high risk of viral infections. To date, there is a paucity of information on HIV infection among PWUDs in remote Brazilian regions. This study determined the prevalence and factors associated with HIV-1 infection among PWUDs in northern Brazil.

Methods

Sociodemographic, economic, drug use and health-related information were collected through interviews from a community-recruited, multi-site sample of 1753 PWUDs. The blood samples collected were tested for the presence of HIV-1 using chemiluminescence immunoassay and PCR or western blotting. Logistic regressions identified factors independently associated with HIV-1 infection.

Results

In total, 266 (15.2%) PWUDs were HIV-1 positive. Hepatitis B virus and/or hepatitis C virus nucleic acid was detected in 65 (3.7%) PWUDs infected by HIV-1. The factors associated with HIV-1 infection were male gender, older age, a lower educational level and a lower income, crack cocaine use, a longer drug use history and a history of drug injection and engagement in unsafe sex, sex work and a higher number of sexual partners.

Conclusions

The current study provides unique, initial insights into HIV and co-infection status and pertinent risk factors among PWUDs in northern Brazil, with clear and diverse implications for urgently improved prevention and treatment intervention needs.
Thaumatin-Like Protein-1 Gene (Bx-tlp-1) Is Associated with the Pathogenicity ofBursaphelenchus xylophilus
Authors: Meng Fanli , Li Yongxia , Wang Xuan , Feng Yuqian , Liu Zhenkai , Zhang Wei , Zhang Xingyao
Published: October 2019

The pine wood nematode Bursaphelenchus xylophilus is a destructive species affecting pine trees worldwide; however, the underlying mechanism leading to pathogenesis remains unclear. In this study, a B. xylophilus gene encoding thaumatin-like protein-1 (Bx-tlp-1) was silenced by RNA interference to clarify the relationship between the Bx-tlp-1 gene and pathogenicity. The in vitro knockdown of Bx-tlp-1 with double-stranded RNA (dsRNA) decreased B. xylophilus reproduction and pathogenicity. Treatments with dsRNA targeting Bx-tlp-1 decreased expression by 90%, with the silencing effect maintained even in the F3 offspring. Pine trees inoculated with B. xylophilus treated with Bx-tlp-1 dsRNA decreased the symptom of wilting, and the disease severity index was 56.7 at 30 days after inoculation. Additionally, analyses of the cavitation of intact pine stem samples by X-ray microtomography revealed that the xylem cavitation area of pine trees inoculated with B. xylophilus treated with Bx-tlp-1 dsRNA was 0.46 mm2at 30 days after inoculation. Results from this study indicated that the silencing of Bx-tlp-1 has effects on B. xylophilus fitness. The data presented here provide the foundation for future analyses of Bx-tlp-1 functions related to B. xylophilus pathogenicity.
The comprehensive pathophysiological changes in a novel rat model of postinflammatory visceral hypersensitivity
Authors: Ma Jing , Li Jianhui , Qian Meirui , He Nan , Cao Ying , Liu Yaping , Wu Kaichun , He Shuixiang
Published: October 2019

So far, a comprehensive animal model that can mimic both the central and peripheral pathophysiological changes of irritable bowel syndrome (IBS) is lacking. Here, we developed a novel IBS rat model combining trinitro‐benzene‐sulfonic acid (TNBS) and chronic unpredictable mild stress (CUMS) (designated as TC‐IBS) and compared it with the TNBS‐induced and CUMS‐induced models. TC‐IBS showed a pronounced depression phenotype with increased corticotropin‐releasing hormone receptor (CRHR)1 and CRHR2 expression at the frontal cortex and increased serum ACTH concentration. Visceral hypersensitivity (VH), as evidenced by colorectal distention (CRD) test, was highest in TC‐IBS, accompanied by increased serum 5‐hydroxytryptamine (5‐HT) level and colonic 5‐HT receptor 3A (5‐HT3AR)/5‐HT receptor 2B expression, impaired tight junction protein expression including occludin, zonula occludens‐1, and phosphorylated myosin light chain. Palonosetron, a second generation of 5‐HT3AR antagonist, alleviated VH significantly in TC‐IBS. 16S rRNA sequencing showed that TNBS plus CUMS induced a significant disturbance of the gut microbiota. Cytokine profile analysis of TC‐IBS model indicated an innate immune activation both in serum and colonic mucosa. Further, fecal microbiota transplantation improved VH and some pathophysiological changes in TC‐IBS. In summary, we established a postinflammatory IBS model covering multifactorial pathophysiological changes, which may help to develop therapies that target specific IBS subtype.—Ma, J., Li, J., Qian, M., He, N., Cao, Y., Liu, Y., Wu, K., He, S. The comprehensive pathophysiological changes in a novel rat model of postinflammatory visceral hypersensitivity. FASEB J. 33, 13560‐13571 (2019). www.fasebj.org
Nutrient Deficiency-Related Dermatoses after Bariatric Surgery
Authors: Chu Andy S. , Mataga Megan A. , Krueger Loren , Barr Priscilla A.
Published: October 2019

Obesity is a global epidemic that increases the risk of weight-related comorbidities in modern society. It is complex, multifactorial, and largely preventable. Noninvasive treatments for obesity include diet, exercise, and medication. However, bariatric surgeries are becoming popular procedures for those who do not achieve success with noninvasive weight management treatment. Bariatric surgeries often result in dietary restriction and/or malabsorption, which lead to drastic weight loss. Individuals who had bariatric surgeries need lifelong follow-up and monitoring to ensure adequate intake of nutrients. Nutrient deficiencies can ensue when long-term vitamin and mineral supplementation is not followed. Severe nutrient deficiencies may lead to dermatoses that can be corrected by nutrient repletion and careful monitoring. A case report of nutrient deficiency-related dermatoses is followed by a review of obesity and its treatments with a focus on bariatric surgeries.

GENERAL PURPOSE

To provide information on obesity, bariatric surgery, and the nutrient deficiency-related dermatoses that may result from these surgeries.

TARGET AUDIENCE

This continuing education activity is intended for physicians, physician assistants, NPs, and nurses with an interest in skin and wound care.

LEARNING OBJECTIVES/OUTCOMES

After participating in this educational activity, the participant should be better able to:

1. Examine issues related to obesity and bariatric surgery.

2. Identify the sources and role of specific nutrients.

3. Recognize the clinical signs and symptoms of nutrient deficiency following bariatric surgery.
Attitudes and Approaches Towards Repeat Valve Surgery in Recurrent Injection Drug Use-associated Infective Endocarditis: A Qualitative Study
Authors: Hayden Margaret , Moore Amber
Published: October 2019

Objective:

The aim of this study was to explore the diversity of attitudes and approaches towards treating patients with recurrent injection drug use-associated infective endocarditis (IDU-IE) with a focus on surgical decision-making.

Methods:

Nineteeen qualitative, semistructured interviews were performed with healthcare providers at a single academic medical center. Purposive sampling was used to recruit participants with the goal of sampling a diversity of providers involved in the care of patients with IDU-IE. An inductive, grounded theory approach was used to analyze data.

Results:

Nineteen healthcare providers (12 physicians, 3 social workers, 2 registered nurses, 2 advanced practice providers) with experience caring for patients with IDU-IE across a variety of disciplines and departments participated in the study. Three themes emerged from the interviews: providers feel underprepared to care for patients with IDU-IE; implicit and explicit bias remain pervasive; and criteria for surgical decision-making are not transparent. When discussing surgical decision-making, participants relied on 2 predominant bioethical concepts: futility and rationing.

Conclusions:

There was a wide divergence of opinions on how to approach repeat valve surgeries, ranging from those who endorsed strict single surgery policies to those who felt patients should be offered as many surgeries as needed. Therefore, there is a need to further develop general principles for the care of recurrent IDU-IE to provide more reliable and equitable care to these patients. This will require input from an interdisciplinary group and should address empirical data, and also the appropriateness of futility and rationing of care questions.
Screening prognosis-related genes in glioblastoma by microarray analysis
Authors: Wang Hongguang , Zhang Yi , Zhang Chen , Tong Xiaoguang
Published: October 2019

This study was aimed to explore the prognosis-related biomarkers in glioblastoma and guide the therapy. The gene expression profile of glioblastoma samples with different prognosis outcomes was downloaded from National Center of Biotechnology Information Gene Expression Omnibus. The differently expressed genes (DEGs) among different samples were identified through pairwise comparison via Limma package of R. The DEGs were clustered using the Mfuzz package of R. The clusters with gene expression increasing or decreasing with the prognosis were selected, and functional enrichment of the selected genes was analyzed via the Database for Annotation, Visualization and Integrated Discovery. A protein–protein interaction (PPI) network of the selected genes was constructed through the Search Tool for Retrieval of Interacting Proteins and visualized by Cytoscape. The Cancer Genome Atlas database and IVY-GAP database were used to verify the DEGs. We analyzed the correlation between subtypes and the DEGs. Totally, 2649 DEGs were identified and divided into 10 clusters. Expression value of the genes in clusters 2 and 9 kept increasing and decreasing, respectively, with the improved prognosis. The DEGs of cluster 2/9 were enriched in 23/24 Gene Ontology terms and 6/4 Kyoto Encyclopedia of Genes and Genomes pathways. Annotation of transcription factor binding sites of DEGs revealed that most genes were regulated by transcription factors. In the PPI network, CACNA1D, GNAO1, STAT3 and ERBB3 had 11, 11, 11 and 10 node degree, respectively. Bioinformatics methods could help to identify significant genes and pathways in glioblastoma. CACNA1D, GNAO1, STAT3 and ERBB3 might serve as the prognostic biomarkers in glioblastoma.
Investigating the Role of Childhood Adiposity in the Development of Adult Type 2 Diabetes in a 64-year Follow-up Cohort
Authors: Nianogo Roch A. , Arah Onyebuchi A.
Published: October 2019

Background:

The contribution of childhood obesity to adult type 2 diabetes (T2DM), not through adult adiposity, as well as the causal pathways through which childhood obesity increases adult T2DM risk are not well understood. This study investigated the contribution of childhood obesity to incident T2DM including pathways not through adult adiposity, and explored whether race modified this contribution.

Methods:

We used data from the Virtual Los Angeles Cohort, an agent-based longitudinal birth cohort composed of 98,230 simulated individuals born in 2009 and followed until age 65 years. We applied the parametric mediational g-formula to the causal mediation analysis investigating the impact of childhood obesity on the development of adult T2DM.

Results:

The marginal adjusted odds ratio (aOR) for the total effect of childhood obesity on adult T2DM was 1.37 (95% CI = 1.32, 1.46). Nearly all the effect of childhood obesity on adult T2DM was mostly attributable to pathways other than through adult obesity; the aOR for the pure direct effect was 1.36 (95% CI = 1.31, 1.41). In all racial subpopulations, a similar 3% of the total effect of childhood obesity on adult T2DM was attributable to its effect on adult obesity.

Conclusions:

Childhood obesity remains a risk factor for adult T2DM separate from its effects on adult obesity. This study emphasizes the potential benefits of early interventions and illustrates that agent-based simulation models could serve as virtual laboratories for exploring mechanisms in obesity research.
Hexokinase II Upregulation Contributes to Asiaticoside-Induced Protection of H9c2 Cardioblasts During Oxygen–Glucose Deprivation/Reoxygenation
Authors: Zhang Jing , Yao Mingyan , Jia Xinwei , Xie Junmin , Wang Yanfei
Published: October 2019

Asiaticoside (AS), one of the main functional components of Centella asiatica, has been reported to protect neurons from ischemia-hypoxia–induced injury. However, the role of AS in myocardial oxygen–glucose deprivation/reoxygenation (OGD/R) injury has not been investigated. The aim of this study was to investigate the role of AS in OGD/R-treated H9c2 cardiomyocytes and the underlying mechanism involved. Cell viability was detected using MTT assay. Cell apoptosis was measured using flow cytometry. The oxidative stress was assessed by detecting the malonaldehyde (MDA) content and activities of superoxide dismutase, glutathione peroxidase, and catalase (CAT). The glucose consumption and lactate production were determined to reflect glycolysis rate. The expression levels of hexokinase II (HK2) were detected using reverse transcription quantitative polymerase chain reaction and Western blot. H9c2 cells were transfected with small interfering RNA targeting HK2 (si-HK2) to knockdown HK2. Results showed that AS improved cell viability and inhibited apoptosis in OGD/R-injured H9c2 cells. AS pretreatment prevented OGD/R-induced oxidative stress, as evidenced by the decreased MDA content, and increased activities of superoxide dismutase, glutathione peroxidase, and CAT. The decreased glucose consumption and lactate production in OGD/R-injured H9c2 cells were reversed after AS treatment. Mechanically, AS induced the expression of HK2 in OGD/R-injured H9c2 cells. Knockdown of HK2 abolished the protective effects of AS on OGD/R-injured H9c2 cells. In conclusion, the protective effects of AS on cardiomyocytes from OGD/R-induced injury were mediated at least partly by upregulating HK2.
Systematic Review on the Content of Outcome Measurement Instruments on Scar Quality
Authors: Carrière Michelle E. , Kwa Kelly A. A. , de Haas Louise E. M. , Pijpe Anouk , Tyack Zephanie , Ket Johannes C. F. , van Zuijlen Paul P. M. , de Vet Henrica C. W. , Mokkink Lidwine B.
Published: October 2019

Background:

Measurements of scar quality are essential to evaluate the effectiveness of scar treatments and to monitor scars. A large number of scar scales and measurement devices have been developed, which makes instrument selection challenging. The aim of this study was to provide an overview of the content (ie, included items) of all outcome measurement instruments that measure scar quality in different types of scars (burn, surgical, keloid, and necrotizing fasciitis), and the frequency at which the instruments and included items are used.

Methods:

A systematic search was performed in PubMed and Embase.com up to October 31, 2018. All original studies reporting on instruments that measured at least 1 characteristic of scar quality were included and the instrument’s content was extracted.

Results:

We included 440 studies for data extraction. Included instruments (N = 909) were clinician-reported scales (41%), measurement devices (30%), patient-reported scales (26%), and combined clinician- and patient-reported scales (3%). The Observer scale of the Patient and Observer Scar Assessment Scale, the Cutometer, the Patient Scale of the Patient and Observer Scar Assessment Scale, and the modified Vancouver Scar Scale were the most often used instrument in each of these categories, respectively. The most frequent assessed items were thickness, vascularity, pigmentation, pliability, pain, and itch.

Conclusion:

The results of this study lay the foundation for our future research, which includes an international Delphi study among many scar experts, and an international focus group study among scar patients, aiming to elucidate how scar quality must be defined and measured from both professional and patient perspectives.
Successful Balanced Gait after Reconstruction of the Weight-bearing Mid Plantar Region Using a Free Contralateral Medial Plantar Flap
Authors: Karakawa Ryo , Yoshimatsu Hidehiko , Miyashita Hiroki , Kuramoto Yukiko , Shibata Tomoyoshi , Yano Tomoyuki
Published: October 2019

Although soft tissue sarcoma, especially in the sole of the foot, is a rare disease, weight-bearing region reconstruction considering postoperative gait is needed. For functionally satisfactory sole reconstruction, it is important to cover the weight-bearing region with a nonbulky but durable skin paddle that can withstand a significant amount of shear pressure. We herein present a case in which a free contralateral medial plantar flap was used for reconstruction of the weight-bearing mid plantar region for a 41-year-old man who suffered from mid-foot sarcoma. Gait analysis was performed 6 months after the operation with the lower limb loading gauge sheet, and the result indicated that postoperative balanced gait was obtained. The free medial plantar flap transfer after sole sarcoma resection has several advantages. First, the characteristic of this flap with solid anchoring to deep tissue to resist shearing makes it possible to lower the chances of postoperative ulceration. Second, the medial plantar flap has optimal thickness and good color and texture match for sole reconstruction. Third, a sensate flap can be achieved if the medial plantar nerve is included. Although further clinical investigations such as long-term follow-up will be required to confirm its efficacy, this method would be one option for treating sole sarcoma.
Evaluation of the Intraoperative Blood Flow of Pedicled Perforator Flaps Using Indocyanine Green-fluorescence Angiography
Authors: Jakubietz Rafael G. , Schmidt Karsten , Bernuth Silvia , Meffert Rainer H. , Jakubietz Michael G.
Published: October 2019

Background:

Although indocyanine-green fluorescence angiography (ICG-FA) has been established as a useful tool to assess perfusion in free tissue transfer, only few studies have applied this modality to pedicled perforator flaps. As both volume and reach of pedicled perforator flaps are limited and tip necrosis often equals complete flap failure, ICG-FA may help to detect hypoperfusion in pedicled flaps.

Methods:

In 5 patients, soft tissue reconstruction was achieved with pedicled perforator flaps. ICG-FA was utilized intraoperatively to visualize flap perfusion.

Results:

Three pedicled anterolateral thigh flap flaps and 2 propeller flaps were transferred. ICG-FA detected hypoperfusion in 2 flaps. No flap loss occurred; in 2 cases, prolonged wound healing was encountered.

Conclusions:

ICG-FA confirmed clinical findings and reliably detected tissue areas with hypoperfusion. A clear cut-off point between nonvital tissue and such that stabilized in the following clinical course could not be found. ICG-FA is a promising technology which could also be used in pedicled perforator flaps.
Association of Traumatic Brain Injury With Vestibular Dysfunction and Dizziness in Post-9/11 Veterans
Authors: Swan Alicia A. , Nelson Jeremy T. , Pogoda Terri K. , Akin Faith W. , Riska Kristal M. , Hall Courtney D. , Amuan Megan E. , Yaffe Kristine , Pugh Mary Jo
Published: October 2019

Objective:

To describe the prevalence and impact of vestibular dysfunction and nonspecific dizziness diagnoses and explore their associations with traumatic brain injury (TBI) severity, mechanism, and postconcussive comorbidities among post-9/11 veterans.

Setting:

Administrative medical record data from the US Departments of Defense and Veterans Affairs (VA).

Participants:

Post-9/11 veterans with at least 3 years of VA care.

Design:

Cross-sectional, retrospective, observational study.

Main Measures:

International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for TBI, vestibular dysfunction, dizziness, and other commonly associated postconcussive conditions; Neurobehavioral Symptom Inventory.

Results:

Of the 570 248 post-9/11 veterans in this sample, 0.45% had a diagnosis of vestibular dysfunction and 2.57% had nonspecific dizziness. Those with either condition were more likely to have evidence of TBI (57.11% vs 28.51%) and reported more disruption from neurobehavioral symptoms. Blast and nonblast injuries were associated with greater symptom disruption, particularly in combination.

Conclusions:

There was a consistent, significant association between TBI and vestibular dysfunction or nonspecific dizziness, after controlling for sociodemographic factors, injury mechanism, and comorbid conditions. Given that most deployed post-9/11 veterans report blast and/or nonblast injuries, the need for prompt identification and management of these conditions and symptoms is clear.