bluuebunny/crossref_metadata_2025 huggingface dataset:
Health promotion in Brazil: qualitative survey with primary school teachers
Authors: Graciano Andrea Monteiro de Castro , Cardoso Natalia Mendes Matos , Teixeira Suélen Alves , Mattos Flavio de Freitas , Gomes Viviane Elisângela , Borges-Oliveira Ana Cristina
Published: July 2018

School health promotion programs can reduce common health problems like obesity, diabetes and respiratory complications. This qualitative study aimed to investigate the perceptions of a group of teachers regarding issues related to the promotion of health in school. The 15 teachers sampled were from public primary schools in a city in southeastern Brazil. Interviews with teachers were conducted and data was analyzed employing content. Teacher practices regarding the promotion of health appeared to be aimed at their students and their daily habits and their practices. Teachers described approaching health promotion through their lesson content and suggested that the school should seek help from other institutions in their health promotion activities like prevention activities, monitoring of improvements in student and teacher health. Teachers mentioned a strong relationship between knowledge and the pursuit of good health. The need to identify major determinants of the disease/health process was highlighted and the connection between lifestyle, socio-economic status and the disease/health process was described. Awareness of the influence concerning both the environment and the school surroundings was demonstrated. It is important that the teachers are aware of the environment that surrounds them as well as the reality of the lives of all those involved with the school.
Evaluating Azoxystrobin Seed Coating Against Maize Late Wilt Disease Using a Sensitive qPCR-Based Method
Authors: Degani Ofir , Movshowitz Daniel , Dor Shlomit , Meerson Ari , Goldblat Yuval , Rabinovitz Onn
Published: July 2018

Harpophora maydis, a phytopathogenic fungus, causes late wilt, a severe vascular maize disease characterized by relatively rapid wilting of maize plants near fertilization. The disease is currently controlled using resistant varieties. Here, we evaluated seed coating efficiency with azoxystrobin against H. maydis in a series of in vitro and in vivo trials. A real-time polymerase chain reaction (qPCR)-based method was developed and proved to be a sensitive, accurate tool for monitoring H. maydis DNA inside infected seeds, sprouts, and tissues of mature plants. In the early growth stages, the chemical coating drastically reduced the pathogen DNA prevalence in host tissues and minimized the suppressing effect on the plants’ biomass and development. In an infested field, the qPCR assay identified the pathogen 20 days after seeding, up to a month before conventional PCR detection. In the resistant fodder maize cultivar 32D99, which showed only minor disease symptoms, the seed coating blocked fungal progression and increased cob and plant weight by 39 and 60%, respectively. Nevertheless, this treatment was unable to protect a sensitive maize hybrid, cultivar Prelude, at the disease wilting breakout (60 days after sowing). These results encourage further examination of azoxystrobin and other fungicides in the field using the qPCR detection method to evaluate their efficiency.
Detection of Phytophthora cinnamomi in Forest Soils by PCR on DNA Extracted from Leaf Disc Baits
Authors: Sena Kenton , Dreaden Tyler J. , Crocker Ellen , Barton Chris
Published: July 2018

Phytophthora cinnamomi Rands causes root rot in a number of important forest tree species around the world, including American chestnut (Castanea dentata) and shortleaf pine (Pinus echinata). Conventional methods for detecting P. cinnamomi in forest soils may require too much time and space to permit widescale and long-term screening of the large sample numbers required for landscape-scale distribution analysis. This project compared conventional detection methods (baiting with full rhododendron leaves or leaf discs and subsequent culturing on selective media) with a molecular detection method using DNA extracted from leaf baits. These methods were comparable, and the DNA-based method was correlated with culture-based methods. In a field-validation screening using the leaf bait polymerase chain reaction method, P. cinnamomi was found across a range of topographic conditions, including dry ridge-top sites and moist lowland sites. Soil texture analysis supports the traditional association of P. cinnamomi with finer-textured soils. Further large-scale surveys are necessary to elucidate landscape-scale distribution patterns in eastern U.S. forests.
Root Rot Caused by Species of Fusarium on Brassica carinata in South Dakota
Authors: Okello Paul N. , Petrović Kristina , Kontz Brian , Ali Shaukat , Marek Laura F. , Mathew Febina M.
Published: July 2018

Brassica carinata is an emerging oilseed crop in the United States, and root diseases caused by Fusarium have the potential to cause yield losses in production. In this study, B. carinata plants were randomly sampled at vegetative and seed development plant stages from South Dakota State University experimental plots. Reddish-brown lesions were observed on roots of sampled plants from which F. acuminatum, F. oxysporum, F. solani, and F. sporotrichioides were recovered. The Fusarium species were identified based on morphology and phylogenetic analyses of the translation elongation factor 1-α gene region. Pathogenicity of the four Fusarium species was evaluated on five B. carinata accessions using a modified inoculum layer method in the greenhouse. At 21 days after inoculation, root rot severity caused by Fusarium on the B. carinata accessions was assessed on a rating scale of 0 to 4 and evaluated using relative treatment effects (RTEs). The F. oxysporum isolate caused significant differences in RTE (P = 0.01) among the B. carinata accessions. However, there were no significant differences in RTE among the B. carinata accessions in response to F. acuminatum (P = 0.82), F. solani (P = 0.76), and F. sporotrichioides (P = 0.47) isolates.
Optimism and Psychological Resilience are Beneficially Associated With Measures of Clinical and Experimental Pain in Adults With or at Risk for Knee Osteoarthritis
Authors: Thompson Kathryn A. , Bulls Hailey W. , Sibille Kimberly T. , Bartley Emily J. , Glover Toni L. , Terry Ellen L. , Vaughn Ivana A. , Cardoso Josue S. , Sotolongo Adriana , Staud Roland , Hughes Laura B. , Edberg Jeffrey C. , Redden David T. , Bradley Laurence A. , Goodin Burel R. , Fillingim Roger B.
Published: July 2018

Objectives:

This cross-sectional study examined the associations among optimism, psychological resilience, endogenous pain inhibition, and clinical knee pain severity. Two hypotheses were tested. First, we hypothesized that experimentally tested endogenous pain inhibition would mediate the relationship between optimism and clinical knee pain severity. Second, it was also hypothesized that optimism would moderate the relationships of psychological resilience with endogenous pain inhibition and clinical knee pain severity, particularly for individuals with high optimism.

Methods:

A total of 150 individuals with or at risk for symptomatic knee osteoarthritis completed the Life Orientation Test-Revised, the Brief Resilience Scale, and the revised Short-Form McGill Pain Questionnaire-2 to assess optimism, psychological resilience, and clinical knee pain severity, respectively. Endogenous pain inhibition was examined experimentally using a conditioned pain modulation (CPM) protocol with algometry (test stimulus) and a cold pressor task (conditioning stimulus).

Results:

As hypothesized, results showed that increased CPM significantly mediated the association between higher optimism and lower clinical knee pain severity. Further, optimism moderated the association between psychological resilience and CPM. However, contrary to our hypothesis, greater psychological resilience was associated with enhanced CPM in individuals with low optimism only.

Discussion:

This study suggests that an optimistic outlook may beneficially impact clinical pain severity by altering endogenous pain modulatory capacity. Furthermore, individuals with low optimism (ie, pessimists) may be more adept at engaging resources that promote psychological resilience, which in turn, enhances endogenous pain modulatory capacity. Therefore, this study supports consideration of psychological resilience factors when evaluating experimental and clinical pain outcomes.
Opportunistic CT Screening for Osteoporosis in Patients With Pelvic and Acetabular Trauma: Technique and Potential Clinical Impact
Authors: Donohue David , Decker Summer , Ford Jonathan , Foley Robert , Dunbar Kirstin , Kumm Todd , Achors Kyle , Mir Hassan
Published: July 2018

Objectives:

To present a technique for the use of computed tomography (CT) scans in opportunistic screening for osteoporosis in patients with pelvic and acetabular fractures and to quantify the potential clinical impact in a geriatric trauma population.

Design:

Retrospective cohort study.

Setting:

Level 1 trauma center.

Patients:

A total of 335 patients older than 60 years of age who presented to a Level 1 trauma center with a diagnosis of pelvic or acetabular fracture and were evaluated with a CT scan between the years 2010 and 2016. A subset of 255 patients were evaluated with a dual-energy x-ray absorptiometry scan within 6 months of the CT scan.

Intervention:

Measurement of Hounsfield units (HU) was performed at the midpoint of the femoral neck using a standardized, ovoid section, followed by Livewire measurement. Application of this technique retrospectively to a population of geriatric patients with pelvic or acetabular fractures.

Main Outcome Measurements:

(1) HUs were measured in a cross section at the midpoint of the femoral neck and, discriminant function analysis was used to establish thresholds for normal bone mineral density, osteopenia, and osteoporosis. (2) Change in the number of diagnoses of osteoporosis after application of the protocol the geriatric trauma cohort.

Results:

Patients with osteopenia were identified correctly 67.5% of the time (14.3% were incorrectly grouped as normal, and 18.3% were grouped as having osteopenia). Patients with osteoporosis were identified correctly 88.9% of the time (the remaining 11.1% were assigned to osteopenic). The results of discriminant function analysis were used to establish CT thresholds for osteopenia (345 HUs) and osteoporosis (262 HUs).

Conclusion:

CT imaging obtained for pelvic and acetabular fractures can identify patients with osteoporosis without additional radiation exposure or cost. The fitted ovoid region of interest is a standard feature in most CT scan platforms and is quite simple to perform.

Level of Evidence:

Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.
SHORT-TERM COMPUTER-ASSISTED QUANTIFICATION OF PLUS DISEASE AFTER TREATMENT OF TYPE 1 RETINOPATHY OF PREMATURITY WITH INTRAVITREAL BEVACIZUMAB OR RETINAL LASER PHOTOCOAGULATION
Authors: Cabrera Michelle T. , Chia Thomas , Wallace David K. , Ulrich J. Niklas , Freedman Sharon F. , Ding Leona , Gertsch Kevin R.
Published: July 2018

Purpose:

To compare objectively measured changes in plus disease after bevacizumab and laser for Type 1 retinopathy of prematurity.

Methods:

ROPtool (a computer program) analyzed fundus images at baseline, 1 week, and subsequent examinations.

Results:

Six infants (9 eyes) were treated with bevacizumab and 7 (12 eyes) with laser. One week after treatment, bevacizumab compared with laser resulted in a greater median percent change from pretreatment in tortuosity (−53.8 vs. −0.2%, P < 0.001) and overall plus disease (−20.1 vs. −3.1%, P < 0.001). Change in dilation did not differ (−3.5 vs. −5.5%, P = 0.48). After week 1, all median ROPtool parameters continued to decrease for both groups. At last follow-up (median 3, range: 2–10 weeks), both bevacizumab and laser significantly decreased tortuosity (−54.3 and −23.8%), dilation (−8.7 and −7.5%), and overall plus disease (−27.3 and −10.3%).

Conclusion:

Improvement in plus disease, in particular tortuosity, likely occurs more quickly after bevacizumab compared with laser, particularly at 1 week after treatment. These results guide clinical expectations for plus disease resolution after both treatment modalities.
Neuroinvasive Seronegative West Nile Virus in the Setting of R-CHOP Chemotherapy for Diffuse Large B-Cell Lymphoma
Authors: Yuen Alexander D. , Liu Jason Y. , Betancourt Jaime
Published: July 2018

West Nile virus (WNV) is a mosquito-borne infectious disease that can produce potentially life-threatening meningoencephalitis in immunocompromised individuals. In 2017, there were 536 human cases of WNV in California, with 43 fatalities reported to the California Department of Public Health. Peak mosquito transmission periods are in the late summer and early fall when mosquitoes are maximally viremic. In addition to risk factors such as advanced age, malignancy, or prior organ transplantation, the probability of progression to severe, neuroinvasive disease has been reported to be significantly higher in individuals suffering from lymphoma receiving rituximab in addition to other oncologic treatments. Here, we describe the case of a patient who recently received chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone for diffuse large B-cell lymphoma, complicated by meningoencephalitis due to seronegative neuroinvasive WNV infection, ultimately resulting in death.
Hypertrophic Herpes Simplex—Pseudocarcinoma
Authors: Parker Laura R. , Stanford Brian J. , Nahass Ronald G.
Published: July 2018

Individuals with human immunodeficiency virus (HIV) are commonly coinfected with herpes simplex virus type 2 (HSV-2) and human papilloma virus (HPV). Herpes simplex virus type 2 in HIV-infected individuals can present as atypical hypertrophic lesions, and HPV-induced malignant lesions can present as atypical hyperkeratotic lesions. We report a case of an atypical hypertrophic HSV-2 lesion in a well-managed HIV-infected male with a history of nonmalignant Buschke-Lowenstein tumor (giant condyloma) of HPV and squamous cell carcinoma of the scrotum. Determining the definitive diagnosis of hypertrophic HSV-2 in this patient was confounded by the macroscopic clinical presentation of the proliferative lesion and by the patient's history of squamous cell carcinoma, in the same perineal region. Knowledge of hypertrophic HSV-2 is imperative when considering the etiologic agent of anogenital lesions in HIV-infected individuals.
Urban-Acquired Leptospirosis in Washington, DC
Authors: Lerner Andrea , Frost Spencer , Siegel Marc O.
Published: July 2018

Leptospirosis is rarely reported in the United States. Although primarily considered a disease of the tropics or of resource limited areas, leptospirosis is being reported more frequently in industrialized urban areas. We report a case of severe leptospirosis in a man living in Washington, DC, with occupational exposure to rats. A review of the literature was conducted, with a focus on the urban form of the disease, using the MEDLINE database from inception to May 2018.
Experimental muscle hyperalgesia modulates sensorimotor cortical excitability, which is partially altered by unaccustomed exercise
Authors: De Martino Enrico , Zandalasini Matteo , Schabrun Siobhan , Petrini Laura , Graven-Nielsen Thomas
Published: July 2018

Impaired corticomotor function is reported in patients with lateral epicondylalgia, but the causal link to pain or musculotendinous overloading is unclear. In this study, sensorimotor cortical changes were investigated using a model of persistent pain combined with an overloading condition. In 24 healthy subjects, the effect of nerve growth factor (NGF)-induced pain, combined with delayed-onset muscle soreness (DOMS), was examined on pain perception, pressure pain sensitivity, maximal force, and sensorimotor cortical excitability. Two groups (NGF alone and NGF + DOMS) received injections of NGF into the extensor carpi radialis brevis (ECRB) muscle at day 0, day 2, and day 4. At day 4, the NGF + DOMS group undertook wrist eccentric exercise to induce DOMS in the ECRB muscle. Muscle soreness scores, pressure pain thresholds over the ECRB muscle, maximal grip force, transcranial magnetic stimulation mapping of the cortical ECRB muscle representation, and somatosensory-evoked potentials from radial nerve stimulation were recorded at day 0, day 4, and day 6. Compared with day 0, day 4 showed in both groups: (1) increased muscle soreness (P < 0.01); (2) reduced pressure pain thresholds (P < 0.01); (3) increased motor map volume (P < 0.01); and (4) decreased frontal N30 somatosensory-evoked potential. At day 6, compared with day 4, only the DOMS + NGF group showed: (1) increased muscle soreness score (P < 0.01); (2) decreased grip force (P < 0.01); and (3) decreased motor map volume (P < 0.05). The NGF group did not show any difference on the remaining outcomes from day 4 to day 6. These data suggest that sustained muscle pain modulates sensorimotor cortical excitability and that exercise-induced DOMS alters pain-related corticomotor adaptation.
How We Got Smart
Authors: Sundgren Nathan C. , Gokulakrishnan Ganga , Kelly Frances C. , Kainer Kellie S. , Hagan Joseph L. , Witt Melissa A. , D'Ambrosio Deborah , Graf Jeanine M. , Suresh Gautham K.
Published: July 2018

Communication around high-risk deliveries is critical to ensure patient safety. A hospital-wide system change in paging the neonatal resuscitation team (NRT) to deliveries was implemented but disliked. An interdisciplinary team seized the opportunity to explore opportunities for an enhanced system to improve communication. The team designed a new screen to our smart panel (responder 5 staff terminal, Rauland, Mount Prospect, Illinois) to page NRT with the location and primary indication for which they were needed at delivery. Surveys assessed user satisfaction among labor and delivery and NRT. Before and after implementation of the smart panel, we assessed number of NRT pages, frequency of NRT being paged prior to the delivery, the time between page and delivery, and use of the code button to summon help. Labor and delivery and NRT user satisfaction greatly improved with the smart panel. Frequency of NRT being paged before birth increased with fewer code pages being used to summon NRT to deliveries. A touch screen–based notification system can enhance timely notification to summon NRT to deliveries while concurrently enhancing satisfaction of providers in both the delivery room and on the NRT.
An outcome analysis of nurse practitioner care in a community hospital in Taiwan
Authors: Hu Jia-Ying , Tung Heng-Hsin , Tsay Shiow-Luan , Lin Wei-Cheng
Published: July 2018

Purpose:

The purpose of this study is to examine the outcome of nurse practitioner care.

Data sources:

A descriptive survey design was conducted, with hospital-acquired conditions (HACs) used as an indicator of effectiveness of care. The two test groups included an attending physician–nurse practitioner group and an attending physician–resident physician group, which were compared in terms of effectiveness, using a 360° satisfaction–feedback survey provided to a peer group, as well as patients and their family members.

Conclusion:

According to patients and their family members, as well as the peer group, nurse practitioners performed better in comparison to resident physicians. In addition, the use of an HAC rating as an objective indicator of care efficiency indicated that nurse practitioners surpass resident physicians. This study not only confirmed that the attending physician–nurse practitioner model works well, based on the outcome analysis, but it also provided a new perspective and new evidence to show the value of nurse practitioner care in Taiwan.

Implications for practice:

Continuously increasing the training and education of nurse practitioners, while establishing a more comprehensive system for monitoring and evaluating their efficiency in accordance with hospital guidelines, is recommended and should lead to the provision of better services to meet patients' needs.
Cognitive outcomes after critical illness
Authors: Sakusic Amra , Rabinstein Alejandro A.
Published: July 2018

Purpose of review

There is an increasing realization in the critical care community that persistent cognitive impairment is a common and disabling complication after ICU care. In this review, we discuss the best available information on the magnitude of the problem, its possible mechanisms, risk factors, management strategies and prognosis.

Recent findings

Estimates of the incidence of persistent cognitive impairment after critical illness vary widely across studies but the most solid prospective information indicates that it may occur in 20–40% of patients discharged from the ICU. From the available evidence, it is difficult to discriminate between de novo cognitive impairment and exacerbation of preexistent cognitive decline. The pathogenesis is multifactorial but inflammatory mechanisms causing derangements of endothelial function and blood–brain barrier integrity might play an important role. Brain atrophy and white matter tract disruption can be structural correlates of the cognitive decline. Prolonged delirium in the ICU is the strongest risk factor for the development of subsequent persistent cognitive impairment. Management strategies are currently limited to those designed to prevent and improve delirium. Cognitive trajectories may vary but a substantial proportion of patients with cognitive impairment 3 months after ICU discharge are still cognitively impaired at 12 months.

Persistent cognitive impairment is a major complication of critical illness. Our knowledge of this problem remains incomplete. Collaborative research is indispensable to improve our understanding of this disabling sequel and to identify ways to prevent it.
Regulatory dendritic cells: profiling, targeting, and therapeutic application
Authors: Thomson Angus W. , Ezzelarab Mohamed B.
Published: July 2018

Purpose of review

There is currently increased focus on improved understanding of how dendritic cell tolerogenicity is determined and maintained, and on their therapeutic potential. We review recent progress in profiling of regulatory dendritic cells (DCreg), innovative approaches to enhancing dendritic cell tolerogenicity in situ, ex-vivo generation of DCreg and initial clinical testing of these cells in organ transplantation.

Recent findings

“Omics" studies indicate that the distinctive properties of DCreg are the result of a specific transcriptional program characterized by activation of tolerance-enhancing genes, rather than the retention of an immature state. In situ dendritic cell-directed targeting of nanovesicles bearing immune regulatory molecules can trigger in-vivo expansion of Ag-specific regulatory cells. Innovative approaches to ex-vivo modification of dendritic cells to enhance their regulatory function and capacity to migrate to secondary lymphoid organs has been described. Cross-dressing (with donor major histocompatibility complex molecules) of graft-infiltrating host dendritic cells that regulate antidonor T-cell responses has been implicated in “spontaneous" liver transplant tolerance. Clinical trials of DCreg therapy have begun in living donor renal and liver transplantation.

Further definition of molecules that can be targeted to promote the function and stability of DCreg in vivo may lead to standardization of DCreg manufacturing for therapeutic application.
Prognostic Value of Pretreatment Metabolic PET Parameters in Cervical Cancer Patients With Metabolic Complete Response After Concurrent Chemoradiotherapy
Authors: Son Seung Hyun , Jeong Shin Young , Chong Gun Oh , Lee Yoon Hee , Park Shin-Hyung , Lee Chang-Hee , Hong Chae Moon , Jeong Ju Hye , Lee Sang-Woo , Ahn Byeong-Cheol , Lee Jaetae
Published: July 2018

Purpose

Cervical cancer may recur after concurrent chemoradiotherapy (CCRT), even in patients with metabolic complete response (mCR) on post-CCRT 18F-FDG PET. We retrospectively analyzed the value of metabolic parameters, measured by pretreatment PET, as prognostic factors for predicting recurrence and death in cervical cancer patients with mCR.

Methods

In 61 patients who reached mCR on post-CCRT, metabolic PET parameters including SUVmax, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors, as well as those of the metastatic lymph nodes, were measured by pre-CCRT PET. Total MTV and total TLG were also measured from primary tumors and metastatic lymph nodes. Survival analyses for disease-free survival (DFS) and overall survival (OS) were performed.

Results

Eleven patients (18.0%) presented with recurrence of cervical cancer, and 12 (19.7%) died during follow-up. SUVmax, MTV, TLG of metastatic lymph nodes, and total TLG could significantly predict DFS, and nodal SUVmax could predict OS. Para-aortic lymph node metastasis also significantly correlated with both DFS and OS. In multivariate analysis, nodal SUVmax and para-aortic lymph nodes metastasis were prognostic factors for DFS, and the best predictor was nodal SUVmax. For OS, nodal MTV and para-aortic lymph node metastasis were significant prognostic factors in multivariate analysis, and the best predictor was para-aortic lymph node metastasis.

Conclusions

Metabolic PET parameters, SUVmax or MTV values of metastatic lymph nodes, may be surrogate prognostic markers for recurrence or death in patients with locally advanced cervical cancer who reached mCR after definitive CCRT.
68Ga-PSMA Uptake in Middle Lobe Syndrome
Authors: Pedersen Mette Abildgaard , Bouchelouche Kirsten , Vendelbo Mikkel Holm
Published: July 2018

Prostate cancer cells have abundant expression of the cell surface protein prostate-specific membrane antigen (PSMA). In recent years, PET radioligands detecting this protein has therefore gained substantial interest in prostate cancer staging. It turned out that PSMA expression can be evident in both malignant and benign lesions, and we have previously reported that pulmonary opacities and bronchiectasis can be avid on 68Ga-PSMA PET/CT. Here, we present a case with 68Ga-PSMA accumulation in nonobstructive middle lobe syndrome, which further indicate that benign changes in the lungs may be falsely interpreted as malignant disease.
18F-FDG PET/CT in an Atypical Case of Relapsed IgG4-Related Disease Presenting as Inflammatory Pseudotumor in Gall Bladder Fossa With Extensive Disease Involvement
Authors: Vadi Shelvin Kumar , Kumar Rajender , Mittal Bhagwant Rai , Parihar Ashwin Singh , Singh Harmandeep , Singh Shashank , Rana Surinder
Published: July 2018

Immunoglobulin G4–related disease (IgG4-RD) with multisystem involvement is known to mimic various malignancies and can be diagnosed with high clinical suspicion. We hereby report an atypical case of IgG4-RD, who presented as an inflammatory pseudotumor resembling gall bladder malignancy with hepatic, omental, and subcutaneous involvement. The characteristic tracer uptake pattern described on FDG PET/CT may not be always present in IgG4-RD, especially in the setting of postabdominal surgery. FDG PET/CT revealed the disease progression despite glucocorticoids and aided in response evaluation after second-line drug, rituximab.
18F-FDG PET/CT With Diffusely High FDG Uptake Throughout Subcutaneous Adipose Tissues
Authors: Kong Melissa Cindy , Nadel Helen Ruth
Published: July 2018

A 9-year-old girl presented with facial rash, angioedema, fevers, and night sweats. She was diagnosed with chronic active Epstein-Barr virus infection and placed on chronic steroid treatment.18F-FDG PET/CT performed 3 weeks following presentation revealed diffuse subcutaneous soft tissue FDG activation throughout the entire body, with likely localization to white subcutaneous adipose tissue. This highly unusual appearance may have been due to the patient being treated with corticosteroids at the time of the scan.
Supporting self-management in palliative care throughout the cancer care trajectory
Authors: Schulman-Green Dena , Brody Abraham , Gilbertson-White Stephanie , Whittemore Robin , McCorkle Ruth
Published: July 2018

Purpose of review

Despite increased survivorship and the subsequent need for chronic management of cancer, the association of self-management and palliative care is still emerging within cancer care. Routine and timely use of self-management strategies in the palliative setting can help reduce self-management burden and maximize quality of life. In this review, we consider the complementary relationship of self-management and palliative care and how they support living with cancer as a chronic illness.

Recent findings

Recent studies provide evidence of support among patients, family caregivers and healthcare professionals for integration of self-management interventions into palliative cancer care. As a guiding framework, components of the revised Self and Family Management Framework correspond to the provision of palliative care across the care trajectory, including the phases of curative care, palliative care, end-of-life care and bereavement. Additional work among self-management partners facing cancer and other life-limiting illnesses, that is patients, family caregivers and healthcare professionals, would be useful in developing interventions that incorporate self-management and palliative care to improve health outcomes.

There is an increasing acceptance of the complementarity of self-management and palliative care in cancer care. Their integration can support patients with cancer and their family caregivers across the care trajectory.
Extended-spectrum β-lactamase-producing and carbapenemase-producing Enterobacteriaceae
Authors: Wilson Hayley , Török M. Estée
Published: July 2018

Antimicrobial resistance (AMR) is a global public-health emergency, which threatens the advances made by modern medical care over the past century. The World Health Organization has recently published a global priority list of antibiotic-resistant bacteria, which includes extended-spectrum β-lactamase-producing Enterobacteriaceae and carbapenemase-producing Enterobacteriaceae. In this review, we highlight the mechanisms of resistance and the genomic epidemiology of these organisms, and the impact of AMR.
VERA: agent-based modeling transmission of antibiotic resistance between human pathogens and gut microbiota
Authors: Glushchenko OE , Prianichnikov NA , Olekhnovich EI , Manolov AI , Odinzova VE , Tyaht AB , Kostrukova ES , Ilina EN
Published: July 2018

The resistance of bacterial pathogens to antibiotics is one of the most important issues of the modern health care. The human microbiota can accumulate resistance determinants and transfer them to pathogenic microflora by means of horizontal gene transfer (HGT). Thus, at the moment it is important to develop methods of prediction and monitoring of antibiotics resistance in human population. We represent the agent-based VERA model, which allows to simulate the spread of pathogen with account of possible horizontal transfer of resistance determinants from commensal microbiota community. The model considers the opportunity of residents to stay in the town or in medical institution, have wrong self-treatment, reception of several antibiotics types, transfer and accumulation of resistance determinants from a microbiota to a pathogen. In this model we have also created assessment of optimum intensity of observation of infection spread among the population. Investigating model behavior we show a number of nonlinear dependencies, including the exponential nature of dependence of total of the diseased on average resistance of a pathogen. As the model infection we considered infection with Shigella spp, though it could be applied to a wide range of other pathogens.

Availability and implementation

Source code and binaries VERA and VERA.viewer are freely available for download at github.com/lpenguin/microbiota-resistome. The code is written in Java, JavaScript and R for Linux platform.
Radial F-actin Organization During Early Neuronal Development
Authors: Praveen Meka Durga , Scharrenberg Robin , Zhao Bing , König Theresa , Schaefer Irina , Schwanke Birgit , Kobler Oliver , Klykov Sergei , Richter Melanie , Eggert Dennis , Windhorst Sabine , Dotti Carlos G. , Kreutz Michael R. , Mikhaylova Marina , Calderon de Anda Froylan
Published: July 2018

The centrosome is thought to be the major neuronal microtubule-organizing center (MTOC) in early neuronal development, producing microtubules with a radial organization. In addition, albeit in vitro, recent work showed that isolated centrosomes could serve as an actin-organizing center (Farina et al., 2016), raising the possibility that neuronal development may, in addition, require a centrosome-based actin radial organization. Here we report, using super-resolution microscopy and live-cell imaging, F-actin organization around the centrosome with dynamic F-actin aster-like structures with F-actin fibers extending and retracting actively. Photoconversion/photoactivation experiments and molecular manipulations of F-actin stability reveal a robust flux of somatic F-actin towards the cell periphery. Finally, we show that somatic F-actin intermingles with centrosomal PCM-1 satellites. Knockdown of PCM-1 and disruption of centrosomal activity not only affect F-actin dynamics near the centrosome but also in distal growth cones. Collectively the data show a radial F-actin organization during early neuronal development, which might be a cellular mechanism for providing peripheral regions with a fast and continuous source of actin polymers; hence sustaining initial neuronal development.
Antibiotic resistance evasion is explained by rare mutation frequency and not by lack of compensatory mechanisms
Authors: Evangelopoulos Dimitrios , Prosser Gareth A. , Rodgers Angela , Dagg Belinda M. , Khatri Bhagwati , Ho Mei Mei , Gutierrez Maximiliano G. , Cortes Teresa , de Carvalho Luiz Pedro S.
Published: July 2018

Drug resistant infections represent one of the most challenging medical problems of our time. D-cycloserine is an antibiotic used for decades without appearance and dissemination of antibiotic resistant strains, making it an ideal model compound to understand what drives resistance evasion. We investigated whyMycobacterium tuberculosisfails to become resistant to D-cycloserine. To address this question we employed a combination of bacterial genetics, genomics, biochemistry and fitness analysisin vitro, in macrophages and in mice. Altogether, our results suggest that the ultra-low mutation frequency associated with D-cycloserine resistance is the dominant factor delaying the appearance of clinical resistance to this antibiotic in bacteria infecting humans, and not lack of potential compensatory mechanisms.

One Sentence Summary

We show that the lack of D-cycloserine resistance inMycobacterium tuberculosisis due its ultra-low mutation frequency rather than lack of compensatory mechanisms.
Basal Forebrain Deep Brain Stimulation Impacts the Regulation of Extracellular Vesicle Related Proteins in the Rat Brain
Authors: Li Wenxue , Montes Laura Lozano , Nair Jayakrishnan , Dimanico Marta , Mazloum Reza , Hu Zehan , Scolari Brigitte , Dengjel Jörn , Theilig Franziska , Harvey Michael , Zhang Xiaozhe , Rainer Gregor
Published: July 2018

Extracellular vesicle (EV) signaling has attracted considerable attention in recent years because EVs play a key role in long distance cellular communication functions. EV studies have begun to reveal aspects of physiological and physiopathological regulation in numerous applications, although many areas remain to date largely unexplored. Deep brain stimulation (DBS) has shown remarkable therapeutic benefits of patients with neuropsychiatric disorders, but despite of the long and successful history of use, the mechanisms of action on neural ensemble activity are not yet fully understood. Here we explore how DBS of the basal forebrain impacts EV signaling in the rat brain. We employed differential centrifugations to isolate the EVs prefrontal cortex (PFC), hippocampus and striatum. We then performed quantitative analysis of EV-associated proteins using an MS-based proteomics method. We identified a considerable number of EV-associated proteins are modulated by DBS in three brain regions, some of which have been previously linked with central nervous system disorders. Particularly, neurofilament proteins NFL and NFM were both significantly changed in EVs of PFC, hippocampus and striatum after DBS stimulation compared with controls. The SOD1 protein, associated previously with neurodegenerative diseases, was significantly increased only in PFC. Our study is the first, to our knowledge, to use EV protein analysis to examine DBS effects on brain physiological regulation. Our findings open an entirely new perspective on brain area specific DBS effects.
Static stability predicts the continuum of interleg coordination patterns inDrosophila
Authors: Szczecinski Nicholas S. , Bockemühl Till , Chockley Alexander S. , Büschges Ansgar
Published: July 2018

During walking, insects must coordinate the movements of their six legs for efficient locomotion. This interleg coordination is speed-dependent; fast walking in insects is associated with tripod coordination patterns, while slow walking is associated with more variable, tetrapod-like patterns. To date, however, there has been no comprehensive explanation as to why these speed-dependent shifts in interleg coordination should occur in insects. Tripod coordination would be sufficient at low walking speeds. The fact that insects use a different interleg coordination pattern at lower speeds suggests that it is more optimal or advantageous at these speeds. Furthermore, previous studies focused on discrete tripod and tetrapod coordination patterns. Experimental data, however, suggest that changes observed in interleg coordination are part of a speed-dependent spectrum. Here, we explore these issues in relation to static stability as an important aspect of interleg coordination inDrosophila. We created a model that uses basic experimentally measured parameters in fruit flies to find the interleg phase relationships that maximize stability for a given walking speed. Based on this measure, the model predicted a continuum of interleg coordination patterns spanning the complete range of walking speeds. Furthermore, for low walking speeds the model predicted tetrapod-like patterns to be most stable, while at high walking speeds tripod coordination emerged as most optimal. Finally, we validated the basic assumption of a continuum of interleg coordination patterns in a large set of experimental data from walking fruit flies and compared these data with the model-based predictions.

Summary statement

A simple stability-based modelling approach can explain why walking insects use different leg coordination patterns in a speed-dependent way.
The molecular logic of Nanog-induced self-renewal
Authors: Heurtier Victor , Owens Nick , Gonzalez Inma , Mueller Florian , Proux Caroline , Mornico Damien , Clerc Philippe , Dubois Agnès , Navarro Pablo
Published: July 2018

Transcription factor networks, together with histone modifications and signalling pathways, underlie the establishment and maintenance of gene regulatory architectures associated with the molecular identity of each cell type. However, how master transcription factors individually impact the epigenomic landscape and orchestrate the behaviour of regulatory networks under different environmental constraints is only very partially understood. Here, we show that the transcription factor Nanog deploys multiple distinct mechanisms to enhance embryonic stem cell self-renewal. In the presence of LIF, which fosters self-renewal, Nanog rewires the pluripotency network by promoting chromatin accessibility and binding of other pluripotency factors to thousands of enhancers. In the absence of LIF, Nanog blocks differentiation by sustaining H3K27me3, a repressive histone mark, at developmental regulators. Among those, we show that the repression of Otx2 plays a preponderant role. Our results underscore the versatility of master transcription factors, such as Nanog, to globally influence gene regulation during developmental processes.
Genetic differentiation is determined by geographic distance inClarkia pulchella
Authors: Bontrager Megan , Angert Amy L.
Published: July 2018

Both environmental differences and geographic distances may contribute to the genetic differentiation of populations on the landscape. Understanding the relative importance of these drivers is of particular interest in the context of geographic range limits, as both swamping gene flow and lack of genetic diversity are hypothesized causes of range limits. We investigated the landscape genetic structure of 32 populations of the annual wildflowerClarkia pulchellafrom across the species’ geographic range in the interior Pacific North-west. We tested whether climatic differences between populations influenced the magnitude of their genetic differentiation. We also investigated patterns of population structure and geographic gradients in genetic diversity. Contrary to our expectations, we found an increase in genetic diversity near the species’ northern range edge. We found no notable contribution of climatic differences to genetic differentiation, indicating that any processes that might operate to differentiate populations based on temperature or precipitation are not affecting the putatively neutral loci in these analyses. Rather, these results support seed and pollen movement at limited distances relative to the species’ range and that this movement and the subsequent incorporation of immigrants into the local gene pool are not influenced by temperature or precipitation similarities among populations. We found that populations in the northern and southern parts of the range tended to belong to distinct genetic groups and that central and eastern populations were admixed between these two groups. This pattern could be the result of a past or current geographic barrier associated with the Columbia Plateau, or it could be the result of spread from separate sets of refugia after the last glacial maximum.
Perineuronal nets set the strength of thalamic recruitment of interneurons in the adult visual cortex
Authors: Faini Giulia , Aguirre Andrea , Landi Silvia , Pizzorusso Tommaso , Ratto Gian Michele , Deleuze Charlotte , Bacci Alberto
Published: July 2018

In the neocortex, the closure of critical periods (CPs) of plasticity is paralleled by the accumulation of perineuronal nets (PNNs) around parvalbumin (PV)-positive inhibitory interneurons. Accordingly, PNN degradation in adult mammals re-opens cortical plasticity. However, how PNNs tune cortical function and plasticity is unknown. We found that PNNs modulated the gain of visual responses in the adult mouse visual cortex in vivo. Removal of PNNs in adult V1 strongly increased thalamic neurotransmission selectively on layer 4 PV cells. This produced a differential gating of feed-forward inhibition on principal neurons and other PV cells, with no alterations of unitary inhibitory synaptic transmission and neuronal excitability. These effects depended on visual input, as they were strongly attenuated by monocular deprivation in PNN-depleted adult mice. Thus, PNNs control visual processing and plasticity by selectively setting the strength of thalamic recruitment of PV cells. We conclude that PNN accumulation during circuit maturation likely prevents excessive thalamic excitation of PV cells at the expense of cortical plasticity.
BET inhibition induces HEXIM1- and RAD51-dependent conflicts between transcription and replication
Authors: Bowry Akhil , Piberger Ann Liza , Petermann Eva
Published: July 2018

BET bromodomain proteins are epigenetic readers required for oncogenic transcription activities, and BET inhibitors have been rapidly advanced into clinical trials. Understanding the effects of BET inhibition on other nuclear processes such as DNA replication will be important for future clinical applications. Here we show that BET inhibition causes replication stress in cancer and non-cancer cells due to a rapid burst in global RNA synthesis and interference of transcription with replication. We identify BRD4 as the main BET inhibitor target in this process and provide evidence that BRD4 inhibition causes transcription-replication interference through release of P-TEFb from its inhibitor HEXIM1, promoting RNA Polymerase II phosphorylation. Unusually, BET inhibitor-induced transcription-replication interference does not activate the classic ATM/ATR-dependent DNA damage response. We show however that they promote foci formation of the homologous recombination factor RAD51. Both HEXIM1 and RAD51 are required for BET inhibitor-induced fork slowing, but rescuing fork slowing by HEXIM1 or RAD51 depletion activate a DNA damage response. Our data support a new mechanism where BRD4 inhibition slows replication and suppresses DNA damage through concerted action of transcription and homologous recombination machineries. They shed new light on the roles of DNA replication and recombination in the action of this new class of cancer drugs.
Schizophrenia-associated genomic copy number variants and subcortical brain volumes in the UK Biobank
Authors: Warland Anthony , Kendall Kimberley M , Rees Elliott , Kirov George , Caseras Xavier
Published: July 2018

Schizophrenia is a highly heritable disorder for which anatomical brain alterations have been repeatedly reported in clinical samples. Unaffected at-risk groups have also been studied in an attempt to identify brain changes that do not reflect reverse causation or treatment effects. However, no robust associations have been observed between neuroanatomical phenotypes and known genetic risk factors for schizophrenia. We tested subcortical brain volume differences between 49 unaffected participants carrying at least one of the 12 copy number variants associated with schizophrenia in UK Biobank and 9,063 individuals who did not carry any of the 93 copy number variants reported to be pathogenic. Our results show that CNV carriers have reduced volume in some of the subcortical structures previously shown to be reduced in schizophrenia. Moreover, these associations were partially accounted for by the association between pathogenic copy number variants and cognitive impairment, which is one of the features of schizophrenia.
Panoptic vDISCO imaging reveals neuronal connectivity, remote trauma effects and meningeal vessels in intact transparent mice
Authors: Cai Ruiyao , Pan Chenchen , Ghasemigharagoz Alireza , Todorov Mihail I. , Foerstera Benjamin , Zhao Shan , Bhatia Harsharan S. , Mrowka Leander , Theodorou Delphine , Rempfler Markus , Xavier Anna , Kress Benjamin T. , Benakis Corinne , Liesz Arthur , Menze Bjoern , Kerschensteiner Martin , Nedergaard Maiken , Erturk Ali
Published: July 2018

Analysis of entire transparent rodent bodies could provide holistic information on biological systems in health and disease. However, it has been challenging to reliably image and quantify signal from endogenously expressed fluorescent proteins in large cleared mouse bodies due to the low signal contrast. Here, we devised a pressure driven, nanobody based whole-body immunolabeling technology to enhance the signal of fluorescent proteins by up to two orders of magnitude. This allowed us to image subcellular details in transparent mouse bodies through bones and highly autofluorescent tissues, and perform quantifications. We visualized for the first-time whole-body neuronal connectivity of an entire adult mouse and discovered that brain trauma induces degeneration of peripheral axons. We also imaged meningeal lymphatic vessels and immune cells through the intact skull and vertebra in naive animals and trauma models. Thus, our new approach can provide an unbiased holistic view of biological events affecting the nervous system and the rest of the body.