bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased risk of lung cancer in patients with eczema: a nationwide cohort study in Taiwan
Authors: Juan Chao‐Kuei , Shen Jui‐Lung , Lin Cheng‐Li , Kim Karen Wang , Chen Wen‐Chi
Published: September 2016

Background

The association between lung cancer and eczema remains controversial. Previous studies have yielded conflicting results. This retrospective population‐based cohort study is aimed at clarifying the risk of lung cancer associated with eczema.

Patients and Methods

By using the Taiwan National Health Insurance Research Database, we identified 43,719 patients who had been newly diagnosed with eczema in the years 2000 to 2010. The comparison cohort included 87,438 randomly selected, age‐matched patients without eczema. The cases of these two cohorts were followed until 2011. The Cox proportional hazard regression model was used to calculate the risk of lung cancer in eczema patients. The database did not contain any information regarding smoking, alcohol consumption, socioeconomic status, or family history.

Results

After adjusting for age and comorbidity, the population with eczema had a 2.80‐fold greater risk of developing lung cancer compared with the population in the comparison cohort (adjusted hazard ratio 2.80, 95 % confidence interval 2.59–3.03). Eczema patients with comorbid diseases including asthma, chronic obstructive ­pulmonary disease, alcoholic liver damage, or diabetes were at a higher risk of lung cancer compared with the non‐eczema patients without comorbidity.

Conclusions

Eczema is associated with a greater risk for the development of lung cancer. Further studies with more comprehensive information on potential confounders are warranted.
Gerbstoffe ausPotentilla officinaliswirken entzündungshemmend im UV‐Erythem‐Test und bei Anwendung auf atopischer Haut
Authors: Hoffmann Julia , Wölfle Ute , Schempp Christoph M. , Casetti Federica
Published: September 2016

Hintergrund

Das Rhizom vonPotentilla officinalis(PO) ist reich an Gerbstoffen und wird traditionell zur äußerlichen Behandlung von Entzündungen der Haut und der Schleimhäute verwendet. Ziel der vorliegenden Arbeit war die Bestätigung der antiinflammatorischen Eigenschaften von PO mittels eines UV‐Erythem‐Tests und einer klinischen Anwendungsstudie bei atopischer Haut.

Probanden und Methodik

Die antiinflammatorische Wirkung eines PO‐Extrakts (standardisiert auf 2 % Trockensubstanz) wurde in einer prospektiven, randomisierten, placebokontrollierten Doppelblindstudie mit 40 gesunden Erwachsenen im UV‐Erythem‐Test im Vergleich zu 1 % Hydrocortisonacetat untersucht. Im Rahmen einer prospektiven nicht kontrollierten Studie wurde die Wirkung und Verträglichkeit der 2 % PO‐Creme an zwölf Erwachsenen und zwölf Kindern mit atopischer Haut nach Anwendung über zwei Wochen in einem definierten Testareal anhand eines Teil‐SCORAD untersucht. Zusätzlich wurde die Beeinflussung der Hautrötung im Testareal photometrisch gemessen.

Ergebnisse

Im UV‐Erythem‐Test zeigte die PO‐Creme eine signifikante Reduktion des Erythemindex im Vergleich zum Vehikel. Die antiinflammatorische Wirkung des Verums entsprach der der 1 % Hydrocortisonacetat‐Creme. Die klinische Studie bei Atopikern zeigte eine signifikante Abnahme des Teil‐SCORAD und des Erythems im Testareal. Es wurden keine Unverträglichkeitsreaktionen beobachtet.

Schlussfolgerungen

PO als 2%ige Zubereitung besitzt entzündungshemmende Eigenschaften und ist wirksam und gut verträglich auf atopischer Haut.
Mapping ‘hydroscapes’ along the iso‐ to anisohydric continuum of stomatal regulation of plant water status
Authors: Meinzer Frederick C. , Woodruff David R. , Marias Danielle E. , Smith Duncan D. , McCulloh Katherine A. , Howard Ava R. , Magedman Alicia L.
Published: September 2016

The concept of iso‐ vs. anisohydry has been used to describe the stringency of stomatal regulation of plant water potential (ψ). However, metrics that accurately and consistently quantify species’ operating ranges along a continuum of iso‐ to anisohydry have been elusive. Additionally, most approaches to quantifying iso/anisohydry require labour‐intensive measurements during prolonged drought. We evaluated new and previously developed metrics of stringency of stomatal regulation of ψ during soil drying in eight woody species and determined whether easily‐determined leaf pressure–volume traits could serve as proxies for their degree of iso‐ vs. anisohydry. Two metrics of stringency of stomatal control of ψ, (1) a ‘hydroscape’ incorporating the landscape of ψ over which stomata control ψ, and (2) the slope of the daily range of ψ as pre‐dawn ψ declined, were strongly correlated with each other and with the leaf osmotic potential at full and zero turgor derived from pressure–volume curves.
Prairie wetland communities recover at different rates following hydrological restoration
Authors: Bortolotti Lauren E. , Vinebrooke Rolf D. , St. Louis Vincent L.
Published: September 2016

Prairie pothole wetlands provide many ecosystem services, including supporting biodiversity and filtering water on the landscape. However, over half of these wetlands have been drained for agriculture, thereby requiring restoration to re‐establish ecosystem services.

We assessed the recovery of hydrologically restored wetlands based on water chemistry and taxonomic shifts within and across five biological communities (phytoplankton, benthic diatoms, zooplankton, macroinvertebrates, submersed aquatic vegetation [SAV]). We sampled 24 wetlands in southeastern Saskatchewan, Canada, spanning three restoration states: recently restored (restored 1–3 years before the study; n = 8), older restored (restored 7–14 years before the study; n = 8) and natural (never drained; n = 8).

Within approximately a decade of the re‐establishment of these previously drained wetlands, water chemistry, macroinvertebrate and SAV communities closely resembled those in natural wetlands. Here, total phosphorus and carbon dioxide concentrations declined, while salinity and pH increased, with time since restoration. No detectable differences in diatom and zooplankton communities persisted among the restored and natural sites; however, cyanobacteria were more representative of the restored wetlands

Our findings suggest that hydrological restoration is an effective tool for re‐establishing baseline water quality and the capacity of prairie wetlands to support biodiversity across multiple trophic levels. However, given that there is a decadal lag in the re‐establishment of certain species, it is preferable to protect and retain intact wetlands on the landscape.
Control of Rate of Solute Transport in Newly Developed Portable Agar Gel Blood Purification System
Authors: Yamashita Akihiro C. , Sakiyama Ryoichi , Hamada Hiroyuki , Tojo Kakuji J.
Published: September 2016

Ablood purification module was developed with edible agar or Gelrite, in which activated charcoal was dispersed. Tap water (or normal saline) was boiled, and agar (or Gelrite) powder was dissolved in it. The solution was hardened with no additive or activated charcoal in a

plastic cylindrical hard shell with a perforated bottom plate to assemble module A (agar only), module AC (agar with various amounts of charcoal), or module GC (Gelrite with various amounts of charcoal), respectively. The hardened gel was thrust with a plastic straw 21 times in the flow direction. Aqueous test solution was prepared for device evaluation. Bromophenol blue (BPB) concentration decreased only by 10% with module A, whereas it gradually decreased according to the amount of activated charcoal dispersed in the agar with module AC; moreover, it reached its lower limit found by direct use of the same amount of intact activated charcoal. Module GC was shown to remove creatinine continuously from bovine whole blood. A portable artificial kidney system may be constructed by combining these modules with a small hemofilter for removing excess water.
Prevention of Damage to Cuffed Catheters
Authors: Agraharkar Mahendra , Siddiqui Mohammad , Ahuja Tejinder
Published: September 2016

Cuffed catheters, although not ideal for long‐term use, are now used more frequently due to an increase in the aging population, in whom the vessels are not suitable for either arteriovenous fistulas or polytetrafluoroethylene (PTFE) grafts. Infections and thrombosis remain the major causes for removal or change of catheters.

We recently identified eight catheter defects that required replacement of catheters. Of these, two were due to patient negligence: one catheter was accidentally severed while the patient was shaving; the other was snipped during a haircut. One was believed to have a manufacturing defect. One catheter sustained needle‐prick damage near the hub while irrigating the catheter. Two catheters were lost due to needle pricks during skin closure, and one catheter sustained similar damage while fixing the suture wing to the skin. The other two were damaged by suture material slicing through the lumen of the catheter as it expanded due to increased blood flow during repeated dialyses. Importantly, several of these injuries to the catheters were not immediately obvious and were detected only after repeated use of the catheters.

Delayed bleeding of cuffed catheters necessitating change or removal has not been reported. Such bleeding may be due to manufacturing defects, patient carelessness, or iatrogenic causes. Avoiding the use of sutures can minimize the latter. Skin closure strips and a double transparent dressing may serve the same purposes, such as securing the catheter and aiding wound healing. In addition, these dressings have the added advantage of being waterproof, bacteria‐proof, and cost effective.
Use of Systemic Blood Urea Nitrogen Levels Obtained 30 Minutes before the End of Hemodialysis to Portray Equilibrated, Postdialysis Blood Urea Nitrogen Values
Authors: Ing Todd S. , Blagg Christopher R. , Delano Barbara G. , Gandhi Vasant C. , Ting George O. , Twardowski Zbylut J. , Williams Amy W. , Woredekal Yalem W. , Kjellstrand Carl M.
Published: September 2016

Blood urea nitrogen (BUN) levels obtained at 30 minutes before the end of dialysis were found to be closely similar to equilibrated, postdialysis BUN values obtained 30 minutes after the end of dialysis. Because of this similarity, the former BUN values can be used to derive equilibrated urea reduction ratio, or equilibrated Kt/V instead.
Effect of Valsalva Maneuver on QT Dispersion in Hemodialysis Patients
Authors: Akkaya Vakur , Y2ld2z Alaattin , Tükek Tufan , Aysuna Nilgun , At2lgan Dursun , Bozfak2oglu Semra , Ark Ergin
Published: September 2016

Increased QT dispersion seems to be related to an increased risk of arrhythmia and sudden death, a common cause of mortality in hemodialysis (HD) patients. Increase in sympathetic tone has been documented in HD patients. In this study, we aimed to investigate the effect of changes in the autonomic tone on QT dispersion (QTd) in HD patients.

Twenty HD patients (M/F 13/7; age, mean ±SD, 28 ± 10 years) and 22 age‐ and sex‐matched healthy controls (M/F 12/10; age, 30 ± 10 years) were included. The patients were dialyzed three‐times weekly; time on dialysis was 17 ± 8 months. The QT durations were measured from 12 lead surface EKGs and were corrected for RR intervals. Corrected maximum (QTc max) and minimum (QTcmin) QT intervals and their difference (QT c d) were recorded. The effect of the Valsalva maneuver in the release phase on QT c intervals and dispersion was assessed.

The HD patients had prolonged values compared to controls: QT c d, 59 ± 17 ms versus 35 ± 7 ms, p < 0.001; QT c max, 458 ± 41 ms versus 397 ± 21 ms, p < 0.001; and QT c min, 398 ± 36 ms versus 362 ± 25 ms, p < 0.001. After the Valsalva maneuver no changes were observed in controls: QT c max, 397 ± 21 ms versus 396 ± 22 ms, p = 0.9; QT c min, 362 ± 24 ms versus 358 ± 19 ms, p = 0.5; and QT c d, 35 ± 7 ms versus 38 ± 10 ms, p = 0.15. Whereas, in HD patients all values were significantly shortened: QTcmax, 458 ± 41 ms versus 427 ± 35 ms, p = 0.003; QTc min, 398 ± 36 ms versus 379 ± 34 ms, p = 0.04; and QTc d, 59 ± 17 ms versus 48 ± 15 ms, p = 0.01. The decrease in QTmax was more prominent than the decrease in QTmin, hence QT dispersion was significantly decreased after the Valsalva maneuver, but differences from controls were still significant.

In conclusion, increased sympathetic activity may have a role in the prolonged QT duration and increased QT dispersion in HD patients.
Clinical Determination of Dry Body Weight
Authors: Charra Bernard , Jean Guillaume , Hurot Jean-Marc , Terrat Jean-Claude , Vanel Thierry , VoVan Cyril , Maazoun Foued , Chazot Charles
Published: September 2016

While nephrologists wait for the ideal, non invasive, inexpensive, precise, and reproducible tool to evaluate extracellular volume (ECV), they need to exert their clinical acumen in the quest of that holy grail, dry weight (DW).

Estimation of DW using a clinical approach based on blood pressure (BP) and ECV is feasible and reliable as shown by successful experiences in various dialysis modes over more than three decades. But a need still exists to resolve difficulties associated with accurate assessment of BP (methods and circumstances of measurement, and the confounding effects of antihypertensive drugs) and ECV (evaluation of weight changes unrelated to ECV, lack of specificity and sensitivity of clinical symptoms, lag time, confusion in terminology). An essential point in clinical assessment of DW is that a normal BP is at the same time the target and the crucial index of DW achievement. For this reason, a trialand‐error “probe” process has to be used at intervals to make sure that the dry weight target point is correctly estimated.

The various “non clinical” methods proposed for dry weight assessment increase the complexity and the cost of hemodialysis. They are, in the present state of things, more clinical research than practice tools. They do not replace clinical judgment.
Remote Monitoring of Daily Nocturnal Hemodialysis
Authors: Hoy Christopher D.
Published: September 2016

Daily nocturnal hemodialysis (DNHD) is a new variant of home hemodialysis that allows patients to dialyze at home, at night, while they sleep, providing longer duration and greater frequency of treatments. This paper describes a 3‐year experience with remote monitoring of DNHD patients over the Internet, and we review the remote monitoring experience of the Toronto program, which pioneered DNHD. Technology, structure, and costs are reviewed. Remote monitoring enhanced safety, accuracy of data collection, patient catchment area, and the overall comfort of patients, providers, and regulators.
Pathophysiology and Treatment of Hyperhomocysteinemia in End‐Stage Renal Disease Patients
Authors: Sunder–Plassmann G. , Hörl Walter H.
Published: September 2016

The pathophysiology of hyperhomocysteinemia in end‐stage renal disease (ESRD) patients includes impaired remethylation of homocysteine (Hcy) to methionine, inhibition of extrarenal Hcy metabolism by uremic solutes, a block in decarboxylation of cysteinesulfinic acid, impaired [adenosylmethionine]/[adenosylhomocysteine] ratio, and a probable impairment of renal Hcy metabolism and excretion.

Treatment of hyperhomocysteinemia in ESRD patients includes administration of folic acid (1 – 15 mg per day). No additional effects have been observed with higher folic acid doses, folinic acid, or 5‐methyltetrahydrofolate. Oral supplementation with vitamin B 6 and vitamin B 12 has no effect, but some studies reported a decrease of plasma Hcy with high intravenous vitamin doses. Effective reduction of plasma total Hcy (tHcy) in patients treated with super‐flux hemodialyzers suggests the removal of uremic toxins with inhibitory activities against enzymes involved in the extrarenal Hcy metabolism.
A Composite Index of Compliance for Chronic In‐Center Hemodialysis Patients
Authors: Servilla Karen S. , Tzamaloukas Antonios H. , Carter Charles , Murata Glen H.
Published: September 2016

We developed a composite compliance index as the sum of the compliance scores for interdialytic weight gain (IDWG), pre‐dialysis serum potassium and phosphorus concentrations (each scored from zero to 3, with 3 indicating the poorest compliance), and skipping hemodialysis sessions (scored from zero to 9, with 9 indicating the poorest compliance). We used this composite score to prospectively evaluate compliance in 25 prevalent hemodialysis patients over a period of 1 year. We then followed these patients for another 3.5 years. The patients studied were divided into two groups: group A (poor compliance) consisted of 9 subjects with composite score ≥ 9 (13.2 ± 3.2); group B (better compliance) consisted of 16 subjects with composite score < 9 (4.7 ± 1.8). Age, duration of hemodialysis, and frequency of diabetes mellitus did not differ between the groups. Group A contained higher fractions of subjects with history of alcoholism (66.7% vs 12.5%, p = 0.010), other substance addiction (44.4% vs 0%, p = 0.010), and severe psychosocial problems (88.9% vs 18.8%, p = 0.002). Mean survival from the beginning of observation, estimated by actuarial life‐table survival analysis, was 1.19 years in group A and 2.60 years in group B (p = 0.0265). A composite compliance index incorporating domains indicating adherence to diet, medications, and dialysis schedule identified other behavioral problems in poorly compliant patients. Hemodialysis patients characterized by this composite index as poorly compliant had shortened survival.
Comparison of Staff‐Assisted Home Hemodialysis with In‐Center Hemodialysis and In‐Hospital Hemodialysis
Authors: Agraharkar Mahendra , Du Yong , Ahuja Tejinder , Barclay Cynthia
Published: September 2016

Home hemodialysis (HHD) is superior to in‐center hemodialysis (ICHD) in terms of survival, quality of life, and cost‐effectiveness. However, assistance from family members in performing HHD is not always available to patients, and professional assistance for HHD can be cost prohibitive. For certain patients, ICHD can be impractical due to difficulties in transportation, which may necessitate ambulance transportation or hospitalization for in‐hospital hemodialysis (IHHD). We describe 4 patients that have had problems receiving ICHD for various reasons. Two of these patients had problems with transportation, while the other two could not remain on dialysis for the prescribed duration of time and, therefore, received inadequate dialysis. These patients had difficulty while receiving ICHD in meeting the adequacy criteria set by Dialysis Outcomes Quality Initiative. One of these patients had a neuropsychiatric disorder and displayed disruptive behavior. When these 4 patients were switched to staff‐assisted home hemodialysis (SAHD), the dialysis core indicators improved compared with ICHD, and the patients needed significantly fewer hospitalization days. In this paper, we demonstrate that, in patients that cannot be easily transferred, and in patients with neuropsychiatric disorders, SAHD can be a less expensive and more efficacious modality of dialysis.
Colour in digital pathology: a review
Authors: Clarke Emily L , Treanor Darren
Published: September 2016

Colour is central to the practice of pathology because of the use of coloured histochemical and immunohistochemical stains to visualize tissue features. Our reliance upon histochemical stains and light microscopy has evolved alongside a wide variation in slide colour, with little investigation into the implications of colour variation. However, the introduction of the digital microscope and whole‐slide imaging has highlighted the need for further understanding and control of colour. This is because the digitization process itself introduces further colour variation which may affect diagnosis, and image analysis algorithms often use colour or intensity measures to detect or measure tissue features. The US Food and Drug Administration have released recent guidance stating the need to develop a method of controlling colour reproduction throughout the digitization process in whole‐slide imaging for primary diagnostic use. This comprehensive review introduces applied basic colour physics and colour interpretation by the human visual system, before discussing the importance of colour in pathology. The process of colour calibration and its application to pathology are also included, as well as a summary of the current guidelines and recommendations regarding colour in digital pathology.
Dental complications of gastro‐oesophageal reflux disease: guidance for physicians
Authors: Lee Robert J. , Aminian Amin , Brunton Paul
Published: September 2016

There is potential for gastro‐oesophageal reflux disease (GORD) to be under‐diagnosed by physicians. A quick, focused examination, requiring no special equipment, of a patients’ dentition can assist in making a more accurate diagnosis where GORD is suspected. Guidance is provided for physicians as to what intra‐oral signs are suggestive of intrinsic dental erosion, which is a clinical feature of GORD and its associated conditions. Use of this information will, it is suggested, improve outcomes for patients where GORD is suspected.
Cell‐type‐specific modulation of innate immune signalling by vitamin D in human mononuclear phagocytes
Authors: Kundu Rhiannon , Theodoraki Aikaterini , Haas Carolin T. , Zhang Yanjing , Chain Benjamin , Kriston‐Vizi Janos , Noursadeghi Mahdad , Khoo Bernard
Published: September 2016

Vitamin D is widely reported to inhibit innate immune signalling and dendritic cell (DC) maturation as a potential immunoregulatory mechanism. It is not known whether vitamin D has global or gene‐specific effects on transcriptional responses downstream of innate immune stimulation, or whether vitamin D inhibition of innate immune signalling is common to different cells. We confirmed vitamin D inhibition of nuclear factor‐κB (NF‐κB) and p38 mitogen‐activated protein kinase (MAPK) signalling in monocyte‐derived DC (MDDC) stimulated with lipopolysaccharide (LPS). This was associated with global but modest attenuation of LPS‐induced transcriptional changes at genome‐wide level. Surprisingly, vitamin D did not inhibit innate immune NF‐κB activation in monocyte‐derived macrophages. Consistent with our findings in MDDC, ex vivo vitamin D treatment of primary peripheral blood myeloid DC also led to significant inhibition of LPS‐inducible NF‐κB activation. Unexpectedly, in the same samples, vitamin D enhanced activation of both NF‐κB and MAPK signalling in primary peripheral blood monocytes. In a cross‐sectional clinical cohort, we found no relationship between peripheral blood vitamin D levels and LPS‐inducible activation of NF‐κB and MAPK pathways in monocytes of myeloid DC. Remarkably, however, in vivo supplementation of people with vitamin D deficiency in this clinical cohort also enhanced LPS‐inducible MAPK signalling in peripheral blood monocytes. Therefore, we report that vitamin D differentially modulates the molecular response to innate immune stimulation in monocytes, macrophages and dendritic cells. These results are of importance in the design of studies on vitamin D supplementation in infectious and immunological diseases.
Induced regulatory T cells are phenotypically unstable and do not protect mice from rapidly progressive glomerulonephritis
Authors: Ghali Joanna R. , Alikhan Maliha A. , Holdsworth Stephen R. , Kitching A. Richard
Published: September 2016

Regulatory T (Treg) cells are a suppressive CD4+ T‐cell subset. We generated induced Treg (iTreg) cells and explored their therapeutic potential in a murine model of rapidly progressive glomerulonephritis. Polyclonal naive CD4+ T cells were cultured in vitro with interleukin‐2 (IL‐2), transforming growth factor‐β1, all‐trans‐retinoic acid and monoclonal antibodies against interferon‐γ and IL‐4, generating Foxp3+ iTreg cells. To enhance their suppressive phenotype, iTreg cultures were modified with the addition of a monoclonal antibody against IL‐12p40 or by using RORγt–/– CD4+ T cells. Induced Treg cells were transferred into models of delayed‐type hypersensitivity and experimental glomerulonephritis. The iTreg cells exhibited comparable surface receptor expression and in vitro suppressive ability to natural Treg cells, but did not regulate antigen‐specific delayed‐type hypersensitivity or systemic inflammatory immune responses, losing Foxp3 expression in vivo. In glomerulonephritis, transferred iTreg cells did not prevent renal injury or modulate systemic T helper type 1 immune responses. Induced Treg cells cultured with anti‐IL‐12p40 had an enhanced suppressive phenotype in vitro and regulated dermal delayed‐type hypersensitivity in vivo, but were not protective against renal injury, losing Foxp3 expression, especially in the transferred cells recruited to the kidney. Use of RORγt–/– CD4+ T cells or iTreg cells generated from sensitized CD4+ Foxp3– cells did not regulate renal or systemic inflammatory responses in vivo. In conclusion, iTreg cells suppress T‐cell proliferation in vitro, but do not regulate experimental glomerulonephritis, being unstable in this inflammatory milieu in vivo.
India's Mahatma Gandhi National Rural Employment Act: Assessing the quality of access and adequacy of benefits in MGNREGS public works
Authors: Ehmke Ellen
Published: September 2016

The extension of social protection to all has become a central policy objective, both nationally and internationally. A considerable number of middle‐ and low‐income countries have undertaken substantial efforts to extend social protection, while the international community reaffirmed its commitment to the extension of social protection through the adoption of the ILO Recommendation concerning National Floors of Social Protection, No. 202 (2012). This article reviews the legal provisions and the implementation of the Indian Mahatma Gandhi National Rural Employment Guarantee Act (MGNREGA), legislated in 2005, and does so in the light of the more recent provisions of ILO Recommendation No. 202. Since its introduction ten years ago, MGNREGA has provided a source of income to rural workers, increased wage rates, achieved high female participation rates and created durable assets. India's local governance bodies, Panchayati Raj Institutions (PRI), have been empowered and involved in the processes of planning and monitoring. However, despite successes, there have been considerable shortcomings in implementation. This article highlights two central themes: first, the innovative policy framework of the Act, which brings together rights‐based entitlements, demand‐driven employment, and citizen‐centred monitoring. Second, it assesses the accessibility and adequacy of benefits in the implementation of MGNREGA. We conclude that MGNREGA offers potential for South‐South learning, both in terms of policy‐design and implementation.
Paid parental leave and other supports for parents with young children: The United States in international comparison
Authors: Adema Willem , Clarke Chris , Frey Valerie
Published: September 2016

The United States is at a crossroads in its policies for families and women. Currently, the United States provides basic support for children, fathers, and mothers in the form of unpaid parental leave, child‐related tax breaks, and limited public child care. In contrast, the other member states of the Organisation for Economic Co‐operation and Development (OECD) empower families through paid parental leave and comprehensive investments in infants and children. The potential gains from strengthening these policies in the United States are enormous. Paid parental leave and subsidized child‐care help to get and keep more women in the workforce, contribute to economic growth, offer cognitive and health benefits to children, and give parents options in defining their preferred work‐life strategy. Indeed, the United States has been falling behind the rest of the OECD in many social and economic indicators by not adequately investing in children, fathers and mothers. Given the significant payoffs to these family supports, this article focuses on issues of reconciling work and care commitments for families with young children, and, in particular, on paid parental leave policies within the OECD and the United States.
Utility of Pain Drawings Rated for Non‐Organic Pain in Chronic Low Back Pain Populations: A Qualitative Systematic Review
Authors: Hartzell Meredith M. , Liegey‐Dougall Angela , Kishino Nancy D. , Gatchel Robert J.
Published: September 2016

Pain drawings are useful for comprehensively assessing chronic pain. They are brief to administer and score, easy to use, and provide information about patient outcomes. In the present study, pain drawings evaluating non‐organic pain were examined for utility and effectiveness. A qualitative systematic review revealed that non‐organic pain drawings, although diverse in nature, are highly reliable and valid and relate to many constructs. Pain drawing ratings may be a general screener for psychosocial distress, as they relate to demographics, medication use, personality, cognition, quality of life, self‐reported disability, and work outcomes. Although utilization of non‐organic pain scales has become less frequent, the concept of non‐organic pain remains relevant, despite new terminology usage, such as somatization and central sensitization.
Residual Fat Stigma After Weight Loss: The Mediating Role of Perceived Effort
Authors: Stambush Mark A. , Hill‐Mercer Ashley E. , Mattingly Brent A.
Published: September 2016

The current research examined if the method of weight loss influences individuals' perceptions of a formerly fat target. Participants were randomly assigned to one of three weight loss descriptions: diet/exercise, diet pill, or no weight loss description (control). Targets who lost weight via diet pill were ascribed more negative attributions relative to those who lost weight via diet/exercise. This relationship was mediated by the amount of perceived effort expended to achieve weight loss. Furthermore, these findings suggest that individuals who lose weight are still susceptible to the negative attributions and stigmatizations associated with fatness, particularly if a less effortful method is used.
Hypervigilance‐avoidance in children with anxiety disorders: magnetoencephalographic evidence
Authors: Wessing Ida , Romer Georg , Junghöfer Markus
Published: September 2016

Background

An altered pattern of threat processing is deemed critical for the development of anxiety disorders (AD). According to the hypervigilance‐avoidance hypothesis, AD patients show hypervigilance to threat cues at early stages of processing but avoid threat cues at later stages of processing. Consistently, adults with AD show enhanced neurophysiological responses to threat in early time windows and reduced responses to threat in late time windows. The presence of such a hypervigilance‐avoidance effect and its underlying neural sources remain to be determined in clinically anxious children.

Methods

Twenty‐three children diagnosed with an AD and 23 healthy control children aged 8–14 years saw faces with angry and neutral expressions while whole‐head magnetoencephalography (MEG) was recorded. Neural sources were estimated based on L2‐Minimum Norm inverse source modeling and analyzed in early, midlatency, and late time windows.

Results

In visual cortical regions, early threat processing was relatively enhanced in patients compared to controls, whereas this relation was inverted in a late interval. Consistent with the idea of affective regulation, the right dorsolateral prefrontal cortex revealed relatively reduced inhibition of early threat processing but revealed enhanced inhibition at a late interval in patients. Both visual‐sensory and prefrontal effects were correlated with individual trait anxiety.

Conclusions

These results support the hypothesis of early sensory hypervigilance followed by later avoidance of threat in anxiety disordered children, presumably modulated by early reduced and later enhanced prefrontal inhibition. This neuronal hypervigilance‐avoidance pattern unfolds gradually with increasing trait anxiety, reflecting a progressively biased allocation of attention to threat.
Alopecia areata totalis and universalis: a multicenter review of 132 patients in Spain
Authors: Vañó‐Galván S. , Fernández‐Crehuet P. , Grimalt R. , Garcia‐Hernandez M.J. , Rodrigues‐Barata R. , Arias‐Santiago S. , Molina‐Ruiz A. , Garcia‐Lora E. , Dominguez‐Cruz J. , Brugues A. , Ferrando J. , Serrano‐Falcón C. , Serrano S. , Paoli J. , Camacho F.
Published: September 2016

Background

Alopecia areata totalis (AAT) and universalis (AAU) pose a therapeutic challenge.

Objective

To describe the clinical and epidemiological features, therapeutic response and prognostic factors in a large series of patients diagnosed with AAT and AAU.

Methods

This retrospective multicenter study included patients diagnosed with AAT/AAU with a minimum follow‐up of 12 months. Response was assessed based on the regrowth of scalp hair.

Results

In all, 132 patients (92 women and 40 men) – 80 (61%) diagnosed with AAU and 52 (39%) diagnosed with AAT – were included. The median time between the presentation of alopecia areata (AA) and the development of extensive AA was 1 year and it was less than 4 years in 121 patients (91%). There was an initial response to treatment in 64% of patients, although only 14% presented a persistent response. Adverse side effects from the medications used were detected in 33% of patients. The prognostic factors associated with poor response were the presence of AAU and a positive family history of AA.

Conclusions

Treatment of AAT and AAU is challenging. Although an initial regrowth may be achieved, the duration of response is usually short. There were no significant differences on the effectiveness or duration of response between the various systemic therapies.
Lytic transglycosylases LtgA and LtgD perform distinct roles in remodeling, recycling and releasing peptidoglycan in Neisseria gonorrhoeae
Authors: Schaub Ryan E. , Chan Yolande A. , Lee Mijoon , Hesek Dusan , Mobashery Shahriar , Dillard Joseph P.
Published: September 2016

Neisseria gonorrhoeae releases peptidoglycan (PG) fragments during infection that provoke a large inflammatory response and, in pelvic inflammatory disease, this response leads to the death and sloughing of ciliated cells of the Fallopian tube. We characterized the biochemical functions and localization of two enzymes responsible for the release of proinflammatory PG fragments. The putative lytic transglycosylases LtgA and LtgD were shown to create the 1,6‐anhydromuramyl moieties, and both enzymes were able to digest a small, synthetic tetrasaccharide dipeptide PG fragment into the cognate 1,6‐anhydromuramyl‐containing reaction products. Degradation of tetrasaccharide PG fragments by LtgA is the first demonstration of a family 1 lytic transglycosylase exhibiting this activity. Pulse‐chase experiments in gonococci demonstrated that LtgA produces a larger amount of PG fragments than LtgD, and a vast majority of these fragments are recycled. In contrast, LtgD was necessary for wild‐type levels of PG precursor incorporation and produced fragments predominantly released from the cell. Additionally, super‐resolution microscopy established that LtgA localizes to the septum, whereas LtgD is localized around the cell. This investigation suggests a model where LtgD produces PG monomers in such a way that these fragments are released, whereas LtgA creates fragments that are mostly taken into the cytoplasm for recycling.
Condition‐dependent co‐regulation of genomic clusters of virulence factors in the grapevine trunk pathogen Neofusicoccum parvum
Authors: Massonnet Mélanie , Morales‐Cruz Abraham , Figueroa‐Balderas Rosa , Lawrence Daniel P. , Baumgartner Kendra , Cantu Dario
Published: September 2016

The ascomycete Neofusicoccum parvum, one of the causal agents of Botryosphaeria dieback, is a destructive wood‐infecting fungus and a serious threat to grape production worldwide. The capability to colonize woody tissue, combined with the secretion of phytotoxic compounds, is thought to underlie its pathogenicity and virulence. Here, we describe the repertoire of virulence factors and their transcriptional dynamics as the fungus feeds on different substrates and colonizes the woody stem. We assembled and annotated a highly contiguous genome using single‐molecule real‐time DNA sequencing. Transcriptome profiling by RNA sequencing determined the genome‐wide patterns of expression of virulence factors both in vitro (potato dextrose agar or medium amended with grape wood as substrate) and in planta. Pairwise statistical testing of differential expression, followed by co‐expression network analysis, revealed that physically clustered genes coding for putative virulence functions were induced depending on the substrate or stage of plant infection. Co‐expressed gene clusters were significantly enriched not only in genes associated with secondary metabolism, but also in those associated with cell wall degradation, suggesting that dynamic co‐regulation of transcriptional networks contributes to multiple aspects of N. parvum virulence. In most of the co‐expressed clusters, all genes shared at least a common motif in their promoter region, indicative of co‐regulation by the same transcription factor. Co‐expression analysis also identified chromatin regulators with correlated expression with inducible clusters of virulence factors, suggesting a complex, multi‐layered regulation of the virulence repertoire of N. parvum.
Pepsin in saliva as a biomarker for oropharyngeal reflux compared with 24‐hour esophageal impedance/pH monitoring in pediatric patients
Authors: Fortunato J. E. , D'Agostino R. B. , Lively M. O.
Published: September 2016

Background

Pepsin in saliva is a proposed biomarker for oropharyngeal reflux. Pepsin may be prevalent in saliva from subjects with gastro‐esophageal reflux and may correlate with proximal reflux by intraluminal impedance/pH monitoring (MII/pH).

Methods

Patients (3 days to 17.6 years, n=90) undergoing 24‐hour MII/pH monitoring and asymptomatic controls (2 months to 13.7 years, n=43) were included. Salivary pepsin was determined using a pepsin enzyme‐linked immunosorbent assay. Eight saliva samples were collected from patients undergoing 24‐hr MII/pH: (i) before catheter placement, (ii) before and 30 minutes after each of three meals, and (iii) upon awakening. One sample was collected from each control.

Key Results

In MII/pH subjects, 85.6% (77/90) had at least one pepsin‐positive sample compared with 9.3% (4/43) in controls. The range of pepsin observed in individual subjects varied widely over 24 hours. The average pepsin concentration in all samples obtained within 2 hours following the most recent reflux event was 30.7±135 ng/mL, decreasing to 16.5±39.1 ng/mL in samples collected more than 2 hours later. The frequency of pepsin‐positive samples correlated significantly with symptom index (rS=0.332, P=.0014), proximal (rS=0.340, P=.0010), and distal (rS=0.272, P=.0095) MII events.

Conclusions & Inferences

Concentration of salivary pepsin may not be an accurate measure of severity of reflux because of the wide range observed in individuals over 24 hours. Saliva samples must be obtained soon after a reflux event. Defining a regimen for optimal saliva collection may help to achieve the goal of using salivary pepsin as a biomarker for oropharyngeal reflux.

Clinical Trial registry

NCT01091805.
APETALA2 antagonizes the transcriptional activity of AGAMOUS in regulating floral stem cells in Arabidopsis thaliana
Authors: Huang Zhigang , Shi Ting , Zheng Binglian , Yumul Rae Eden , Liu Xigang , You Chenjiang , Gao Zhihong , Xiao Langtao , Chen Xuemei
Published: September 2016

APETALA2 (AP2) is best known for its function in the outer two floral whorls, where it specifies the identities of sepals and petals by restricting the expression of AGAMOUS (AG) to the inner two whorls in Arabidopsis thaliana. Here, we describe a role of AP2 in promoting the maintenance of floral stem cell fate, not by repressing AG transcription, but by antagonizing AG activity in the center of the flower.

We performed a genetic screen with ag‐10 plants, which exhibit a weak floral determinacy defect, and isolated a mutant with a strong floral determinacy defect. This mutant was found to harbor another mutation in AG and was named ag‐11. We performed a genetic screen in the ag‐11 background to isolate mutations that suppress the floral determinacy defect. Two suppressor mutants were found to harbor mutations in AP2.

While AG is known to shut down the expression of the stem cell maintenance gene WUSCHEL (WUS) to terminate floral stem cell fate, AP2 promotes the expression of WUS.

AP2 does not repress the transcription of AG in the inner two whorls, but instead counteracts AG activity.
Genome‐wide association analysis reveals distinct genetic architectures for single and combined stress responses in Arabidopsis thaliana
Authors: Davila Olivas Nelson H. , Kruijer Willem , Gort Gerrit , Wijnen Cris L. , van Loon Joop J. A. , Dicke Marcel
Published: September 2016

Plants are commonly exposed to abiotic and biotic stresses.

We used 350 Arabidopsis thaliana accessions grown under controlled conditions. We employed genome‐wide association analysis to investigate the genetic architecture and underlying loci involved in genetic variation in resistance to: two specialist insect herbivores, Pieris rapae and Plutella xylostella; and combinations of stresses, i.e. drought followed by P. rapae and infection by the fungal pathogen Botrytis cinerea followed by infestation by P. rapae.

We found that genetic variation in resistance to combined stresses by drought plus P. rapae was limited compared with B. cinerea plus P. rapae or P. rapae alone. Resistance to the two caterpillars is controlled by different genetic components. There is limited overlap in the quantitative trait loci (QTLs) underlying resistance to combined stresses by drought plus P. rapae or B. cinerea plus P. rapae and P. rapae alone. Finally, several candidate genes involved in the biosynthesis of aliphatic glucosinolates and proteinase inhibitors were identified to be involved in resistance to P. rapae and P. xylostella, respectively.

This study underlines the importance of investigating plant responses to combinations of stresses. The value of this approach for breeding plants for resistance to combinatorial stresses is discussed.
Why do plants produce so many terpenoid compounds?
Authors: Pichersky Eran , Raguso Robert A.
Published: September 2016

All plants synthesize a suite of several hundred terpenoid compounds with roles that include phytohormones, protein modification reagents, anti‐oxidants, and more. Different plant lineages also synthesize hundreds of distinct terpenoids, with the total number of such specialized plant terpenoids estimated in the scores of thousands. Phylogenetically restricted terpenoids are implicated in defense or in the attraction of beneficial organisms. A popular hypothesis is that the ability of plants to synthesize new compounds arose incrementally by selection when, as a result of gradual changes in their biotic partners and enemies, the ‘old’ plant compounds were no longer effective, a process dubbed the ‘coevolutionary arms race’. Another hypothesis posits that often the sheer diversity of such compounds provides benefits that a single compound cannot. In this article, we review the unique features of the biosynthetic apparatus of terpenes in plants that facilitate the production of large numbers of distinct terpenoids in each species and how facile genetic and biochemical changes can lead to the further diversification of terpenoids. We then discuss evidence relating to the hypotheses that given ecological functions may be enhanced by the presence of mixtures of terpenes and that the acquisition of new functions by terpenoids may favor their retention once the original functions are lost.
How functional disability relates to dentition in community‐dwelling older adults in Brazil
Authors: Antunes JLF , de Andrade FB , Peres MA
Published: September 2016

Objective

To assess the association between dentition status and functional disabilities among community‐dwelling older individuals.

Subjects and methods

A total of 5012 individuals aged 65–74 were interviewed in 2013 during a nationwide community‐based survey. This cross‐sectional study used a questionnaire including information on dentition, locomotion impairment, difficulties in basic and instrumental activities of daily life, socio‐demographic characteristics, behaviour and general health status. Poisson regression models assessed prevalence ratios (PR) and 95% confidence intervals (95% CI).

Results

About 31.3% of older people in Brazil reported having ≥21 preserved teeth, the condition for a functional dentition without prosthetic appliances. This proportion was significantly lower among individuals with locomotion impairment and difficulties in basic and instrumental activities of daily life. After adjusting for relevant covariates, functional dentition remained statistically associated with severe (PR = 0.69, 95% CI = 0.15–0.63) and total (PR = 0.69, 95% CI = 0.26–0.44) locomotion impairments, and difficulties in basic activities of daily life (PR = 0.70, 95% CI = 0.53–0.93).

Conclusion

Having a functional dentition was significantly less prevalent among those affected by functional disabilities, and this association is unlikely to be due to insufficient control for relevant covariates. The association between dentition and functional disability is bidirectional and involves a complex interplay of one upon the other, and of factors that influence both outcomes.
WHAT CAUSES PATRONAGE REFORM? IT DEPENDS ON THE TYPE OF CIVIL SERVICE REFORM
Authors: SCHUSTER CHRISTIAN
Published: September 2016

Public employment in most developing countries is governed by political patronage. Patronage provides many incumbents with governability and electoral advantage. What causes governments to forsake patronage in favour of civil service reform? This article reviews scholarly explanations. It finds that studies usefully identify diverse socioeconomic and political‐institutional factors which can affect reform incentives. The causal effects of these factors – their weight, mechanisms and signs – are contested, however. This article partially resolves this contestation by considering which reform studies explain: different bureaucratic structures develop asynchronously and feature different determinants. To illustrate, political competition is argued to incentivize reform to ‘blanket in’ party appointees; or do the opposite by reducing expectations to reap longer‐term state capacity benefits. Yet, ‘blanketing in’ necessitates bureaucratic job stability, while state capacity requires merit recruitment of skilled bureaucrats – two poorly correlated reforms. The causes of patronage reform thus depend on the type of civil service reform.
The emerging role of long non‐coding RNAs in cutaneous melanoma
Authors: Leucci Eleonora , Coe Elizabeth A. , Marine Jean‐Christophe , Vance Keith W.
Published: September 2016

Malignant melanoma is a highly aggressive form of skin cancer, the incidence of which is rising rapidly. Although MAPK‐targeting therapies and immune checkpoint blockade are emerging as attractive therapeutic approaches, their utility is limited to only a subset of patients who often acquire resistance. A better understanding of the aetiologies and genetic underpinnings of melanoma is therefore critical for the development of adjuvant or alternative therapeutic strategies aimed at increasing the proportion of responders and improving treatment efficacy. A key step in identifying novel therapeutic targets may be the shift in focus from the protein‐coding components to the non‐coding portion of the genome. The latter, representing about 98% of the genome, serves as a template for the transcription of many thousands of long non‐coding RNAs (lncRNAs). Intriguingly, lncRNA loci are frequently mutated or altered in a variety of cancers, including melanoma, and there is growing evidence that lncRNAs can function as cancer‐causing oncogenes or tumour suppressors. In this review, we summarize recent data highlighting the importance of lncRNAs in the biology of melanoma and their potential utility as biomarkers and therapeutic targets.