bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of cinacalcet withdrawal in Australian dialysis patients
Authors: Ruderman Irene , Holt Stephen G. , Kirkland Geoffrey S. , Maslen Sophie , Hawley Carmel M. , Oliver Veronica , Krishnasamy Rathika , Gray Nicholas A. , Talaulikar Girish S. , Nelson Craig L. , Rajaram Yogeshwar , Gock Hilton , Au Eric , Elder Grahame J. , Mainra Rahul , Toussaint Nigel D.
Published: July 2018

Background

Secondary hyperparathyroidism (SHPT) in chronic kidney disease is associated with cardiovascular and bone pathology. Measures to achieve parathyroid hormone (PTH) target values and control biochemical abnormalities associated with SHPT require complex therapies, and severe SHPT often requires parathyroidectomy or the calcimimetic cinacalcet. In Australia, cinacalcet was publicly funded for dialysis patients from 2009 to 2015 when funding was withdrawn following publication of the EVOLVE study, which resulted in most patients on cinacalcet ceasing therapy. We examined the clinical and biochemical outcomes associated with this change at Australian renal centres.

Aim

To assess changes to biochemical and clinical outcomes in dialysis patients following cessation of cinacalcet.

Methods

We conducted a retrospective study of dialysis patients who ceased cinacalcet after August 2015 in 11 Australian units. Clinical outcomes and changes in biochemical parameters were assessed over a 24‐ and 12‐month period, respectively, from cessation of cinacalcet.

Results

A total of 228 patients was included (17.7% of all dialysis patients from the units). Patients were aged 63 ± 15 years with 182 patients on haemodialysis and 46 on peritoneal dialysis. Over 24 months following cessation of cinacalcet, we observed 26 parathyroidectomies, 3 episodes of calciphylaxis, 8 fractures and 50 deaths. Eight patients recommenced cinacalcet, meeting criteria under a special access scheme. Biochemical changes from baseline to 12 months after cessation included increased levels of serum PTH from 54 (interquartile range 27–90) pmol/L to 85 (interquartile range 41–139) pmol/L (P < 0.0001), serum calcium from 2.3 ± 0.2 mmol/L to 2.5 ± 0.1 mmol/L (P < 0.0001) and alkaline phosphatase from 123 (92–176) IU/L to 143 (102–197) IU/L (P < 0.0001).

Conclusion

Significant increases in serum PTH, calcium and alkaline phosphatase occurred over a 12‐month period following withdrawal of cinacalcet. Longer‐term follow up will determine if these biochemical and therapeutic changes are associated with altered rates of parathyroidectomies and cardiovascular mortality and morbidity.
Relationship between pulse pressure and inflammation with left ventricular diastolic dysfunction in chronic kidney disease patients
Authors: Yong Kenneth , Mori Trevor , Chew Gerard , Beilin Lawrence J. , Puddey Ian , Watts Gerald , Dogra Gursharan , Boudville Neil , Lim Wai
Published: July 2018

Background

Diastolic dysfunction (DD) is an important cause of cardiovascular disease (CVD) mortality in chronic kidney disease (CKD) patients. Non‐traditional risk factors, such as arterial stiffness and inflammation, are implicated in the pathogenesis of DD in CKD patients.

Aim

To determine the association between inflammatory markers (interleukin (IL)‐12, IL‐18, highly sensitive C‐reactive protein (hsCRP)) and non‐invasive markers of arterial stiffness (24‐h pulse pressure (PP)) with DD in stages 3–4 CKD patients.

Methods

We performed a sub‐analysis of 78 non‐diabetic stages 3–4 CKD subjects to determine the relationship between 24‐h PP, IL‐12, IL‐18 and hsCRP with DD.

Results

DD was present in 38 subjects (49%). Subjects with DD were significantly older (61.0 ± 1.9 vs 50.2 ± 2.0 years; P < 0.001) and had higher 24‐h PP (48(95% confidence interval 45, 52) vs 43(95% confidence interval 41, 45) mmHg; P < 0.005); 24‐h PP was associated with DD (P = 0.02), but this was no longer significant after adjustment for age (P = 0.31). Serum IL‐12, IL‐18 and hsCRP levels were not significantly different between subjects with or without DD.

Conclusion

Asymptomatic subclinical DD was present in 50% of a cohort of stages 3–4 CKD patients but was not associated with IL‐12, IL‐18 or hsCRP. The association between 24‐h PP and DD was no longer apparent following adjustment for age, but given the small sample size, our findings will need to be explored in larger‐sized cohorts of individuals with moderate‐stage CKD.
Why is change a challenge in acute mental health wards? A cross‐sectional investigation of the relationships between burnout, occupational status and nurses’ perceptions of barriers to change
Authors: Laker Caroline , Cella Matteo , Callard Felicity , Wykes Til
Published: July 2018

Changes in UK psychiatric wards have been difficult to implement. Specific areas of nursing staff resistance remain unclear. Previous healthcare research suggests that burnout is common and that managers’ regard changes more positively than direct care staff. We will therefore examine whether burnout and workforce characteristics influence psychiatric nurses’ perceptions of barriers to change. Psychiatric nurses (N = 125) completed perceptions measures of ‘barriers to change’ (VOCALISE: subscales included ‘powerlessness, confidence and demotivation’); and ‘burnout’ (Maslach Burnout Inventory: subscales included ‘emotional exhaustion, personal accomplishment and depersonalization ‘). Staff characteristics, such as length of employment, occupational status, education, ethnicity, gender and age, were also collected. Correlations between these measures informed random‐effects regression models, which were conducted to predict the barriers to change score and to explore differential effects in the subscales of VOCALISE. Perceptions of barriers to change (VOCALISE) were correlated with burnout (r = 0.39), occupational status (r = −0.18) and age (r = 0.22). Burnout (Coef. β: 10.52; P > 0.001) and occupational status (Coef. β: −4.58; P = 0.05) predicted VOCALISE. Emotional exhaustion (Coef. β: 0.18; P < 0.001) and low personal accomplishment (Coef. β: 0.21; P = 0.001) predicted powerlessness. Emotional exhaustion predicted low motivation regarding changes (Coef. β: 0.11; P = 0.005). Low confidence predicted high levels of depersonalization (Coef β: 0.23; P = 0.01). Direct care staff expressed significantly more powerlessness (Coef. β: −2.60; P = 0.02) and significantly less confidence (Coef. β: −3.07; P = 0.002) than managers. For changes to be successful in psychiatric wards, burnout will need to be addressed. Future change strategies may consider involving direct care staff to improve perceptions of barriers to change.
Workaholism and occupational health: A translational review
Authors: Aziz Shahnaz , Moyer Fiona
Published: July 2018

The purpose of this article was to provide a detailed review of workaholism, a topic within the realm of Occupational Health Psychology. Workaholism has become a commonplace term used in the popular culture to depict individuals who are addicted to work. It is typically characterized as an addiction and defined as the compulsive tendency to work excessively hard. Given the deleterious effects of workaholism, this article provides a review of what we know about this phenomenon, as well as how we can combat it. First, an overview of workaholism is presented, including definitions and measures, followed by a discussion on antecedents (personality factors and work environment) and correlates in the organizational, individual, and family domains. Next, a section on combatting levels of workaholism is summarized. Finally, avenues for future research on this topic are discussed. Essentially, this review article will add to the existing literature on Industrial/Organizational Psychology and health issues associated with organizational behavior, as well as serve as a resource for both researchers and practitioners who strive to enhance the well‐being of their employees.
The effect of a self‐help psychoeducation programme for people with coronary heart disease: A randomized controlled trial
Authors: Wang Wenru , Lim Jian Yang , Lopez Violeta , Wu Vivien Xi , Lee Chi‐Hang , He Hong‐Gu , Jiang Ying
Published: July 2018

Aim

To examine the effect of a self‐help psychoeducation program for people with coronary heart disease in Singapore.

Background

Cardiac rehabilitation has shown benefits for mitigating many cardiac risk factors and can lead to improvement in health‐related quality of life and psychological well‐being in people with heart disease. However, traditional hospital‐based cardiac rehabilitation faces substantial challenges. A self‐management cardiac rehabilitation program offers an avenue to increase uptake and empowers patients to manage their condition at home.

Design

A two‐arm, randomized controlled trial.

Methods

A total of 129 patients with coronary heart disease were recruited from an outpatient clinic in a public hospital in Singapore from April 2015–January 2016. They were randomly assigned to the intervention group or the control group. Participants in the intervention group received the 4‐week home‐based self‐help psychoeducation program. Outcomes were measured at baseline and at 4 weeks and 16 weeks from the baseline.

Results

There were no significant differences in health‐related quality of life, psychological status (i.e., perceived stress level, anxiety, and depression levels), or cardiac physiological risk parameters between the intervention and the control groups immediately after the program or at different time points. There was also no significant difference in unplanned health service use at the 16 week posttest point between the two groups.

Conclusions

This study did not find any significant effect of our program on outpatients with coronary heart disease. Nonetheless, findings on participant characteristics may offer healthcare professionals valuable insights to help facilitate future development of an effective cardiac rehabilitation program catered to outpatients with coronary heart disease.

Trial registration

The study has been registered with ISRCTN registry. The trial registration number is ISRCTN15839687.
Connections between academic burnout, resilience, and psychological well‐being in nursing students: A longitudinal study
Authors: Ríos‐Risquez Mᵃ Isabel , García‐Izquierdo Mariano , Sabuco‐Tebar Emiliana de los Ángeles , Carrillo‐Garcia César , Solano‐Ruiz Carmen
Published: July 2018

Aims

The aim of this study was to explore the longitudinal associations between academic burnout and resilience and psychological well‐being, and the stability of these variables in a sample of university nursing students.

Background

Nursing students frequently suffer academic burnout, which is brought on by different situations experienced during the training process and that can concern his psychological well‐being. Resilience is a personal resource that allows adverse situations to be handled in a successful way.

Design

Longitudinal design.

Methods

Data were collected at two moments separated by 18 months (2014–2016), with 218 students at T1 and 113 at T2. At each time a questionnaire was given to them, with questions about socioeconomic demographics and three validated scales to measure academic burnout, resilience, and psychological well‐being.

Results

The three dimensions that make up academic burnout remained steady over time, while resilience increased and psychological well‐being improved. Hierarchical regression analyses revealed the longitudinal effect of emotional exhaustion at T1 and at T2 they showed the longitudinal effect of resilience on psychological well‐being at T2. The inverse hierarchical regression analyses did not reveal significant relationships for any of the variables measured at T2 in connection with psychological well‐being measured at T1.

Conclusions

Emotional exhaustion was the most relevant dimension of academic burnout when predicting psychological well‐being in the analysed sample. Moreover, resilience has an important positive effect on psychological well‐being in the analysed sample. The practical implications of the results are discussed from the perspective of academic training and some recommendations are given for future research in this field.
Trends and variations in per capita expenditure on adult intellectual disabilities health and social care across Scotland, and by urban/rural class
Authors: Okon Marian , Henderson Angela , Kinnear Deborah , Cooper Sally‐Ann
Published: July 2018

Background

Following the global financial crisis in 2007/08, the UK implemented an austerity programme which may impact on services. Scotland comprises both densely populated urban conurbations and highly dispersed remote rural and island communities.

Method

Expenditure data were extracted from Scottish Government statistics. Per capita expenditure was calculated using adjusted Scotland's 2011 census data.

Results

There was a 3.41% decrease in real term expenditure on adult intellectual disabilities services between 2012/13 and 2014/15 (>£32 million). In 2014/15, per capita expenditure on adult intellectual disabilities health care ranged from £1,211 to £17,595; social care from £21,147 to £83,831; and combined health and social care expenditures from £37,703 to £85,929. Per capita expenditure on combined health and social care was greater in rural areas, with more on intellectual disabilities social care, though less on health care.

Conclusions

Scottish expenditure on adult intellectual disabilities services has not kept abreast of rising living costs. It varies considerably across the country: a postcode lottery.
Modelling cadmium‐induced cardiotoxicity using human pluripotent stem cell‐derived cardiomyocytes
Authors: Shen Jiaxi , Wang Xiaochen , Zhou Danni , Li Tongyu , Tang Ling , Gong Tingyu , Su Jun , Liang Ping
Published: July 2018

Cadmium, a highly ubiquitous toxic heavy metal, has been widely recognized as an environmental and industrial pollutant, which confers serious threats to human health. The molecular mechanisms of the cadmium‐induced cardiotoxicity (CIC) have not been studied in human cardiomyocytes at the cellular level. Here we showed that human pluripotent stem cell‐derived cardiomyocytes (hPSC‐CMs) can recapitulate the CIC at the cellular level. The cadmium‐treated hPSC‐CMs exhibited cellular phenotype including reduced cell viability, increased apoptosis, cardiac sarcomeric disorganization, elevated reactive oxygen species, altered action potential profile and cardiac arrhythmias. RNA‐sequencing analysis revealed a differential transcriptome profile and activated MAPK signalling pathway in cadmium‐treated hPSC‐CMs, and suppression of P38 MAPK but not ERK MAPK or JNK MAPK rescued CIC phenotype. We further identified that suppression of PI3K/Akt signalling pathway is sufficient to reverse the CIC phenotype, which may play an important role in CIC. Taken together, our data indicate that hPSC‐CMs can serve as a suitable model for the exploration of molecular mechanisms underlying CIC and for the discovery of CIC cardioprotective drugs.
The expression of MMP‐1 and MMP‐9 is up‐regulated by smooth muscle cells after their cross‐talk with macrophages in high glucose conditions
Authors: Macarie Razvan Daniel , Vadana Mihaela , Ciortan Letitia , Tucureanu Monica M. , Ciobanu Andrea , Vinereanu Dragos , Manduteanu Ileana , Simionescu Maya , Butoi Elena
Published: July 2018

Patients with diabetes mellitus have an increased risk of myocardial infarction and coronary artery disease‐related death, exhibiting highly vulnerable plaques. Many studies have highlighted the major role of macrophages (MAC) and smooth muscle cells (SMC) and the essential part of metalloproteases (MMPs) in atherosclerotic plaque vulnerability. We hypothesize that in diabetes, the interplay between MAC and SMC in high glucose conditions may modify the expression of MMPs involved in plaque vulnerability. The SMC‐MAC cross‐talk was achieved using trans‐well chambers, where human SMC were grown at the bottom and human MAC in the upper chamber in normal (NG) or high (HG) glucose concentration. After cross‐talk, the conditioned media and cells were isolated and investigated for the expression of MMPs, MCP‐1 and signalling molecules. We found that upon cross‐talk with MAC in HG, SMC exhibit: (i) augmented expression of MMP‐1 and MMP‐9; (ii) significant increase in the enzymatic activity of MMP‐9; (iii) higher levels of soluble MCP‐1 chemokine which is functionally active and involved in MMPs up‐regulation; (iv) activated PKCα signalling pathway which, together with NF‐kB are responsible for MMP‐1 and MMP‐9 up‐regulation, and (v) impaired function of collagen assembly. Taken together, our data indicate that MCP‐1 released by cell cross‐talk in diabetic conditions binds to CCR2 and triggers MMP‐1 and MMP‐9 over‐expression and activity, features that could explain the high vulnerability of atherosclerotic plaque found at diabetic patients.
Aldolase A as a prognostic factor and mediator of progression via inducing epithelial–mesenchymal transition in gastric cancer
Authors: Jiang Zhonghua , Wang Xiaohong , Li Jing , Yang Hongmei , Lin Xin
Published: July 2018

Glycolysis is regarded as the hallmark of cancer development and progression, which involves a multistep enzymatic reaction. This study aimed to explore the clinicopathological significance and potential role of glycolytic enzyme aldolase A (ALDOA) in the carcinogenesis and progression of gastric cancer (GC). ALDOA was screened from three paired liver metastasis tissues and primary GC tissues and further explored with clinical samples and in vitro studies. The ALDOA protein level significantly correlated with a larger tumor diameter (P = .004), advanced T stage (P < .001), N stage (P < .001) and lymphovascular invasion (P = .001). Moreover, the expression of ALDOA was an independent prognostic factor for the 5‐year overall survival and disease‐free survival of patients with GC in both univariate and multivariate survival analyses (P < .05). Silencing the expression of ALDOA in GC cell lines significantly impaired cell growth, proliferation and invasion ability (P < .05). Knockdown of the expression of ALDOA reversed the epithelial–mesenchymal transition process. Mechanically, ALDOA could affect the hypoxia‐inducible factor (HIF)‐1α activity as demonstrated by the HIF‐1α response element–luciferase activity in GC cells. Collectively, this study revealed that ALDOA was a potential biomarker of GC prognosis and was important in the carcinogenesis and progression of human GC.
Kallistatin attenuates endothelial senescence by modulating Let‐7g‐mediated miR‐34a‐SIRT1‐eNOS pathway
Authors: Guo Youming , Chao Lee , Chao Julie
Published: July 2018

Kallistatin, a plasma protein, protects against vascular and organ injury. This study is aimed to investigate the role and mechanism of kallistatin in endothelial senescence. Kallistatin inhibited H2O2‐induced senescence in human endothelial cells, as indicated by reduced senescence‐associated‐β‐galactosidase activity, p16INK4a and plasminogen activator inhibitor‐1 expression, and elevated telomerase activity. Kallistatin blocked H2O2‐induced superoxide formation, NADPH oxidase levels and VCAM‐1, ICAM‐1, IL‐6 and miR‐34a synthesis. Kallistatin reversed H2O2‐mediated inhibition of endothelial nitric oxide synthase (eNOS), SIRT1, catalase and superoxide dismutase (SOD)‐2 expression, and kallistatin alone stimulated the synthesis of these antioxidant enzymes. Moreover, kallistatin's anti‐senescence and anti‐oxidant effects were attributed to SIRT1‐mediated eNOS pathway. Kallistatin, via interaction with tyrosine kinase, up‐regulated Let‐7g, whereas Let‐7g inhibitor abolished kallistatin's effects on miR‐34a and SIRT1/eNOS synthesis, leading to inhibition of senescence, oxidative stress and inflammation. Furthermore, lung endothelial cells isolated from endothelium‐specific kallistatin knockout mice displayed marked reduction in mouse kallistatin levels. Kallistatin deficiency in mouse endothelial cells exacerbated senescence, oxidative stress and inflammation compared to wild‐type mouse endothelial cells, and H2O2 treatment further magnified these effects. Kallistatin deficiency caused marked reduction in Let‐7g, SIRT1, eNOS, catalase and SOD‐1 mRNA levels, and elevated miR‐34a synthesis in mouse endothelial cells. These findings indicate that endogenous kallistatin through novel mechanisms protects against endothelial senescence by modulating Let‐7g‐mediated miR‐34a‐SIRT1‐eNOS pathway.
The involvement of Toll‐like receptor 9 in the pathogenesis of erosive autoimmune arthritis
Authors: Fischer Anita , Abdollahi‐Roodsaz Shahla , Böhm Christina , Niederreiter Birgit , Meyer Brigitte , Yau Anthony C. Y. , Lönnblom Erik , Joosten Leo A. B. , Koenders Marije , Lehmann Christian H. K. , Dudziak Diana , Krönke Gerhard , Holmdahl Rikard , Steiner Günter
Published: July 2018

Endogenous nucleic acids and their receptors may be involved in the initiation of systemic autoimmune diseases including rheumatoid arthritis (RA). As the role of the DNA sensing Toll‐like receptor (TLR) 9 in RA is unclear, we aimed to investigate its involvement in the pathogenesis of autoimmune arthritis using three different experimental models of RA. The data obtained revealed involvement of TLR9 in the T cell‐dependent phase of inflammatory arthritis. In rats with pristane‐induced arthritis (PIA), TLR9 inhibition before disease onset reduced arthritis significantly and almost completely abolished bone erosion. Accordingly, serum levels of IL‐6, α‐1‐acid‐glycoprotein and rheumatoid factor were reduced. Moreover, in TLR9−/− mice, streptococcal cell wall (SCW)‐induced arthritis was reduced in the T cell‐dependent phase, whereas T cell‐independent serum‐transfer arthritis was not affected. Remarkably, while TLR7 expression did not change during in vitro osteoclastogenesis, TLR9 expression was higher in precursor cells than in mature osteoclasts and partial inhibition of osteoclastogenesis was achieved only by the TLR9 antagonist. These results demonstrate a pivotal role for TLR9 in the T cell‐dependent phases of inflammatory arthritis and additionally suggest some role during osteoclastogenesis. Hence, endogenous DNA seems to be crucially involved in the pathophysiology of inflammatory autoimmune arthritis.
Rho GTPases are involved in S1P‐enhanced glomerular endothelial cells activation with anti‐myeloperoxidase antibody positive IgG
Authors: Sun Xiao‐Jing , Chen Min , Zhao Ming‐Hui
Published: July 2018

Sphingosine‐1‐phosphate (S1P) is a crucial regulator in vascular inflammation. Our recent study found that under pathophysiological concentration in active anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV), S1P participated in MPO‐ANCA‐positive IgG‐induced glomerular endothelial cell (GEnC) activation via a S1P receptor (S1PR)‐dependent way. However, the downstream signalling pathways are not fully clear yet. In this study, we demonstrated that Rho guanosine triphosphatases (GTPases) signalling pathways, RhoA and Rac1 in particular, were implicated in MPO‐ANCA‐positive IgG‐mediated GEnCs activation enhanced by pathophysiological concentration of S1P in AAV. These results provide mechanistic insights into vascular barrier dysfunction in AAV, which may facilitate the development of effective therapies.
Changes in the appendicular skeleton during metamorphosis in the axolotl salamander (Ambystoma mexicanum)
Authors: Thampi Parvathy , Liu Jinpeng , Zeng Zheng , MacLeod James N.
Published: July 2018

Axolotl salamanders (Ambystoma mexicanum) remain aquatic in their natural state, during which biomechanical forces on their diarthrodial limb joints are likely reduced relative to salamanders living on land. However, even as sexually mature adults, these amphibians can be induced to metamorphose into a weight‐bearing terrestrial stage by environmental stress or the exogenous administration of thyroxine hormone. In some respects, this aquatic to terrestrial transition of axolotl salamanders through metamorphosis may model developmental and changing biomechanical skeletal forces in mammals during the prenatal to postnatal transition at birth and in the early postnatal period. To assess differences in the appendicular skeleton as a function of metamorphosis, anatomical and gene expression parameters were compared in skeletal tissues between aquatic and terrestrial axolotls that were the same age and genetically full siblings. The length of long bones and area of cuboidal bones in the appendicular skeleton, as well as the cellularity of cartilaginous and interzone tissues of femorotibial joints were generally higher in aquatic axolotls compared with their metamorphosed terrestrial siblings. A comparison of steady‐state mRNA transcripts encoding aggrecan core protein (ACAN), type II collagen (COL2A1), and growth and differentiation factor 5 (GDF5) in femorotibial cartilaginous and interzone tissues did not reveal any significant differences between aquatic and terrestrial axolotls.
Monitoring chemotherapy‐induced alopecia with trichoscopy
Authors: Rossi Alfredo , Caterina Fortuna Maria , Caro Gemma , Cardone Michele , Garelli Valentina , Grassi Sara , Carlesimo Marta
Published: July 2018

Background

Chemotherapy‐induced alopecia (CIA) ranks among the psychologically most devastating effects of cancer treatment for oncological patients, with an overall incidence of 65%. Nowadays trichoscopy is largely employed in the diagnosis of alopecia, but no description of CIA trichoscopic pattern is present in literature.

Aims

We want to create an organic description of CIA trichoscopic aspects.

Methods

Oncological patients candidate to chemotherapy drugs, afferent to our trichological outpatient were studied. Anamnesis, clinical exam, clinical global photography, pull test, trichogram, and trichoscopy were conducted at the different moments of therapeutic treatment.

Results

A definite trichoscopic pattern in the different phases of treatment was observed. After the first 3 weeks of chemotherapy rare and scattered black dots, broken hairs, flame hairs and pohl pinkus appeared. At the end of chemotherapy besides the features described above, numerous thin hair in regrowth were detected, together to rare terminal hair, scattered black dots and circle hair. Three months after chemotherapy a progressive increase of follicular units and elongation of the existing hair were visible.

Conclusions

We propose an description of CIA trichoscopic pattern and its evolution during the different phases of chemotherapy.
Real‐Time Cerebral Hemodynamic Response to Tactile Somatosensory Stimulation
Authors: Hage Benjamin , Way Emily , Barlow Steven M. , Bashford Gregory R.
Published: July 2018

BACKGROUND AND PURPOSE

Recent studies in rodents suggest that somatosensory stimulation could provide neuroprotection during ischemic stroke by inducing plasticity in the cortex–vasculature relationship. While functional magnetic resonance imaging (fMRI) has shown that somatosensory stimulation increases cerebral blood flow (CBF) over several seconds, subsecond changes in CBF in the basal cerebral arteries have rarely been studied due to temporal resolution limitations. This study characterized hemodynamic changes in the middle cerebral arteries (MCAs) during somatosensory stimulation with high temporal resolution (100 samples/s) using functional transcranial Doppler ultrasound (fTCD).

METHODS

Pneumotactile somatosensory stimulation, consisting of punctate pressure pulses traversing the glabrous skin of the hand at 25 cm/s, was used to induce CBF velocity (CBFV) response curves. Changes in CBFV were measured in the bilateral MCAs using fTCD. All 12 subjects underwent three consecutive trials consisting of 20 seconds of stimulation followed by 5 minutes of rest.

RESULTS

Sharp, bilateral increases in CBFV of about 20% (left MCA = 20.5%, right MCA = 18.8%) and sharp decreases in pulsatility index of about 8% were observed during stimulation. Left lateralization of up to 3.9% was also observed. The magnitude of the initial increase in CBFV showed significant adaptation between subsequent trials.

CONCLUSIONS

Pneumotactile somatosensory stimulation is a potent stimulus that can evoke large, rapid hemodynamic changes, with adaptation between successive stimulus applications. Due to its high temporal resolution, fTCD is useful for identifying quickly evolving hemodynamic responses, and for correlating changes in hemodynamic parameters such as pulsatility index (PI) and CBFV.
Organizational Communication and Individual Behavior: Implications for Supply Chain Risk Management
Authors: DuHadway Scott , Carnovale Steven , Kannan Vijay R.
Published: July 2018

Risk is a significant issue for supply chain managers. Not only must they contend with multiple dimensions of risk in decision‐making, they must reconcile decision‐making with broader organizational interests. This study examines the influence of organizational communication regarding supply chain risk on individual decision‐making strategies and the perceptions of risk. A multi‐stage experimental design is applied, in which decision‐makers make decisions across three dimensions of risk and adjust their risk‐taking behavior after being presented with organizational communication regarding supply chain risk levels. The relationship between organizational communication and the perceptions of supply chain risk is then explored after decision‐makers are allowed to adjust their supply chain strategies. The results suggest that decision‐makers adapt sourcing strategies in response to organizational communication regarding supply chain risk. Specifically, they make riskier decisions when the organization communicates improvements in supply chain risk levels. However, when given specific instructions to reduce risk, they do not adjust their supply chain strategies.
Effects of indirect facilitation on functional diversity, dominance and niche differentiation in tropical alpine communities
Authors: Danet Alain , Anthelme Fabien , Gross Nicolas , Kéfi Sonia
Published: July 2018

Question

Positive interactions between plants have well‐known effects on community species richness and biomass via micro‐environment improvements. However, the effects of indirect facilitation performed by a nurse on an associated plant community, occurring e.g., through protection against grazing, have not attracted much attention in the literature so far, in particular regarding the functional traits of the associated plant communities. Because characteristics of trait distributions can reveal selective pressures at play, they offer valuable information for the study of grazing pressure. Here, we tested the extent to which indirect facilitation affects the amount of distinct trait combinations (H1), trait dominance (H2) and niche differentiation between species (H3) of associated plant communities living under nurse plants.

Location

Tropical alpine peatlands, Cordillera Real, Bolivia.

Methods

We set up a grazing exclusion experiment over two dominant nurse cushion species: one providing indirect facilitation under grazing pressure and the other not. We measured three functional traits in the associated communities, which are known to vary depending on the grazing level: LDMC, leaf thickness and maximum height. We assessed the amount of distinct trait combinations by computing the volume of the phenotypic space (H1). The variation in trait dominance was quantified with kurtosis and skewness of the trait distributions (H2). The variation in niche differentiation was evaluated using mean intra‐population trait variance relative to intra‐community trait variance (H3).

Results

We did not find a significant effect of grazing and indirect facilitation on the volume of the phenotypic space (H1). However, our study revealed a significant effect of indirect facilitation on dominance in the associated communities by maintaining the evenness of the trait distributions (maximum height and leaf thickness) in grazed compared to ungrazed plots (H2), and on niche differentiation by maintaining trait overlaps (LDMC and maximum height) between species in grazed compared to ungrazed contexts (H3).

Conclusion

Our results suggest that indirect facilitation promotes the co‐existence of contrasting functional strategies (H2) and species niches (H3) in associated plant communities subject to grazing. These results reflect the buffering effect of indirect facilitation on the grazing selective pressures exerted on associated plant communities living under the protection of nurses.
Gain‐of‐function variants of FtsA form diverse oligomeric structures on lipids and enhance FtsZ protofilament bundling
Authors: Schoenemann Kara M. , Krupka Marcin , Rowlett Veronica W. , Distelhorst Steven L. , Hu Bo , Margolin William
Published: July 2018

Escherichia coli requires FtsZ, FtsA and ZipA proteins for early stages of cell division, the latter two tethering FtsZ polymers to the cytoplasmic membrane. Hypermorphic mutants of FtsA such as FtsA* (R286W) map to the FtsA self‐interaction interface and can bypass the need for ZipA. Purified FtsA forms closed minirings on lipid monolayers that antagonize bundling of FtsZ protofilaments, whereas FtsA* forms smaller oligomeric arcs that enable bundling. Here, we examined three additional FtsA*‐like mutant proteins for their ability to form oligomers on lipid monolayers and bundle FtsZ. Surprisingly, all three formed distinct structures ranging from mostly arcs (T249M), a mixture of minirings, arcs and straight filaments (Y139D) or short straight double filaments (G50E). All three could form filament sheets at higher concentrations with added ATP. Despite forming these diverse structures, all three mutant proteins acted like FtsA* to enable FtsZ protofilament bundling on lipid monolayers. Synthesis of the FtsA*‐like proteins in vivo suppressed the toxic effects of a bundling‐defective FtsZ, exacerbated effects of a hyper‐bundled FtsZ, and rescued some thermosensitive cell division alleles. Together, the data suggest that conversion of FtsA minirings into any type of non‐miniring oligomer can promote progression of cytokinesis through FtsZ bundling and other mechanisms.
Hop‐family Helicobacter outer membrane adhesins form a novel class of Type 5‐like secretion proteins with an interrupted β‐barrel domain
Authors: Coppens Fanny , Castaldo Gaetano , Debraekeleer Ayla , Subedi Suresh , Moonens Kristof , Lo Alvin , Remaut Han
Published: July 2018

The human stomach pathogen Helicobacter pyloriattaches to healthy and inflamed gastric tissue through members of a paralogous family of ‘Helicobacter outer membrane proteins’ (Hops), including adhesins BabA, SabA, HopQ, LabA and HopZ. Hops share a conserved 25 kDa C‐terminal region that is thought to form an autotransporter‐like transmembrane domain. Instead, our results show that Hops contain a non‐continuous transmembrane domain, composed of seven predicted β–strands at the C–terminus and one at the N‐terminus. Folding and outer membrane localization of the C–terminal β–domain critically depends on a predicted transmembrane β‐strand within the first 16 N‐terminal residues. The N‐terminus is shown to reside in the periplasm, and our crystal and small angle X‐ray scattering structures for the SabA extracellular domain reveal a conserved coiled‐coil stem domain that connects to transmembrane β‐strand 1 and 2. Taken together, our data show that Hop adhesins represent a novel outer membrane protein topology encompassing an OmpA‐like 8–stranded β‐barrel that is interrupted by a 15–108 kDa domain inserted inside the first extracellular loop. The insertion of large, folded domains in an extracellular loop is unprecedented in bacterial outer membrane proteins and is expected to have important consequences on how these proteins reach the cell surface.
Connectivity of centermost chromatophores in Rhodobacter sphaeroides bacteria
Authors: Noble Jade M. , Lubieniecki Johann , Savitzky Benjamin H. , Plitzko Jürgen , Engelhardt Harald , Baumeister Wolfgang , Kourkoutis Lena F.
Published: July 2018

The size of whole Rhodobacter sphaeroides prevents 3D visualization of centermost chromatophores in their native environment. This study combines cryo‐focused ion beam milling with cryo‐electron tomography to probe vesicle architecture both in situ and in 3D. Developing chromatophores are membrane‐bound buds that remain in topological continuity with the cytoplasmic membrane and detach into vesicles when mature. Mature chromatophores closest to the cell wall are typically isolated vesicles, whereas centermost chromatophores are either linked to neighboring chromatophores or contain smaller, budding structures. Isolated chromatophores comprised a minority of centermost chromatophores. Connections between vesicles in growing bacteria are through ~10 nm‐long, ~5 nm‐wide linkers, and are thus physical rather than functional in terms of converting photons to ATP. In cells in the stationary phase, chromatophores fuse with neighboring vesicles, lose their spherical structure, and greatly increase in volume. The fusion and morphological changes seen in older bacteria are likely a consequence of the aging process, and are not representative of connectivity in healthy R. sphaeroides. Our results suggest that chromatophores can adopt either isolated or connected morphologies within a single bacterium. Revealing the organization of chromatophore vesicles throughout the cell is an important step in understanding the photosynthetic mechanisms in R. sphaeroides.
Aspartate deficiency limits peptidoglycan synthesis and sensitizes cells to antibiotics targeting cell wall synthesis in Bacillus subtilis
Authors: Zhao Heng , Roistacher Daniel M. , Helmann John D.
Published: July 2018

Peptidoglycan synthesis is an important target for antibiotics and relies on intermediates derived from central metabolism. As a result, alterations of metabolism may affect antibiotic sensitivity. An aspB mutant is auxotrophic for aspartate (Asp) and asparagine (Asn) and lyses when grown in Difco sporulation medium (DSM), but not in LB medium. Genetic and physiological studies, supported by amino acid analysis, reveal that cell lysis in DSM results from Asp limitation due to a relatively low Asp and high glutamate (Glu) concentrations, with Glu functioning as a competitive inhibitor of Asp uptake by the major Glu/Asp transporter GltT. Lysis can be specifically suppressed by supplementation with 2,6‐diaminopimelate (DAP), which is imported by two different cystine uptake systems. These studies suggest that aspartate limitation depletes the peptidoglycan precursor meso‐2,6‐diaminopimelate (mDAP), inhibits peptidoglycan synthesis, upregulates the cell envelope stress response mediated by σM and eventually leads to cell lysis. Aspartate limitation sensitizes cells to antibiotics targeting late steps of PG synthesis, but not steps prior to the addition of mDAP into the pentapeptide sidechain. This work highlights the ability of perturbations of central metabolism to sensitize cells to peptidoglycan synthesis inhibitors.
LEAFY activity is post‐transcriptionally regulated by BLADE ON PETIOLE2 and CULLIN3 in Arabidopsis
Authors: Chahtane Hicham , Zhang Bo , Norberg Mikael , LeMasson Marie , Thévenon Emmanuel , Bakó László , Benlloch Reyes , Holmlund Mattias , Parcy François , Nilsson Ove , Vachon Gilles
Published: July 2018

The Arabidopsis LEAFY (LFY) transcription factor is a key regulator of floral meristem emergence and identity. LFY interacts genetically and physically with UNUSUAL FLORAL ORGANS, a substrate adaptor of CULLIN1–RING ubiquitin ligase complexes (CRL1). The functionally redundant genes BLADE ON PETIOLE1 (BOP1) and ‐2 (BOP2) are potential candidates to regulate LFY activity and have recently been shown to be substrate adaptors of CULLIN3 (CUL3)–RING ubiquitin ligases (CRL3).

We tested the hypothesis that LFY activity is controlled by BOPs and CUL3s in plants and that LFY is a substrate for ubiquitination by BOP‐containing CRL3 complexes.

When constitutively expressed, LFY activity is fully dependent on BOP2 as well as on CUL3A and B to regulate target genes such as APETALA1 and to induce ectopic flower formation. We also show that LFY and BOP2 proteins interact physically and that LFY‐dependent ubiquitinated species are produced in vitro in a reconstituted cell‐free CRL3 system in the presence of LFY, BOP2 and CUL3.

This new post‐translational regulation of LFY activity by CRL3 complexes makes it a unique transcription factor subjected to a positive dual regulation by both CRL1 and CRL3 complexes and suggests a novel mechanism for promoting flower development.
The genus Closterium, a new model organism to study sexual reproduction in streptophytes
Authors: Tsuchikane Yuki , Sekimoto Hiroyuki
Published: July 2018

Contents

Summary
99

I.
Introduction
99

II.
Life cycle of Closterium
100

III.
Sexual reproductive processes in the heterothallic Closterium peracerosum‐strigosum‐littorale complex
101

IV.
Homothallism in the C. psl. complex
102

V.
Sexual reproduction and inheritance of mating types in Closterium ehrenbergii
102

VI.
mt‐determining gene of the C. psl. complex
103

VII.
Future perspectives
103

Acknowledgements
103

References
103

Closterium occupies a key phylogenetic position as an ancestor of land plants and is the best‐characterized Charophycean alga in terms of the process of sexual reproduction. Zygospores form as a result of sexual reproduction between genetically determined mating type plus (mt+) and mating type minus (mt−) cells in heterothallic strains, or between clonal cells in homothallic strains. Here we review knowledge on the intercellular communication and mating type determination for successful sexual reproduction in Closterium. Using genomic information and transgenic techniques, the genus could be a model organism to study the mechanisms and evolution of sexual reproduction in streptophytes.
Articulation work from the middle—a study of how technicians mediate users and technology
Authors: Pallesen Trine , Jacobsen Peter H.
Published: July 2018

This article studies the work performed by technicians in a large demonstration project, EcoGrid 2.0, in the Danish island Bornholm. Based on observations of household visits conducted by technicians, we demonstrate how these act as ‘middlemen’, mediating and linking together the smart technology of the demonstration and the involved users. Formally, technicians’ work is to keep users online; however, they also perform a number of invisible tasks to keep users engaged and active. Our ethnographic study shows two broad categories of invisible work: first, technicians continually facilitate the willingness of users, recurrently affirming the social contract between users and demonstration project. Second, technicians facilitate the abilities of users by improvising informal training sessions of how to operate the system. These findings are used to discuss the importance of invisible articulation work of technical service workers in large scale real‐world experiments.
One‐year follow‐up of the prospective registry of patients using the wearable defibrillator (WEARIT‐II Registry)
Authors: Kutyifa Valentina , Moss Arthur J. , Klein Helmut U. , McNitt Scott , Zareba Wojciech , Goldenberg Ilan
Published: July 2018

Background

The WEARIT‐II Registry demonstrated efficacy and safety of the wearable cardioverter defibrillator (WCD) for at‐risk cardiac patients. However, 1‐year outcomes in this population have not been reported.

Methods

The WEARIT‐II Registry enrolled 2,000 U.S. patients prescribed the WCD. One‐year mortality data from start of WCD use were prospectively collected for 1,846 patients (93%).

Outcome data were analyzed by disease etiology and implantable cardioverter defibrillator (ICD) implantation following WCD use.

Results

During 12 months of follow‐up, 73 patients died (4%). Kaplan‐Meier survival analysis showed differences in all‐cause mortality from WCD prescription between patients with ischemic versus nonischemic cardiomyopathy versus congenital/inherited heart disease (4% vs 3% vs 7%, P = 0.013). Patients with ventricular arrhythmia events during WCD use had a higher 1‐year mortality (10% vs 3%, P = 0.042). Renal disease, increasing age, prior syncope, and nonbeta‐blocker use predicted mortality. One‐year mortality was similar in patients who did versus did not receive an ICD following WCD use in ischemic (3% vs 4%, P = 0.470) and nonischemic cardiomyopathy (3% vs 3%, P = 0.892). Patients with congenital/inherited heart disease with no implanted ICD had a trend toward a higher rate of mortality than those who received an ICD (8% vs 3%, P = 0.082). Multivariate models confirmed these findings.

Conclusion

One‐year follow‐up from the WEARIT‐II Registry shows an overall good survival in patients prescribed the WCD. Short‐term use of WCD allows appropriate risk stratification for decision on an ICD implantation in at‐risk ischemic and nonischemic cardiomyopathy patients. Congenital/inherited heart disease patients had a higher risk of 1‐year mortality even without an implanted ICD post‐WCD.
A 3‐year longitudinal study of skeletal effects and growth in children after kidney transplantation
Authors: Swolin‐Eide Diana , Hansson Sverker , Magnusson Per
Published: July 2018

This prospective study investigated growth and skeletal development for 3 years after kidney transplantation in pediatric patients, 3.4‐15.0 years of age. Growth, BMD, bone resorption markers (CTX and TRACP5b), bone formation markers (PINP, ALP, and osteocalcin), PTH, and vitamin D were assessed at start, 3, 12, and 36 months after transplantation. Median GFR was 63 (range 37‐96) mL/min/1.73 m2 after 3 years. The median height SDS increased from −1.7 to −1.1, and median BMI SDS increased from −0.1 to 0.6 over 3 years, which shows that transplantation had a favorable outcome on growth. Fat mass increased after transplantation at all time points, whereas lean mass increased after 1 year and 3 years. Total BMC increased at all time points. No changes were observed for total BMD. Bone resorption markers decreased initially after 3 months and remained stable throughout the study, whereas the bone formation markers decreased initially, but successively increased over the study period. In conclusion, this study demonstrates that height SDS and BMI SDS increased, along with the increased formation markers that reveal a positive bone acquisition after kidney transplantation, which was reflected by the significant increase in total body BMC.
Comparison of efficacy of aminolaevulinic acid photodynamic therapy vs. adapalene gel plus oral doxycycline for treatment of moderate acne vulgaris–A simple, blind, randomized, and controlled trial
Authors: Nicklas Claudia , Rubio Rocío , Cárdenas Consuelo , Hasson Ariel
Published: July 2018

Background

Although progress has been made in the study of photodynamic therapy for acne, studies using current recommended therapies as active comparators are lacking.

Methods

Randomized, controlled trial involving 46 patients with moderate inflammatory facial acne, 23 patients received two sessions of PDT separated by 2 weeks (ALA 20% incubated 1.5 hours before red light irradiation with 37 J/cm2 fluence) and 23 patients received doxycycline 100 mg/d plus adapalene gel 0.1%. In both groups, from the sixth week, we started adapalene gel 0.1% as maintenance therapy until 12 weeks of follow‐up. Primary end point was the reduction of acne lesions at the 6‐week follow‐up, which was evaluated by 2 investigators blinded to the intervention.

Results

The median percent reductions in noninflammatory lesion count (P = 0.013) and total lesions (P = 0.038) at 6 weeks was found to be significantly higher in the group receiving PDT. At 12 weeks there was a greater reduction of inflammatory lesions in PDT group with 84% vs. 74% for group who received doxycycline plus adapalene (P = 0.020) as well as in reducing total lesions with 79% vs. 67% respectively (P = 0.026). No severe side‐effects were observed for either therapy.

Conclusions

ALA‐PDT offers promise as an alternative treatment for moderately severe inflammatory acne that has a higher effectiveness than the combination of doxycycline and adapalene gel in reducing noninflammatory and total lesions at 6 weeks. There were significantly superior reductions at 12 weeks in the combination of PDT group followed by adapalene gel in total, inflammatory, and noninflammatory lesions.