bluuebunny/crossref_metadata_2025 huggingface dataset:
Reversal by Two Dihydropyridine Compounds of Resistance to Multiple Anticancer Agents in Mouse P388 Leukemia in vivo and in vitro
Authors: Kiue Akira , Sano Tetsuro , Naito Aya , Inada Haruaki , Suzuki Ken‐ichi , Okumura Masaya , Kikuchi Junko , Sato Shin‐ichi , Takano Hiroshi , Kohno Kimitoshi , Kuwano Michihiko
Published: March 2014

We investigated whether two representative 1,4‐dihydropyridine derivatives, NK‐250 and NK‐252, could potentiate the antitumor activity of multiple anticancer agents including vincristine (VCR), vinblastine, vindesine and actinomycin D in drug‐resistant tumor cells and their parental drug‐sensitive tumor cells. NK‐250 and NK‐252 at 5–10 μM almost completely reversed VCR resistance in cultured VCR‐resistant P388/VCR cells derived from the mouse drug‐sensitive P388/S leukemia cell line and also potentiated the cytocidal activity of VCR in drug‐sensitive P388/S cells. NK‐250 and NK‐252 at 1–10 μM inhibited the photoaffinity labeling by [3H]azidopine of the cell‐surface 170,000‐molecular‐weight P‐glycoprotein. In chemotherapeutic experiments with leukemia‐bearing mice, NK‐250 or NK‐252 was orally administered in combination with different drugs of the MDR phenotype administered intraperitoneally. The antitumor activity of the various combinations was found to be augmented in mice bearing P388/S‐ and P388/VCR‐leukemia. Among the combinations examined, the combination of NK‐250 and VCR was the most effective. These two 1,4‐dihydropyridines, NK‐250 and NK‐252, are unique compounds because they were effective not only in circumventing the drug resistance, but also in potentiating the action of antitumor drugs against drug‐sensitive tumors.
Molecular and cellular pathology of hepatocellular carcinoma
Authors: NG IRENE OL
Published: March 2014

Abstract Mutations of the p53 gene are common in hepatocellular carcinoma (HCC) and have been found in 13–33% of HCC in Asia and 23% of HCC in Hong Kong. In addition, p53 overexpression has been found to be associated with poorer cellular differentiation and larger tumour size and may be a late event in hepatocarcinogenesis. The p53 gene is important in controlling cell cycle, apoptosis and DNA repair. The cyclin‐dependent kinase inhibitor p21WAF1/CIP1, which is downstream of p53, is regulated by both p53‐dependent and p53‐independent pathways. We found that HCC with p53 mutations had lower levels of p21 expression than those without p53 mutations. Moreover, p21 protein expression of the tumours was significantly higher in the tumours than in the corresponding non‐tumorous livers. When the tumours were stratified into two groups, those with higher expression were found to have a significantly lower incidence of multiple tumour nodules and lower incidence of tumour microsatellite formation. p21 Expression was, however, not associated with p53 expression. Higher p21 expression is associated with solitary tumour nodules and fewer tumour microsatellites, but may not be enough to suppress tumour progression. Insulin‐like growth factor II (IGF‐II) gene has complex regulation of transcription resulting in multiple mRNA being produced and different mRNA occur in the adult and foetus. Using northern blot analysis, repression of normal adult promoter and re‐expression of foetal promoters of IGF‐II are common events in HCC, with repression of the normal adult promoter in 93% of the HCC transcripts and re‐expression of the foetal transcripts (6 and 5 kb, respectively) in 40% of tumours. In addition, IGF‐II expression was significantly more frequent in older patients. This may suggest that spontaneous expression of IGF‐II late in life may promote the growth of tumours which have already arisen through other mechanisms, but foetal re‐expression, itself, may not be enough to contribute to tumour progression.
Response of the Human Neurogenic Bladder to KCl, Carbachol, ATP and CaCl2
Authors: SAITO M. , KONDO A. , KATO T. , HASEGAWA S. , MIYAKE K.
Published: March 2014

Summary— The in vitro pharmacological responses of the human neurogenic bladder to KCl, carbachol, ATP and CaCl2 have been analysed.

The contractility (contractile strength and ED50) of neurogenic bladders was significantly increased when treated with carbachol, ATP and CaCl2. In contrast, there was no apparent difference in the responsiveness of neurogenic bladders when treated with KCl.

There was no apparent correlation between pharmacological responsiveness and clinical parameters, such as gender, age or cystometric data, in the neurogenic bladders.
TREATMENT OF OVERACTIVE BLADDER: OTHER DRUG MECHANISMS
Authors: ANDERSSON KARL‐ERIK
Published: March 2014

The well‐known side effects of antimuscarinic drugs have focused interest on other ways of treating overactive bladder. Targets for pharmacologic intervention may be found in the central nervous system (CNS) or peripherally. Several CNS transmitter systems can modulate voiding, but few drugs with a defined CNS site of action have been demonstrated to be clinically useful. The mechanism of action of imipramine, which may be effective in the treatment of overactive bladder, has not yet been clarified. Like imipramine, duloxetine is an inhibitor of serotonin (5‐HT) and norepinephrine reuptake. Duloxetine has shown some promise in the treatment of urinary incontinence, but, as with the selective serotonin reuptake inhibitors, its effectiveness in the treatment of overactive bladder has not been proven. Drugs affecting norepinephrine, dopamine or γ‐aminobutyric acid (GABA) receptors and mechanisms may be useful. There is also evidence for a central site of action of α1‐adrenoceptor (AR) antagonists. Traditionally, drugs for the treatment of overactive bladder have had a peripheral site of action. Drugs acting on ARs or membrane channels, as well as prostaglandin synthase inhibitors and several other agents, have been used with moderate success. However, recent developments may lead to more effective drugs, including potassium channel openers, prostaglandins, selective and nonselective inhibitors of cyclooxygenase and those acting on the β3‐ARs in the human detrusor. Drugs that reduce afferent activity represent an attractive therapeutic approach, and transmitters of afferent nerves and their receptors are possible targets for pharmacologic interventions.
Intractable incontinence in the elderly
Authors: OUSLANDER J.G.
Published: March 2014

The number of people living into extreme old age is rising exponentially in the USA, Europe and other developed countries. Urinary incontinence is prevalent in this population. While many very old (age > 75 years) incontinent individuals are relatively healthy and respond well to various treatments, a substantial proportion has impaired cognitive function and impaired mobility. These impairments make urinary incontinence much more difficult to assess, manage and cure than in younger populations. Irrespective of age and disability, a basic assessment of incontinence should be carried out to identify potentially reversible causes and indications for further evaluation. The outcome of such an assessment may not be cure or improvement of incontinence, but better quality of life and the prevention of morbid and expensive medical conditions that may result from poorly managed incontinence. Incontinence in this population should generally not be considered ‘intractable’ until a trial of noninvasive therapy (i.e. behavioural and/or pharmacological) has been undertaken. Some very frail elderly respond well to a toileting programme such as prompted voiding, and a small but significant proportion benefit from the careful addition of a bladder relaxant drug to the toileting programme. Others, depending on their ability and willingness to toilet and their preferences for further treatment, may be candidates for surgical intervention. Pads and garments should not be used so that they foster dependency, or as a primary treatment until other specific interventions have been tried. Indwelling catheters should be used only for specific and well‐documented indications, because of the risks of urinary tract infection and sepsis associated with their long‐term use. The dictionary defines ‘intractable’ as ‘not easily relieved or cured’. In the elderly, cure for incontinence, and most other chronic conditions, is the exception rather than rule. Relief (or amelioration), improvement in function and quality of life, and the exclusion of treatable medical conditions that cause morbidity and expense when undiagnosed, are generally achievable and more important goals than complete cure.
Heart rate variability during social interactions in children with and without psychopathology: a meta‐analysis
Authors: Shahrestani Sara , Stewart Elizabeth M. , Quintana Daniel S. , Hickie Ian B. , Guastella Adam J.
Published: March 2014

Background

The inability to regulate autonomic activity during social interactions is believed to contribute to social and emotional dysregulation in children. Research has employed heart rate variability (HRV) during both socially engaging and socially disengaging dyadic tasks between children and adults to assess this.

Methods

We conducted a meta‐analysis including evidence from 18 studies comprising 1,544 children who were categorized as either healthy or at risk/diagnosed with psychopathology. Within these groups, we assessed the impact of social engagement and disengagement tasks on HRV.

Results

Results showed that social engagement tasks left HRV unaltered to a baseline. Social disengagement, however, was associated with decreases in HRV. In a task that included disengagement and then engagement, HRV was reduced during disengagement but was then restored during the reunion phase (engagement). Children at risk or with a diagnosis for psychopathology, however, failed to show any change in HRV during dyadic social interaction tasks. This was despite a social stressor, the Trier Social Stress Test, causing significantly reduced HRV in both groups.

Conclusions

This meta‐analysis provides support to suggest HRV may provide a worthwhile context specific marker for the effective regulation of dyadic social interactions in children.
Skin viscoelasticity in incipient gravitational syndrome
Authors: Piérard Gérald E , Paquet Philippe , Piérard‐Franchimont Claudine
Published: March 2014

Background

The gravitational syndrome resulting from venous pressure elevation occasionally develops on the legs during pregnancy. The limb tends to enlarge and become stiffer. The body contours are altered.

Aims

To assess incipient gravitational edema due to chronic venous insufficiency using measurements of the skin tensile strength.

Method

A total of 21 women aged 28–37 years were enrolled in the study. Evaluations were made twice in each subject following an alternate use and avoidance of daytime elastic contention. Skin viscoelasticity was measured on the mid portion of the calves using a computerized suction device.

Results

The discretely increased consistency of skin showing abnormal rheological characteristics at the site of incipient gravitational edema was significantly improved by contention therapy. Under progressive suction measurements, both skin distensibility, biologic elasticity and hysteresis were increased after wearing tight stockings. The biologic elasticity appears to be the most sensitive parameter pointing to the diagnosis of gravitational syndrome.

Conclusion

Noninvasive measurements of the skin viscoelasticity, particularly the biologic elasticity, represent an objective assessment of both early gravitational edema and its control by contention therapy.
Reinsurance Networks and Their Impact on Reinsurance Decisions: Theory and Empirical Evidence
Authors: Lin Yijia , Yu Jifeng , Peterson Manferd O.
Published: March 2014

This article investigates the role of reinsurance networks in an insurer's reinsurance purchase decision. Drawing on network theory, we develop a framework that delineates how the pattern of linkages among reinsurers determines three reinsurance costs (loadings, contagion costs, and search and monitoring costs) and characterizes an insurer's optimal network structure. Consistent with empirical evidence based on longitudinal data from the U.S. property and casualty insurance industry, our model predicts an inverted U‐shaped relationship between the insurer's optimal percentage of reinsurance ceded and the number of its reinsurers. Moreover, we find that a linked network may be optimal ex ante even though linkages among reinsurers may spread financial contagion, supporting the model's prediction regarding social capital benefits associated with network cohesion. Our theoretical model and empirical results have implications for other networks such as loan sale market networks and over‐the‐counter dealer networks.
The willingness of US pediatric dentists to use atraumatic restorative treatment (ART) with their patients: a conjoint analysis
Authors: Kateeb Elham Talib , Warren John , Gaeth Gary , Damiano Peter , Momany Elizabeth , Kanellis Michael J. , Weber‐Gasparoni Karin , Ansley Timothy
Published: March 2014

Objectives

The atraumatic restorative treatment (ART) was developed as an affordable, patient‐friendly dental caries management procedure that does not need extensive operator training or special skills. The aim of this study was to determine factors that influence the decision to use ART using an innovative marketing research technique known as conjoint analysis.

Methods

A conjoint survey was completed by 723 members of the American Academy of Pediatric Dentistry. Three factors (age of the child, level of cooperation, type of insurance) were varied across three levels to create nine patient scenarios. The weights that practitioners placed on these factors in decisions to use ART in treating carious lesions were determined by conjoint analysis. Factors such as lesion location, depth, and extension were fixed in the nine clinical scenarios.

Results

Seven‐hundred twenty‐three pediatric dentists completed the survey (32 percent). Age of the child was the most important factor in pediatric dentists' decisions to use ART (46 percent) compared with level of cooperation (41 percent) and type of insurance coverage (11 percent). For the age factor, the age of 2 years had the greatest utility (0.55) compared with age 4 (−0.09) and age 6 (−0.46). For types of insurance coverage, having no insurance (0.124) had the greatest utility compared with having public insurance (−0.119).

Conclusions

Although insurance coverage was the least important among the factors, being without insurance, being very young, and being uncooperative was the scenario where pediatric dentists most favored ART when making trade offs between different factors using the conjoint design.
Barriers and facilitators to children's use of speech‐generating devices: a descriptive qualitative study of mothers' perspectives
Authors: Crisp Cheryl , Draucker Claire Burke , Ellett Marsha L. Cirgin
Published: March 2014

Purpose

The purpose of this study was to identify barriers and facilitators to children's use of speech‐generating devices (SGD).

Design and Methods

Interviews with 14 mothers were analyzed with content analysis to identify barriers and facilitators to SGD use.

Results

This study identified a number of specific barriers and facilitators to successful and sustained SGD use by children with complex communication disorders.

Practice Implications

Nurses can use the list of barriers and facilitators provided here as a springboard to discuss the families' experiences with device use.
What “Regulatory State”? Explaining the Stability of Public Spending and Redistribution Functions after Regulatory Reforms of Electricity and Rail Services in the United Kingdom and Germany
Authors: Pflieger Géraldine
Published: March 2014

In Europe, the rise of the regulatory state was accompanied by a broad diffusion of research on the processes of privatisation, liberalisation, and reregulation of utilities, previously managed directly by the state. This article offers an empirical and theoretical discussion of the paradigm of the regulatory state. It proposes to evaluate the transformation of the actual functions of the welfare state in a context of reforms of network industries over the last twenty years. Relying on cases from the electricity and railways sectors, it studies the changing balance between the traditional functions of the welfare state and the new regulatory functions introduced by the reforms. This article explains how, alongside the strengthening of regulatory functions, states maintained and developed powerful redistribution functions. The emerging regulatory state is not substituted for the positive/welfare state, but partly juxtaposed with it, making the structures for governing these sectors much less easy to read.
Diabetes enhances the intrahepatic vascular response to endothelin‐1 in cirrhotic rats: association with the ETA receptor and pERK up‐regulation
Authors: Lee Jing‐Yi , Lee Fa‐Yauh , Huo Teh‐Ia , Wang Sun‐Sang , Huang Hui‐Chun , Lin Han‐Chieh , Chuang Chiao‐Lin , Lee Shou‐Dong
Published: March 2014

Background & Aims

Cirrhosis is characterized by increased intrahepatic vascular resistance and enhanced vasocontractile responsiveness that impedes portal inflow and elevates portal pressure, in which endothelin‐1 (ET‐1) plays a role. Diabetes and glucose influence vasoresponsiveness but their impact on the intrahepatic vascular bed in cirrhosis is unknown. To investigate intrahepatic ET‐1 vasoresponsiveness in cirrhotic rats with and without diabetes and to explore the underlying mechanisms.

Methods

Spraque‐Dawley rats received common bile‐duct ligation (BDL) to induce cirrhosis. Streptozotocin was injected to induce diabetes in the BDL rats (BDL/STZ). In situ liver perfusion was performed to obtain the ET‐1 concentration‐response curves. The basic hemodynamics and hepatic protein expressions of ET‐1 receptors, pERK, ERK, pAkt, Akt, iNOS, eNOS, peNOS and calmodulin were evaluated. The circulating concentrations of N‐terminal pro‐brain natriuretic peptide (NT‐ProBNP), blood urea nitrogen (BUN) and creatinine were also determined.

Results

Body weight, mean arterial pressure, heart rate and survival rate were significantly decreased in the BDL/STZ rats. The perfusion pressure changes in response to ET‐1 were higher in the BDL/STZ group for all perfusates. ETA receptor and pERK expressions were enhanced in the BDL/STZ group. The circulating concentrations of NT‐ProBNP, BUN and creatinine, as well as SMA flow, were not significantly different between the BDL and BDL/STZ groups.

Conclusion

Cirrhotic rats with diabetes showed higher intrahepatic ET‐1 vasoresponsiveness than normoglycemic cirrhotic rats. This effect is not affected by changes in perfused glucose concentration and may be related, at least in part, to intrahepatic ETAR receptor and pERK over‐expression.
Effect of Sacral Neuromodulation on Outcome Measures and Urine Chemokines in Interstitial Cystitis/Painful Bladder Syndrome Patients
Authors: PETERS Kenneth M. , JAYABALAN Nirmal , BUI Don , KILLINGER Kim , CHANCELLOR Michael , TYAGI Pradeep
Published: March 2014

Objectives

Sacral neuromodulation (SNM) may improve interstitial cystitis/painful bladder syndrome (IC/BPS) symptoms of urinary frequency, urgency and perhaps even pain, but objective measures of improvement are lacking. We evaluated the potential for urinary chemokines to serve as measures of treatment response over time to SNM.

Methods

Women with IC/BPS undergoing SNM consented for this study. Three‐day bladder/pain diaries were collected at baseline and validated Interstitial Cystitis Symptom Problem Index (ICSPI) scores and mid‐stream urine specimens were collected at baseline and at 24 weeks after successful implant. Collected urine was screened for infection by dipstick and analyzed for chemokines by luminex xMAP analysis.

Results

At baseline (n = 16), urine levels of CXCL‐1 positively correlated with pain score (r = 0.63, P = 0.009), urgency (r = 0.61, P = 0.01), ICSPI (r = 0.43, P = 0.09) and daily voids (r = 0.44, P = 0.08). ICSPI and pain scores also positively correlated with sIL‐1ra (r = 0.50, P = 0.04) and monocyte chemotactic protein‐1 (MCP‐1) or CCL2 positively correlated with daily voids (r = 0.45, P = 0.07) only. At 24 weeks, the median ICSPI index fell from 28 to 15 (n = 7, P = 0.008). Urine levels of sIL‐1ra (633.8 ± 188.2 vs. 149.9 ± 41.62 pg/mL) and MCP‐1 (448.3 ± 11.6 vs. 176.9 ± 46.16 pg/mL) and CCL5 (20.78 ± 4.09 vs. 11.21 ± 4.12 pg/mL) were also significantly reduced at the follow‐up relative to baseline values (P = 0.04). Multivariable analysis of data revealed that sIL‐1ra and MCP‐1 together explained the majority of variance in data. Levels of CXCL‐1, CXCL‐10, interleukin (IL)‐8, vascular endothelial growth factor (VEGF), platelet‐derived growth factor (PDGF) were also reduced at 24 weeks, but differences were not significant.

Conclusions

Concomitant decrease in urine levels of chemokines especially MCP‐1 was associated with treatment response of SNM. These results support the role of chemokines as downstream effectors of neuromodulation response and could serve as potential non‐invasive measures of treatment response.

Clinical Trial Registration Number: NCT01739946.
Finescale ecological niche modeling provides evidence that lactating gray seals (Halichoerus grypus) prefer access to fresh water in order to drink
Authors: Stewart James E. , Pomeroy Paddy P. , Duck Callan D. , Twiss Sean D.
Published: March 2014

Many phocids are capital breeders, relying on stored reserves to sustain energetic requirements while on land. Their large body size, high energy expenditure during lactation, and the insulative effects of the blubber layer can lead to thermal stress from overheating, especially in warm and temperate climates. Thermal stress can influence fine‐scale site choice on breeding colonies, and behavioral thermoregulation has been proposed as an explanation for the clear preferences shown by breeding female gray seals for proximity to pools of water. However, anecdotal observations suggest that pools of water may also be preferred for drinking, though water intake is difficult to verify without real‐time physiological monitoring. Here, an alternative approach demonstrates that gray seals also require access to water for drinking. Using Ecological Niche Factor Analysis to examine fine‐scale physical determinants of pupping site choice at North Rona, Scotland, we found that lactating mothers showed preference for lower salinity pools. This is most pronounced early in the season, when ambient temperatures and presumably thermal stress are greatest. Given that the cooling effect of fresh and salt water should be equivalent, the most parsimonious explanation for this preference for fresh water pools is that lactating females use these pools for drinking.
Serological and antigenic profiles of clinical isolates of Paracoccidioides spp. from Central Western Brazil
Authors: Queiroz Júnior Luiz de Pádua , de Camargo Zoilo Pires , Tadano Tomoko , Rodrigues Anderson Messias , Takarara Doracilde Terumi , Gegembauer Gregory , Araujo Leticia Mendes , Hahn Rosane Christine
Published: March 2014

Clinical Paracoccidioides spp. isolates from patients with paracoccidioidomycosis (PCM) in Mato Grosso, Brazil exhibit different patterns of serologic reactivity. The results observed for reactions of radial immunodiffusion against the commonly used exoantigens containing a 43‐kDa glycoprotein (gp43) suggest that this fungus exhibits major antigenic variability by geographic region. There is a phylogenetic gap between Paracoccidioides spp. isolates among different regions of Latin America. In particular, those from the central region of Brazil (i.e. Mato Grosso state) exhibit a lower rate of genetic similarity. We aimed at investigating the phylogenetic classification of clinical isolates of Paracoccidioides spp. in Central Brazil and the different antigenic profiles that produce. Exoantigens were obtained from five clinical isolates: two P. brasiliensis (Pb166 and Pb2880) and three P. lutzii (PL2875, PL9840, and PL2912). The protein/glycoprotein profiles of P. lutzii exoantigens were different from each other. Isolate PL9840 exhibited the most distinct bands, and isolates PL2875 and PL2912 exhibited more diffuse bands and a very intense band between 50 and 60 kDa. P. brasiliensis isolates had similar protein profiles, exhibiting a low‐intensity band at 220 kDa and a diffuse band between 50 and 60 kDa. P. lutzii isolates exhibit high species‐specific antigen variability, which we have already been assessed in proteomic studies.
Mapping social processes at work in nursing knowledge development
Authors: Hamilton Patti , Willis Eileen , Henderson Julie , Harvey Clare , Toffoli Luisa , Abery Elizabeth , Verrall Claire
Published: March 2014

In this paper, we suggest a blueprint for combining bibliometrics and critical analysis as a way to review published scientific works in nursing. This new approach is neither a systematic review nor meta‐analysis. Instead, it is a way for researchers and clinicians to understand how and why current nursing knowledge developed as it did. Our approach will enable consumers and producers of nursing knowledge to recognize and take into account the social processes involved in the development, evaluation, and utilization of new nursing knowledge. We offer a rationale and a strategy for examining the socially‐sanctioned actions by which nurse scientists signal to readers the boundaries of their thinking about a problem, the roots of their ideas, and the significance of their work. These actions – based on social processes of authority, credibility, and prestige – have bearing on the careers of nurse scientists and on the ways the knowledge they create enters into the everyday world of nurse clinicians and determines their actions at the bedside, as well as their opportunities for advancement.
Exercise intervention for fatigue‐related symptoms inThai women with breast cancer: A pilot study
Authors: Naraphong Wipasiri , Lane Adrianne , Schafer John , Whitmer Kyra , Wilson Bradley R. A.
Published: March 2014

The purpose of this pilot study was to preliminarily examine the effects of an exercise program on the symptoms of fatigue, sleep disturbance, mood disturbance, symptom distress, and physical fitness for Thai women with breast cancer. Twenty‐three eligible women were randomly assigned to either an experimental group (n = 11) or to a control group (n = 12). Data were collected and analyzed at baseline and again at 4, 7, and 10 weeks. At each time point, fatigue was measured at an expected high point during treatment. Participants in the exercise group demonstrated a trend toward improving the symptoms with mean score changes. Using generalized estimating equations analysis, a significant decrease in mood disturbance was found in the exercise group compared with control at 10 weeks (β = 0.03,P = 0.04). The participants exhibited significantly longer 12‐minute walk distance at 10 weeks than those in the control group (t = 2.28,P = 0.04). These results indicate that exercise during adjuvant chemotherapy may be beneficial for Thai women with breast cancer.
Knockdown of mitochondrial alternative oxidase induces the ‘stress state’ of signaling molecule pools in Nicotiana tabacum, with implications for stomatal function
Authors: Cvetkovska Marina , Dahal Keshav , Alber Nicole A. , Jin Cathy , Cheung Melissa , Vanlerberghe Greg C.
Published: March 2014

The mitochondrial electron transport chain (ETC) includes an alternative oxidase (AOX) that may control the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS act as signaling intermediates in numerous plant processes, including stomatal movement.

The role of AOX in controlling ROS and RNS concentrations under both steady‐state and different stress conditions was evaluated using Nicotiana tabacum plants lacking AOX as a result of RNA interference. A potential functional implication of changes in ROS and RNS homeostasis was also evaluated by examining stomatal function.

The leaves of nonstressed AOX knockdowns maintained concentrations of H2O2 and nitric oxide (NO) normally seen in wildtype plants only under stress conditions. Further, guard cell NO amounts were much higher in knockdowns. These guard cells were altered in size and were less responsive to NO as a signal for stomatal closure. This, in turn, compromised the stomatal response to changing irradiance.

The results reveal a role for AOX in stomata. A working model is that guard cell AOX respiration maintains NO homeostasis by preventing over‐reduction of the ETC, particularly during periods when high concentrations of NO acting as a signal for stomatal closure may also be inhibiting cyt oxidase respiration.
Aldehyde dehydrogenases in acute myeloid leukemia
Authors: Smith Clay , Gasparetto Maura , Humphries Keith , Pollyea Daniel A. , Vasiliou Vasilis , Jordan Craig T.
Published: March 2014

Acute myeloid leukemia (AML) affects approximately 15,000 persons per year in the United States and is the sixth leading cause of cancer‐related deaths. The treatment of AML has advanced little in the past thirty years, in part because of the biologic heterogeneity of the disease and the difficulty in targeting AML cells while sparing normal hematopoietic cells. Advances in preventing and treating AML are likely to occur once the cellular and molecular differences between leukemia and normal hematopoietic cells are better understood. Aldehyde dehydrogenase (ALDH) activity is highly expressed in hematopoietic stem cells (HSCs), while, in contrast, a subset of AMLs are lacking this activity. This difference may be relevant to the development of AML and may also provide a better avenue for treating this disease. In this review, we summarize what is known about the ALDHs in normal HSCs and AML and propose strategies for capitalizing on these differences in the treatment of acute leukemia, and possibly other cancers as well.
The visual and functional impacts of astigmatism and its clinical management
Authors: Read Scott A. , Vincent Stephen J. , Collins Michael J.
Published: March 2014

Purpose

To provide a comprehensive overview of research examining the impact of astigmatism on clinical and functional measures of vision, the short and longer term adaptations to astigmatism that occur in the visual system, and the currently available clinical options for the management of patients with astigmatism.

Recent findings

The presence of astigmatism can lead to substantial reductions in visual performance in a variety of clinical vision measures and functional visual tasks. Recent evidence demonstrates that astigmatic blur results in short‐term adaptations in the visual system that appear to reduce the perceived impact of astigmatism on vision. In the longer term, uncorrected astigmatism in childhood can also significantly impact on visual development, resulting in amblyopia. Astigmatism is also associated with the development of spherical refractive errors. Although the clinical correction of small magnitudes of astigmatism is relatively straightforward, the precise, reliable correction of astigmatism (particularly high astigmatism) can be challenging. A wide variety of refractive corrections are now available for the patient with astigmatism, including spectacle, contact lens and surgical options.

Conclusion

Astigmatism is one of the most common refractive errors managed in clinical ophthalmic practice. The significant visual and functional impacts of astigmatism emphasise the importance of its reliable clinical management. With continued improvements in ocular measurement techniques and developments in a range of different refractive correction technologies, the future promises the potential for more precise and comprehensive correction options for astigmatic patients.
Deciding Between Work and Family: An Episodic Approach
Authors: Shockley Kristen M. , Allen Tammy D.
Published: March 2014

This study examined work–family conflict decision‐making based on a within–person, episodic approach. Based on 274 episodes across 78 individuals, we investigated the frequency of decisions that result in work interference with family (WIF) versus family interference with work (FIW), as well as the relation of work and family situational variables and previous work–family conflict (WFC) episodes on those decisions. No difference in the frequency with which participants reported WIF episodes versus FIW episodes was observed. Results indicated that work/family role sender pressure, work/family instrumental support, work/family activity importance, work emotional support, and the direction of the previous WFC decision each predicted WFC decisions. Dominance analysis indicated that role sender pressure was the most important predictor. In addition, we compare and discuss within‐person variation with between‐person variation. Contributions of the study to work–family research and practice are discussed.
Knowledge‐How and Cognitive Achievement
Authors: Carter J. Adam , Pritchard Duncan
Published: March 2014

According to reductive intellectualism, knowledge‐how just is a kind of propositional knowledge (e.g., Stanley & Williamson 2001; Stanley 2011a, 2011b; Brogaard, 2008a, 2008b, 2009, 2011, 2009, 2011). This proposal has proved controversial because knowledge‐how and propositional knowledge do not seem to share the same epistemic properties, particularly with regard to epistemic luck. Here we aim to move the argument forward by offering a positive account of knowledge‐how. In particular, we propose a new kind of anti‐intellectualism. Unlike neo‐Rylean anti‐intellectualist views, according to which the possession of knowledge‐how is just a matter of possessing certain abilities, we submit that knowledge‐how is a particular kind of cognitive achievement attained just when cognitive ability is connected in the right way with successful performance.
Different mechanisms for Arabidopsis thaliana hybrid necrosis cases inferred from temperature responses
Authors: Muralidharan S. , Box M. S. , Sedivy E. L. , Wigge P. A. , Weigel D. , Rowan B. A.
Published: March 2014

Temperature is a major determinant of plant growth, development and success. Understanding how plants respond to temperature is particularly relevant in a warming climate. Plant immune responses are often suppressed above species‐specific critical temperatures. This is also true for intraspecific hybrids of Arabidopsis thaliana that express hybrid necrosis due to inappropriate activation of the immune system caused by epistatic interactions between alleles from different genomes. The relationship between temperature and defence is unclear, largely due to a lack of studies that assess immune activation over a wide range of temperatures. To test whether the temperature‐based suppression of ectopic immune activation in hybrids exhibits a linear or non‐linear relationship, we characterised the molecular and morphological phenotypes of two different necrotic A. thaliana hybrids over a range of ecologically relevant temperatures. We found both linear and non‐linear responses for expression of immunity markers and for morphological defects depending on the underlying genetic cause. This suggests that the influence of temperature on the trade‐off between immunity and growth depends on the specific defence components involved.
Migration and Inequality in the Rural United States: Connecting Urban to Rural and Local to Global
Authors: Golding Shaun A.
Published: March 2014

This article draws from several overlapping literatures to frame urban–rural migration in the United States as the cause of emerging dimensions of inequality. To begin, the article reviews the amenity migration field of research, noting that scholars often underestimate or overlook inequality within rural destinations because common research lenses and methodological decisions inadvertently mask it. The article then describes a second thread of research that explicitly implicates migration as a driver of inequality and a third that draws connections to gentrification. Finally, the article reviews more recent research that characterizes inequality in rural destinations using a more global sociological perspective. The author draws attention to work, which recognizes that migration constitutes a material and theoretical connection between inequality experienced locally and societal inequality at the national and global scales.
The Political Lives of Girls
Authors: Taft Jessica K.
Published: March 2014

Girls are increasingly being publically celebrated as community leaders, models for ideal citizenship, and central to economic development. Contemporary girlhood is rich with political implications and significance. In this essay, I outline some of the scholarship on the public discourses that idealize girls as model neoliberal citizens and address important findings and contributions from empirical research on the political lives of girls: girls' political beliefs, political socialization, political identities, and their practices of political and civic engagement. There is a growing body of scholarship that suggests that studying the political lives of girls enables and requires a re‐thinking of some key concepts in political sociology, including the meaning of politics, of engagement, and of citizenship for different populations.
Probabilistic Solution of Vibro-Impact Systems Under Additive Gaussian White Noise
Authors: Zhu H. T.
Published: March 2014

This paper presents a solution procedure for the stationary probability density function (PDF) of the response of vibro-impact systems under additive Gaussian white noise. The constraint is a unilateral zero-offset barrier. The vibro-impact system is first converted into a system without barriers using the Zhuravlev nonsmooth coordinate transformation. The stationary PDF of the converted system is governed by the Fokker–Planck equation which is solved by the exponential-polynomial closure (EPC) method. A vibro-impact Duffing oscillator with either elastic or lightly inelastic impacts is considered in a numerical analysis. Meanwhile, the level of nonlinearity in displacement is also examined in this study as well as the case of negative linear stiffness. Comparison with the simulated results shows that the EPC method can present a satisfactory PDF for displacement and velocity when the polynomial order is taken as 4 in the investigated cases. The tail of the PDF also works well with the simulated result.
Impact of Inlet Filter Pressure Loss on Single and Two-Spool Gas Turbine Engines for Different Control Modes
Authors: Igie Uyioghosa , Minervino Orlando
Published: March 2014

Inlet filtration systems are designed to protect industrial gas turbines from air borne particles and foreign objects, thereby improving the quality of air for combustion and reducing component fouling. Filtration systems are of varying grades and capture efficiencies, with the higher efficiency systems filters providing better protection but higher pressure losses. For the first time, two gas turbine engine models of different configurations and capacities have been investigated for two modes of operation (constant turbine entry temperature (TET) and load/power) for a two- and three-stage filter system. The main purpose of this is to present an account on factors that could decide the selection of filtration systems by gas turbine operators, solely based on performance. The result demonstrates that the two-spool engine is only slightly more sensitive to intake pressure loss relative to the single-spool. This is attributed to higher pressure ratio of the two-spool as well as the deceleration of the high pressure compressor (HPC)/high pressure turbine (HPT) shaft rotational speed in a constant TET operation. The compressor of the single-spool engine and the low pressure compressor (LPC) of the two-spool shows similar behavior: slight increase in pressure ratio and reduced surge margin at their constant rotational speed operation. Loss in shaft power is observed for both engines, about 2.5% at 1000 Pa loss. For constant power operation there is an increase in fuel flow and TET, and as a result the creep life was estimated. The result obtained indicates earlier operating hours to failure for the three-stage system over the two-stage by only a few thousand hours. However, this excludes any degradation due to fouling that is expected to be more significant in the two-stage system.
Inflammable Mucus
Authors: Berndt Jason D.
Published: March 2014

Inflammasomes play a role in nonimmune cells of the intestine to produce a mucus barrier that protects against infection.
Efficacy and Tolerability of Micafungin Monotherapy for Candidemia and Deep-Seated Candidiasis in Adults with Cancer
Authors: Farmakiotis Dimitrios , Tarrand Jeffrey J. , Kontoyiannis Dimitrios P.
Published: March 2014

The response rate among 58 patients with cancer and candidemia or deep-seated candidiasis treated with micafungin monotherapy was 81%. Intensive care unit (ICU) stay, concomitant nonfungal infections, and acute kidney injury were significantly associated with the 30-day crude mortality rate. Severe neutropenia was an independent predictor of micafungin failure. The efficacy and safety of micafungin in cancer patients with invasive candidiasis were comparable to those reported for patients without malignancy and for cancer patients treated with caspofungin.
A Highly Active and Negatively Charged Streptococcus pyogenes Lysin with a Rare
d
-Alanyl-
l
-Alanine Endopeptidase Activity Protects Mice against Streptococcal Bacteremia
Authors: Lood Rolf , Raz Assaf , Molina Henrik , Euler Chad W. , Fischetti Vincent A.
Published: March 2014

Bacteriophage endolysins have shown great efficacy in killing Gram-positive bacteria. PlyC, a group C streptococcal phage lysin, represents the most efficient lysin characterized to date, with a remarkably high specificity against different streptococcal species, including the important pathogen
Streptococcus pyogenes
. However, PlyC is a unique lysin, in terms of both its high activity and structure (two distinct subunits). We sought to discover and characterize a phage lysin active against
S. pyogenes
with an endolysin architecture distinct from that of PlyC to determine if it relies on the same mechanism of action as PlyC. In this study, we identified and characterized an endolysin, termed PlyPy (
p
hage
ly
sin from

S.
py
ogenes

), from a prophage infecting
S. pyogenes
. By
in silico
analysis, PlyPy was found to have a molecular mass of 27.8 kDa and a pI of 4.16. It was active against a majority of group A streptococci and displayed high levels of activity as well as binding specificity against group B and C streptococci, while it was less efficient against other streptococcal species. PlyPy showed the highest activity at neutral pH in the presence of calcium and NaCl. Surprisingly, its activity was not affected by the presence of the group A-specific carbohydrate, while the activity of PlyC was partly inhibited. Additionally, PlyPy was active
in vivo
and could rescue mice from systemic bacteremia. Finally, we developed a novel method to determine the peptidoglycan bond cleaved by lysins and concluded that PlyPy exhibits a rare
d
-alanyl-
l
-alanine endopeptidase activity. PlyPy thus represents the first lysin characterized from
Streptococcus pyogenes
and has a mechanism of action distinct from that of PlyC.
Triclosan-Induced Aminoglycoside-Tolerant Listeria monocytogenes Isolates Can Appear as Small-Colony Variants
Authors: Kastbjerg Vicky G. , Hein-Kristensen Line , Gram Lone
Published: March 2014

Exposure of the human food-borne pathogen
Listeria monocytogenes
to sublethal concentrations of triclosan can cause resistance to several aminoglycosides. Aminoglycoside-resistant isolates exhibit two colony morphologies: normal-size and pinpoint colonies. The purposes of the present study were to characterize the small colonies of
L. monocytogenes
and to determine if specific genetic changes could explain the triclosan-induced aminoglycoside resistance in both pinpoint and normal-size isolates. Isolates from the pinpoint colonies grew poorly under aerated conditions, but growth was restored by addition of antibiotics. Pinpoint isolates had decreased hemolytic activity under stagnant conditions and a changed spectrum of carbohydrate utilization compared to the wild type and isolates from normal-size colonies. Genome sequence comparison revealed that all seven pinpoint isolates had a mutation in a heme gene, and addition of heme caused the pinpoint isolates to revert to normal colony size. Triclosan-induced gentamicin-resistant isolates had mutations in several different genes, and it cannot be directly concluded how the different mutations caused gentamicin resistance. However, since many of the mutations affected proteins involved in respiration, it seems likely that the mutations affected the active transport of the antibiotic and thereby caused resistance by decreasing the amount of aminoglycoside that enters the bacterial cell. Our study emphasizes that triclosan likely has more targets than just
fabI
and that exposure to triclosan can cause resistance to antibiotics that enters the cell via active transport. Further studies are needed to elucidate if
L. monocytogenes
pinpoint isolates could have any clinical impact, e.g., in persistent infections.
In Vitro
Activity of the New Fluoroketolide Solithromycin (CEM-101) against Macrolide-Resistant and -Susceptible Mycoplasma genitalium Strains
Authors: Jensen Jørgen Skov , Fernandes Prabhavathi , Unemo Magnus
Published: March 2014

Mycoplasma genitalium
has become well established as an etiological agent of sexually transmitted infections, but due to its fastidious growth requirements, only a few
M. genitalium
strains are available to determine the MICs of currently used and new antimicrobial agents. Recent clinical trials have suggested that treatment with azithromycin has decreasing efficacy due to an increasing prevalence of macrolide resistance, and alternative treatment with moxifloxacin is similarly under pressure from emerging resistance. Thus, there is an urgent need for new antimicrobials. The
in vitro
activity of the newly developed fluoroketolide solithromycin (CEM-101) was evaluated against a collection of 40
M. genitalium
strains, including 15 with high-level macrolide resistance and 5 multidrug-resistant strains with resistance to both macrolides and quinolones. Furthermore, the MIC of solithromycin was correlated with mutations in the 23S rRNA gene and in the genes encoding ribosomal proteins L4 and L22. The
in vitro
results showed that solithromycin has activity against
M. genitalium
superior to that of other macrolides, doxycycline, and fluoroquinolones. Accordingly, this new fluoroketolide might be an effective option for treatment of
M. genitalium
infections. However, the efficacy of solithromycin in clinical trials with follow-up for test of cure and detection of genotypic and phenotypic resistance needs to be evaluated prior to widespread use. In a phase 2 clinical trial, solithromycin was highly effective as a single oral dose against
C. trachomatis
and
Neisseria gonorrhoeae
, suggesting that solithromycin could be a treatment option for several sexually transmitted infections, including in syndromic treatment of urethral and vaginal discharge.