bluuebunny/crossref_metadata_2025 huggingface dataset:
Same-Session Dorsal Vein Ligation and Testing by Intracavernous Injection Prior to Penile Prosthesis Implantation (DVL-ICI-PPI)
Authors: Shaeer Osama , Shaeer Kamal
Published: May 2014

Introduction

Complications of penile prosthesis implantation (PPI) are rare, nevertheless can be grave. In cases with veno-occlusive dysfunction (VOD), alternative surgical techniques such as dorsal vein ligation (DVL) are controversial. Some patients may opt for trial at DVL to avoid the possible complications of PPI. However, this may be associated with disappointment if DVL fails and another procedure is required.

Aim

The aim if this study is to evaluate the results of a combined approach involving DVL, same-session testing by intracavernous injection (ICI) of prostaglandin E1 (PGE1), and immediate implantation of a penile prosthesis (PPI) in case of poor response to DVL.

Main Outcome Measures

Long-term erectile function in cases with favorable intraoperative response to DVL.

Methods

Twenty-six patients with refractory VOD were operated upon. Through a peno-pubic incision, DVL was performed, followed by ICI of 20 µg PGE1 in two divided doses, 10 µg each, 15 minutes apart. Group 1 exhibited full rigidity in response to the first dose. Group 2 exhibited full rigidity in response to the second dose. PPI was not performed for either. Group 3 exhibited suboptimal response to both doses, and PPI was performed through the same incision. Patients were followed up from 24 to 48 months using International Index of Erectile Function-5 scoring.

Results

For Group 1 (n = 8), six patients experienced normal erectile function following DVL throughout the whole follow-up period of 48 months (23.1% of all patients), and two patients relapsed. Group 2 (n = 6) (23.1%) reported normal erectile function for an average of 6 months, then relapsed. Group 3 (n = 12) had a penile prosthesis implanted in the same setting.

Conclusion

Combined DVL-ICI-PPI can spare around 23.1% of young patients with VOD from PPI, at no additional risk. Full response to 10 µg PGE1 at intraoperative testing carries good prognosis to DVL on the long run. Investigation of a larger number of patients is necessary before reaching a final conclusion.
Activation of β-Adrenergic Receptors During Sexual Arousal Facilitates Vaginal Lubrication by Regulating Vaginal Epithelial Cl− Secretion
Authors: Sun Qing , Huang Jiehong , Yang Deng-Liang , Cao Xiao-Nian , Zhou Wen-Liang
Published: May 2014

Introduction

Vaginal lubrication, an indicator of sexual arousal and tissue health, increases significantly during genital sexual arousal. Adrenergic alpha-receptors (AR) are an important regulator of genital physiological responses involved in mediating vascular and nonvascular smooth muscle contractility; the role of β-AR in sexual arousal, however, has not yet been investigated.

Aim

The goal of this study was to reveal the functional role of β-AR in modulating vaginal lubrication during sexual arousal and the mechanisms underlying the process.

Methods

The effects of adrenaline on vaginal epithelial ion transport, intracellular cyclic adenosine monophosphate (cAMP) content ([cAMP]i), and vaginal lubrication were investigated using short-circuit current (ISC) of rat vaginas incubated in vitro, enzyme-linked immunosorbent assay (ELISA), and measurement of vaginal lubrication in vivo, respectively. The expressions of β-AR in vaginal epithelium were analyzed by reverse transcription-polymerase chain reaction, western blot, and immunofluorescence.

Main Outcome Measures

Changes of ISC responses; mRNA, protein expressions and localization of β-AR; [cAMP]i; vaginal lubrication.

Results

Serosal application of adrenaline induced an increase of ISC across rat vaginal epithelium that blocked by propranolol, a β-AR antagonist, rather than phentolamine, an α-AR antagonist. β1/2-AR were both present in rat and human vaginal epithelial cells. Removing Cl− or application of CFTR(inh)-172, an inhibitor of cystic fibrosis transmembrane conductance regulator (CFTR), abolished adrenaline-induced ISC responses. The elevated levels of [cAMP]i induced by adrenaline were prevented by the pretreatment with propranolol. Vaginal lubrication measured in vivo showed that adrenaline or pelvic nerve stimulation caused a marked increase in vaginal lubrication, whereas pretreatment with propranolol or CFTR(inh)-172 reduced the effect.

Conclusions

Activation of epithelial β-AR facilitates vaginal lubrication during sexual arousal by stimulating vaginal epithelial Cl− secretion in a cAMP-dependent pathway. Thus, vaginal epithelial β-AR might be another regulator of vaginal sexual arousal responses.
Erection Hardness Score for the Evaluation of Erectile Dysfunction: Further Psychometric Assessment in Patients Treated by Intracavernous Prostaglandins Injections after Radical Prostatectomy
Authors: Parisot Juliette , Yiou René , Salomon Laurent , de la Taille Alexandre , Lingombet Odile , Audureau Etienne
Published: May 2014

Introduction

Erectile dysfunction (ED) affects quality of life in patients treated by radical prostatectomy (RP). The Erection Hardness Score (EHS) is a single-item scale that has demonstrated good psychometric properties for assessing erectile function (EF) in patients treated by sildenafil, but its applicability to other treatment contexts has not yet been tested.

Aim

This study aims to test the validity and time and treatment responsiveness of the EHS to assess ED in men with post-RP ED treated with alprostadil injections.

Methods

This is a 1-year follow-up cohort study of 75 patients treated by RP for localized prostate cancer in a urology department setting between January 2007 and December 2008. Data were prospectively collected at 6 and 12 months post-RP.

Main Outcome Measures

The EHS, the International Index of Erectile Function (IIEF) reference questionnaire, the Global Assessment Questionnaire (GAQ), and Numeric Pain Scale (NPS) were collected. Convergent validity (Spearman correlation coefficients with IIEF domains), known-groups validity (comparing EHS scores across ED severity groups), time and treatment responsiveness (effect size with/without treatment and over the follow-up period), and predictive ability (area under the receiver operating characteristics curve [AUC-ROC]) were analyzed for this study.

Results

The EHS showed good convergent validity (all Spearman coefficients significant at the P < 0.05 level), adequate known-groups validity (global differentiation between IIEF-EF severity groups; P < 0.001), and treatment responsiveness (effect size: +1.8 [6 months], +2.1 [12 months]), but limited time responsiveness and predictive ability of the EHS for a normal EF at 12 months follow-up when compared with the IIEF-EF domain (AUC-ROC: 0.72 vs. 0.85; P < 0.01).

Conclusion

Our findings support the overall good psychometric properties of the EHS in patients with post-RP ED treated with alprostadil injections. However, evidence for limited predictive validity and responsiveness to change over time should be considered for its use in clinical follow-up in this population.
A FAST FRACTIONAL DIFFERENCE ALGORITHM
Authors: Jensen Andreas Noack , Nielsen Morten Ørregaard
Published: May 2014

We provide a fast algorithm for calculating the fractional difference of a time series. In standard implementations, the calculation speed (number of arithmetic operations) is of order T2, where T is the length of the time series. Our algorithm allows calculation speed of order TlogT. For moderate and large sample sizes, the difference in computation time is substantial. Copyright © 2014 John Wiley & Sons, Ltd.
Infiltrating neutrophils aggravate metabolic liver failure in fah‐deficient mice
Authors: Qi Ziping , Wang Xin , Wei Haiming , Sun Rui , Tian Zhigang
Published: May 2014

Background & Aims

Mice deficient in tyrosine catabolic enzyme fumarylacetoacetate hydrolase (fah−/−) was a useful animal model for studying liver failure. Tyrosine metabolic toxicants accumulate in hepatocytes over time in fah−/− mice, leading to hepatocyte necrosis which we propose release many type of damage associated molecular patterns (DAMPs) and cause chronic inflammation. However, whether immune‐mediated inflammations cause a second wave of liver damage in fah−/− mice have never been investigated.

Methods

The progressive changes in body weight, survival rate and liver inflammation were examined after the protective drug (NTBC) withdrawal. Cell depletion and receptor blocking were used to define the key immune cells and molecules in liver injury.

Results

After removing of NTBC, fah−/− mice lost their body weight gradually, and finally died when the body weight largely reduced (low to 70%), along with increased serum ALT and total bilirubin. Importantly, a large amount of liver‐infiltrating neutrophils were observed. Neutrophils depletion reduced the liver failure, and resulted in a better survival of fah−/− mice after NTBC withdrawal. The liver tissues produce more CCR2 chemokine, with neutrophils expressing more CCR2. CCR2 inhibition reduced the number of liver‐infiltrating neutrophils and increased the expression of repair cytokine IL‐22, with a longer survival of fah−/− mice after NTBC withdrawal.

Conclusions

The excess infiltrating neutrophils exacerbate liver failure in fah−/− mice which can be attenuated by blocking CCR2.
VALUATION OF BARRIER OPTIONS VIA A GENERAL SELF‐DUALITY
Authors: Alòs Elisa , Chen Zhanyu , Rheinländer Thorsten
Published: May 2014

Classical put–call symmetry relates the price of puts and calls under a suitable dual market transform. One well‐known application is the semistatic hedging of path‐dependent barrier options with European options. This, however, in its classical form requires the price process to observe rather stringent and unrealistic symmetry properties. In this paper, we develop a general self‐duality theorem to develop valuation schemes for barrier options in stochastic volatility models with correlation.
ARROW–DEBREU EQUILIBRIA FOR RANK‐DEPENDENT UTILITIES
Authors: Xia Jianming , Zhou Xun Yu
Published: May 2014

We provide conditions on a one‐period‐two‐date pure exchange economy with rank‐dependent utility agents under which Arrow–Debreu equilibria exist. When such an equilibrium exists, we show that the state‐price density is a weighted marginal rate of intertemporal substitution of a representative agent, where the weight depends on the differential of the probability weighting function. Based on the result, we find that asset prices depend upon agents' subjective beliefs regarding overall consumption growth, and we offer a direction for possible resolution of the equity premium puzzle.
Using molecular prey detection to quantify rock lobster predation on barrens‐forming sea urchins
Authors: Redd K. S. , Ling S. D. , Frusher S. D. , Jarman S. , Johnson C. R.
Published: May 2014

We apply qPCR molecular techniques to detect in situ rates of consumption of sea urchins (Centrostephanus rodgersii and Heliocidaris erythrogramma) by rock lobsters (Jasus edwardsii). A non‐lethal method was used to source faecal samples from trap‐caught lobsters over 2 years within two no‐take research reserves. There was high variability in the proportion of lobsters with faeces positive for sea urchin DNA across years and seasons dependent on lobster size. Independent estimates of lobster predation rate on sea urchins (determined from observed declines in urchin abundances in the reserves relative to control sites) suggest that rates of molecular prey detection generally overestimated predation rates. Also, small lobsters known to be incapable of directly predating emergent sea urchins showed relatively high rates of positive tests. These results indicate that some lobsters ingest non‐predatory sources of sea urchin DNA, which may include (i) ingestion of C. rodgersii DNA from the benthos (urchin DNA is detectable in sediments and some lobsters yield urchin DNA in faeces when fed urchin faeces or sediment); (ii) scavenging; and/or predation by rock lobsters on small pre‐emergent urchins that live cryptically within the reef matrix (although this possibility could not be assessed). While the DNA‐based approach and direct monitoring of urchin populations both indicate high predation rates of large lobsters on emergent urchins, the study shows that in some cases absolute predation rates and inferences of predator–prey interactions cannot be reliably estimated from molecular signals obtained from the faeces of benthic predators. At a broad semi‐quantitative level, the approach is useful to identify relative magnitudes of predation and temporal and spatial variability in predation.
Graft rupture after high‐dose intravenous immunoglobulin therapy in a renal transplant patient
Authors: Sin Yong‐Hun , Kim Yong‐Jin , Oh Joon Seok , Lee Jin Ho , Kim Seong Min , Kim Joong Kyung
Published: May 2014

Cases of life‐threatening thromboses in pulmonary, coronary, cerebral and peripheral vessels are associated with high‐dose intravenous immunoglobulin (IVIg) therapy that is generally considered safe. We experienced a patient with a renal graft rupture that developed after high‐dose IVIg was administered for desensitization. A needle biopsy performed 4 days prior to the rupture revealed the presence of glomerular thrombosis and mesangiolysis. The ruptured nephrectomy specimen contained renal infarction around the haemorrhagic segment and arterial wall thickening with intimal fibrosis. This might have contributed to rupturing associated with small arterial and glomerular arteriolar thrombi. This is the first case of a graft rupture as a complication of high‐dose IVIg we have encountered.
Successful treatment of BK virus nephropathy using therapeutic drug monitoring of mycophenolic acid
Authors: Kobayashi Akimitsu , Yamamoto Izumi , Nakada Yasuyuki , Kidoguchi Satoshi , Matsuo Nanae , Tanno Yudo , Ohkido Ichiro , Tsuboi Nobuo , Yamamoto Hiroyasu , Yokoyama Keitaro , Yokoo Takashi
Published: May 2014

We report the successful management of BK virus nephropathy (BKVN) using therapeutic drug monitoring (TDM) of mycophenolic acid (MPA). A 40‐year‐old woman was admitted for a protocol biopsy 3 months following primary kidney transplantation. Histological features were distributed in mainly two sections: the corticomedullary junction and cortical area. In the former, massive interstitial mononuclear cell infiltration and mild to moderate tubulitis with nuclear inclusion bodies were found. SV40 staining was positive in the injured tubules. These findings were compatible with BKVN. In the latter, focal interstitial inflammation and severe tubulitis without cytopathic changes were identified outside of SV40‐positive areas. Based on the histological findings, we diagnosed BKVN and we also suspected of the complication with acute T‐cell‐mediated rejection. We started steroid pulse therapy and reduced the dosage of immunosuppressive therapy under careful monitoring, using not only a trough level of tacrolimus but also a 12‐h area under the curve (AUC0–12) of MPA. After the treatment, the patient maintained kidney function. This case report demonstrates the usefulness of MPA AUC0–12 for more accurate adjustment of immunosuppressive therapy and the difficulty of pathological differentiation of BKVN and acute cellular rejection.
A case of IgG4‐positive plasma cell‐rich tubulointerstitial nephritis in a kidney allograft mimicking IgG4‐related kidney disease
Authors: Nishikawa Kouhei , Takeda Asami , Masui Satoru , Kanda Hideki , Yamada Yasushi , Arima Kiminobu , Morozumi Kunio , Sugimura Yoshiki
Published: May 2014

A 51‐year‐old woman received an ABO blood type‐incompatible renal transplant. She was administered rituximab and basiliximab and underwent plasma exchanges for induction therapy, followed by administration of tacrolimus, mycophenolate mofetil and methylprednisolone as maintenance immunosupression therapy. A planned renal biopsy 2 years after transplantation revealed infiltration of plasma cells in the renal interstitium, although there was no ‘storiform’ fibrosis surrounding these cells. There were also no findings of rejection, BK virus nephropathy, or atypical plasma cells. Immunohistochemical stainings showed a large number of IgG4‐positive plasma cells, most of which expressed kappa‐type light chains. A CT scan showed a mass at the renal hilum. The serum IgG4 level was high. Based on these findings, the patient was suspected of having IgG4‐related kidney disease. Nine months after the biopsy, her serum creatinine level increase to 1.56 mg/dL and the dose of methylprednisolone was therefore increased to 16 mg/day. Three months after this increase in steroid, a CT scan showed the hilum mass had disappeared. A follow‐up biopsy 5 months later showed that infiltration of plasma cells in the renal interstitium had decreased markedly, although focal and segmental severely fibrotic lesions with IgG4‐positive plasma cells were observed. Serum IgG4 levels decreased immediately after the increase in steroid dose and remained <100 mg/dL despite a reduction in methylprednisolone to 6 mg/day. Serum creatinine levels also remained stable at around 1.6 mg/dL. To our knowledge, this is the first report of IgG4‐positive plasma cell‐rich tubulointerstitial nephritis mimicking IgG4‐related kidney disease after kidney transplantation.
Nitric oxide production and blood pressure reduction during haemodialysis
Authors: Chang Chiz‐Tzung , Chien Ming‐Hui , Yang Kai‐Liang , Yu Chien‐Chih , Hsu Jing‐Fang , Wang I‐Kuan , Lim Paik‐Seong , Huang Chiu‐Ching
Published: May 2014

Aim

A decrease of systolic blood pressure in excess of 20 mmHg during haemodialysis treatment (IDD) is common for haemodialysis patients. Intradialytic hypotension (IDH) is symptomatic IDD by definition. Overproduction of nitric oxide (NO) is a possible cause of IDD. Dialysate nitrate and nitrite amount can be used as an indicator of intradialysis NO production. Our aim was to find the predictor of NO production in IDD patients.

Methods

Partial dialysate samples were collected during the whole haemodialysis session and total dialysate nitrate and nitrite amount was measured to assess the association of intradialysis NO production with blood pressure change.

Results

There were 31 IDD patients and 71 patients who did not develop IDD (NIDD) included in the study. Among the IDD patients, 13 were IDH patients with a mean systolic blood pressure lower than that of the other 18 symptomless IDD patients (96.6 ± 3.4 mmHg vs 125.0 ± 3.8 mmHg, P < 0.001). The median value of NO production was higher in the IDD than in the NIDD patients (447.7 μg vs 238.8 μg, P < 0.001). The NO production correlated linearly with blood pressure reduction (R = 0.487, P < 0.001). The multivariate analysis showed that NO production was positively associated with predialysis systolic blood pressure.

Conclusion

Nitric oxide production during haemodialysis was higher in IDD than in NIDD patients. IDH often occurred when systolic blood pressure was reduced to below 100 mmHg. The amount of NO produced during haemodialysis, which may be associated with predialysis systolic blood pressure, can be used to predict intradialysis blood pressure decrease.
A Japanese patient with familial ALS and a p.K510M mutation in the gene for FUS (FUS) resulting in the totally locked‐in state
Authors: Mochizuki Yoko , Kawata Akihiro , Maruyama Hirofumi , Homma Taku , Watabe Kazuhiko , Kawakami Hideshi , Komori Takashi , Mizutani Toshio , Matsubara Shiro
Published: May 2014

We describe a Japanese patient with familial amyotrophic lateral sclerosis (ALS) and a p.K510M mutation in the fused in sarcoma gene (FUS). The patient's condition was characterized clinically by an early onset and rapid progression. The patient eventually required mechanical ventilation and progressed to the totally locked‐in state. Neuropathologically, multiple system degeneration with many FUS‐immunoreactive structures was observed. The involvement of the globus pallidus, subthalamic nucleus, substantia nigra, cerebellar efferent system, and both upper and lower motor neurons in the present patient was comparable to that described for ALS patients with different mutations in FUS, all of whom progressed to the totally locked‐in state. However, the patient also exhibited degeneration of the cerebellar afferent system and posterior column. Furthermore, the appearance of non‐compact FUS‐immunoreactive neuronal cytoplasmic inclusions and many FUS‐immunoreactive glial cytoplasmic inclusions were unique to the present patient. These features suggest that the morphological characteristics of the FUS‐immunoreactive structures and distribution of the lesions vary with the diversity of mutations in FUS.
Peripheral odontogenic myxoma presenting as a gingival mass – a unique presentation with calcification
Authors: Jose M. , Basheer S. , Balan A. , Shameena P.M.
Published: May 2014

Myxomas of the jaws are considered to arise from odontogenic ectomesenchyme. They bear a close resemblance to the mesenchymal portion of a developing tooth. Peripheral odontogenic myxomas are very rare and less aggressive compared with the central odontogenic myxomas. No case of peripheral odontogenic myxoma with calcification has been reported to date. The purpose of this article is to document a case of peripheral odontogenic myxoma with calcification, located on the posterior maxillary gingiva.
Neurotransmitter Transporter Family Including SLC6A6 and SLC6A13 Contributes to the 5‐Aminolevulinic Acid (ALA)‐Induced Accumulation of Protoporphyrin IX and Photodamage, through Uptake of ALA by Cancerous Cells
Authors: Tran Tai Tien , Mu Anfeng , Adachi Yuka , Adachi Yasushi , Taketani Shigeru
Published: May 2014

δ‐Aminolevulinic acid (ALA)‐induced protoporphyrin accumulation is widely used in the treatment of cancer, as photodynamic therapy (PDT). To clarify the mechanisms of ALA uptake by tumor cells, we have examined the ALA‐induced accumulation of protoporphyrin by the treatment of colon cancer DLD‐1 and epithelial cancer HeLa cells with γ‐aminobutyric acid (GABA)‐related compounds. When the cells were treated with GABA, taurine and β‐alanine, the level of protoporphyrin was decreased, suggesting that plasma membrane transporters involved in the transport of neurotransmitters contribute to the uptake of ALA. By transfection with neurotransmitter transporters SLC6A6, SLC6A8 and SLC6A13 cDNA, the ALA‐ and ALA methylester‐dependent accumulation of protoporphyrin markedly increased in HEK293T cells, dependent on an increase in the uptake of ALA. When ALA‐treated cells were exposed to white light, the extent of photodamage increased in SLC6A6‐ and SLC6A13‐expressing cells. Conversely, knockdown of SLC6A6 or SLC6A13 with siRNAs in DLD‐1 and HeLa cells decreased the ALA‐induced accumulation. The expression of SLC6A6 and SLC6A13 was found in some cancer cell lines. Immunohistochemical studies revealed that the presence of these transporters was elevated in colon cancerous cells. These results indicated that neurotransmitter transporters including SLC6A6 and SLC6A13 mediate the uptake of ALA and can play roles in the enhancement of ALA‐induced accumulation of protoporphyrin in cancerous cells.
Business model innovation – state of the art and future challenges for the field
Authors: Spieth Patrick , Schneckenberg Dirk , Ricart Joan E.
Published: May 2014

Business model innovation is receiving increased attention in corporate practice and research alike. We propose in this article a role‐based approach to categorize the literature and argue that the respective roles of explaining the business, running the business, and developing the business can serve as three interrelated perspectives to present an overview of the current business model innovation field and to accommodate the selected contributions of this special issue. We refer to contributions from entrepreneurship, innovation and technology management, and corporate strategy to explicate the three elaborated perspectives and to summarize the main contents of the special issue articles. We conclude by reflecting on main theoretical challenges for studies on business model innovation which stem from the uncertain boundaries of the phenomenon, and we propose some theoretical stances and analytic levels to develop future avenues for research.
Female athlete's heart: Systolic and diastolic function related to circulatory dimensions
Authors: Hedman K. , Tamás É. , Henriksson J. , Bjarnegård N. , Brudin L. , Nylander E.
Published: May 2014

There are relatively few studies on female athletes examining cardiac size and function and how these measures relate to maximal oxygen uptake (VO2max). When determining sports eligibility, it is important to know what physiological adaptations and characteristics may be expected in female athletes, taking body and cardiac size into account. The purposes of this study were (a) to compare right and left heart dimensions and function in female endurance athletes (ATH) and in non‐athletic female controls of similar age (CON); and (b) to explore how these measures related to VO2max. Forty‐six ATH and 48 CON underwent a maximal bicycle exercise test and an echocardiographic examination at rest, including standard and color tissue Doppler investigation. All heart dimensions indexed for body size were larger in ATH (all P < 0.01). The diastolic mitral E/A ratio was 27% higher in ATH (P < 0.001) while systolic left and right atrio‐ventricular longitudinal displacement was 7% (P = 0.002) and 15% (P < 0.001) larger in ATH, respectively. Half (50.3%) of the variability in VO2max could be explained by left ventricular end‐diastolic volume. Our results could be useful in evaluating female endurance athletes with suspected cardiac disease and contribute to understanding differences between female athletes and non‐athletes.
Roles of lipids as signaling molecules and mitigators during stress response in plants
Authors: Okazaki Yozo , Saito Kazuki
Published: May 2014

Lipids are the major constituents of biological membranes that can sense extracellular conditions. Lipid‐mediated signaling occurs in response to various environmental stresses, such as temperature change, salinity, drought and pathogen attack. Lysophospholipid, fatty acid, phosphatidic acid, diacylglycerol, inositol phosphate, oxylipins, sphingolipid, and N–acylethanolamine have all been proposed to function as signaling lipids. Studies on these stress‐inducible lipid species have demonstrated that each lipid class has specific biological relevance, biosynthetic mechanisms and signaling cascades, which activate defense reactions at the transcriptional level. In addition to their roles in signaling, lipids also function as stress mitigators to reduce the intensity of stressors. To mitigate particular stresses, enhanced syntheses of unique lipids that accumulate in trace quantities under normal growth conditions are often observed under stressed conditions. The accumulation of oligogalactolipids and glucuronosyldiacylglycerol has recently been found to mitigate freezing and nutrition‐depletion stresses, respectively, during lipid remodeling. In addition, wax, cutin and suberin, which are not constituents of the lipid bilayer, but are components derived from lipids, contribute to the reduction of drought stress and tissue injury. These features indicate that lipid‐mediated defenses against environmental stress contributes to plant survival.
Transfusion of stored blood impairs host defenses against Gram‐negative pathogens in mice
Authors: Prestia Kevin , Bandyopadhyay Sheila , Slate Andrea , Francis Richard O. , Francis Kevin P. , Spitalnik Steven L. , Fidock David A. , Brittenham Gary M. , Hod Eldad A.
Published: May 2014

Background

Although human red blood cell (RBC) units may be refrigerator stored for up to 42 days, transfusion of older RBCs acutely delivers a large bolus of iron to mononuclear phagocytes. Similarly, iron dextran circulates in plasma for hours to days and is progressively cleared by mononuclear phagocytes, which return iron to plasma. Finally, malaria infection continuously delivers iron to macrophages by intra‐ and extravascular hemolysis. Studies suggest that iron administration increases infectious risk.

Study Design and Methods

To assess the effects of increased iron availability on susceptibility to infection, we infected mice with model Gram‐negative intracellular or extracellular pathogens (Salmonella typhimurium or Escherichia coli, respectively), accompanied by RBC transfusion, iron dextran administration, or malarial coinfection.

Results

In our mouse models, transfusion of older RBCs exacerbates infection with both Gram‐negative pathogens. Although iron dextran exacerbates E. coli infection to a similar extent as transfusion of corresponding amounts of iron, higher iron doses are required to produce comparable effects with S. typhimurium. Coinfection of mice with Plasmodium yoelii and S. typhimurium produces overwhelming Salmonella sepsis. Finally, treating mice with antibiotics abrogates the enhancing effect on E. coli infection of both older RBC transfusion and iron dextran administration.

Conclusions

Transfusion of older RBCs exacerbates Gram‐negative infection to a similar extent as malaria coinfection or iron dextran administration. Appropriate antibiotic therapy abrogates the effect of older RBC transfusions on infection with E. coli. Iron delivery to macrophages may be an underappreciated mechanism mediating, at least some, adverse effects of RBC transfusions.
The China Growth Miracle: The Role of the Formal and the Informal Institutions
Authors: Chan Kenneth S. , Xu Xianxiang , Gao Yuanhua
Published: May 2014

This paper examines why China, in spite of its ordinary institutions, can grow so rapidly and for so long. Since each region in China has different quality of institutions and growth rates, we look into provincial and city data for this investigation. The variables formal and informal institutions are added into the conventional cross‐section growth equation. The quality of the formal (informal) institution is taken from an opinion survey on the effectiveness of city governance conducted by the World Bank in 2006 (can be measured by the share of township‐and‐village enterprise in each province during 1978–2002 or by the trust index from surveys). We conclude that it is the informal institution that drives the rapid growth in China. Further investigation, using panel data and Arellano‐Bond system GMM estimator, which controls for the missing fixed effect in cross‐provincial regressions and provides useful instrument, confirms.
Orf virus IL‐10 accelerates wound healing while limiting inflammation and scarring
Authors: Wise Lyn M. , Stuart Gabriella S. , Real Nicola C. , Fleming Stephen B. , Mercer Andrew A.
Published: May 2014

Interleukin (IL)‐10 plays a critical role in controlling wound inflammation and scar formation. Orf virus, a zoonotic parapoxvirus, induces proliferative skin lesions that resolve with minimal scarring. Orf virus encodes a range of factors that subvert the host's response to infection, including a homolog of IL‐10. This study investigated, using a murine full‐thickness wound model, whether purified orf virus IL‐10 (ovIL‐10) can regulate skin repair and scarring. Repeat injections of ovIL‐10 into wounded skin accelerated wound closure. Histological analyses of wound sections revealed that treatment with ovIL‐10 accelerated wound reepithelialization, granulation tissue coverage of the wound bed, and improved wound revascularization. In addition, wounds treated with ovIL‐10 showed a reduction in macrophage infiltration, myofibroblast differentiation, and wound contraction. Treatment of wounds with ovIL‐10 also resulted in a reduction in visible scarring that was consistent with the extent of scar tissue formed. Quantitative polymerase chain reaction analysis confirmed that ovIL‐10 reduced the expression of key mediators of inflammation and granulation tissue formation. These findings show that ovIL‐10, like mammalian IL‐10, limits inflammation and scar tissue formation and reveal a new role for both mammalian and viral IL‐10 in mediating tissue repair.
Modulation of the inflammatory response by increasing fetal wound size or interleukin‐10 overexpression determines wound phenotype and scar formation
Authors: Morris Michael W. , Allukian Myron , Herdrich Benjamin J. , Caskey Robert C. , Zgheib Carlos , Xu Junwang , Dorsett‐Martin Wanda , Mitchell Marc E. , Liechty Kenneth W.
Published: May 2014

Wound size impacts the threshold between scarless regeneration and reparative healing in the fetus with increased inflammation showed in fetal scar formation. We hypothesized that increased fetal wound size increases pro‐inflammatory and fibrotic genes with resultant inflammation and fibroplasia and that transition to scar formation could be reversed by overexpression of interleukin‐10 (IL‐10). To test this hypothesis, 2‐mm and 8‐mm dermal wounds were created in mid‐gestation fetal sheep. A subset of 8‐mm wounds were injected with a lentiviral vector containing the IL‐10 transgene (n = 4) or vehicle (n = 4). Wounds were harvested at 3 or 30 days for histology, immunohistochemistry, analysis of gene expression by microarray, and validation with real‐time polymerase chain reaction. In contrast to the scarless 2‐mm wounds, 8‐mm wounds showed scar formation with a differential gene expression profile, increased inflammatory cytokines, decreased CD45+ cells, and subsequent inflammation. Lentiviral‐mediated overexpression of the IL‐10 gene resulted in conversion to a regenerative phenotype with decreased inflammatory cytokines and regeneration of dermal architecture. In conclusion, increased fetal wounds size leads to a unique gene expression profile that promotes inflammation and leads to scar formation and furthermore, these results show the significance of attenuated inflammation and IL‐10 in the transition from fibroplasia to fetal regenerative healing.
Results from Australia’s 2014 Report Card on Physical Activity for Children and Youth
Authors: Schranz Natasha , Olds Tim , Cliff Dylan , Davern Melanie , Engelen Lina , Giles-Corti Billie , Gomersall Sjaan , Hardy Louise , Hesketh Kylie , Hills Andrew , Lubans David , Macdonald Doune , Macniven Rona , Morgan Philip , Okely Tony , Parish Anne-Maree , Plotnikoff Ron , Shilton Trevor , Straker Leon , Timperio Anna , Trost Stewart , Vella Stewart , Ziviani Jenny , Tomkinson Grant
Published: May 2014

Background:

Like many other countries, Australia is facing an inactivity epidemic. The purpose of the Australian 2014 Physical Activity Report Card initiative was to assess the behaviors, settings, and sources of influences and strategies and investments associated with the physical activity levels of Australian children and youth.

Methods:

A Research Working Group (RWG) drawn from experts around Australia collaborated to determine key indicators, assess available datasets, and the metrics which should be used to inform grades for each indicator and factors to consider when weighting the data. The RWG then met to evaluate the synthesized data to assign a grade to each indicator.

Results:

Overall Physical Activity Levels were assigned a grade of D-. Other physical activity behaviors were also graded as less than average (D to D-), while Organized Sport and Physical Activity Participation was assigned a grade of B-. The nation performed better for settings and sources of influence and Government Strategies and Investments (A- to a C). Four incompletes were assigned due to a lack of representative quality data.

Conclusions:

Evidence suggests that physical activity levels of Australian children remain very low, despite moderately supportive social, environmental and regulatory environments. There are clear gaps in the research which need to be filled and consistent data collection methods need to be put into place.
Impact of the Active Healthy Kids Canada Report Card: A 10-Year Analysis
Authors: Tremblay Mark S. , Barnes Joel D. , Bonne Jennifer Cowie
Published: May 2014

For 20 years Active Healthy Kids Canada (AHKC) has worked to inspire the country to engage all children and youth in physical activity (PA). The primary vehicle to achieve this is the AHKC Report Card on Physical Activity for Children and Youth, which has been released annually since 2005. Using 10 years of experience with this knowledge translation and synthesis mechanism, this paper aggregates and consolidates diverse evidence demonstrating the impact of the Report Card and related knowledge translation activities. Over the years many evaluations, consultations, assessments, and surveys have helped inform changes in the Report Card to improve its impact. Guided by a logic model, the various assessments have traversed areas related to distribution and reach, meeting stakeholder needs, use of the Report Card, its influence on policy, and advancing the mission of AHKC. In the past 10 years, the Report Card has achieved > 1 billion media impressions, distributed > 120,000 printed copies and > 200,000 electronic copies, and benefited from a collective ad value > $10 million. The Report Card has been replicated in 14 countries, 2 provinces, 1 state and 1 city. AHKC has received consistent positive feedback from stakeholders and endusers, who reported that the Report Card has been used for public awareness/education campaigns and advocacy strategies, to strengthen partnerships, to inform research and program design, and to advance and adjust policies and strategies. Collectively, the evidence suggests that the Report Card has been successful at powering the movement to get kids moving, and in achieving demonstrable success on immediate and intermediate outcomes, although the long-term goal of improving the PA of Canadian children and youth remains to be realized.
Results from Ghana’s 2014 Report Card on Physical Activity for Children and Youth
Authors: Ocansey Reginald , Aryeetey Richmond , Sofo Seidu , Delali Margaret Badasu , Pambo Prince , Nyawornota Vida Korleki
Published: May 2014

Background:

Limited evidence exists on indicators of physical activity (PA) and guidelines for children and youth in Ghana, despite the growing burden of physical inactivity, obesity, and related morbidity. A baseline description of PA indicators of Ghanaian children and youth is hereby presented in the 2014 Ghanaian Physical Activity Report Card.

Methods:

Data for the report card were obtained from a very limited available literature on PA among children and youth in Ghana. PA experts independently assigned grades to indicators based on available evidence, which were then harmonized and agreed to by group consensus.

Results:

The report card is based on limited evidence. Thus, 2 indicators were not graded (Active Play, and Family and Peer Support). For sedentary behavior, a B grade was assigned based on evidence from the 2012 Ghana School Health Survey which indicated that 21% of children and youth were sedentary. Organized Sports was graded a C, while the remainder of indicators (Overall PA levels, Active Transportation, School, Community, and Government) were graded a D.

Conclusions:

About one-third of Ghanaian children and youth engage in inadequate PA. More research on PA behavior and enabling environments is needed to better grade the indicators of PA in the future and to inform policy and interventions in Ghana. Appropriate school physical education and after-school sports policies and programs are warranted.
Results from Scotland’s 2013 Report Card on Physical Activity for Children and Youth
Authors: Reilly John J. , Dick Smita , McNeill Geraldine , Tremblay Mark S.
Published: May 2014

Background:

The Active Healthy Kids Scotland Report Card aims to consolidate existing evidence, facilitate international comparisons, encourage more evidence-informed physical activity and health policy, and improve surveillance of physical activity.

Methods:

Application of the Active Healthy Kids Canada Report Card process and methodology to Scotland, adapted to Scottish circumstances and availability of data.

Results:

The Active Healthy Kids Scotland Report Card 2013 consists of indicators of 7 Health Behaviors and Outcomes and 3 Influences on Health Behaviors and Outcomes. Grades of F were assigned to Overall Physical Activity, Sedentary Behavior (recreational screen time), and Obesity Prevalence. A C was assigned to Active Transportation and a D- was assigned to Diet. Two indicators, Active and Outdoor Play and Organized Sport Participation, could not be graded. Among the Influences, Family Influence received a D, while Perceived Safety, Access, and Availability of Spaces for Physical Activity and the National Policy Environment graded more favorably with a B.

Conclusions:

The Active Healthy Kids Canada process and methodology was readily generalizable to Scotland. The report card illustrated low habitual physical activity and extremely high levels of screen-based sedentary behavior, and highlighted several opportunities for improved physical activity surveillance and promotion strategies.
Results from the United States’ 2014 Report Card on Physical Activity for Children and Youth
Authors: Dentro Kara N. , Beals Kim , Crouter Scott E. , Eisenmann Joey C. , McKenzie Thomas L. , Pate Russell R. , Saelens Brian E. , Sisson Susan B. , Spruijt-Metz Donna , Sothern Melinda S. , Katzmarzyk Peter T.
Published: May 2014

Background:

The National Physical Activity Plan Alliance partnered with physical activity experts to develop a report card that provides a comprehensive assessment of physical activity among United States children and youth.

Methods:

The 2014 U.S. Report Card on Physical Activity for Children and Youth includes 10 indicators: overall physical activity levels, sedentary behaviors, active transportation, organized sport participation, active play, health-related fitness, family and peers, school, community and the built environment, and government strategies and investments. Data from nationally representative surveys were used to provide a comprehensive evaluation of the physical activity indicators. The Committee used the best available data source to grade the indicators using a standard rubric.

Results:

Approximately one-quarter of children and youth 6 to 15 years of age were at least moderately active for 60 min/day on at least 5 days per week. The prevalence was lower among youth compared with younger children, resulting in a grade of D- for overall physical activity levels. Five of the remaining 9 indicators received grades ranging from B- to F, whereas there was insufficient data to grade 4 indicators, highlighting the need for more research in some areas.

Conclusions:

Physical activity levels among U.S. children and youth are low and sedentary behavior is high, suggesting that current infrastructure, policies, programs, and investments in support of children’s physical activity are not sufficient.
Results from South Africa’s 2014 Report Card on Physical Activity for Children and Youth
Authors: Draper Catherine , Basset Susan , de Villiers Anniza , Lambert Estelle V. , _ _
Published: May 2014

Background:

There is current concern for the health and well-being of children and youth in South Africa, including habits of physical activity (PA) and sedentary behavior. The 2014 Healthy Active Kids South Africa Report Card evaluates the current activity status of children and youth.

Methods:

The Research Working Group was comprised of 23 experts in physical education, nutrition, sport science, public health and journalism. The search was based on a systematic review of peer-reviewed literature (previous 5 years), dissertations, and nonpeer-reviewed reports (‘gray’ literature) dealing with the PA and nutritional status of South African children and youth 6−18 years of age. Key indicators were identified and data extracted. Grades for each indicator were discussed and assigned.

Results:

Overall PA levels received a D grade, as roughly 50% or more of children and youth were not meeting recommended levels. Organized sports participation fared better with a C, and government policies were promising, receiving a B. Screen time and sedentary behavior were a major concern and received a grade of F. Under- and over-weight were highlighted, but overweight is on the rise and this indicator was assigned a D grade. Most of the other indicators in South Africa remained the same or became worse so that grades declined from C- to D. In particular, sedentary behavior, soft-drink and fast food consumption, and an ineffectual regulatory environment to control advertising to children were a concern. There is need to engage parents and communities for advocacy and social mobilization.
Antigenic Metabolites
Authors: Gough Nancy R.
Published: May 2014

Glycolytic metabolites react with bacterially produced riboflavin precursors to form antigens recognized by a T cell subtype.
Dual Action Pain Modulator
Authors: Gough Nancy R.
Published: May 2014

TNF-α and its receptor TNFR1 provide an inhibiting input for peptidergic pain neurons and an enhancing input to nonpeptidergic pain neurons.
Observational Cohort Study of Pregnancy Outcome after First-Trimester Exposure to Fluoroquinolones
Authors: Padberg Stephanie , Wacker Evelin , Meister Reinhard , Panse Mary , Weber-Schoendorfer Corinna , Oppermann Marc , Schaefer Christof
Published: May 2014

Fluoroquinolones are avoided during pregnancy due to developmental toxicity in animals. The aim of this study was to assess the fetal risk after intrauterine fluoroquinolone exposure. We performed an observational study of a prospectively ascertained cohort of pregnant women exposed to a fluoroquinolone during the first trimester. Pregnancy outcomes were compared to those of a cohort exposed to neither fluoroquinolones nor teratogenic or fetotoxic drugs. The outcomes evaluated were major birth defects (structural abnormalities of medical, surgical, or cosmetic relevance), spontaneous abortion, and elective termination of pregnancy. Pregnancy outcomes of 949 women with fluoroquinolone treatment were compared with those of 3,796 nonexposed controls. Neither the rate of major birth defects (2.4%; adjusted odds ratio [OR
adj
], 0.91; 95% confidence interval [CI], 0.6 to 1.5) nor the risk of spontaneous abortion (adjusted hazard ratio [HR
adj
], 1.01; 95% CI, 0.8 to 1.3) was increased. However, there was a nonsignificant increase in major birth defects after exposure to moxifloxacin (6/93, 6.5%; crude odds ratio [OR
crude
], 2.40; 95% CI, 0.8 to 5.6). Neither a critical exposure time window within the first trimester nor a specific pattern of birth defects was demonstrated for any of the fluoroquinolones. The rate of electively terminated pregnancies was increased among the fluoroquinolone-exposed women (HR
adj
, 1.32; 95% CI, 1.03 to 1.7). The gestational ages at delivery and birth weights did not differ between groups. Our study did not detect an increased risk of spontaneous abortion or major birth defects. These reassuring findings support the recommendation to allow fluoroquinolone use in early pregnancy in selected cases. After the use of moxifloxacin, a detailed fetal ultrasound examination should be considered.