bluuebunny/crossref_metadata_2025 huggingface dataset:
Phosphoinositide 3-kinase/AKT/mTORC1/2 Signaling Determines Sensitivity of Burkitt's Lymphoma Cells to BH3 mimetics
Authors: Spender Lindsay C. , Inman Gareth J.
Published: January 2012

Burkitt's lymphoma (BL), driven by translocation and overexpression of the c-MYC gene, is an aggressive, highly proliferative lymphoma, and novel therapeutic strategies are required to overcome drug resistance following conventional treatments. The importance of the prosurvival BCL-2 family member BCL-XL in BL cell survival suggests that antagonistic BH3-mimetic compounds may have therapeutic potential. Here, we show that treatment of BL cell lines with ABT-737 induces caspase-3/7 activation and apoptosis with varying potency. Using selective inhibitors, we identify phosphoinositide 3-kinase (PI3K) as a proproliferative/survival pathway in BL cells and investigate the potential of combined pharmacologic inhibition of both the BCL-2 family and PI3K signaling pathway. PI3K/AKT inhibition and ABT-737 treatment induced synergistic caspase activation, augmented BL cell apoptosis, and rendered chemoresistant cells sensitive. Targeting mTORC1/2 with PP242 was also effective, either as a monotherapy or, more generally, in combination with ABT-737. The combined use of a dual specificity PI3K/mTOR inhibitor (PI 103) with ABT-737 proved highly efficacious. PI 103 treatment of BL cells was associated with an increase in BIM/MCL-1 expression ratios and loss of c-MYC expression. Furthermore, blocking c-MYC function using the inhibitor 10058-F4 also induced apoptosis synergistically with ABT-737, suggesting that maintenance of expression of BCL-2 family members and/or c-MYC by the PI3K/AKT/mTOR pathway could contribute to BL cell survival and resistance to ABT-737. The combined use of BH3 mimetics and selective mTORC1/2 inhibitors may therefore be a useful novel therapeutic approach for the treatment of B-cell malignancy, including chemoresistant lymphomas. Mol Cancer Res; 10(3); 347–59. ©2012 AACR.
Integrin-Dependent Akt1 Activation Regulates PGC-1 Expression and Fatty Acid Oxidation
Authors: Beeson Craig C. , Beeson Gyda C. , Buff Haley , Eldridge Juanita , Zhang Aiguo , Seth Arun , Demcheva Marina , Vournakis John N. , Muise-Helmericks Robin C.
Published: January 2012

Background: Poly-N-acetyl glucosamine nanofibers derived from a marine diatom have been used to increase cutaneous wound healing. These nanofibers exert their activity by specifically activating integrins, which makes them a useful tool for dissecting integrin-mediated pathways. We have shown that short-fiber poly-N-acetyl glucosamine nanofiber (sNAG) treatment of endothelial cells results in increased cell motility and metabolic rate in the absence of increased cell proliferation. Results: Using a Seahorse Bioanalyzer to measure oxygen consumption in real time, we show that sNAG treatment increases oxygen consumption rates, correlated with an integrin-dependent activation of Akt1. Akt1 activation leads to an increase in the expression of the transcriptional coactivator, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). This is not due to increased mitochondrial biogenesis, but is associated with an increase in the expression of pyruvate dehydrogenase kinase 4 (PDK4), suggesting regulation of fatty acid oxidation. Blockade of fatty acid oxidation with etomoxir, an O-carnitine palmitoyltransferase-1 inhibitor, blocks the sNAG-dependent increased oxygen consumption. 3H-palmitate uptake experiments indicate a PDK4-dependent increase in fatty acid oxidation, which is required for nanofiber-induced cell motility. Conclusions: Our findings imply a linear pathway whereby an integrin-dependent activation of Akt1 leads to increased PGC-1α and PDK4 expression resulting in increased energy production by fatty acid oxidation.
Noncutaneous Melanoma Have Distinct Features from Each Other and Cutaneous Melanoma
Authors: Tas Faruk , Keskin Serkan , Karadeniz Ahmet , Dağoğlu Nergiz , Sen Fatma , Kilic Leyla , Yildiz Ibrahim
Published: January 2012

Objective: Compared to the cutaneous melanoma, noncutaneous melanomas are relatively rare and have a distinct pattern of behavior. We performed this study to define the clinical characteristics and outcomes of patients with noncutaneous melanomas and emphasize how they differ from cutaneous melanomas. Methods: 216 patients who were diagnosed with noncutaneous melanoma were assessed and their medical records between 2000 and 2010 were retrieved from the cancer registry. 475 patients with cutaneous melanoma were used for comparison. Results: Of the 216 noncutaneous melanoma patients, 83 had mucosal melanoma, 101 had ocular melanoma and 32 had unknown primaries. For mucosal melanoma, the head and neck was the most common anatomic site (53%), followed by the gastrointestinal tract (37%), female genital (6%) and urinary tract (4%). The majority of the ocular melanomas (94%) originated in the uvea. 32 patients demonstrated a primary unknown disease with regional metastasis as the dominant behavior (72%). Age was found to be statistically significantly different among melanoma patients (p < 0.001). Younger patients had more cutaneous and unknown primary melanomas, whereas older patients had more ocular and mucosal melanoma. In subset analyses, we found significant differences between cutaneous and ocular (p = 0.038) or mucosal (p < 0.001) melanomas. The ratios of metastasis on admission were higher in patients with mucosal (27.7%) and unknown primary (28.1%) melanomas, and lower for ocular (3%) melanomas (p < 0.001). Patients with cutaneous melanoma had an intermediate (12%) ratio. Patients with ocular melanoma had better outcome than patients with other melanoma sites (p < 0.05). While overall survival for cutaneous melanoma was significantly negatively correlated with male gender (p < 0.001), advanced stages (p < 0.001) and old age (p = 0.005), stage IV disease was the only independent prognostic factor in patients with ocular melanoma (p = 0.006). No prognostic factor for outcome was found for either mucosal or unknown primary melanomas. Conclusion: The clinical presentations and prognoses of different primary sites of melanoma are distinctive. Therefore, approaches to these melanomas should be different.
Prognostic Impact of Ki-67 Overexpression in Subgroups Categorized according to St. Gallen with Early Stage Breast Cancer
Authors: Matsubara Nobuaki , Mukai Hirofumi , Itoh Kuniaki , Nagai Shunji
Published: January 2012

Background: Ki-67 overexpression has been reported to be related to a poor prognosis for early stage breast cancer. We analyzed whether Ki-67 has a prognostic impact on risk subgroups based on the recommendations at St. Gallen in 2007. Methods: To determine the impact of Ki-67 on each risk group, a retrospective analysis was performed in patients with breast cancer who underwent curative surgery. Ki-67 was examined by immunohistochemistry with a predefined cutoff level of 10%. Results: A total of 1,166 patients were eligible for this analysis. During the follow-up period, distant metastasis was observed in 164 patients (14.1%), and 80 patients (6.9%) died. Ki-67 overexpression (Ki-67 ≧10%) was identified as an independent prognostic factor for distant-metastatic-free survival (DFS) and overall survival (OS) by univariate and multivariate analysis. In the intermediate-risk group, the difference between Ki-67 overexpression and no overexpression was statistically significant in 5-year DFS (90.9 vs. 83.4%, p = 0.002) and OS (98.1 vs. 95.8%, p = 0.002). However, in both the low- and high-risk groups, Ki-67 overexpression was not an independent prognostic factor for either 5-year DFS or OS. Conclusions: Ki-67 overexpression indicates an unfavorable prognostic impact for DFS and OS. However, this impact is restricted only to those patients classified at intermediate risk.
Adult Phenotypes in Angelman- and Rett-Like Syndromes
Authors: Willemsen M.H. , Rensen J.H.M. , van Schrojenstein-Lantman de Valk H.M.J. , Hamel B.C.J. , Kleefstra T.
Published: January 2012

Background: Angelman- and Rett-like syndromes share a range of clinical characteristics, including intellectual disability (ID) with or without regression, epilepsy, infantile encephalopathy, postnatal microcephaly, features of autism spectrum disorder, and variable other neurological symptoms. The phenotypic spectrum generally has been well studied in children; however, evolution of the phenotypic spectrum into adulthood has been documented less extensively. To obtain more insight into natural course and prognosis of these syndromes with respect to developmental, medical, and socio-behavioral outcomes, we studied the phenotypes of 9 adult patients who were recently diagnosed with 6 different Angelman- and Rett-like syndromes. Methods: All these patients were ascertained during an ongoing cohort study involving a systematic clinical genetic diagnostic evaluation of over 250, mainly adult patients with ID of unknown etiology. Results: We describe the evolution of the phenotype in adults with EHMT1, TCF4, MECP2, CDKL5, and SCN1A mutations and 22qter deletions and also provide an overview of previously published adult cases with similar diagnoses. Conclusion: These data are highly valuable in adequate management and follow-up of patients with Angelman- and Rett-like syndromes and accurate counseling of their family members. Furthermore, they will contribute to recognition of these syndromes in previously undiagnosed adult patients.
Nrf3-Pla2g7 Interaction Plays an Essential Role in Smooth Muscle Differentiation From Stem Cells
Authors: Xiao Qingzhong , Pepe Anna E. , Wang Gang , Luo Zhenling , Zhang Li , Zeng Lingfang , Zhang Zhongyi , Hu Yanhua , Ye Shu , Xu Qingbo
Published: January 2012

Objective—

Phospholipase A
2
, group 7 (Pla2g7) is an important mediator in cardiovascular development and diseases because of its divergent physiological and pathological functions in inflammation and oxidative stress. However, little is known about the functional role of Pla2g7 in smooth muscle cell (SMC) differentiation from stem cells.

Methods and Results—

In the present study, embryonic stem cells were cultivated on collagen IV-coated plates to allow SMC differentiation. Pla2g7 gene expression and activity were upregulated significantly following 4 to 14 days of cell differentiation and colocalized with SMC differentiation markers in the differentiated SMCs. Knockdown of Pla2g7 resulted in downregulation of smooth muscle–specific markers in vitro and impairment of SMC differentiation in vivo, whereas enforced expression of Pla2g7 enhanced SMC differentiation and increased reactive oxygen species generation. Importantly, enforced expression of Pla2g7 significantly increased the binding of serum response factor to SMC differentiation gene promoters, resulting in SMC differentiation, which was abolished by free radical scavenger and flavoprotein inhibitor of NADPH oxidase but not hydrogen peroxide inhibitor. Moreover, we demonstrated that nuclear factor erythroid 2-related factor 3 (Nrf3) regulates Pla2g7 gene expression through direct binding to the promoter regions of Pla2g7 gene.

Conclusion—

Our findings demonstrated that Pla2g7 plays a crucial physiological role in SMC differentiation from stem cells, and the fine interactions between Nrf3 and Pla2g7 are essential for SMC differentiation.
Metabolic Syndrome in Adolescence
Authors: Efstathiou Stamatis P. , Skeva Irini I. , Zorbala Evi , Georgiou Evangelos , Mountokalakis Theodore D.
Published: January 2012

Background—

There are well-established predisposing factors for the development of metabolic syndrome (MetS) in childhood or adolescence, but no specific risk profile has been identified as yet. The Prediction of Metabolic Syndrome in Adolescence (PREMA) study was conducted (1) to construct a classification score that could detect children at high risk for MetS in adolescence and (2) to test its predictive accuracy.

Methods and Results—

In the derivation cohort (1270 children), data from natal and parental profile and from initial laboratory assessment at 6 to 8 years of age were used to detect independent predictors of MetS at 13 to 15 years of age according to the International Diabetes Federation definition. In the validation cohort (1091 adolescents), the discriminatory capacity of the derived prediction score was tested on an independent adolescent population. MetS was diagnosed in 105 adolescents in the derivation phase (8%), whereas birth weight <10th percentile (odds ratio, 6.02; 95% confidence interval, 2.53–10.12,
P
<0.001), birth head circumference <10th percentile (odds ratio, 4.15; 95% confidence interval, 2.04–7.14,
P
<0.001), and parental overweight or obesity (in at least 1 parent; odds ratio, 3.22; 95% confidence interval, 1.30–5.29,
P
<0.01) were independently associated with diagnosis of MetS in adolescence. Among adolescents in the validation cohort (86 [8%] with MetS), the presence of all these 3 predictors predicted MetS with a sensitivity of 91% and a specificity of 98%.

Conclusions—

The coexistence of low birth weight, small head circumference, and parental history of overweight or obesity may be useful for detection of children at risk of developing MetS in adolescence.
Technological Power as a Strategic Dilemma: CO2 Capture and Storage in the International Oil and Gas Industry
Authors: Tjernshaugen Andreas
Published: January 2012

This article offers a comparative analysis of the emergence of CO2 capture and storage (CCS) activities and strategies in three multinational oil and gas companies. Exxon/ExxonMobil was first to make plans for a major, pioneering CCS project, but later pursued a relatively cautious strategy. In contrast, BP showed little interest in CCS up until 1997, but from that point on developed a particularly ambitious strategy. Statoil, meanwhile, has been relatively strongly involved in CCS activities for a long time. An explanatory framework with potential for wider application is developed, highlighting how the overall compatibility of CCS with oil and gas industry characteristics created a strategic dilemma for the companies. In explaining their responses, the article emphasizes the process towards institutionalization of CCS as a widely recognized mitigation option, and the three companies' different climate change strategies.
Conflict and Cooperation along International Rivers: Crafting a Model of Institutional Effectiveness
Authors: Berardo Ramiro , Gerlak Andrea K.
Published: January 2012

The management of international rivers is increasingly marked by a heightened attention to and growth in institutions at the river-basin level to promote cooperation and resolve conflicts between states in a basin. Yet, little theoretical and empirical research exists to understand when these institutions are most effective. Here we draw from diverse literatures, including work on social and ecological systems, international institutions, common-pool resources, and international waters, to capture and integrate the design elements associated with effective collaborative management along an international river. We apply and test the validity of our model in a plausibility probe through the analysis of the conflict between Argentina and Uruguay over the construction of pulp mills along the Uruguay River, and the role of the established and functioning river basin organization—the Administrative Commission of the Uruguay River (CARU)—in this conflict. We re-examine our model based on our case findings to highlight the challenge and role of public input and representation in institutional effectiveness along international rivers.
On the North Atlantic Ocean Heat Content Change between 1955–70 and 1980–95
Authors: Zhai Xiaoming , Sheldon Luke
Published: January 2012

The upper-ocean heat content of the North Atlantic has undergone significant changes over the last 50 years but the underlying physical mechanisms are not yet well understood. In the present study, the authors examine the North Atlantic ocean heat content change in the upper 700 m between the 1955–70 and 1980–95 periods. Consistent with previous studies, the large-scale pattern consists of warming of the tropics and subtropics and cooling of the subpolar ocean. However, this study finds that the most significant heat content change in the North Atlantic during these two time periods is the warming of the Gulf Stream region. Numerical experiments strongly suggest that this warming in the Gulf Stream region is largely driven by changes of the large-scale wind forcing. Furthermore, the increased ocean heat content in the Gulf Stream region appears to feedback on to the atmosphere, resulting in warmer surface air temperature and enhanced precipitation there.
An Analysis of Low- and High-Frequency Summer Climate Variability around the Caribbean Antilles
Authors: Gouirand Isabelle , Jury Mark R. , Sing Bernd
Published: January 2012

This study contrasts the pattern of low-frequency (LF) and high-frequency (HF) climate variability in the eastern Caribbean. A low-pass Butterworth filter is used to study oscillations in rainfall and regional SST on time scales of greater and less than 8 yr in the period 1901–2002. The results show that the southern and northern Antilles are dominated by HF variability, whereas rainfall fluctuations in the eastern Antilles oscillate at quasi-decadal periods over the 102-yr record. In the southern Antilles, the HF rainfall signal derives from a late-summer response to the ENSO phase: warm and dry versus cool and wet. In the northern Antilles, the HF signal relates to a combination of an ENSO and North Atlantic Oscillation (NAO) phase: a warm ENSO and a negative NAO bring wetter conditions, while a cool ENSO and a positive NAO bring drier conditions. The early rainfall LF signal in SST is characterized by a dipole between the North Atlantic and South Atlantic and is associated with cross-equatorial winds that promote convection in the Caribbean. The study analyzes the upper-ocean structure—in particular, a low (high) salinity signal in the tropical North Atlantic (North Pacific) that relates to LF (HF) climate variability.
ENSO’s Impact on the Gap Wind Regions of the Eastern Tropical Pacific Ocean*
Authors: Alexander Michael A. , Seo Hyodae , Xie Shang Ping , Scott James D.
Published: January 2012

The recently released NCEP Climate Forecast System Reanalysis (CFSR) is used to examine the response to ENSO in the northeast tropical Pacific Ocean (NETP) during 1979–2009. The normally cool Pacific sea surface temperatures (SSTs) associated with wind jets through the gaps in the Central American mountains at Tehuantepec, Papagayo, and Panama are substantially warmer (colder) than the surrounding ocean during El Niño (La Niña) events. Ocean dynamics generate the ENSO-related SST anomalies in the gap wind regions as the surface fluxes damp the SSTs anomalies, while the Ekman heat transport is generally in quadrature with the anomalies. The ENSO-driven warming is associated with large-scale deepening of the thermocline; with the cold thermocline water at greater depths during El Niño in the NETP, it is less likely to be vertically mixed to the surface, particularly in the gap wind regions where the thermocline is normally very close to the surface. The thermocline deepening is enhanced to the south of the Costa Rica Dome in the Papagayo region, which contributes to the local ENSO-driven SST anomalies. The NETP thermocline changes are due to coastal Kelvin waves that initiate westward-propagating Rossby waves, and possibly ocean eddies, rather than by local Ekman pumping. These findings were confirmed with regional ocean model experiments: only integrations that included interannually varying ocean boundary conditions were able to simulate the thermocline deepening and localized warming in the NETP during El Niño events; the simulation with variable surface fluxes, but boundary conditions that repeated the seasonal cycle, did not.
Propagation of Kuroshio Extension Meanders between 143° and 149°E
Authors: Tracey Karen L. , Watts D. Randolph , Donohue Kathleen A. , Ichikawa Hiroshi
Published: January 2012

A two-dimensional array of current- and pressure-recording inverted echo sounders provided synoptic measurements of the upper and deep fluctuations in the Kuroshio Extension between 143° and 149°E with mesoscale resolution. Downstream-propagating meanders with periods of 3–60 days were always present between June 2004 and September 2005. Propagation speeds were estimated by two methods: spectral analysis of path displacements and complex empirical orthogonal functions (CEOF) analysis of along-path anomalies. The two methods produced similar results. Phase speeds increased smoothly from 10 km day−1 (0.12 m s−1) for meanders with wavelengths and periods [λ, T] = [420 km, 40 days] to 35 km day−1 (0.41 m s−1) for [λ, T] = [220 km, 6 days] meanders. This empirically derived dispersion relationship is indistinguishable from that obtained for Gulf Stream meanders downstream of Cape Hatteras. The deep ocean was populated with remotely generated, upstream-propagating eddies composed of a nearly depth-independent current structure. Upper meanders and deep eddies jointly spun up when they encountered each other with the deep eddy offset about a quarter wavelength ahead of the upper meander. Subsequently, as the upper and deep features moved past each other and the vertical offset changed, intensification ceased.
Web‐Based Teaching Module Improves Success Rates of Postpyloric Positioning of Nasoenteric Feeding Tubes
Authors: Lee Jessica M. , Fernandez Forrest , Staff Ilene , Mah John W.
Published: January 2012

Background: Bedside protocols improve success rates of postpyloric nasoenteric tube (NET) placement by nutrition teams and experienced individuals. However, many hospitals require novice practitioners to perform these procedures and often choose fluoroscopy, endoscopy, or newer alternative devices to achieve success. Little is known about the ability to train inexperienced practitioners or the effectiveness of the methods used to implement these protocols. Web‐based learning is a potential tool to improve knowledge and procedural skills. The authors created a self‐directed Web‐based teaching module (WBTM) to educate and standardize placement of postpyloric NETs. Methods: Forty‐three first‐, second‐, or third‐year residents or medical or physician assistant students took pretests for knowledge and confidence surveys, viewed the WBTM, placed NET at the bedside, then took a posttest and confidence survey while awaiting confirmation of tube position by abdominal radiograph. Success was acknowledged if the tip of the NET was beyond the pylorus. A retrospective chart review was used to determine a historical success rate, which was used as a control. Results: Knowledge and confidence significantly improved. Overall success rate of postpyloric NET placement for all participants on first attempt was 74.4% vs 46.7% in the control (P = .005). Improvement occurred in all subgroups, including those with no prior experience, who were successful 70.4% of the time (P = .009). Conclusions: This WBTM is simple to implement, inexpensive, and resource efficient. The improvement in postpyloric NET placement, especially among novice practitioners, demonstrates the benefit and applicability of this method of standardized education.
Prophylactic Anticoagulation Decreases Catheter‐Related Thrombosis and Occlusion in Children With Home Parenteral Nutrition
Authors: Vegting I. L. , Tabbers M. M. , Benninga M. A. , Wilde J. C. , Serlie M. J. , Tas T. A. , Jonkers C. F. , van Ommen C. H.
Published: January 2012

Background: Home parenteral nutrition (PN) has improved the survival of children with intestinal failure. Important complications include catheter‐related thrombosis, occlusion, and infection. This study evaluated the efficacy and safety of prophylactic anticoagulation in the prevention of these complications. Methods: Medical records were retrospectively reviewed of all children (0–18 years) with PN between January 1994 and March 2007 in 1 tertiary center. After introduction of prophylactic low molecular weight heparin or vitamin K antagonists in March 2007, all patients were prospectively followed until March 2010. Results: In sum, 14 patients did not receive prophylaxis; 13 switched from no prophylaxis to prophylaxis in March 2007; and 5 directly received prophylaxis. Median age of PN onset was 4 months (range, 0.1–202) in the nonprophylaxis group (n = 27) and 25 (range, 2–167) in the prophylaxis group (n = 18); 16 children received low molecular weight heparin and 2, vitamin K antagonists. Catheter‐related thrombosis developed in 9 patients with no prophylaxis (33%) and 1 with prophylaxis (6%) (P = .034). Cumulative 5‐year thrombosis‐free survival was 48% and 93% in the nonprophylaxis and prophylaxis groups, respectively (P = .047). Per 1,000 PN days, the nonprophylaxis and prophylaxis groups had 2.6 and 0.1 occlusions (P = .04) and 4.6 and 2.1 infections (P = .06), respectively. Cumulative infection‐free survival after 3 years was 19% and 46% in the nonprophylaxis and prophylaxis groups, respectively (P = .03). Bleeding complications did not occur. Conclusion: Thromboprophylaxis significantly decreased catheter‐related thrombosis and occlusion in children with PN without complications.
Prevalence of Biofilms and Their Response to Medical Treatment in Chronic Rhinosinusitis without Polyps
Authors: Tatar Emel Çadallı , Tatar İlkan , Öcal Bülent , Korkmaz Hakan , Saylam Güleser , Özdek Ali , Çelik Hakan Hamdi
Published: January 2012

Objective

The aim of this study was to investigate the prevalence of biofilms and the effects of medical treatment modalities in chronic rhinosinusitis (CRS) patients without nasal polyps.

Study Design

Randomized controlled trial.

Settings

Tertiary referral hospital.

Subjects and Methods

The authors randomly divided 32 adult patients with CRS without nasal polyps into 2 groups. In the first group (n = 16), oral clarithromycin was administered 500 mg/bid for 2 weeks and then 250 mg/d for the following 6 weeks. In the second group (n = 16), an 8‐week course of 200‐mcg/d topical mometasone furoate was added to the clarithromycin regimen, identical to the first group. The pre‐ and posttreatment nasal tissue samples were evaluated by scanning electron microscopy for biofilm prevalence and graded from 0 to 3 according to density and extension.

Results

Biofilms were detected in 24 of 32 patients (75%) before the treatment (grades 1‐3). Biofilms were detected in 14 of 32 patients (43.8%) after the treatment (grades 1‐2). When each group was evaluated independently, there was a significant improvement after the treatment in both groups I and II. When the biofilm grades of group I were compared to those of group II, there was no significant difference both in the pre‐ and posttreatment evaluation.

Conclusion

The prevalence of biofilms in CRS without polyps was 75% in our study. Regression of biofilms to 43% was observed under medical treatment. Adding nasal steroids to macrolides gave no further benefit.
Vertical Incision Intraoral Silicone Chin Augmentation
Authors: Aynehchi Behrad B. , Burstein David H. , Parhiscar Afshin , Erlich Mark A.
Published: January 2012

Objective

Solid silicone augmentation mentoplasty is a common procedure with consistent aesthetic results in properly selected patients. While many plastic surgeons employ the external approach, the intraoral method affords excellent aesthetic outcomes while avoiding an external scar. This is the largest series in the literature describing the midline intraoral incision approach with minimal disruption of soft tissues.

Study Design

Case series.

Setting

Academic medical center.

Subjects and Methods

One hundred twenty‐five patients underwent chin augmentation with solid silicone implants between 2004 and 2010. Among these implants, 105 were placed transorally. Eighty‐five patients were followed for at least 1 year. Demographic information, indications, patient satisfaction questionnaire results, and complications were recorded.

Results

All implants yielded satisfactory results with no displacement, infection, tissue reaction, lower lip incompetence, mental nerve injury, or intraoral implant contamination. Two cases of superficial mucosal irritation at the suture site were observed and resolved without consequence. Symmetry, projection, and overall balance of facial components were excellent. Although all patients were satisfied with the functional and aesthetic results, 20% stated they would like further augmentation. Patients were extremely satisfied with the lack of an external scar.

Conclusions

Based on our series, the intraoral technique with a midline incision avoiding disruption of the mentalis muscle is recommended for its ease, simplicity, patient satisfaction, low complication rate, and circumvention of an external scar. The external approach should be considered in cases that require a very large implant.
Effectiveness of Personalized and Interactive Health Risk Calculators
Authors: Harle Christopher A. , Downs Julie S. , Padman Rema
Published: January 2012

Background

Risk calculators are popular websites that provide individualized disease risk assessments to the public. Little is known about their effect on risk perceptions and health behavior.

Objective

This study sought to test whether risk calculator features—namely, personalized estimates of one’s disease risk and feedback about the effects of risk-mitigating behaviors—improve risk perceptions and motivate healthy behavior.

Design

A web-based experimental study using simple randomization was conducted to compare the effects of 3 prediabetes risk communication websites.

Setting

The study was conducted in the context of ongoing health promotion activities sponsored by a university’s human resources office.

Patients

Participants were adult university employees.

Intervention

The control website presented nonindividualized risk information. The personalized noninteractive website presented individualized risk calculations. The personalized interactive website presented individualized risk calculations and feedback about the effects of hypothetical risk-mitigating behaviors.

Measurements

Pre- and postintervention risk perceptions were measured in absolute and relative terms. Health behavior was measured by assessing participant interest in follow-up preventive health services.

Results

On average, risk perceptions decreased by 2%. There was no general effect of personalization or interactivity in aligning subjective risk perceptions with objective risk calculations or in increasing healthy behaviors. However, participants who previously overestimated their risk reduced their perceptions by 16%. This was a significantly larger change than the 2% increase by participants who underestimated their risk.

Limitations

Results may not generalize to different populations, different diseases, or longer-term outcomes.

Conclusions

Compared to nonpersonalized information, individualized risk calculators had little positive effect on prediabetes risk perception accuracy or health behavior. Risk perception accuracy was improved in people who receive relatively “good news” about risk rather than “bad news.”
Effect of fiber volume fraction on the energy absorption capacity of composite materials
Authors: Melo José Daniel D. , Villena John Edward N.
Published: January 2012

In this investigation, the effect of fiber volume fraction on the energy absorption capacity of fiber-reinforced composite materials was studied using dynamic mechanical analysis measurements. Laminates were fabricated with and without vacuum bag using plain weave E-glass fabric and three types of polymer matrix: epoxy, polyester, and vinyl ester. The higher energy absorption displayed by samples processed under vacuum was related to the shorter distance between adjacent fibers which produces stresses of higher magnitude in the matrix, thus promoting higher energy dissipation. However, when the energy dissipation is divided by the material density, the higher material density of vacuum processed laminates offsets the effects of increased loss modulus at higher fiber volume fraction.
Human Tail
Authors: Kumar Dipti , Kapoor Akshay
Published: January 2012

Human tail refers to a congenital cutaneous appendix protruding from the lumbosacral region. It is usually associated with an underlying spina bifida occulta, a form of spinal dysraphism. A contiguous fibrolipoma can sometimes be seen extending from the subcutaneous portion of the tail into the inferior spinal cord, resulting in tethered cord syndrome. Management of such lesions includes complete neurologic examination and magnetic resonance imaging. Early diagnosis and microsurgical intervention can prevent development or progression of severe neurologic defects in later life.
Vincristine-Related Neuropathy Versus Acute Inflammatory Demyelinating Polyradiculoneuropathy in Children With Acute Lymphoblastic Leukemia
Authors: Brigo Francesco , Balter Rita , Marradi Pierluigi , Ferlisi Monica , Zaccaron Ada , Fiaschi Antonio , Frasson Emma , Bertolasi Laura
Published: January 2012

The objective of this study was to evaluate whether electroneurography could help in differentiating between vincristine-induced neuropathy and acute inflammatory demyelinating polyradiculoneuropathy. We performed electroneurography in 7 children from September 2006 to March 2009 admitted to receive chemotherapy including vincristine for acute lymphoblastic leukemia, in whom severe acute limb weakness developed, suggesting vincristine-induced neuropathy. Three of 7 patients had electroneurography, suggesting acute inflammatory demyelinating polyradiculoneuropathy. They received intravenous immunoglobulins without discontinuing chemotherapy, and within 10 days their electroclinical conditions improved. Although electroneurography showed only absent F waves, preventing us from reaching a definitive neurophysiological diagnosis of acute inflammatory demyelinating polyradiculoneuropathy, children’s presenting clinical manifestations, their disease course, and rapid and complete recovery after intravenous immunoglobulins argued strongly in its favor. A prompt, correct differential diagnosis of vincristine neuropathy and acute inflammatory demyelinating polyradiculoneuropathy in patients with acute lymphoblastic leukemia receiving vincristine is essential to improve disease outcome and prolong life expectancy.
Patterns of Cognitive and Fine Motor Deficits in a Case of Dandy-Walker Continuum
Authors: Economou Alexandra , Katsetos Christos D.
Published: January 2012

Cerebellar vermian hypoplasia in the context of Dandy-Walker complex is a relatively common disorder associated with a variety of cognitive and behavioral deficits in addition to impairment in motor control. Few studies, however, have examined the neuropsychological profiles of children with isolated hypoplasias of the cerebellum. Herein, we report a 6-year-old girl with Dandy-Walker continuum presenting with mild mental retardation and an inability to produce intelligible speech, despite adequate comprehension of single items and simple instructions. She was able to articulate vowels but not consonants, and fine motor function was deficient. Visual memory was intact for single items but not for multiple items, and visuospatial perception was impaired. An inability to form intelligible speech is not typically reported in cases of isolated vermian hypoplasia. The case extends our knowledge of the phenotypes associated with cerebellar hypoplasia and its relation to fine motor and articulatory control.
Urgent Referrals for Seizure Evaluation to a Tertiary Care Neurology Center
Authors: Arkilo Dimitrios , Griesemer David , Padulsky Kristen , Lam Danielle , Wang Sonya , Hyder Douglas
Published: January 2012

This study evaluates the outcome of urgent neurologic referrals. This was a retrospective review of all referrals to the Floating Hospital for Children in 1 month. The total number of patients referred to our center was 223. Amongst those, 108 were new patients and 195 were follow-up visits; 30 patients were deemed urgent, yet 6 of them did not present to their visit. Urgent and routinely scheduled patients were compared based on the need for further evaluation or medication initiation following their visit. The frequency of visit outcomes was statistically similar between urgently and nonurgently referred patients. We did observe though, that diagnostic testing and medication were initiated more frequently for the patients urgently referred for seizure compared with those routinely scheduled patients for seizure evaluation. For this reason, we suggest that pediatric neurologists preferentially should hold clinic space open for urgent referrals for patients with new-onset seizure.
‘No Decision About Me, Without Me’: A place for social marketing within the new Public Health architecture?
Authors: Reynolds Lucy
Published: January 2012

July 2011 marked the 40th anniversary of social marketing. However, while the previous Labour administration dedicated sustained resources and support to developing the field of social marketing, this was followed by a time of uncertainty during the Coalition Government’s ascent to power. This paper explores the potential future position of social marketing within David Cameron’s evolving public health landscape, outlining areas of synergy between social marketing’s key features, and the coalition’s emergent public health architecture. The paper concludes with an exploration of the development opportunities nascent within social marketing, suggesting that support for the new commissioners (GP and local authority), and an enhanced emphasis on evaluation of financial and social outcomes, will be required if the evidence base for strong practice is to continue to grow and evolve.
Congenital Absence of Left Circumflex Artery With Origin of Left Anterior Descending Artery From Right Sinus of Valsalva
Authors: Innasimuthu Antony Leslie , Kumar Sanjay , Gandhi Chintan , Nathaniel Sangeetha , Chuah Som
Published: January 2012

The authors report a case of two congenital coronary artery anomalies in the same patient presenting with symptoms suggestive of angina. These two anomalies have been reported in isolation or with other congenital malformation complexes but not together. On reviewing the literature, the authors report this as the first patient presenting with both these congenital anomalies. In this case report, the authors briefly review presenting symptoms of the patient, coronary angiogram, and the literature regarding these congenital coronary anomalies.
History and clinical use of thoracoscopy/pleuroscopy in respiratory medicine
Authors: Loddenkemper R. , Mathur P.N. , Lee P. , Noppen M.
Published: January 2012

Thoracoscopy was introduced over 100 years ago and for 40 years has been mainly used in the pneumothorax treatment of tuberculosis in those cases where pleuro-pulmonary adhesions prevented collapse of the lung. In the 1950s, the pneumothorax treatment of tuberculosis came to an end and thoracoscopy was used in a few centres by chest physicians as a diagnostic and therapeutic method in several pleuro-pulmonary diseases. In the 1990s, thoracic surgeons introduced the technique for minimally invasive surgery, known as “surgical thoracoscopy” or more precisely “video-assisted thoracic surgery” (VATS), which is performed under general anaesthesia with one-lung ventilation. In contrast, medical thoracoscopy/pleuroscopy can be performed under local anaesthesia or conscious sedation, in an endoscopy suite, using non-disposable rigid or semi-rigid instruments. Thus, it is considerably less invasive and less expensive. Today, medical thoracoscopy/pleuroscopy is increasingly used by chest physicians, mainly in patients with pleural effusion or pneumothorax including talc poudrage as best conservative pleurodesis treatment. Meanwhile, the technique is considered to be one of the main areas of interventional pneumology.
Characterisation of full-length cDNA sequences provides insights into the Eimeria tenella transcriptome
Authors: Amiruddin Nadzirah , Lee Xin-Wei , Blake Damer P , Suzuki Yutaka , Tay Yea-Ling , Lim Lik-Sin , Tomley Fiona M , Watanabe Junichi , Sugimoto Chihiro , Wan Kiew-Lian
Published: January 2012

Background

Eimeria tenella is an apicomplexan parasite that causes coccidiosis in the domestic fowl. Infection with this parasite is diagnosed frequently in intensively reared poultry and its control is usually accorded a high priority, especially in chickens raised for meat. Prophylactic chemotherapy has been the primary method used for the control of coccidiosis. However, drug efficacy can be compromised by drug-resistant parasites and the lack of new drugs highlights demands for alternative control strategies including vaccination. In the long term, sustainable control of coccidiosis will most likely be achieved through integrated drug and vaccination programmes. Characterisation of the E. tenella transcriptome may provide a better understanding of the biology of the parasite and aid in the development of a more effective control for coccidiosis.

Results

More than 15,000 partial sequences were generated from the 5' and 3' ends of clones randomly selected from an E. tenella second generation merozoite full-length cDNA library. Clustering of these sequences produced 1,529 unique transcripts (UTs). Based on the transcript assembly and subsequently primer walking, 433 full-length cDNA sequences were successfully generated. These sequences varied in length, ranging from 441 bp to 3,083 bp, with an average size of 1,647 bp. Simple sequence repeat (SSR) analysis identified CAG as the most abundant trinucleotide motif, while codon usage analysis revealed that the ten most infrequently used codons in E. tenella are UAU, UGU, GUA, CAU, AUA, CGA, UUA, CUA, CGU and AGU. Subsequent analysis of the E. tenella complete coding sequences identified 25 putative secretory and 60 putative surface proteins, all of which are now rational candidates for development as recombinant vaccines or drug targets in the effort to control avian coccidiosis.

Conclusions

This paper describes the generation and characterisation of full-length cDNA sequences from E. tenella second generation merozoites and provides new insights into the E. tenella transcriptome. The data generated will be useful for the development and validation of diagnostic and control strategies for coccidiosis and will be of value in annotation of the E. tenella genome sequence.
A genomics approach to understanding the role of auxin in apple (Malus x domestica)fruit size control
Authors: Devoghalaere Fanny , Doucen Thomas , Guitton Baptiste , Keeling Jeannette , Payne Wendy , Ling Toby John , Ross John James , Hallett Ian Charles , Gunaseelan Kularajathevan , Dayatilake GA , Diak Robert , Breen Ken C , Tustin D Stuart , Costes Evelyne , Chagné David , Schaffer Robert James , David Karine Myriam
Published: January 2012

Background

Auxin is an important phytohormone for fleshy fruit development, having been shown to be involved in the initial signal for fertilisation, fruit size through the control of cell division and cell expansion, and ripening related events. There is considerable knowledge of auxin-related genes, mostly from work in model species. With the apple genome now available, it is possible to carry out genomics studies on auxin-related genes to identify genes that may play roles in specific stages of apple fruit development.

Results

High amounts of auxin in the seed compared with the fruit cortex were observed in 'Royal Gala' apples, with amounts increasing through fruit development. Injection of exogenous auxin into developing apples at the start of cell expansion caused an increase in cell size. An expression analysis screen of auxin-related genes involved in auxin reception, homeostasis, and transcriptional regulation showed complex patterns of expression in each class of gene. Two mapping populations were phenotyped for fruit size over multiple seasons, and multiple quantitative trait loci (QTLs) were observed. One QTL mapped to a region containing an Auxin Response Factor (ARF106). This gene is expressed during cell division and cell expansion stages, consistent with a potential role in the control of fruit size.

Conclusions

The application of exogenous auxin to apples increased cell expansion, suggesting that endogenous auxin concentrations are at least one of the limiting factors controlling fruit size. The expression analysis of ARF106 linked to a strong QTL for fruit weight suggests that the auxin signal regulating fruit size could partially be modulated through the function of this gene. One class of gene (GH3) removes free auxin by conjugation to amino acids. The lower expression of these GH3 genes during rapid fruit expansion is consistent with the apple maximising auxin concentrations at this point.
Growth independent rhamnolipid production from glucose using the non-pathogenic Pseudomonas putida KT2440
Authors: Wittgens Andreas , Tiso Till , Arndt Torsten T , Wenk Pamela , Hemmerich Johannes , Müller Carsten , Wichmann Rolf , Küpper Benjamin , Zwick Michaela , Wilhelm Susanne , Hausmann Rudolf , Syldatk Christoph , Rosenau Frank , Blank Lars M
Published: January 2012

Background

Rhamnolipids are potent biosurfactants with high potential for industrial applications. However, rhamnolipids are currently produced with the opportunistic pathogen Pseudomonas aeruginosa during growth on hydrophobic substrates such as plant oils. The heterologous production of rhamnolipids entails two essential advantages: Disconnecting the rhamnolipid biosynthesis from the complex quorum sensing regulation and the opportunity of avoiding pathogenic production strains, in particular P. aeruginosa. In addition, separation of rhamnolipids from fatty acids is difficult and hence costly.

Results

Here, the metabolic engineering of a rhamnolipid producing Pseudomonas putida KT2440, a strain certified as safety strain using glucose as carbon source to avoid cumbersome product purification, is reported. Notably, P. putida KT2440 features almost no changes in growth rate and lag-phase in the presence of high concentrations of rhamnolipids (> 90 g/L) in contrast to the industrially important bacteria Bacillus subtilis, Corynebacterium glutamicum, and Escherichia coli. P. putida KT2440 expressing the rhlAB-genes from P. aeruginosa PAO1 produces mono-rhamnolipids of P. aeruginosa PAO1 type (mainly C10:C10). The metabolic network was optimized in silico for rhamnolipid synthesis from glucose. In addition, a first genetic optimization, the removal of polyhydroxyalkanoate formation as competing pathway, was implemented. The final strain had production rates in the range of P. aeruginosa PAO1 at yields of about 0.15 g/gglucose corresponding to 32% of the theoretical optimum. What's more, rhamnolipid production was independent from biomass formation, a trait that can be exploited for high rhamnolipid production without high biomass formation.

Conclusions

A functional alternative to the pathogenic rhamnolipid producer P. aeruginosa was constructed and characterized. P. putida KT24C1 pVLT31_rhlAB featured the highest yield and titer reported from heterologous rhamnolipid producers with glucose as carbon source. Notably, rhamnolipid production was uncoupled from biomass formation, which allows optimal distribution of resources towards rhamnolipid synthesis. The results are discussed in the context of rational strain engineering by using the concepts of synthetic biology like chassis cells and orthogonality, thereby avoiding the complex regulatory programs of rhamnolipid production existing in the natural producer P. aeruginosa.