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Fish oil contains the marine ω-3 polyunsaturated fatty acids (ω-3 PUFAs) docosahexaenoic (DHA) and eicosapentaenoic acid (EPA). The consumption of diets rich in these fatty acids is associated with a decreased incidence of prostate cancer. However, there is limited knowledge regarding the non-marine ω-3 PUFA α-linolenic acid (ALA). To study which ω-3 PUFAs are more effective in prostate cancer prevention, and whether the mechanisms of action are conserved between them, we investigated the effect of DHA, EPA and ALA on the human prostate cancer cell lines PC-3 and LNCaP. Different trends of inhibition of PC-3 cell proliferation were observed for the three ω-3 PUFA, with DHA having the most pronounced effects on cell proliferation, while ALA had the minimum effects of the three ω-3 PUFAs. All the ω-3 PUFAs decreased fatty acid synthase (FASN) mRNA. Concerning genes involved in inflammation, cell cycle and apoptosis, DHA regulated the most genes in all categories, followed by EPA and then ALA. In addition, DHA and EPA increased the gene expression of the pro-apoptotic protein activating transcription factor 3 mRNA. Moreover, these two fatty acids significantly induced apoptosis. In conclusion, while some mechanisms of cancer cell inhibition are conserved among ω-3 PUFA, the extent, magnitude, and duration of transcriptional changes vary for each individual fatty acid.

Introduction: Breast irradiation in combination with breast reconstruction is associated with increased complications. Because of the diminishing threshold for radiotherapy, breast reconstruction irradiation is rising. Our aim was to evaluate factors affecting outcomes in irradiated breast reconstructions., Methods: A review of consecutive patients who underwent mastectomy, radiation, and breast reconstruction was conducted. Patient demographics, operative procedure, breast irradiation timing, and postoperative complications were collected., Results: One hundred fifty-four patients (157 breast reconstructions) were included with a mean follow-up of 6 years. Average age at reconstruction was 50 years. One hundred nine cases were immediate and 48 cases were delayed. Sixty-eight cases were autologous reconstructions and 89 cases were implant-based. Thirty-seven cases used acellular dermal matrices (ADMs); 60% of cases were radiated before reconstruction and 40% were radiated afterward. Major complications occurred in 43% of patients and minor complications occurred in 17%. The presence of ADM led to an increase in complication rate with a 2.3-fold greater chance of requiring reoperation (P = 0.03). No significant difference in complication rates was associated with presence of hypertension, diabetes, smoking, elevated body mass index, autologous versus implant-based reconstructions, delayed versus immediate reconstructions, and time between radiation and reconstruction., Conclusions: Radiation after prosthetic reconstruction may produce an increase in failure rates. The use of ADMs in the face of breast irradiation increases the likelihood of a complication requiring reoperation.

PPARβ/δ is a ligand-activated transcription factor that regulates various cellular functions via induction of target genes directly or in concert with its associated transcriptional repressor, BCL-6. Matrix remodeling proteinases are frequently over-expressed in pancreatic cancer and are involved with metastasis. The present study tested the hypothesis that PPARβ/δ is expressed in human pancreatic cancer cells and that its activation could regulate MMP-9, decreasing cancer cells ability to transverse the basement membrane. In human pancreatic cancer tissue there was significantly higher expression of MMP-9 and PPARβ/δ, and lower levels of BCL-6 mRNA. PPARβ/δ activation reduced the TNF α -induced expression of various genes implicated in metastasis and reduced the invasion through a basement membrane in cell culture models. Through the use of short hairpin RNA inhibitors of PPARβ/δ, BCL-6, and MMP-9, it was evident that PPARβ/δ was responsible for the ligand-dependent effects whereas BCL-6 dissociation upon GW501516 treatment was ultimately responsible for decreasing MMP-9 expression and hence invasion activity. These results suggest that PPARβ/δ plays a role in regulating pancreatic cancer cell invasion through regulation of genes via ligand-dependent release of BCL-6 and that activation of the receptor may provide an alternative therapeutic method for controlling migration and metastasis.

Severity of the Harlequin deformity seen in unicoronal synostosis may be augmented when frontoparietal suture synostosis has an associated fusion of the frontosphenoidal suture or in cases of isolated frontosphenoidal synostosis. The purpose of the current study is to characterize various suture fusion patterns along the coronal ring using a modified orbital index (MOI), orbital angle (OA), and endocranial base (EB) angle.This study is a retrospective single institution cohort study. Charts were reviewed over the past 12 years; patients with isolated UCS were included. MOI, OA, and EB were used to identify 3 groups of UCS patients.Twenty-one patients were identified for inclusion in skeletal dysmorphology analysis using MOI, OA, and EB measures. Frontoparietal synostosis patients were diagnosed at significantly younger ages than frontoparietal + frontosphenoidal patients (P = 0.0001). Ipsilateral MOI measures were more severe for frontoparietal patients compared with frontoparietal + frontosphenoidal patients (P = 0.0239). There was a trend for more severe ipsilateral OA measures in frontoparietal patients compared with frontoparietal + frontosphenoidal patients (P = 0.181).Modified orbital index, OA, and EB measurements are useful in the diagnosis of suture fusion patterns in UCS patients. Frontoparietal synostosis has more severe Harlequin deformity compared with frontoparietal + frontosphenoidal patients. Frontosphenoidal fusion coinciding with frontoparietal synostosis may blunt the severity of skeletal dysmorphology in UCS patients and be associated with a delayed diagnosis. Attention must be paid to assessing the frontosphenoidal suture to assure adequate surgical release.

Conjugated linoleic acids (CLAs) are a group of dietary fatty acids that are widely marketed as weight loss supplements. The isomer responsible for this effect is the trans-10, cis-12 CLA (10E12Z-CLA) isomer. 10E12Z-CLA treatment during differentiation of 3T3-L1 adipocytes induces expression of prostaglandin-endoperoxide synthase-2 (Cyclooxygenase-2; COX-2). This work demonstrates that COX-2 is also induced in fully differentiated 3T3-L1 adipocytes after a single treatment of 10E12Z-CLA at both the mRNA (20-40 fold) and protein level (7 fold). Furthermore, prostaglandin (PG)F(2α), but not PGE(2), is significantly increased 10 fold. In female BALB/c mice fed 0.5% 10E12Z-CLA for 10 days, COX-2 was induced in uterine adipose (2 fold). In vitro, pharmacological COX-2 inhibition did not block the effect of 10E12Z-CLA on adipocyte-specific gene expression although PGF(2α) was dose-dependently decreased. These studies demonstrate that PGF(2α) was not by itself responsible for the reduction in adipocyte character due to 10E12Z-CLA treatment. However, PGF(2α), either exogenously or endogenously in response to 10E12Z-CLA, increased the expression of the potent mitogen and epidermal growth factor (EGF) receptor (EGFR) ligand epiregulin in 3T3-L1 adipocytes. Blocking PGF(2α) signaling with the PGF(2α) receptor (FP) antagonist AL-8810 returned epiregulin mRNA levels back to baseline. Although this pathway is not directly responsible for adipocyte dependent gene expression, these results suggest that this signaling pathway may still have broad effect on the adipocyte and surrounding cells., (Copyright © 2012. Published by Elsevier Inc.)

Omega-3-PUFAs, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), are associated with prevention of various aspects of metabolic syndrome. In the present studies, the effects of oil rich in EPA on gene expression and activation of nuclear receptors was examined and compared with other ω3-PUFAs. The EPA-rich oil (EO) altered the expression of FA metabolism genes in THP-1 cells, including stearoyl CoA desaturase (SCD) and FA desaturase-1 and -2 (FASDS1 and -2). Other ω3-PUFAs resulted in a similar gene expression response for a subset of genes involved in lipid metabolism and inflammation. In reporter assays, EO activated human peroxisome proliferator-activated receptor α (PPARα) and PPARβ/γ with minimal effects on PPARγ, liver X receptor, retinoid X receptor, farnesoid X receptor, and retinoid acid receptor γ (RARγ); these effects were similar to that observed for purified EPA. When serum from a 6 week clinical intervention with dietary supplements containing olive oil (control), DHA, or two levels of EPA were applied to THP-1 cells, the expression of SCD and FADS2 decreased in the cells treated with serum from the ω3-PUFA-supplemented individuals. Taken together, these studies indicate regulation of gene expression by EO that is consistent with treating aspects of dyslipidemia and inflammation.

Breast conservation therapy (BCT) has evolved as a favorable approach to the management of early-stage breast cancer. Shortcomings of BCT include the potential need for re-excision in the event of positive tumor margins as well as the untoward sequelae of radiation therapy. Both of those factors have led to a substantial proportion of patients undergoing BCT who ultimately report suboptimal aesthetic outcomes. Application of plastic surgery principles to the management of this patient subset has been shown to be beneficial from both an oncologic and cosmetic perspective.The aim of this study was to identify factors that may predict which patients would benefit most from involvement of a plastic surgeon before BCT. A retrospective analysis was performed on 762 patients undergoing lumpectomy during a 10-year study period at a single institution. Younger women and patients with tumor size approaching 2 cm were noted to have a significantly higher likelihood of oncologic outcomes that ultimately required breast reconstruction. Integration of oncoplastic techniques in the surgical management of patients undergoing BCT would likely contribute to improvement in aesthetic outcomes and overall patient satisfaction.

The trans-10, cis-12 (10e12z) conjugated linoleic acid (CLA) isomer of CLA is responsible for loss of lipid storage or adipose tissue in vitro or in vivo. This isomer also induces inflammatory signaling in both mouse and human adipocytes in vitro. However, when these events occur and whether they are significant enough to affect other cell types are unclear. In these experiments, the 3T3-L1 cell line has been used to examine the interaction between inflammatory signaling and decreased differentiation or lipid storage induced by 10e12z CLA. In assays measuring both lipid accumulation and gene expression, differentiating 3T3-L1 cells exhibit concurrent induction of inflammatory signaling, as measured by cyclooxygenase-2 expression, and a decrease in adipocyte marker gene expression. Furthermore, in fully differentiated adipocytes, as identified in microarray assays and confirmed with real-time polymerase chain reaction, 10e12z CLA also significantly affected expression of both matrix metalloprotein-3 (MMP-3), collagen VI α 3 ColVI alpha 3 (VIα3) and the cytokine epiregulin, demonstrating that the effects of 10e12z broadly impact adipocyte function. In agreement with other experimental systems, 10e12z CLA inhibited RAW 264.7 cell proliferation; however, in response to adipocyte-conditioned media, 10e12z-CLA-treated adipocytes induced proliferation of this cell line, suggesting that the effect of 10e12z CLA is context dependent. These results are largely consistent with the known activation of the inflammatory mediator nuclear factor-κB in adipocytes in vitro and in vivo by 10e12z CLA treatment and demonstrate that adipose is an important target tissue of this isomer that impacts other cell types., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue condition with clinical features that may include ocular hypertelorism, cleft palate, craniosynostosis, and vascular dilation and tortuosity. Here we describe a patient with LDS confirmed by genetic analysis (R528H mutation of TGFBR2) who presented at 3 months of age in respiratory distress of unknown origin. In addition to expressing several of the classic findings of LDS, including a novel finding of squamosal suture craniosynostosis, CT angiography revealed aortic dilation at the sinus of valsalva, pulmonary artery dilation that extrinsically compressed the right mainstem bronchus causing bronchomalacia, and an apical herniation of the right lung. This is the first documentation of concomitant airway and pulmonary findings in a patient with LDS. We suggest that (1) vascular abnormalities be considered as a cause of unexplained respiratory distress in a patient with LDS, and (2) pediatric patients exhibiting any of the physical findings listed above be evaluated for LDS with particular attention paid to vascular, airway, and/or pulmonary malformations., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: To compare the effectiveness of interventions aimed at reducing the rate of acute paediatric hospital admissions., Design: Systematic review., Data Sources: Medline, Embase, PsychINFO, The Cochrane Library, Science Citation Index Expanded from inception to September 2010; hand searches of the reference lists of included papers and other review papers identified in the search., Review Methods: Controlled trials were included. Articles were screened for inclusion independently by two reviewers. Data extraction and quality appraisal were performed by one reviewer and checked by a second with discrepancies resolved by discussion with a third if necessary., Results: Seven papers were included. There is some evidence to suggest that short stay units may reduce admission rates. However, there is a general lack of detail in the reporting of interventions and the methods used in their evaluation which precludes detailed interpretation and extrapolation of the results. The authors found no evidence that the use of algorithms and guidelines to manage the admission decision was effective in reducing acute admission rates. Furthermore, the authors were unable to locate any eligible papers reporting the effects on admission rates of admission decision by paediatric consultant, telephone triage by paediatric consultant or the establishment of next day emergency paediatric clinics., Conclusion: There is little published evidence upon which to base an optimal strategy for reducing paediatric admission rates. The evidence that does exist is subject to substantial bias. There is a pressing need for high quality, well conducted research to enable informed service change.

Increased cholesterol efflux from macrophage-derived foam cells (MDFCs) is an important protective mechanism to decrease lipid load in the atherosclerotic plaque. Dietary alpha-linolenic acid (ALA), an omega-3 polyunsaturated fatty acid (PUFA), decreases circulating cholesterol, but its role in cholesterol efflux has not been extensively studied. Stearoyl CoA desaturase 1 (SCD1) is the rate-limiting enzyme in the synthesis of monounsaturated fatty acids (MUFAs). Endogenous MUFAs are preferentially incorporated into triglycerides, phospholipids and cholesteryl ester, which are abundant in atherosclerotic plaque. This study investigated the mechanisms by which ALA regulated SCD1 and subsequent effect on cholesterol storage and transport in MDFCs. Small interfering RNA (siRNA) also was applied to modify SCD1 expression in foam cells. Alpha-linolenic acid treatment and SCD1 siRNA significantly decreased SCD1 expression in MDFCs. The reduction of SCD1 was accompanied with increased cholesterol efflux and decreased intracellular cholesterol storage within these cells. Alpha-linolenic acid activated the nuclear receptor farnesoid-X-receptor, which in turn increased its target gene small heterodimer partner (SHP) expression, and decreased liver-X-receptor dependent sterol regulatory element binding protein 1c transcription, ultimately resulting in repressed SCD1 expression. In conclusion, repression of SCD1 by ALA favorably increased cholesterol efflux and decreased cholesterol accumulation in foam cells. This may be one mechanism by which dietary omega-3 PUFAs promote atherosclerosis regression., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Walnuts contain bioactive molecules that may contribute to their beneficial effects, including alpha-linolenic acid (ALA) and phytosterols. In these studies, extracts of walnut, purified compounds, or postprandial serum were examined for effects on breast cancer cell proliferation and gene expression. Extracts derived from walnut oil decreased proliferation of MCF-7 cells, as did ALA and β-sitosterol. The gene expression response of ALA in the mouse breast cancer cell line TM2H indicates this molecule has multiple cellular targets with peroxisome proliferator-activated receptor (PPAR) target genes, liver X receptor (LXR), and farnesoid X receptor (FXR) target genes being affected. In transactivation assays, walnut oil extracts increased activity of FXR to a greater extent than the other tested nuclear receptors. When examined separately, walnut components ALA and β-sitosterol were the most efficacious activators of FXR. When serum from individuals fed walnut components were applied to MCF-7 cells, there was a correlation between body mass index and breast cancer cell proliferation in vitro. Taken together, these data support an effect of walnut and its bioactive constituents on mammary epithelial cells and that multiple molecular targets may be involved.

Targeting cancer stem cells is of paramount importance in successfully preventing cancer relapse. Recently, in silico screening of public gene-expression datasets identified cyclooxygenase-derived cyclopentenone prostaglandins (CyPGs) as likely agents to target malignant stem cells. We show here that Δ(12)-PGJ(3), a novel and naturally produced CyPG from the dietary fish-oil ω-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA; 20:5) alleviates the development of leukemia in 2 well-studied murine models of leukemia. IP administration of Δ(12)-PGJ(3) to mice infected with Friend erythroleukemia virus or those expressing the chronic myelogenous leukemia oncoprotein BCR-ABL in the hematopoietic stem cell pool completely restored normal hematologic parameters, splenic histology, and enhanced survival. More importantly, Δ(12)-PGJ(3) selectively targeted leukemia stem cells (LSCs) for apoptosis in the spleen and BM. This treatment completely eradicated LSCs in vivo, as demonstrated by the inability of donor cells from treated mice to cause leukemia in secondary transplantations. Given the potency of ω-3 polyunsaturated fatty acid-derived CyPGs and the well-known refractoriness of LSCs to currently used clinical agents, Δ(12)-PGJ(3) may represent a new chemotherapeutic for leukemia that targets LSCs.

2-Arachidonyl glycerol (2-AG) is an endogenous arachidonic acid derivative capable of suppressing interleukin (IL)-2 production by activated T cells. 2-AG-mediated IL-2 suppression is dependent on cyclooxygenase-2 (COX-2) metabolism and peroxisome proliferator activated receptor γ (PPARγ) activation. The objective of the present studies was to examine whether 15-deoxy-Δ(12,14)-PGJ(2)-glycerol ester (15d-PGJ(2)-G), a putative metabolite of 2-AG, can mimic the actions of 2-AG on IL-2 regulation through PPARγ activation. 15d-PGJ(2)-G bound PPARγ-ligand binding domain in a PPARγ competitive binding assay. 15d-PGJ(2)-G treatment activated PPARγ in a reporter assay, and PPARγ activation was attenuated when a PPARγ antagonist, 2-chloro-5-nitro-N-4-pyridinylbenzamide (T0070907), was present. 15d-PGJ(2)-G treatment suppressed IL-2 production by activated Jurkat cells, which was partially attenuated when pretreated with T0070907. Moreover, IL-2 suppression was pronounced when 15d-PGJ(2)-G was present 30 min before or after T-cell activation. Concordant with IL-2 suppression, 15d-PGJ(2)-G treatment decreased nuclear factor of activated T cells (NFAT) transcriptional activity in transiently transfected Jurkat cells. It is noteworthy that T0070907 alone markedly increased NFAT reporter activity, suggesting the existence of endogenous PPARγ activation and modulation of NFAT. Because COX-2 metabolism of 2-AG is important for IL-2 suppression, the effect of 2-AG on COX-2 and PPARγ mRNA expression was investigated. 2-AG treatment decreased the up-regulation of COX-2 mRNA after T-cell activation, which suggests negative feedback limiting COX-2-mediated metabolism of 2-AG. PPARγ mRNA expression was increased upon activation, and 2-AG treatment produced a modest decrease in PPARγ mRNA expression. Collectively, our findings suggest that 15d-PGJ(2)-G activates PPARγ to decrease NFAT transcriptional activity and IL-2 expression in activated T cells.

An increase in cross-disciplinary, collaborative team science initiatives over the last few decades has spurred interest by multiple stakeholder groups in empirical research on scientific teams, giving rise to an emergent field referred to as the science of team science (SciTS). This study employed a collaborative team science concept-mapping evaluation methodology to develop a comprehensive research agenda for the SciTS field. Its integrative mixed-methods approach combined group process with statistical analysis to derive a conceptual framework that identifies research areas of team science and their relative importance to the emerging SciTS field. The findings from this concept-mapping project constitute a lever for moving SciTS forward at theoretical, empirical, and translational levels.

Small gauge vitrectomy utilizing 23- and 25-gauge instrumentation has definite advantages, but also limitations, due to the physics of smaller instruments and sutureless surgery. Higher infusion and aspiration pressures are needed to remove the vitreous using 23- and 25-gauge probes. The advantages include decreased surgical times, less tissue manipulation, reduced inflammation and pain postoperatively with more rapid visual recovery. A disadvantage is greater instrument flexion than 20-gauge probes, making small gauge vitrectomy more appropriate for indications such as vitreous opacities, epiretinal membranes, macular holes, and simple retinal detachments. There are also some increased complications related to small gauge vitrectomy, including dislocation of cannulas intraoperatively, early postoperative hypotony, choroidal detachment, and possibly an increased risk of infectious endophthalmitis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The cylindrical shape of soft-bodied invertebrates is well suited to functions in skeletal support and locomotion, but may result in a previously unrecognized cost-large non-uniformities in muscle strain and strain rate among the circular muscle fibres of the body wall. We investigated such gradients of strain and strain rate in the mantle of eight long-finned squid Doryteuthis pealeii and two oval squid Sepioteuthis lessoniana. Transmural gradients of circumferential strain were present during all jets (n = 312); i.e. for a given change in the circumference of the outer surface of the mantle, the inner surface experienced a greater proportional change. The magnitude of the difference increased with the amplitude of the mantle movement, with circular muscle fibres at the inner surface of the mantle experiencing a total range of strains up to 1.45 times greater than fibres at the outer surface during vigorous jets. Differences in strain rate between the circular fibres near the inner versus the outer surface of the mantle were also present in all jets, with the greatest differences occurring during vigorous jetting. The transmural gradients of circumferential strain and strain rate we describe probably apply not only to squids and other coleoid cephalopods, but also to diverse soft-bodied invertebrates with hollow cylindrical or conical bodies and muscular organs.

We investigated the ultrastructure, contractile properties, and in vivo length changes of the fast-acting funnel retractor muscle of the long-finned squid Doryteuthis pealeii. This muscle is composed of obliquely striated, spindle-shaped fibers ~3 mum across that have an abundant sarcoplasmic reticulum, consisting primarily of membranous sacs that form 'dyads' along the surface of each cell. The contractile apparatus consists of 'myofibrils' approximately 0.25-0.5 microm wide in cross section arrayed around the periphery of each cell, surrounding a central core that contains the nucleus and large mitochondria. Thick myofilaments are approximately 25 nm in diameter and approximately 2.8 microm long. 'Dense bodies' are narrow, resembling Z lines, but are discontinuous and are not associated with the cytoskeletal fibrillar elements that are so prominent in slower obliquely striated muscles. The cells approximate each other closely with minimal intervening intercellular connective tissue. Our physiological experiments, conducted at 17 degrees C, showed that the longitudinal muscle fibers of the funnel retractor were activated rapidly (8 ms latent period following stimulation) and generated force rapidly (peak twitch force occurred within 50 ms). The longitudinal fibers had low V(max) (2.15 +/-0.26 L(0) s(-1), where L(0) was the length that generated peak isometric force) but generated relatively high isometric stress (270+/-20 mN mm(-2) physiological cross section). The fibers exhibited a moderate maximum power output (49.9 W kg(-1)), compared with vertebrate and arthropod cross striated fibers, at a V/V(max) of 0.33+/-0.044. During ventilation of the mantle cavity and locomotion, the funnel retractor muscle operated in vivo over a limited range of strains (+0.075 to -0.15 relative to resting length, L(R)) and at low strain rates (from 0.16 to 0.91 L(R) s(-1) ), corresponding to a range of V/V(max) from 0.073 to 0.42. During the exhalant phase of the jet the range of strains was even narrower: maximum range less than +/-0.04, with the muscle operating nearly isometrically during ventilation and slow, arms-first swimming. The limited length operating range of the funnel retractor muscles, especially during ventilation and slow jetting, suggests that they may act as muscular struts.

Background: A national study of radiologic technologists' radiation safety practices in 2003 documented poor compliance. In addition, the 2003 study found that years of work experience and length of employment at a work site were significantly related to adherence with safety practices. The current study is a refinement and extension of the 2003 study., Purpose: To determine the degree of compliance with personnel radiation safety practices and patient radiation safety practices as correlated with initial professional education, highest level of education, years of employment in the radiologic sciences and type of work site., Method: A 33-item questionnaire was mailed to a random sample of 1500 California radiologic technologists certified by the American Registry of Radiologic Technologists. The return rate was 32%., Results: Mean scores were 77.1% for compliance with patient safety practices and 70.5% for compliance with personnel safety practices. Performance on individual items ranged from 95.6% to 27.4% compliance. Two independent variables, years of employment in the radiologic sciences and work site, were significantly related to adherence with safety practices (P < .05)., Conclusion: The results of this study corroborated those of the national study and indicated the need for educational and organizational interventions to increase compliance with safety practices for patients and personnel.

When incorporated into the diet, pistachios have a beneficial effect on lipid and lipoprotein profiles. However, little is known about potential anti-inflammatory properties. This study was conducted to determine whether pistachio oil and an organic extract from pistachio oil extract (PE) regulated expression of inflammation-related genes. A mouse macrophage cell line (RAW 264.7 cells) was treated with pistachio oil and gene expression microarray analyses were performed. Pistachio oil significantly affected genes involved in immune response, defense response to bacteria, and gene silencing, of which INF-induced protein with tetratricopeptide repeats 2 (Ifit-2) was the most dramatically reduced. PE reduced the LPS-induced Ifit-2 by 78% and the bioactive molecules contained in PE, linoleic acid, and beta-sitosterol recapitulated this inhibition. Promoter analysis identified two adjacent IFN-stimulated response elements, which lie between -110 and -85bp of the 5'-flanking region of the Ifit-2 promoter, as being responsive to LPS activation and inhibition by PE. Our results indicate that pistachio oil and bioactive molecules present therein decrease Ifit-2 expressions, and due to the sensitivity of this effect, this gene is a potential biomarker for monitoring diet-induced changes in inflammation.

Understanding the extent to which changes in muscle form and function underlie ontogenetic changes in locomotory behaviors and performance is important in understanding the evolution of musculoskeletal systems and also the ecology of different life stages. We explored ontogenetic changes in the structure, myosin heavy chain (MHC) expression and contractile properties of the circular muscles that provide power for jet locomotion in the long-finned squid Doryteuthis pealeii. The circular muscle fibers of newly hatched paralarvae had different sizes, shapes, thick filament lengths, thin:thick filament ratio, myofilament organization and sarcoplasmic reticulum (SR) distribution than those of adults. Viewed in cross section, most circular muscle cells were roughly triangular or ovoid in shape with a core of mitochondria; however, numerous muscle cells with crescent or other unusual cross-sectional shapes and muscle cells with unequal distributions of mitochondria were present in the paralarvae. The frequency of these muscle cells relative to 'normal' circular muscle cells ranged from 1:6 to 1:10 among the 19 paralarvae we surveyed. The thick filaments of the two types of circular fibers, superficial mitochondria-rich (SMR) and central mitochondria-poor (CMP), differed slightly in length among paralarvae with thick filament lengths of 0.83+/-0.15 microm and 0.71+/-0.1 microm for the SMR and CMP fibers, respectively (P 0.05; ANOVA). During ontogeny the thick filament lengths of both the CMP and SMR fibers increased significantly to 1.78+/-0.27 microm and 3.12+/-0.56 microm, respectively, in adults (P<0.0001 for both comparisons; ANOVA with Tukey's highly significant difference post hoc tests). When sectioned parallel to their long axes, the SMR and CMP fibers of both paralarvae and adults exhibited the myofilament arrangements typical of obliquely striated muscle cells but the angle of obliquity of the dense bodies was 22.8+/-2.4 deg. and 4.6+/-0.87 deg. for paralarvae and adults, respectively. There were also differences in the distribution of the anastomosing network of SR. In paralarvae, the outer and central zones of SR were well developed but the intramyoplasmic zone was greatly reduced in some cells or was scattered non-uniformly across the myoplasm. Whereas in adults the intramyoplasmic SR region was composed primarily of flattened tubules, it was composed primarily of rounded vesicles or tubules when present in the paralarvae. The ontogenetic differences in circular muscle structure were correlated with significant differences in their contractile properties. In brief tetanus at 20 degrees C, the mean unloaded shortening velocity of the paralarval circular muscle preparations was 9.1 L(0) s(-1) (where L(0) was the preparation length that generated the peak isometric stress), nearly twice that measured in other studies for the CMP fibers of adults. The mean peak isometric stress was 119+/-15 mN mm(-2) physiological cross section, nearly half that measured for the CMP fibers of adults. Reverse transcriptase-polymerase chain reaction analysis of paralarval and adult mantle samples revealed very similar expression patterns of the two known isoforms of squid MHC. The ontogenetic differences in the structure and physiology of the circular muscles may result in more rapid mantle movements during locomotion. This prediction is consistent with jet pulse durations observed in other studies, with shorter jet pulses providing hydrodynamic advantages for paralarvae.

Background: : Management of patients with Treacher Collins syndrome is complicated and involves multiple disciplines working in concert to achieve a common outcome. This article reviews the experience at the Australian Craniofacial Unit and describes the protocol for management., Methods: : Fifty patients were treated during the last 30 years. The records of these patients were reviewed to establish what interventions they required and how these fit into a protocol for management., Results: : The protocol for management of Treacher Collins syndrome can be divided into 3 epochs. In the first epoch from birth to age 2, airway and feeding problems were the main focus. Four patients required tracheostomy. Of these, 1 died and the others received mandibular distraction. Hearing is evaluated and addressed early. Eleven patients (23%) required repair of a cleft palate. In the second epoch (aged 2-12 y), speech therapy is critical as is a focus on integrating into the education system. During this epoch, reconstruction of the upper face was performed either with bone grafts or with vascularized bone flaps. Both required repeat bone grafts later. In the third epoch (aged 13-18 y), orthognathic surgery was performed. Revision surgery and further bone grafting were performed again at around age 18. Patients reported being generally happy with their appearance and with few exceptions were able to complete education, gain employment, and feel socially accepted., Conclusions: : Management of patients with Treacher Collins syndrome should be through a multidisciplinary protocol to achieve good results while minimizing confusion and unnecessary surgery.

Conjugated linoleic acid (CLA) is a mixture of dietary fatty acids that has various beneficial effects including decreasing cancer, atherosclerosis, diabetes and inflammation in animal models. Some controversy exists on the specific isomers of CLA that are responsible for the benefits observed. This study was conducted to examine how different CLA isomers regulate gene expression in RAW 264.7. A mouse macrophage cell line, RAW 264.7, was treated with five different CLA isomers (9E,11E-, 9Z,11E-, 9Z,11Z-, 10E,12Z- and 11Z,13E-CLA). Gene expression microarrays were performed, and several significantly regulated genes of interest were verified by a real-time polymerase chain reaction (PCR). Examination of the biological functions of various significantly regulated genes by the five CLA isomers showed distinct properties. Isomers 9E,11E-, 9Z,11Z-, 10E,12Z- and 11Z,13E-CLA decreased production of proinflammatory cytokines such as interleukin (IL)-1alpha, IL-1beta and IL-6. Many of CLA's effects are believed to be mediated by the fatty acid receptors such as the peroxisome proliferator-activated receptors (PPAR) and retinoid-X-receptors (RXR). Using PPAR and RXR specific antagonists and coactivator recruitment assays, it was evident that multiple mechanisms were responsible for gene regulation by CLA isomers. Coactivator recruitment by CLA isomers showed their distinct properties as selective receptor modulators for PPARgamma and RXRalpha. These studies demonstrate distinct isomer differences in gene expression by CLA and will have important ramifications for determining the potential therapeutic benefit of these dietary fatty acids in prevention of inflammation-related diseases.

Purpose: Therapies to target prostate cancer bone metastases have only limited effects. New treatments are focused on the interaction between cancer cells, bone marrow cells and the bone matrix. Osteoclasts play an important role in the development of bone tumors caused by prostate cancer. Since Src kinase has been shown to be necessary for osteoclast function, we hypothesized that dasatinib, a Src family kinase inhibitor, would reduce osteoclast activity and prostate cancer (PC-3) cell-induced osteoclast formation., Results: Dasatinib inhibited RANKL-induced osteoclast differentiation of bone marrow-derived monocytes with an EC(50) of 7.5 nM. PC-3 cells, a human prostate cancer cell line, were able to differentiate RAW 264.7 cells, a murine monocytic cell line, into osteoclasts, and dasatinib inhibited this differentiation. In addition, conditioned medium from PC-3 cell cultures was able to differentiate RAW 264.7 cells into osteoclasts and this too, was inhibited by dasatinib. Even the lowest concentration of dasatinib, 1.25 nmol, inhibited osteoclast differentiation by 29%. Moreover, dasatinib inhibited osteoclast activity by 58% as measured by collagen 1 release., Experimental Design: We performed in vitro experiments utilizing the Src family kinase inhibitor dasatinib to target osteoclast activation as a means of inhibiting prostate cancer bone metastases., Conclusion: Dasatinib inhibits osteoclast differentiation of mouse primary bone marrow-derived monocytes and PC-3 cell-induced osteoclast differentiation. Dasatinib also inhibits osteoclast degradation activity. Inhibiting osteoclast differentiation and activity may be an effective targeted therapy in patients with prostate cancer bone metastases.

Despite having a similar structure, various conjugated linoleic acid (CLA) isomers have a distinct gene expression pattern in RAW 264.7 (RAW) cells, a mouse macrophage cell line. Among the 5 CLA isomers tested [9cis(Z),11trans(E)-, 9Z,11Z-, 9E,11E-, 10E,12Z-, and 11Z,13E-CLA], only 9E,11E-CLA induced the endogenous antiinflammatory molecule, interleukin (IL)-1 receptor antagonist (IL-1Ra), in RAW cells. In this study, the mechanism and effects of IL-1Ra regulation by 9E,11E-CLA in RAW cells was studied in detail. 9E,11E-CLA induced IL-1Ra in a dose- and time-dependent manner, whereas it decreased lipopolysaccharide (LPS)-induced IL-1alpha, IL-1beta, and IL-6 mRNA levels and protein levels. To determine the importance of IL-1Ra in the antiinflammatory effects of this particular CLA isomer, IL-1Ra protein levels were repressed in RAW cells using small interference RNA inhibitor expression. In the presence of IL-1Ra small interference RNA, the induction of this molecule was ablated, as was the decrease of LPS-induced IL-1alpha and IL-6 mRNA levels by 9E,11E-CLA. The IL-1Ra increase due to this CLA isomer was transcriptionally regulated, although there was no response element(s) affected by 9E,11E-CLA in the first 1.5 kb of the IL-1Ra promoter. The phosphoinositide 3-kinase inhibitors, LY294002 and the mammalian target of rapamycin inhibitor rapamycin, abolished the IL-1Ra induction by 9E,11E-CLA, whereas other kinase inhibitors did not affect this response. Taken together, 9E,11E-CLA exerts unique antiinflammatory effects by increasing an endogenous repressor of IL-1 signaling.

Purpose: The goal of this study was to see how the availability of ranibizumab affected the referral patterns for low vision (LV) evaluation., Methods: This study used a retrospective review and a comparison of all patients newly referred from retinal Practice 1 (J.T.T., R.N.S.) for LV consultation, from July 2005 to June 2006 (Year 1, preranibizumab) and from July 2006 to June 2007 (Year 2, ranibizumab available), and a retrospective review of patients referred by retinal Practice 2 (M.J.E.) since February 2007., Results: Practice 1: In Year 1, 24 patients with choroidal neovascularization were referred for LV, and in Year 2, only 12 were referred. There was a trend for those patients referred in Year 2 to have worse visual acuity and Pelli-Robson contrast sensitivity than those in Year 1. In Years 1 and 2, 18 and 11 patients with other conditions were referred for LV consultation, respectively. For these patients without choroidal neovascularization, there was no significant difference between groups for visual acuity or contrast sensitivity. Practice 2: The mean best-corrected visual acuity of patients with bilateral choroidal neovascularization referred was 20/145, and no patient had visual acuity > or =20/100., Conclusion: Although the use of antivascular endothelial growth factor agents puts visual acuity in a zone more favorable for successful LV intervention, patients with better acuities may not be referred for LV evaluation despite their residual visual impairments and their scotomas, and despite the fact that without LV intervention, they are having difficulty with reading and other activities of daily living. The frequent visits required for monthly injection, the tendency to wait until a course of therapy is complete before referring patients, and a lesser appreciation for the need for LV intervention in patients with only moderate visual loss may be factors in explaining this.

The dynamics of pulsed jetting in squids throughout ontogeny is not well understood, especially with regard to the development of vortex rings, which are common features of mechanically generated jet pulses (also known as starting jets). Studies of mechanically generated starting jets have revealed a limiting principle for vortex ring formation characterized in terms of a ;formation number' (F), which delineates the transition between the formation of isolated vortex rings and vortex rings that have; pinched off' from the generating jet. Near F, there exists an optimum in pulse-averaged thrust with (potentially) low energetic cost, raising the question: do squids produce vortex rings and if so, do they fall near F, where propulsive benefits presumably occur? To better understand vortex ring dynamics and propulsive jet efficiency throughout ontogeny, brief squid Lolliguncula brevis ranging from 3.3 to 9.1 cm dorsal mantle length (DML) and swimming at speeds of 2.43-22.2 cms(-1) (0.54-3.50 DMLs(-1)) were studied using digital particle image velocimetry (DPIV). A range of jet structures were observed but most structures could be classified as variations of two principal jet modes: (1) jet mode I, where the ejected fluid rolled up into an isolated vortex ring; and (2) jet mode II, where the ejected fluid developed into a leading vortex ring that separated or ;pinched off' from a long trailing jet. The ratio of jet length [based on the vorticity extent (L(omega))] to jet diameter [based on peak vorticity locations (D(omega))] was <3.0 for jet mode I and >3.0 for jet mode II, placing the transition between modes in rough agreement with F determined in mechanical jet studies. Jet mode II produced greater time-averaged thrust and lift forces and was the jet mode most heavily used whereas jet mode I had higher propulsive efficiency, lower slip, shorter jet periods and a higher frequency of fin activity associated with it. No relationship between L(omega)/D(omega) and speed was detected and there was no apparent speed preference for the jet modes within the speed range considered in this study; however, propulsive efficiency did increase with speed partly because of a reduction in slip and jet angle with speed. Trends in higher slip, lower propulsive efficiency and higher relative lift production were observed for squid <5.0 cm DML compared with squid >/=5.0 cm DML. While these trends were observed when jet mode I and II were equally represented among the size classes, there was also greater relative dependence on jet mode I than jet mode II for squid <5.0 cm DML when all of the available jet sequences were examined. Collectively, these results indicate that approximately 5.0 cm DML is an important ontogenetic transition for the hydrodynamics of pulsed jetting in squids. The significance of our findings is that from early juvenile through to adult life stages, L. brevis is capable of producing a diversity of vortex ring-based jet structures, ranging from efficient short pulses to high-force longer duration pulses. Given that some of these structures had L(omega)/D(omega)s near F, and F represented the delineation between the two primary jet modes observed, fluid dynamics probably played an integral role in the evolution of squid locomotive systems. When this flexibility in jet dynamics is coupled with the highly versatile fins, which are capable of producing multiple hydrodynamic modes as well, it is clear that squid have a locomotive repertoire far more complex than originally thought.

Squid paralarvae (hatchlings) rely predominantly on a pulsed jet for locomotion, distinguishing them from the majority of aquatic locomotors at low/intermediate Reynolds numbers (Re), which employ oscillatory/undulatory modes of propulsion. Although squid paralarvae may delineate the lower size limit of biological jet propulsion, surprisingly little is known about the hydrodynamics and propulsive efficiency of paralarval jetting within the intermediate Re realm. To better understand paralarval jet dynamics, we used digital particle image velocimetry (DPIV) and high-speed video to measure bulk vortex properties (e.g. circulation, impulse, kinetic energy) and other jet features [e.g. average and peak jet velocity along the jet centerline (U(j) and U(jmax), respectively), jet angle, jet length based on the vorticity and velocity extents (L(omega) and L(V), respectively), jet diameter based on the distance between vorticity peaks (D(omega)), maximum funnel diameter (D(F)), average and maximum swimming speed (U and U(max), respectively)] in free-swimming Doryteuthis pealeii paralarvae (1.8 mm dorsal mantle length) (Re(squid)=25-90). Squid paralarvae spent the majority of their time station holding in the water column, relying predominantly on a frequent, high-volume, vertically directed jet. During station holding, paralarvae produced a range of jet structures from spherical vortex rings (L(omega)/D(omega)=2.1, L(V)/D(F)=13.6) to more elongated vortex ring structures with no distinguishable pinch-off (L(omega)/D(omega)=4.6, L(V)/D(F)=36.0). To swim faster, paralarvae increased pulse duration and L(omega)/D(omega), leading to higher impulse but kept jet velocity relatively constant. Paralarvae produced jets with low slip, i.e. ratio of jet velocity to swimming velocity (U(j)/U or U(jmax)/U(max)), and exhibited propulsive efficiency [eta(pd)=74.9+/-8.83% (+/-s.d.) for deconvolved data] comparable with oscillatory/undulatory swimmers. As slip decreased with speed, propulsive efficiency increased. The detection of high propulsive efficiency in paralarvae is significant because it contradicts many studies that predict low propulsive efficiency at intermediate Re for inertial forms of locomotion.

Introduction: A dramatic rise in positional plagiocephaly has been noted over the last decade. Methods for treating and following outcomes are varied. We present our results from a passive soft helmet molding therapy using a surface scanning laser to provide objective outcomes., Methods: One hundred seventy-five infants with positional plagiocephaly were treated at our institution over a 6-month period. The helmets used were soft foam helmets modified to fit each patient. Results were measured using a three-dimensional surface scanning laser and objective measurements of asymmetry. Compliance was also documented., Results: The scanning laser allowed for objective measurements of symmetry over time and was useful in following outcomes. Improvement in head shape was noted after about 4 months of therapy. Patients who were more compliant with therapy achieved better results., Conclusion: Use of the three-dimensional scanning laser and objective scoring system shows significant improvement in patients who were compliant with helmet therapy.

Indocyanine green (ICG) is one of several vital dyes that are used in vitreoretinal surgery to aid visualization of diaphanous collagenous tissues in what has been called chromovitrectomy. As shown herein, much has been written about the use and rather narrow safety profile of ICG. The discussion surrounding its applications would have ended long ago were it not for the occasional patient who keeps returning to the office with permanent central scotomas after ICG-assisted macular hole surgery. The purpose of this Viewpoint is to reemphasize potential methods of proper use and clarify safety issues of this particular vital dye that enhances surgical technique but not necessarily visual outcome.

Squids encounter vastly different flow regimes throughout ontogeny as they undergo critical morphological changes to their two locomotive systems: the fins and jet. Squid hatchlings (paralarvae) operate at low and intermediate Reynolds numbers (Re) and typically have rounded bodies, small fins, and relatively large funnel apertures, whereas juveniles and adults operate at higher Re and generally have more streamlined bodies, larger fins, and relatively small funnel apertures. These morphological changes and varying flow conditions affect swimming performance in squids. To determine how swimming dynamics and propulsive efficiency change throughout ontogeny, digital particle image velocimetry (DPIV) and kinematic data were collected from an ontogenetic range of long-finned squid Doryteuthis pealeii and brief squid Lolliguncula brevis swimming in a holding chamber or water tunnel (Re = 20-20 000). Jet and fin wake bulk properties were quantified, and propulsive efficiency was computed based on measurements of impulse and excess kinetic energy in the wakes. Paralarvae relied predominantly on a vertically directed, high frequency, low velocity jet as they bobbed up and down in the water column. Although some spherical vortex rings were observed, most paralarval jets consisted of an elongated vortical region of variable length with no clear pinch-off of a vortex ring from the trailing tail component. Compared with paralarvae, juvenile and adult squid exhibited a more diverse range of swimming strategies, involving greater overall locomotive fin reliance and multiple fin and jet wake modes with better defined vortex rings. Despite greater locomotive flexibility, jet propulsive efficiency of juveniles/adults was significantly lower than that of paralarvae, even when juvenile/adults employed their highest efficiency jet mode involving the production of periodic isolated vortex rings with each jet pulse. When the fins were considered together with the jet for several juvenile/adult swimming sequences, overall propulsive efficiency increased, suggesting that fin contributions are important and should not be overlooked in analyses of the swimming performance of squids. The fins produced significant thrust and consistently had higher propulsive efficiency than did the jet. One particularly important area of future study is the determination of coordinated jet/fin wake modes that have the greatest impact on propulsive efficiency. Although such research would be technically challenging, requiring new, powerful, 3D approaches, it is necessary for a more comprehensive assessment of propulsive efficiency of the squid dual-mode locomotive system.

Worldwide public media greatly affect women's decisions about infant feeding and may not reflect evidence-based practices. The aims of this research were to (1) describe the characteristics of printed articles having infant-feeding content, (2) describe this thematic content, and (3) compare the thematic content found in groupings based on media type and language (English and Chinese). Four Chinese-language newspapers, the English-language newspaper, and 3 bilingual parenting magazines were analyzed. A multiphase qualitative and quantitative content analysis found 5 themes (social context, mothers' information, effects on baby, the value of breast milk, and the utility of formula). Significant differences were found based on media type and language. Although breastfeeding was usually positively framed in all the media, Chinese media had more inaccurate information. Through this analysis, areas where actions could be taken to improve the quality of information about infant feeding received by the public have been identified.

A 45-year-old woman underwent pars plana vitrectomy for vitreous hemorrhage in the right eye 20 years prior to presentation. She also had prior phacoemulsification and intraocular lens implantation and subsequent laser capsulotomy in the right eye. Multiple preretinal metallic fragments were visible on the retinal surface and were presumed to be stainless steel fragments from the vitrectomy instrument. The fragments were documented by color photography, fluorescein angiography, optical coherence tomography, and echography. Visual acuity was 20/30, electrophysiologic testing was normal, and no signs of toxicity were present. No surgical intervention was planned.

The centrally located, mitochondria-poor (CMP) and superficially located, mitochondria-rich (SMR) circular muscle fibres in the mantles of some squids provide one of the few known examples of specialization in an obliquely striated muscle. Little is known of the mechanical properties or of the mechanisms and performance consequences of specialization in these fibres. We combined morphological and physiological approaches to study specialization in the SMR and CMP fibres of the long-finned squid Doryteuthis pealeii. The mean thick filament length was 3.12+/-0.56 mum and 1.78+/-0.27 mum for the SMR and CMP fibres, respectively. The cross-sectional areas of the whole fibre and the core of mitochondria were significantly higher in the SMR fibres, but the area occupied by the myofilaments did not differ between the two fibre types. The area of sarcoplasmic reticulum visible in cross sections was significantly higher in CMP fibres than in SMR fibres. In live bundles of muscle fibres partially isolated from the mantle, mean peak isometric stress during tetanus was significantly greater in SMR [335 mN mm(-2) physiological cross section (pcs)] than in CMP (216 mN mm(-2) pcs) fibres. SMR fibres had a lower average twitch:tetanus ratio (SMR=0.073; CMP=0.18) and a twofold lower unloaded maximum shortening velocity at 20 degrees C (SMR=2.4 L(0) s(-1); CMP=5.1 L(0) s(-1)), where L(0) was the preparation length that yielded the highest tetanic force. The structural differences in the two muscle fibre types play a primary role in determining their mechanical properties, and the significant differences in mechanical properties indicate that squid have two muscle gears. A simple model of the mantle shows that a gradient of strain and strain rate exists across the mantle wall, with fibres adjacent to the outer edge of the mantle experiencing 1.3- to 1.4-fold lower strain and strain rate than fibres adjacent to the inner edge of the mantle. The model also predicts that the CMP fibres generate virtually no power for slow jetting while the SMR fibres are too slow to generate power for the escape jets. The transmural differences in strain and strain rate predicted by the model apply to any cylindrical animal that has circumferentially oriented muscle fibres and an internal body cavity.

In most patients with an atrial septal defect or patent foramen ovale, a single defect of the interatrial septum may be closed with a single device. However, patients with multiple defects of the interatrial septum may require the use of multiple devices, which involves some technical challenges. We present 5 cases requiring 2 closure devices with clinical and echocardiographic follow up ranging from 3 months to 4 years, demonstrating a high success and low complication rates.

Background: Radiation protection practices range from strict adherence to safety practices to complacency to unsafe procedures. Variations in compliance with safety practices can result in unnecessary radiation exposure to technologists and patients., Objective: The objectives of this study were to advance the education and practice of the radiologic sciences by determining the degree of compliance with radiation safety practices as correlated to professional education, continuing education, years of employment in the radiologic sciences and work site., Method: A 32-item questionnaire was mailed to a national random sample of 2000 certified radiologic technologists. A return rate of 23.9% yielded 454 questionnaires suitable for analysis., Results: Mean scores for knowledge of and compliance with safety practices were 82% and 72%, respectively. Performance on individual items ranged from 95% compliance to 34% compliance. Two independent variables (ie, years of employment in the radiologic sciences and work site) were significantly related (P < .05) to adherence to safety practices., Conclusion: Results indicated the need for educational and organizational interventions to increase compliance with safety practices.

Negative pressure wound therapy has become an increasingly important part of wound management. Over the last decade, numerous uses for this method of wound management have been reported, ranging from acute and chronic wounds, to closure of open sternal and abdominal wounds, to assistance with skin grafts. The biophysics behind the success of this treatment largely have focused on increased wound blood flow, increased granulation tissue formation, decreased bacterial counts, and stimulation of wound healing pathways through shear stress mechanisms. The overall success of negative pressure wound therapy has led to a multitude of clinical applications, which are discussed in this article.

Selenium is an essential micronutrient that suppresses the redox-sensitive transcription factor NF-kappaB-dependent pro-inflammatory gene expression. To understand the molecular mechanisms underlying the anti-inflammatory property of selenium, we examined the activity of a key kinase of the NF-kappaB cascade, IkappaB-kinase beta (IKKbeta) subunit, as a function of cellular selenium status in murine primary bone marrow-derived macrophages and RAW264.7 macrophage-like cell line. In vitro kinase assays revealed that selenium supplementation decreased the activity of IKKbeta in lipopolysaccharide (LPS)-treated macrophages. Stimulation by LPS of selenium-supplemented macrophages resulted in a time-dependent increase in 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) formation, an endogenous inhibitor of IKKbeta activity. Further analysis revealed that inhibition of IKKbeta activity in selenium-supplemented cells correlated with the Michael addition product of 15d-PGJ2 with Cys-179 of IKKbeta, while the formation of such an adduct was significantly decreased in the selenium-deficient macrophages. In addition, anti-inflammatory activities of selenium were also mediated by the 15d-PGJ2-dependent activation of the peroxisome proliferator-activated nuclear receptor-gamma in macrophages. Experiments using specific cyclooxygenase (COX) inhibitors and genetic knockdown approaches indicated that COX-1, and not the COX-2 pathway, was responsible for the increased synthesis of 15d-PGJ2 in selenium-supplemented macrophages. Taken together, our results suggest that selenium supplementation increases the production of 15d-PGJ2 as an adaptive response to protect cells against oxidative stress-induced pro-inflammatory gene expression. More specifically, modification of protein thiols by 15d-PGJ2 represents a previously undescribed code for redox regulation of gene expression by selenium.

This study investigated student learning outcomes using a case-based approach focused on cellular respiration. Students who used the case study, relative to students who did not use the case study, exhibited a significantly greater learning gain, and demonstrated use of higher-order thinking skills. Preliminary data indicate that after engaging with the case study, students were more likely to answer a question addressing misconceptions about cellular respiration correctly when compared with students who did not use the case study. More rigorous testing is needed to fully elucidate whether case-based learning can effectively clarify student misconceptions related to biological processes., (Copyright © 2007 International Union of Biochemistry and Molecular Biology, Inc.)

Liver insufficiency and damage are major causes of death and disease worldwide and may result from exposure to environmental toxicants, specific combinations or dosages of pharmaceuticals, and microbial metabolites. The generation of reactive intermediates, in particular 4-hydroxynonenal (4-HNE), is a common event in liver damage caused by a variety of hepatotoxic drugs and solvents. The peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that are involved in the transcriptional regulation of lipid metabolism as well as other biological functions. Importantly, we have observed that the PPARbeta/delta-/- mouse is more susceptible to chemically induced hepatotoxicity than its wild-type counterpart, and our objective in this study was to elucidate the mechanism(s) by which PPARbeta/delta confers protection to hepatocytes. We hypothesized that PPARbeta/delta plays a protective role by responding to toxic lipids and altering gene expression accordingly. In support, oxidized-VLDL and constituents including 13-S-hydroxyoctadecadienoic acid (13-S-HODE) and 4-HNE are PPARbeta/delta ligands. A structure-activity relationship was established where 4-HNE and 4-hydroperoxynonenal (4-HpNE) enhanced the activity of the PPARbeta/delta subtype while 4-hyroxyhexenal (4-HHE), 4-oxo-2-Nonenal (4-ONE), and trans-4,5-epoxy-2(E)-decenal did not activate this receptor. Increasing PPARbeta/delta activity with a synthetic agonist decreased sensitivity of hepatocytes to 4-HNE and other toxic agents, whereas inhibition of this receptor had the opposite result. Gene expression microarray analysis identified several important PPARbeta/delta-regulated detoxification enzymes involved in 4-HNE metabolism that are regulated at the transcript level. This research established 4-HNE as an endogenous modulator of PPARbeta/delta activity and raises the possibility that agonists of this nuclear receptor may be utilized to prevent or treat liver disease associated with oxidative damage.

Objective: To critically assess the evidence of supplements containing Trifolium pratense (red clover) isoflavones in the reduction of hot flush frequency in menopausal women., Data Sources: Systematic literature searches were performed in (Medline (1951 - April 2006), Embase (1974 - April 2006), CINAHL (1982 - April 2006), Amed (1985 - April 2006) and The Cochrane Library (Issue 2, 2006). Reference lists located were checked for further relevant publications. Experts in the field and manufacturers of identified products were contacted for unpublished material. No language restrictions were imposed., Review Methods: Studies were selected according to predefined inclusion and exclusion criteria. All randomized clinical trials of monopreparations containing T. pratense isoflavones for treating hot flushes were included. Study selection, data extraction and validation were performed by at least two reviewers with disagreements being settled by discussion. Weighted means and 95% confidence intervals were calculated and sensitivity analyses were performed., Results: Seventeen potentially relevant articles were retrieved for further evaluation. Five were suitable for inclusion in the meta-analysis. The meta-analysis indicates a reduction in hot flush frequency in the active treatment group (40-82 mg daily) compared with the placebo group (weighted mean difference -1.5 hot flushes daily; 95% CI -2.94 to 0.03; p=0.05)., Conclusion: There is evidence of a marginally significant effect of T. pratense isoflavones for treating hot flushes in menopausal women. Whether the size of this effect can be considered clinically relevant is unclear. Whereas there is no apparent evidence of adverse events during short-term use, there are no available data on the safety of long-term administration.

Purpose: To compare the anatomic and functional results of 3 different epimacular dissection techniques on macular hole surgery., Methods: Vitrectomy was performed in 123 eyes for macular hole in a retrospective, consecutive case series by one surgeon. The surgical technique was identical except for the method of epimacular dissection, which was performed using 1 of 3 techniques sequentially. The first group of 29 eyes had abrasion of the macula with a sharp pick (epiretinal dissection [ERD]), the second group of 32 eyes had partial or complete removal of the internal limiting membrane (ILM), without ILM staining. The third group of 62 eyes had complete removal of the ILM using indocyanine green (ICG) to stain the ILM., Results: The mean preoperative visual acuity was 20/125 -2 in the ERD and ILM groups and 20/160 -2 in the ICG groups (P = .167). Long-term successful closure of the macular hole was achieved with one operation in 22 of 29 ERD eyes (75.9%), 31 of 32 ILM eyes (96.7%), and 62 of 62 ICG eyes (100%). The mean visual acuity at 3 months was 20/63 +2 (ERD), 20/80 (ILM), and 20/125 (ICG) (P < .001), with significantly poorer visual acuity in the ICG group. The final visual acuity (mean, 2.27 years) was 20/63 +1 (ERD), 20/50 -2 (ILM), and 20/80 -1 (ICG, P = .073), with no significant differences in mean visual acuity, visual acuity gain, gain of > or =3 lines, or percentage > or =20/40., Conclusions: Removal of the ILM decreases persistent and recurrent macular holes. ICG staining and complete removal of the ILM slows the rate of visual recovery but does not appear to have any long-term deleterious effect on the results of macular hole surgery.

Objectives: The aim of this review is to systematically summarize and assess all prospective, controlled, cost-effectiveness studies of complementary therapies carried out in the UK., Data Sources: Medline (via PubMed), Embase, CINAHL, Amed (Alternative and Allied Medicine Database, British Library Medical Information Centre), The Cochrane Library, National Health Service Economic Evaluation Database (via Cochrane) and Health Technology Assessments up to October 2005., Review Methods: Articles describing prospective, controlled, cost-effectiveness studies of any type of complementary therapy for any medical condition carried out in the UK were included. Data extracted included the main outcomes for health benefit and cost. These data were extracted independently by two authors, described narratively and also presented as a table., Results: Six cost-effectiveness studies of complementary medicine in the UK were identified: four different types of spinal manipulation for back pain, one type of acupuncture for chronic headache and one type of acupuncture for chronic back pain. Four of the six studies compared the complementary therapy with usual conventional treatment in pragmatic, randomized clinical trials without sham or placebo arms. Main outcome measures of effectiveness favored the complementary therapies but in the case of spinal manipulation (four studies) and acupuncture (one study) for back pain, effect sizes were small and of uncertain clinical relevance. The same four studies included a cost-utility analyses in which the incremental cost per quality adjusted life year (QALY) was less than pound10 000. The complementary therapy represented an additional health care cost in five of the six studies., Conclusions: Prospective, controlled, cost-effectiveness studies of complementary therapies have been carried out in the UK only for spinal manipulation (four studies) and acupuncture (two studies). The limited data available indicate that the use of these therapies usually represents an additional cost to conventional treatment. Estimates of the incremental cost of achieving improvements in quality of life compare favorably with other treatments approved for use in the National Health Service. Because the specific efficacy of the complementary therapies for these indications remains uncertain, and the studies did not include sham controls, the estimates obtained may represent the cost-effectiveness non-specific effects associated with the complementary therapies.

Administration of ammonium salts of perfluorooctanoate (PFOA) to rats results in peroxisome proliferation and benign liver tumors, events associated with activation of the nuclear receptor (NR) peroxisome proliferator-activated receptor-alpha (PPARalpha). Due to its fatty acid structure, PFOA may activate other NRs, such as PPARbeta, PPARgamma, liver X receptor (LXR), or retinoid X receptor (RXR). In this study, the activation of human, mouse, and rat PPARalpha, PPARbeta, PPARgamma, LXRbeta, and RXRalpha by PFOA (including its linear and branched isomers) and perfluorooctane sulfonate (PFOS) was investigated and compared to several structural classes of natural fatty acids and appropriate positive control ligands. An NR ligand-binding domain/Gal4 DNA-binding domain chimeric reporter system was used. Human, mouse, and rat PPARalpha were activated by PFOA isomers and PFOS. PPARbeta was less sensitive to the agents tested, with only PFOA affecting the mouse receptor. PFOA and PFOS also activated human, mouse, and rat PPARgamma, although the maximum induction of PPARgamma was much less than that seen with rosiglitazone, suggesting that PFOA and PFOS are partial agonists of this receptor. Neither LXRbeta nor the common heterodimerization partner RXRalpha was activated by PFOA in any species examined. Taken together, these data show that of the NRs studied, PPARalpha is the most likely target of PFOA and PFOS, although PPARgamma is also activated to some extent. Compared to naturally occurring long-chain fatty acids, e.g. linoleic and alpha-linolenic acids, these perfluorinated fatty acid analogs were more selective and less potent in their activation of the NRs.

2-Arachidonyl glycerol (2-AG) is an endogenous arachidonic acid derivative that binds cannabinoid receptors CB1 and CB2 and is hence termed an endocannabinoid. 2-AG also modulates a variety of immunological responses, including expression of the autocrine/paracrine T cell growth factor interleukin (IL)-2. The objective of the present studies was to determine the mechanism responsible for IL-2 suppression by 2-AG. Because of the labile properties of 2-AG, 2-AG ether, a nonhydrolyzable analog of 2-AG, was also used. Both 2-AG and 2-AG ether suppressed IL-2 expression independently of CB1 and CB2, as demonstrated in leukocytes derived from CB1/CB2-null mice. Moreover, we demonstrated that both 2-AG and 2-AG ether treatment activated peroxisome proliferator-activated receptor gamma (PPARgamma), as evidenced by forced differentiation of 3T3-L1 cells into adipocytes, induction of aP2 mRNA levels, and activation of a PPARgamma-specific luciferase reporter in transiently transfected 3T3-L1 cells. Consequently, the putative role of PPARgamma in IL-2 suppression by 2-AG and 2-AG ether was examined in Jurkat T cells. Concordant with PPARgamma involvement, the PPARgamma-specific antagonist 2-chloro-5-nitro-N-(4-pyridyl)-benzamide (T0070907) blocked 2-AG- and 2-AG ether-mediated IL-2 suppression. Likewise, 2-AG suppressed the transcriptional activity of two transcription factors crucial for IL-2 expression, nuclear factor of activated T cells and nuclear factor kappaB, in the absence but not in the presence of T0070907. 2-AG treatment also induced PPARgamma binding to a PPAR response element in activated Jurkat T cells. Together, the aforementioned studies identify PPARgamma as a novel intracellular target of 2-AG, which mediates the suppression of IL-2 by 2-AG in a manner that is independent of CB1 and/or CB2.