Minimal Weight Loss Research Articles

Influence of packaging system and long term storage on physiological attributes, biochemical quality, volatile composition and antioxidant properties of pomegranate fruit

Commercially ripe pomegranate fruit were packed in ventilatedcarton with polyliner (referred to as passive modified atmosphere packaging, MAP), individual shrink wrap and open top carton (control) andstored under 7±0.5°C and 92±2% RH for 4 months. Incidence of physiological disorders and changes in biochemical properties, phenolic compounds, total phenolics, total flavonoids, total tannins, total anthocyanins, antioxidant activity and vitamin C were analysed monthly. The results showed that fruit stored under polyliner and individual shrink wrapped significantly minimized weight loss compared to control. Significantly higher fruit decay incidence was observed after 3 months, irrespective of package type. TSS content, citric acid, and L-malic concentrations decreased considerably in all packaging systems with increasing storage time. Fructose and glucose concentrations fluctuated during storage with the lowest value observed at the end of storage infruit packed under polyliner and shrink wrapped packaging. Amongst phenolic compounds identified, catechin and rutin increased by 65.43% and 139.39%, respectively, in fruit packed inside polyliners and individual shrink wrap after 4 months of cold storage. Total phenolic and total tannin concentrations declined by 23.86 and 65.89% in fruit stored under polyliner and individual shrink wrap packaging after 3 months of storage, respectively. Furthermore, total anthocyanin concentration was significantly higher in fruit packed in MAP (103.59gL−1 of cyanidin-3-glucoside of pomegranate) than individual shrink wrap (84.78gL−1) after4 months of storage. Volatiles organic compounds including ethanol, alpha-pinene and beta-pine accumulation increased significantly with prolonged storage regardless of packaging material used.

A test of reactive scope: Reducing reactive scope causes delayed wound healing

Reactive scope predicts that all animals have an adaptive ability to respond to stressors in their environment, termed reactive homeostasis, and that only when an animal’s response to stressful stimuli exceeds a certain threshold (homeostatic overload) will stress have pathological effects. While this framework has successfully helped interpret effects of stressors on wildlife, no study has designed an experiment to directly test this framework. This study was designed to expose house sparrows (Passer domesticus) to treatments that would result in varying ranges of reactive homeostasis during chronic stress, which based on the reactive scope model should cause birds with the lowest reactive homeostasis range to exhibit signs of pathology during a subsequent challenge. To modulate the reactive homeostasis range, we altered allostatic load of birds by exposing them to chronic stress while either elevating, blocking, or not manipulating corticosterone. After concluding chronic stress treatments, birds were exposed to the subsequent challenge of a superficial wound. Individuals treated with corticosterone during chronic stress (high allostatic load) experienced the most pathology, including both weight loss and slower wound healing. Unmanipulated birds (medium allostatic load) also experienced weight loss but had normal healing rates, while birds with blocked corticosterone (low allostatic load) had minimal weight loss and normal healing rates. Our results indicate that increased allostatic load reduces the reactive homeostasis range, thereby causing individuals to cross the homeostatic overload threshold sooner, and thus support the reactive scope framework.

Abstract LB-112: PLK1 inhibition in genetically characterized triple-negative breast cancer (TNBC) patient-derived xenograft (PDX) models results in robust antitumor activity including significant and durable tumor regression

Abstract Background: PLK1 plays multiple critical cell cycle roles and numerous preclinical studies have validated the impact of PLK1 inhibition in tumors. A Phase II trial of a PLK1 inhibitor in AML showed significantly increased ORR and OS (Döhner et al 2014), but results in solid tumors have been uniformly modest. However, recent studies indicate that PLK1 inhibition may yield greater responses in specific genetic subtypes. Maire et al (2012) reported impressive response and survival data in TNBC PDX models, and PLK1 has been implicated in promoting growth and survival in cooperation with MYC, PTEN-loss, the PI3K/mTOR pathway and AR signaling in prostate cancer and other models (Zhang et al 2014, Hou et al 2013, Liu et al 2011 and Tan et al 2013). We therefore tested whether the highly selective PLK1 inhibitor NMS-P937 could differentially inhibit the growth of a diverse panel of genetically-characterized TNBC PDX models, enabling selection of a potentially higher responding patient population. Methods: Ten genetically-characterized TNBC PDX models containing a broad set of mutations were tested for sensitivity to NMS-P937. After implantation and establishment in SCID mice (n = 3 per group), NMS-P937 was administered at different doses and schedules over a 24-day treatment period. Body weight, tumor growth and growth delay after cessation of treatment were measured. Results: Nine models were evaluable and significant tumor growth inhibition (50-90%) was noted in four. Mutations in the responding models have been proposed to enhance response to PLK1 inhibition in other tumor types, but not previously in TNBC. All lines with sensitivity-enhancing mutations responded while lines without did not. In the most sensitive model, NMS-P937 caused uniform, near-complete regressions that were stable for 21 days after dosing, with minimal body weight loss. This model harbors an amplified AR locus; though Hou et al proposed a connection between PLK1 and AR signaling, the extent and durability of the response was unanticipated. Further characterization of all models will be provided. Conclusion: This study appears to be the first report of a PLK1 inhibitor evaluation in a diverse panel of genetically-characterized models in any tumor type. Our results demonstrate that differentially sensitive molecular subtypes of TNBC can be identified and that underlying genetic profiles can be exploited to identify TNBC patients who may benefit most from PLK1 inhibitors. We are continuing to explore additional predictive genetic markers of NMS-P937 sensitivity in TNBC as well as other solid tumors, and planning for a clinical trial in selected TNBC patients. Citation Format: Benjamin Palleiko, Mark R. Miglarese, Michael King, Sandra L. Silberman. PLK1 inhibition in genetically characterized triple-negative breast cancer (TNBC) patient-derived xenograft (PDX) models results in robust antitumor activity including significant and durable tumor regression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-112.

Abstract 3008: Preclinical characterization of AMG 900, a pan-aurora kinase inhibitor, alone and in combination with taxanes in ovarian cancer

Abstract BACKGROUND: Aurora kinases (AK) A and B play essential roles in multiple stages of mitosis and are frequently overexpressed in a subset of human cancers, including ovarian cancer (OC). AMG 900, a potent and highly selective small molecule inhibitor of AKs, showed promising single-agent activity in heavily pretreated patients with advanced OC in a Phase 1b clinical trial. In this study, we report the preclinical effects of AMG 900 in a panel of well-characterized human cancer cell lines representing clinically-relevant OC subtypes. METHODS: The anti-proliferative effects of AMG 900 were evaluated using a 5-day cell count assay. Cell lines were classified as sensitive to AMG 900 when lethality was > 15% at 10 nM. Molecular markers were profiled including TP53 mutation status, AURKA, CCNE1, MYC copy number, and p53, p21 and cyclin E1 protein by reverse phase protein array. Flow cytometry and imaging methods were used to evaluate the mechanism of action of AMG 900 alone and in combination with chemotherapy. The combination of AMG 900 plus docetaxel was evaluated in an IGROV-1 ovarian endometrioid carcinoma xenograft model. RESULTS: One third of the cell lines (11 of 35) were classified as sensitive to AMG 900 and showed enrichment for TP53 mutations and serous OC subtype. However, 10 of 24 resistant cell lines harbored TP53 mutations, indicating that TP53 mutational status alone was not sufficient for predicting AMG 900 sensitivity. Inhibition of AK activity by AMG 900 in OC cells resulted in aborted cell division leading to polyploidy and cell death (suggestive of aurora-B dominant phenotype). Re-plating of remnant cells after AMG 900 treatment showed an attenuation of cell regrowth, where TP53mut IGROV-1 cells showed minimal regrowth compared to TP53wt OVCAR-5 cells. AMG 900 inhibited proliferation at low nanomolar concentrations in the majority of OC cell lines and enhanced the effects of paclitaxel, carboplatin, and doxorubicin in IGROV-1 cells. In tumor-bearing mice, administration of AMG 900 at 7.5 mg/kg (PO) for two days per week or docetaxel at 10 mg/kg (IP) weekly for four cycles significantly inhibited the growth of IGROV-1 tumor xenografts (P < .0001 vs. vehicle alone). Notably, co-administration of AMG 900 with docetaxel enhanced efficacy and induced a delay in tumor regrowth compared to docetaxel alone. Single-agent-treated mice showed minimal body weight loss (BWL), whereas combination-treated mice showed moderate BWL (average < 10%) that was largely reversible (2 of 12 animals removed due to toxicity). CONCLUSIONS: AMG 900 alone or in combination with chemotherapy such as paclitaxel may be a promising clinical strategy to treat patients with ovarian cancer. Citation Format: Ondrej Kalous, Dylan Conklin, Kanthinh Manivong, William Wayne, Kelly Hanestad, Jude Canon, Robert Loberg, Gregory Friberg, Erick Gamelin, Florian D. Vogl, Gloria Juan, Angela Coxon, Dennis Slamon, Richard Finn, Marc Payton. Preclinical characterization of AMG 900, a pan-aurora kinase inhibitor, alone and in combination with taxanes in ovarian cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3008.

Experimental Granulomatous Pulmonary Nocardiosis in BALB/C Mice.

Pulmonary nocardiosis is a granulomatous disease with high mortality that affects both immunosuppressed and immunocompetent patients. The mechanisms leading to the establishment and progression of the infection are currently unknown. An animal model to study these mechanisms is sorely needed. We report the first in vivo model of granulomatous pulmonary nocardiosis that closely resembles human pathology. BALB/c mice infected intranasally with two different doses of GFP-expressing Nocardia brasiliensis ATCC700358 (NbGFP), develop weight loss and pulmonary granulomas. Mice infected with 109 CFUs progressed towards death within a week while mice infected with 108 CFUs died after five to six months. Histological examination of the lungs revealed that both the higher and lower doses of NbGFP induced granulomas with NbGFP clearly identifiable at the center of the lesions. Mice exposed to 108 CFUs and subsequently to 109 CFUs were not protected against disease severity but had less granulomas suggesting some degree of protection. Attempts to identify a cellular target for the infection were unsuccessful but we found that bacterial microcolonies in the suspension used to infect mice were responsible for the establishment of the disease. Small microcolonies of NbGFP, incompatible with nocardial doubling times starting from unicellular organisms, were identified in the lung as early as six hours after infection. Mice infected with highly purified unicellular preparations of NbGFP did not develop granulomas despite showing weight loss. Finally, intranasal delivery of nocardial microcolonies was enough for mice to develop granulomas with minimal weight loss. Taken together these results show that Nocardia brasiliensis microcolonies are both necessary and sufficient for the development of granulomatous pulmonary nocardiosis in mice.

Cerebellar sub-divisions differ in exercise-induced plasticity of noradrenergic axons and in their association with resilience to activity-based anorexia

The vermis or “spinocerebellum” receives input from the spinal cord and motor cortex for controlling balance and locomotion, while the longitudinal hemisphere region or “cerebro-cerebellum” is interconnected with non-motor cortical regions, including the prefrontal cortex that underlies decision-making. Noradrenaline release in the cerebellum is known to be important for motor plasticity but less is known about plasticity of the cerebellar noradrenergic (NA) system, itself. We characterized plasticity of dopamine β-hydroxylase-immunoreactive NA fibers in the cerebellum of adolescent female rats that are evoked by voluntary wheel running, food restriction (FR) or by both, in combination. When 8 days of wheel access was combined with FR during the last 4 days, some responded with excessive exercise, choosing to run even during the hours of food access: this exacerbated weight loss beyond that due to FR alone. In the vermis, exercise, with or without FR, shortened the inter-varicosity intervals and increased varicosity density along NA fibers, while excessive exercise, due to FR, also shortened NA fibers. In contrast, the hemisphere required the FR-evoked excessive exercise to evoke shortened inter-varicosity intervals along NA fibers and this change was exhibited more strongly by rats that suppressed the FR-evoked excessive exercise, a behavior that minimized weight loss. Presuming that shortened inter-varicosity intervals translate to enhanced NA release and synthesis of norepinephrine, this enhancement in the cerebellar hemisphere may contribute towards protection of individuals from the life-threatening activity-based anorexia via relays with higher-order cortical areas that mediate the animal’s decision to suppress the innate FR-evoked hyperactivity.

Elevation of CpG frequencies in influenza A genome attenuates pathogenicity but enhances host response to infection

Previously, we demonstrated that frequencies of CpG and UpA dinucleotides profoundly influence the replication ability of echovirus 7 (Tulloch et al., 2014). Here, we show that that influenza A virus (IAV) with maximised frequencies of these dinucleotides in segment 5 showed comparable attenuation in cell culture compared to unmodified virus and a permuted control (CDLR). Attenuation was also manifested in vivo, with 10-100 fold reduced viral loads in lungs of mice infected with 200PFU of CpG-high and UpA-high mutants. However, both induced powerful inflammatory cytokine and adaptive (T cell and neutralising antibody) responses disproportionate to their replication. CpG-high infected mice also showed markedly reduced clinical severity, minimal weight loss and reduced immmunopathology in lung, yet sterilising immunity to lethal dose WT challenge was achieved after low dose (20PFU) pre-immunisation with this mutant. Increasing CpG dinucleotide frequencies represents a generic and potentially highly effective method for generating safe, highly immunoreactive vaccines.

Reducing variation in pork production systems through maternal and pre- and post-weaning nutrition strategies

Variation is inherent in any biological system and is a challenge to manage in modern pork-production businesses. In the case of the growing and finishing herd, inherent variation within a population of pigs represents a significant cost as a result of the need to select on farm to meet market specifications, poor matching of diet specifications to nutrient requirements, grading losses, higher pre-weaning mortality, and challenges associated with health management. As a consequence, any management practice that can be applied to reduce variation at the point of sale has the potential to improve the profitability and overall efficiency of a pig enterprise. The present paper considers nutritional interventions of sows during gestation, lactation and the weaning to oestrus interval to minimise inherent variation in the progeny and then pre- and post-weaning nutrition of piglets to limit further variation. Prior to birth, there are many factors that can influence variation in the birthweight and growth potential of the progeny. In gestating sows, dietary energy will not influence variation in birthweight, but supplementation with free arginine and glutamine will reduce variation in birthweight of piglets born and piglets born alive. In lactating sows, maintenance of feed intake to optimise milk production and minimise weight loss of the sow during lactation not only minimises variation in progeny weight at weaning, but enhances subsequent birthweight heterogeneity due to the influence of the sow’s metabolic status on follicle and oocyte quality. Supplementation with dextrose during the weaning to oestrus interval can also reduce variation in birthweight due to a pronounced effect on plasma glucose and insulin concentrations. Prior to weaning, light weight piglets appear to have an enhanced capacity for growth compared with their larger counterparts. To this end, split suckling has been shown to reduce weaning-weight variation, despite no effect on average growth rate or weaning weight for litters with nine piglets or more born alive. Supplemental milk before weaning has reduced variation in weaning weights, but creep feeding has proved equivocal in this regard. Post-weaning, it appears that remedial feeding strategies will do little to improve the growth potential of light-weight pigs, and while high specification diets may contribute to a slight reduction in variation at slaughter, this strategy is unlikely to be economically viable. As with many aspects of commercial pork production, it would seem that the greatest potential to reduce variation in the slaughter weight of market pigs vests with careful management of gestating and lactating sows, with some potential for dietary interventions to further reduce variation in birth and weaning weights.

Abstract B151: In FGFR2 driven tumors, preclinical pharmacokinetics (PK), pharmacodynamics (PD) and efficacy translate into clinical activity of ARQ 087

Abstract Background: ARQ 087 is a potent FGFR1-3 tyrosine kinase inhibitor which is currently in a Phase 1/2 clinical study in patients with FGFR-driven solid tumors. We present a comparison of preclinical-clinical PK, PD, and efficacy data. Methods: In vitro proliferation studies were conducted in FGFR2 driven cell lines (Ba/F3 transfected, SNU-16, NCI-H716, AN3CA). In vivo studies were conducted in BaF3/FGFR2, SNU-16, ANC3A, and NCI-H716 xenograft models. Approximately 5×10^6 cells implanted subcutaneously and allowed to grow to an appropriate size (200-400mg) before initiating treatment with ARQ 087 (25-150 mg/kg QD). Treatment periods were from 10-21 days (model dependent), and ARQ 087 was generally well tolerated with minimal weight-loss. Levels of pFGFR, and other downstream markers of FGFR pathway inhibition, were tracked in cells and tumors to determine the effects of ARQ 087 on FGFR pathway activity. Patients with solid tumors were enrolled in the ARQ 087-101 trial (NCT01752920) at 20-425 mg QD, and plasma was collected on cycle 1 day 1, 8, 22, and day 1 and 15 of subsequent cycles for PK and PD (FGF levels). Human and mouse plasma samples, were quantified for ARQ 087 levels. Results: ARQ 087 is a potent inhibitor of cell lines with FGFR2 genetic alterations with IC50 values as low as 40 nM. In FGFR2 driven cell lines ARQ 087 inhibited pFGFR as well and downstream signaling proteins. SNU-16 xenograft models showed 69-99-% tumor growth inhibition (TGI), with plasma Cmax values of 1.2-4.9 μM. BaF3/FGFR2 xenografts had a TGI of up to 94% with plasma Cmax of 2.8-7.7 μM. AN3CA xenografts showed TGI 054% and a Cmax of 0.1-3.1 μM. In the dose escalation phase of ARQ 087-101 mean plasma Cmax concentrations at steady state were 2 μM at the MTD (400 mg QD). The recommended phase 2 dose for ARQ 087 is 300 mg QD, which provides comparable plasma concentrations. Two cholangiocarcinoma patients with FGFR2 translocations were treated at 400mg QD. A RECIST partial response (-34% in tumor size) was observed in a patient with an FGFR2-BICC1 fusion, whose steady state ARQ 087 Cmax level was 1.7 μM. A minor tumor response (-26%) was seen in a patient with an FGFR2-KIAA1217 fusion, and a steady state ARQ 087 Cmax was 1.5 μM. Finally, patients treated with ARQ 087 showed changes in circulating FGFs 19/21/23, which supports the monitoring of these FGFs as biomarkers for target engagement. Conclusions: In our studies with ARQ 087, FGFR2 dysregulation correlates with efficacy. The translation of results from FGFR2 preclinical models into clinical efficacy in patients with FGFR2 fusion driven cholangiocarcinoma is encouraging and is currently evaluated in the ongoing clinical trial. Citation Format: Terence G. Hall, Ronald E. Savage, Brian Schwartz, Yi Yu, Yunxia Wang, Julia Kazakin, Giovanni Abbadessa, Anthony W. Tolcher, Kyriakos P. Papadopoulos, Walid Shaib, Bassel el-Rayes. In FGFR2 driven tumors, preclinical pharmacokinetics (PK), pharmacodynamics (PD) and efficacy translate into clinical activity of ARQ 087. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr B151.

Predictive factors for survival and correlation to toxicity in advanced Stage III non-small cell lung cancer patients with concurrent chemoradiation.

Concurrent chemoradiotherapy is the standard treatment for locally advanced Stage III non-small cell lung cancer in patients with a good performance status and minimal weight loss. This study aimed to define subgroups with different survival outcomes and identify correlations with the radiation-related toxicities. We retrospectively reviewed 381 locally advanced Stage III non-small cell lung cancer patients with a good performance status or weight loss of <10% who received concurrent chemoradiotherapy between 2004 and 2011. Three-dimensional conformal radiotherapy was administered once daily, combined with weekly chemotherapy. The Kaplan-Meier method was used for survival comparison and Cox regression for multivariate analysis. Multivariate analysis was performed using all variables with P values <0.1 from the univariate analysis. Median survival of all patients was 24 months. Age > 75 years, the diffusion lung capacity for carbon monoxide ≤80%, gross tumor volume ≥100 cm(3) and subcarinal nodal involvement were the statistically significant predictive factors for poor overall survival both in univariate and multivariate analyses. Patients were classified into four groups according to these four predictive factors. The median survival times were 36, 29, 18 and 14 months in Groups I, II, III and IV, respectively (P < 0.001). Rates of esophageal or lung toxicity ≥Grade 3 were 5.9, 14.1, 12.5 and 22.2%, respectively. The radiotherapy interruption rate differed significantly between the prognostic subgroups; 8.8, 15.4, 22.7 and 30.6%, respectively (P = 0.017). Severe toxicity and interruption of radiotherapy were more frequent in patients with multiple adverse predictive factors. To maintain the survival benefit in patients with concurrent chemoradiotherapy, strategies to reduce treatment-related toxicities need to be deeply considered.

Host Genetic Variations and Sex Differences Potentiate Predisposition, Severity, and Outcomes of Group A Streptococcus-Mediated Necrotizing Soft Tissue Infections.

Host genetic variations play an important role in several pathogenic diseases, and we previously provided strong evidence that these genetic variations contribute significantly to differences in susceptibility and clinical outcomes of invasive group A Streptococcus (GAS) patients, including sepsis and necrotizing soft tissue infections (NSTIs). The goal of the present study was to investigate how genetic variations and sex differences among four commonly used mouse strains contribute to variation in severity, manifestations, and outcomes of NSTIs. DBA/2J mice were more susceptible to NSTIs than C57BL/6J, BALB/c, and CD-1 mice, as exhibited by significantly greater bacteremia, excessive dissemination to the spleen, and significantly higher mortality. Differences in the sex of the mice also contributed to differences in disease severity and outcomes: DBA/2J female mice were relatively resistant compared to their male counterparts. However, DBA/2J mice exhibited minimal weight loss and developed smaller lesions than did the aforementioned strains. Moreover, at 48 h after infection, compared with C57BL/6J mice, DBA/2J mice had increased bacteremia, excessive dissemination to the spleen, and excessive concentrations of inflammatory cytokines and chemokines. These results indicate that variations in the host genetic context as well as sex play a dominant role in determining the severity of and susceptibility to GAS NSTIs.

Nutritional management in critically ill trauma patients is challenging

Background The physiological stress following major trauma in critical illness leads to rapid malnutrition and provision of optimal nutritional support in these circumstances can be challenging. Case report We present a complex trauma case where relatively aggressive nutritional support failed to minimise weight loss. Conclusion Nutritional support plays an integral role in the care of critically ill major trauma patients and needs to be continuously monitored in the subacute and rehabilitation phase.

Limited-Stage Small-Cell Lung Cancer: An Age Limit for Combined Modality Therapy?

Limited-Stage Small-Cell Lung Cancer: An Age Limit for Combined Modality Therapy?

Rare Case of Acute Pancreatitis With Normal Lipase Level

Introduction: Acute pancreatitis can be diagnosed with one of the following criteria: clinical symptoms of pancreatitis, radiological findings and/or elevated serological markers for pancreatitis. However, there is very limited literature on acute pancreatitis with normal lipase level. Case description: 64 yo female with h/o hypertension and chronic back pain, presented with acute onset severe non-radiating epigastric pain, nausea and vomiting. She was not a smoker but drinks 4-5 glasses of hard liquor once every week. Significant examination findings: BP 153/100 mmHg, HR irregularly irregular, severe epigastric tenderness with no guarding or rigidity. Significant lab results included: lipase 30 U/L, calcium level 9.9 mg/dl, WBC count 17500 thou/uL, glucose 132 mg/dl, total bilirubin 1.7 mg/dl, direct bilirubin 0.5 mg/dl, normal transaminases. The liver function test normalized on day 2. CT abdomen and pelvis with IV contrast: acute edematous pancreatitis with extensive atherosclerotic plaques with 30% narrowing in the proximal SMA and no gall stones. IgG-713 mg/dl, IgG4- 45.9 mg/dl (normal). On admission in the ED, she was also found to be in atrial fibrillation with RVR (175/min) and further tests for causes of atrial fibrillation revealed elevated free T4 level- 3.44 and suppressed TSH- 0.01- primary hyperthyroidism. She had no symptoms of hyperthyroidism except for minimal weight loss. She was improved with conservative management and was discharged. Discussion: There are very few cases of acute pancreatitis with normal lipase level in literature. Lipase level has 55-100% sensitivity and 94-100% negative predictive value in the diagnosis of acute pancreatitis. Whereas contrast enhanced CT scan has 92% sensitivity and 100% specificity in diagnosing pancreatitis. Autoimmune pancreatitis should be a consideration in patients with normal lipase level and checking IgG4 level can be of value. When negative in such patients like our patient, clinical and imaging findings can suffice the diagnosis of acute pancreatitis.Figure 1

Investigating the structure and biocompatibility of niobium and titanium oxides as coatings for orthopedic metallic implants

Applying sol gel based coatings to orthopedic metallic implant materials can significantly improve their properties and lifespan in vivo. For this work, niobium (Nb2O5) and titanium (TiO2) oxides were prepared via solution processing in order to determine the effect of atomic arrangement (amorphous/crystalline) on bioactivity. Thermal evaluation on the synthesized materials identified an endotherm for Nb2O5 at 75°C with 40% weight loss below 400°C, and minimal weight loss between 400 and 850°C. Regarding TiO2 an endotherm was present at 92°C with 25% weight loss below 400°C, and 4% between 400 and 850°C. Phase evolution was determined using High Temperature X-ray Diffraction (HT-XRD) where amorphous-Nb2O5 (450°C), hexagonal-Nb2O5 (525°C), orthorhombic-Nb2O5 (650°C), amorphous-TiO2 (275°C) and tetragonal TiO2 (500°C) structures were produced. Simulated body fluid (SBF) testing was conducted over 1, 7 and 30days and resulted in positive chemical and morphological changes for crystalline Nb2O5 (525°C) and TiO2 (500°C) after 30days of incubation. Rod-like CaP deposits were observed on the surfaces using Scanning Electron Microscopy (FE-SEM) and Grazing Incidence-X-ray Diffraction (GI-XRD) shows that the deposits were X-ray amorphous. Cell viability was higher with the TiO2 (122%) samples when compared to the growing cell population while Nb2O5 samples exhibited a range of viability (64–105%), partially dependent on materials atomic structure.

Abstract 2592: Anti-tumor activity of icotinib (BPI-2009H) and BPI-403B in the BxPC-3 pancreatic cancer cell line

Abstract Introduction: The purpose of this research was to investigate the anti-tumor effect of BPI-2009H and BPI-403B, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in the human pancreatic cancer cell lines BxPC-3 and Panc-1, in vitro and in vivo and determine the maximum tolerated dose (MTD) of the compound in mouse. Experimental Design: In vitro, human pancreatic cancer cell lines, BxPC-3 and Panc-1 were exposed to varying concentrations of BPI-2009H and BPI-403B, the concentration of compound required to inhibit growth by fifty percent (IC50) was estimated. In vivo, tumor growth inhibition of low dose BPI-2009H was tested in xenografted nude mice with BxPC-3 pancreatic cancer tumors. The maximum tolerated dose (MTD) was established via oral administration of low, mid and high doses to Harlan mice of both BPI-2009H and BPI-403B. Upon determination of the MTD, the in vivo efficacy of high dose BPI-2009H was evaluated via tumor growth inhibition study on xenografted nude mice with BxPC-3 pancreatic cancer tumors. Results: BPI-2009H, as a single agent, inhibited the growth of BxPC-3 cells in a dose dependent manner, with a relative IC50 value of 25.8 μM. BPI-403B, as a single agent, inhibited growth of BxPC-3 cells in a dose dependent manner as well, with a relative IC50 value of 2.7 μM. BPI-2009H and BPI-403B were tested up to 50μM in Panc-1 cells with no apparent effect at the upper limit of the study for either of the compounds. In vivo, the mice treated with BPI-403B demonstrated a statistically significant tumor growth delay, 14.3 days. 20% of the mice experienced tumor regression. The compound was well tolerated with minimal body weight loss. At low doses, BPI-2009H did not show any statistically significant tumor growth delay, but upon increasing the dose to the MTD, significant signs of anticancer activity was demonstrated, with an increase in tumor growth delay. Conclusions: The in vitro and in vivo findings show that both BPI-2009H and BPI-403B have antiproliferative effects against BxPC-3 pancreatic cancer cells. These compounds are both well tolerated and may prove to be an alternative option of EGFR-TKI to erlotinib treatment in pancreatic cancer cases. Citation Format: Victoria Lynn Wilde, Don Zhang, Jirong Peng, Michael A. Green, Michael N. Greco, Michael Costanzo. Anti-tumor activity of icotinib (BPI-2009H) and BPI-403B in the BxPC-3 pancreatic cancer cell line. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2592. doi:10.1158/1538-7445.AM2015-2592

Effect of short-term weight loss on mental stress-induced cardiovascular and pro-inflammatory responses in women

Epidemiologic evidence links psychosocial stress with obesity but experimental studies examining the mechanisms that mediates the effect of stress on adiposity are scarce. The aim of this study was to investigate whether changes in adiposity following minimal weight loss affect heightened stress responses in women, and examine the role of the adipokine leptin in driving inflammatory responses. Twenty-three overweight or obese, but otherwise healthy, women (M age = 30.41 ± 8.0 years; BMI = 31.9 ± 4.1 kg/m2) completed standardized acute mental stress before and after a 9-week calorie restriction program designed to modify adiposity levels. Cardiovascular (blood pressure and heart rate) and inflammatory cytokines (leptin and interleukin-6; IL-6) responses to mental stress were assessed several times between baseline and a 45-min post-stress recovery period. There were modest changes in adiposity measures while the adipokine leptin was markedly reduced (−27%) after the intervention. Blood pressure reactivity was attenuated (−3.38 ± 1.39 mmHg) and heart rate recovery was improved (2.07 ± 0.96 Bpm) after weight loss. Blood pressure responses were inversely associated with changes in waist to hip ratio post intervention. Decreased levels of circulating leptin following weight loss were inversely associated with the IL-6 inflammatory response to stress (r = −0.47). We offered preliminary evidence suggesting that modest changes in adiposity following a brief caloric restriction program may yield beneficial effect on cardiovascular stress responses. In addition, reductions in basal leptin activity might be important in blunting pro-inflammatory responses. Large randomized trials of the effect of adiposity on autonomic responses are thus warranted.

A rare case of clear cell carcinoma of the breast evaluated by 18F-FDG PET/CT

Stage IIIB includes patients with T4, any N, M0, and any T, N3, M0. Surgery may be indicated only for carefully selected T4N0M0 patients with or without neoadjuvant chemotherapy or chemoradiotherapy. Patients with N3 lymph node involvement are not considered as surgical candidates. For patients with unresectable disease, good performance score, and minimal weight loss, treatment with combined chemotherapy and radiotherapy has resulted in better survival than treatment with radiotherapy alone. Multiple daily fractions of radiotherapy have not resulted in improved survival compared with standard fractionation once daily. Concurrent chemoradiotherapy appears to be associated with improved survival compared with sequential chemotherapy and radiotherapy. Treatment of stage IIIB due to malignant pleural effusion is addressed in the section that deals with stage IV disease.

Efficacy of antimicrobial pullulan-based coating to improve internal quality and shelf-life of chicken eggs during storage.

There has been a growing interest in the use of natural materials as a delivery mechanism for antimicrobials and coatings in foods. The aim of the present study was to evaluate the effectiveness of pullulan coatings to improve internal quality and shelf-life of fresh eggs during 10 wk of storage at 25 and 4 °C. Three treatments of eggs were evaluated as follows; non-coated (control; C), coated with pullulan (P), and coated with pullulan containing nisin (N). The effects of the pullulan coatings on microbiological qualities, physical properties, and freshness parameters were investigated and compared with non-coated eggs. For non-coated eggs, as storage time increased, yolk index, albumen index, and Haugh unit value decreased and weight loss increased. However, pullulan coatings (P or N) minimized weight loss (<1.5%) and preserved the albumen and yolk quality of eggs (with a final B grade) 3 wk longer than non-coated eggs at 25 °C. At 4 °C, both P- and N-coated eggs went from AA to A grade after 9 wk and maintained the grade for 10 wk (4 wk longer than that of non-coated eggs). This study is the first to demonstrate that pullulan coatings can preserve the internal quality, prolong the shelf-life, and minimize weight loss of fresh eggs.

Weight reduction after severe brain injury: a challenge during the rehabilitation course.

There is a paucity of studies, which have described malnutrition in patients with acquired brain injury (ABI) across etiology. This study describes weight change, malnutrition, and potential associations in patients with ABI at a subacute inpatient rehabilitation hospital. This is a descriptive cohort study. Ninety-eight patients were admitted in a 3-month period, of whom n = 76 met inclusion criteria. The Malnutrition Universal Screening Tool was used for categorizing patients according to risk of malnutrition. Patients had experienced weight loss of 5.59% ± 5.89% (p < .001) at admission at the rehabilitation hospital, and patients with traumatic brain injury had experienced a greater weight loss than patients with stroke (p < .01). Thirty percent of patients were at high risk for malnutrition, and 52% of these patients received enteral or parenteral nutrition at admission at the rehabilitation hospital. No association was found between risk of malnutrition and severity of injury, complications, functional outcome, or length of stay. RESULTS underline the importance that nurses, especially in acute care, adhere to clinical guidelines to minimize weight loss. Special attention should be on patients with traumatic brain injury. Weight gain in the following course of rehabilitation may facilitate positive rehabilitation outcomes.