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Sufficient number of probiotics in product are required to confer its health benefits to consumers. However, the viability of probiotics can detriment during processing. An approach of emulsion method to provide a physical barrier of probiotics against adverse environmental conditions has received considerable level of interest. Various matrices were used to emulsified probiotics in food product. However, the usage of water/oil/water (W1/O/W2) base to emulsify probiotics for beverages application remained scarce. Thus, this study was to determine the suitability of using W1/O/W2 base to emulsify Lactobacillus plantarum NBRC 3070 to be incorporated into pasteurized soursop juice (Annona muricata L.). Hence, emulsion efficiency (EE%) of L. plantarum NBRC 3070 in W1/O/W2 base, the stability of emulsified cells (log10 CFU/mL) and physicochemical changes of soursop juice (pH, titratable acidity, total soluble solid, viscosity, colour, sensory) during storage were determined. In this study, emulsified L. plantarum NBRC 3070 (109 CFU/mL) was incorporated into soursop juice and stored at 4°C for four weeks. Results obtained with 86.02% ± 0.69 emulsion efficiency (%) of L. plantarum NBRC 3070. Insignificant changes (p>0.05) were notified from viability of emulsified probiotics, pH, titratable acidity and viscosity during storage. Meanwhile, satisfactory parameters (colour, sensory and coliform counts) were obtained at the satisfactory level. As for the conclusion, W1/O/W2 base was able to maintain the survivability of L. plantarum NBRC 3070 in soursop juice during storage and quality of the product. Optimization of parameters such as water/oil compositions and storage time can be further explored to enhance product quality.

This work presents a characteristic study of Cylindrical Surrounding Gate Nanowire Field Effect Transistor for two different channel material (Si, GaAs). The device simulation has been carried out both in Semi-classical regime using the Drift-Diffusion method and quantum regime using the Self-Consistent Non-Equilibrium Green's Function approach. The necessary process flow for modeling the proposed device emphasizing the comparative benefits of different channel materials has been described in this paper. Simulation results show that Si device exhibits better threshold voltage and subthreshold swing but GaAs device is better in on-to-off state current ratio and drain induced barrier lowering (DIBL).

Clinical breast cancers in which at least 10% of cells express the estrogen receptor are labeled as “ER positive.” First line therapy for these patients is typically continuous administration of anti-estrogen drugs at maximum tolerated dose (MTD) until progression. In the vast majority of patients, resistance to hormone therapy evolves in the breast cancer cells within 2 years leading to treatment failure and tumor progression. In prior studies, we have demonstrated continuous application of MTD chemotherapy results in evolutionary dynamics (termed “competitive release”) that accelerates proliferation of treatment-resistance populations. In contrast, evolution-informed application of treatment reduces drug administration to maintain substantial populations of therapy-sensitive cells to reduce proliferation of resistant phenotypes. Prior pre-clinical and clinical studies have shown this strategy can delay or prevent proliferation of resistant cells and prolong time to progression (TTP). We hypothesize that similar dynamics may be observed in hormonal therapy of ER+ breast cancers. Here we address two important dynamics. First, we consider a clinical scenario in which symptoms are sufficiently severe or life-threatening to require rapid and substantial tumor reduction. Can this be achieved while retaining evolutionary dynamics to subsequently delay proliferation of resistance? A second, related question is defining the cost of resistance to anti-estrogen therapy. Here, we investigated the evolutionary dynamics of resistance to anti-estrogen therapy using ER+ MCF-7 orthotropic xenografts treated with both continuous Tamoxifen as well as cycles in which estrogen stimulation is combined with estrogen suppression. As expected, continuous administration of anti-estrogen drugs successfully suppressed tumor growth. However we found that brief interruptions in drug administration permitted equal tumor control while administering up to 50% less drug and maintaining cell phenotypes that retained high levels of ER expression and lower levels of MDR1 expression. In follow-on experiments combining hormonal and chemo-therapies; we obtained similar tumor control to hormonal therapy alone but with more necrosis and significantly lower ER expression in the surviving population.

The aim of this study was to develop self-report and clinician-rated versions of an insight scale that would be easy to administer, sensitive to small changes, and inclusive of the core dimensions of clinical insight into psychosis. Ten-item self-report (VAGUS-SR) and five-item clinician-rated (VAGUS-CR) scales were designed to measure the dimensions of insight into psychosis and evaluated in 215 and 140 participants, respectively (www.vagusonline.com). Tests of reliability and validity were performed. Both the VAGUS-SR and VAGUS-CR showed good internal consistency and reliability. They demonstrated good convergent and discriminant validity. Both versions were strongly correlated with one another and with the Schedule for the Assessment of Insight and Birchwood Insight Scale. Exploratory factor analyses identified three possible latent components of insight. The VAGUS-CR and VAGUS-SR are valid, reliable and easy to administer. They are build on previous insight scales with separate clinician-rated and self-report versions. The VAGUS-SR exhibited a multidimensional factor structure. Using a 10-point Likert scale for each item, the VAGUS has the capacity to detect small, temporally sensitive changes in insight, which is essential for intervention studies with neurostimulation or rapidly acting medications.

I have worked in mental healthcare with people living with serious mental illness for almost 12 years, and I am in my third year of doctoral training in clinical psychology. My brother has lived with “schizophrenia” for over 10 years. I write from the perspectives of a training clinician and a family member – a family member who did not realize how clinically insensitive her experiences with her brother were until now. This is an essay of humility and hope.

Conventional cancer treatment strategies assume that maximum patient benefit is achieved through maximum killing of tumor cells. However, by eliminating the therapy-sensitive population, this strategy accelerates emergence of resistant clones that proliferate unopposed by competitors-an evolutionary phenomenon termed "competitive release." We present an evolution-guided treatment strategy designed to maintain a stable population of chemosensitive cells that limit proliferation of resistant clones by exploiting the fitness cost of the resistant phenotype. We treated MDA-MB-231/luc triple-negative and MCF7 estrogen receptor-positive (ER(+)) breast cancers growing orthotopically in a mouse mammary fat pad with paclitaxel, using algorithms linked to tumor response monitored by magnetic resonance imaging. We found that initial control required more intensive therapy with regular application of drug to deflect the exponential tumor growth curve onto a plateau. Dose-skipping algorithms during this phase were less successful than variable dosing algorithms. However, once initial tumor control was achieved, it was maintained with progressively smaller drug doses. In 60 to 80% of animals, continued decline in tumor size permitted intervals as long as several weeks in which no treatment was necessary. Magnetic resonance images and histological analysis of tumors controlled by adaptive therapy demonstrated increased vascular density and less necrosis, suggesting that vascular normalization resulting from enforced stabilization of tumor volume may contribute to ongoing tumor control with lower drug doses. Our study demonstrates that an evolution-based therapeutic strategy using an available chemotherapeutic drug and conventional clinical imaging can prolong the progression-free survival in different preclinical models of breast cancer.

Cognitive adaptation training (CAT) is a home-based, manualized treatment that utilizes environmental supports to improve target behaviors and functional outcomes in persons with schizophrenia. Although clinical trials have shown CAT to be effective across functional, clinical, and treatment adherence domains, when the intervention is withdrawn clients experience significant declines. The aim of the current study was to test a modified version of CAT, which decreases the duration of intensive CAT intervention while utilizing ongoing case management-supported CAT to maintain the fundamental components of the treatment. Twenty-three people participated in an outcome study of the modified version of CAT, evaluating improvements after 4 months of CAT specialist intervention and after an additional 5 months of case manager support. Analysis revealed significant improvements in adaptive functioning, psychiatric symptomatology, and goal attainment, which were maintained throughout case management follow-up. This suggests that an intervention that has previously demonstrated good functional outcomes in randomized trials might sustain its impacts in an abbreviated format with support from existing case managers.

A woman in her midtwenties with a history of major depressive disorder and a recent major depressive episode with mood-congruent psychotic features died by suicide. Two weeks before her death, she demonstrated exceptional elevations on the nondisplay of imperfection factor of Hewitt and Flett’s Perfectionistic Self-Presentation Scale. Perfectionism and especially perfectionistic self-presentation have been strongly associated with suicide across several populations, accounting for unique variance in suicidality beyond depression and hopelessness. Yet interpersonal facets of perfectionism are not recognized as clinical risk factors for suicide. There is also a paucity of research on perfectionism in relation to psychotic symptoms. This case account illustrates the role of perfectionistic self-presentation in suicides that occur seemingly without warning and, to our knowledge, this is the first examination of perfectionistic self-presentation and suicide in a case where psychotic features occurred. This study, though single case-based, draws attention to perfectionism and perfectionistic self-presentation and their potential roles in suicide, especially when accompanied by other risk factors. Future research in this area may elucidate the role of perfectionism in suicide, singularly and in the context of a comprehensive clinical risk assessment, demonstrating whether perfectionism confers information about suicide risk beyond known clinical risk factors.

Introduction: Disseminated cancers are typically treated with the highest possible dose of drug (i.e. maximum tolerated dose) to achieve the goal of killing as many tumor cells as possible. However, these therapies eventually fail due to emergence of resistant clones. We have predicted, using mathematical models of Darwinian dynamics, that treatment regimens that adapt the dosing to the tumor spatial variability and tumor microenvironment, can retard the emergence of chemoresistance. Here we present an evolutionary-guided treatment strategy (Adaptive Therapy, AT) designed to maintain stable chemosensitive populations while limiting the proliferation of chemoresistant clones by exploiting the fitness cost of the resistant phenotype. We also evaluated how this novel treatment strategy modifies tumor vascularity. Methods: Four cohorts (composed by 12, 11, 13, and 10 mice, respectively) of nude mice were injected with 10x106 MDA-MB-231 (triple-negative breast cancer) cells in the mammary fat pad. Control animals didn't receive any treatment. Mice under standard therapy received 20mg/kg of Tamoxifen twice per week for a total of 5 times. We defined two different Tamoxifen AT algorithms (Table 1), under which AT mice were treated. Table 1.Adaptive Therapy treatment algorithmsAT-1Initial Dose = 20 mg/kg (highest dose)> If VT(n)≤ .8*VT(n-1) ->Dose decreased by 50%> If VT(n)≥ 1.2*VT(n-1) ->Dose increased by 50%> If the tumor volume is within 20% range, we will apply same dose as previous dose.Lower Limit: 150mm3 and skip the doseAT-2Starting dose = 15 mg/kg> If VT(n)≥ 1.25*VT(n-2) ->Dose = 15 mg/kg> If VT(n) < 1.25*VT(n-2) ->Skip Dose When the tumors achieve the volume of, approximately 300 mm3, MRI T2 and Diffusion Weighted acquisitions were performed on a horizontal Agilent ASR 310 7T scanner, with 205/120/HDS gradients and 310 mm bore to determine volume and cellularity, respectively. Thereafter, dynamic contrast enhanced (DCE-) MRI was preformed following bolus of 0.1mmol/kg Magnevist to assess distribution of blood flow. Images were processed with different in-house developed MATLAB scripts to obtain reliable information from these images. At the end of the monitoring time, tumors were collected and processed for H&E and CD31 immunohistochemistry staining to study the viable and necrotic tissue, and vessel presence, respectively. The slides were examined using the Aperio ScanScope XT microscope. Using different selected slides, an algorithm was built in order to analyze all tissue samples (software Spectrum Version 10.2.5.2352, Aperio Technologies with a pixel-wise resolution. Results and Discussion: Tumor growth was monitored during the treatment period using the MRI techniques previously described. The AT treatment algorithm has been modified to fine tune the dose and scheduling based on tumor volume. Among these three protocols (2 AT and one ST), AT-1 resulted in the most significant cancer control. AT-1 protocol was able to maintain tumors at a small size for >120 days. Also, AT-1 has demonstrated to decrease the percent tumor necrosis (data not shown), and increase vascular density. New experiments and data analysis are currently undergoing in order to get more information and a deeper insight on how the AT can benefit the in-vivo cancer treatment. Conclusion: In summary, initial results demonstrate that AT, guided by MRI measurement of tumor volume, can maintain a stable small tumor burden with prolonged progression free survival compared to standard high dose therapy. Also, AT is able to maintain the lower necrotic volume and the higher vessel density, which, in addition with the tumor volume, was correlated with tumor stabilization. Citation Format: Pedro M. Enriquez-Navas, Jonathan Wojtkowiak, Epi Ruiz, Sabrina Hassan, Robert J. Gillies, Robert A. Gatenby. Adaptive therapy modifies tumor vascularity. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr B11.

CONTEXT: The early postpartum period is a time of high risk for a major depressive episode (or postpartum depression), with a prevalence of 13%. During this time, there is a heightened vulnerability for low mood because postpartum blues is common. Severe postpartum blues can herald the onset of postpartum depression. The neurobiological mechanisms to explain postpartum blues and the high risk for the onset of postpartum depression in the first few weeks after delivery are unclear. Estrogen levels drop 100- to 1000-fold during the first 3 to 4 days postpartum, and changes in estrogen levels have an inverse relationship with monoamine oxidase A (MAO-A) density. However, MAO-A levels have never been measured in the early postpartum period. OBJECTIVE: To determine whether brain MAO-A binding is elevated in the early postpartum period. DESIGN: Case-control study. SETTING: Tertiary care academic psychiatric hospital in Toronto, Ontario, Canada. PARTICIPANTS: Fifteen healthy women who were 4 to 6 days postpartum and 15 healthy women who had not recently been postpartum underwent carbon 11-labeled harmine positron emission tomography scanning. All women were nonsmoking and medication free. MAIN OUTCOME MEASURE: MAO-A total distribution volume, an index of MAO-A density, was measured in prefrontal cortex, anterior cingulate cortex, anterior temporal cortex, thalamus, dorsal putamen, hippocampus, and midbrain. RESULTS: MAO-A total distribution volume was significantly elevated (mean, 43%) throughout all analyzed brain regions during the early postpartum period. CONCLUSIONS: Elevated MAO-A levels in the early postpartum period can be interpreted as a marker of a monoamine-lowering process that contributes to the mood change of postpartum blues. Rather than a purely psychosocial model, we propose a neurobiological model of estrogen decline, followed by elevated MAO-A binding, low mood, and subsequently a period of high risk for major depressive episodes. Our model has important implications for preventing postpartum depression and for developing therapeutic strategies that target or compensate for elevated MAO-A levels during postpartum blues.