Cue-Reactors: Individual Differences in Cue-Induced Craving after Food or Smoking Abstinence

Background: Pavlovian conditioning plays a critical role in both drug addiction and binge eating. Recent animal research suggests that certain individuals are highly sensitive to conditioned cues, whether they signal food or drugs. Are certain humans also more reactive to both food and drug cues? Methods: We examined cue-induced craving for both cigarettes and food, in the same individuals (n = 15 adult smokers). Subjects viewed smoking-related or food-related images after abstaining from either smoking or eating. Results: Certain individuals reported strong cue-induced craving after both smoking and food cues. That is, subjects who reported strong cue-induced craving for cigarettes also rated stronger cue-induced food craving. Conclusions: In humans, like in nonhumans, there may be a ‘‘cue-reactive’ ’ phenotype, consisting of individuals who are highly sensitive to conditioned stimuli. This finding extends recent reports from nonhuman studies. Further understanding this subgroup of smokers may allow clinicians to individually tailor therapies for smoking cessation

Extracellular Matrix Aggregates from Differentiating Embryoid Bodies as a Scaffold to Support ESC Proliferation and Differentiation

Embryonic stem cells (ESCs) have emerged as potential cell sources for tissue engineering and regeneration owing to its virtually unlimited replicative capacity and the potential to differentiate into a variety of cell types. Current differentiation strategies primarily involve various growth factor/inducer/repressor concoctions with less emphasis on the substrate. Developing biomaterials to promote stem cell proliferation and differentiation could aid in the realization of this goal. Extracellular matrix (ECM) components are important physiological regulators, and can provide cues to direct ESC expansion and differentiation. ECM undergoes constant remodeling with surrounding cells to accommodate specific developmental event. In this study, using ESC derived aggregates called embryoid bodies (EB) as a model, we characterized the biological nature of ECM in EB after exposure to different treatments: spontaneously differentiated and retinoic acid treated (denoted as SPT and RA, respectively). Next, we extracted this treatment-specific ECM by detergent decellularization methods (Triton X-100, DOC and SDS are compared). The resulting EB ECM scaffolds were seeded with undifferentiated ESCs using a novel cell seeding strategy, and the behavior of ESCs was studied. Our results showed that the optimized protocol efficiently removes cells while retaining crucial ECM and biochemical components. Decellularized ECM from SPT EB gave rise to a more favorable microenvironment for promoting ESC attachment, proliferation, and early differentiation, compared to native EB and decellularized ECM from RA EB. These findings suggest that various treatment conditions allow the formulation of unique ESC-ECM derived scaffolds to enhance ESC bioactivities, including proliferation and differentiation for tissue regeneration applications. © 2013 Goh et al

Massless D-strings and moduli stabilization in type I cosmology

We consider the cosmological evolution induced by the free energy F of a gas of maximally supersymmetric heterotic strings at finite temperature and weak coupling in dimension D>=4. We show that F, which plays the role of an effective potential, has minima associated to enhanced gauge symmetries, where all internal moduli can be attracted and dynamically stabilized. Using the fact that the heterotic/type I S-duality remains valid at finite temperature and can be applied at each instant of a quasi-static evolution, we find in the dual type I cosmology that all internal NS-NS and RR moduli in the closed string sector and the Wilson lines in the open string sector can be stabilized. For the special case of D=6, the internal volume modulus remains a flat direction, while the dilaton is stabilized. An essential role is played by light D-string modes wrapping the internal manifold and whose contribution to the free energy cannot be omitted, even when the type I string is at weak coupling. As a result, the order of magnitude of the internal radii expectation values on the type I side is (lambda_I alpha')^{1/2}, where lambda_I is the ten-dimensional string coupling. The non-perturbative corrections to the type I free energy can alternatively be described as effects of "thermal E1-instantons", whose worldsheets wrap the compact Euclidean time cycle.Comment: 39 pages, 1 figur

Is Gly16Arg β₂ Receptor Polymorphism Related to Impulse Oscillometry in a Real-Life Asthma Clinic Setting?

PURPOSE: We evaluated whether Gly16Arg beta2-receptor genotype relates to impulse oscillometry (IOS) in a real-life clinic setting. METHODS: Patients with persistent asthma taking inhaled corticosteroid ± long-acting beta-agonist (ICS ± LABA) were evaluated. We compared genotype groups comprising either no Arg copies (i.e. GlyGly) versus one or two Arg copies (i.e. ArgArg or ArgGly). IOS outcomes included total airway resistance at 5 Hz (R5), central airway resistance at 20 Hz (R20), peripheral airway resistance (R5–R20), reactance at 5 Hz, area under reactance curve (AX) and resonant frequency (RF). In addition, we recorded ACQ-5 and salbutamol use. RESULTS: One hundred and twelve ICS-treated asthmatic patients (mean ICS dose 1238 µg/day), mean age 43 years, ACQ 2.34, FEV1 82 %, R5 177 % were identified—89 were also taking LABA. 61 patients were GlyGly, while 14 were ArgArg and 37 were ArgGly. There were no significant differences in IOS outcomes, ACQ or salbutamol use between the genotypes. The allelic risk (as odds ratio) for less well-controlled asthma (as ACQ > 1.5) was 1.1 (95 % CI 0.72–1.68) in relation to each Arg copy with a corresponding odds ratio for abnormal R5–R20 > 0.07kPA/l.s being 0.91 (95 % CI 0.57–1.44). 71 % of patients had an ACQ > 1.5 in the GlyGly group, versus 67 % in GlyArg/ArgArg group, with corresponding figures for abnormal R5–R20 > 0.07 kPa/l.s being 69 versus 73 %. CONCLUSION: In a real-life clinic setting for patients with poorly controlled persistent asthma taking ICS ± LABA, we found no evidence of any relationship of Gly16Arg to IOS, ACQ or salbutamol use

Epidemiology and patterns of care for invasive breast carcinoma at a community hospital in Southern India

<p>Abstract</p> <p>Background</p> <p>Breast cancer incidence in India is on rise. We report epidemiological, clinical and survival patterns of breast cancer patients from community perspective.</p> <p>Methods</p> <p>All breast cancer patients treated at this hospital from July 2000 to July 2005 were included. All had cytological or histological confirmation of breast cancer. TNM guidelines for staging and Immunohistochemistry to assess the receptor status were used. Either lumpectomy with axillary lymph node dissection or Modified radical mastectomy (MRM) was done for operable breast cancer, followed by 6 cycles of adjuvant chemotherapy with FAC or CMF regimens to patients with pT >1 cm or lymph node positive or estrogen receptor negative and radiotherapy to patients after breast conservation surgery, pT size > 5 cm, 4 or more positive nodes and stage IIIB disease. Patients with positive Estrogen receptor or Progesterone receptor were advised Tamoxifene 20 mg per day for 3 years. Descriptive analysis was performed. Independent T test and Chi-square test were used. Overall survival time was computed by Kaplan – Meier method.</p> <p>Results</p> <p>Of 1488 cancer patients, 122 (8.2%) had breast cancer. Of 122 patients, 96.7% had invasive breast carcinoma and 3.3% had sarcoma. 94% came from the rural and semi urban areas. Premenopausal women were 27%. The median age was 50 years. Stage I-6.8%, II-45.8%, III-22%, IV-6.8%, Bilateral breast cancer – 2.5%. The mean pT size was 3.9 cm. ER and PR were positive in 31.6% and 28.1% respectively. MRM was done in 93.8%, while 6.3% patients underwent breast conservation surgery. The mean of the lymph nodes dissected were 3. CMF and FAC regimens were used in 48.8% and 51.2% of patients respectively. FAC group were younger than the CMF group (43.6 yr vs. 54 yrs, P = 0.000). Toxicities were more in FAC than CMF group, alopecia (100% vs. 26.2%), grade2 or more emesis (31.8% vs. 9.2%), grade2 or more fatigue (40.9% vs.19%), anemia (43.1% vs. 16.6%). Median Survival for the cohort was 50.8 months. ER positive patients had better median survival (P = 0.05).</p> <p>Conclusion</p> <p>MRM was the most frequent surgical option. CMF and FAC showed equivalent survival. FAC chemotherapy was more toxic than CMF. ER positive tumors have superior survival. Overall 3 year survival was 70 percent</p

A mouse model of sitosterolemia: absence of Abcg8/sterolin-2 results in failure to secrete biliary cholesterol

BACKGROUND: Mutations in either of two genes comprising the STSL locus, ATP-binding cassette (ABC)-transporters ABCG5 (encoding sterolin-1) and ABCG8 (encoding sterolin-2), result in sitosterolemia, a rare autosomal recessive disorder of sterol trafficking characterized by increased plasma plant sterol levels. Based upon the genetics of sitosterolemia, ABCG5/sterolin-1 and ABCG8/sterolin-2 are hypothesized to function as obligate heterodimers. No phenotypic difference has yet been described in humans with complete defects in either ABCG5 or ABCG8. These proteins, based upon the defects in humans, are responsible for regulating dietary sterol entry and biliary sterol secretion. METHODS: In order to mimic the human disease, we created, by a targeted disruption, a mouse model of sitosterolemia resulting in Abcg8/sterolin-2 deficiency alone. Homozygous knockout mice are viable and exhibit sitosterolemia. RESULTS: Mice deficient in Abcg8 have significantly increased plasma and tissue plant sterol levels (sitosterol and campesterol) consistent with sitosterolemia. Interestingly, Abcg5/sterolin-1 was expressed in both liver and intestine in Abcg8/sterolin-2 deficient mice and continued to show an apical expression. Remarkably, Abcg8 deficient mice had an impaired ability to secrete cholesterol into bile, but still maintained the ability to secrete sitosterol. We also report an intermediate phenotype in the heterozygous Abcg8+/- mice that are not sitosterolemic, but have a decreased level of biliary sterol secretion relative to wild-type mice. CONCLUSION: These data indicate that Abcg8/sterolin-2 is necessary for biliary sterol secretion and that loss of Abcg8/sterolin-2 has a more profound effect upon biliary cholesterol secretion than sitosterol. Since biliary sitosterol secretion is preserved, although not elevated in the sitosterolemic mice, this observation suggests that mechanisms other than by Abcg8/sterolin-2 may be responsible for its secretion into bile

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Disruption of the acetate kinase (ack) gene of Clostridium acetobutylicum results in delayed acetate production

In microorganisms, the enzyme acetate kinase (AK) catalyses the formation of ATP from ADP by de-phosphorylation of acetyl phosphate into acetic acid. A mutant strain of Clostridium acetobutylicum lacking acetate kinase activity is expected to have reduced acetate and acetone production compared to the wild type. In this work, a C. acetobutylicum mutant strain with a selectively disrupted ack gene, encoding AK, was constructed and genetically and physiologically characterized. The ack− strain showed a reduction in acetate kinase activity of more than 97% compared to the wild type. The fermentation profiles of the ack− and wild-type strain were compared using two different fermentation media, CGM and CM1. The latter contains acetate and has a higher iron and magnesium content than CGM. In general, fermentations by the mutant strain showed a clear shift in the timing of peak acetate production relative to butyrate and had increased acid uptake after the onset of solvent formation. Specifically, in acetate containing CM1 medium, acetate production was reduced by more than 80% compared to the wild type under the same conditions, but both strains produced similar final amounts of solvents. Fermentations in CGM showed similar peak acetate and butyrate levels, but increased acetoin (60%), ethanol (63%) and butanol (16%) production and reduced lactate (−50%) formation by the mutant compared to the wild type. These findings are in agreement with the proposed regulatory function of butyryl phosphate as opposed to acetyl phosphate in the metabolic switch of solventogenic clostridia

Exploratory Analysis in Learning Analytics

This article summarizes the methods, observations, challenges and implications for exploratory analysis drawn from two learning analytics research projects. The cases include an analysis of a games-based virtual performance assessment and an analysis of data from 52,000 students over a 5-year period at a large Australian university. The complex datasets were analyzed and iteratively modeled with a variety of computationally intensive methods to provide the most effective outcomes for learning assessment, performance management and learner tracking. The article presents the research contexts, the tools and methods used in the exploratory phases of analysis, the major findings and the implications for learning analytics research methods