Pickering emulsions based on food byproducts: A comprehensive study of soluble and insoluble contents.

HYPOTHESIS: Pickering emulsions can be produced using raw particles obtained from uncracked vegetal food byproducts as sole stabilizers. The complexity brought by these non-purified ingredients will be their strength since insoluble particles and soluble compounds shall display good complementary properties, at the interface and the continuous phase. EXPERIMENTS: Emulsions were monitored over a one-month storage as regards to oil droplet diameter as main indicator of stability. Then, two main studies were carried out: 1) on the whole powders (water binding capacity, dry matter and insoluble content, size and morphology); 2) on the soluble content (size, charge, pH, Brix degree, surface tension measurements). FINDINGS: All byproducts stabilized-emulsions were stable during storage. They display various oil droplet sizes with sugar beet < apple < oat. Direct observation of the oil-water interfaces showed adsorption of the solid particles, and some voids corresponding to soluble elements from the byproducts' powders. The latter displayed surface-active properties. The insoluble particles are driving the oil droplet size and protecting against coalescence while soluble compounds can also adsorb at the interface, lowering droplet size, and also act as thickening agents from the continuous phase (pectins). Vegetal byproducts are thus meta ingredients, able to stabilize clean-label emulsions.

Pleomorphic xanthoastrocytoma of childhood: MR imaging and diffusion MR imaging features.

BACKGROUND AND PURPOSE: Pleomorphic xanthoastrocytomas are rare astrocytic neoplasms of childhood and young adulthood. The purpose of this retrospective review was to evaluate MR imaging features of pediatric pleomorphic xanthoastrocytomas with an emphasis on diffusion MR imaging. MATERIALS AND METHODS: Review of the neuro-oncology data base revealed 11 pediatric patients (range, 4.7-16.1 years) with pleomorphic xanthoastroacytomas with 9 of these patients having preoperative MR imaging available. Six patients had preoperative diffusion MR imaging. Demographics, histopathology slides, conventional imaging characteristics (location, cystic component, hemorrhage, enhancement, vasogenic edema, inner table scalloping), and ADC metrics (mean tumor ADC and tumor to normal brain ADC ratio) were evaluated. RESULTS: Three pleomorphic xanthoastrocytomas had anaplastic features. Ten tumors were supratentorial. Two-thirds (6 of 9) of all tumors were either predominantly cystic or had cystic components, and three-fourths (6 of 8) of the supratentorial tumors had associated inner table scalloping. Seven of the 9 tumors had marked vasogenic edema (>10 mm). Mean tumoral ADC (n = 7) was 912 ± 219 × 10(-6) mm(2)/s (min-max: 617-1189). The tumor to normal brain ADC ratio was 1.14 ± 0.26 (min-max: 0.75-1.47). CONCLUSIONS: Pleomorphic xanthoastrocytoma should be entertained in the differential diagnosis of peripheral supratentorial tumors that appear during childhood. Cysts, inner table scalloping, and marked vasogenic edema are relatively frequent features. Relatively low ADC values and ADC ratios are not uncommon in pleomorphic xanthoastrocytoma.

Multilevel analysis of environmental Salmonella prevalences and management practices on 49 broiler breeder farms in four south-eastern States, USA.

A two-part serial survey of 49 broiler breeder farms was conducted in four south-eastern states: Arkansas, Alabama, Georgia and North Carolina. Broiler breeder farms from three to five broiler company complexes in each state were visited on two separate occasions to document management practices and perform environmental sampling for Salmonella prevalence estimation. Salmonella was detected in 88% of the broiler breeder houses that were sampled and was identified on all 49 farms enrolled. Many management characteristics were consistent across the different states and companies. Multilevel analysis was used to evaluate management characteristics as risk factors for Salmonella prevalence and to estimate the proportion of variance residing at the different hierarchical sampling levels. Management characteristics associated with increased Salmonella prevalence included treatment of the flock for any disease, having dusty conditions in the house, having dry conditions under the slats and walking through the house more than one time per day to pick-up dead birds. After adjusting for state as a fixed effect, the percentages of variance in Salmonella prevalence occurring at the complex, farm, visit, house and individual sample levels were 5.2%, 6.8%, 11.8%, 2.8% and 73.4%, respectively. The intraclass correlations for samples collected from the same house; for samples from different houses during the same visit; for samples from different visits to the same farm; and for samples from different farms in the same complex were as follows: 0.27, 0.24, 0.12 and 0.05, respectively.

The Type 1 Diabetes PhysioLab Platform: a validated physiologically based mathematical model of pathogenesis in the non-obese diabetic mouse.

Type 1 diabetes is an autoimmune disease whose clinical onset signifies a lifelong requirement for insulin therapy and increased risk of medical complications. To increase the efficiency and confidence with which drug candidates advance to human type 1 diabetes clinical trials, we have generated and validated a mathematical model of type 1 diabetes pathophysiology in a well-characterized animal model of spontaneous type 1 diabetes, the non-obese diabetic (NOD) mouse. The model is based on an extensive survey of the public literature and input from an independent scientific advisory board. It reproduces key disease features including activation and expansion of autoreactive lymphocytes in the pancreatic lymph nodes (PLNs), islet infiltration and beta cell loss leading to hyperglycaemia. The model uses ordinary differential and algebraic equations to represent the pancreas and PLN as well as dynamic interactions of multiple cell types (e.g. dendritic cells, macrophages, CD4+ T lymphocytes, CD8+ T lymphocytes, regulatory T cells, beta cells). The simulated features of untreated pathogenesis and disease outcomes for multiple interventions compare favourably with published experimental data. Thus, a mathematical model reproducing type 1 diabetes pathophysiology in the NOD mouse, validated based on accurate reproduction of results from multiple published interventions, is available for in silico hypothesis testing. Predictive biosimulation research evaluating therapeutic strategies and underlying biological mechanisms is intended to deprioritize hypotheses that impact disease outcome weakly and focus experimental research on hypotheses likely to provide insight into the disease and its treatment.

Occult metastatic lung carcinoma presenting as locally advanced uterine carcinosarcoma on positron emission tomography/computed tomography imaging.

Increasingly, positron emission tomography/computed tomography (PET/CT) is being used as a tumor surveillance modality for multiple tumor types. A 73-year-old postmenopausal female with stage IV nonsmall cell lung cancer presented after a PET/CT demonstrated focal uptake in the superior and lateral aspects of the uterus. The patient reported a history of intermittent postmenopausal bleeding and an endometrial biopsy documented uterine carcinosarcoma. Postoperative pathologic review and immunohistochemical staining with thyroid transcription factor-1 revealed metastatic adenocarcinoma consistent with her lung primary in her uterus and adnexa. Our case represents a rare occurrence in which lung cancer has metastasized to multiple female pelvic organs. Increasing use of PET/CT may lead to the discovery of occult metastases masquerading as a second primary malignancy.

[Diogenes syndrome: a transnosographic approach]. / Le syndrome de Diogène, une approche transnosographique.

Diogenes syndrome is a behavioural disorder of the elderly. Symptoms include living in extreme squalor, a neglected physical state and unhygienic conditions. This is accompanied by a self-imposed isolation, the refusal of external help and a tendency to accumulate heteroclite objects. This particular geriatric syndrome has been described for the first time only quite recently, as the 2 primary descriptions by geriatricians and psychiatrists date from 1966 and 1975 respectively. Its rare occurrence contrasts with the fact that it is well-known, partly due to it being named after the Greek philosopher "Diogene de Sinope", who taught cynicism philosophy and a return to a natural way of life, and partly because of its rare characteristics. The Diogenes syndrome is a fascinating object of study for the clinician who takes care of patients living in uncommon conditions, on the edge of society and unaware of the particularity of their lifestyles. Patients suffering from Diogenes syndrome are usually discovered by chance, either because of a somatic illness, or as a result of social intervention related to their behavioural problems. Management of the syndrome is difficult and ethically challenging, as the patient does not seek help. Moreover, 46% of patients have a 5 year mortality rate. Hospitalisation has to be avoided whenever possible and ambulatory treatment and social measures should be favoured. Psychotropic treatment prescription may be necessary, depending on clinical features and the possible underlying psychiatric disease. Although several clinical hypotheses have been suggested, the true ethiopathogeny of the syndrome remains unclear. Most authors agree that this behaviour does not reflect free will and has consequently no theoretical relationship to the Greek philosopher. There is no true consensus about diagnostic criteria. They include the main features of the syndrome and exclude known psychiatric syndromes. Clark and Mankikar, who named this syndrome, reckon it may represent stress-related defence mechanisms of the elderly or may be related to natural ageing process. However, psychiatric pathologies as paranoid and paranoiac psychoses, mood disorders and obsessive and compulsive disorders have been described to be associated with it in the literature. Dementia, in particular temporo-frontal dementia, should be looked for and excluded clinically. Alcohol abuse seems to be an aggravating rather than a precipitating factor. Finally, the link between these pathologies and Diogenes syndrome is not yet determined: are they triggering, co-morbid or etiological factors? Should this syndrome be considered as a true illness or as a symptom? This paper presents Diogenes syndrome as a behavioural disorder and distinguishes 2 types: the "active type"--patients who collect from outside to clutter inside--and the "passive type"--patients who passively become invaded by their rubbish. Active type patients fill their home to fill in the vacuum of their life, as it deteriorates and looses its narcissical appeal. Passive type patients accumulate by default and emptiness. A psychopathological understanding is presented here, referring to psychoanalytical theories of the Moi-peau (ego-skin) described by Anzieu. The Moi-peau represents a structure of the psyche founded on the following principle: any psychic function develops itself according to a bodily function from which it transposes its functioning at a mental level. The skin has three functions: the containing shell, the protective barrier of the psyche, and a medium of exchange. The Moi-peau is organised as a double-wall acting both as a defence mechanism and as a filter between the psyche and the external world. It preserves the relationship and the cohesion "container-content". As a result of a narcissical wound, the Moi-peau is damaged and looses its function of a container. In the case of Diogenes Syndrome, the accumulated items repair the Moi-peau and the home becomes an "exterior-proof", thus playing the role of the Moi-peau. This behaviour therefore plays a repairing role for psychic functioning, allowing psychic survival.

beta-Cell death during progression to diabetes.

The hallmark of type 1 diabetes is specific destruction of pancreatic islet beta-cells. Apoptosis of beta-cells may be crucial at several points during disease progression, initiating leukocyte invasion of the islets and terminating the production of insulin in islet cells. beta-Cell apoptosis may also be involved in the occasional evolution of type 2 into type 1 diabetes.

Damage control, rather than unresponsiveness, effected by protective DX5+ T cells in autoimmune diabetes.

The progression of autoimmune diabetes is regulated. We examined here the cellular controls exerted on disease that developed in the BDC2.5 T cell receptor-transgenic model. We found that all BDC2.5 mice with a monoclonal, beta cell-reactive, T cell repertoire developed diabetes before 4 weeks of age; transfer of splenocytes from young standard NOD (nonobese diabetic) mice into perinatal monoclonal BDC2.5 animals protected them from diabetes. The protective activity was generated by CD4+ alphabeta T cells, which operated for a short time at disease initiation, could be partitioned according to DX5 cell surface marker expression and split into two components. Protection did not involve clonal deletion or anergy of the autoreactive BDC2.5 cells, permitting their full activation and attack of pancreatic islets; rather, it tempered the aggressiveness of the insulitic lesion and the extent of beta cell destruction.

A molecular chart of thymocyte positive selection.

As a new slant on T lymphocyte repertoire selection, we have examined batteries of TCR sequences in thymi from transgenic mice engineered to exhibit limited, focussed TCR diversity. We have tracked the fate of differentiating thymocytes expressing a set of particular TCR through the positive selection process. Subtly different TCR sequences can promote different maturation pathways and commitment choices. Two distinct routes are followed by CD8-lineage cells interacting with MHC class I molecules, via TCR(hi) CD4(+)CD8(+) or CD4(+)CD8(int) intermediates, while CD4-lineage cells mature exclusively via a CD4(+)CD8(int) stage. The CD8-lineage routes are partially exclusive, indicating that the latter cell type is not always preceded by the former. The distribution of sequences also indicates that CD4 / CD8-lineage commitment is not strictly correlated with the class of MHC molecule engaged, and that some mechanism prevents mismatched intermediates from achieving full maturity.

Genetic influences on the end-stage effector phase of arthritis.

K/BxN T cell receptor transgenic mice are a model of inflammatory arthritis, most similar to rheumatoid arthritis, that is critically dependent on both T and B lymphocytes. Transfer of serum, or just immunoglobulins, from arthritic K/BxN animals into healthy recipients provokes arthritis efficiently, rapidly, and with high penetrance. We have explored the genetic heterogeneity in the response to serum transfer, thereby focussing on the end-stage effector phase of arthritis, leap-frogging the initiating events. Inbred mouse strains showed clear variability in their responses. A few were entirely refractory to disease induction, and those which did develop disease exhibited a range of severities. F1 analyses suggested that in most cases susceptibility was controlled in a polygenic additive fashion. One responder/nonresponder pair (C57Bl/6 x NOD) was studied in detail via a genome scan of F2 mice; supplementary information was provided by the examination of knock-out and congenic strains. Two genomic regions that are major, additive determinants of the rapidity and severity of K/BxN serum-transferred arthritis were highlighted. Concerning the first region, on proximal chromosome (chr)2, candidate assignment to the complement gene C5 was confirmed by both strain segregation analysis and functional data. Concerning the second, on distal chr1, coinciding with the Sle1 locus implicated in susceptibility to lupus-like autoimmune disease, a contribution by the fcgr2 candidate gene was excluded. Two other regions, on chr12 and chr18 may also contribute to susceptibility to serum-transferred arthritis, albeit to a more limited degree. The contributions of these loci are additive, but gene dosage effects at the C5 locus are such that it largely dominates. The clarity of these results argues that our focus on the terminal effector phase of arthritis in the K/BxN model will bear fruit.

How much TCR does a T cell need?

Kinetic features of TCR:MHC/peptide interactions dictate their outcome in vitro, some important parameters of which include the number of molecules engaged and the duration of engagement. We explored the in vivo significance of these findings in transgenic mice expressing TCRs in a quantitatively and temporally controlled manner. As anticipated, reduced TCR levels resulted in attenuated reactivity, but response thresholds were substantially lower than expected-at as low as 1/20th the normal TCR numbers and with no indication of phenotypic skewing at suboptimal levels. We also studied survival of T lymphocytes stripped of their TCRs. Unlike B cells, T cells lacking antigen receptors did not die precipitously; instead, populations decayed gradually, just as previously reported in the absence of MHC molecules.

Autoimmunity provoked by infection: how good is the case for T cell epitope mimicry?

Autoimmune diseases remain one of the mysteries that perplex immunologists. What makes the immune system, which has evolved to protect an organism from foreign invaders, turn on the organism itself? A popular answer to this question involves the lymphoid network's primordial function: autoimmunity is a by-product of the immune response to microbial infection. For decades there have been tantalizing associations between infectious agents and autoimmunity: beta-hemolytic streptococci and rheumatic fever; B3 Coxsackieviruses and myocarditis; Trypanosoma cruzi and Chagas' disease; diverse viruses and multiple sclerosis; Borrelia burgdorfii and Lyme arthritis; and B4 Coxsackievirus, cytomegalovirus or rubella and type 1 diabetes, to name the most frequently cited examples. In addition, animal models have provided direct evidence that infection with a particular microbe can incite a particular autoimmune disease. Nonetheless, many of the associations appear less than convincing and, even for those that seem to be on solid footing, there is no real understanding of the underlying mechanism(s).

T lymphocytes need IL-7 but not IL-4 or IL-6 to survive in vivo.

The role of IL-4, -6 and -7 in the survival of T lymphocytes was studied in vivo. The decay of polyclonal populations of CD4(+) and CD8(+) T cells was monitored in thymectomized anti-cytokine receptor mAb-treated and/or cytokine-deficient mice. The lack of IL-4 or -6 did not have any detectable effect on T cell survival, but IL-7 played an important role in the survival of the naive T cell compartment, especially of naive CD4(+) T cells.

The shaping of the T cell repertoire.

By combining a TCRbeta transgene with a TCRalpha minilocus comprised of a single V and two J gene segments, we engineered a mouse line exhibiting ample but focused TCR diversity, restricted to CDR3alpha. Using single-cell PCR and high-throughput sequencing, we have exploited this system to scrutinize T cell repertoire selection and evolution. Some striking observations emerged: (1) thymic selection produces a repertoire that is very "bumpy," with marked overrepresentation of a subset of sequences; (2) MHC class I- and class II-restricted TCRs can be distinguished by minute, single-residue changes in CDR3alpha; and (3) homeostatic expansion and survival in the periphery can markedly remold the postselection repertoire, likely reflecting variability in the potential of cells displaying different TCRs to respond to homeostatic cues.

Self-esteem matters: racial & gender differences among rural southern adolescents.

Self-esteem does matter! It matters so much that Oprah dedicated an entire issue of "O" magazine to address the subject. "It's a woman's most treasured possession" (Winfrey, 2000a). Self-esteem has a profound influence on adolescent health promotion behaviors. This study contributes to understanding the role self-esteem plays in the behavior of adolescents. Utilizing a secondary data analysis, race and gender self-esteem differences among adolescents were investigated. The sample of 1,237 students (46% African-American and 52% White) from rural southern areas consisted of 744 females and 493 males. Self-esteem was assessed using the Miller Self-esteem Questionnaire (SEQ). The Hendricks Perceptual Health Promoting Determinants Model (HPHD) provided the theoretical framework for the study. The results of the study revealed a statistically significant difference in various aspects of self-esteem according to race and gender. African-Americans and males had a higher self-esteem which is consistent with many prior studies.

Role of the forkhead transcription family member, FKHR, in thymocyte differentiation.

While performing a large-scale analysis of mRNA transcripts in the murine thymus, our attention was drawn to the forkhead family transcription factor FKHR. Here we demonstrate that FKHR is expressed in thymocytes, most prominently in those that are undergoing positive selection. Interestingly, FKHR transcripts show a highly regionalized pattern of expression, concentrated in the innermost areas of the medulla. We define the FKHR binding site as (G/C)(A/C)N(G/a)T(A/c)AA(T/c) A(T/g)(T/g)(G/c), a sequence found in the regulatory elements of many genes, including certain that encode molecules crucial for thymocyte differentiation. To study the function of FKHR, we engineered mice expressing a dominant-negative mutant specifically in T cells in a tetracycline-regulatable fashion. In these animals, T cell differentiation appeared quite normal; however, total thymocyte numbers were decreased, owing to reductions in all four of the CD4/CD8 subsets, and incorporation of the thymidine analogue bromo-deoxyuridine was increased, again in all four subsets. These data suggest that, in thymocytes, FKHR may be involved in cell survival and/or cycling.

A revival of the B cell paradigm for rheumatoid arthritis pathogenesis?

Dominant paradigms for the understanding of rheumatoid arthritis (RA) pathogenesis have changed over the years. A predominant role of B lymphocytes, and perhaps of the rheumatoid factor they produced, was initially invoked. In more recent years, recognition of antigens in the joint by T cells sparking an inflammatory cascade has been a more favored interpretation. Here, we re-examine some of the arguments that underpin this proposed role of joint T cells, in light of recent results from transgenic mice in which a self-reactive T-cell receptor provokes disease, but from outside the joint and indirectly via B lymphocytes and immunoglobulins.

Effect of hypertension on the development of diabetic cardiomyopathy.

The effect of hypertension on the progression of diabetic cardiomyopathy was examined by attempting to induce a similar level of diabetes in both spontaneously hypertensive rats (SHR) and Wistar rats. Streptozotocin (STZ) was injected into SHR (45 mg/kg) and Wistar rats (55 mg/kg) before (eight weeks of age) and after (twelve weeks of age) the development of hypertension in the SHR. For both groups of animals, induction of diabetes resulted in depressed weight gain, increased food and fluid consumption, hypoinsulinemia, hyperglycemia, and hypertriglyceridemia. For the rats injected at eight weeks of age, an oral glucose tolerance test (OGTT) demonstrated that although the SHR were significantly less diabetic than Wistar rats, the degree of cardiac dysfunction was equivalent in both strains. These results suggest that hypertension was interacting with the diabetic condition to impair cardiac performance. Injecting SHR at twelve weeks of age increased the severity of diabetes but interestingly did not depress heart function compared with the non-diabetic SHR group. Injecting Wistar rats at this age also increased the severity of diabetes, but unlike the SHR diabetic animals, these rats still had impaired cardiac performance. These results suggest that hypertension exacerbates the cardiac dysfunction seen during diabetes, especially when SHR rats are injected with STZ prior to the elevation of blood pressure. Moreover, in the SHR, the development of LV hypertrophy at the time of STZ injection may have compensated for the damaging effects of diabetes on the myocardium, thereby enabling the heart to perform normally.

Pinpointing when T cell costimulatory receptor CTLA-4 must be engaged to dampen diabetogenic T cells.

Engagement of the T cell costimulatory receptor CTLA-4 can potently down-regulate an immune response. For example, in a T cell receptor transgenic mouse model of autoimmune diabetes, CTLA-4 interactions keep pancreatic islet-reactive T cells in check, evidenced by the finding that mAb blockade of CTLA-4 rapidly provokes diabetes in animals that would not normally succumb until many months later. Interestingly, this effect is only observed early in the course of disease, before insulitis is stably entrenched. Here, we have exploited a highly synchronous and easily manipulable transfer system to determine precisely when CTLA-4 must be engaged to check the diabetogenicity of islet-reactive T cells. Our results indicate that CTLA-4 interactions during initial priming of the T cells in the pancreatic lymph nodes are not determinant. Rather, the critical interactions occur when the T cells secondarily reencounter their antigen in the target organ, the pancreatic islets. In addition, we made use of CTLA-4-deficient mice to bolster our interpretation that CTLA-4 engagement has a dampening rather than an enhancing influence on diabetes progression.

A cassette vector for high-level reporter expression driven by a hybrid invariant chain promoter in transgenic mice.

A plasmid cassette vector was designed to generate transgenic mice expressing reporter cDNAs at high levels in antigen-presenting cells under the control of the murine invariant chain (Ii) promoter. Analysis of several transgenic mice harboring a chimeric Ii cDNA placed in this vector showed that it can drive expression of the reporter protein to levels comparable to those of endogenous Ii. Furthermore, its expression pattern overlaps quite well with that of endogenous Ii. This vector should therefore be a convenient and versatile tool for the generation of transgenic mouse lines in which a desired protein may be expressed in Ii-positive cells at levels similar to those of endogenous Ii. Such a vector would be ideal for complementation studies of Ii-deficiency by specific Ii variants.