Transcriptome analysis of ankylosing spondylitis patients before and after TNF-α inhibitor therapy reveals the pathways affected.

Tumor necrosis factor-α (TNF-α) inhibitors are highly effective in suppressing inflammation in ankylosing spondylitis (AS) patients, and operate by suppression of TFN-α and downstream immunological pathways. To determine the mechanisms of action of TNF-α inhibitors in AS patients, we used transcriptomic and bioinformatic approaches on peripheral blood mononuclear cells from AS patients pre and post treatment. We found 656 differentially expressed genes, including the genome-wide significant AS-associated genes, IL6R, NOTCH1, IL10, CXCR2 and TNFRSF1A. A distinctive gene expression profile was found between male and female patients, mainly because of sex chromosome-linked genes and interleukin 17 receptor C, potentially accounting for the differences in clinical manifestation and treatment response between the genders. In addition to immune and inflammation regulatory pathways, like intestinal immune network for IgA production, cytokine-cytokine receptor interaction, Ras signaling pathway, allograft rejection and hematopoietic cell lineage, KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses revealed that infection-associated pathways (influenza A and toxoplasmosis) and metabolism-associated pathways were involved in response to TNF-α inhibitor treatment, providing insight into the mechanism of TNF-α inhibitors.

Environmental enrichment choices of shelter cats.

Choices made by cats between different types of environmental enrichment may help shelters to prioritize how to most effectively enrich cat housing, especially when limited by space or funds. This study investigates the environmental enrichment use of cats in a choice test. Twenty-six shelter cats were kept singularly in choice chambers for 10days. Each chamber had a central area and four centrally-linked compartments containing different types of environmental enrichment: 1) an empty control, 2) a prey-simulating toy, 3) a perching opportunity, and 4) a hiding opportunity. Cat movement between compartments was quantitatively recorded using a data-logger. Enriched compartments were visited significantly more frequently during the light period than during the dark period. Cats spent a significantly greater percentage of time in the hiding compartment (median=55%, IQR=46) than in the toy compartment (median=2%, IQR=9), or in the empty control compartment (median=4%, IQR=4). These results provide additional evidence to support the value of a hiding box to cats housed in a novel environment, in that they choose hiding relative to other types of environmental enrichment.

Does previous use affect litter box appeal in multi-cat households?

It is commonly assumed that cats actively avoid eliminated materials (especially in multi-cat homes), suggesting regular litter box cleaning as the best defense against out-of-box elimination. The relationship between previous use and litter box appeal to familiar subsequent users is currently unknown. The purpose of this study was to investigate the relationship between previous litter box use and the identity of the previous user, type of elimination, odor, and presence of physical/visual obstructions in a multi-cat household scenario. Cats preferred a clean litter box to a dirty one, but the identity of the previous user had no impact on preferences. While the presence of odor from urine and/or feces did not impact litter box preferences, the presence of odorless faux-urine and/or feces did - with the presence of faux-feces being preferred over faux-urine. Results suggest neither malodor nor chemical communication play a role in litter box preferences, and instead emphasize the importance of regular removal of physical/visual obstructions as the key factor in promoting proper litter box use.

Transcriptomic analysis of monocytes and macrophages derived from CLL patients which display differing abilities to respond to therapeutic antibody immune complexes.

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia. While therapeutic antibodies show clinical activity in CLL patients, resistance inevitably develops resulting in treatment failure. Identifying mechanisms of antibody resistance and methods to reduce resistance would be valuable in managing CLL. Monocyte derived cells (MDCs), also known as nurse like cells (NLCs) in CLL [1], [2], are known to be crucial components of the CLL microenvironment network and following "maturation" in in vitro culture systems are able to provide support for the survival of the malignant B cells from CLL patients. In addition to their protective role, MDCs are key effector cells in mediating responses to therapeutic antibody therapies [3]. We have determined that macrophages from patients with early stable CLL are able to elicit superior cytotoxic response to therapeutic antibodies than macrophages derived from patients with progressive CLL. We have exploited this unique finding to gain insight into antibody resistance. Thus, we have profiled monocytes on day 0 and MDCs on day 7 from antibody sensitive and antibody resistant CLL patients (GEO accession number GEO: GSE71409). We show that there are no significant differences in transcriptomes from the monocytes or MDCs derived from sensitive or resistant patient samples. However, we show that MDCs acquire an M2-like macrophage transcriptomic signature following 7 days culture regardless of whether they were derived from sensitive or resistant patient samples.

Behavioural and faecal glucocorticoid metabolite responses of single caging in six cats over 30†days.

OBJECTIVES: The aim was to characterize the behaviour and faecal glucocorticoid metabolite (FGM) responses of six cats (Felis catus) to single caging for 30 days. DESIGN: In this observational study, changes in outcome measures were monitored with habituation to caging. Continuous focal observations of the activity, location in the cage, and posture were conducted from video recordings for one 24-hour period/week/cat. Cat-Stress-Scores were recorded daily. All faecal samples were collected for analysis of FGM. RESULTS: The percentage time spent eating increased, while percentage time spent grooming decreased, from week 1 to week 2. Cat-Stress-Score declined significantly from week 1 to week 2. FGM concentrations were significantly greater in week 1 than in week 5. A posthabituation time budget of the behaviour of the cats in the single cages showed that inactivity dominated the time budget and the cats were located on the shelf almost half of the time. CONCLUSIONS: Results suggests that a shelf was a resource of value to the cats, and that its inclusion in enclosure design is important. Quantitative and qualitative behavioural data indicated that there was an initial stress response to caging that stabilised after the first week, while FGM concentration took longer to stabilise.

Bcl-xL anti-apoptotic network is dispensable for development and maintenance of CML but is required for disease progression where it represents a new therapeutic target.

The dismal outcome of blast crisis chronic myelogenous leukemia (CML-BC) patients underscores the need for a better understanding of the mechanisms responsible for the development of drug resistance. Altered expression of the anti-apoptoticBcl-xL has been correlated with BCR-ABL leukemogenesis; however, its involvement in the pathogenesis and evolution of CML has not been formally demonstrated yet. Thus, we generated an inducible mouse model in which simultaneous expression of p210-BCR-ABL1 and deletion of bcl-x occurs within hematopoietic stem and progenitor cells. Absence of Bcl-xL did not affect development of the chronic phase-like myeloproliferative disease, but none of the deficient mice progressed to an advanced phenotype, suggesting the importance of Bcl-xL in survival of progressing early progenitor cells. Indeed, pharmacological antagonism of Bcl-xL, with ABT-263, combined with PP242-induced activation of BAD markedly augmented apoptosis of CML-BC cell lines and primary CD34(+) progenitors but not those from healthy donors, regardless of drug resistance induced by bone marrow stromal cell-generated signals. Moreover, studies in which BAD or Bcl-xL expression was molecularly altered strongly support their involvement in ABT-263/PP242-induced apoptosis of CML-BC progenitors. Thus, suppression of the antiapoptotic potential of Bcl-xL together with BAD activation represents an effective pharmacological approach for patients undergoing blastic transformation.

A multidisciplinary approach to the evaluation and treatment of temporomandibular joint and cervical spine dysfunction.

This article presents a multidisciplinary approach to the management of temporomandibular joint (TMJ) and cervical spine dysfunction in a heterogeneous population of patients. A methodology for the systematic evaluation and treatment of patients is outlined; case histories are used to illustrate the workings of the model. A study to assess the efficacy of treatment was performed on 27 female and three male adult patients. Results indicated that patients achieved an 87% recovery rate at discharge with an 83% success rate six months after discharge. A control study was undertaken using 16 female and three male adults to establish indications for TMJ occlusal splint therapy in patients who present with questionable TM dysfunction. The multidisciplinary model presented in this article provides a system of patient evaluation and treatment that can be easily adopted by clinicians involved in a team approach to TMJ and cervical spine dysfunction.

Psychotherapy with physicians' families: when attributes in medical practice become liabilities in family life.

Personality attributes typically found in successful physicians can lead to difficulties in family life. This paper identifies physicians' positive characteristics and demonstrates with case-history material how these characteristics can contribute to interactional problems with family members. Ways of engaging physicians in treatment and avoiding some of the common pitfalls in working with this group are discussed.

Production of Deoxynivalenol and Zearalenone by Isolates of Fusarium graminearum Schw.

Production of deoxynivalenol (DON) on rice, corn, wheat, and barley grains by Fusarium graminearum Schw. NRRL 5883 was investigated. Highest yields (91.9-202 ppm) were obtained on rice; yields on the other substrates were: corn (34.1-84.5 ppm), wheat (3.6-24.4 ppm), and barley (0-6.6 ppm). Fusarium isolates (49) from corn inoculated in the field with strains of F. graminearum , collected from corn plants infected with stalk rot, were tested for DON production on corn. Twenty of these were also tested for zearalenone production. One isolate produced more than 200 ppm DON, 13 produced 20-50 ppm, 17 produced 10-20 ppm, and the rest produced less than 10 ppm. All 20 isolates tested produced zearalenone; 18 produced higher levels of zearalenone (15.4-369 ppm) than of DON. The other 2 isolates formed essentially the same levels of zearalenone and DON-37 and 30 ppm, and 15 and 16 ppm, respectively.

Production of deoxynivalenol and zearalenone by isolates of Fusarium graminearum Schw.

The production of deoxynivalenol (DONI) on rice, corn, wheat, and barley grains by Fusarium graminearum Schw. NRRL 5883 was investigated. Highest yields (91.9-202 ppm) were obtained on rice; yields on the other substrates were: corn (34.1-84.5 ppm), wheat (3.6-24.4 ppm), and barley (0-6.6 ppm). Fifty isolates of Fusarium from corn inoculated in the field in 1979 with a mixture of strains of F. graminearum, originally collected from corn plants infected with stalk rot, were tested for DONI production on corn. Twenty of these were also tested for zearalenone production. One isolate produced more than 200 ppm DONI, 13 produced 20-50 ppm, 17 produced 10-20 ppm, and the rest produced less than 10 ppm. The only isolate that did not produce DONI was not identified as F. graminearum. All 20 isolates tested produced zearalenone; 18 produced higher levels of zearalenone (15.4-369 ppm) than of DONI. The other 2 isolates formed essentially the same levels of zearalenone and DONI-37 and 30 ppm, and 15 and 16 ppm, respectively.

Group therapy with anorexic and bulimic patients: implications for therapeutic intervention.

The incidence of anorexia nervosa and bulimia has increased markedly during the last decade. Although numerous studies have appeared regarding the dynamics of the eating-disordered patient, few have attempted to link the unique pathology of these patients to specific psychotherapeutic interventions. This paper is based on the authors' experience as co-therapists with a group of eating-disordered patients over an eight months' period. It addresses itself to therapeutic interventions related to the particular dynamics of bulimics and anorexics.

Computed tomography of bowel perforation.

The authors present 2 cases of intestinal perforation which were not associated with free intraperitoneal air detectable on abdominal radiographs. Computed tomography demonstrated evidence of intraperitoneal leakage of orally administered contrast material and thereby provided the correct diagnosis.

Production of vomitoxin on corn by Fusarium graminearum NRRL 5883 and Fusarium roseum NRRL 6101.

Two vomitoxin-producing isolates of Fusarium spp. were grown on cracked corn for 1 to 8 weeks at 15, 20, 25, 28, and 32 degrees C. Maximum production of vomitoxin by Fusarium graminearum Schw. NRRL 5883 occurred at 30 degrees C and 40 days, and that by Fusarium roseum Schw. NRRL 6101 occurred at 26 degrees C and 41 days. These optimum production points were determined from response surface contour graphs in relation to temperature and time. Only small amounts of vomitoxin were produced at 15 and 20 degrees C by each strain. A 133-microgram quantity of vomitoxin, with an indicated purity of 95%, was isolated per gram of corn fermented with F. graminearum NRRL 5883.

Experimental cerebral zygomycosis in alloxan-diabetic rabbits: variation in virulence among zygomycetes.

We investigated the potential of 33 different zygomycete isolates to cause cerebral disease following the intranasal instillation of their spores into ketotic rabbits with alloxan induced diabetes. The isolates represented six thermotolerant species of Rhizopus (R. arrhizus, R. chinensis, R. microsporus, R. oligosporus, R. oryzae, and R. rhizopodiformis), Absidia corymbifera, Cunninghamella bertholletiae, and Rhizomucor pusillus. All 13 isolates of the thermotolerant Rhizopus species proved to be cerebral pathogens as confirmed by culture and histopathology. One isolate of R. oligosporus and one isolate of R. rhizopodiformis, however, were less pathogenic than isolates of other Rhizopus species tested. Cerebral pathogenicity was noted with 2 of 5 isolates of Rh. pusillus and only 1 of 13 A. corymbifera isolates. Two thermotolerant C. bertholletiae cultures, recovered from human lesions, did not cause either cerebral or pulmonary disease in ketotic rabbits. The incidence of pulmonary zygomycosis caused by the isolates of the species of the four genera under study was as follows: Rhizomucor 24%, Rhizopus 22%, Absidia 9%, and Cunninghamella 0%. This study confirms the pathogenic potential of the thermotolerant species of Rhizopus to cause cerebral zygomycosis in ketotic diabetic rabbits and also revealed the potential of Rh. pusillus and A. corymbifera occasionally to cause the same disease in animals and humans.

Elaboration of vomitoxin and zearalenone by Fusarium isolates and the biological activity of Fusarium-produced toxins.

Sixteen Fusarium isolates belonging to F. graminearium Schw. and F. culmorum (W.G. Smith) Sacc. produced vomitoxin and zearalenone on cracked corn at 28 degrees C. Quantitation for vomitoxin was by gas-liquid chromatography. This toxin was produced in quantities of 5 to 236 microgram/g of fermented corn. Vomitoxin showed weak antibiotic activity against Penicillium digitatum Sacc., Mucor ramannianus Möller, and Saccharomyces bayanus Sacc., but did not inhibit gram-positive, gram-negative, or acid fast bacteria. The two molds and the yeast were inhibited by T-2 toxin at 5 micrograms, and diacetoxyscirpenol inhibited the molds at 5 micrograms and the yeast at 50 micrograms.