Inflammatory Bowel Disease: Epidemiology, Evaluation, Treatment, and Health Maintenance.

The incidence and prevalence of inflammatory bowel disease are rising. Crohn's disease and ulcerative colitis each have distinct features. Treatments are changing rapidly, and there are many new drugs in the pipeline. Health maintenance also plays a key role in the care of this patient population.

The Bio:Fiction film festival: Sensing how a debate about synthetic biology might evolve.

Synthetic biology (SB) is a new techno-scientific field surrounded by an aura of hope, hype and fear. Currently it is difficult to predict which way the public debate - and thus the social shaping of technology - is heading. With limited hard evidence at hand, we resort to a strategy that takes into account speculative design and diegetic prototyping, accessing the Bio:Fiction science film festival, and its 52 short films from international independent filmmakers. Our first hypothesis was that these films could be used as an indicator of a public debate to come. The second hypothesis was that SB would most likely not follow the debate around genetic engineering (framing technology as conflict) as assumed by many observers. Instead, we found good evidence for two alternative comparators, namely nanotechnology (technology as progress) and information technology (technology as gadget) as stronger attractors for an upcoming public debate on SB.

Pilot study of the efficacy of constraint-induced movement therapy for infants and toddlers with cerebral palsy.

The evidence for Constraint-Induced Movement Therapy (CIMT) effectiveness for infants and toddlers with unilateral cerebral palsy is minimal. We performed a pilot study of CIMT using one-month usual care, one-month intervention, and one-month maintenance (return to usual care) phases on five infants (7- to 18-month old). For the CIMT phase, the infants received 2 hr of occupational therapy and 1 hr of parent-implemented home program for five days/week. The infants were casted for the first 23 days, and bimanual therapy was provided for the last three days. Fine motor skills for the more affected arm and gross motor skills improved significantly during the CIMT; these gains were maintained at one-month follow-up. Individual infant data show mixed effects. This pilot study provides initial evidence that CIMT is feasible for infants with unilateral cerebral palsy, and presents preliminary data for CIMT on fine and gross motor performance.

Repair of small and medium size ventral hernias with a Proceed Ventral Patch: a single center retrospective analysis.

PURPOSE: Ventral hernias are common surgical targets. The Bard(®) Ventralex™ Hernia Patch was introduced for the repair of such hernias in the early 2000s. Ethicon (Johnson & Johnson) introduced the Proceed™ Ventral Patch (PVP™) in the late 2000s for the same indication. The effectiveness and safety of the Bard(®) Ventralex™ Hernia Patch has been proven in a series of studies. There are no medical studies on the PVP™ in humans. This study examines the effectiveness and safety of PVP™ in the closure of ventral hernias. METHOD: A single center retrospective analysis of patients' data was conducted. Fifty-seven patients with small and medium size ventral hernias were treated with patches in the period between May 2009 and December 2010. The charts of these patients were reviewed. Demographic data, diagnosis at surgery, duration of surgery, length of hospital stay, postoperative complications and recurrence were recorded. RESULTS: Fifty-seven patients were analyzed including 21 females and 36 males with a mean age of 56.7 years. The diagnosis at surgery included 36 cases of umbilical hernia, eight cases of epigastric hernia, seven incision hernias and six recurrent umbilical hernias. The mean duration of surgery was 30.7 min, and the mean length of hospital stay was 3.3 days. Four postoperative complications (7.1 %) and one case of hernia recurrence (1.7 %) were recorded. CONCLUSION: Ventral hernia closure with PVP™ is safe and effective. The rates of complication and recurrence are comparable to those of the Bard(®) Ventralex™ Hernia Patch.

Protocol for the isolation and culture of mouse dorsal root ganglion neurons for imaging applications.

Sensory neurons play pervasive roles throughout biology. In vitro studies to probe their functions hinge on the successful application of primary cell culture. Here, we present a protocol for the isolation and culture of mouse dorsal root ganglion neurons for imaging applications. We describe steps for extracting dorsal root ganglia, preparing cultures, maintaining them for days in vitro, and performing immunocytochemical labeling. We also include special considerations with respect to additional downstream applications. For complete details on the use and execution of this protocol, please refer to Smith et al. (2021).1.

Epigenetics Regulates Reproductive Development in Plants.

Seed, resulting from reproductive development, is the main nutrient source for human beings, and reproduction has been intensively studied through genetic, molecular, and epigenetic approaches. However, how different epigenetic pathways crosstalk and integrate to regulate seed development remains unknown. Here, we review the recent progress of epigenetic changes that affect chromatin structure, such as DNA methylation, polycomb group proteins, histone modifications, and small RNA pathways in regulating plant reproduction. In gametogenesis of flowering plants, epigenetics is dynamic between the companion cell and gametes. Cytosine DNA methylation occurs in CG, CHG, CHH contexts (H = A, C, or T) of genes and transposable elements, and undergoes dynamic changes during reproduction. Cytosine methylation in the CHH context increases significantly during embryogenesis, reaches the highest levels in mature embryos, and decreases as the seed germinates. Polycomb group proteins are important transcriptional regulators during seed development. Histone modifications and small RNA pathways add another layer of complexity in regulating seed development. In summary, multiple epigenetic pathways are pivotal in regulating seed development. It remains to be elucidated how these epigenetic pathways interplay to affect dynamic chromatin structure and control reproduction.

The Rat Genome Database (RGD): developments towards a phenome database.

The Rat Genome Database (RGD) (http://rgd.mcw.edu) aims to meet the needs of its community by providing genetic and genomic infrastructure while also annotating the strengths of rat research: biochemistry, nutrition, pharmacology and physiology. Here, we report on RGD's development towards creating a phenome database. Recent developments can be categorized into three groups. (i) Improved data collection and integration to match increased volume and biological scope of research. (ii) Knowledge representation augmented by the implementation of a new ontology and annotation system. (iii) The addition of quantitative trait loci data, from rat, mouse and human to our advanced comparative genomics tools, as well as the creation of new, and enhancement of existing, tools to enable users to efficiently browse and survey research data. The emphasis is on helping researchers find genes responsible for disease through the use of rat models. These improvements, combined with the genomic sequence of the rat, have led to a successful year at RGD with over two million page accesses that represent an over 4-fold increase in a year. Future plans call for increased annotation of biological information on the rat elucidated through its use as a model for human pathobiology. The continued development of toolsets will facilitate integration of these data into the context of rat genomic sequence, as well as allow comparisons of biological and genomic data with the human genomic sequence and of an increasing number of organisms.

Tools and strategies for physiological genomics: the Rat Genome Database.

The broad goal of physiological genomics research is to link genes to their functions using appropriate experimental and computational techniques. Modern genomics experiments enable the generation of vast quantities of data, and interpretation of this data requires the integration of information derived from many diverse sources. Computational biology and bioinformatics offer the ability to manage and channel this information torrent. The Rat Genome Database (RGD; http://rgd.mcw.edu) has developed computational tools and strategies specifically supporting the goal of linking genes to their functional roles in rat and, using comparative genomics, to human and mouse. We present an overview of the database with a focus on these unique computational tools and describe strategies for the use of these resources in the area of physiological genomics.

Prefrontal GABA levels in cocaine-dependent subjects increase with pramipexole and venlafaxine treatment.

RATIONALE: There is evidence that prefrontal lobe GABA levels are low in cocaine-dependent (CD) individuals, and treatment with GABA agonists decreases cocaine self-administration. OBJECTIVES: The aim of the study is to measure changes in GABA levels in CD subjects at baseline and after 8 weeks of treatment with pramipexole, venlafaxine, or placebo. METHODS: CD subjects enrolled in a treatment trial for cocaine dependence were recruited for this proton (1H) magnetic resonance spectroscopy (MRS) study. GABA levels in the prefrontal lobe were measured before and after treatment. RESULTS: Mean percentage changes in GABA levels were as follows: pramipexole +17.0+/-28.0%, venlafaxine +13.0+/-11.0%, and placebo -2.1+/-19.5%. Pramipexole-treated subjects had significantly increased brain GABA levels compared to placebo (p=0.031). Venlafaxine treatment was nonsignificantly associated with increased GABA levels compared to placebo (p=0.16). The overall statistical model for the effect of drug treatment vs placebo on brain GABA levels, including adjustment for baseline levels, was highly significant (p=0.002). Despite significant changes in GABA levels, there were no significant differences in the number of urine samples positive for cocaine metabolites. CONCLUSIONS: This study demonstrates that 1H MRS can measure changes in GABA levels following pharmacologic treatment. The increase in GABA levels, although significant, is modest compared to other MRS studies of depression or epilepsy associated with clinical improvements. The failure to see larger increases in GABA levels and an associated reduction in cocaine consumption may reflect the relatively low doses of medication used.

Frontal lobe GABA levels in cocaine dependence: a two-dimensional, J-resolved magnetic resonance spectroscopy study.

Non-invasive measures of brain gamma-aminobutyric acid (GABA) concentrations may be especially useful in the identification of cocaine-related changes in brain chemistry that can be used to guide the development of future treatments for cocaine-dependent persons. This study assessed whether brain GABA levels in cocaine-dependent subjects with and without an alcohol disorder differ from GABA levels in healthy comparison subjects. Two-dimensional, proton magnetic resonance spectroscopy was used to determine GABA levels in the left prefrontal lobe of cocaine-dependent subjects (N=35) recruited from a National Institute on Drug Abuse (NIDA)-sponsored treatment trial of cocaine dependence and a comparison group (N=20). At treatment baseline, mean GABA concentrations were 0.93+/-0.27 mM/kg in cocaine-dependent subjects and 1.32+/-0.44 mM/kg in the comparison sample (t [d.f.=53]=3.65, P<0.001). Cocaine-dependent subjects with a history of a co-morbid alcohol disorder (N=23) had significantly lower baseline GABA levels (0.87 mM/kg) (t [d.f.=41]=4.31, P<0.001) than the comparison group. However, cocaine-dependent subjects without an alcohol disorder (N=12) also had lower GABA levels (1.04 mM/kg) than the comparison subjects (t [d.f.=30]=2.09, P=0.045), suggesting that cocaine dependence alone can decrease GABA levels.

TRPV4 calcium entry and surface expression attenuated by inhibition of myosin light chain kinase in rat pulmonary microvascular endothelial cells.

In previous studies, blockade or gene deletion of either myosin light chain kinase (MLCK) or the mechanogated transient receptor potential vanilloid 4 (TRPV4) channel attenuated mechanical lung injury. To determine their effects on calcium entry, rat pulmonary microvascular endothelial cells (RPMVEC) were labeled with fluo-4 and calcium entry initiated with the TRPV4 agonist, 4α-phorbol 12, 13-didecanoate (4αPDD). Mean calcium transients peaked at ∼25 sec and persisted ∼500 sec. The 4αPDD response was essentially abolished in calcium-free media, or after pretreatment with the MLCK inhibitor, ML-7. ML-7 also attenuated the 4αPDD-induced inward calcium current measured directly using whole-cell patch clamp. Pretreatment with dynasore, an inhibitor of dynamin produced an initial calcium transient followed by a 4αPDD transient of unchanged peak intensity. Automated averaging of areas under the curve (AUC) of calcium transients in individual cells indicated total calcium activity with a relationship between treatment groups of ML-7 + 4αPDD < 4αPDD only < dynasore + 4αPDD. Measurement of biotinylated surface TRPV4 protein indicated a significant reduction after ML-7 pretreatment, but no significant change with dynasore treatment. RPMVEC monolayer electrical resistances were decreased by only 3% with 10 µmol/L 4αPDD and the response was dose-related. Dynasore alone produced a 29% decrease in resistance, but neither ML-7 nor dynasore affected the subsequent 4αPDD resistance response. These studies suggest that MLCK may inhibit mechanogated calcium responses through reduced surface expression of stretch activated TRPV4 channels in the plasma membrane.

Relapse of inflammatory bowel disease associated with use of nonsteroidal anti-inflammatory drugs.

To determine whether an association exists between relapse in inflammatory bowel disease and use of nonsteroidal anti-inflammatory drugs (NSAIDs), a retrospective records review was conducted of patients with Crohn's disease, ulcerative colitis, or indeterminate colitis examined at an outpatient tertiary care center between July 17, 2000, and November 1, 2001. Extracted data collected during the patient's last visit included medication use, maintenance therapy, disease activity, and smoking status. Use of NSAIDs was defined as a daily dose or more of any type the month before relapse. Of 60 patients (22, relapse; 38, remission), 9 (41%) in relapse and 10 (26%) in remission used NSAIDs. Maintenance therapy varied from 68% (relapse) to 92% (remission). The adjusted odds ratio between medication use and relapse was 6.31 (95% confidence interval, 1.16-34.38; P = .03). Use of NSAIDs was associated with relapse. A prospective cohort study that corrects for maintenance therapy is needed to evaluate this relationship.

Exploring phenotypic data at the rat genome database.

The laboratory rat, Rattus norvegicus, is an important model of human health and disease, and experimental findings in the rat have direct relevance to human-based research. The Rat Genome Database (RGD, http://rgd.mcw.edu) is a model-organism database that provides access to wide variety of curated rat data such as genes and their homologs, quantitative trait loci, phenotypes, comparative mapping, and genome analysis. We present an overview of the database followed by specific examples that can be used to gain experience in employing RGD to explore the wealth of functional data available for the rat. We show how to make associations with the genome and use comparative tools to link the rat with human and mouse in order to integrate results from these three species of critical biomedical importance.

The diagnostic yield of stool pathogen studies during relapses of inflammatory bowel disease.

GOALS: We sought to determine the yield of stool analysis for bacterial culture, ova and parasites, and Clostridium difficile toxin in suspected relapses of inflammatory bowel disease (IBD). BACKGROUND: The diagnostic yield of such stool studies has not been examined recently in the United States. STUDY: The medical records of consecutive IBD patients who underwent stool testing for relapses at our institution between July 1, 2000, and November 25, 2001, were abstracted for demographics, stool test results, recent antibiotic exposure, and hospitalization. RESULTS: Fifty-four patients were evaluated during 62 relapses with 99 stool samples. Twelve stool tests were positive. C. difficile accounted for the majority of positive tests (10/12). Of these, 9 (90%) were associated with antibiotic use in the prior month versus 10 (22%) in the C. difficile-negative group (P < 0.001). Hospitalization, prednisone use, or sulfasalazine use did not differ significantly with C. difficile status. Eight C. difficile-positive patients improved clinically with targeted antibiotic therapy. Two bacterial cultures (4%) were positive for Campylobacter jejuni and Plesiomonas shigelloides. CONCLUSION: Stool studies yielded a pathogen, mainly C. difficile, in 20% of the relapsing IBD patients. Antibiotic use was significantly associated with a positive C. difficile toxin. Toxin-positive patients improved clinically with targeted antibiotics.

Videotaped cue for urge to drink alcohol.

BACKGROUND: The urge to drink alcohol can be robustly and reliably induced via actual exposure to a person's preferred alcoholic beverage. Unfortunately, these exposure paradigms are unwieldy for functional magnetic resonance imaging studies. The goal of this study was to examine whether viewing a personalized videotaped cue could induce alcohol craving. The following hypotheses were tested: (1) individualized cue videotapes can reliably elicit the urge to drink alcohol in alcohol-dependent participants and (2) alcohol drinking histories can predict reactivity to cue. METHODS: DSM-IV criteria were used to identify an alcohol-dependent group (ADG). Controls included a light-drinking group and a moderate-drinking group. Urge to drink alcohol was assessed at baseline and after each of five in vivo exposure conditions: water (W), alcohol 1 (A1), mood induction (M), alcohol 2 (A2), and relaxation (R). The entire exposure session was videotaped. Each participant's video footage was digitally edited to produce a 17.5-min cue that was presented to the participant 24 to 72 hr later. Ratings of urge to drink alcohol across the five exposure conditions were compared for both the in vivo and the video exposure sessions. RESULTS: Fourteen participants (five in the light-drinking group, four in the moderate-drinking group, and five in the ADG) completed both sessions. Participants in each group showed differences between neutral cue exposure (W and R) and alcohol-related cue exposure (A1, M, and A2) in both the in vivo cue session (p < 0.002) and the videotape session (p < 0.02). Post hoc comparisons among the groups to alcohol-related cues established that, in both sessions (p(in vivo) = 0.04; p(videotape) = 0.04), the ADG demonstrated the greatest urge to drink. CONCLUSIONS: Alcohol cue reactivity can be reliably induced and assessed in alcohol-dependent participants via personalized videotapes. History of alcohol consumption is positively correlated with the degree of cue reactivity. This study advances our ability to assess alcohol cue reactivity in the absence of alcohol.