Mesh for Hernia Repair as Cause of Bowel Obstruction.

Ventral hernia repairs are commonly treated by abdominal wall repair where a prosthetic mesh is placed over the hernia site, to prevent future hernia recurrences. Risks of a ventral hernia repair include urinary retention, seroma, recurrence, and in rare cases, bowel injury or obstruction. Our patient's clinical presentation and history, supported by an abdominal X-ray and CT findings, were consistent with the diagnosis of small bowel obstruction (SBO) due to adhesions between the patient's small bowel and the mesh used for abdominal wall hernia repair. Our patient underwent an exploratory laparotomy due to exquisite abdominal wall tenderness and evidence of SBO. Appropriate identification of the cause of our patient's SBO, careful and meticulous treatment, and appropriate inpatient monitoring all contributed to a successful outcome.

Treatment outcomes of substance abusing males who completed a 90-day residential treatment programme in Barbados

OBJECTIVE: To analyse the post-treatment outcomes of male substance abusers who completed a minimum of 90 days at a residential treatment facility in Barbados. SUBJECTS AND METHODS: A sample of 150 male clients who completed 90 days or more of the treatment programme from 2004–2014 was used for the main study. A pilot study was conducted with fifteen subjects to assess the validity and reliability of the Substance Abuse Foundation Evaluation-1 (SAFE-1) questionnaire designed for the study. Correlation coefficients were used to measure the strength of association between variables, and a p-value of0.05 was used to determine statistical significance. RESULTS: To date, data on 37 respondents were used for analysis. Positive significant relationships emerged between number of days in treatment and length of sobriety, and social support, spiritual health and length of sobriety. There was no significant relationship between drug of choice and length of sobriety, nor between trauma and relapse. Self-referred clients reported longer lengths of sobriety and clients who had more than 20 years of drug use prior to treatment were more likely to stay sober longer after treatment. Clients between three and six years post treatment were more likely to request additional support. CONCLUSIONS: There are specific factors that positively impact length of sobriety after treatment. Thus, substance abuse treatment centres should seek to incorporate these factors into their programming so as to better inform their inpatient and after care services.

The citrus flavone nobiletin reduces pro-inflammatory and pro-labour mediators in fetal membranes and myometrium: implications for preterm birth.

Spontaneous preterm birth is the leading cause of infant death and of neurological disabilities in survivors. A significant proportion of spontaneous preterm births are associated with infection. Infection activates inflammation which induces a cascade of events that leads to myometrial contractions and rupture of fetal membranes. In non-gestational tissues, the citrus flavone nobiletin has been shown to exert potent anti-inflammatory properties. Thus, in this study, we sought to determine the effect of nobiletin on pro-inflammatory mediators in human fetal membranes and myometrium. Human fetal membranes and myometrium were treated with bacterial endotoxin lipopolysaccharide (LPS) in the absence or presence of nobiletin. In addition, the effect of nobiletin in fetal membranes taken from spontaneous preterm deliveries with and without infection (i.e. histological chorioamnionitis) was also examined. In human fetal membranes and myometrium, nobiletin significantly decreased LPS-stimulated expression of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6 and IL-8) and MMP-9 expression and pro-MMP-9 secretion. Additionally, nobiletin significantly decreased COX-2 expression and subsequent prostaglandin (PG) E2 production. Notably, nobiletin was also able to reduce the expression and production of pro-inflammatory cytokines and MMP-9 in fetal membranes taken from women after spontaneous preterm birth. In conclusion, our study demonstrates that nobiletin can reduce infection-induced pro-inflammatory mediators in human fetal membranes and myometrium. These in vitro studies further support the increasing volume and quality of evidence that high fruit and vegetable intake in pregnancy is associated with a decreased risk of adverse pregnancy outcomes.

Effect of silibinin in reducing inflammatory pathways in in vitro and in vivo models of infection-induced preterm birth.

Infection-induced preterm birth is the largest cause of infant death and of neurological disabilities in survivors. Silibinin, from milk thistle, exerts potent anti-inflammatory activities in non-gestational tissues. The aims of this study were to determine the effect of silibinin on pro-inflammatory mediators in (i) human fetal membranes and myometrium treated with bacterial endotoxin lipopolysaccharide (LPS) or the pro-inflammatory cytokine IL-1ß, and (ii) in preterm fetal membranes with active infection. The effect of silibinin on infection induced inflammation and brain injury in pregnant mice was also assessed. Fetal membranes and myometrium (tissue explants and primary cells) were treated with 200 µM silibinin in the presence or absence of 10 µg/ml LPS or 1 ng/ml IL-1ß. C57BL/6 mice were injected with 70 mg/kg silibinin with or without 50 µg LPS on embryonic day 16. Fetal brains were collected after 6 h. In human fetal membranes, silibinin significantly decreased LPS-stimulated expression of IL-6 and IL-8, COX-2, and prostaglandins PGE2 and PGF2α. In primary amnion and myometrial cells, silibinin also decreased IL-1ß-induced MMP-9 expression. Preterm fetal membranes with active infection treated with silibinin showed a decrease in IL-6, IL-8 and MMP-9 expression. Fetal brains from mice treated with silibinin showed a significant decrease in LPS-induced IL-8 and ninjurin, a marker of brain injury. Our study demonstrates that silibinin can reduce infection and inflammation-induced pro-labour mediators in human fetal membranes and myometrium. Excitingly, the in vivo results indicate a protective effect of silibinin on infection-induced brain injury in a mouse model of preterm birth.

Second-hand smoke levels in UK pubs and bars: do the English Public Health White Paper proposals go far enough?

BACKGROUND: The English Public Health White Paper proposes introducing smoke-free workplaces except in pubs and bars that do not prepare and serve food. The bar area will be non-smoking in exempted pubs. OBJECTIVE: To explore the likely impact of these proposals in UK pubs and bars. METHODS: A total of 59 pubs and bars within Greater Manchester in 2001 were chosen. Thirteen were mechanically ventilated, 12 were naturally ventilated and 34 had extractor fans; 23 provided non-smoking areas. We measured time-weighted average concentrations of respirable suspended particles (RSP), solanesol tobacco-specific particles and vapour-phase nicotine (VPN) over a 4-h sampling period on a Tuesday or Saturday night. RESULTS: Second-hand smoke (SHS) levels in smoking areas were high (mean RSP 114.5 microg/m3, VPN 88.2 microg/m3, solanesol 101.7 microg/m3). There were only small (5-13 per cent) reductions in bar areas. Mean levels were lower in non-smoking areas: by 33 per cent for RSPs, 52 per cent for solanesol particles and 69 per cent for VPN. Compared with other settings (homes and other workplaces) with unrestricted smoking, mean SHS levels were high throughout all areas of the pubs regardless of ventilation strategy. CONCLUSION: Partial measures, like those in the English Public Health White Paper, will leave bar staff in exempted pubs unprotected from the occupational hazard of SHS.

Arabidopsis RTM1 and RTM2 genes function in phloem to restrict long-distance movement of tobacco etch virus.

Restriction of long-distance movement of tobacco etch virus (TEV) in Arabidopsis ecotype Col-0 plants requires the function of at least three genes: RTM1 (restricted TEV movement 1), RTM2, and RTM3. The mechanism of TEV movement restriction remains poorly understood, although it does not involve a hypersensitive response or systemic acquired resistance. A functional characterization of RTM1 and RTM2 was done. The RTM1 protein was found to be soluble with the potential to form self-interacting complexes. The regulatory regions of both the RTM1 and RTM2 genes were analyzed using reporter constructs. The regulatory sequences from both genes directed expression of beta-glucuronidase exclusively in phloem-associated cells. Translational fusion proteins containing the green fluorescent protein and RTM1 or RTM2 localized to sieve elements when expressed from their native regulatory sequences. Thus, components of the RTM system may function within phloem, and sieve elements in particular, to restrict TEV long-distance movement.

Silencing on the spot. Induction and suppression of RNA silencing in the Agrobacterium-mediated transient expression system.

The Agrobacterium-mediated transient expression assay in intact tissues has emerged as a rapid and useful method to analyze genes and gene products in plants. In many cases, high levels of active protein can be produced without the need to produce transgenic plants. In this study, a series of tools were developed to enable strong or weak induction of RNA silencing and to suppress RNA silencing in the absence of stable transgenes. Transient delivery of a gene directing production of a double-stranded green fluorescent protein (GFP) transcript rapidly induced RNA silencing of a codelivered GFP reporter gene, effectively preventing accumulation of GFP protein and mRNA. RNA silencing triggered by the strong dsGFP inducer was partially inhibited by the tobacco etch virus silencing suppressor, P1/HC-Pro. In the absence of the strong double-stranded GFP inducer, the functional GFP gene served as a weak RNA silencing inducer in the transient assay, severely limiting accumulation of the GFP mRNA over time. The weak silencing induced by the GFP gene was suppressed by P1/HC-Pro. These results indicate RNA silencing can be triggered by a variety of inducers and analyzed entirely using transient gene delivery systems. They also indicate that RNA silencing may be a significant limitation to expression of genes in the Agrobacterium-mediated transient assay but that this limitation can be overcome by using RNA silencing suppressors.

RD114-pseudotyped oncoretroviral vectors. Biological and physical properties.

Limited functional expression of the viral envelope receptor is a recognized barrier to efficient oncoretroviral mediated gene transfer. To circumvent this barrier we evaluated a number of envelope proteins with respect to gene transfer efficiency into primitive human hematopoietic stem cell populations. We observed that oncoretroviral vectors pseudotyped with the envelope protein of feline endogenous virus (RD114) could efficiently transduce human repopulating cells capable of establishing multilineage hematopoiesis in immunodeficient mice after a single exposure to RD114-pseudotyped vector. Comparable rates of gene transfer with amphotropic and GALV-pseudotyped vectors have been reported, but only after multiple exposures to the viral supernatant. Oncoretroviral vectors pseudotyped with the RD114 or the amphotropic envelopes had similar stability in vitro, indicating that the increased efficiency in gene transfer is at the receptor level likely due to increased receptor expression or an increased receptor affinity for the RD114 envelope. We also found that RD114-pseudotype vectors can be efficiently concentrated, thereby removing any adverse effects of the conditioned media to the long-term repopulating potential of the target human hematopoietic stem cell. These studies demonstrate the potential of RD114-pseudotyped vectors for clinical use.

Long-distance movement and replication maintenance functions correlate with silencing suppression activity of potyviral HC-Pro.

The tobacco etch potyviral protein, HC-Pro, is a multifunctional proteinase required for long-distance movement in plants and maintenance of genome replication at the single-cell level. It also functions in a counterdefensive capacity as a suppressor of posttranscriptional gene silencing (PTGS). To determine whether the requirements for HC-Pro during long distance movement and replication maintenance are due to the silencing suppressor function of the protein, a series of HC-Pro alanine scanning and other site-directed mutants were analyzed. Using a transient silencing suppression assay in Agrobacterium-injected leaf tissue, several suppression-defective mutants were identified. Each of six HC-Pro mutations, which were shown previously to confer long-distance movement and replication maintenance defects, conferred PTGS suppression defects. Interestingly, the genes encoding these defective HC-Pro derivatives were themselves susceptible targets of PTGS, resulting in low levels of mRNA and protein accumulation. Mutations that inactivated the proteinase domain active site had no effect on PTGS suppression function. The results are consistent with the hypothesis that the role of HC-Pro in long-distance movement and genome replication depends on PTGS suppression function and that this function is independent of HC-Pro proteolytic activity.

Diabetic neuropathy masquerading as glossodynia.

BACKGROUND: Diabetic neuropathy, or DN, occurs in approximately 50 percent of patients who have type 2 diabetes mellitus, or DM. Oral burning and symptoms consistent with glossodynia (burning mouth syndrome) may occur secondary to DN. CASE DESCRIPTION: A 54-year-old woman reported to a university dental clinic with a chief complaint of oral burning. No clinical signs were evident. Her medical history was positive for type 2 DM. The initial diagnosis was glossodynia, and she was evaluated with relevant blood studies, which indicated that her diabetes was not well-controlled. The patient was referred back to her physician, and her symptoms abated once her diabetic condition was under control. CLINICAL IMPLICATIONS: It is important to consider DN within the differential diagnoses of patients who have symptoms consistent with glossodynia but have no clinical signs. Dentists are invaluable in ascertaining underlying systemic disease considerations in patients with oral symptomatology. Cooperation between dentists and physicians often is helpful and necessary in caring for patients who have uncontrolled type 2 DM and oral symptoms.

Virus-encoded suppressor of posttranscriptional gene silencing targets a maintenance step in the silencing pathway.

Certain plant viruses encode suppressors of posttranscriptional gene silencing (PTGS), an adaptive antiviral defense response that limits virus replication and spread. The tobacco etch potyvirus protein, helper component-proteinase (HC-Pro), suppresses PTGS of silenced transgenes. The effect of HC-Pro on different steps of the silencing pathway was analyzed by using both transient Agrobacterium tumefaciens-based delivery and transgenic systems. HC-Pro inactivated PTGS in plants containing a preexisting silenced beta-glucuronidase (GUS) transgene. PTGS in this system was associated with both small RNA molecules (21-26 nt) corresponding to the 3' proximal region of the transcribed GUS sequence and cytosine methylation of specific sites near the 3' end of the GUS transgene. Introduction of HC-Pro into these plants resulted in loss of PTGS, loss of small RNAs, and partial loss of methylation. These results suggest that HC-Pro targets a PTGS maintenance (as opposed to an initiation or signaling) component at a point that affects accumulation of small RNAs and methylation of genomic DNA.

Strain-specific interaction of the tobacco etch virus NIa protein with the translation initiation factor eIF4E in the yeast two-hybrid system.

The NIa protein of potyviruses provides VPg and proteolytic functions during virus replication. It has also been shown to confer host genotype-specific movement functions in plants. Specifically, NIa from tobacco etch virus (TEV)-Oxnard, but not from most other strains, confers the ability to move long distances in Nicotiana tabacum cultivar "V-20." This led to the hypothesis that all or part of NIa may interact with one or more cellular factors. To identify cellular proteins that interact with NIa in a host- or strain-specific manner, a yeast two-hybrid search of a tomato cDNA library was done. Ten proteins that interacted with NIa were recovered, with translation initiation factor eIF4E being by far the most common protein identified. Interaction of eIF4E with NIa was shown to be TEV strain-specific. eIF4E from both tomato and tobacco interacted well with NIa from the HAT strain, but not from the Oxnard strain. However, using chimeric NIa proteins, the determinant for systemic infection of V20 plants was found to be genetically distinct from the determinant controlling eIF4E interaction. In TEV-eIF4E coexpression experiments, evidence suggesting that eIF4E provides a positive effect on genome amplification was obtained.

Arabidopsis RTM2 gene is necessary for specific restriction of tobacco etch virus and encodes an unusual small heat shock-like protein.

Arabidopsis plants have a system to specifically restrict the long-distance movement of tobacco etch potyvirus (TEV) without involving either hypersensitive cell death or systemic acquired resistance. At least two dominant genes, RTM1 and RTM2, are necessary for this restriction. Through a series of coinfection experiments with heterologous viruses, the RTM1/RTM2-mediated restriction was shown to be highly specific for TEV. The RTM2 gene was isolated by a map-based cloning strategy. Isolation of RTM2 was confirmed by transgenic complementation and sequence analysis of wild-type and mutant alleles. The RTM2 gene product is a multidomain protein containing an N-terminal region with high similarity to plant small heat shock proteins (HSPs). Phylogenetic analysis revealed that the RTM2 small HSP-like domain is evolutionarily distinct from each of the five known classes of plant small HSPs. Unlike most other plant genes encoding small HSPs, expression of the RTM2 gene was not induced by high temperature and did not contribute to thermotolerance of seedlings. The RTM2 gene product was also shown to contain a large C-terminal region with multiple repeating sequences.

Cloning of the Arabidopsis RTM1 gene, which controls restriction of long-distance movement of tobacco etch virus.

The locus RTM1 is necessary for restriction of long-distance movement of tobacco etch virus in Arabidopsis thaliana without causing a hypersensitive response or inducing systemic acquired resistance. The RTM1 gene was isolated by map-based cloning. The deduced gene product is similar to the alpha-chain of the Artocarpus integrifolia lectin, jacalin, and to several proteins that contain multiple repeats of a jacalin-like sequence. These proteins comprise a family with members containing modular organizations of one or more jacalin repeat units and are implicated in defense against viruses, fungi, and insects.