Gene expression analysis on the early development of pig embryos exposed to malathion

Malathion is a widely used pesticide and there is evidence that it could alter mammal's germ and somatic cells, as well as cell lines. There are not enough studies showing how the nonacute malathion doses affect gene expression. This study analyzes gene expression alterations in pig morular embryos exposed in vitro, for 96 h, to several malathion concentrations after in vitro fertilization. cDNA libraries of isolated morular embryos were created and differential screenings performed to identify target genes. Seven clones were certainly identified. Genes related to mitochondrial metabolism as cytochrome c subunits I and III, nuclear genes such as major histocompatibility complex I (MHC I), and a hypothetical protein related with a splicing factor were the target of malathion's deregulation effect. The widespread use of malathion as a pesticide should be regarded with reproductive implications and more detailed analysis would yield more about molecular mechanisms of malathion injury on embryo cells.     

Cost Minimisation Using Clinic-Based Treatment for Common Hand Conditions – A Prospective Economic Analysis

INTRODUCTION

The purpose of this study was to compare the cost of treatment of Dupuytren''s disease, ganglia and trigger digits in the out-patient department with the operating theatre.

PATIENTS AND METHODS

All patients seen in a new patient hand clinic with a diagnosis of Dupuytren''s disease, trigger digit or ganglion of the wrist or hand requiring treatment were prospectively identified over a 6-month period. The numbers undergoing a procedure in the out-patient clinic or theatre were recorded. Costings of theatre time and out-patient time, as well as national tariff income, were obtained from the hospital management.

RESULTS

Over the 6-month period, 80, 26, and 52 patients were treated with regard to Dupuytren''s disease, ganglia and trigger digits, respectively. Of these, 37, 23, and 44 were treated by an out-patient procedure, and 43, 3 and 8 underwent a formal operation. The total cost of the out-patient procedures was calculated at £1560 over 6 months. To perform these as formal operations would have cost £64,896. The cost savings were, therefore, £63,336, or £126,672 per annum.

CONCLUSIONS

Out-patient interventions for Dupuytren''s disease, ganglia and trigger digits result in significant cost savings over formal surgical treatment.     

Threats of Cross-Contamination on Effects of a Sexual Risk Reduction Intervention: Fact or Fiction

This study sought to empirically evaluate the extent and impact of cross-contamination on the effects of a STI/HIV intervention trial previously shown to be effective in reducing high-risk sexual behaviors among African–American adolescent females. Participants were recruited through community health agencies in the Southeastern United States and comprised 522 sexually active 14- to 18- year-old African–American females who completed self-administered questionnaires and face-to-face interviews at baseline, 6- and 12-month time points. Participants were randomized to a STI/HIV risk reduction group or a general health promotion group. The STI/HIV intervention group participated in four group sessions addressing constructs such as HIV knowledge, communication, condom use self-efficacy and condom use behaviors. The control group participated in four group sessions focused on general health topics. The study setting afforded multiple opportunities for cross-talk between intervention and control group participants. Consistent condom use, defined as condom use during every vaginal sex act, was the primary outcome measure. Other outcome measures included various sexual behaviors, observed condom application skills and psychosocial variables associated with HIV preventive behaviors. Approximately 73% of participants reported some level of cross-talk. Linear and binary GEE models assessing the impact of the STI/HIV intervention on contaminated vs. uncontaminated control group participants indicated no differential effects of the intervention. Furthermore, equivalence tests demonstrated that contaminated and uncontaminated control groups were equivalent. Findings from this study provide empirical evidence suggesting that behavioral and psychosocial outcomes may be resistant to cross-contamination in randomized controlled trials testing safer sex interventions among African–American adolescent females.     

Genomic rearrangements at the BRCA1 locus in Spanish families with breast/ovarian cancer

BACKGROUND: Large genomic rearrangements (LGRs) account for a substantial proportion of the BRCA1 disease-causing changes, or variations, identified in families with hereditary breast/ovarian cancer [HB(O)C]. Great differences in the spectrum and prevalence of BRCA1 LGR have been observed among populations. Here we report the first comprehensive analysis of BRCA1 LGRs conducted in Spain. METHODS: We used multiplex ligation-dependent probe amplification (MLPA) to screen for BRCA1 LGRs in the index case individuals of 384 HB(O)C families who previously tested negative for BRCA1 and BRCA2 point variations, small insertions, and deletions. An alternative set of MLPA probes, long-range PCR, and real-time PCR were used to confirm positive results. RESULTS: We have identified 8 different BRCA1 rearrangements (del exon 1-24, del exon 8-13, del exon 11-15, del exon 14, dup exon 19-20, dup exon 20, exon 21-22 amplification, and del exon 23-24). With the exception of del exon 8-13, they are novel alterations. Overall, BRCA1 LGRs explain 1.4% of the Spanish HB(O)C families, and they account for 8.2% of all BRCA1 pathogenic variations identified in our study population. BRCA1 genetic variants affecting hybridization of commercially available MLPA probes are very rare in our population. CONCLUSIONS: Screening for BRCA1 LGRs should be mandatory in Spanish HB(O)C families. A high proportion of country-specific rearrangements are scattered along the gene. MLPA is a robust method to screen for LGRs in our population. MLPA analysis of positive samples with an alternative set of probes, together with long-range PCR and real-time PCR, is a feasible approach to confirm results in cases in which LGR breakpoints have not been characterized.     

Inhibition of choriodecidual cytokine production and inflammatory gene expression by selective I-��B kinase (IKK) inhibitors

BACKGROUND AND PURPOSE

Inflammation of the extraplacental membranes plays a key role in the pathogenesis of preterm labour. The aim of this study was to screen a number of commercially available small molecule nuclear factor-kappa B inhibitors to identify candidates suitable for clinical evaluation as anti-inflammatory agents for the prevention of preterm birth.

EXPERIMENTAL APPROACH

Nine inhibitors were evaluated across a range of concentrations for their ability to inhibit lipopolysaccharide (LPS)-stimulated cytokine production in primary term choriodecidual cells in culture without affecting cell viability. Expression of 112 inflammation- and apoptosis-related genes was evaluated using boutique oligonucleotide arrays.

KEY RESULTS

Two IKKβ inhibitors were found to be highly effective and non-toxic inhibitors of choriodecidual cytokine production: parthenolide and [5-(p-fluorophenyl)-2-ureido] thiophene-3-carboxamide (TPCA-1). Both compounds also inhibited LPS-stimulated nuclear translocation of p65/RelA. Expression of 38 genes on the arrays (34%) was significantly (P < 0.05) inhibited by TPCA-1 or parthenolide. Of the 14 genes significantly stimulated by LPS, all were inhibited by TPCA-1 and 12 were inhibited by parthenolide. Overall, gene expression was more robustly inhibited by TPCA-1 than parthenolide; however, expression of two genes was only inhibited by parthenolide. Neither compound significantly altered the expression profile of anti-apoptosis genes on the arrays.

CONCLUSIONS AND IMPLICATIONS

These studies provide evidence that pharmacological inhibition of IKKβ activity holds promise as a potential strategy for the prevention and/or treatment of inflammation-driven preterm birth. TPCA-1 appeared the most promising compound among those tested in this study. Different inhibitors may have subtly different effect profiles despite having similar modes of action.     

Association between oral health and gastric precancerous lesions

Although recent studies have suggested that tooth loss is positively related to the risk of gastric non-cardia cancer, the underlying oral health conditions potentially responsible for the association remain unknown. We investigated whether clinical and behavioral measures of oral health are associated with the risk of gastric precancerous lesions. We conducted a cross-sectional study of 131 patients undergoing upper gastrointestinal endoscopy. Cases were defined as those with gastric precancerous lesions including intestinal metaplasia or chronic atrophic gastritis on the basis of standard biopsy review. A validated structured questionnaire was administered to obtain information on oral health behaviors. A comprehensive clinical oral health examination was performed on a subset of 91 patients to evaluate for periodontal disease and dental caries experience. A total of 41 (31%) cases of gastric precancerous lesions were identified. Compared with non-cases, cases were significantly more likely to not floss their teeth [odds ratio (OR) = 2.89, 95% confidence interval (CI): 1.09-7.64], adjusting for age, sex, race, body mass index, smoking status, educational attainment and Helicobacter pylori status in serum. Among participants who completed the oral examination, cases (n = 28) were more likely to have a higher percentage of sites with gingival bleeding than non-cases [OR = 2.63, 95% CI: 1.37-5.05 for a standard deviation increase in bleeding sites (equivalent to 19.7%)], independent of potential confounders. Our findings demonstrate that specific oral health conditions and behaviors such as gingival bleeding and tooth flossing are associated with gastric precancerous lesions.     

African-American Female Adolescents Who Engage in Oral, Vaginal and Anal Sex: “Doing It All” as a Significant Marker for Risk of Sexually Transmitted Infection

African-American female adolescents who engaged in vaginal sex only (N = 272) were compared to adolescents who engaged in two types (vaginal plus oral or anal; N = 295) and three types (vaginal, oral and anal; N = 144) on a constellation of other sexual risk behaviors (SRBs) and on sexually transmitted infections (STIs). Adjusted contrasts among groups revealed that adolescents who engaged in two and in three types of sex as compared to those who engaged in vaginal sex only were more likely to engage in six of the seven SRBs, but were just as likely to have a STI. One SRB, having ≥ 4 lifetime sex partners, was in turn associated with STI. Two-way interactions indicated that having a casual sex partner and having multiple sex partners in the last 60 days increased the likelihood of STI, but only for adolescents who engaged in all three types.