Targeting post-translational modifications of histones for cancer therapy.

Post-translational modifications (PTMs) on histones including acetylation, methylation, phosphorylation, citrullination, ubiquitination, ADP ribosylation, and sumoylation, play important roles in different biological events including chromatin dynamics, DNA replication, and transcriptional regulation. Aberrant histones PTMs leads to abnormal gene expression and uncontrolled cell proliferation, followed by development of cancers. Therefore, targeting the enzymes required for specific histone PTMs holds a lot of potential for cancer treatment. In this review article, we retrospect the latest studies in the regulations of acetylation, methylation, and phosphorylation of histones. We also summarize inhibitors/drugs that target these modifications for cancer treatment.

Emergency department (ED) utilization by HIV-infected ED patients in the United States in 2009 and 2010 - a national estimation.

OBJECTIVES: The aim of the study was to describe the emergency department (ED) resource utilization patterns of ED visits by patients reported to be HIV-infected in the USA in 2009 and 2010 and to compare them with those of the general ED patient population. METHODS: We identified demographics, HIV infection status, and ED utilization patterns in 2009 and 2010 from a weighted sample of US ED visits using the National Hospital Ambulatory Medical Care Survey, a nationally representative survey. Data on visits by patients aged ≥ 13 years were analysed using procedures for multiple-stage survey data. RESULTS: In 2009 and 2010, 1 192 535 visits were documented for HIV-infected patients. The estimated annual ED visit rates were 633 per 1000 known HIV-infected persons and 438 per 1000 non-HIV-infected persons [rate difference 195; 95% confidence interval (CI) 194, 197]. While no difference was recorded in the level of acuity between HIV-infected ED patients and general ED patients, the total number of diagnostic/screening services ordered and medications administered in the ED was significantly higher for visits by HIV-infected patients. HIV-infected patients making ED visits also had a longer duration of stays [mean 5.4 h (95% CI 4.6, 6.2 h) vs. 3.6 h (95% CI 3.5, 3.8 h) for HIV-uninfected patients] and were more likely to be admitted [28% (95% CI 22, 34%) vs. 15% (95% CI 14, 16%), respectively] than their non-HIV-infected counterparts. CONCLUSIONS: ED visits by HIV-infected individuals occur at rates higher than those of visits by the general population, and consume significantly more ED resources than visits by the general population. These national findings represent baseline prior to full implementation of the 2010 Patient Protection and Affordable Care Act.

HLA-B*15:02 is associated with anemia in patients with chronic hepatitis C treated with pegylated interferon-α and ribavirin.

To investigate the relationship between human leukocyte antigen (HLA) class I and II alleles and treatment-induced anemia in chronic hepatitis C (CHC) patients receiving combination therapy with pegylated interferon-α (PEG-IFN-α) and ribavirin (RBV). One hundred six naïve CHC patients (59 females and 47 males; mean age, 53.08 years) who underwent combination treatment were enrolled. The patients were considered positive for hemoglobin (Hb)-related side effects if the Hb concentrations dropped below 10 g/dl during PEG-IFN-α plus RBV treatment. The HLA-A, -B, -C, -DR, and -DQ loci were investigated by sequence-based genotyping. The effects of the clinical characteristics, virologic variables, and the HLA alleles on treatment-induced anemia were evaluated by a logistic regression analysis. Forty patients (37.7%) had Hb levels below 10 g/dl during the treatment course. Low baseline Hb levels and an advanced liver fibrosis stage were associated with decreases in Hb levels to below 10 g/dl. The occurrence of treatment-related anemia (Hb < 10 g/dl) was significantly associated with HLA-B*15:02 as shown by multivariate analysis (adjusted odds ratio, 8.13; 95% confidence interval: 1.19-55.70; P-value after Holm's procedure, 0.03). HLA-B*15:02 is associated with treatment-induced anemia in Taiwanese CHC patients receiving combination therapy with PEG-IFN-α plus RBV.

The water exchange method for colonoscopy-effect of coaching.

The growing popularity of water immersion is supported by its long history as an adjunct to air insufflation; after facilitating colonoscope passage, the infused water is conveniently removed during withdrawal. Water exchange, a modification of water immersion to minimize discomfort in scheduled unsedated patients in the U.S. is new. Even though it may be superior in reducing pain and increasing adenoma detection, the paradigm shift to complete exclusion of air during insertion necessitates removal of infused water containing residual feces, a step often perceived as laborious and time-consuming. The nuances are the efficient steps to remove infused water predominantly during insertion to maintain minimal distension and deliver salvage cleansing. Mastery of the novel maneuvers with practice returns insertion time towards baseline. In this observational study the impact of direct verbal coaching on the primary outcome of intention-to-treat cecal intubation was assessed. The results showed that 14 of 19 (74%) experienced colonoscopists achieved 100% intention-to-treat cecal intubation. Initiation of the examination with water exchange did not preclude completion when conversion to the more familiar air insufflation method was deemed necessary to achieve cecal intubation (total 98%). The overall intention-to-treat cecal intubation rate was 88%, 90% in male and 87% in female. Only 2.7% of bowel preparation was rated as poor during withdrawal. The mean volume of water infused and cecal intubation time was 1558 ml and 18 min, respectively. Direct coaching appears to facilitate understanding of the nuances of the water exchange method. Studies of individual learning curves are necessary.

Removal of infused water predominantly during insertion (water exchange) is consistently associated with a greater reduction of pain score - review of randomized controlled trials (RCTs) of water method colonoscopy.

INTRODUCTION: Variation in the outcomes in RcTs comparing water-related methods and air insufflation during the insertion phase of colonoscopy raises challenging questions regarding the approach. This report reviews the impact of water exchange on the variation in attenuation of pain during colonoscopy by water-related methods. METHODS: Medline (2008 to 2011) searches, abstracts of the 2011 Digestive Disease Week (DDW) and personal communications were considered to identify RcTs that compared water-related methods and air insufflation to aid insertion of the colonoscope. Results: Since 2008 nine published and one submitted RcTs and five abstracts of RcTs presented at the 2011 DDW have been identified. Thirteen RcTs (nine published, one submitted and one abstract, n=1850) described reduction of pain score during or after colonoscopy (eleven reported statistical significance); the remaining reports described lower doses of medication used, or lower proportion of patients experiencing severe pain in colonoscopy performed with water-related methods compared with air insufflation (Tables 1 and 2). The water-related methods notably differ in the timing of removal of the infused water - predominantly during insertion (water exchange) versus predominantly during withdrawal (water immersion). Use of water exchange was consistently associated with a greater attenuation of pain score in patients who did not receive full sedation (Table 3). CONCLUSION: The comparative data reveal that a greater attenuation of pain was associated with water exchange than water immersion during insertion. The intriguing results should be subjected to further evaluation by additional RcTs to elucidate the mechanism of the pain-alleviating impact of the water method.

Removal of infused water predominantly during insertion (water exchange) is consistently associated with an increase in adenoma detection rate - review of data in randomized controlled trials (RCTs) of water-related methods.

INTRODUCTION: Variation in outcomes in RcTs comparing water-related methods and air insufflation raises challenging questions regarding the new approach. This report reviews impact of water exchange - simultaneous infusion and removal of infused water during insertion on adenoma detection rate (ADR) defined as proportion of patients with a least one adenoma of any size. METHODS: Medline (2008-2011) searches, abstract of 2011 Digestive Disease Week (DDW) meeting and personal communications were considered to identify RcTs that compared water-related methods and air insufflation to aid insertion of colonoscope. RESULTS: Since 2008, eleven reports of RcTs (6 published, 1 submitted and 4 abstracts, n=1728) described ADR in patients randomized to be examined by air and water-related methods. The water-related methods differed in timing of removal of the infused water -predominantly during insertion (water exchange) (n=825) or predominantly during withdrawal (water immersion) (n=903). Water immersion was associated with both increases and decreases in ADR compared to respective air method patients and the net overall change (-7%) was significant. On the other hand water exchange was associated with increases in ADR consistently and the net changes (overall, 8%; proximal overall, 11%; and proximal <10 mm, 12%) were all significant. CONCLUSION: Comparative data generated the hypothesis that significantly larger increases in overall and proximal colon ADRs were associated with water exchange than water immersion or air insufflation during insertion. The hypothesis should be evaluated by RCTs to elucidate the mechanism of water exchange on adenoma detection.

US national estimation of emergency department utilization by patients given 'HIV/AIDS-related illness' as their primary diagnosis.

BACKGROUND: The emergency department (ED) is one of the most frequent sources of medical care for many HIV-infected individuals. However, the characteristics and ED utilization patterns of patients with HIV/AIDS-related illness as the primary ED diagnosis (HRIPD) are unknown. METHODS: We identified the ED utilization patterns of HRIPD visits from a weighted sample of US ED visits (1993-2005) using the National Hospital Ambulatory Medical Care Survey, a nationally representative survey. Data on visits by patients≥18 years old were analysed using procedures for multiple-stage survey data. We compared the utilization patterns of HRIPD vs. non-HRIPD visits, and patterns across three periods (1993-1996, 1997-2000 and 2001-2005) to take into account changes in HIV epidemiology. RESULTS: Overall, 492 000 HRIPD visits were estimated to have occurred from 1993 to 2005, corresponding to 5-in-10 000 ED visits. HRIPD visits experienced longer durations of stay (5.2 h vs. 3.4 h; P=0.001), received more diagnostic tests (5.1 vs. 3.3; P<0.001), were prescribed more medications (2.5 vs. 1.8; P<0.001) and were more frequently seen by physicians (99.5%vs. 93.8%; P<0.001) compared with non-HRIPD visits. HRIPD visits were more likely to result in admission [adjusted odds ratio (OR) 7.67; 95% confidence interval (CI) 5.14-11.44]. The proportion of HRIPD visits that required emergent/urgent care or were seen by attending physicians, and the number of diagnostic tests ordered, significantly increased over time (P<0.05), while the wait time (P=0.003) significantly decreased between the second and third study periods (P<0.05). CONCLUSIONS: Although HRIPD visits were infrequent relative to all ED visits, HRIPD visits utilized significantly more resources than non-HRIPD visits and the utilization also increased over time.

High-risk sexual behaviours and genital chlamydial infections in high school students in Southern Taiwan.

The objective of this study was to determine the prevalence of high-risk sexual behaviours and sexually transmitted infections (STIs) and associated risk factors in Taiwanese high school students. Students in grades 10 and 11 (mean age: 15.9 +/- 0.9; range: 13-20 years) at two schools were recruited. An anonymous online real-time computer-assisted self-interviewing questionnaire was designed to assess demographic factors and sexual behaviours. Urine specimens were tested for genital chlamydial and gonococcal infections. The same survey and screening was conducted one year later on the same group of students. Overall, 670 individual students (993 visits) were enrolled with 323 students in both surveys. Twenty-seven percent had had sexual intercourse, and more than three quarters (79%) of them had engaged in high-risk sexual behaviours. Having friends using drugs increased the odds of practicing high-risk sexual behaviours (odds ratio [OR] 1.99, 95% CI: 1.13 to 3.50). Among 182 sexually active students, 8.8% had chlamydial (female: 12.5%; male: 5.3%) and 1.1% had gonococcal infections. Having sex with someone met on the Internet was the most significant risk factor for acquiring chlamydia (OR 8.14, 95% CI: 2.82 to 23.51). In conclusion, this adolescent population reported high prevalence of high-risk sexual behaviours and had a high prevalence of chlamydia supportive of a potential epidemic of STIs and HIV.

Turning points, reproduction number, and impact of climatological events for multi-wave dengue outbreaks.

OBJECTIVES: To study climatological and public health events which might have affected the 2007 two-wave dengue outbreak in Taiwan, an island with both tropical and subtropical regions, where the 2007 dengue incidence exceeded the combined total of the previous four years. METHODS: A multi-phase Richards model was fitted to weekly cumulative dengue data to pinpoint the turning points of the outbreak. We obtained the 'initial' reproduction numbers for the two waves of the outbreak. By means of correlation analysis we explored the possible impact of climatological events on the occurrence of turning points. RESULTS: Three turning points occurred around early August, late August/early September, and late October/early November. The 'initial' reproduction number for the first wave was R(i) = 4.67 (95% CI: 0*-10.92), where 0* = max{0, lower bound}, and R(i) = 3.93 (95% CI: 1.74-6.13) for the second wave. The highest correlation was between dengue incidence and two climatological variables: maximum temperature at a lag of 5 weeks (r = 0.66 and 0.71) and total precipitation at a lag of seven weeks (r = 0.53). Conclusions The first two turning points were partially attributable to two typhoons around early to mid-August that brought a sharp drop in temperature and substantial rainfall. The drop in temperature first drove the dengue incidence down, then the rainfall drove it up at the beginning of fall. In recent years, Taiwan has witnessed increasingly frequent large summer dengue outbreaks that persisted into early winter, perhaps due to warmer autumns. This highlights the possible impact of global warming on the spread of infectious diseases.

Production and characterization of monoclonal antibodies specific to pangasius catfish, basa, and tra.

Four IgG (subclass IgG1) class monoclonal antibodies (MAbs) strongly reactive to Asian farm-raised Pangasius catfish, tra (Pangasius hypophthalmus) and basa (Pangasius bocourti), have been developed. These MAbs were raised by immunizing an animal with thermal-stable crude sarcoplasmic protein extract of cooked tra. The MAbs were selected by screening hybridoma clones against more than 70 common fish and meat protein extracts. Two MAbs, T7E10 and T1G11, were found to be specific to the Asian Pangasius catfish, tra, and basa, with no cross-reactions with any of the common fish and meat species or with the food additive proteins (bovine serum albumin, soy proteins, milk proteins, egg proteins, and gelatin) tested. MAb T7E10 recognized 2 antigenic proteins (molecular weight approximately 36 and 75 kDa) in raw and cooked tra and basa extracts, while T1G11 bound to several proteins (molecular weight between 13 and 18 kDa) in tra and basa extracts. Two other MAbs, F7B8 and F1G11, recognized a common protein (36 KDa) and cross-reacted with all the fish extracts tested and with several mammalian species. These MAbs can be employed individually or in combination in various formats of immunoassays for rapid identification of Pangasius catfish, either raw or cooked. They can also be used to study the biological, biochemical, and physiological aspects of thermal-stable antigenic proteins. This is the first study identifying these thermal-stable antigenic proteins present in Pangasius catfish as species-specific biomarkers.

Suboptimal therapy and clinical management of gonorrhoea in an area with high-level antimicrobial resistance.

The choice of antimicrobial agents for the treatment of gonorrhoea is critical in areas where the prevalence of drug resistance is high. This study aimed to evaluate the antibiotic treatment of gonorrhoea in endemic areas. During 1999-2004, all Neisseria gonorrhoeae infections (n = 90) were evaluated. Patients' medical records and antibiotic treatment regimens were retrospectively reviewed if their isolates were viable (n = 65). In vitro antimicrobial susceptibility of N. gonorrhoeae isolates was performed. Urethritis (89%) and pelvic inflammatory disease (42%) were the most common presentations among men (n = 53) and women (n = 12), respectively. Of 54 patients with uncomplicated N. gonorrhoeae infection, 32 of them received appropriate antibiotics, including cefuroxime (n = 20), ceftriaxone (n = 10), ciprofloxacin (n = 1) and azithromycin (n = 1) during follow-ups. Among 65 patients, 53.8% were notified to the health authority. Check-ups of other sexually transmitted diseases were carried out in only 46% of patients. Not all isolates were susceptible to penicillin, 96.9% were resistant to tetracycline and 86% were resistant to ciprofloxacin. Ceftriaxone, cefixime, spectinomycin and azithromycin were active in vitro against all isolates. In conclusion, It is crucial to develop treatment guidelines according to regional antimicrobial resistances and educational programmes to improve clinical care for genital gonococcal diseases.

Focus-on-Teens, sexual risk-reduction intervention for high-school adolescents: impact on knowledge, change of risk-behaviours, and prevalence of sexually transmitted diseases.

A community-based intervention, Focus-on-Kids (FOK) has demonstrated risk-behaviour reduction of urban youth. We modified FOK to Focus-on-Teens (FOT) for high schools. High school adolescents (n=1190) were enrolled over successive school semesters. The small-group sessions were presented during the school-lunch hours. Confidential surveys were conducted at baseline, immediate, six-, and 12-month postintervention for demographics, parental communication/monitoring, sexual risk behaviours and sexually transmitted diseases (STDs)/HIV/condom-usage knowledge. Sexually active participants were encouraged to volunteer for urine-based STDs testing at the School-Based Health Centres. Many (47.4%) students reported having had sexual intercourse at baseline. Overall behaviours changed towards 'safer' sex behaviours (intent-to-use and using condoms, communicating with partner/parents about sex/condoms/STDs) with time (P<0.05). Proportion of students with complete correct knowledge of STDs/HIV increased to 88% at time 4 from 80% at baseline after adjusting for age, gender and sexual activity (P<0.05). High prevalence of STDs was detected in 875 participants who reported for urine testing at time 1: trichomonas, 11.8%; chlamydia, 10.1% and gonorrhoea, 4.1%. Prevalence decreased significantly for 310 participants who re-tested; chlamydia: 27.4% to 6.1% and gonorrhoea: 11.3% to 3.2%. FOT was successfully implemented as an STDs/HIV risk-reduction intervention. Sustained improvements of knowledge about STDs/HIV/condom usage, decreases in sexual risk behaviours supported the effectiveness of this intervention.

Evaluation of Escherichia coli O157:H7 in apple juice with Cornus fruit (Cornus officinalis Sieb. et Zucc.) extract by conventional media and thin agar layer method.

Escherichia coli O157:H7 survival in apple juice supplemented with Cornus fruit (Cornus officinalis Sieb. et Zucc.) extract was studied. Inoculated samples with or without Cornus fruit extract were kept at 21 and 7 degrees C. Microbial analysis was conducted on days 0, 1, 3, 5, and 7. MacConkey sorbitol agar (MSA), tryptic soy agar (TSA), and thin agar layer (TAL) medium were used to compare the recovery of bacteria stressed under combination treatment. Influence of temperature, storage time, and Cornus fruit on survival of cells was evaluated. The most dramatic reduction of E. coli O157:H7 was observed in apple juice with Cornus fruit extract at 21 degrees C. At 7 degrees C, E. coli O157:H7 was reduced by 2.3logcfu/ml in the apple juice with Cornus fruit extract compared to the control sample on day 7. TAL and TSA were more efficient than MSA. Cornus fruit extract can be used in combination with temperature and storage time controls to inactivate E. coli O157:H7 in apple juice. This study has shown that TAL is a viable method of recovering and differentiating injured microorganisms and apple juice supplemented with Cornus fruit has potential as a value-added beverage with antimicrobial effects and potential health benefits.

Evaluation of a commercial lateral flow feed test for rapid detection of beef and sheep content in raw and cooked meats.

Meat species adulteration is a common problem in the retail market. This study investigated the feasibility of a commercial lateral flow immunoassay designed to detect ruminant muscle tissue in feedstuffs, such as "meat-and-bone meal" (MBM) for detection of beef and/or sheep flesh in meat mixtures, and developed a simple method for meat sample extraction. Laboratory adulterated samples including raw, cooked (100°C, 30min), and sterilized (121°C, 15min) beef-in-chicken, beef-in-turkey, and lamb-in-pork at 0 to 1.00% (w/w) adulteration levels were extracted by different solvents (tap water, NaCl, and PB-NaCl with and without EDTA; and a kit-provided "Extraction Solvent") using three mixing methods. The test rapidly (20min) detected 0.50% (w/w) bovine or ovine meat; Extraction Solvent was the most efficient extractant tested; EDTA coupled with heating (100°C, 10min) improved the assay sensitivity; and all the mixing methods achieved the same results. This immunoassay can be conveniently applied to detect low levels of beef/sheep meat in a wide range of meat products.

Entrainment pattern between sympathetic and phrenic nerve activities in the Sprague-Dawley rat: hypoxia-evoked sympathetic activity during expiration.

Sympathetic and respiratory motor activities are entrained centrally. We hypothesize that this coupling may partially underlie changes in sympathetic activity evoked by hypoxia due to activity-dependent changes in the respiratory pattern. Specifically, we tested the hypothesis that sympathetic nerve activity (SNA) expresses a short-term potentiation in activity after hypoxia similar to that expressed in phrenic nerve activity (PNA). Adult male, Sprague-Dawley (Zivic Miller) rats (n = 19) were anesthetized (Equithesin), vagotomized, paralyzed, ventilated, and pneumothoracotomized. We recorded PNA and splanchnic SNA (sSNA) and generated cycle-triggered averages (CTAs) of rectified and integrated sSNA before, during, and after exposures to hypoxia (8% O(2) and 92% N(2) for 45 s). Inspiration (I) and expiration (E) were divided in half, and the average and area of integrated sSNA were calculated and compared at the following time points: before hypoxia, at the peak breathing frequency during hypoxia, immediately before the end of hypoxia, immediately after hypoxia, and 60 s after hypoxia. In our animal model, sSNA bursts consistently followed the I-E phase transition. With hypoxia, sSNA increased in both halves of E, but preferentially in the second rather than the first half of E, and decreased in I. After hypoxia, sSNA decreased abruptly, but the coefficient of variation in respiratory modulation of sSNA was significantly less than that at baseline. The hypoxic-evoked changes in sympathetic activity and respiratory pattern resulted in sSNA in the first half of E being correlated negatively to that in the second half of E (r = -0.65, P < 0.05) and positively to Te (r = 0.40, P < 0.05). Short-term potentiation in sSNA appeared not as an increase in the magnitude of activity but as an increased consistency of its respiratory modulation. By 60 s after hypoxia, the variability in the entrainment pattern had returned to baseline. The preferential recruitment of late expiratory sSNA during hypoxia results from either activation by expiratory-modulated neurons or by non-modulated neurons whose excitatory drive is not gated during late E.