A new site-specific integration system for mycobacteria

Site-specific integration into the mycobacterial chromosome can produce stable transformants useful for understanding pathogenesis. However, gene expression can be problematic at certain sites of integration. We have used the Streptomyces phiC31 integration system to integrate vector DNA into Mycobacterium smegmatis, M. bovis BCG, and M. tuberculosis through site-specific recombination. A single dominant insertion site was found in M. smegmatis, as previously reported. Three different insertion sites were found in M. bovis BCG. In M. smegmatis, integrated vectors appear to be far more stable than episomal plasmids during unselected passage in vitro, although excision products are detectable. Plasmids based on the phiC31 integration system could make useful tools for the study of mycobacterial genetics.     

Fever Evaluations after Colorectal Surgery: Identification of Risk Factors that Increase Yield and Decrease Cost

Purpose This study was designed to evaluate the yield and cost of fever evaluations in average-risk inpatients after elective colorectal surgery. Methods A 12-month, retrospective study was performed on patients who developed a postoperative fever ≥ 38°C after elective colorectal surgery. A positive fever evaluation was defined as a blood culture, urine culture, chest x-ray, or abdominal CT result that led to a change in patient management. Logistic regression, Fisher’s exact test, and chi-squared test were used; odds ratios were calculated. Results Of 133 patients, 26 percent had a positive evaluation. Blood culture, urine culture, chest x-ray, and CT were positive in 3, 8, 7, and 46 percent, respectively. Risk factors for a positive fever evaluation were temperature ≥ 38.5°C, fever evaluation after postoperative Day 6, and a clinical manifestation of systemic inflammatory response syndrome other than fever (all, P < 0.01). The cost per positive fever evaluation for the entire group, patients with 2 risk factors, or patients with 3 risk factors was $5,600, $4,200, and $2,140, respectively. Conclusions The current approach to fever evaluation after elective colorectal surgery is low yield and costly. High fever, late postoperative fever, and systemic inflammatory response syndrome are risk factors for a positive fever evaluation after colorectal surgery. Read at meeting of The American Society of Colon and Rectal Surgeons, St. Louis, Missouri, June 2 to 7, 2007.     

Blood pressure-lowering efficacy of amiloride versus enalapril as add-on drugs in patients with uncontrolled blood pressure receiving hydrochlorothiazide

A large proportion of patients with hypertension need a second drug to reach satisfactory control of blood pressure (BP), but there are few well-designed controlled trials comparing the efficacy of drugs added as a second option. In a double-blind randomized clinical trial, 82 patients with uncontrolled BP, receiving hydrochlorothiazide 25 mg daily, were selected to receive amiloride 2.5-5 mg/day (n = 39) or enalapril 10-20 mg/day (n = 43). Ambulatory blood pressure monitoring (ABPM) was done before and after 12-weeks of treatment. Office BP was measured in the 4(th), 8(th), and 12(th) weeks. The doses of amiloride and enalapril were doubled in the fourth week, and propranolol was added in the 8th week if office BP was above 140/90 mm Hg. There was a greater BP reduction in patients treated with enalapril. The ABPM delta values between the groups were 3.6 +/- 2.2, 3.9 +/- 2.2, and 1.1 +/- 2.7 mmHg for 24-h, daily, and nightly systolic blood pressure, respectively, favoring enalapril. For diastolic blood pressure (DBP), the deltas were 1.7 +/- 2.0, 3.2 +/- 1.5, and 1.2 +/- 1.9 mmHg, respectively (p = 0.039 for daily DBP). Office SBP decreased more and sooner in patients allocated to enalapril (p = 0.003). More patients taking amiloride required propranolol to control BP (p = 0.035). Potassium increased 0.3 mEq/L on the average in both groups. Cough, albeit predominantly mild, was reported more frequently by participants treated with enalapril. We conclude that enalapril is more effective than amiloride to lower BP of patients on hydrochlorothiazide with uncontrolled BP.     

Eugenol and its association with levodopa in 6‐hydroxydopamine‐induced hemiparkinsonian rats: Behavioural and neurochemical alterations

Parkinson's disease is a neurodegenerative disorder that affects the central nervous system and is mainly characterized by the loss of dopaminergic neurons and pro‐oxidant mechanisms. Eugenol has been widely studied due to its anti‐inflammatory and antioxidant activities, making it a promising neuroprotective agent. This study aimed to investigate the effects of eugenol and its combined action with levodopa in the 6‐hydroxydopamine‐induced Parkinson's disease model. Wistar rats were subjected to intrastriatal injection of 6‐hydroxydopamine (21 μg) and then treated with eugenol (0.1, 1, or 10 mg/kg), levodopa (25 mg/kg) or their combination (eugenol 10 mg/kg + levodopa 12.5 mg/kg) orally for 14 days. On the 14th day, the animals were subjected to behavioural tests, and after euthanization and dissection of the brain areas, neurochemical analyses were performed. The results showed that eugenol reduced the oxidative stress and behavioural disturbances induced by 6‐hydroxydopamine. The eugenol and levodopa combination was more effective in some behavioural parameters and body‐weight gain in addition to promoting an increase in reduced glutathione levels compared to levodopa alone. Thus, the neuroprotective activity of eugenol was observed against motor and neurochemical disorders. Additionally, the eugenol and levodopa combination was promising when compared to conventional treatment.     

Vaccines for immunoprevention of cancer

The immunoprevention of cancer and cancer recurrence is an important area of concern for the scientific community and society as a whole. Researchers have been working for decades to develop vaccines with the potential to alleviate these health care and economic burdens. So far, vaccines have made more progress in preventing cancer than in eliminating already established cancer. In particular, vaccines targeting oncogenic viruses, such as the human papillomavirus and the hepatitis B virus, are exceptional examples of successful prevention of virus-associated cancers, such as cervical cancer and hepatocellular carcinoma. Cancer-preventive vaccines targeting nonviral antigens, such as tumor-associated antigens and neoantigens, are also being extensively tested. Here, we review the currently approved preventive cancer vaccines; discuss the challenges in this field by covering ongoing preclinical and clinical human trials in various cancers; and address various issues related to maximizing cancer vaccine benefit.     

Personality Networks and Emotional and Behavioral Problems: Integrating Temperament and Character Using Latent Profile and Latent Class Analyses

Recent research indicates that adaptive functioning and well-being depends on the integration of three dissociable systems of learning and memory that regulate associative conditioning, intentionality and self-awareness. Our study objective was to describe how different integrated configurations of these systems (i.e. different expressions of personality) relate to the presence of internalizing, externalizing and total problems. In total, 699 adolescents completed the JTCI and Achenbach’s YSR. Latent profile analyses revealed two temperament profiles and six character profiles. Adolescents with a steady temperament, and those with healthy characters, were significantly less likely to present clinical levels of problems. The integration of a steady temperament and healthy character profiles in a Mature-Steady joint temperament-character network was also associated with significantly less clinical problems. In sum, our person-centered study indicates that adaptive expressions of associative conditioning, intentionality, and self-awareness (i.e. integrated personalities) are critical for mental health.