Aetiological agents of ventilator-associated pneumonia and its resistance pattern – a threat for treatment

Background

Ventilator-associated pneumonia (VAP) is a common type of nosocomial pneumonia encountered in intensive care units. There are several aetiological agents which make treatment challenging. Improper antibiotic treatment of ventilated patients may lead to the emergence of multidrug resistant (MDR) pathogens.

Method

A prospective study was performed over a period of 20 months. Our study had two arms: the first, ‘Incidence and risk factors of VAP in a tertiary care hospital’ was the subject of an earlier publication; we therefore present the second investigative arm in this work. The aetiological agents of patients on mechanical ventilation (MV) were identified by standard bacteriological method. The susceptibility pattern was evaluated by Kirby-Bauer disc diffusion method. Extended spectrum beta lactamase (ESBL) testing was performed by combination disc method, and metallo-beta lactamase (MBL) testing was performed by EDTA disk synergy test (EDS).

Results

Late-onset VAP was associated with Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli, while early-onset VAP was commonly caused by members of Enterobacteriaceae, Candida albicans and Staphylococcus aureus. 72.2 per cent of VAP patients had monomicrobial and 27.8 per cent had polymicrobial infection. Out of the 24 isolates obtained from patients with VAP, seven (29.2 per cent) were MDR pathogens. ESBL and MBL production was detected in 40 per cent and 20 per cent of Klebsiella pneumoniae isolated in our study. Around 50 per cent of isolates associated with late-onset VAP were MDR, while 22.2 per cent isolates obtained from patients with earlyonset VAP were MDR.

Conclusion

VAP is a nosocomial pneumonia that is common among ventilated patients. The aetiological agents vary from common organisms to MDR pathogens that are difficult to treat. A proper knowledge of MDR pathogens and early isolation followed by prevention of prolonged antibiotic therapy can reduce the mortality of late onset VAP.     

p70S6 kinase mediates breast cancer cell survival in response to surgical wound fluid stimulation

In early breast cancer, local relapses represent a determinant and not simply an indicator of risk for distant relapse and death. Notably, 90% of local recurrences occur at or close to the same quadrant of the primary cancer. Relevance of PI3K/mTOR/p70S6K signaling in breast tumorigenesis is very well documented. However, the pathway/s involved in the process of breast cancer local relapse are not well understood. The ribosomal protein p70S6K has been implicated in breast cancer cell response to post‐surgical inflammation, supporting the hypothesis that it may be crucial also for breast cancer recurrence. Here, we show that p70S6K activity is required for the survival of breast cancer cells challenged in “hostile” microenvironments. We found that impairment of p70S6K activity in breast cancer cells strongly decreased their tumor take rate in nude mice. In line with this observation, if cells were challenged to grow in anchorage independence or in clonogenic assay, growth of colonies was strongly dependent on an intact p70S6K signaling. This in vitro finding was particularly evident when breast cancer cells were grown in the presence of wound fluids harvested following surgery from breast cancer patients, suggesting that the stimuli present in the post‐surgical setting at least partially relied on activity of p70S6K to stimulate breast cancer relapse. From a mechanistic point of view, our results indicated that p70S6K signaling was able to activate Gli1 and up‐regulate the anti‐apoptotic protein Bcl2, thereby activating a survival response in breast cancer cells challenged in hostile settings. Our work highlights a previously poorly recognized function of p70S6K in preserving breast cancer cell survival, which could eventually be responsible for local relapse and opens the way to the design of new and more specific therapies aiming to restrain the deleterious effects of wound response.     

Improved latrine cleanliness through behaviour change and changes in quality of latrine construction: a longitudinal intervention study in rural Burundi

Latrine cleanliness increased in the intervention group compared to the control group (increase from 21 to 31 % of latrines classified as clean in intervention [N = 198] and decrease from 37 to 27 % in control [N = 91]). Improved habitual latrine cleaning lead to latrines being 3.5 times more likely to improve in observed latrine cleanliness (χ² = 16.36, p < .001) and so did improvements in quality of latrine construction, eg households that had installed a lid were 7.39 times more likely to have a cleaner latrine (χ² = 4.46, p < .05). Changes in psychosocial factors, namely forgetting, personal norm, satisfaction with cleanliness, explained much of the change in habitual latrine cleaning (adj. r² = .46). Behaviour change interventions targeting psychosocial factors and quality of latrine construction seem promising to ensure clean and hygienic latrines.     

Spot-checks to measure general hygiene practice

A variety of hygiene behaviors are fundamental to the prevention of diarrhea. We used spot-checks in a survey of 761 households in Burundi to examine whether something we could call general hygiene practice is responsible for more specific hygiene behaviors, ranging from handwashing to sweeping the floor. Using structural equation modeling, we showed that clusters of hygiene behavior, such as primary caregivers’ cleanliness and household cleanliness, explained the spot-check findings well. Within our model, general hygiene practice as overall concept explained the more specific clusters of hygiene behavior well. Furthermore, the higher general hygiene practice, the more likely children were to be categorized healthy (r = 0.46). General hygiene practice was correlated with commitment to hygiene (r = 0.52), indicating a strong association to psychosocial determinants. The results show that different hygiene behaviors co-occur regularly. Using spot-checks, the general hygiene practice of a household can be rated quickly and easily.     

Polymorphism of the thiopurine S-methyltransferase gene in African- Americans

The molecular basis for the genetic polymorphism of thiopurine S - methyltransferase (TPMT) has been estab-lished for Caucasians, but it remains to be elucidated in African populations. In the current study, we determined TPMT genotypes in a population of 248 African-Americans and compared it with allele frequencies in 282 Caucasian Americans. TPMT genotype was determined in all individuals with TPMT activity indicative of a heterozygous genotype (</=10.1 U/ml pRBC, n = 23African- Americans, n = 21 Caucasians) and a control group with TPMT activity indicative of a homozygous wild-type genotype (>10.2 U/ml pRBC, n = 23 African-Americans, n = 21 Caucasians). No mutant alleles were found in the high activity control groups. The overall mutant allele frequencies were similar in African-Americans and Caucasians (4.6 and 3.7% of alleles, respectively). However, while TPMT*3C was the most prevalent mutant allele in African-Americans (52.2% of mutant alleles), it represented only 4.8% of mutant alleles in Caucasians ( P < 0.001). In contrast, TPMT*3A and TPMT*2 were less common in African-Americans (17.4 and 8.7% of mutant alleles), whereas TPMT*3A was the most prevalent mutant allele in Caucasians (85.7% of mutant alleles). A novel allele ( TPMT*8 ), containing a single nucleotide transition (G644A), leading to an amino acid change at codon 215 (Arg-->His), was found in one African-American with intermediate activity. These data indicate that the same TPMT mutant alleles are found in American black and white populations, but that the predominant mutant alleles differ in these two ethnic groups.      

Molecular characteristics of two esophageal carcinosarcomas: a hint for theclonality of carcinomatic and sarcomatic tumor components

AIM To study the clonality of the esophageal carcinosarcoma by using molecular approaches.METHODS Two esophageal carcinosarcomas were included in the study. Tumor area from dysplasticlesion, squamout cell carcinoma, basaloid cell carcinoma and spindle cell elements were microdissectedseparately. Each element was analyzed with 14 microsatellite markers and direct sequenced for p53 gene andras gene mutation.RESULTS Both tumors displayed a typical histologic feature of carcinosarcoma. Both cases showed thedivergent differentiation by immunohistochemistry study. In case 1 the identical LOH at p53 and hMLH1 lociwas detected. The heterogenous LOH was detected only in carcinosarcoma at RB1 and BRCA1 loci, whilethe LOH at ACTC locus was seen only in sarcoma. The same mutation of the splice site of exon 6-intron 6displayed in the two tumor elements. In case 2, a coordinate LOH at RB locus was demonstrated in threetypes of tumor elements: sqamous carcinoma, basaloid carcinoma and spindle cell element. A heterogenousLOH was seen only in spindle cells at TAP1 locus. No mutation in exon 5-8 of p53 gene has been found incase 2. No mutation of K-ras gene was found.CONCLUSION Although the different differentiation, the two elements of esophageal carcinosarcoma mayhave a single clonality. The p53 gene mutation occurred before the two differentiation directions switched.The distinct molecular genotype can be determined through molecular biological analysis. The microsatelliteprofiling can serve as an approach to find out which genetic alteration occurs before or after thedifferentiation is determines.     

Does laser therapy improve the wound healing process after tooth extraction? A systematic review

Laser therapy could amplify the oral wound healing process by stimulating cell regeneration after injury, attenuating pain, and modulating the immune system. The purpose of this systematic review was to evaluate whether the application of laser therapy improved alveolar healing after tooth extractions. Eight electronic databases were screened: MedLine (PubMed), The Cochrane Library, Web of Science, Scopus, Lilacs, Ibecs, Scielo, and BBO. Three reviewers independently assessed the title and abstracts of potentially relevant studies. Only clinical trials and animal experiments that evaluated the wound healing effect of laser therapy after tooth extraction were included. A total of 16 studies fulfilled all criteria, thus 8 animal experiments and 8 clinical trials were included. Different types of laser were evaluated, such as CO₂, GaAlAs, Nd:YAG, Diode Laser, HeNe, and High‐frequency Pulsed Diode Laser. Although HF, Diode and GaAs lasers were able to enhance wound healing process in clinical studies, four trials and one animal experiment showed no improvement in wound healing with laser therapy after tooth extractions. In general, the current available evidence in the literature showed that laser therapy improved the wound healing process, but these findings were limited to the type of laser applied and its specific settings. Further well‐designed and randomized controlled trials are needed to support a benefit effect of using laser therapy after tooth extraction. PROSPERO registration number: CRD42014007509 (2014).     

The influence of parental education on child mental health in Spain

Purpose

To analyze the association between parental education and offspring’s mental health in a nationally representative Spanish sample, and assess the contribution of other socioeconomic factors to the association.

Methods

We conducted a secondary analysis of data on 4- to 15-year-olds participating in the 2006 Spanish National Health Survey. Mental health was assessed using the parent-reported Strengths & Difficulties Questionnaire. Parents’ respective educational levels were summarized in a single variable. Univariate and multivariate analyses, controlling for family-, child- and parent-related characteristics, were used to study the association.

Results

The final sample comprised 5,635 children. A strong association between parental education and parent-reported child mental health was observed among 4- to 11-year-olds, with odds ratios (ORs) increasing as parental educational level decreased. Where both parents had a sub-university level, maternal education showed a stronger association than did paternal education. Following adjustment for covariates, parental education continued to be the strongest risk factor for parent-reported child mental health problems, OR = 3.7 (95% CI 2.4–5.8) for the lowest educational level, but no association was found among 12- to 15-year-olds. Male sex, immigrant status, activity limitation, parent’s poor mental health, low social support, poor family function, single-parent families, low family income and social class were associated with parent-reported child mental health problems in both age groups.

Conclusions

Our results show that there is a strong association between parental education and parent-reported child mental health, and that this is indeed stronger than that for income and social class. Among adolescents, however, the effect of parental education would appear to be outweighed by other factors.