Long-term Characteristics of Healthcare-associated Infections in a Neonatal Intensive Care Unit

Background/PurposeHealthcare-associated infections in neonatal intensive care units (NICUs) are associated with a significant risk of morbidity and mortality. Knowledge regarding pathogens, primary sources of infection and antibiotic resistance in the NICU is essential for developing management strategies. This study aimed to analyze the long-term characteristics of healthcare-associated infections in a tertiary referral center in southern Taiwan.MethodsInfants < 30 days old, with positive blood, cerebrospinal fluid, urine or tissue fluid cultures during hospitalization in the NICU of National Cheng Kung University Hospital from July 1989 to June 2008 were included in the study.ResultsIn total, 1,417 organisms and episodes were identified during the study period. Gram-positive organisms, Gram-negative organisms and fungi constituted 923 (65.1%), 358 (25.3%) and 136 (9.6%) of the pathogens, respectively. Of the Gram-positive organisms, coagulase-negative staphylococci (51.5%), Staphylococcus aureus (34.8%) and Enterococcus spp. (6.1%) were the major pathogens; and 27% of Staphylococcus aureus isolates were oxacillin-resistant. For the Gram-negative organisms, Klebsiella pneumoniae (22%), Pseudomonas aeruginosa (21.8%), Escherichia coli (16.7%) and Enterobacter cloacae (16.7%) were dominant. Also, Candida albicans accounted for 50% of fungal infections. The most common source of infection was bloodstream infection (59.0%), and 5.6% of these were catheter-related. Skin and soft tissue infections were also frequent (26.3%).ConclusionBloodstream and skin/soft tissue infections caused by commensal species play an important role in healthcare-associated infections in the NICU. New measures should be developed in response to the changing patterns in the NICU

Evolutionary conservation of DNA-contact residues in DNA-binding domains

<p>Abstract</p> <p>Background</p> <p>DNA-binding proteins are of utmost importance to gene regulation. The identification of DNA-binding domains is useful for understanding the regulation mechanisms of DNA-binding proteins. In this study, we proposed a method to determine whether a domain or a protein can has DNA binding capability by considering evolutionary conservation of DNA-binding residues.</p> <p>Results</p> <p>Our method achieves high precision and recall for 66 families of DNA-binding domains, with a false positive rate less than 5% for 250 non-DNA-binding proteins. In addition, experimental results show that our method is able to identify the different DNA-binding behaviors of proteins in the same SCOP family based on the use of evolutionary conservation of DNA-contact residues.</p> <p>Conclusion</p> <p>This study shows the conservation of DNA-contact residues in DNA-binding domains. We conclude that the members in the same subfamily bind DNA specifically and the members in different subfamilies often recognize different DNA targets. Additionally, we observe the co-evolution of DNA-contact residues and interacting DNA base-pairs.</p

FAM129B, an antioxidative protein, reduces chemosensitivity by competing with Nrf2 for Keap1 binding.

BackgroundThe transcription factor Nrf2 is a master regulator of antioxidant response. While Nrf2 activation may counter increasing oxidative stress in aging, its activation in cancer can promote cancer progression and metastasis, and confer resistance to chemotherapy and radiotherapy. Thus, Nrf2 has been considered as a key pharmacological target. Unfortunately, there are no specific Nrf2 inhibitors for therapeutic application. Moreover, high Nrf2 activity in many tumors without Keap1 or Nrf2 mutations suggests that alternative mechanisms of Nrf2 regulation exist.MethodsInteraction of FAM129B with Keap1 is demonstrated by immunofluorescence, colocalization, co-immunoprecipitation and mammalian two-hybrid assay. Antioxidative function of FAM129B is analyzed by measuring ROS levels with DCF/flow cytometry, Nrf2 activation using luciferase reporter assay and determination of downstream gene expression by qPCR and wester blotting. Impact of FAM129B on in vivo chemosensitivity is examined in mice bearing breast and colon cancer xenografts. The clinical relevance of FAM129B is assessed by qPCR in breast cancer samples and data mining of publicly available databases.FindingsWe have demonstrated that FAM129B in cancer promotes Nrf2 activity by reducing its ubiquitination through competition with Nrf2 for Keap1 binding via its DLG and ETGE motifs. In addition, FAM129B reduces chemosensitivity by augmenting Nrf2 antioxidative signaling and confers poor prognosis in breast and lung cancer.InterpretationThese findings demonstrate the important role of FAM129B in Nrf2 activation and antioxidative response, and identify FMA129B as a potential therapeutic target. FUND: The Chang Gung Medical Foundation (Taiwan) and the Ministry of Science and Technology (Taiwan)

Outcomes at late childhood of Chinese-speaking preschoolers with developmental language disorders comorbid with behavioral-emotional

As part of an ongoing clinical service program for children with developmental delay in morphosyllabic Chinese-speaking Taiwan, we investigated the late childhood cognitive, functional and psychiatric outcomes of a specific cohort of preschool children with developmental language delay comorbi d wi th behavi oral-emoti onal problems. The institutional database of a developmental clinic was reviewed and preschoolers meeting the inclusion criteria were invited to be subjects. Follow-up evaluations included Wechsler Intelligence tests, parents’ version of the Child Behavioral Checklist and psychiatric interview of the adolescents themselves. Of the eligible subjects (initial preschool visit at average of 3.8 ± 1.3 years old), 44 individuals completed follow-up evaluations at average of 11.8 ± 1.5 years old. The follow-up results showed that 75% of the late childhood children still had problems in language and 38.6% had problems in academic performance. The mean nonverbal cognitive score at follow-up was 83.9 ± 15.4 while the mean verbal cognitive measure was 83 ±17.3. Total 75% of the subjects had current psychiatric disorders and the most frequent di agnosi s was attenti on defici t/hyperactivity disorder, which was noted to be increased from 50% in the preschool period to 70.5% in late childhood. We concluded that the majority of Chinese-speaking preschoolers with language delay and behavioral-emotional problems turned out to have communication and psychiatric conditions when they reached late childhood. Western researches on developmental course of preschool children with alphabetic language impairment could be extended to morphosyllabic Chinese. Specialized services are warranted for this group of preschool children to lessen prolonged vulnerabilities. Our findings may be helpful in the context of an Asian developing country, so that priorities can be established for the allocation of finite resources for intervention

Automatic Morphological Subtyping Reveals New Roles of Caspases in Mitochondrial Dynamics

Morphological dynamics of mitochondria is associated with key cellular processes related to aging and neuronal degenerative diseases, but the lack of standard quantification of mitochondrial morphology impedes systematic investigation. This paper presents an automated system for the quantification and classification of mitochondrial morphology. We discovered six morphological subtypes of mitochondria for objective quantification of mitochondrial morphology. These six subtypes are small globules, swollen globules, straight tubules, twisted tubules, branched tubules and loops. The subtyping was derived by applying consensus clustering to a huge collection of more than 200 thousand mitochondrial images extracted from 1422 micrographs of Chinese hamster ovary (CHO) cells treated with different drugs, and was validated by evidence of functional similarity reported in the literature. Quantitative statistics of subtype compositions in cells is useful for correlating drug response and mitochondrial dynamics. Combining the quantitative results with our biochemical studies about the effects of squamocin on CHO cells reveals new roles of Caspases in the regulatory mechanisms of mitochondrial dynamics. This system is not only of value to the mitochondrial field, but also applicable to the investigation of other subcellular organelle morphology