Pre-Operative Risk Factors Predict Post-Operative Respiratory Failure after Liver Transplantation

OBJECTIVE: Post-operative pulmonary complications significantly affect patient survival rates, but there is still no conclusive evidence regarding the effect of post-operative respiratory failure after liver transplantation on patient prognosis. This study aimed to predict the risk factors for post-operative respiratory failure (PRF) after liver transplantation and the impact on short-term survival rates. DESIGN: The retrospective observational cohort study was conducted in a twelve-bed adult surgical intensive care unit in northern Taiwan. The medical records of 147 liver transplant patients were reviewed from September 2002 to July 2007. Sixty-two experienced post-operative respiratory failure while the remaining 85 patients did not. MEASUREMENTS AND MAIN RESULTS: Gender, age, etiology, disease history, pre-operative ventilator use, molecular adsorbent re-circulating system (MARS) use, source of organ transplantation, model for end-stage liver disease score (MELD) and Child-Turcotte-Pugh score calculated immediately before surgery were assessed for the two groups. The length of the intensive care unit stay, admission duration, and mortality within 30 days, 3 months, and 1 year were also evaluated. Using a logistic regression model, post-operative respiratory failure correlated with diabetes mellitus prior to liver transplantation, pre-operative impaired renal function, pre-operative ventilator use, pre-operative MARS use and deceased donor source of organ transplantation (p<0.05). Once liver transplant patients developed PRF, their length of ICU stay and admission duration were prolonged, significantly increasing their mortality and morbidity (p<0.001). CONCLUSIONS: The predictive pre-operative risk factors significantly influenced the occurrence of post-operative respiratory failure after liver transplantation

Normalizing single-cell RNA sequencing data: challenges and opportunities

Single-cell transcriptomics is becoming an important component of the molecular biologist's toolkit. A critical step when analyzing data generated using this technology is normalization. However, normalization is typically performed using methods developed for bulk RNA sequencing or even microarray data, and the suitability of these methods for single-cell transcriptomics has not been assessed. We here discuss commonly used normalization approaches and illustrate how these can produce misleading results. Finally, we present alternative approaches and provide recommendations for single-cell RNA sequencing users

Plasmodial sugar transporters as anti-malarial drug targets and comparisons with other protozoa

Glucose is the primary source of energy and a key substrate for most cells. Inhibition of cellular glucose uptake (the first step in its utilization) has, therefore, received attention as a potential therapeutic strategy to treat various unrelated diseases including malaria and cancers. For malaria, blood forms of parasites rely almost entirely on glycolysis for energy production and, without energy stores, they are dependent on the constant uptake of glucose. Plasmodium falciparum is the most dangerous human malarial parasite and its hexose transporter has been identified as being the major glucose transporter. In this review, recent progress regarding the validation and development of the P. falciparum hexose transporter as a drug target is described, highlighting the importance of robust target validation through both chemical and genetic methods. Therapeutic targeting potential of hexose transporters of other protozoan pathogens is also reviewed and discussed

Long Lasting Local and Systemic Inflammation after Cerebral Hypoxic ischemia in Newborn Mice

Background: Hypoxic ischemia (HI) is an important cause of neonatal brain injury and subsequent inflammation affects neurological outcome. In this study we performed investigations of systemic and local activation states of inflammatory cells from innate and adaptive immunity at different time points after neonatal HI brain injury in mice. Methodology/Principal Findings: We developed a multiplex flow cytometry based method combined with immunohistochemistry to investigate cellular immune responses in the brain 24 h to 7 months after HI brain injury. In addition, functional studies of ex vivo splenocytes after cerebral hypoxic ischemia were performed. Both central and peripheral activation of CD11b + and CD11c + antigen presenting cells were seen with expression of the costimulatory molecule CD86 and MHC-II, indicating active antigen presentation in the damaged hemisphere and in the spleen. After one week, naïve CD45rb + T-lymphocytes were demonstrated in the damaged brain hemisphere. In a second phase after three months, pronounced activation of CD45rb 2 T-lymphocytes expressing CD69 and CD25 was seen in the damaged hemisphere. Brain homogenate induced proliferation in splenocytes after HI but not in controls. Conclusions/Significance: Our findings demonstrate activation of both local and systemic immune responses months after hypoxic ischemic neonatal brain injury. The long term immune activation observed is of general importance for future studies of the inflammatory response after brain injury as most previous studies have focused on the first few weeks afte

Feasibility and effects of preventive home visits for at-risk older people: Design of a randomized controlled trial

Abstract Background The search for preventive methods to mitigate functional decline and unwanted relocation by older adults living in the community is important. Preventive home visit (PHV) models use infrequent but regular visits to older adults by trained practitioners with the goal of maintaining function and quality of life. Evidence about PHV efficacy is mixed but generally supportive. Yet interventions have rarely combined a comprehensive (biopsychosocial) occupational therapy intervention protocol with a home visit to older adults. There is a particular need in the USA to create and examine such a protocol. Methods/Design The study is a single-blind randomized controlled pilot trial designed to assess the feasibility, and to obtain preliminary efficacy estimates, of an intervention consisting of preventive home visits to community-dwelling older adults. An occupational therapy-based preventive home visit (PHV) intervention was developed and is being implemented and evaluated using a repeated measures design. We recruited a sample of 110 from a population of older adults (75+) who were screened and found to be at-risk for functional decline. Participants are currently living in the community (not in assisted living or a skilled nursing facility) in one of three central North Carolina counties. After consent, participants were randomly assigned into experimental and comparison groups. The experimental group receives the intervention 4 times over a 12 month follow-up period while the comparison group receives a minimal intervention of mailed printed materials. Pre- and post-intervention measures are being gathered by questionnaires administered face-to-face by a treatment-blinded research associate. Key outcome measures include functional ability, participation, life satisfaction, self-rated health, and depression. Additional information is collected from participants in the experimental group during the intervention to assess the feasibility of the intervention and potential modifiers. Fidelity is being addressed and measured across several domains. Discussion Feasibility indications to date are positive. Although the protocol has some limitations, we expect to learn enough about the intervention, delivery and effects to support a larger trial with a more stringent design and enhanced statistical power. Trial Registration ClinicalTrials.gov ID NCT0098528