Adult respiratory distress syndrome secondary to end-stage liver disease—successful outcome following liver transplantation

The adult respiratory distress syndrome (ARDS) com­plicating liver failure carries a 100% mortality. Two cases of ARDS that resolved following liver transplantation have been reported, one associated with acute allograft rejection, and the second due to sepsis. There is, however, a great reluctance to transplant these very-high-risk patients. We report the first series of patients with ARDS secondary to liver failure who successfully underwent OLTX. No patient had sepsis or pneumonia. Posttransplant mechanical ventilation was required for a median of 14 days (range 6-37 days). All patients in this series are alive and well, with a follow-up of 6-15 months. This demonstrates that ARDS associated with liver failure, an otherwise uniformly lethal complica­tion, can respond dramatically to OLTX. © 1993 by William & Wilkins

Identification of flavin-containing monooxygenase 5 (FMO5) as a regulator of glucose homeostasis and a potential sensor of gut bacteria

We have previously identified flavin-containing monooxygenase 5 (FMO5) as a regulator of metabolic aging. The aim of the present study was to investigate the role of FMO5 in glucose homeostasis and the impact of diet and gut flora on the phenotype of mice in which the Fmo5 gene has been disrupted (Fmo5−/− mice). In comparison with wild-type (WT) counterparts, Fmo5−/− mice are resistant to age-related changes in glucose homeostasis and maintain the higher glucose tolerance and insulin sensitivity characteristic of young animals. When fed a high-fat diet, they are protected against weight gain and reduction of insulin sensitivity. The phenotype of Fmo5−/− mice is independent of diet and the gut microbiome and is determined solely by the host genotype. Fmo5−/− mice have metabolic characteristics similar to those of germ-free mice, indicating that FMO5 plays a role in sensing or responding to gut bacteria. In WT mice, FMO5 is present in the mucosal epithelium of the gastrointestinal tract where it is induced in response to a high-fat diet. In comparison with WT mice, Fmo5−/− mice have fewer colonic goblet cells, and they differ in the production of the colonic hormone resistin-like molecule β. Fmo5−/− mice have lower concentrations of tumor necrosis factor α in plasma and of complement component 3 in epididymal white adipose tissue, indicative of improved inflammatory tone. Our results implicate FMO5 as a regulator of body weight and of glucose disposal and insulin sensitivity and, thus, identify FMO5 as a potential novel therapeutic target for obesity and insulin resistance

Lasered Graphene Microheaters Modified with Phase-Change Composites: New Approach to Smart Patch Drug Delivery

The combination of paraffin wax and O,O′-bis(2-aminopropyl) polypropylene glycol–block–polyethylene glycol–block–polypropylene glycol was used as a phase-change material (PCM) for the controlled delivery of curcumin. The PCM was combined with a graphene-based heater derived from the laser scribing of polyimide film. This assembly provides a new approach to a smart patch through which release can be electronically controlled, allowing repetitive dosing. Rather than relying on passive diffusion, delivery is induced and terminated through the controlled heating of the PCM with transfer only occurring when the PCM transitions from solid to liquid. The material properties of the device and release characteristics of the strategy under repetitive dosing are critically assessed. The delivery yield of curcumin was found to be 3.5 µg (4.5 µg/cm(2)) per 3 min thermal cycle

Effect of Flavin-Containing Monooxygenase Genotype, Mouse Strain, and Gender on Trimethylamine N-oxide Production, Plasma Cholesterol Concentration, and an Index of Atherosclerosis

The objectives of the study were to determine the contribution, in mice, of members of the flavin-containing monooxygenase (FMO) family to the production of trimethylamine N-oxide (TMAO), a potential proatherogenic molecule, and whether, under normal dietary conditions, differences in TMAO production were associated with changes in plasma cholesterol concentration or with an index of atherosclerosis (Als). Concentrations of urinary trimethylamine (TMA) and TMAO and of plasma cholesterol were measured in 10-week-old male and female C57BL/6J and CD-1 mice and in mouse lines deficient in various Fmo genes (Fmo1(-/-), 2(-/-), 4(-/-) and Fmo5(-/-) ). In females most TMA N-oxygenation was catalyzed by FMO3, but in both genders 11-12% of TMA was converted to TMAO by FMO1. Gender-, Fmo genotype- and strain-related differences in TMAO production were accompanied by opposite effects on plasma cholesterol concentration. In all cases, plasma cholesterol was negatively correlated with TMAO production. Fmo genotype had no effect on Als. Als was positively correlated with TMAO in male C57BL/6J, Fmo1(-/-), 2(-/-), 4(-/-) and Fmo5(-/-) mice, but not in females, which produced substantially higher TMAO concentrations. The positive correlation in males was dependent on the inclusion of Fmo1(-/-), 2(-/-), 4(-/-) mice. In contrast, in male wild-type C57BL/6J and CD-1 mice Als was negatively correlated with TMAO. Thus, although a correlation between Als and TMAO was observed for a particular combination of mouse strain/gender/genotype this was not generally the case. Our results, therefore, indicate that under normal dietary conditions TMAO does not increase plasma cholesterol or act as a proatherogenic molecule

Supporting surveillance capacity for antimicrobial resistance: Laboratory capacity strengthening for drug resistant infections in low and middle income countries.

Development of antimicrobial resistance (AMR) threatens our ability to treat common and life threatening infections. Identifying the emergence of AMR requires strengthening of surveillance for AMR, particularly in low and middle-income countries (LMICs) where the burden of infection is highest and health systems are least able to respond. This work aimed, through a combination of desk-based investigation, discussion with colleagues worldwide, and visits to three contrasting countries (Ethiopia, Malawi and Vietnam), to map and compare existing models and surveillance systems for AMR, to examine what worked and what did not work. Current capacity for AMR surveillance varies in LMICs, but and systems in development are focussed on laboratory surveillance. This approach limits understanding of AMR and the extent to which laboratory results can inform local, national and international public health policy. An integrated model, combining clinical, laboratory and demographic surveillance in sentinel sites is more informative and costs for clinical and demographic surveillance are proportionally much lower. The speed and extent to which AMR surveillance can be strengthened depends on the functioning of the health system, and the resources available. Where there is existing laboratory capacity, it may be possible to develop 5-20 sentinel sites with a long term view of establishing comprehensive surveillance; but where health systems are weaker and laboratory infrastructure less developed, available expertise and resources may limit this to 1-2 sentinel sites. Prioritising core functions, such as automated blood cultures, reduces investment at each site. Expertise to support AMR surveillance in LMICs may come from a variety of international, or national, institutions. It is important that these organisations collaborate to support the health systems on which AMR surveillance is built, as well as improving technical capacity specifically relating to AMR surveillance. Strong collaborations, and leadership, drive successful AMR surveillance systems across countries and contexts

Assessment of the infectious diseases surveillance system of the Republic of Armenia: an example of surveillance in the Republics of the former Soviet Union

BACKGROUND: Before 1991, the infectious diseases surveillance systems (IDSS) of the former Soviet Union (FSU) were centrally planned in Moscow. The dissolution of the FSU resulted in economic stresses on public health infrastructure. At the request of seven FSU Ministries of Health, we performed assessments of the IDSS designed to guide reform. The assessment of the Armenian infectious diseases surveillance system (AIDSS) is presented here as a prototype. DISCUSSION: We performed qualitative assessments using the Centers for Disease Control and Prevention (CDC) guidelines for evaluating surveillance systems. Until 1996, the AIDSS collected aggregate and case-based data on 64 infectious diseases. It collected information on diseases of low pathogenicity (e.g., pediculosis) and those with no public health intervention (e.g., infectious mononucleosis). The specificity was poor because of the lack of case definitions. Most cases were investigated using a lengthy, non-disease-specific case-report form Armenian public health officials analyzed data descriptively and reported data upward from the local to national level, with little feedback. Information was not shared across vertical programs. Reform should focus on enhancing usefulness, efficiency, and effectiveness by reducing the quantity of data collected and revising reporting procedures and information types; improving the quality, analyses, and use of data at different levels; reducing system operations costs; and improving communications to reporting sources. These recommendations are generalizable to other FSU republics. SUMMARY: The AIDSS was complex and sensitive, yet costly and inefficient. The flexibility, representativeness, and timeliness were good because of a comprehensive health-care system and compulsory reporting. Some data were questionable and some had no utility

Sebomic identification of sex- and ethnicity-specific variations in residual skin surface components (RSSC) for bio-monitoring or forensic applications

Background: “Residual skin surface components” (RSSC) is the collective term used for the superficial layer of sebum, residue of sweat, small quantities of intercellular lipids and components of natural moisturising factor present on the skin surface. Potential applications of RSSC include use as a sampling matrix for identifying biomarkers of disease, environmental exposure monitoring, and forensics (retrospective identification of exposure to toxic chemicals). However, it is essential to first define the composition of “normal” RSSC. Therefore, the aim of the current study was to characterise RSSC to determine commonalities and differences in RSSC composition in relation to sex and ethnicity. Methods: Samples of RSSC were acquired from volunteers using a previously validated method and analysed by high-pressure liquid chromatography–atmospheric pressure chemical ionisation–mass spectrometry (HPLC-APCI-MS). The resulting data underwent sebomic analysis. Results: The composition and abundance of RSSC components varied according to sex and ethnicity. The normalised abundance of free fatty acids, wax esters, diglycerides and triglycerides was significantly higher in males than females. Ethnicity-specific differences were observed in free fatty acids and a diglyceride. Conclusions: The HPLC-APCI-MS method developed in this study was successfully used to analyse the normal composition of RSSC. Compositional differences in the RSSC can be attributed to sex and ethnicity and may reflect underlying factors such as diet, hormonal levels and enzyme expression.Peer reviewedFinal Published versio

Dimers, orientifolds and anomalies

We study 4dN = 1 gauge theories engineered via D-branes at orientifolds of toric singularities, where gauge anomalies are cancelled without the introduction of non-compact flavor branes. Using dimer model techniques, we derive geometric criteria for establishing whether a given singularity can admit anomaly-free D-brane configurations purely based on its toric data and the type of orientifold projection. Our results therefore extend the dictionary between geometric properties of singularities and physical properties of the corresponding gauge theories