The effect of Liver Transplantation on the quality of life of the recipient's main caregiver - a systematic review

Introduction: Liver transplantation (LT) is a transformative, life-saving procedure with life-long sequale for patients and their caregivers. The impact of LT on the patient's main caregiver can be underestimated. We carried out a systematic review of the impact of LT on the Health Related Quality of Life (HRQL) of LT patients’ main caregivers. Methods: We searched 13 medical databases from 1996 to 2015. We included studies with HRQL data on caregivers of patients following LT then quality assessed and narratively synthesized the findings from these studies. Results: Of 7076 initial hits, only five studies fell within the scope of this study. In general, they showed caregiver burden persisted in the early period following LT. One study showed improvements, however the other four showed caregiver's levels of stress, anxiety and depression, remained similar or got worse post-LT and remained above that of the normal population. It was suggested that HRQL of the patient impacted on the caregiver and vice versa and may be linked to patient outcomes. No data was available investigating which groups were at particular risk of low HRQL following LT or if any interventions could improve this. Conclusion: The current information about LT caregivers’ needs and factors that impact on their HRQL are not adequately defined. Large studies are needed to examine the effects of LT on the patients’ family and caregivers in order to understand the importance of caregiver support to maximise outcomes of LT for the patient and their caregivers

The Effect of Basal Diet on Lactate-Producing Bacteria and the Susceptibility of Sheep to Lactic Acidosis

The influence of a diet of either pasture or hay on the development of lactic acidosis in sheep was investigated using a grain challenge approach. Twenty-four Merino wethers with a mean live weight of 36.7 (s.e. 3.6) kg were used; 12 were adapted to grass pasture and 12 to hay (lucerne and oaten hay, 60 : 40) for 4 weeks before being given 1 kg of crushed barley via stomach tube. Six sheep in each group were also given virginiamycin (VM; 50 mg/kg barley) with the grain to test the efficacy of this antibiotic in controlling the bacteria responsible for the development of acidosis. Changes in volatile fatty acid (VFA), pH, lactate and bacterial count in the rumen and faecal pH and dry matter (DM) were measured for a 24-h period following administration of the barley. Daily intakes of hay were measured for a 10-day period following grain engorgement. Total ruminal VFA increased (P < 0.01) over time and tended (P = 0.08) to be higher in sheep adapted to hay than in those adapted to pasture (67.5 v. 59.8 mmol/l). The molar proportions of VFA changed (P< 0.01) over time in favour of propionate in both groups. Ruminal pH was higher (P< 0.001) in pasture-adapted sheep, but declined (P< 0.001) in both groups over time following the introduction of barley. This decline in pH was associated with increases in ruminal concentration of VFA in pasture-adapted sheep and VFA and lactate in hay-adapted sheep. The addition of VM resulted in a higher (P < 0.001) proportion of propionate and a trend towards higher (P = 0.24) faecal pH and DM content. Faecal pH and DM content declined (P < 0.001) over time and was lower for the pasture-adapted sheep. The introduction of either barley alone or barley with VM from both hay and pasture diets increased (P < 0.05) the viable counts of total bacteria, Streptococcus bovis and lactic acid bacteria. Bacterial isolates were purified and identified by complete sequencing of the 16S rRNA gene to determine the predominant bacteria during the overfeeding of grain. Isolates from medium selective for S. bovis were all identified as this species when VM was not given. VM had no effect on counts of viable bacteria, but inhibited the growth of S. bovis

Epstein-Barr virus transcription factor Zta acts through distal regulatory elements to directly control cellular gene expression

Lytic replication of the human gamma herpes virus Epstein-Barr virus (EBV) is an essential prerequisite for the spread of the virus. Differential regulation of a limited number of cellular genes has been reported in B-cells during the viral lytic replication cycle. We asked whether a viral bZIP transcription factor, Zta (BZLF1, ZEBRA, EB1), drives some of these changes. Using genome-wide chromatin immunoprecipitation coupled to next-generation DNA sequencing (ChIP-seq) we established a map of Zta interactions across the human genome. Using sensitive transcriptome analyses we identified 2263 cellular genes whose expression is significantly changed during the EBV lytic replication cycle. Zta binds 278 of the regulated genes and the distribution of binding sites shows that Zta binds mostly to sites that are distal to transcription start sites. This differs from the prevailing view that Zta activates viral genes by binding exclusively at promoter elements. We show that a synthetic Zta binding element confers Zta regulation at a distance and that distal Zta binding sites from cellular genes can confer Zta-mediated regulation on a heterologous promoter. This leads us to propose that Zta directly reprograms the expression of cellular genes through distal elements

Molecular flexibility of citrus pectins by combined sedimentation and viscosity analysis

The flexibility/rigidity of pectins plays an important part in their structure-function relationship and therefore on their commercial applications in the food and biomedical industries. Earlier studies based on sedimentation analysis in the ultracentrifuge have focused on molecular weight distributions and qualitative and semi-quantitative descriptions based on power law and Wales-van Holde treatments of conformation in terms of "extended" conformations [Harding, S. E., Berth, G., Ball, A., Mitchell, J.R., &amp; Garcìa de la Torre, J. (1991). The molecular weight distribution and conformation of citrus pectins in solution studied by hydrodynamics. Carbohydrate Polymers, 168, 1-15; Morris, G. A., Foster, T. J., &amp; Harding, S.E. (2000). The effect of degree of esterification on the hydrodynamic properties of citrus pectin. Food Hydrocolloids, 14, 227-235]. In the present study, four pectins of low degree of esterification 17-27% and one of high degree of esterification (70%) were characterised in aqueous solution (0.1 M NaCl) in terms of intrinsic viscosity [η], sedimentation coefficient (s°20,w) and weight average molar mass (Mw). Solution conformation/flexibility was estimated qualitatively using the conformation zoning method [Pavlov, G.M., Rowe, A.J., &amp; Harding, S.E. (1997). Conformation zoning of large molecules using the analytical ultracentrifuge. Trends in Analytical Chemistry, 16, 401-405] and quantitatively (persistence length Lp) using the traditional Bohdanecky and Yamakawa-Fujii relations combined together by minimisation of a target function. Sedimentation conformation zoning showed an extended coil (Type C) conformation and persistence lengths all within the range Lp=10-13 nm (for a fixed mass per unit length)

Transplantation of multiple abdominal viscera.

Two children with the short-gut syndrome and secondary liver failure were treated with evisceration and transplantation en bloc of the stomach, small intestine, colon, pancreas, and liver. The first patient died perioperatively, but the second lived for more than 6 months before dying of an Epstein-Barr virus-associated lymphoproliferative disorder that caused biliary obstruction and lethal sepsis. There was never evidence of graft rejection or of graft-vs-host disease in the long-surviving child. The constituent organs of the homograft functioned and maintained their morphological integrity throughout the 193 days of survival

Peer observation of teaching: A decoupled process

This article details the findings of research into the academic teaching staff experience of peer observation of their teaching practice. Peer observation is commonly used as a tool to enhance a teacher’s continuing professional development. Research participants acknowledged its ability to help develop their teaching practice, but they also reported that it could operate superficially as a tick box exercise, that its outcomes were frequently decoupled from formal staff development processes, and that its purpose and usefulness therefore seemed unclear. This article argues that the presence of decoupling reinforces the need to account for structural factors that can interact with peer observation of teaching to ensure it is a meaningful exercise for all teaching staff. It concludes that the published academic literature is perhaps guilty of overplaying the role of personal choice and individual tutor characteristics when addressing the complex issue that is staff disengagement with peer observation of teaching

Forecasting the burden of type 2 diabetes mellitus in Qatar to 2050: A novel modeling approach.

AIMS: We developed and demonstrated a novel mathematical modeling approach to forecast the burden of type 2 diabetes mellitus (T2DM) and to investigate T2DM epidemiology for the purpose of informing public health policy and programming. METHODS: A population-level compartmental mathematical model was constructed and applied to Qatar. The model was stratified according to sex, age group, risk factor status, and T2DM status, and was parameterized by nationally-representative data. RESULTS: T2DM prevalence increased from 16.7% in 2012 to at least 24.0% by 2050. The rise in T2DM was most prominent among 45-54 years old. T2DM health expenditure was estimated to increase by 200-600% and to account for up to 32% of total health expenditure by 2050. Prevalence of obesity, smoking, and physical inactivity was predicted to increase from 41.4% to 51.0%, from 16.4% to 19.4%, and from 45.9% to 53.0%, respectively. The proportion of T2DM incidence attributed to obesity, smoking and physical inactivity was estimated at 57.5%, 1.8%, and 5.4%, respectively in 2012, and 65.7%, 2.1%, and 6.0%, respectively in 2050. Exploring different scenarios for the trends in risk factors, T2DM prevalence reached up to 37.7% by 2050. CONCLUSIONS: Using our innovative approach, a rising T2DM epidemic is predicted to continue in the next decades, driven by population growth, ageing and adverse trends in risk factors. Obesity was the principal risk factor explaining two-thirds of T2DM incidence. T2DM must be a national priority addressed by preventive and therapeutic interventions targeting T2DM and its modifiable risk factors

Interprofessional, student-led intervention to improve insulin prescribing to patients in an Acute Surgical Receiving Unit

Our aim was to test the feasibility of interprofessional, workplace-based learning about improvement through a 4-week placement for one medical and two pharmacy final year students in an Acute Surgical Receiving Unit (ASRU). The target was insulin because this is a common, high-risk medicine in this ASRU and the intervention was medicines reconciliation. Baseline data were collected from 10 patients and used to construct a cause and effect diagram and a process map through feedback and discussions with staff. Hypoglycaemia occurred in four patients but hyperglycaemia occurred in eight patients, of whom six were placed on intravenous insulin infusion (IVII). We estimated that £2454 could be saved by preventing one patient from going on IVII. The students designed and tested a sticker to improve medicines reconciliation for insulin patients. An online form was created to capture clinician feedback on the layout and usability of the sticker. The intervention was associated with improvements in the reliability of medicines reconciliation. The students’ work contributed to a larger project to reduce the risk of hypoglycaemia in the ASRU. This proved beneficial in enabling the students to engage with the clinical team. Nonetheless, it was challenging for students from two Universities to get a shared understanding of improvement methods and work effectively with the clinical team. The students said that they learnt more about quality improvement in a working healthcare environment than they would ever learn in a classroom and they valued the opportunity to work with students from other healthcare backgrounds in practice. Despite the additional staff time required to support students from two Universities, both have supported continuation of this work

T helper cell subsets specific for pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis

Background: We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis. Methods: Peripheral blood human memory CD4+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines. Results: Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood. Conclusions: Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions

Severe childhood malaria syndromes defined by plasma proteome profiles

BACKGROUND Cerebral malaria (CM) and severe malarial anemia (SMA) are the most serious life-threatening clinical syndromes of Plasmodium falciparum infection in childhood. Therefore it is important to understand the pathology underlying the development of CM and SMA, as opposed to uncomplicated malaria (UM). Different host responses to infection are likely to be reflected in plasma proteome-patterns that associate with clinical status and therefore provide indicators of the pathogenesis of these syndromes. METHODS AND FINDINGS Plasma and comprehensive clinical data for discovery and validation cohorts were obtained as part of a prospective case-control study of severe childhood malaria at the main tertiary hospital of the city of Ibadan, an urban and densely populated holoendemic malaria area in Nigeria. A total of 946 children participated in this study. Plasma was subjected to high-throughput proteomic profiling. Statistical pattern-recognition methods were used to find proteome-patterns that defined disease groups. Plasma proteome-patterns accurately distinguished children with CM and with SMA from those with UM, and from healthy or severely ill malaria-negative children. CONCLUSIONS We report that an accurate definition of the major childhood malaria syndromes can be achieved using plasma proteome-patterns. Our proteomic data can be exploited to understand the pathogenesis of the different childhood severe malaria syndromes