Emergency open cholecystectomy is associated with markedly lower incidence of postoperative nausea and vomiting (PONV) than elective open cholecystectomy: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>During a previous study to define and compare incidence risks of postoperative nausea and vomiting (PONV) for elective laparoscopic and open cholecystectomy at two hospitals in Jamaica, secondary analysis comparing PONV risk in elective open cholecystectomy to that after emergency open cholecystectomy suggested that it was markedly reduced in the latter group. The decision was made to collect data on an adequate sample of emergency open cholecystectomy cases and further explore this unexpected finding in a separate study.</p> <p>Methods</p> <p>Data were collected for 91 emergency open cholecystomy cases identified at the two paricipating hospitals from May 2007 retrograde, as was done for the 175 elective open cholecystectomy cases (from the aforementioned study) with which the emergency cases were to be compared. Variables selected for extraction and statistical analysis included all those known, suspected and plausibly associated with the risk of PONV and with urgency of surgery.</p> <p>Results</p> <p>Emergency open cholecystectomy was associated with a markedly reduced incidence risk of PONV compared to elective open cholecystectomy (6.6% versus 28.6%, P < 0.001). The suppressive effect of emergency increased after adjustment for confounders in a multivariable logistic regression model (odds ratio 0.103, P < 0.001). This finding also identifies, by extrapolation, an association between reduced risk of PONV and preoperative nausea and vomiting, which occurred in 80.2% of emergency cases in the 72 hour period preceding surgery.</p> <p>Conclusions</p> <p>The incidence risk of postoperative nausea and vomiting is markedly decreased after emergency open cholecystectomy compared to elective open cholecystectomy. The study, by extrapolation, also identifies a paradoxical association between pre-operative nausea and vomiting, observed in 80.2% of emergency cases, and suppression of PONV. This association, if confirmed in prospective cohort studies, may have implications for PONV prophylaxis if it can be exploited at a sub-clinical level.</p

Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy

Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential (ΔΨm). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control

The pharmacological regulation of cellular mitophagy

Small molecules are pharmacological tools of considerable value for dissecting complex biological processes and identifying potential therapeutic interventions. Recently, the cellular quality-control process of mitophagy has attracted considerable research interest; however, the limited availability of suitable chemical probes has restricted our understanding of the molecular mechanisms involved. Current approaches to initiate mitophagy include acute dissipation of the mitochondrial membrane potential (ΔΨm) by mitochondrial uncouplers (for example, FCCP/CCCP) and the use of antimycin A and oligomycin to impair respiration. Both approaches impair mitochondrial homeostasis and therefore limit the scope for dissection of subtle, bioenergy-related regulatory phenomena. Recently, novel mitophagy activators acting independently of the respiration collapse have been reported, offering new opportunities to understand the process and potential for therapeutic exploitation. We have summarized the current status of mitophagy modulators and analyzed the available chemical tools, commenting on their advantages, limitations and current applications

Heterosis Is Prevalent for Multiple Traits in Diverse Maize Germplasm

BACKGROUND: Heterosis describes the superior phenotypes observed in hybrids relative to their inbred parents. Maize is a model system for studying heterosis due to the high levels of yield heterosis and commercial use of hybrids. METHODS: The inbred lines from an association mapping panel were crossed to a common inbred line, B73, to generate nearly 300 hybrid genotypes. Heterosis was evaluated for seventeen phenotypic traits in multiple environments. The majority of hybrids exhibit better-parent heterosis in most of the hybrids measured. Correlations between the levels of heterosis for different traits were generally weak, suggesting that the genetic basis of heterosis is trait-dependent. CONCLUSIONS: The ability to predict heterosis levels using inbred phenotype or genetic distance between the parents varied for the different traits. For some traits it is possible to explain a significant proportion of the heterosis variation using linear modeling while other traits are more difficult to predict

Female Chimpanzees Use Copulation Calls Flexibly to Prevent Social Competition

The adaptive function of copulation calls in female primates has been debated for years. One influential idea is that copulation calls are a sexually selected trait, which enables females to advertise their receptive state to males. Male-male competition ensues and females benefit by getting better mating partners and higher quality offspring. We analysed the copulation calling behaviour of wild female chimpanzees (Pan troglodytes schweinfurthii) at Budongo Forest, Uganda, but found no support for the male-male competition hypothesis. Hormone analysis showed that the calling behaviour of copulating females was unrelated to their fertile period and likelihood of conception. Instead, females called significantly more while with high-ranking males, but suppressed their calls if high-ranking females were nearby. Copulation calling may therefore be one potential strategy employed by female chimpanzees to advertise receptivity to high-ranked males, confuse paternity and secure future support from these socially important individuals. Competition between females can be dangerously high in wild chimpanzees, and our results indicate that females use their copulation calls strategically to minimise the risks associated with such competition

Genetic dissection of heterosis using epistatic association mapping in a partial NCII mating design

Heterosis refers to the phenomenon in which an F1 hybrid exhibits enhanced growth or agronomic performance. However, previous theoretical studies on heterosis have been based on bi-parental segregating populations instead of F1 hybrids. To understand the genetic basis of heterosis, here we used a subset of F1 hybrids, named a partial North Carolina II design, to perform association mapping for dependent variables: original trait value, general combining ability (GCA), specific combining ability (SCA) and mid-parental heterosis (MPH). Our models jointly fitted all the additive, dominance and epistatic effects. The analyses resulted in several important findings: 1) Main components are additive and additive-by-additive effects for GCA and dominance-related effects for SCA and MPH, and additive-by-dominant effect for MPH was partly identified as additive effect; 2) the ranking of factors affecting heterosis was dominance > dominance-by-dominance > over-dominance > complete dominance; and 3) increasing the proportion of F1 hybrids in the population could significantly increase the power to detect dominance-related effects, and slightly reduce the power to detect additive and additive-by-additive effects. Analyses of cotton and rapeseed datasets showed that more additive-by-additive QTL were detected from GCA than from trait phenotype, and fewer QTL were from MPH than from other dependent variables

Heterosis as Investigated in Terms of Polyploidy and Genetic Diversity Using Designed Brassica juncea Amphiploid and Its Progenitor Diploid Species

Fixed heterosis resulting from favorable interactions between the genes on their homoeologous genomes in an allopolyploid is considered analogous to classical heterosis accruing from interactions between homologous chromosomes in heterozygous plants of a diploid species. It has been hypothesized that fixed heterosis may be one of the causes of low classical heterosis in allopolyploids. We used Indian mustard (Brassica juncea, 2n = 36; AABB) as a model system to analyze this hypothesis due to ease of its resynthesis from its diploid progenitors, B. rapa (2n = 20; AA) and B. nigra (2n = 16; BB). Both forms of heterosis were investigated in terms of ploidy level, gene action and genetic diversity. To facilitate this, eleven B. juncea genotypes were resynthesized by hybridizing ten near inbred lines of B. rapa and nine of B. nigra. Three half diallel combinations involving resynthesized B. juncea (11×11) and the corresponding progenitor genotypes of B. rapa (10×10) and B. nigra (9×9) were evaluated. Genetic diversity was estimated based on DNA polymorphism generated by SSR primers. Heterosis and genetic diversity in parental diploid species appeared not to predict heterosis and genetic diversity at alloploid level. There was also no association between combining ability, genetic diversity and heterosis across ploidy. Though a large proportion (0.47) of combinations showed positive values, the average fixed heterosis was low for seed yield but high for biomass yield. The genetic diversity was a significant contributor to fixed heterosis for biomass yield, due possibly to adaptive advantage it may confer on de novo alloploids during evolution. Good general/specific combiners at diploid level did not necessarily produce good general/specific combiners at amphiploid level. It was also concluded that polyploidy impacts classical heterosis indirectly due to the negative association between fixed heterosis and classical heterosis

A Dynamic and Complex Network Regulates the Heterosis of Yield-Correlated Traits in Rapeseed (Brassica napus L.)

Although much research has been conducted, the genetic architecture of heterosis remains ambiguous. To unravel the genetic architecture of heterosis, a reconstructed F2 population was produced by random intercross among 202 lines of a double haploid population in rapeseed (Brassica napus L.). Both populations were planted in three environments and 15 yield-correlated traits were measured, and only seed yield and eight yield-correlated traits showed significant mid-parent heterosis, with the mean ranging from 8.7% (branch number) to 31.4% (seed yield). Hundreds of QTL and epistatic interactions were identified for the 15 yield-correlated traits, involving numerous variable loci with moderate effect, genome-wide distribution and obvious hotspots. All kinds of mode-of-inheritance of QTL (additive, A; partial-dominant, PD; full-dominant, D; over-dominant, OD) and epistatic interactions (additive × additive, AA; additive × dominant/dominant × additive, AD/DA; dominant × dominant, DD) were observed and epistasis, especially AA epistasis, seemed to be the major genetic basis of heterosis in rapeseed. Consistent with the low correlation between marker heterozygosity and mid-parent heterosis/hybrid performance, a considerable proportion of dominant and DD epistatic effects were negative, indicating heterozygosity was not always advantageous for heterosis/hybrid performance. The implications of our results on evolution and crop breeding are discussed

Impact of DOTS expansion on tuberculosis related outcomes and costs in Haiti

BACKGROUND: Implementation of the World Health Organization's DOTS strategy (Directly Observed Treatment Short-course therapy) can result in significant reduction in tuberculosis incidence. We estimated potential costs and benefits of DOTS expansion in Haiti from the government, and societal perspectives. METHODS: Using decision analysis incorporating multiple Markov processes (Markov modelling), we compared expected tuberculosis morbidity, mortality and costs in Haiti with DOTS expansion to reach all of the country, and achieve WHO benchmarks, or if the current situation did not change. Probabilities of tuberculosis related outcomes were derived from the published literature. Government health expenditures, patient and family costs were measured in direct surveys in Haiti and expressed in 2003 US$. RESULTS: Starting in 2003, DOTS expansion in Haiti is anticipated to cost$4.2 million and result in 63,080 fewer tuberculosis cases, 53,120 fewer tuberculosis deaths, and net societal savings of $131 million, over 20 years. Current government spending for tuberculosis is high, relative to the per capita income, and would be only slightly lower with DOTS. Societal savings would begin within 4 years, and would be substantial in all scenarios considered, including higher HIV seroprevalence or drug resistance, unchanged incidence following DOTS expansion, or doubling of initial and ongoing costs for DOTS expansion. CONCLUSION: A modest investment for DOTS expansion in Haiti would provide considerable humanitarian benefit by reducing tuberculosis-related morbidity, mortality and costs for patients and their families. These benefits, together with projected minimal Haitian government savings, argue strongly for donor support for DOTS expansion