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BackgroundIntraoperative evaluation with fluorescence angiography using indocyanine green (ICG) offers a dynamic assessment of gastric conduit perfusion and can guide anastomotic site selection during an esophagectomy. This study aims to evaluate the predictive value of ICG for the prevention of anastomotic leak following esophagectomy.MethodsA comprehensive search of electronic databases using the search terms “indocyanine/fluorescence” AND esophagectomy was completed to include all English articles published between January 1946 and 2018. Articles were selected by two independent reviewers. The quality of included studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) instrument.ResultsSeventeen studies were included for meta-analysis after screening and exclusions. The pooled anastomotic leak rate when ICG was used was found to be 10%. When limited to studies without intraoperative modifications, the pooled sensitivity, specificity, and diagnostic odds ratio were 0.78 (95% CI 0.52–0.94; p = 0.089), 0.74 (95% CI 0.61–0.84; p = 0.012), and 8.94 (95% CI 1.24–64.21; p = 0.184), respectively. Six trials compared ICG with an intraoperative intervention to improve perfusion to no ICG. ICG with intervention was found to have a risk reduction of 69% (OR 0.31, 95% CI 0.15–0.63).ConclusionsIn non-randomized trials, the use of ICG as an intraoperative tool for visualizing microvascular perfusion and conduit site selection to decrease anastomotic leaks is promising. However, poor data quality and heterogeneity in reported variables limits generalizability of findings. Randomized, multi-center trials are needed to account for independent risk factors for leak rates and to better elucidate the impact of ICG in predicting and preventing anastomotic leaks.

The procambium and cambium are meristematic tissues from which vascular tissue is derived. Vascular initials differentiate into phloem towards the outside of the stem and xylem towards the inside. A small peptide derived from CLV-3/ESR1-LIKE 41 (CLE41) is thought to promote cell divisions in vascular meristems by signalling through the PHLOEM INTERCALLATED WITH XYLEM (PXY) receptor kinase. pxy mutants, however, display only small reductions in vascular cell number, suggesting a mechanism exists that allows plants to compensate for the absence of PXY. Consistent with this idea, we identify a large number of genes specifically upregulated in pxy mutants, including several AP2/ERF transcription factors. These transcription factors are required for normal cell division in the cambium and procambium. These same transcription factors are also upregulated by ethylene and in ethylene-overproducing eto1 mutants. eto1 mutants also exhibit an increase in vascular cell division that is dependent upon the function of at least 2 of these ERF genes. Furthermore, blocking ethylene signalling using a variety of ethylene insensitive mutants such as ein2 enhances the cell division defect of pxy. Our results suggest that these factors define a novel pathway that acts in parallel to PXY/CLE41 to regulate cell division in developing vascular tissue. We propose a model whereby vascular cell division is regulated both by PXY signalling and ethylene/ERF signalling. Under normal circumstances, however, PXY signalling acts to repress the ethylene/ERF pathway.

To ensure equitable representation of women and BIPOC (Black, Indigenous, person of colour) individuals in surgical specialties, it is first necessary to understand the presence and extent of the disparities that exist. We explored the websites of the 17 Canadian faculties of medicine to examine sex and racial diversity in surgical specialties and in surgical leadership positions in Canada. We categorized faculty members of each department of surgery as either male or female and White or BIPOC. The relative percentage of female academic surgeons was very low compared with Canadian demographic data, and the relative percentage of BIPOC academic surgeons was similar to Canadian demographic data. Our observations suggest that actions must be taken to improve diversity and inclusion in surgery.

Sarcopenia measured through body composition analysis is emerging as an important prognosticator among various malignancies, including oesophageal cancer. Skeletal muscle index (SMI) as determined by the third lumbar vertebrae on cross‐sectional CT images has been demonstrated as a predictor of overall survival in oesophageal cancer, using pre‐defined cut off values for sarcopenia. However, this is largely within the setting of resectable disease. The primary objective of this systematic review and meta‐analysis was to determine the effect of sarcopenia defined by SMI on overall‐survival in patients with unresectable oesophageal cancer. On 30 January 2021, a systematic search of the literature was conducted to identify the role of SMI among patients with unresectable oesophageal cancer, with overall survival as the primary outcome. Databases included MEDLINE, EMBASE, Scopus, Web of Science, and Cochrane Library. Inclusion criteria included age >18, diagnosis of oesophageal cancer, and non‐operative management. A meta‐analysis was conducted using RevMan 5.4.1 using an inverse variance, random effects model. After the removal of duplicates, 2755 unique search results were obtained. Manual screening of titles and s resulted in 287 full text articles that were reviewed. Of these, five studies met the inclusion criteria with data evaluating the effect of sarcopenia defined by SMI on overall survival. A total of 783 patients, the majority of which were male (n = 638, 81%), with a mean age of 68 ± 2.3 years were included. 641 (82%) patients were diagnosed with squamous cell carcinoma. Sarcopenia, as determined by SMI using pre‐defined cut‐off values, was reported in 517 patients (66%). Meta‐analysis demonstrated decreased overall survival in the sarcopenia group compared with the non‐sarcopenia group (HR = 1.51; 95% CI 1.21–1.89; P = 0.0003; I2 = 0%; Figure 1). No significant publication bias was noted on assessment of funnel plot and Egger's test (P = 0.295). Sarcopenia as defined by SMI is predictive of overall survival among patients with nonoperative oesophageal cancer. Further analysis on the effect of sarcopenia on treatment related adverse effects and complications, particularly related to chemotherapy, radiotherapy, and oesophageal stenting, is needed to identify the degree of prognostication offered by body composition analysis. Studies on the modifiability of sarcopenia will help determine the utility of nutritional interventions.

As one of the most abundant polysaccharides on Earth, xylan will provide more than a third of the sugars for lignocellulosic biofuel production when using grass or hardwood feedstocks. Xylan is characterized by a linear β(1,4)-linked backbone of xylosyl residues substituted by glucuronic acid, 4-O-methylglucuronic acid or arabinose, depending on plant species and cell types. The biological role of these decorations is unclear, but they have a major influence on the properties of the polysaccharide. Despite the recent isolation of several mutants with reduced backbone, the mechanisms of xylan synthesis and substitution are unclear. We identified two Golgi-localized putative glycosyltransferases, GlucUronic acid substitution of Xylan (GUX)-1 and GUX2 that are required for the addition of both glucuronic acid and 4-O-methylglucuronic acid branches to xylan in Arabidopsis stem cell walls. The gux1 gux2 double mutants show loss of xylan glucuronyltransferase activity and lack almost all detectable xylan substitution. Unexpectedly, they show no change in xylan backbone quantity, indicating that backbone synthesis and substitution can be uncoupled. Although the stems are weakened, the xylem vessels are not collapsed, and the plants grow to normal size. The xylan in these plants shows improved extractability from the cell wall, is composed of a single monosaccharide, and requires fewer enzymes for complete hydrolysis. These findings have implications for our understanding of the synthesis and function of xylan in plants. The results also demonstrate the potential for manipulating and simplifying the structure of xylan to improve the properties of lignocellulose for bioenergy and other uses.

The standard treatment of atropine and oximes is insufficiently effective against all organophosphorus nerve agents. Bispyridinium non-oxime nicotinic antagonists are promising components to add to treatments. One of these, MB327, improves the survival of guinea-pigs after intoxication with tabun, sarin or soman. We extend our previous study of unsubstituted bispyridinium non-oximes with C1 to C10 alkane linkers to analogues having 4- tert- butylpyridinium rings and the same linker range. We report their effects on nicotinic-mediated calcium responses in muscle-derived (CN21) cells where nicotinic responses were inhibited in a concentration-dependent manner. A clear structure-activity relationship resulted: the inhibitory potency increased as the linker lengthened. Previous data showed the inhibition of human acetylcholinesterase in vitro increased similarly and that in general the toxicity to mice increased accordingly. However, the shorter analogues MB327 (4- tert- butyl C3) and MB442 (unsubstituted C5) compared favourably in toxicity to some oximes used to treat nerve agent poisoning. Like MB327, the non-oxime MB442, selected by the process described, improved the survival of guinea-pigs intoxicated with soman when combined with hyoscine and physostigmine or atropine and avizafone. Our research has now afforded two compounds able to protect guinea-pigs against nerve agent toxicity through a mechanism not previously exploited deliberately for this purpose.

Forward genetic screens have led to the isolation of several genes involved in secondary cell wall formation. A variety of evidence, however, suggests that the list of genes identified is not exhaustive. To address this problem, microarray data have been generated from tissue undergoing secondary cell wall formation and used to identify genes that exhibit a similar expression pattern to the secondary cell wall-specific cellulose synthase genes IRREGULAR XYLEM1 (IRX1) and IRX3. Cross-referencing this analysis with publicly available microarray data resulted in the selection of 16 genes for reverse genetic analysis. Lines containing an insertion in seven of these genes exhibited a clear irx phenotype characteristic of a secondary cell wall defect. Only one line, containing an insertion in a member of the COBRA gene family, exhibited a large decrease in cellulose content. Five of the genes identified as being essential for secondary cell wall biosynthesis have not been previously characterized. These genes are likely to define entirely novel processes in secondary cell wall formation and illustrate the success of combining expression data with reverse genetics to address gene function.

PurposePost-operative pneumonia after esophagectomy is a major contributor to morbidity and mortality. Prior studies have demonstrated a link between the presence of pathologic oral flora and the development of aspiration pneumonia. The objective of this systematic review and meta-analysis was to evaluate the effect of pre-operative oral care on the incidence of post-operative pneumonia after esophagectomy.MethodsA systematic search of the literature was performed on September 2, 2022. Screening of titles and abstracts, full-text articles, and evaluation of methodological quality was performed by two authors. Case reports, conference proceedings, and animal studies were excluded. A meta-analysis of peri-operative oral care on the odds of post-operative pneumonia after esophagectomy was performed using Revman 5.4.1 with a Mantel-Haenszel, random-effects model.ResultsA total of 736 records underwent title and abstract screening, leading to 28 full-text studies evaluated for eligibility. A total of nine studies met the inclusion criteria and underwent meta-analysis. Meta-analysis revealed a significant reduction in post-operative pneumonia among patients undergoing pre-operative oral care intervention compared to those without an oral care intervention (OR 0.57, 95% CI 0.43–0.74, p < 0.0001; I2 = 49%).ConclusionPre-operative oral care interventions have significant potential in the reduction of post-operative pneumonia after esophagectomy. North American prospective studies, as well as studies on the cost-benefit analysis, are required.

Standard treatment of poisoning by organophosphorus anticholinesterases uses atropine to reduce the muscarinic effects of acetylcholine accumulation and oximes to reactivate acetylcholinesterase (the effectiveness of which depends on the specific anticholinesterase), but does not directly address the nicotinic effects of poisoning. Bispyridinium molecules which act as noncompetitive antagonists at nicotinic acetylcholine receptors have been identified as promising compounds and one has been shown to improve survival following organophosphorus poisoning in guinea-pigs. Here, we have investigated the structural requirements for antagonism and compared inhibitory potency of these compounds at muscle and neuronal nicotinic receptors and acetylcholinesterase. A series of compounds was synthesised, in which the length of the polymethylene linker between the two pyridinium moieties was increased sequentially from one to ten carbon atoms. Their effects on nicotinic receptor-mediated calcium responses were tested in muscle-derived (CN21) and neuronal (SH-SY5Y) cells. Their ability to inhibit acetylcholinesterase activity was tested using human erythrocyte ghosts. In both cell lines, the nicotinic response was inhibited in a dose-dependent manner and the inhibitory potency of the compounds increased with greater linker length between the two pyridinium moieties, as did their inhibitory potency for human acetylcholinesterase activity in vitro. These results demonstrate that bispyridinium compounds inhibit both neuronal and muscle nicotinic receptors and that their potency depends on the length of the hydrocarbon chain linking the two pyridinium moieties. Knowledge of structure-activity relationships will aid the optimisation of molecular structures for therapeutic use against the nicotinic effects of organophosphorus poisoning.

In a screen to identify novel cellulose deficient mutants, three lines were shown to be allelic and define a novel complementation group, irregular xylem5 (irx5). IRX5 was cloned and encodes a member of the CesA family of cellulose synthase catalytic subunits (AtCesA4). irx5 plants have an identical phenotype to previously described mutations in two other members of this gene family (IRX1 and IRX3). IRX5, IRX3, and IRX1 are coexpressed in exactly the same cells, and all three proteins interact in detergent solubilized extracts, suggesting that three members of this gene family are required for cellulose synthesis in secondary cell walls. The association of IRX1 and IRX3 was reduced to undetectable levels in the absence of IRX5. Consequently, these data suggest that IRX5, IRX3, and IRX1 are all essential components of the cellulose synthesizing complex and the presence of all three subunits is required for the correct assembly of this complex.