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• Carboxyhemoglobin (CO-Hb) was reported to likely reflect hemolysis and inflammation, both risk factors for cardiac surgery–associated acute kidney injury (CSA-AKI). • CO-Hb is easily obtainable and available on routine blood gas in cardiac surgery patients at no additional costs or equipment. • Patients with CO-Hb ≥1.4% at intensive care unit admission showed a significantly higher rate of CSA-AKI. • CO-Hb at intensive care unit admission may serve as a practical and biologically logical biomarker in both clinical and research settings. • Specifically for research purposes, CO-Hb could be used for risk stratification and population enrichment in trials of CSA-AKI prevention to increase statistical power, decrease the sample size, and lower the cost of trials. Carboxyhemoglobin (CO-Hb) is a marker of hemolysis and inflammation, both risk factors for cardiac surgery–associated AKI (CSA-AKI). However, the association between CO-Hb and CSA-AKI remains unknown. A retrospective cohort study. Tertiary university-affiliated metropolitan hospital: single center. Adult on-pump cardiac surgery patients from July 2014 to June 2022 (N = 1,698). None. Patients were stratified into quartiles based on CO-Hb levels at intensive care unit (ICU) admission. A progressive increased risk of CSA-AKI was observed with higher CO-Hb levels at ICU admission. On multivariable logistic regression analysis, the highest quartile (CO-Hb ≥ 1.4%) showed an independent association with the occurrence of CSA-AKI (odds ratio 1.45 compared to the lowest quartile [CO-Hb < 1.0%], 95% CI 1.023-2.071; p = 0.038). Compared to patients with CO-Hb <1.4%, patients with CO-Hb ≥ 1.4% at ICU admission had significantly higher postoperative creatinine (135 vs 116 μmol/L, p < 0.001), higher rates of postoperative RRT (6.7% vs 2.3%, p < 0.001) and AKI (p < 0.001) on univariable analysis and shorter time to event for AKI or death (p < 0.001). CO-Hb ≥ 1.4% at ICU admission is an independent risk factor for CSA-AKI, which is easily obtainable and available on routine arterial blood gas measurements. Thus, CO-Hb may serve as a practical and biologically logical biomarker for risk stratification and population enrichment in trials of CSA-AKI prevention. [ABSTRACT FROM AUTHOR]

Septic shock is common and associated with significant morbidity and mortality. The ADRENAL trial examined the use of hydrocortisone in patients with septic shock, demonstrating no difference in patient-centred outcomes but a decrease in the time to shock resolution. The change in clinical practice related to the publication of the ADRENAL trial is currently unknown. A retrospective cohort study examining the use of hydrocortisone in patients with septic shock was conducted in 12 intensive care units (ICUs). A segmented linear regression was performed to identify a stepwise change in hydrocortisone administration and 90-day mortality associated with the publication of the ADRENAL trial. We included 4,198 patients with a mean age of 58 years (standard deviation, SD17), and the median noradrenaline equivalent score (NEE) was 0.07 μg/kg/min (IQR 0.02–0.17). Segmented regression analysis for hydrocortisone administration identified two breakpoints, 3 months before and 6 months after publication, leading to three periods: Pre-publication, Transition, and Post-publication. Compared to the pre-publication period, the Transition and Post-publication cohorts had a higher proportion of hydrocortisone administration (28% vs. 34% vs. 43%; p < 0.0001). Furthermore, after adjustment for temporal change, the transition period had a significant change in the slope of the proportion of patients receiving hydrocortisone (−0.1% per month vs. +1.4% per month; p = 0.026), whereas this was not statistically significant during the post-publication period (+0.1% per month, p = 0.66). After adjusting for confounders, the Transition and Post-publication periods were independently associated with an increase in hydrocortisone (OR 1.4, 95% CI 1.14–1.77; p = 0.0015 and OR 2.03; 95% CI 1.74–2.36; p < 0.001, respectively). Furthermore, after adjusting for confounders, when compared to the Pre-transition period, the use of hydrocortisone was associated with a statistically significant decrease in 90-day mortality (14% vs. 24% absolute difference, aHR for hydrocortisone effect −0.81; 95% CI 0.65–0.99; p = 0.044). Publication of the ADRENAL trial changed clinical practice in Queensland ICUs with increased prescription of hydrocortisone for patients with septic shock with an associated reduction in mortality. [ABSTRACT FROM AUTHOR]

New Mexican members of the SSAT (and thus of the Mexican Chapter of the SSAT) have now become possible, because as all its members are surgeons affiliated with the Mexican Association of General Surgery (AMCG) and the Latin American Federation of Surgery (FELAC). We view this collaboration between the SSAT and our Mexican chapter of the SSAT as being of great relevance to the education of Mexican surgeons as well as their participation in the yearly SSAT meeting in the USA. Keywords: Surgery; Alimentary tract; Society surgery; Research EN Surgery Alimentary tract Society surgery Research 519 522 4 03/21/22 20220301 NES 220301 The Society of Surgery of the Alimentary Tract (the SSAT) had its origin in the late 1950s, created by a group of academic surgeons from well-known surgical centers in the USA. [Extracted from the article]

Abstract: In this paper, the dispersion compensation techniques are compared on the basis of eye opening, eye closure, bit error rate and Q-factor. These techniques are applied to CSRZ system, which operates at bit rates of 2.5, 5, 10, 15 and 20Gbps bit rates. The technique using fiber Bragg grating (FBG) for dispersion compensation is the best technique as this technique gives larger values of eye opening at 10 and 20Gbps bit rate, smaller values of eye closure at 10 and 20Gbps, minimum value of BER at 15Gbps and maximum value of Q-factor at 15Gbps when compared with other techniques. The RDF technique is the next best technique since this technique gives maximum value of eye opening when other techniques give almost similar values of eye opening at 15Gbps, minimum value of eye closure at 15Gbps, minimum value of BER at 15Gbps and maximum value of Q-factor at 15Gbps when compared with other techniques. The DCF is the next best technique as this technique gives maximum and minimum values of eye opening and eye closure at 20Gbps (next best to FBG at 20Gbps). [Copyright &y& Elsevier]

Eukaryotic type Ser/Thr protein kinases have recently been shown to regulate a variety of cellular functions in bacteria. PknA, a transmembrane Ser/Thr protein kinase from Mycobacterium tuberculosis, when constitutively expressed in Escherichia coli resulted in cell elongation and therefore has been thought to be regulating morphological changes associated with cell division. Bioinformatic analysis revealed that PknA has N-terminal catalytic, juxtamembrane, transmembrane, and C-terminal extracellular domains, like known eukaryotic type Ser/Thr protein kinases from other bacteria. To identify the minimum region capable of exhibiting phosphorylation activity of PknA, we created several deletion mutants. Surprisingly, we found that the catalytic domain itself was not sufficient for exhibiting phosphorylation ability of PknA. However, the juxtamembrane region together with the kinase domain was necessary for the enzymatic activity and thus constitutes the catalytic core of PknA. Utilizing this core, we deduce that the autophosphorylation of PknA is an intermolecular event. Interestingly, the core itself was unable to restore the cell elongation phenotype as manifested by the full-length protein in E. coli; however, its co-expression along with the C-terminal region of PknA can associate them in trans to reconstitute a functional protein in vivo. Therefore, these findings argue that the transmembrane and extracellular domains of PknA, although dispensable for phosphorylation activities, are crucial in responding to signals. Thus, our results for the first time establish the significance of different domains in a bacterial eukaryotic type Ser/Thr kinase for reconstitution of its functionality. [ABSTRACT FROM AUTHOR]

D -galactonate, a widely prevalent sugar acid, was first reported as a nutrient source for enteric bacteria in the 1970s. Since then, decades of research enabled a description of the modified Entner-Doudoroff pathway involved in its degradation and reported the structural and biochemical features of its metabolic enzymes, primarily in Escherichia coli K-12. However, only in the last few years, the D -galactonate transporter has been characterized, and the regulation of the dgo operon, encoding the structural genes for the transporter and enzymes of D -galactonate metabolism, has been detailed. Notably, in recent years, multiple evolutionary studies have identified the dgo operon as a dominant target for adaptation of E. coli in the mammalian gut. Despite considerable research on dgo operon, numerous fundamental questions remain to be addressed. The emerging relevance of the dgo operon in host–bacterial interactions further necessitates the study of D -galactonate metabolism in other enterobacterial strains. • Enteric bacteria use D -galactonate as a carbon and energy source. • DgoT, a Major Facilitator superfamily transporter, transports D -galactonate. • Dehydratase DgoD, kinase DgoK, and aldolase DgoA catabolize D -galactonate. • DgoR, a GntR/FadR family member, represses dgo genes; D -galactonate is its effector. • dgo genes are implicated in the interaction of enteric bacteria with their host. [ABSTRACT FROM AUTHOR]

The Escherichia coli envelope stress response is controlled by the alternative sigma factor, σ[supE], and is induced when unfolded outer membrane proteins accumulate in the periplasm. The response is initiated by sequential cleavage of the membrane-spanning antisigma factor, RseA. RseB is an important negative regulator of envelope stress response that exerts its negative effects on σ[supE] activity through its binding to RseA. In this study, we analyze the interaction between RseA and RseB. We found that tight binding of RseB to RseA required intact RseB. Using programs that performed global and local sequence alignment of RseB and RseA, we found regions of high similarity and performed alanine substitution mutagenesis to test the hypothesis that these regions were functionally important. This protocol is based on the hypothesis that functionally dependent regions of two proteins co-evolve and therefore are likely to be sequentially conserved. This procedure allowed us to identify both an N-terminal and C-terminal region in RseB important for binding to RseA. We extensively analyzed the C-terminal region, which aligns with a region of RseA coincident with the major RseB binding determinant in RseA. Both allele-specific suppression analysis and cysteine-mediated disuffide bond formation indicated that this C-terminal region of similarity of RseA and RseB identifies a contact site between the two proteins. We suggest a similar protocol can be successfully applied to pairs of non-homologous but functionally linked proteins to find specific regions of the protein sequences that are important for establishing functional linkage. [ABSTRACT FROM AUTHOR]

Postoperative complications, particularly respiratory complications, are of significant clinical concern in patients undergoing elective thoracic surgery. Dexamethasone (DXM), commonly administered to prevent postoperative nausea and vomiting (PONV), has potential anti-inflammatory effects that might be beneficial in reducing these complications. We aimed to investigate whether intraoperative DXM administration could mitigate the occurrence of respiratory complications following elective thoracic surgery. We conducted a single-center observational study, including patients who underwent elective thoracic surgery from 2012 to 2020. The primary outcome was the onset of acute respiratory failure within 7 days post-surgery. Secondary outcomes encompassed other postoperative complications, duration of hospital stay, and mortality within 30 days post-surgery. An overlap propensity score analysis was employed to estimate the treatment effect. We included 1,247 adult patients, 897 who received dexamethasone (DXM) and 350 who served as controls. Intraoperative dexamethasone administration was associated with a significant reduction in respiratory complications with an adjusted relative risk (RR) of 0.65 (95% CI: 0.43−0.97). There was also a significant decline in composite infectious criteria with an adjusted RR of 0.76 (95% CI: 0.63−0.93). Cardiac complications were also assessed as a composite criterion, and a significant reduction was observed (adjusted RR, 0.68; 95% CI, 0.51−0.9). However, there were no association with mechanical complications, mortality within 30 days (adjusted RR of 0.43, 95% CI: 0.17–1.09) or in the length of hospital stay (adjusted RR of 0.85, 95% CI: 0.71–1.02). Dexamethasone administration was associated with a reduction in postoperative respiratory complications. Further prospective studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer (BC) subtype, with dismal prognosis and limited option in advanced settings, yet stromal tumor infiltrating lymphocytes (sTILs) in this subtype has a predictive role. Patients and methods: The International Breast Cancer Study Group (IBCSG) Trial 22–00 is a randomized phase III clinical trial testing the efficacy of low-dose metronomic oral Cyclophosphamide-Methotrexate (CM) maintenance following standard adjuvant chemotherapy treatment for early-stage hormone receptor-negative breast cancer patients. A case-cohort sampling was used. We characterized immune cells infiltrates in patients with TNBC by 6 plex immunofluorescence (IF) staining for CD4, FOXP3, CD3, cytokeratine and CD8 We confirmed that high immune CD3+ T cells as well as stromal and intra-epithelial Tregs (CD4+Foxp3+ T cells) infiltrates were associated with a better Distant Recurrence-Free Interval (DRFI), especially in LN+ patient, regardless of the treatment. More importantly, we showed that the spatial distribution of immune cells at baseline is crucial, as CM maintenance was detrimental for T cells excluded LN+ TNBC patients. immune spatial classification on immune cells infiltrates seems crucial and could help patients' selection in clinical trial and greatly improve responses to specific therapies. [Display omitted] • High immune infiltrates were associated with a better DRFI in patients with TNBC. • CM treatment is detrimental in node positive TNBC if high CD8/Tregs ratio. • High CD3/CD4 ratio is associated with a better DRFI in node positive TNBC. [ABSTRACT FROM AUTHOR]

Long-chain fatty acids (LCFAs) are used as a rich source of metabolic energy by several bacteria including important pathogens. Because LCFAs also induce oxidative stress, which may be detrimental to bacterial growth, it is imperative to understand the strategies employed by bacteria to counteract such stresses. Here, we performed a genetic screen in Escherichia coli on the LCFA, oleate, and compared our results with published genomewide screens of multiple non-fermentable carbon sources. This large-scale analysis revealed that among components of the aerobic electron transport chain (ETC), only genes involved in the biosynthesis of ubiquinone, an electron carrier in the ETC, are highly required for growth in LCFAs when compared with other carbon sources. Using genetic and biochemical approaches, we show that this increased requirement of ubiquinone is to mitigate elevated levels of reactive oxygen species generated by LCFA degradation. Intriguingly, we find that unlike other ETC components whose requirement for growth is inversely correlated with the energy yield of non-fermentable carbon sources, the requirement of ubiquinone correlates with oxidative stress. Our results therefore suggest that a mechanism in addition to the known electron carrier function of ubiquinone is required to explain its antioxidant role in LCFA metabolism. Importantly, among the various oxidative stress combat players in E. coli, ubiquinone acts as the cell's first line of defense against LCFAinduced oxidative stress. Taken together, our results emphasize that ubiquinone is a key antioxidant during LCFA metabolism and therefore provides a rationale for investigating its role in LCFA-utilizing pathogenic bacteria. [ABSTRACT FROM AUTHOR]