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The World Register of Marine Species (WoRMS) currently registers all Pacific cupped oysters that were formerly members of the genus Crassostrea in a new genus, Magallana. Magallana gigas is designated [...]

Sublethal behavioural effects of exposure to paralytic shellfish toxins (PST; saxitoxin and its derivatives) from the toxic dinoflagellate Alexandrium fundyense were investigated in newly settled winter flounder Pseudopleuronectes americanus, larval sheepshead minnow Cyprinodon variegatus and larval mummichog Fundulus heteroclitus through an A. fundyense–copepod–fish food chain. Consumption of as few as six to 12 toxin-containing copepods was lethal to the fishes. After consuming fewer toxin-containing copepods, all three fish species exhibited sublethal effects from vector-mediated exposure. Prey-capture ability of mummichogs was reduced in larvae that had consumed toxic copepods, Coullana canadensis. After consuming toxic C. canadensis or mixed copepods, mummichog larvae had reduced swimming performance. Swimming activity was also significantly reduced in winter flounder after consuming toxic copepods, including time spent in motion and distance travelled. Prey capture and predator avoidance were reduced in first-feeding sheepshead minnow larvae that had consumed toxic dinoflagellate cells. Adverse effects on prey capture or predator avoidance may reduce larval survival and facilitate the transmission of PST through the food web. This study provides baseline information on sublethal effects of PST exposure on fishes using a novel food-chain approach with zooplankton as vectors. [ABSTRACT FROM AUTHOR]

Abstract Background Inhibition of kinases involved in the DNA damage response sensitizes cells to genotoxic agents by abrogating checkpoint-induced cell cycle arrest. CHK1 and WEE1 act in a pathway upstream of CDK1 to inhibit cell cycle progression in response to damaged DNA. Therapeutic targeting of either CHK1 or WEE1, in combination with chemotherapy, is under clinical evaluation. These studies examine the overlap and potential for synergy when CHK1 and WEE1 are inhibited in cancer cell models. Methods Small molecules MK-8776 and MK-1775 were used to selectively and potently inhibit CHK1 and WEE1, respectively. Results In vitro, the combination of MK-8776 and MK-1775 induces up to 50-fold more DNA damage than either MK-8776 or MK-1775 alone at a fixed concentration. This requires aberrant cyclin-dependent kinase activity but does not appear to be dependent on p53 status alone. Furthermore, DNA damage takes place primarily in S-phase cells, implying disrupted DNA replication. When dosed together, the combination of MK-8776 and MK-1775 induced more intense and more durable DNA damage as well as anti-tumor efficacy than either MK-8776 or MK-1775 dosed alone. DNA damage induced by the combination was detected in up to 40% of cells in a treated xenograft tumor model. Conclusions These results highlight the roles of WEE1 and CHK1 in maintaining genomic integrity. Importantly, the strong synergy observed upon inhibition of both kinases suggests unique yet complimentary anti-tumor effects of WEE1 and CHK1 inhibition. This demonstration of DNA double strand breaks in the absence of a DNA damaging chemotherapeutic provides preclinical rationale for combining WEE1 and CHK1 inhibitors as a cancer treatment regimen.

Factor VIII deficiency, also known as hemophilia A, is the most common inherited bleeding disorder. Deficiency of Factor VIII results in dysfunction of platelet aggregation due to decreased activation of Factor X to Xa. We present the case of a 68-year-old male with mild hemophilia A (Factor VIII activity, 16%) who underwent a three-vessel coronary artery bypass graft and patent foramen ovale repair, with no increased bleeding utilizing a recombinant Factor VIII (kogenate) preoperative bolus and continuous infusion. His postoperative course was complicated by a sternal wound dehiscence requiring washout, sternal wire removal and omental flap coverage on postoperative Day 21. However, he required no postoperative blood transfusions., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Background: Pretreatment clinical staging is used to decide the course of treatment in early-stage esophageal cancer. Few studies assess the effect of inaccurate clinical staging on oncologic outcomes., Methods: We queried the National Cancer Database to identify patients undergoing esophagectomy for clinical stage cT1bN0 esophageal carcinoma between 2010 and 2019. Patients were categorized as being upstaged if, on final pathology, they had histopathologic disease that would have warranted treatment with neoadjuvant therapy. The textbook oncologic outcome was defined as margin-negative resection, 15 lymph nodes examined, a hospital stay of <21 days, no unplanned 30-day readmission or mortality, and stage-appropriate use of neoadjuvant therapy., Results: In total, 916 patients met inclusion criteria; 378 (41.2%) had a pathologic stage that differed from their pretreatment clinical stage. By multivariable regression, factors associated upstaging included: presentation between 2015 and 2019 (odds ratio 1.92 95% confidence interval [1.19, 3.13]), delay to esophagectomy of >30 days (odds ratio 2.38 95% confidence interval [1.13, 5.57]), larger tumor size (>2 cm relative to <2 cm, odds ratio 2.73 95% confidence interval [1.72, 4.39]), and poorly differentiated histology (odds ratio 2.79 95% confidence interval [1.75, 4.49]). The rate of textbook oncologic outcome assuming reliable clinical staging was 43.8%; accounting for upstaging, the rate of textbook oncologic outcome was 22.5% (P < .001)., Conclusion: In patients with cT1bN0 esophageal cancer, tumor size and histology are associated with the risk of inaccurate pretreatment clinical staging. Inaccuracies in clinical staging impact the rate at which providers achieve optimal oncologic outcomes., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: Addiction medications (AM) are effective in improving recovery outcomes, but many barriers still exist that reduce their implementation among young adults. While the perception of AM has been explored within clinicians and counselors in many settings, it has not yet been documented within collegiate recovery communities (CRC). The aim of this brief report is to assess the acceptability and intent to use AM among students in recovery, and to evaluate the effect of attitudes, perceived AM effectiveness, and social norms on these outcomes., Methods: Using the Theory of Planned Behavior, CRC students (N = 162; 44% female) within the United States completed an online survey., Results: Results from a hierarchical linear model indicated that the perceived acceptance of AM use by important others was significantly related to the intent to use AM ( β = 0.47, P < 0.01) and encourage others to use AM ( β = 0.16, P < 0.05). Positive attitudes about AM predicted acceptability of AM use ( β = 0.42, P < 0.01) and encouraging other CRC students to use AM ( β = 0.38, P < 0.01). Perceived AM effectiveness was positively associated with acceptability ( β = 0.36, P < 0.01) and encouragement of others ( β = 0.27, P < 0.01)., Conclusions: Results highlight the importance of promoting effectiveness, improving attitudes, and tapping social networks to increase AM use and acceptability among CRC students. Implications for CRC policy and programming are discussed., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.)

Background: Previous studies have shown that overall survival after lung resection for pulmonary carcinoid tumors is favorable. It is unclear what the prognosis is for observation rather than resection for small carcinoid tumors., Methods: We queried the National Cancer Database to identify patients presenting with primary pulmonary carcinoid tumors between 2004 and 2017. We included patients with small (<3 cm) primary pulmonary carcinoids, who were observed or underwent a lung resection. To minimize confounding by indication, we used propensity score matching, while accounting for age, sex, race, insurance type, Charlson-Deyo comorbidity score, typical and atypical histology, tumor size, and year of diagnosis. We used Kaplan-Meier survival analyses to compare 5-year overall survival in the matched cohorts., Results: Of 8435 patients with small pulmonary carcinoids, 783 (9.3%) underwent observation and 7652 (91%) underwent surgical resection. After propensity score matching, surgical resection was associated with improved 5-year overall survival (66% vs 81%, P < .001). No significant difference in overall survival was found between wedge and anatomic resection (88% vs 88%, P = .83). In patients undergoing resection, lymph node sampling at the time of wedge and anatomic resection increased 5-year overall survival (90% vs 86%, P = .0042; 88% vs 82%, P = .04, respectively)., Conclusions: Surgical resection of small pulmonary carcinoids is associated with improved survival compared with observation. When surgical resection is performed, wedge and anatomic resection result in similar survival, and lymph node sampling improves survival., (Published by Elsevier Inc.)

Background: Prior studies evaluating the safety and efficacy of local excision relative to surgical resection in early-stage rectal adenocarcinoma have primarily included low rectal cancers treated with abdominoperineal resection as control comparison cohorts. The role of local excision in early-stage rectal adenocarcinoma is incompletely defined., Methods: We queried the National Cancer Database to identify patients with cT1 N0 M0 rectal adenocarcinoma between 2004 and 2019. Patients undergoing abdominoperineal resection were excluded. Multivariable regression was used to identify factors associated with use of local excision instead of low anterior resection. Patients undergoing local excision were propensity score matched for age, sex, demographic characteristics, Charlson-Deyo comorbidity class score, and tumor grade and size to those undergoing low anterior resection. Short-term clinical outcomes and 5-year overall survival for matched cohorts were compared by standard methods., Results: A total of 5,693 patients met inclusion criteria; 1,973 patients underwent local excision and 3,720 low anterior resection. Age (adjusted odds ratio 1.26; 95% confidence interval, 1.17-1.37), tumor histology (poorly differentiated histology: adjusted odds ratio 0.66; 95% confidence interval, 0.51-0.86), and size (>4 cm: adjusted odds ratio 0.20; 95% confidence interval, 0.16-0.25) were associated with choice of intervention. On comparison of matched cohorts, patients undergoing LE demonstrated shorter hospital stay (2.4 ±9.8 vs 5.6 ±8.1 days; P < .001) and lower readmission rate (4% vs 7%; P = .002) but higher margin-positive resection rates (8% vs 2%; P < .001). Overall survival profiles for patients undergoing local excision were comparable with those for low anterior resection., Conclusion: In patients with cT1 N0 M0 rectal adenocarcinoma, local excision is associated with a higher margin-positive resection rate than low anterior resection but affords accelerated postprocedure recovery and comparable rates of overall survival., (Published by Elsevier Inc.)

Background: Acute kidney injury (AKI) is a common complication of cardiac surgery. An intraoperative monitor of kidney perfusion is needed to identify patients at risk for AKI. The authors created a noninvasive urinary oximeter that provides continuous measurements of urinary oxygen partial pressure and instantaneous urine flow. They hypothesized that intraoperative urinary oxygen partial pressure measurements are feasible with this prototype device and that low urinary oxygen partial pressure during cardiac surgery is associated with the subsequent development of AKI., Methods: This was a prospective observational pilot study. Continuous urinary oxygen partial pressure and instantaneous urine flow were measured in 91 patients undergoing cardiac surgery using a novel device placed between the urinary catheter and collecting bag. Data were collected throughout the surgery and for 24 h postoperatively. Clinicians were blinded to the intraoperative urinary oxygen partial pressure and instantaneous flow data. Patients were then followed postoperatively, and the incidence of AKI was compared to urinary oxygen partial pressure measurements., Results: Intraoperative urinary oxygen partial pressure measurements were feasible in 86/91 (95%) of patients. When urinary oxygen partial pressure data were filtered for valid urine flows greater than 0.5 ml · kg-1 · h-1, then 70/86 (81%) and 77/86 (90%) of patients in the cardiopulmonary bypass (CPB) and post-CPB periods, respectively, were included in the analysis. Mean urinary oxygen partial pressure in the post-CPB period was significantly lower in patients who subsequently developed AKI than in those who did not (mean difference, 6 mmHg; 95% CI, 0 to 11; P = 0.038). In a multivariable analysis, mean urinary oxygen partial pressure during the post-CPB period remained an independent risk factor for AKI (relative risk, 0.82; 95% CI, 0.71 to 0.95; P = 0.009 for every 10-mmHg increase in mean urinary oxygen partial pressure)., Conclusions: Low urinary oxygen partial pressures after CPB may be associated with the subsequent development of AKI after cardiac surgery., (Copyright © 2021, the American Society of Anesthesiologists. All Rights Reserved.)

Objective: The purpose of this study was to determine the relationship between blood product transfusion, with or without recombinant human activated factor VIIa, and survival after lung transplantation., Design: Retrospective analysis of a single center with follow-up out to 6 years post-transplantation., Setting: Single-center academic lung transplantation program., Participants: The study comprised 265 adult patients who underwent single or bilateral sequential lung transplantation from March 2011 to June 2017., Interventions: Overall survival using Kaplan-Meier curves was compared among the following 3 cohorts: those not transfused with blood products, those transfused with blood products, and those given blood products and recombinant human activated factor VIIa. Cox proportional hazards regression was used to estimate hazard ratios (HRs), confidence intervals (CIs), and p values., Measurements and Main Results: Seventy-eight patients received no packed red blood cell transfusions, 149 received packed red blood cell transfusions, and 38 received both packed red blood cell transfusions and recombinant human activated factor VII. Packed red blood cell transfusion was associated with an increased risk of mortality that did not reach statistical significance (HR 2.168, CI 0.978-4.805; p = 0.057). Additional packed red blood cells beyond 15 U were associated with worsened survival (HR 1.363, CI 1.137-1.633; p = 0.001), but recombinant human activated factor VIIa did not increase the risk of mortality., Conclusion: Blood product transfusion during and after lung transplantation is associated with decreased survival, especially with large-volume transfusions. Survival is not worse with recombinant human activated factor VIIa administration, but additional studies are needed to determine whether recombinant human activated factor VIIa administration reduces the need for blood product transfusions., Competing Interests: Declaration of interest for all other authors None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Early life adversity and insecure attachment style are known risk factors for perinatal depression. The biological pathways linking these experiences, however, have not yet been elucidated. We hypothesized that overlap in patterns of DNA methylation in association with each of these phenomena could identify genes and pathways of importance. Specifically, we wished to distinguish between allostatic-load and role-transition hypotheses of perinatal depression. We conducted a large-scale analysis of methylation patterns across 5 × 10 6 individual CG dinucleotides in 54 women participating in a longitudinal prospective study of perinatal depression, using clustering-based criteria for significance to control for multiple comparisons. We identified 1580 regions in which methylation density was associated with childhood adversity, 3 in which methylation density was associated with insecure attachment style, and 6 in which methylation density was associated with perinatal depression. Shorter telomeres were observed in association with childhood trauma but not with perinatal depression or attachment insecurity. A detailed analysis of methylation density in the oxytocin receptor gene revealed similar patterns of DNA methylation in association with perinatal depression and with insecure attachment style, while childhood trauma was associated with a distinct methylation pattern in this gene. Clinically, attachment style was strongly associated with depression only in pregnancy and the early postpartum, whereas the association of childhood adversity with depression was time-invariant. We concluded that the broad DNA methylation signature and reduced telomere length associated with childhood adversity could indicate increased allostatic load across multiple body systems, whereas perinatal depression and attachment insecurity may be narrower phenotypes with more limited DNA methylation signatures outside the CNS, and no apparent association with telomere length or, by extension, allostatic load. In contrast, the finding of matching DNA methylation patterns within the oxytocin receptor gene for perinatal depression and attachment insecurity is consistent with the theory that the perinatal period is a time of activation of existing attachment schemas for the purpose of structuring the mother-child relationship, and that such activation may occur in part through specific patterns of methylation of the oxytocin receptor gene.

Background: Tracheostomy is an important adjunct for lung transplant patients requiring prolonged ventilation. We explored the effects of post-transplant tracheostomy on survival and bronchiolitis obliterans syndrome after lung transplant., Methods: A retrospective, single center analysis was performed on all lung transplant recipients during the Lung Allocation Score (LAS) era. Risk factors for post-transplant tracheostomy or death within 30 days were assessed. Kaplan-Meier estimates and Cox proportional hazards models were used to examine the association between tracheostomy within 30 days after transplant and survival at 1 and 3 years. A total of 403 patients underwent single or bilateral lung transplant between May 2005 and February 2016 with complete data for 352 cases, and 35 patients (9.9%) underwent tracheostomy or died (N = 10, 2.8%) within 30 days., Results: In adjusted analyses, primary graft dysfunction grade 3 (PGD3) was associated with a composite end point of tracheostomy or death within 30 days (HR 3.11 (1.69, 5.71), P-value < .001). Tracheostomy within 30 days was associated with decreased survival at 1(HR 4.25 [1.75, 10.35] P-value = .001) and 3 years (HR 2.74 [1.30, 5.76], P-value = .008), as well as decreased bronchiolitis obliterans (BOS)-free survival at 1 (HR 1.87 [1.02, 3.41] P-value = .042) and 3 years (HR 2.15 [1.33, 3.5], P-value = .002)., Conclusion: Post-transplant tracheostomy is a marker for advanced lung allograft dysfunction with significant reduction in long-term overall and BOS-free survival., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The apolipoprotein epsilon 4 (APOE4) allele is a well-established genetic risk factor for Alzheimer's disease (AD). However, there are mixed findings as to how the APOE4 allele modifies the effects of both higher low-density lipoprotein cholesterol (LDL) and statin use on cognitive functioning., Objective: This study sought to examine the effects of LDL levels and statin use on verbal learning and memory, as modified by the presence of the APOE4 allele, in a sample of cognitively unimpaired, older adults at risk for AD., Methods: Neuropsychological, LDL, statin use, and APOE4 data were extracted from an ongoing longitudinal study at the Banner Alzheimer's Institute in Arizona. Participants were cognitively unimpaired based on Mini-Mental State Examination scores within a normal range, aged 47-75, with a family history of probable AD in at least one first-degree relative., Results: In the whole sample, higher LDL was associated with worse immediate verbal memory in APOE4 non-carriers, but did not have an effect on immediate verbal memory in APOE4 carriers. In APOE4 non-carriers, statin use was associated with better verbal learning, but did not have an effect on verbal learning in APOE4 carriers. Among women, higher LDL in APOE4 carriers was associated with worse verbal learning than in APOE4 non-carriers, and statin use in APOE4 non-carriers was associated with better verbal learning and immediate and delayed verbal memory but worse performances on these tasks in APOE4 carriers., Conclusion: LDL and statin use may have differential effects on verbal learning and/or memory depending on genetic risk for AD. Women appear to be particularly vulnerable to statin use depending on their APOE4 status.