Search

Abstract There is no current consensus on the follow up of kidney function in patients undergoing cardiopulmonary bypass (CPB). The main objectives of this pilot study is to collect preliminary data on kidney function decline encountered on the first postoperative visit of patients who have had CPB and to identify predictors of kidney function decline post hospital discharge. Design: Retrospective chart review. Adult patients undergoing open heart procedures utilizing CPB. Patient demographics, type of procedure, pre-, intra-, and postoperative clinical, hemodynamic echocardiographic, and laboratory data were abstracted from electronic medical records. Acute kidney disease (AKD), and chronic kidney disease (CKD) were diagnosed based on standardized criteria. Interval change in medications, hospital admissions, and exposure to contrast, from hospital discharge till first postoperative visit were collected. AKD, and CKD as defined by standardized criteria on first postoperative visit. 83 patients were available for analysis. AKD occurred in 27 (54%) of 50 patients and CKD developed in 12 (42%) out of 28 patients. Older age was associated with the development of both AKD and CKD. Reduction in right ventricular cardiac output at baseline was associated with AKD (OR: 0.5, 95% CI: 0.3, 0.79, P = 0.01). Prolongation of transmitral early diastolic filling wave deceleration time was associated with CKD (OR: 1.02, 95% CI: 1.01, 1.05, P = 0.03). In-hospital acute kidney injury (AKI) was a predictor of neither AKD nor CKD. AKD and CKD occur after CPB and may not be predicted by in-hospital AKI. Older age, right ventricular dysfunction and diastolic dysfunction are important disease predictors. An adequately powered longitudinal study is underway to study more sensitive predictors of delayed forms of kidney decline after CPB.

Antimicrobial resistance in the intensive care unit is an ongoing global healthcare concern associated with high mortality and morbidity rates and high healthcare costs. Select groups of bacterial pathogens express different mechanisms of antimicrobial resistance. Clinicians face challenges in managing patients with multidrug-resistant bacteria in the form of a limited pool of available antibiotics, slow and potentially inaccurate conventional diagnostic microbial modalities, mimicry of non-infective conditions with infective syndromes, and the confounding of the clinical picture of organ dysfunction associated with sepsis with postoperative surgical complications such as hemorrhage and fluid shifts. Potential remedies for antimicrobial resistance include specific surveillance, adequate and systematic antibiotic stewardship, use of pharmacokinetic and pharmacodynamic techniques of therapy, and antimicrobial monitoring and adequate employment of infection control policies. Novel techniques of combating antimicrobial resistance include the use of aerosolized antibiotics for lung infections, the restoration of gut microflora using fecal transplantation, and orally administered probiotics. Newer antibiotics are urgently needed as part of the armamentarium against multidrug-resistant bacteria. In this review we discuss mechanisms and patterns of microbial resistance in a select group of drug-resistant bacteria, and preventive and remedial measures for combating antibiotic resistance in the critically ill.

This study aimed to assess the efficacy and safety of bedside removal of tunnelled hemodialysis catheter (TDC) by noninterventional nephrologists among adult patients. It is a retrospective study that involved 53 patients from March 2020 to February 2022 at the King Abdulaziz University Hospital (KAUH) Hemodialysis Centre in Jeddah, Saudi Arabia. Of the 53 participants, 60.4% were male and 40.6% female, and their mean age was 50.94 ± 18.89 years. The most common comorbidities were hypertension (HTN) in 47 (88.7%), diabetes mellitus (DM) in 24 (45.3%), and DM and HTN together in 23 (43.4%) patients. The most common site of TDC removal was the right internal jugular vein (77.4%). In 84.9% of the cases, the TDC was removed as an inpatient procedure, and in the majority of the cases (64.2%), the TDC was removed by a noninterventional nephrologist. The most common reasons for TDC removal were sepsis or clinical concerns for infection (64.2%) and TDC not needed (20.8%) due to recovery of the renal function or access maturation. Most patients (96.2%) suffered no complications; only one of 34 (%) patients with catheter removal by a noninterventional nephrologist had bleeding, which required more observation and monitoring before discharge on the same day. Our study revealed that the bedside TDC removal was well tolerated with a minimal complication rate.

Background: Implementation of an anesthesiology-led cardiac implantable electronic device (CIED) service can be viewed to have economic and efficiency challenges. This study evaluates the cost savings of an anesthesiology-led CIED service. Methods: A total of 830 patients presented in the pre-implementation period from 1 March 2016 to 31 December 2017, and 1981 patients presented in the post-implementation period from 1 January 2018 to 31 October 2021. Interrupted time-series analysis for single-group comparisons was used to evaluate the cost savings resulting from reduction in operating room (OR) start delays for patients with CIEDs. Results: OR start-time delay was reduced by 10.6 min (95%CI: −20.5 to −0.83), comparing pre- to post-implementation. For an OR cost of USD 45/min, we estimated the direct cost to the department to be USD 1.68/min. The intervention translated into a total cost reduction during the intervention period of USD 250,000 (USD 18,000 to USD 470,000) per year for the institution and USD 9800 (USD 730 to USD 17,000) per year for the department. The yearly cost of employing a full-time team of CIED specialists would have been USD 135,456. The service triggered electrophysiology consultation on 13 device malfunctions. Conclusions: An anesthesiology-led CIED service resulted in substantial cost savings, increased OR efficiency and patient safety.

Background: Electronic dashboards measure intensive care unit (ICU) performance by tracking quality indicators, especially pinpointing sub-standard metrics. This helps ICUs scrutinize and change current practices in an effort to improve failing metrics. However, its technological value is lost if end users are unaware of its importance. This results in decreased staff participation, leading to unsuccessful initiation of the dashboard. Therefore, the purpose of this project was to improve cardiothoracic ICU providers’ understanding of electronic dashboards by providing an educational training bundle in preparation for an electronic dashboard initiation. Methods: A Likert survey assessing providers’ knowledge, attitudes, skills, and application of electronic dashboards was conducted. Subsequently, an educational training bundle, consisting of a digital flier and laminated pamphlets, was made available to providers for four months. After bundle review, providers were assessed using the same pre-bundle Likert survey. Results: A comparison of summated scores from pre-bundle (mean = 38.75) and post-bundle surveys (mean = 46.13) yielded an increased summated score overall (mean = 7.38, p ≤ 0.001). Conclusion: An educational bundle improved providers’ understanding and increased their likelihood of using electronic dashboards upon its initiation. Further studies are needed to continue increasing staff participation such as providing specific education to navigate the interface for data retrieval and interpretation.

The present study investigated the effect of autophagy induction and cathepsin B (CTSB) inhibition on developmental competence of poor quality oocytes. Bovine cumulus oocyte complexes (COCs) were classified as good or poor according to their morphology. Autophagy activity was detected in good and poor germinal vesicle (GV) oocytes. Then E-64, a CTSB inhibitor, rapamycin (Rapa), an autophagy inducer, and combined administration was achieved during invitro maturation (IVM) of poor quality COCs followed by detection of autophagy activity. In the next experiment, E-64, Rapa, and E64 + Rapa, were added during IVM to good and poor quality COCs followed by invitro fertilization and culture for 8 days to investigate whether inhibition of CTSB and/or induction of autophagy improve embryonic development and quality. Autophagy activity was significantly lower in poor quality GV oocytes than in good quality ones. E-64, Rapa and E-64 + Rapa treatment during IVM significantly increased autophagy activity in poor quality oocytes. Addition of Rapa in good quality COCs did not increase the blastocyst rate, whereas E-64 increased the blastocyst rate and total cell number (TCN) with decreasing TUNEL-positive cells. In contrast, Rapa treatment in poor quality COCs significantly increased the blastocyst rate and TCN with decreasing TUNEL-positive cells. These results indicate oocyte quality has different responses to intracellular autophagy induction and CTSB activity control by potential autophagy and catabolic status, however, synergetic effect of autophagy induction and CTSB inhibition can increase developmental competence of both good and poor quality COCs, especially rescue effect in poor quality COCs.

Lysosomal cathepsin, in particular cathepsin B (CTSB), plays an important role in implantation, pregnancy, and embryonic development. However, little is known about the mechanism related to the dynamic status of lysosomal cathepsins in bovine oocytes and preimplantation embryos. In the present study, we investigated the dynamics of gene expression, activity, and immunolocalization of CTSB, as well as the activities of lysosome, in bovine oocytes and preimplantation embryos. After gene expression analysis of several cathepsin-related genes, transcript levels of CTSB, CTSD and CTSZ were highest in Metaphase II (MII) oocytes followed by a significant decrease from the 8-cell embryo stage. Activity of CTSB showed a significant increase in 1-cell and morula stage embryos. Lysosomal activity was also significant higher in 1-cell and morula stages, which was consistent with CTSB activities. However, immunolocalization of CTSB did not show the similar pattern of CTSB and lysosomal activities. We also found significantly higher expression levels of CTSB transcript in the trophectoderm (TE) compared to inner cell mass (ICM), whereas activity and immunolocalization of CTSB showed an opposite pattern, i.e. significantly higher in ICM than TE. These patterns were confirmed by the same analysis using separated ICM and TE. Our results suggest that lysosomal CTSB has a pivotal role during embryonic development and differentiation, especially fertilization and the differentiation period.

The association of gender with mortality in trauma remains a subject of debate. Geriatric trauma patients have a higher risk of mortality compared to younger patients. We sought to evaluate the association of gender with mortality in a group of geriatric trauma patients presenting to an academic level 1 trauma center (trauma center designated by New York State capable of handling the most severe injuries and most complex cases). Methods: We performed a retrospective review of geriatric trauma patients who were admitted to our trauma center between January 2018 and December 2020. Data collected included vital signs, demographics, injury, and clinical characteristics, laboratory data and outcome measures. The study controlled for co-morbidities, injury severity score (ISS), and systolic blood pressure (SBP) in the ED. Multivariable logistic regression analysis was performed to evaluate the association of gender and mortality. Results: 4432 geriatric patients were admitted during the study period, there were 1635 (36.9%) men and 3859 (87.2%) were White with an average age of 81 ± 8.5 years. The mean ISS was 6.7 ± 5.4 and average length of stay was 6 ± 6.3 days. There were 165 deaths. Male gender (OR 1.94, 95% CI 1.38 to 2.73), ISS (OR 1.12, 95% CI 1.09 to 1.14), Emergency Department SBP less than 90 mmHg (OR 6.17, 95% CI 3.17 to 12.01), and having more than one co-morbidity (OR 2.28, 95% CI 1.55 to 3.35) were independently predictive of death on multivariable logistic regression analysis. Conclusion: Male gender, Emergency Department systolic blood pressure less than 90 mmHg, having more than one co-morbidity, and injury severity are independent predictors of mortality among geriatric trauma patients.

Background: Pulmonary arterial hypertension (PAH) is a progressive proliferative vasculopathy associated with mechanical and electrical changes, culminating in increased vascular resistance, right ventricular (RV) failure, and death. With a main focus on invasive tools, there has been an underutilization of echocardiography, electrocardiography, and biomarkers to non-invasively assess the changes in myocardial and pulmonary vascular structure and function during the course of PAH.Methods: A SU5416-hypoxia rat model was used for inducing PAH. Biventricular functions were measured using transthoracic two-dimensional (2D) echocardiography/Doppler (echo/Doppler) at disease onset (0 week), during progression (3 weeks), and establishment (5 weeks). Similarly, electrocardiography was performed at 0, 3, and 5 weeks. Invasive hemodynamic measurements and markers of cardiac injury in plasma were assessed at 0, 3, and 5 weeks.Results: Increased RV systolic pressure (RVSP) and rate of isovolumic pressure rise and decline were observed at 0, 3, and 5 weeks in PAH animals. EKG showed a steady increase in QT-interval with progression of PAH, whereas P-wave height and RS width were increased only during the initial stages of PAH progression. Echocardiographic markers of PAH progression and severity were also identified. Three echocardiographic patterns were observed: a steady pattern (0–5 weeks) in which echo parameter changed progressively with severity [inferior vena cava (IVC) expiratory diameter and pulmonary artery acceleration time (PAAT)], an early pattern (0–3 weeks) where there is an early change in parameters [RV fractional area change (RV-FAC), transmitral flow, left ventricle (LV) output, estimated mean PA pressure, RV performance index, and LV systolic eccentricity index], and a late pattern (3–5 weeks) in which there is only a late rise at advanced stages of PAH (LV diastolic eccentricity index). RVSP correlated with PAAT, PAAT/PA ejection times, IVC diameters, RV-FAC, tricuspid systolic excursion, LV systolic eccentricity and output, and transmitral flow. Plasma myosin light chain (Myl-3) and cardiac troponin I (cTnI) increased progressively across the three time points. Cardiac troponin T (cTnT) and fatty acid-binding protein-3 (FABP-3) were significantly elevated only at the 5-week time point.Conclusion: Distinct electrocardiographic and echocardiographic patterns along with plasma biomarkers were identified as useful non-invasive tools for monitoring PAH progression.

Postovulatory aging is a major problem that limits the success of many assisted reproductive technologies (ARTs). Oxidative stress is a leading cause of oocyte aging. This study investigated the effects of lycopene supplementation of in vitro maturation (IVM) medium during the aging of mouse oocytes on the oocytes’ morphology and oxidative stress status. Mouse cumulus-oocyte complexes (COCs) were collected and cultured in the IVM medium either for 17 h, (freshly matured oocytes), or for 48 h, (in vitro-aged oocytes), with or without lycopene. The rate of fragmented and degenerated oocytes and the oocyte levels of hydrogen peroxide (H2O2), malondialdehyde (MDA), total antioxidant capacity (TAC), reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) were estimated and compared. Oocytes aged with 200 nM lycopene revealed significantly less fragmentation and degeneration, lower H2O2 and MDA levels, and higher TAC, GSH and SOD levels than those aged without lycopene. CAT levels were unchanged by lycopene treatment. Taken together, our data showed beneficial effects of lycopene during in vitro aging of mouse oocytes by reducing the oxidative stress damages that lead to their apoptosis. The present study introduces lycopene as a natural supplement to reduce the postovulatory aging-dependent abnormalities of mammalian oocytes.

OBJECTIVES/GOALS: Insulin dosing is crucial for regulating blood glucose in cardiac surgery patients, yet it requires the use of cumbersome insulin dosing charts. To streamline this process, an electronic insulin calculator (IC) is trialed in the cardiac operating rooms and intensive care unit. This study compares glycemic control prior to and after institution of IC. METHODS/STUDY POPULATION: Using the EHR, a retrospective population of 3,164 cardiac surgery patient charts from 12/19/19 - 11/06/20 were obtained. Baseline, intra-operative, and ICU blood glucose values were obtained from each patients admission. Using this data, a baseline level of glycemic control throughout a cardiac surgery patients stay was established. A preliminary cohort of 244 patients were then chosen to be managed with the new IC. Baseline, intra-operative, and ICU blood glucose values were obtained in this group for comparison. Paired t tests were used to compare the IC group of patients to the retrospective group of patients. Additional subgroup analysis was performed to assess IC efficacy for on pump vs off pump cardiac surgeries. RESULTS/ANTICIPATED RESULTS: The 244 patients managed with the IC showed significantly reduced average blood glucose values during their time in the ICU compared to those previously not managed with the IC (185 mg% vs 153 mg%, p= 0.02). Additionally, a trend towards a reduction in last operating room blood glucose level was also noted. Lastly, average blood glucose levels were significantly reduced for patients undergoing on pump cardiac surgeries compared to off pump surgeries (157 mg% vs 149 mg%, p = 0.03). DISCUSSION/SIGNIFICANCE: Preliminary results suggest IIC to be associated with better intra and postoperative blood glucose control. More data is being collected to test its association with outcomes.

ObjectiveAcute kidney injury (AKI) is a common complication of complex aortic surgery with high mortality, morbidity and health care expense. The current definition of AKI does not allow for structural characterization of the kidneys and utilizes functional indices with substantial limitations leading to delayed diagnosis and ineffective interventions. The aim of this study is to develop a method of early detection of structural renal abnormalities that can precede and predict the occurrence of AKI in this population. We propose a novel combined index of ultrasonography (shear wave elastography), biomarkers of renal stress (urinary insulin growth factor binding protein-7, IGFBP-7 and inhibitor of tissue metalloproteinase-2, TIMP-2) and renal injury markers (urinary neutrophil gelatinase-associated lipocalin -NGAL)- the bio-sonographic index (BSI).MethodsA prospective observational study at a tertiary referral center will be performed enrolling 80 patients undergoing elective open and endovascular repair of the visceral aorta. The BSI will be evaluated at baseline, and at 6 and 24 hours after the procedure. The primary outcome is the occurrence of AKI according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Each patient will be his/her own control. A reference group of 15 healthy volunteers who are not undergoing interventions will be enrolled to test the feasibility of and to refine the novel SWE protocol. The BSI will be tested for its predictability of the occurrence of AKI. Comparisons will be made between individual and combined components of the BSI and traditional markers used in the KDIGO definition; serum creatinine and urine output in terms of baseline status of the kidney. Correlations will be made between the BSI and conventional indices of AKI and exploratory analyses will be conducted to identify individual disease patterns using the BSI.DiscussionWe hypothesize that the BSI will be a sensitive index of early structural abnormalities that precede and predict the occurrence of AKI as defined by KDIGO in complex vascular surgery.Trial registrationClinicalTrials.gov NCT04144894. Registered 1/6/2020.

Introduction: The Integrated Programme of Maternal and Child Health aims to reduce maternal and child mortality in Guinea-Bissau. The purpose of this article is to share our experience in building a training programme on maternal and newborn care for health-care professionals in Guinea-Bissau. Material and Methods: Regional directors of the four target areas chose a group of staff who provide prenatal and childbirth care to attend the course (12 to 15 trainees per region). In each region, 15 highly interactive and practical sessions were scheduled over eight weeks. The trainees’ summative and reactive assessment was obtained using a multiple choice questionnaire (final test) and an anonymous survey, respectively. Results: Attendees included 25 nurses, 17 midwives and 14 doctors. About two thirds had five years’ practice or less. Test median scores were higher among trainees with two to nine years of practice (54.4% to 60.9%), as compared to those with a year or less (47.8%) or 10 or more years (45.7%). Pedagogical variables were rated as ‘good’ or ‘very good’ by 91% to 95% of the attendees. Discussion: Use of an interactive and practical pedagogical methodology produced positive results and was crucial to tailoring the training to local needs. However, adapting the syllabus according to professional categories and experiences should be considered. Conclusion: Our results warrant further development and evaluation of training programmes on maternal and neonatal care in Guinea-Bissau.

Abstract Background Conventional echocardiographic technique for assessment of volume status and cardiac contractility utilizes left ventricular end-diastolic area (LVEDA) and fractional area of change (FAC), respectively. Our goal was to find a technically reliable yet faster technique to evaluate volume status and contractility by measuring left ventricular end-diastolic diameter (LVEDD) and fractional shortening (FS) in a cohort of mechanically ventilated trauma and burn patients using hemodynamic transesophageal echocardiographic (hTEE) monitoring. Methods Retrospective chart review performed at trauma/burn intensive care unit (TBICU). Data on 88 mechanically ventilated surgical intensive care patients cared for between July 2013 and July 2015 were reviewed. Initial measurements of LVEDA, left ventricular end-systolic area (LVESA) and FAC were collected. Post-processing left ventricular end-systolic (LVESD) and end-diastolic diameters (LVEDD) were measured and fractional shortening (FS) was calculated. Two orthogonal measurements of LV diameter were obtained in transverse (Tr) and posteroanterior (PA) orientation. Results There was a significant correlation between transverse and posteroanterior left ventricular diameter measurements in both systole and diastole. In systole, r = 0.92, p

We have recently shown that sperm attachment to bovine endometrial epithelial cells (BEECs) triggers uterine local innate immunity with induction of a pro-inflammatory response in vitro, however details of the mechanism remain unknown. Here, we investigated the involvement of Toll-like receptor 2/4 (TLR2/4) pathway in mediating sperm-BEECs inflammatory process. Immunohistochemistry of the uterine tissue revealed that TLR2 and TLR4 proteins were present in the luminal and glandular epithelia of bovine endometrium. Moreover, BEECs monolayers were treated with TLR2 agonist (Pam; 0, 10, 100, and 1000 ng/ml) or TLR4 agonist (LPS; 0, 0.1, 1, and 10 ng/ml) for 0, 1, 3, or 6 h, followed by evaluating mRNA expression of the pro-inflammatory genes (TNFA, IL-1B, IL-8, and PGES) in BEECs using a real-time PCR. Both Pam and LPS treatments showed a dose-dependent stimulation of mRNA expression of the pro-inflammatory genes. To elucidate the functional role of TLR2/4 in sperm-BEECs interaction, BEECs monolayers were incubated with either TLR2 antagonist or TLR4 antibody for 2 h prior to the co-culture with sperm for 3 h. Importantly, pre-incubation of BEECs with TLR2 antagonist or TLR4 antibody prevented the stimulatory effect of sperm on the transcription of pro-inflammatory genes in BEECs. Furthermore, sperm increased the phosphorylation levels of TLR2/4 downstream targets (p38MAPK and JNK) in BEECs within 1 h of the co-culture. Treatment of BEECs with TLR2 antagonist prior to sperm addition inhibited JNK phosphorylation, while TLR4 antibody inhibited the phosphorylation of both p38MAPK and JNK. In conclusion, the present in vitro findings strongly suggest that bovine endometrial epithelial cells respond to sperm via TLR2/4 signal transduction.

Background: Although the association of neutrophil proportions with mortality in trauma patients has recently been shown, there is a paucity of research on the association with other outcomes. We sought to investigate the association of neutrophil proportions with organ failure in critically-ill trauma patients. Methods: We reviewed a randomly-selected group of trauma patients admitted to our level-1 trauma intensive care unit between July 2007 and December 2016. Data collected included demographics, injury mechanism and severity (ISS), neutrophil-to-lymphocyte ratio (NLR) at admission and at 24 and 48 hours and organ failure data. NLR patterns during the first 48 hours were divided into two trajectories identified by applying factor and cluster analysis to longitudinal measures. Logistic regression was performed for the association between NLR trajectories and any organ failure; negative binomial regression was used to model the number of organ failures and stage of kidney failure measured by KDIGO classification. Results: 207 patients had NLR data at all three time points. The average age was 44.9 years with mean ISS of 20.6. Patients were 72% male and 23% had penetrating trauma. The 74 patients (36%) with Trajectory 1 had a mean NLR at admission of 3.6, which increased to 14.7 at 48 hours. The 133 (64%) patients in Trajectory 2 had a mean NLR at admission of 8.5 which decreased to 6.6 at 48 hours. Mean NLR was different between the two groups at all three time points (all p < 0.01). There was no significant difference in ISS, age or gender between the two trajectory groups. Models adjusted for age, gender and ISS showed that relative to those with trajectory 2, patients with the trajectory 1 were more likely to have organ failure OR 2.96 (1.42–6.18; p < 0.01), higher number of organ failures IRR 1.50 (1.13–2.00, p < 0.01), and degree of AKI IRR 2.06 (1.04–4.06, p = 0.04). In all cases, the estimated associations were higher among men vs. women, and all were significant among men, but not women. Conclusions: Trauma patients with an increasing NLR trajectory over the first 48 hours had increased risk, number and severity of organ failures. Further research should focus on the mechanisms behind this difference in outcome.

Abstract Introduction This problem-based learning discussion (PBLD) provides a case-based opportunity for learners to work through a case of acute pulmonary embolism, a frequently encountered potentially life-threatening condition in the operating room and in the ICU. The PBLD is comprised of a set of learning objectives, a detailed stem question that is punctuated by open-ended and analytical clinical questions designed to test learners' clinical decision-making skills. Also provided are a quiz and a handout providing background material on acute pulmonary embolism, which can be used as the basis of a series of mini-lectures on epidemiology, diagnosis, and management of acute pulmonary embolism. This resource is designed for use in small-group sessions; including but not limited to classroom, roundtable, and meeting group sessions. It has been successfully used with a mixed group of learners, including undergraduate students, residents, fellows, and postgraduate practitioners. Methods The learning objectives stem case and stem questions were delivered to the learners one week prior to meeting. At the end of the session, a short written multiple-choice quiz was delivered to the learners. The answers to the quiz were delivered only after taking the quiz. The answers to the quiz were discussed with the group. At the end of the assembly, learners were asked to anonymously fill out a form to evaluate their experience with this PBLD. The author used this PBLD to teach medical students, residents and fellows participating in the Surgical Intensive Care Unit (SICU). Groups ranged in size from 5 to 10. Results Overall, approximately 80 people participated in this PBLD. Approximately, 60% of learners were residents rotating in the ICU, 25% were medical students, 10% were critical care fellows, and 5% were certified practicing intensivists. Assessment of the PBLD was conducted via an anonymous paper-based survey. Ninety percent of participants responded. Eighty-five percent of respondents rated the PBLD as “excellent. This PBLD was cited as a reason for an ‘outstanding’ evaluation the instructor received for the academic year 2010–2011. Discussion Based on learners' enthusiasm and positive feedback, the instructor is currently preparing a curriculum of PBLDs on similar life-threatening ICU topics to be delivered to trainees during their SICU rotation, with the potential of expanding this protocol to other ICUs. This resource promotes interactive learning about a clinical condition that will be encountered by learners at all levels.

p-cycle networks have attracted a considerable interest in the network survivability literature in recent years. However, most of the existing work assumes a known network topology upon which to apply p-cycle restoration. In the present work, we develop an incremental topology optimization ILP for p-cycle network design, where a known topology can be amended with new fibre links selected from a set of eligible spans. The ILP proves to be relatively easy to solve for small test case instances but becomes computationally intensive on larger networks. We then follow with a relaxation-based decomposition approach to overcome this challenge. The decomposition approach significantly reduces computational complexity of the problem, allowing the ILP to be solved in reasonable time with no statistically significant impact on solution optimality.

Early embryonic loss, caused by reduced embryo developmental competence, is the major cause of subfertility in humans and animals. This embryo developmental competence is determined during oocyte maturation and the first embryo divisions. Therefore, it is essential to identify the underlying molecules regulating these critical developmental stages. Cathepsin L (CTSL), a lysosomal cysteine protease, is involved in regulating cell cycle progression, proliferation and invasion of different cell types. However, CTSL role in mammalian embryo development is unknown. Using bovine in vitro maturation and culture systems, we show that CTSL is a key regulator for embryo developmental competence. We employed a specific CTSL detection assay in live cells to show that CTSL activity correlates with meiotic progression and early embryo development. Inhibiting CTSL activity during oocyte maturation or early embryo development significantly impaired oocyte and embryo developmental competence as evidenced by lower cleavage, blastocyst and hatched blastocyst rates. Moreover, enhancing CTSL activity, using recombinant CTSL (rCTSL), during oocyte maturation or early embryo development significantly improved oocyte and embryo developmental competence. Importantly, rCTSL supplementation during oocyte maturation and early embryo development significantly improved the developmental competence of heat‐shocked oocytes/embryos which are notoriously known for reduced quality. Altogether, these results provide novel evidence that CTSL plays a pivotal role in regulating oocyte meiosis and early embryonic development. [ABSTRACT FROM AUTHOR]

IFNT is important in establishing pregnancy in ruminants. Secreted IFNT in the uterus induces the expression of an interferon-stimulated gene (ISG) in uterine tissues and peripheral blood leukocytes (PBLs). In our previous study, increased lysosome and lysosomal cathepsin (CTS) activity and mRNA expression were observed in PBLs of pregnant cows on day 18 of pregnancy. However, the mechanism of IFNT stimulation in PBLs is unclear. Here, we explored the IFNT-mediated lysosomal activation mechanisms in PBLs during early pregnancy in dairy cows. PBLs collected from the peripheral blood of Holstein cows on day 18 post artificial insemination, after confirmation of their pregnancy status, were used to detect the expression of lysosomal-associated membrane protein (LAMP) 1, 2, CTSB and CTSK. Expression of all genes was significantly higher in PBLs of pregnant cows than in nonpregnant cows. In vitro IFN-mediated stimulation of PBLs collected from cows that did not undergo AI significantly increased lysosomal acidification and expression of LAMP1 and 2, as well as the activities of CTSB and CTSK. Immunodetection analysis showed an increase in LAMP1 and CTSK levels in the PBLs of day 18 pregnant cows. JAK inhibitor significantly decreased lysosomal acidification, CTSK activity, LAMP1, 2, and CTSK expression in the presence of IFNT. These results suggest that IFNT regulates lysosomal function via a type 1IFN-mediated pathway in PBLs during pregnancy recognition. [ABSTRACT FROM AUTHOR]