Polymorphisms of TNF-alpha (- 308), IL-1beta (+ 3954) and IL1-Ra (VNTR) are associated to severe stage of endometriosis in Mexican women: a case control study.

BACKGROUND: Endometriosis is an estrogen-dependent and chronic inflammatory disease affecting up to 10% of women. It is the result of a combined interaction of genetic, epigenetic, environmental, lifestyle, reproductive and local inflammatory factors. In this study, we investigated whether single nucleotide polymorphisms (SNPs) mapping to TNF-alpha (TNF, rs1800629) and IL-1beta (IL1B, rs1143634) and variable number tandem repeat polymorphism mapping to IL1-Ra (IL1RN intron 2, rs2234663) genetic loci are associated with risk for endometriosis in a Mexican mestizo population. METHODS: This study included 183 women with confirmed endometriosis (ENDO) diagnosed after surgical laparoscopy and 186 women with satisfied parity and without endometriosis as controls (CTR). PCR/RFLP technique was used for genotyping SNPs (rs1800629 and rs1143634); PCR for genotyping rs2234663. RESULTS: We found no statistical differences in age between groups nor among stages of endometriosis and the CTR group. We observed no difference in genotype and allele frequencies, nor carriage rate between groups in none of the three studied polymorphisms. The prevalence of TNF*2-allele heterozygotes (p = 0.025; OR 3.8), TNF*2-allele (p = 0.029; OR 3.4), IL1B*2-allele heterozygotes (p = 0.044; OR 2.69) and its carriage rate (p = 0.041; OR 2.64) in endometriosis stage IV was higher than the CTR group. Surprisingly, the carriage rate of IL1RN*2-allele (ENDO: p = 0.0004; OR 0.4; stage I: p = 0.002, OR 0.38; stage II: p = 0.002, OR 0.35; stage III: p = 0.003, OR 0.33), as well as the IL1RN*2-allele frequencies (ENDO: p = 0.0008, OR 0.55; I: p = 0.037, OR 0.60; II: p = 0.002, OR 0.41; III: p = 0.003, OR 0.38) were lower than the CTR group. Women with endometriosis stage IV (severe) had frequencies more alike to the CTR group in the IL1RN*2 allele frequency (31.2% vs. 27.2%) and carriage rate (37.5% vs. 41.9%). CONCLUSION: Although these polymorphisms are not associated with the risk of endometriosis, Mexican mestizo women with severe stage of endometriosis have higher frequencies of TNF*2-, IL1B*2- and IL1RN*2-alleles, which may explain a possible correlation with disease severity rather than predisposition or risk.

Development and validation of a new model for predicting hypocalcaemia after total thyroidectomy: the NuGra model.

BACKGROUND: Hypocalcaemia is the most frequent complication after total thyroidectomy. Finding a method for its early detection has become a priority. A single-center prospective cohort study was conducted to identify risk factors for postoperative hypocalcaemia, develop an early detection model, and test its validity in a different group of patients. METHODS: The sample was composed of patients who underwent a total thyroidectomy between May 2012 and September 2015. Demographic, clinical, laboratory, and surgical data were collected. The incidence of hypocalcaemia and permanent hypoparathyroidism was calculated. Bivariate and multivariate analysis identified several independent predictors of hypocalcaemia, which were used to design a predictive model. The validity of the model was subsequently tested in a different cohort. Area under the ROC curve (AUROC) was calculated to determine its predictive power. RESULTS: The study and validation groups included 352 and 118 patients, respectively. Seventy-three patients developed laboratory-confirmed hypocalcaemia (20.7%), and symptomatic in 43 (12.2%). Multivariate analysis confirmed as independent predictors of hypocalcaemia the higher number of parathyroid glands identified [OR 1.41(0.98, 2.02); p = 0.063] and pre-to-postoperative gradient of parathormone decline [OR 1.06(1.04, 1.08); p < 0.001]. Based on these variables, the NuGra (Number of parathyroid glands identified-Gradient of decline) model was developed for predicting laboratory-confirmed hypocalcaemia. Its predictive power was high (AUROC 0.902, CI 0.857-0.947) for the study and the validation group (AUROC 0.956, CI 0.919-0.993). CONCLUSIONS: A higher number of parathyroid glands identified and a higher gradient of parathormone decline are risk factors for post-thyroidectomy hypocalcaemia. The NuGra model is useful for early prediction of individual risk for hypocalcaemia.

Higher fat mass and fat mass accretion during the first six months of life in exclusively breastfed infants.

BACKGROUND: Early nutrition influences infant growth and body composition, which may play a role in the infant's metabolic programming. Breastfed infants appear to have higher fat mass than formula-fed infants, but most comparisons have been cross-sectional, and evidence is scarce. The aim of this study was to describe fat mass and fat mass accretion during the first six months of life and evaluate differences by type of feeding (OMS). METHODS: Prospective cohort of healthy pregnant women and their infants (Mexico City, 2009-2014). At 1 (T1), 3 (T2) and 6 (T3) months of age, fat mass (FM) (PEAPOD) and type of feeding (feeding questionnaire) were evaluated. RESULTS: We included 109 healthy infants (mean ± SD age: 39 ± 1.1 weeks; birthweight: 2959 ± 294 g). Exclusive/predominant breastfed (EBF) infants had higher FM at T2 and T3 compared with non-EBF (%FM T3: 29.7 ± 5.9% vs 24.7 ± 5.6%, respectively) (p < 0.05). All infants increased their FM throughout time (p < 0.001). EBF infants showed a significant higher FM accretion (ß: 3.61; 95% CI: 1.57-5.66, p < 0.01); the difference was maintained after controlling for confounding variables. CONCLUSIONS: Exclusive/predominant breastfeeding promotes higher accretion of FM during the first six months of life which could have an important effect in the programming of health outcomes later in life.

Anthropometric and clinical correlates of fat mass in healthy term infants at 6 months of age.

BACKGROUND: Body composition in infancy plays a central role in the programming of metabolic diseases. Fat mass (FM) is determined by personal and environmental factors. Anthropometric measurements allow for estimations of FM in many age groups; however, correlations of these measurements with FM in early stages of life are scarcely reported. The aim of this study was to evaluate anthropometric and clinical correlates of FM in healthy term infants at 6 months of age. METHODS: Healthy term newborns (n = 102) from a prospective cohort. Weight, length, skinfolds (biceps, triceps, subscapular and the sum -SFS-) and waist circumference (WC) were measured at 6 months. Body mass index (BMI) and WC/length ratio were computed. Type of feeding during the first 6 months of age was recorded. Air displacement plethysmography was used to asses FM (percentage -%-) and FM index (FMI) was calculated. Correlations and general linear models were performed to evaluate associations. RESULTS: Significant correlations were observed between all anthropometric measurements and FM (% and index)(p < 0.001). Exclusive/predominant breastfed infants had higher FM and anthropometric measurements at 6 months. Models that showed the strongest associations with FM (% and index) were SFS + WC + sex + type of feeding. CONCLUSIONS: Anthropometry showed good correlations with FM at 6 months of age. Skinfolds sum and waist circumference were the strongest anthropometric variables associated to FM. Exclusive/predominant breastfeeding was strongly associated with FM.

A Data-Driven Approach to Team Training for Nurses in a Level II Trauma Center.

This prospective investigation describes the process of designing a targeted, data-driven team training aimed at reducing identified process inefficiencies or flow disruptions (FDs) that threaten the optimal delivery of trauma care. Trained researchers observed and classified FDs during 34 trauma cases in a Level II trauma center. Multidisciplinary trauma personnel generated interventions to identified issues using the human factors intervention matrix (HFIX). This article focuses on one intervention: a formal trauma nurse training program centered around leadership, teamwork, and communication. The training was well perceived and was found to have a significant impact on participant knowledge of course content; t (65) = -13.92, p ≤ .01. By using hospital-specific data to drive intervention development from multidisciplinary team members, it is possible to develop effective solutions aimed at addressing individual threats.

Failure to Target RANKL Signaling Through p38-MAPK Results in Defective Osteoclastogenesis in the Microphthalmia Cloudy-Eyed Mutant.

The Microphthalmia-associated transcription factor (MITF) is a basic helix-loop-helix leucine zipper family factor that is essential for terminal osteoclast differentiation. Previous work demonstrates that phosphorylation of MITF by p38 MAPK downstream of Receptor Activator of NFkB Ligand (RANKL) signaling is necessary for MITF activation in osteoclasts. The spontaneous Mitf cloudy eyed (ce) allele results in production of a truncated MITF protein that lacks the leucine zipper and C-terminal end. Here we show that the Mitf(ce) allele leads to a dense bone phenotype in neonatal mice due to defective osteoclast differentiation. In response to RANKL stimulation, in vitro osteoclast differentiation was impaired in myeloid precursors derived from neonatal or adult Mitf(ce/ce) mice. The loss of the leucine zipper domain in Mitf(ce/ce) mice does not interfere with the recruitment of MITF/PU.1 complexes to target promoters. Further, we have mapped the p38 MAPK docking site within the region deleted in Mitf(ce). This interaction is necessary for the phosphorylation of MITF by p38 MAPK. Site-directed mutations in the docking site interfered with the interaction between MITF and its co-factors FUS and BRG1. MITF-ce fails to recruit FUS and BRG1 to target genes, resulting in decreased expression of target genes and impaired osteoclast function. These results highlight the crucial role of signaling dependent MITF/p38 MAPK interactions in osteoclast differentiation.

[Association between adiposity, inflammation and cardiovascular risk factors in school-aged Mexican children]. / Asociación entre adiposidad, inflamación y factores de riesgo cardiovascular en un grupo de escolares mexicanos.

OBJECTIVE: To evaluate the differences in inflammation markers and cardiovascular risk factors in a group of school-aged children with and without excessive adiposity. To examine the relationship between adiposity, inflammation, and cardiovascular risk factors. METHODS: Cross-sectional study of 285 school children (8-12 years old). Adiposity (body mass index, BMI, total body fat, TBF, and waist circumference), inflammatory markers (C-reactive protein [CRP], interleukin 1ß [IL-1ß], interleukin 6 [IL-6], and tumor necrosis factor-a [TNF-α]) and cardiovascular risk factors were analyzed. Mean differences were calculated and multiple regression models were made. RESULTS: Obese children had higher concentrations of CRP and IL-1ß; children with abdominal obesity also had higher CRP levels. A higher BMI was associated with higher blood pressure, and higher total cholesterol, triglycerides-TAG, and insulin concentrations, and with lower HDL-cholesterol. The CRP and IL-1ß concentrations correlated significantly with the three adiposity indices. The IL-6 concentrations were associated with TAG, and IL-1ß with HDL-cholesterol concentration, after adjustment by BMI. DISCUSSION: In a group of school-aged Mexican children, obesity increases cardiovascular risk and inflammation. Both IL-6 and IL-1ß appear to be factors involved in lipid alterations in these children. More research is needed in order to explore the role of subclinical inflammation in the development of cardiovascular alterations that have already been described in Mexican children with obesity.

Impact of Ischemia and Preservation Times on Survival in Transplant Recipients From After Circulatory Death Donors.

BACKGROUND: The limitation of ischemia times, which damages the organs and impacts transplant outcomes, is a drawback of controlled donation after circulatory death. METHODS: The aim of the study was to analyze the influence of preservation and ischemia times on overall survival and both censured graft survival and overall graft survival. This was an observational and retrospective study of patients undergoing liver transplantation with grafts from controlled donation after circulatory death between November 2013 and November 2022. RESULTS: Sixty-five patients were included in the study. Twenty percent (12 patients) developed early graft dysfunction according to Olthoff's classification, and 7 patients (11.6%) scored ≥7 points according to the Model for Early Allograft Function Scoring scale. Five patients (7.6%) met the criteria for primary graft failure. The retransplantation rate was 9.2% (6 cases). Fifty patients (76.9%) remained alive, and 15 patients (23.1%) died. When analyzing overall survival based on the main preservation and ischemia times, we observed that the best results occurred in the group with a functional warm ischemia time <12 minutes, with a survival rate at 1, 3, and 5 years of 95.8%, 87.1%, and 87.1%, respectively (P = .043). Regarding the analysis of censured graft survival based on the main preservation and ischemia times, we found that the worst results occurred in the group with a cold ischemia time ≥6 hours, with a survival rate of around 48% at 3 and 5 years (P = .047). CONCLUSIONS: High-risk patients have lower overall and graft survival in the short and long term in grafts from controlled donation after circulatory death.

Ophthalmomyiasis Externa and Importance of Risk Factors, Clinical Manifestations, and Diagnosis: Review of the Medical Literature.

OBJECTIVE: This review aims to describe and compare the risk factors, clinical course, diagnosis, and parasitologic features of external ophthalmomyiasis. We also discuss the different preventive measures and the effect of global warming in a large case series reported from January 2000 to December 2022. METHODS: We perform a literature review of reported cases of external ophthalmomyiasis to determine the clinical characteristics, therapeutic management, and information on the organisms that most commonly cause external ophthalmomyiasis. RESULTS: A total of 312 cases of external ophthalmomyiasis were recorded. The most common causative organism was Oestrus ovis (Linnaeus) (Diptera: Oestridae), accounting for 72.1% of cases, followed by Dermatobia hominis (Linnaeus Jr. in Pallas, 1781) (Diptera: Oestridae) at 5.4%, Lucilia sericata (Meigen) (Diptera: Calliphoridae) at 0.96%, and Chrysomyia bezziana (Villeneuve) (Diptera: Calliphoridae) at 0.96%. Before experiencing symptoms, 43.6% of cases reported having direct contact with flies or being hit in the eye, 33% reported no associated risk factors, 9.3% reported living with sheep and goats, and 7.7% reported a history of foreign objects entering the eye. The most common symptoms for those affected by O. ovis were sudden onset, including a foreign body sensation and movement, redness, tearing, itching, swelling, irritation, photophobia, burning, and ocular secretion. In cases caused by D. hominis, symptoms included eyelid edema, pain, redness, itching, movement within the lesion, ocular irritation, and discharge. Regarding occupational or recreational activity, agriculture, and livestock had the highest incidence, followed by trades and technical activities, being a student, and having traveled to an endemic region for work or recreation. CONCLUSION: Patients with red eyes may suffer from external ophthalmomyiasis, which requires a thorough examination to diagnose and treat it early. Moreover, as the temperature increases due to climate change, it is essential to consider how this will affect the spread of different pathogens.

Development and validation of anthropometric-based fat-mass prediction equations using air displacement plethysmography in Mexican infants.

BACKGROUND/OBJECTIVES: Fat-mass (FM) assessment since birth using valid methodologies is crucial since excessive adiposity represents a risk factor for adverse metabolic outcomes. AIM: To develop infant FM prediction equations using anthropometry and validate them against air-displacement plethysmography (ADP). SUBJECTS/METHODS: Clinical, anthropometric (weight, length, body-mass index -BMI-, circumferences, and skinfolds), and FM (ADP) data were collected from healthy-term infants at 1 (n = 133), 3 (n = 105), and 6 (n = 101) months enrolled in the OBESO perinatal cohort (Mexico City). FM prediction models were developed in 3 steps: 1) Variable Selection (LASSO regression), 2) Model behavior evaluation (12-fold cross-validation, using Theil-Sen regressions), and 3) Final model evaluation (Bland-Altman plots, Deming regression). RESULTS: Relevant variables in the FM prediction models included BMI, circumferences (waist, thigh, and calf), and skinfolds (waist, triceps, subscapular, thigh, and calf). The R2 of each model was 1 M: 0.54, 3 M: 0.69, 6 M: 0.63. Predicted FM showed high correlation values (r ≥ 0.73, p < 0.001) with FM measured with ADP. There were no significant differences between predicted vs measured FM (1 M: 0.62 vs 0.6; 3 M: 1.2 vs 1.35; 6 M: 1.65 vs 1.76 kg; p > 0.05). Bias were: 1 M -0.021 (95%CI: -0.050 to 0.008), 3 M: 0.014 (95%CI: 0.090-0.195), 6 M: 0.108 (95%CI: 0.046-0.169). CONCLUSION: Anthropometry-based prediction equations are inexpensive and represent a more accessible method to estimate body composition. The proposed equations are useful for evaluating FM in Mexican infants.

A scoping review and critical evaluation of the methodological quality of clinical practice guidelines on nutrition in the preconception.

Introduction: Clinical practice guidelines (CPGs) contain recommendations for specific clinical circumstances, including maternal malnutrition. This study aimed to identify the CPGs that provide recommendations for preventing, diagnosing, and treating women's malnutrition. Additionally, we sought to assess the methodological quality using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. Methods: An online search for CPGs was performed, looking for those that contained lifestyle and nutritional recommendations to prevent, diagnose and treat malnutrition in women during the preconception period using PubMed and different websites. The reviewers utilized the AGREE II instrument to appraise the quality of the CPGs. We defined high-quality guidelines with a final score of > 70%. Results: The titles and abstracts from 30 guidelines were screened for inclusion, of which 20 guidelines were fully reviewed for quality assessment. The overall quality assessment of CPGs was 73%, and only 55% reached a high-quality classification. The domains in the guidelines classified as high-quality had the highest scores in "Scope and Purpose" and "Clarity of Presentation" with a median of 98.5 and 93%, respectively. Discussion: Further assessment is needed to improve the quality of the guidelines, which is an opportunity to strengthen them, especially in the domains with the lowest scores.

V3 versican isoform alters the behavior of human melanoma cells by interfering with CD44/ErbB-dependent signaling.

Versican is a hyaluronan-binding, extracellular chondroitin sulfate proteoglycan produced by several tumor types, including malignant melanoma, which exists as four different splice variants. The short V3 isoform contains the G1 and G3 terminal domains of versican that may potentially interact directly or indirectly with the hyaluronan receptor CD44 and the EGFR, respectively. We have previously described that overexpression of V3 in MeWo human melanoma cells markedly reduces tumor cell growth in vitro and in vivo. In this study we have investigated the signaling mechanism of V3 by silencing the expression of CD44 in control and V3-expressing melanoma cells. Suppression of CD44 had the same effects on cell proliferation and cell migration than those provoked by V3 expression, suggesting that V3 acts through a CD44-mediated mechanism. Furthermore, CD44-dependent hyaluronan internalization was blocked by V3 expression and CD44 silencing, leading to an accumulation of this glycosaminoglycan in the pericellular matrix and to changes in cell migration on hyaluronan. Furthermore, ERK1/2 and p38 activation after EGF treatment were decreased in V3-expressing cells suggesting that V3 may also interact with the EGFR through its G3 domain. The existence of a EGFR/ErbB2 receptor complex able to interact with CD44 was identified in MeWo melanoma cells. V3 overexpression resulted in a reduced interaction between EGFR/ErbB2 and CD44 in response to EGF treatment. Our results indicate that the V3 isoform of versican interferes with CD44 and the CD44-EGFR/ErbB2 interaction, altering the signaling pathways, such as ERK1/2 and p38 MAPK, that regulate cell proliferation and migration.

Providing Support Differentially Affects Asian American and Latinx Psychosocial and Physiological Well-Being: A Pilot Study.

Although substantial evidence suggests receiving social support has positive implications for well-being, less is known about how providing support can confer benefits, particularly for Asian American and Latinx individuals who are more likely to come from interdependent cultures that emphasize family obligation. Asian American and Latinx college students (N = 48; M age = 21.44, SD = 2.61; 68.75% female) reported on anxiety before taking part in a modified laboratory task that elicited a physiological stress response as measured by total cortisol output. They were randomly assigned to write (a) a supportive note to a family member, (b) a supportive note to a close friend, or (c) about their day in a control condition after the mild lab stressor and reported on psychosocial well-being (i.e., post-task anxiety and self-esteem). Those who provided support to a family member experienced higher self-esteem compared to those in the control condition. However, there was variation in Asian American and Latinx participants' physiological stress response (i.e., total cortisol output). The findings suggest that providing support to close others, particularly family members, can be differentially meaningful for individuals from diverse backgrounds.

Indication for Liver Transplantation After Direct-Acting Agents in the Treatment of Patients With Hepatitis C.

BACKGROUND: The development of new direct-acting antivirals (DAA) for hepatitis C virus (HCV) treatment has reduced the indications for liver transplantation (LT). We analyzed the indications, characteristics, and evolution of patients with HCV infection who were treated with DAA-based therapies and who underwent LT. MATERIAL AND METHODS: A retrospective single-center study was performed. Data were collected of patients undergoing LT owing to HCV infection between January 2016 and August 2020. Overall characteristics of the patients were analyzed and divided into 2 groups according to the indication for LT: hepatocellular carcinoma (HCC) or decompensated cirrhosis (DC). Differences between biliary and vascular complications after surgery and survival time were compared. RESULTS: Of 156 LTs, 33 (22%) were performed in patients with HCV infection in this period, which shows a decrease of nearly 16% when comparing this period with the interferon/ribavirin era. Indications for LT were 56.7% in patients with HCC and 43.3% in patients with DC. After DAA treatment, all patients developed a sustained viral response. Mean age of the global series, HCC group, and DC group were 56.9, 58.71, and 54.4 years, respectively (P = .041); 53.8% of the HCV-DC group initiated DAA treatment by the time to be included at the waiting list, compared with 17.6% of HCV-HCC group (P = .045). There were no statistically significant differences in terms of survival or biliary and vascular complications after LT. CONCLUSION: Patients with HCV are still part of the waiting list, mainly because of HCC. No statistical differences were shown in terms of postoperative complications or survival. Studies with a higher number of patients are needed.

Quality Appraisal of Nutritional Guidelines to Prevent, Diagnose, and Treat Malnutrition in All Its Forms during Pregnancy.

This work aimed to identify clinical practice guidelines (CPGs) that include recommendations for the prevention, diagnosis, and treatment of women's malnutrition during pregnancy and to evaluate the quality of these guidelines using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument. We conducted a literature review using PubMed and different websites from January 2009 to February 2021. The quality of the CPGs was independently assessed by reviewers using the AGREE II instrument, which defines guidelines scoring >70% in the overall assessment as "high quality". The analysis included 43 guidelines. Among the main findings, we identified that only half of the CPGs (51.1%) obtained a final "high quality" evaluation. AGREE II results varied widely across domains and categories. The two domains that obtained the highest scores were scope and purpose with 88.3% (range 39 to 100%) and clarity of presentation with 87.2% (range 25 to 100%). Among the "high quality" CPGs, the best scores were achieved by the three guidelines published by the National Institute of Health and Care Excellence (NICE) and the World Health Organization (WHO). Due to the importance of maternal nutrition in pregnancy, it is essential to join forces to improve the quality of the guidelines, especially in CPGs that do not meet the reference standards for quality.

Quantitative and qualitative peritoneal immune profiles, T-cell apoptosis and oxidative stress-associated characteristics in women with minimal and mild endometriosis.

OBJECTIVES: To assess immunological variables, T-cell apoptosis and oxidative stress markers in the peripheral blood and peritoneal fluid of women with (WEN) and without (WWE) endometriosis. DESIGN: Observational and transverse case-control study. SETTING: National Institute of Perinatology, Mexico City, Mexico. POPULATION AND SAMPLE: Peripheral blood and peritoneal fluid obtained from 30 WWE and 32 WEN. METHODS: Blood was drawn before surgery and peritoneal fluid was collected during surgery but before any surgical procedure had been carried out. Flow cytometry, spectrophotometry, high-performance liquid chromatography and multiplex immunoassay analyses were performed. MAIN OUTCOME MEASURES Peripheral and peritoneal lymphocyte subpopulations (CD3(+), CD4(+) CD3(+), CD8(+) CD3(+), CD16(+) CD56(+), human leucocyte antigen-DR(+) CD3(+) and CD19(+)), intracellular CD4(+) CD3(+) and CD8(+) CD3(+) cytokine synthesis (interleukin-2 [IL-2] and interferon-γ [IFN-γ]), CD3(+) apoptosis, malondialdehyde and ascorbate concentrations and peritoneal cytokine concentrations. RESULTS: No differences were found in peripheral and peritoneal lymphocyte subsets between the groups. Peritoneal T lymphocytes from WEN produced less IL-2 and IFN-γ than those from WWE. Peritoneal malondialdehyde concentrations were higher and ascorbate concentrations were lower in WEN than in WWE. Higher peritoneal concentrations of pro-inflammatory cytokines (IL-1ß, tumour necrosis factor-α and IL-6) and chemokines (IL-10, IL-8, eotaxin, vascular endothelial growth factor, monocyte chemotactic protein-1 and regulated upon activation, normal T-cell expressed, and secreted) and lower concentrations of IFN-γ, IL-1 receptor antagonist and IL-15 were found in WEN. No statistical differences were found in IL-2, IL-4, IL-12 and IL-13 concentrations. CONCLUSION: The alterations observed in WEN were associated with a diminished peritoneal T helper type 1 immune response. Pro-inflammatory, chemotactic, angiogenic and oxidative stress markers were altered in the peritoneal milieu of WEN. These changes appeared to contribute to the peritoneal immune alterations found.

Increased HAS2-driven hyaluronic acid synthesis in shar-pei dogs with hereditary cutaneous hyaluronosis (mucinosis).

The Chinese shar-pei dog is known for its distinctive feature of wrinkled and thickened skin, defined as primary or hereditary cutaneous mucinosis. In a recent report, we identified the mucinous material deposited in the shar-pei skin as the polysaccharide hyaluronan (HA). In the present work, the molecular and cellular mechanisms underlying this phenotype have been identified in dermal fibroblasts isolated from shar-pei dogs. The production of HA, which appeared to be mainly associated with cell membrane protrusions and also intracellular, was higher in shar-pei fibroblasts than in control cells. The HA accumulation is related to a higher mRNA expression of the isoform HAS2 of the HA-synthesizing enzyme family, hyaluronan synthases (HAS). The higher expression of HAS2 in shar-pei fibroblasts was confirmed at the protein level. The other HAS isoenzymes, HAS1 and HAS3, and the HA-degrading enzymes, Hyal1 and Hyal2, were not differentially expressed in shar-pei fibroblasts compared with cells from control dogs. Fibroblasts from shar-pei dogs and from control dogs are morphologically different as observed by transmission electron microscopy. Scanning electron microscopy revealed a large number of cellular protrusions with associated globular deposits. Electron microscopy after labelling with biotinylated HA-binding protein confirmed an increased HA content in shar-pei fibroblasts, which could be localized in several subcellular structures. The authors propose the name hereditary cutaneous hyaluronosis (HCH) for affected dogs, because it better defines the cutaneous mucinosis of shar-pei dogs.

A Theoretical Model of Flow Disruptions for the Anesthesia Team During Cardiovascular Surgery.

OBJECTIVES: This investigation explores flow disruptions observed during cardiothoracic surgery and how they serve to disconnect anesthesia providers from their primary task. We can improve our understanding of this disengagement by exploring what we call the error space or the accumulated time required to resolve disruptions. METHODS: Trained human factors students observed 10 cardiac procedures for disruptions impacting the anesthesia team and recorded the time required to resolve these events. Observations were classified using a human factors taxonomy. RESULTS: Of 301 disruptions observed, interruptions (e.g., those events related to alerts, distractions, searching activity, spilling/dropping, teaching moment, and task deviations) accounted for the greatest frequency of events (39.20%). The average amount of time needed for each disruption to be resolved was 48 seconds. Across 49.87 hours of observation, more than 4 hours were spent resolving disruptions to the anesthesia team's work flow. CONCLUSIONS: By defining a calculable error space associated with these disruptions, this research provides a conceptual metric that can serve in the identification and design of targeted interventions. This method serves as a proactive approach for recognizing systemic threats, affording healthcare workers the opportunity to mitigate the development and incidence of preventable errors precedently.

Acute abdomen secondary to massive bleeding due to rupture of liver metastases of a gastrointestinal stroma tumor.

Hemoperitoneum secondary to non-traumatic liver rupture is a rare cause of an acute abdomen. We present the case of a patient with a hepatic rupture secondary to metastasis of a gastrointestinal stromal tumor (GIST) who required an emergent laparotomy due to hemodynamic instability. Intraoperatively, a lesion of more than 20cm dependent on the posterior gastric wall and a hemoperitoneum secondary to rupture of liver metastases and decapsulation of the Glisson capsule was evidenced. A frequent complication of GIST tumors is its rupture causing gastrointestinal bleeding or hemoperitoneum, as occurred in our case.

El hemoperitoneo secundario a estallido hepático no traumático es una causa poco frecuente de abdomen agudo. Se presenta el caso de una paciente con estallido hepático secundario a metástasis de un tumor del estroma gastrointestinal (GIST) que requirió una laparotomía emergente por inestabilidad hemodinámica. Se evidenció intraoperatoriamente una lesión de más de 20 cm dependiente de la pared posterior gástrica y un hemoperitoneo secundario a estallido de metástasis hepáticas y descapsulación de la cápsula de Glisson. Una complicación frecuente de los GIST es la rotura que ocasiona hemorragia digestiva o hemoperitoneo, como ocurrió en nuestro caso.

Using Broken Windows Theory as the Backdrop for a Proactive Approach to Threat Identification in Health Care.

OBJECTIVES: Historically, health care has relied on error management techniques to measure and reduce the occurrence of adverse events. This study proposes an alternative approach for identifying and analyzing hazardous events. Whereas previous research has concentrated on investigating individual flow disruptions, we maintain the industry should focus on threat windows, or the accumulation of these disruptions. This methodology, driven by the broken windows theory, allows us to identify process inefficiencies before they manifest and open the door for the occurrence of errors and adverse events. METHODS: Medical human factors researchers observed disruptions during 34 trauma cases at a Level II trauma center. Data were collected during resuscitation and imaging and were classified using a human factors taxonomy: Realizing Improved Patient Care Through Human-Centered Operating Room Design for Threat Window Analysis (RIPCHORD-TWA). RESULTS: Of the 576 total disruptions observed, communication issues were the most prevalent (28%), followed by interruptions and coordination issues (24% each). Issues related to layout (16%), usability (5%), and equipment (2%) comprised the remainder of the observations. Disruptions involving communication issues were more prevalent during resuscitation, whereas coordination problems were observed more frequently during imaging. CONCLUSIONS: Rather than solely investigating errors and adverse events, we propose conceptualizing the accumulation of disruptions in terms of threat windows as a means to analyze potential threats to the integrity of the trauma care system. This approach allows for the improved identification of system weaknesses or threats, affording us the ability to address these inefficiencies and intervene before errors and adverse events may occur.