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INTRODUCTION: In the critically ill patient, there is a continuous production of reactive oxygen species (ROS) that need to be neutralized to prevent oxidative stress (OS). Quantitatively speaking, the glutathione system (GSH) is the most important anti-oxidant endogenous defense. To increase it, glutamine supplementation has been shown to be effective by protecting against the oxidative damage and reducing the morbimortality. OBJECTIVE: To assess the effect of adding an alanylglutamine dipeptide to PN on lipid peroxidation lipidica and glutathione metabolism, as well as its relationship with morbidity in critically ill patients. METHODS: Determination through spectrophotometry techniques of glutathione peroxidase, glutathione reductase, total glutathione, and maloniladdehyde at admission adn after seven days of hospitalization at the Intensive Care Unit (ICU) in 20 patients older than 18 years on parenteral nutrition therapy. RESULTS: The group of patients receiving parenteral nutrition with glutamine supplementation had significant increases in total glutathione (42.35+/-13 vs 55.29+/-12 micromol/l; p<0.05) and the enzymatic activity of glutathione peroxidasa (470+/-195 vs 705+/-214 micromol/l; p<0.05) within one week of nutritional therapy, whereas the group on conventional parenteral nutrition did not show significant changes of any of the parameters studied (p>0.05). However, both mortality and ICU stay were not different between the study group, whereas the severity (assessed by the SOFA score) was lower in the group of patients receiving glutamine (SOFA 5+/-2 vs 8+/-1.8; p<0.05). CONCLUSIONS: Glutamine intake in critically ill patients improves the antioxidant defenses, which leads to lower lipid peroxidation and lower morbidity during admission at the ICU. [ABSTRACT FROM AUTHOR]

Introduction : Hearing is fundamental for the development of newborns. The Universal Neonatal Hearing Screening (UNHS) in Brazil seeks to detect hearing loss early to minimize the impact on the child's hearing health. Some coping with underreporting of Sexually Transmitted Infections (STIs), such as congenital syphilis and HIV, are important, considering these situations are correlated with neonatal hearing loss. Objective : To assess the prevalence of congenital syphilis and HIV in newborns from two maternity hospitals in Greater Florianópolis and the impact on hearing, based on the results of the UNHS retest from 2018 to 2022. Methods : Retrospective cross-sectional study with secondary data of newborns treated at a SUS Hearing Health Care Service (SASA) between 2018 and 2022, referred for OAE and BAEP retests. Results : Of the 1211 newborns referred for retesting, 283 presented the investigated infections. Of these, 170 were diagnosed with congenital syphilis (59.86%), 105 were diagnosed with HIV (36.67%), and 8 with both infections (2.82%). When performing the retest, one newborn did not present a satisfactory auditory result, and the others passed when the OAE and BAEP tests were observed. Conclusion : UNHS is effective, and retests are fundamental in the screening and proper monitoring of the hearing health of newborns. Public health guidelines are evidenced, contributing to neonatal health and hearing health screening., (© Association of Otolaryngologists of India 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objectives: Despite clinical relevance, commercially available molecular tools for accurate β-lactamase detection are limited. In this study, we evaluated the performance of the ARM-D Ⓡ Kit, β-Lactamase, a commercially available multiplex PCR assay designed to detect nine β-lactamase genes, including the five major plasmid-mediated carbapenemases, ESBL and AmpC genes circulating in the United States., Methods: A diverse collection of 113 Gram-negative isolates, including 42 with multiple β-lactamases genes, was selected from the U.S. Centers for Disease Control and Prevention (CDC) & Food and Drug Administration (FDA) Antimicrobial Resistance Isolate Bank, to represent the most frequently detected bacterial species carrying plasmid-mediated β-lactam resistance genes., Results: Results were compared with whole genome sequence data. Of 164 β-lactamase gene targets with 49 unique variants, all were detected correctly without any cross-reactivity. The sensitivity and specificity were 100% (164/164) and 99.9% (852/853), respectively., Conclusion: The ARM-D Ⓡ Kit, β-Lactamase detected a wide range of β-lactamase genotypes at a low upfront cost. The Streck assay represents a suitable, comprehensive tool for the detection of key β-lactamase resistance genes of public health concern in the United States., (Published by Elsevier Ltd.)

Purpose: To describe a case of successful treatment of a patient with a rare primary pituitary abscess (PA) and propose a management algorithm., Summary of Background Data: PA is an infrequent entity that can be life-threatening if not promptly diagnosed and treated. PAs can be primary or secondary, the latter in the presence of sellar anomalies, risk factors or a systemic or local infection. Symptoms are nonspecific, making clinical suspicion imperative. Magnetic Resonance Imaging (MRI) is the radiological tool of choice. Despite some characteristic radiographic signs, oftentimes the diagnosis is not suspected until surgical exploration. Treatment includes transsphenoidal decompression surgery with sampling of purulent material and abscess wall for appropriate microbiological staining and cultures (bacteria, mycobacteria and fungus) and prolonged antibiotic treatment. Pituitary hormonal deficiencies must be addressed as well., Methods and Results: We describe a case of a female patient who presented with headaches, anorexia and bitemporal hemianopsia. MRI revealed a peripherally enhancing sellar mass. Transsphenoidal surgery was performed, with intra-operative finding of purulent material. Cytology confirmed the presence of abundant leucocytes, but no pathogen was isolated. Patient completed three weeks of antibiotic therapy, with good clinical and radiological response. Headaches and visual deficits resolved. Hormonal substitution therapy was needed for six months after surgery., Conclusion: This report highlights the importance of early recognition and treatment of PAs. The diagnosis is commonly very difficult before surgery, due to overlapping clinical, radiological and laboratorial findings with various other pathologies. Prompt management, with surgical decompression and appropriate antibiotic treatment, typically results in a low mortality rate and higher chance of full recovery of pituitary function. We propose a management algorithm for sellar masses suspected of being PAs.

Introduction: The most common hearing losses in the population are associated with genetic conditions, use of ototoxic substances or medications, infectious diseases, metabolic diseases and chronic ear diseases and the association of exposure to occupational risks or the natural aging process., Objective: Verify the association between hearing loss in workers and metabolic diseases., Method: Retrospective cross-sectional study with analysis of secondary data of subjects exposed to occupational noise and undergoing drug treatment for metabolic disease, attended in two occupational health clinics (C1 and C2) from January 2020 to December 2022, considering the data of reference examinations from the year 2005., Results: Of the n = 97 subjects evaluated, 73.20% were male, exposed to occupational noise (64.90%), with medication use for treating cardiovascular diseases (89.70%). The most recurrent auditory complaint was tinnitus (28.90%), n = 53 subjects presented sensorineural hearing loss with a statistical association between the decline of hearing loss and medications used for metabolic and hormonal regulation., Conclusion: Here was a higher frequency in the use of medications for treating cardiovascular diseases with a risk of triggering or worsening hearing loss in these subjects and greater impairment and decline of hearing thresholds were observed in the results of C2., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Author(s).)

Background: Malnutrition/sarcopenia is frequent in patients with inflammatory bowel diseases (IBD), and results in muscle catabolism, impacting treatment response, postoperative complications, and quality of life., Objective: This study aims to assess whether the phase angle (PhA) is a parameter for predicting reduced muscle mass in patients with IBD., Methods: Adult patients with IBD were included in this cross-sectional study. For the estimation of muscle mass and the calculation of the PhA, we used bioelectrical impedance analysis (BIA). Crohn's disease (CD) and ulcerative colitis (UC) activity scores were defined using the Harvey-Bradshaw index and partial Mayo score, respectively. The area under the ROC curve was calculated to identify the PhA cut-off point for reduced muscle mass., Results: The sample consisted of 145 patients, with 39 (26.9%) with IBD in the active phase. There was a correlation of the PhA with skeletal muscle mass (SMM) (rs 0.35, P<0.001) and with the skeletal muscle mass index (SMI) (rs 0.427, P<0.001), and the associations remained in the most active form (moderate or severe) of IBD. The ROC curve analysis indicated that the cut-offs points of the PhA ≤5.042 for female and PhA ≤6.079 for male can be used to predict muscle mass reduction., Conclusion: The PhA can be considered a predictor of muscle mass reduction in IBD patients, and we can use it for screening and monitoring the evolution of malnutrition., Background: • This study aims to assess whether the phase angle is a parameter for predicting reduced muscle mass in patients with inflammatory bowel disease., Background: • There was a correlation of the phase angle with skeletal muscle mass and the associations remained in disease activity., Background: • The ROC curve analysis indicated that the cut-off point of the PhA ≤5.042° for women and PhA ≤6,079° for men can be used to predict muscle mass reduction., Background: • The phase angle can be considered a predictor of muscle mass reduction in inflammatory bowel disease.

Objective: The systematic review with meta-analysis aimed to verify the occurrence of a protective effect on hearing loss due to a higher intake of carotenoids, vitamins A, C, E, and folate present in diets., Methods: The search for scientific articles was carried out by 2 independent researchers in electronic databases. Meta-analysis was performed by constructing summary risk measures for each vitamin or antioxidant, combining the risk ratios or adjusted odds ratios (OR) for the various variables observed in the highest categories of vitamin or antioxidant consumption., Results: Five studies involving an estimated 100 549 participants were included in the quantitative synthesis. The summary measures calculated for the highest quartiles/quintiles of the studies were Hazard ratios (HR) .990 for vitamin C; HR 1.07 and OR .925 for vitamin E; HR .921 for folate and OR .906 for vitamin A., Conclusion: Dietary intake of vitamins and antioxidants was inversely associated with the risk of developing hearing loss. Individuals with a higher intake of antioxidants may have better hearing thresholds, especially with the intake of β-carotene., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 The Author(s).)

Objective: To compare the sensitivity and specificity of DNA ploidy with cytology, human papillomavirus (HPV) testing and colposcopy in diagnosis of high-grade cervical intraepithelial neoplasia (CIN) and to assess the role of aneuploidy in cervical lesions with the worst prognosis. A prospective observational cohort study was conducted on 254 women with altered colpocytology., Methods: Colposcopy, biopsy, DNA-ICM and HPV examinations were applied to cervical cytological and histological samples. Participants were evaluated every 6 months and divided into two groups: 'Harm' and 'No-harm'. Logistic regression and multivariate COX model were used to identify independent risk factors for diagnosis and prognosis of high-grade CIN, and ROC curve to assess the sensitivity and specificity of methods., Results: Variables 'age greater than or equal to 30 years', 'lesion size greater than 20%', 'aneuploidy' and 'HPV 16' were associated with diagnosis of high-grade CIN and 'aneuploidy' and 'women living with HIV', with a worse prognosis. Agreement for colposcopy was good, with a sensitivity of 79.3% and specificity of 94.4%; DNA-ICM and cytology were moderate, with sensitivity of 74.6% and 72.3% and specificity of 85.3% and 76.1%, respectively. High-risk HPV and HPV 16 tests were weak, with sensitivity of 75.0% and 43.75% and specificity of 50.0% and 88.64%, respectively., Conclusions: In relation to high-grade CIN diagnosis, DNA-ICM presented similar sensitivity and specificity to cytology and high-risk HPV test when associated with HPV 16. Regarding prognosis, this research certifies that aneuploidy is considered a predictor of more severe cervical injury., (© 2023 John Wiley & Sons Ltd.)

Objective: This study aimed to evaluate cytology diagnosis accuracy using adjuvant methods in clinical routine for oral cancer., Study Design: This prospective study was conducted on 98 patients with clinically potentially malignant or malignant oral cavity lesions. One oral lesion smear was taken from each patient using a cytobrush before biopsy and stored at PreservCyt Thinprep. Samples were cytologically analyzed, and DNA ploidy measurement was performed on the same slide. The diagnostic methods' accuracy was then calculated., Results: In clinical inspection, 61 patients had suspicious lesions for malignancy, whereas 37 had potentially malignant disorders. Cytology associated with DNA image cytometry presented a sensitivity of 81.2% and specificity of 90.9%. When analyzing lesions located in high-risk sites to oral malignancies individually, cytology associated with DNA image cytometry presented a sensitivity of 88.2%, specificity of 100.0%, accuracy of 90.0%, and Kappa value of 0.77 (CI 95%: 0.48-1.00)., Conclusions: Association between cytology and DNA image cytometry is an objective and non-invasive diagnostic method that demonstrated high sensitivity and specificity in diagnosing malignant epithelial squamous cell transformation in the oral cavity., Competing Interests: Declarations of interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To verify the frequency of risk factors for hearing loss in newborns and their possible associations with universal neonatal hearing screening results before and during the COVID-19 pandemic., Methods: Historical cohort study with data analysis of newborns attended in a reference hearing health service of the Unified Health System (SUS) between January 2017 and December 2021., Results: Those born in 2020 and 2021 were 91% less likely to fail the screening than those born in 2017, 2018, and 2019; therefore, they had a lower percentage of referrals for a retest. There was a decrease in congenital syphilis (1.00%), decrease in HIV (0.95%), and an increase in toxoplasmosis (0.58%) and increase in rubella cases in 2021 in relation to 2017. Syphilis had lower frequency rates during the COVID-19 pandemic (2020-2021)., Conclusion: Newborns born in the pandemic year compared to those born pre-pandemic showed a reduction in the presence of two risk indicators for hearing loss and, consequently, a lower chance of failing the UNHS and a lower percentage of referral for retest., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Microplastic pollution is a growing concern mainly in aquatic environments due to its deleterious effects. Some types of microplastics, such as glitter, remain overlooked. Glitter particles are artificial reflective microplastics used by different consumers within arts and handcraft products. In nature, glitter can physically affect phytoplankton by causing shade or acting as a sunlight-reflective surface, influencing primary production. This study aimed to evaluate the effects of five concentrations of non-biodegradable glitter particles in two bloom-forming cyanobacterial strains, Microcystis aeruginosa CENA508 (unicellular) and Nodularia spumigena CENA596 (filamentous). Cellular growth rate, estimated by optical density (OD), demonstrated that the applied highest glitter dosage decreases cyanobacterial growth rate with a more evident effect on M. aeruginosa CENA508. The cellular biovolume of N. spumigena CENA596 increased following the application of high concentrations of glitter. Still, no significant difference was detected in chlorophyll-a and carotenoids' contents for both strains. These results suggest that environmental concentrations of glitter, similar to the highest dosage tested (>200 mg glitter L -1 ), may negatively influence susceptible organisms of the aquatic ecosystems, as observed with M. aeruginosa CENA508 and N. spumigena CENA596., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Marli F. Fiore reports financial support was provided by State of São Paulo Research Foundation (FAPESP). Marli F. Fiore reports financial support was provided by Brazilian National Council for Scientific and Technological Development (CNPq)., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: to verify the frequency of congenital infections in newborns and their possible associations with the universal-neonatal-hearing-screening (UNHS) results, and evaluate a reference UNHS service in the Unified Health System ( Sistema Único de Saúde -SUS), according to quality indicators., Methods: Historical cohort study with data analysis of newborns attending prestigious hearing-health SUS services from January 2017 to December 2021, in Santa Catarina, Brazil. The quality of screening coverage was assessed based on the quality indicators proposed by the Brazilian neonatal-hearing-screening-care guidelines ( Diretrizes de Atenção da Triagem Auditiva Neonatal -DATAN). Logistic-regression analysis, crude OR calculations, Cochran-Mantel-Haenszel OR calculation, and chi-square test were performed to estimate the association between risk indicators for hearing loss and UNHS failure., Results: In the last five years, the prestigious services performed UNHS on 34,801 newborns and met the DATAN quality indicators. Congenital syphilis was the most frequent (1.59%) congenital infection in newborns, followed by HIV (0.87%), whereas the least frequent was rubella (0.029%)., Conclusion: Prestigious UNHS services reached ≥95% hearing screening coverage. Considering all congenital infections, the prevalence was 2.87%, with congenital syphilis the most frequent. Newborns with congenital syphilis or HIV are more likely to fail UNHS.

Introduction: Postpartum haemorrhage is still the main cause of maternal morbidity and mortality. Many treatments are available, but they may threaten fertility potential. As a uterine sparing procedure, we aimed to review uterine compression sutures in order to better understand when they should represent an appropriate option., Material and Methods: A comprehensive search in MEDLINE and PubMed databases including the terms 'postpartum haemorrhage' and 'uterine compression sutures' was performed. Results were revised and articles reviewing or presenting case reports of uterine compression sutures to treat postpartum haemorrhage were included., Results: The first description of uterine compression sutures to control postpartum haemorrhage was published in 1997, by B-Lynch et al. After this publication, many others have reported successful management of postpartum haemorrhage with different suturing techniques. Most of them describe success rates above 75% and the possibility of fertility preservation, with cases of uneventful pregnancy after uterine compression sutures already published. Complications associated with each technique are rare., Discussion: Reports of use of uterine compression sutures include small series of cases or even single case reports which limits the quality of existing evidence to support one technique over another. Nevertheless, uterine compression sutures are recognized as an effective surgical conservative strategy to control postpartum haemorrhage due to uterine atony and its use is recommended, if possible, prior to hysterectomy., Conclusion: Uterine compression sutures are effective, safe and simple to perform in an emergent situation and preserve fertility potential in cases of postpartum haemorrhage.

Introduction: Increased DNA damage is associated with early events in carcinogenesis. The foetus may be more susceptible to effects of environment by transplacental exposure. We aimed to evaluate DNA damage in cells from umbilical cord (arteries and vein) and maternal blood from pregnant women., Methods: Fifty eight pregnant women and their offspring were included in this study. They were submitted to an interview to obtain information about personal history, clinical history, and lifestyle habits. Other Information was obtained from medical records. The samples were prepared for Single Cell Gel/Comet assay and Cytokinesis-block Micronucleus Cytome (CBMN-Cyt) assay., Results: Correlation between DNA damage frequency by Comet assay from newborns and their mothers was statistically significant and was significantly associated with nulliparity and more than 1 h of second stage of labour (umbilical vein and maternal blood). A positive MNi relationship was noticed for age (mother's blood) and inappropriate birth weight for gestational age (maternal blood). When multivariate statistical analyses were applied to measure the degree of association between variables that influenced DNA damage markers in the first evaluation, inadequate birth weight and pregnant weight gain were associated with MNi frequency in maternal and newborns blood, respectively., Discussion: Significant associations between DNA damage in newborns and pregnant women, and birth and pregnancy events suggest molecular evidence of transplacental genotoxic effects. However, a potentially increased risk of degenerative diseases, such as cancers, in this population should be carefully investigated by further prospective cohort studies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Head injury is a frequent reason for admission to the emergency department. In parallel, there is a growing use of anticoagulants in an increasingly aging population, which renders this particular group of trauma patients more frequent. In several countries, including Portugal, a 24-h surveillance period followed by repetition of head computed tomography (CT) is the standard procedure for these patients. However, these recommendations have not been based on studies of prevalence of intracranial hemorrhages in control head CTs, namely in this group of anticoagulated patients. This study intends to evaluate the prevalence of de novo intracranial hemorrhages in control head CTs in anticoagulated patients., Method: An observational study was carried out, which included patients admitted to Hospital de Braga between June 2017 and January 2018, victims of head injury and on anticoagulation therapy, whose admission head CT excluded intracranial hemorrhage., Results: We collected a total of 201 patients, with a mean age of 81.6 years, and 57.5% of them were prescribed warfarin; 181 of these patients repeated the head CT 24 h later. Of these 181 patients, 3 (1.66%) exhibited intracranial hemorrhage in control CT, without surgical indication. All patients were followed up 1 month after the trauma, and there was no readmission requiring hospitalization, surgery or death., Conclusions: In conclusion, de novo intracranial hemorrhage in control head CT of anticoagulated patients is rare. We propose that these patients may be discharged if the admission CT does not reveal intracranial hemorrhage, providing that they are accompanied by a caregiver and informed about red flags., (© 2019. Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Our national protocol for traumatic brain injury dictates that hypocoagulated patients with mild trauma and initial tomography scan with no intracranial traumatic changes must be hospitalized for 24 hours and do a post-surveillance tomography scan. The main goal of this study was to evaluate the clinical relevance of these measures., Material and Methods: A prospective observational study was undertaken in four hospitals. Adult hypocoagulated traumatic brain injury patients with a normal tomography scan were included. The main outcomes evaluated were rate of delayed intracranial hemorrhage, rate of admission in a neurosurgical department, rate of complications related with surveillance and rate of prolonged hospitalization due to complications. An analysis combining data from a previously published report was also done., Results: A total of 178 patients were included. Four patients (2.3%) had a delayed hemorrhage and three (1.7%) were hospitalized in a neurosurgery ward. No cases of symptomatic hemorrhage were identified. No surgery was needed, and all patients had their anticoagulation stopped. Complications during surveillance were reported in seven patients (3.9%), of which two required prolonged hospitalization., Discussion: The rate of complications related with surveillance was higher than the rate of delayed hemorrhages. The initial period of in-hospital surveillance did not convey any advantage since the management of patients was never dictated by neurological changes. Post-surveillance tomography played a role in deciding about anticoagulation suspension and prolongation of hospitalization., Conclusion: Delayed hemorrhage is a rare event and the need for surgery even rarer. The need for in-hospital surveillance should be reassessed.

Background: Aztreonam/avibactam is a combination agent that shows promise in treating infections caused by highly antibiotic-resistant MBL-producing Enterobacterales. This combination can be achieved by combining two FDA-approved drugs: ceftazidime/avibactam and aztreonam. It is unknown whether ceftazidime in the combination ceftazidime/aztreonam/avibactam has a synergistic or antagonistic effect on the in vitro activity of aztreonam/avibactam by significantly increasing or decreasing the MIC., Objectives: To determine whether increasing ceftazidime concentrations affect the MICs of aztreonam/avibactam alone., Methods: A custom 8 × 8 chequerboard broth microdilution (BMD) panel was made using a digital dispenser (Hewlett-Packard, Corvallis, OR, USA). The panel included orthogonal 2-fold dilution series of aztreonam and ceftazidime ranging from 0.5 to 64 mg/L. Avibactam concentration was kept constant at 4 mg/L throughout the chequerboard. Thirty-seven Enterobacterales isolates from the CDC & FDA Antibiotic Resistance Isolate Bank or CDC's internal collection with intermediate or resistant interpretations to aztreonam and ceftazidime/avibactam were included for testing. All isolates harboured at least one of the following MBL genes: blaIMP, blaNDM or blaVIM., Results: Regardless of the concentration of ceftazidime, aztreonam/avibactam with ceftazidime MICs for all 37 isolates were within one 2-fold doubling dilution of the aztreonam/avibactam MIC., Conclusions: Ceftazidime, in the combination ceftazidime/avibactam/aztreonam, did not affect the in vitro activity of aztreonam/avibactam in this sample of isolates. These findings can help assure clinical and public health laboratories that testing of aztreonam/avibactam by BMD can act as a reliable surrogate test when the combination of ceftazidime/avibactam and aztreonam is being considered for treatment of highly antibiotic-resistant MBL-producing Enterobacterales., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Thirty Clostridioides difficile isolates collected in 2016 through the Centers for Disease Control and Prevention Emerging Infections Program were selected for reference antimicrobial susceptibility testing and whole-genome sequencing. Here, we present the genetic characteristics of these isolates and announce their availability in the CDC & FDA Antibiotic Resistance Isolate Bank.

Background: Percutaneous cholecystostomy (PC) is a well-recognized management option for the treatment of acute cholecystitis (AC) in high-risk patients. Patient characteristics, efficacy and particularly the longer-term outcomes for patients having PC across the Hunter New England Local Health District were analysed., Methods: A retrospective audit from January 2013 to September 2017 was undertaken. Patients were followed up until September 2019. All were retrospectively risk assessed using the P-POSSUM risk assessment tool, complications and mortality were recorded. In addition to short-term data, longer-term outcomes including patient's living situation at 6 and 12 months were analysed., Results: A total of 82 patients were assessed at ≥12 months post procedure or until death. Successful initial gallbladder drainage was achieved in 99% of cases. The mean P-POSSUM score for mortality was 11%, confirming that this is a high-risk group; 17% had inpatient complications recorded; 10% of these were major (Clavien-Dindo ≥III). Outpatient complications were seen in 45%, 59% underwent further biliary tree intervention and 24% had recurrent AC. Thirty-day mortality was 12% and 1-year mortality was 22%. Functional capacity changed significantly for 41% of patients at 1 year, with 12% requiring a new admission to high-level nursing home care., Conclusion: Our series represents the largest reported Australasian series of PC for AC published to date. It confirms that PC is well-established and safe in high-risk patients. However, further intervention rates and recurrence rates of AC are high and escalation of dependency of care affects almost half of patients., (© 2020 Royal Australasian College of Surgeons.)

Summary: Gonadotropin-releasing hormone (GnRH) agonists, currently used in the treatment of advanced prostate cancer, have been described as a rare cause of pituitary apoplexy, a potentially life-threatening clinical condition. We report the case of a 69-year-old man with a known pituitary macroadenoma who was diagnosed with prostate cancer and started treatment with GnRH agonist leuprorelin (other hormones were not tested before treatment). Few minutes after drug administration, the patient presented with acute-onset severe headache, followed by left eye ptosis, diplopia and vomiting. Pituitary MRI revealed tumor enlargement and T1-hyperintense signal, compatible with recent bleeding sellar content. Laboratory endocrine workup was significant for low total testosterone. The patient was managed conservatively with high-dose steroids, and symptoms significantly improved. This case describes a rare phenomenon, pituitary apoplexy induced by GnRH agonist. We review the literature regarding this condition: the pathophysiological mechanism involved is not clearly established and several hypotheses have been proposed. Although uncommon, healthcare professionals and patients should be aware of this complication and recognize the signs, preventing a delay in diagnosis and treatment., Learning Points: Pituitary apoplexy (PA) is a potentially life-threatening complication that can be caused by gonadotropin-releasing hormone agonist (GnRHa) administration for the treatment of advanced prostate cancer. This complication is rare but should be taken into account when using GnRHa, particularly in the setting of a known pre-existing pituitary adenoma. PA presents with classic clinical signs and symptoms that should be promptly recognized. Patients should be instructed to seek medical care if suspicious symptoms occur. Healthcare professionals should be aware of this complication, enabling its early recognition, adequate treatment and favorable outcome.

Aztreonam-avibactam is a combination antimicrobial agent with activity against carbapenemase-producing Enterobacteriaceae (CPE) with metallo-β-lactamases (MβLs). Although aztreonam-avibactam is not yet approved by the U.S. Food and Drug Administration (FDA), clinicians can administer this combination by using two FDA-approved drugs: aztreonam and ceftazidime-avibactam. This combination of drugs is recommended by multiple experts for treatment of serious infections caused by MβL-producing CPE. At present, in vitro antimicrobial susceptibility testing (AST) of aztreonam-avibactam is not commercially available; thus, most clinicians receive no laboratory-based guidance that can support consideration of aztreonam-avibactam for serious CPE infections. Here, we report our internal validation for aztreonam-avibactam AST by reference broth microdilution (BMD) according to Clinical and Laboratory Standards Institute (CLSI) guidelines. The validation was performed using custom frozen reference BMD panels prepared in-house at the Centers for Disease Control and Prevention (CDC). In addition, we took this opportunity to evaluate a new panel-making method using a digital dispenser, the Hewlett Packard (HP) D300e. Our studies demonstrate that the performance characteristics of digitally dispensed panels were equivalent to those of conventionally prepared frozen reference BMD panels for a number of drugs, including aztreonam-avibactam. We found the HP D300e digital dispenser to be easy to use and to provide the capacity to prepare complex drug panels. Our findings will help other clinical and public health laboratories implement susceptibility testing for aztreonam-avibactam., (This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.)

Introduction: The present study aimed to estimate the prevalence of Hepatitis C virus (HCV) infection in a prison population., Methods: A total of 147 individuals were interviewed and subjected to venipuncture for collection of blood sample. The study population consisted of male individuals who attended the health unit of the state penitentiary of Florianópolis., Results: The prevalence of HCV infection was 5.4%. Regarding behavioral variables, 95 (64.6%, p<0.0507) subjects reported consuming alcohol and 7 (4.8%, p<0.0476) reported having already used injectable drugs., Conclusions: The prevalence of HCV infection in the studied population was higher than that in the general populations.

Environmental exposure to metals among women, revealed their adverse effects on pregnancy. The fetus is exposed to these toxic elements only via the placenta which are able to accumulate there or cross it, compromising the protective functions of this organ. Numerous studies have shown associations between the prenatal exposition to some metals and an impact on cognitive, motor and intellectual development of the child. Sixty two placental samples were taken at delivery to determine the mineral content (Al, B, Ba, Ca, Cd, Cr, Cu, Fe, K, Li, Mg, Mn, Mo, Na, Ni, Pb, Sr, V, Zn) by ICP-OES. Among these metals, essential ones (B, Ca, Cu, Fe, Mg, Mn, Mo, Na, Zn) can have health beneficial effects at low levels however, in high concentration are potentially toxic. On the other hand, elements such as Al, Cd, Pb, are classified as toxic metals, no matter what its concentration is. The aim of this study is to find the potential relationships between these metals levels, newborn's parameters, pregnancy details and the epidemiologic information obtained using a questionnaire data from the participant pregnant women from Seville (Spain). The main maternal determinant of detectable placenta Cd levels was smoking during pregnancy. Other maternal factors that may affect placenta metal levels were gestational age (Al, B, Ba, and Pb) or dietary supplement (Fe). It has to be stressed that our results have to be interpreted with caution, because of the small study group and the low exposure levels, along with the lack of information on potential sources of exposure to these metals. The use of placenta samples obtained at delivery can be considered strength of this study since the concentration of some metals in placenta can indicate the extent of maternal exposure during gestation., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Posterior fossa lesions may present with behavioural changes and/or progressive neurological deficit. Patients may have symptoms for long periods which may be attributed to other causes such as psychiatric diseases. We report a case of a 44-year-old woman with behavioural changes lasting for 5 years who lost her job, marriage and the guard of her sons. Latterly, she developed neurological deficit, hydrocephalus and intracranial hypertension. A giant left pontocerebellar angle mass was diagnosed. A retrosigmoid craniotomy was performed with total removal and cranial nerve function's preservation. Histology revealed a grade I meningioma. The surgical approach for such huge lesions on pontocerebellar angle is controversial concerning patient's positioning and surgical route. A brief revision is made. Since nowadays medical imaging is more easily accessible, it is mandatory to have a brain image in patients with behavioural changes and/or neurological deficit to exclude potential structural and curable causes such as in this case., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The vascular endothelial growth factor (VEGF) family of proteins are key regulators of physiological systems. Originally linked with endothelial function, they have since become understood to be principal regulators of multiple tissues, both through their actions on vascular cells, but also through direct actions on other tissue types, including epithelial cells, neurons, and the immune system. The complexity of the five members of the gene family in terms of their different splice isoforms, differential translation, and specific localizations have enabled tissues to use these potent signaling molecules to control how they function to maintain their environment. This homeostatic function of VEGFs has been less intensely studied than their involvement in disease processes, development, and reproduction, but they still play a substantial and significant role in healthy control of blood volume and pressure, interstitial volume and drainage, renal and lung function, immunity, and signal processing in the peripheral and central nervous system. The widespread expression of VEGFs in healthy adult tissues, and the disturbances seen when VEGF signaling is inhibited support this view of the proteins as endogenous regulators of normal physiological function. This review summarizes the evidence and recent breakthroughs in understanding of the physiology that is regulated by VEGF, with emphasis on the role they play in maintaining homeostasis. © 2017 American Physiological Society. Compr Physiol 8:955-979, 2018., (Copyright © 2018 American Physiological Society. All rights reserved.)

The FDA-CDC Antimicrobial Resistance Isolate Bank was created in July 2015 as a publicly available resource to combat antimicrobial resistance. It is a curated repository of bacterial isolates with an assortment of clinically important resistance mechanisms that have been phenotypically and genotypically characterized. In the first 2 years of operation, the bank offered 14 panels comprising 496 unique isolates and had filled 486 orders from 394 institutions throughout the United States. New panels are being added., (Copyright © 2018 American Society for Microbiology.)

Purpose: To verify subjective memory complaints and their relation to verbal fluency in older people participating in community groups., Methods: An epidemiological quantitative study performed in community groups for older people in Florianópolis, state of Santa Catarina, Brazil. Data were collected by structured interview using the Memory Complaint Questionnaire (MAC-Q) and the Verbal Fluency Test (VFT) by semantic categories "animals/minute". For an inferential descriptive analysis, data with p < 5% were considered., Results: Self-reported memory complaints were found in 35.7% of the sample. No association or correlation of VFT with the perception of memory obtained by MAC-Q, nor with its score was found. The VFT analysis of in individuals who reported negative perception of memory presented statistical significance. We found significant association between the perception (MAC-Q score) and presence of memory lapses (reported by the older people in question and added to the questionnaire)., Conclusion: We found no relation between subjective memory complaints and verbal fluency of active older people. Mnemonic complaints were correlated to the negative perception of memory and to the duration of the complaint. However, subjective memory complaints were an indicator for those individuals with negative perception of memory, being one aspect that must be considered in older people's speech when investigating a possible cognitive deterioration. Such data can assist in formulating public health care policies aimed at older people in the city, which emphasizes the importance of verifying subjective memory complaints in this population.

Key Points: Combining nitric oxide (NO)-mediated increased blood flow with angiopoietin-1-Tie2 receptor signalling induces arteriolargenesis - the formation of arterioles from capillaries - in a model of physiological angiogenesis. This NO-Tie-mediated arteriolargenesis requires endogenous vascular endothelial growth factor (VEGF) signalling. Inhibition of VEGF signalling increases pericyte coverage in microvessels. Together these findings indicate that generation of functional neovasculature requires close titration of NO-Tie2 signalling and localized VEGF induction, suggesting that the use of exogenous VEGF expression as a therapeutic for neovascularization may not be successful., Abstract: Signalling through vascular endothelial growth factor (VEGF) receptors and the tyrosine kinase with IgG and EGF domains-2 (Tie2) receptor by angiopoietins is required in combination with blood flow for the formation of a functional vascular network. We tested the hypothesis that VEGF and angiopoietin-1 (Ang1) contribute differentially to neovascularization induced by nitric oxide (NO)-mediated vasodilatation, by comparing the phenotype of new microvessels in the mesentery during induction of vascular remodelling by over-expression of endothelial nitric oxide synthase in the fat pad of the adult rat mesentery during inhibition of angiopoietin signalling with soluble Tie2 (sTie2) and VEGF signalling with soluble Fms-like tyrosine kinase receptor-1 (sFlt1). We found that NO-mediated angiogenesis was blocked by inhibition of VEGF with sFlt1 (from 881 ± 98% increase in functional vessel area to 279 ± 72%) and by inhibition of angiopoietin with sTie2 (to 337 ± 67%). Exogenous angiopoietin-1 was required to induce arteriolargenesis (8.6 ± 1.3% of vessels with recruitment of vascular smooth muscle cells; VSMCs) in the presence of enhanced flow. sTie2 and sFlt1 both inhibited VSMC recruitment (both 0%), and VEGF inhibition increased pericyte recruitment to newly formed vessels (from 27 ± 2 to 54 ± 3% pericyte ensheathment). We demonstrate that a fine balance of VEGF and angiopoietin signalling is required for the formation of a functional vascular network. Endogenous VEGF signalling prevents excess neovessel pericyte coverage, and is required for VSMC recruitment during increased nitric oxide-mediated vasodilatation and angiopoietin signalling (NO-Tie-mediated arteriogenesis). Therapeutic vascular remodelling paradigms may therefore require treatments that modulate blood flow to utilize endogenous VEGF, in combination with exogenous Ang1, for effective neovascularization., (© 2016 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

This study aimed to evaluate the temporal and spacial distribution of the mucins produced by goblet cells and intestinal alkaline phosphatase (IAP) expression during the development of the small intestine of the rat. Intestines were removed from rats on the 15th, 17th and 18th days of intratuterine life (i.u.) and on the 3rd, 10th, 17th and 25th days after birth (a.b.). Intestines were processed for routine histological procedures and sections were submitted to histochemistry using PAS to stain neutral glycoproteins and Alcian blue for acidic glycoproteins, as well as immunohistochemistry to detect IAP. In rats, glycoprotein production was seen to begin in the intestinal epithelium cell at around the 17th day of i.u. life; however, this production was not accompanied by morphological indications of the presence of goblet cells. By the 18th i.u. day, the villus epithelium was undergoing differentiation and the first goblet cells could be identified from this time. At around the 10th day a.b., both compartments of the small intestine were detected; i.e. the villi and the crypts. At this timepoint, goblet cells were present in the villi, and also in the upper regions of the crypts. On the 3rd, 10th 17th and 25th days a.b., the presence of the goblet cells increased and presented regional differences in the sections evaluated. IAP was not detected during i.u. life, but was weakly detected in the cells of the villi from the 3rd day a.b., along the entire extension of the villi. On the 10th day, IAP was detected at the tip of the villi, while on the 25th day, it was detected along the extension of the villi, but with a weaker intensity. In conclusion, a temporal and spacial distribution of goblet cells and IAP activity occurs during the development of the small intestine, suggesting a possible regulatory control in accordance with the suckling and weaning phases of food intake in the rat's life., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Introduction: This study aimed to estimate the prevalence of human immunodeficiency virus (HIV) infection among prison inmates and to define the behavioral profile of infected individuals., Methods:: In total, 147 individuals were interviewed and provided biological material. The study population consisted of male individuals who presented at the health unit of the Florianopolis State Penitentiary., Results:: The prevalence of HIV infection was 2.1% (95% confidence interval, 0.4-5.8). With respect to the behavioral profile of individuals, no variable showed statistical significance., Conclusions:: The prevalence of HIV infection among prison inmates was higher than that reported for the general population.

This article reports the rationale for the Brazilian Cardioprotective Nutritional Program (BALANCE Program) Trial. This pragmatic, multicenter, nationwide, randomized, concealed, controlled trial was designed to investigate the effects of the BALANCE Program in reducing cardiovascular events. The BALANCE Program consists of a prescribed diet guided by nutritional content recommendations from Brazilian national guidelines using a unique nutritional education strategy, which includes suggestions of affordable foods. In addition, the Program focuses on intensive follow-up through one-on-one visits, group sessions, and phone calls. In this trial, participants 45 years or older with any evidence of established cardiovascular disease will be randomized to the BALANCE or control groups. Those in the BALANCE group will receive the afore mentioned program interventions, while controls will be given generic advice on how to follow a low-fat, low-energy, low-sodium, and low-cholesterol diet, with a view to achieving Brazilian nutritional guideline recommendations. The primary outcome is a composite of death (any cause), cardiac arrest, acute myocardial infarction, stroke, myocardial revascularization, amputation for peripheral arterial disease, or hospitalization for unstable angina. A total of 2468 patients will be enrolled in 34 sites and followed up for up to 48 months. If the BALANCE Program is found to decrease cardiovascular events and reduce risk factors, this may represent an advance in the care of patients with cardiovascular disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Millennial- and multi-centennial scale climate variability during the Holocene has been well documented, but its impact on the distribution and timing of extreme river floods has yet to be established. Here we present a meta-analysis of more than 2000 radiometrically dated flood units to reconstruct centennial-scale Holocene flood episodes in Europe and North Africa. Our data analysis shows a general increase in flood frequency after 5000 cal. yr BP consistent with a weakening in zonal circulation over the second half of the Holocene, and with an increase in winter insolation. Multi-centennial length phases of flooding in UK and central Europe correspond with periods of minimum solar irradiance, with a clear trend of increasing flood frequency over the last 1000 years. Western Mediterranean regions show synchrony of flood episodes associated with negative phases of the North Atlantic Oscillation that are out-of-phase with those evident within the eastern Mediterranean. This long-term flood record reveals complex but geographically highly interconnected climate-flood relationships, and provides a new framework to understand likely future spatial changes of flood frequency.

Background: The risk factors that characterize metabolic syndrome (MetS) may be present in childhood and adolescence, increasing the risk of cardiovascular disease in adulthood., Objective: Evaluate the prevalence of MetS and the importance of its associated variables, including insulin resistance (IR), in children and adolescents in the city of Guabiruba-SC, Brazil., Methods: Cross-sectional study with 1011 students (6-14 years, 52.4% girls, 58.5% children). Blood samples were collected for measurement of biochemical parameters by routine laboratory methods. IR was estimated by the HOMA-IR index, and weight, height, waist circumference and blood pressure were determined. Multivariate logistic regression models were used to examine the associations between risk variables and MetS., Results: The prevalence of MetS, IR, overweight and obesity in the cohort were 14%, 8.5%, 21% and 13%, respectively. Among students with MetS, 27% had IR, 33% were overweight, 45.5% were obese and 22% were eutrophic. IR was more common in overweight (48%) and obese (41%) students when compared with eutrophic individuals (11%; p = 0.034). The variables with greatest influence on the development of MetS were obesity (OR = 32.7), overweight (OR = 6.1), IR (OR = 4.4; p ≤ 0.0001 for all) and age (OR = 1.15; p = 0.014)., Conclusion: There was a high prevalence of MetS in children and adolescents evaluated in this study. Students who were obese, overweight or insulin resistant had higher chances of developing the syndrome.

Evidence-based strategies to improve the hepatitis B virus (HBV) vaccination coverage rates might help to reduce the burden caused by co-infection with HBV and human immunodeficiency virus (HIV). In this study, the aim was to evaluate the vaccination coverage and immunity against HBV among HIV-infected individuals in South Brazil, and identify factors that are associated with compliance patterns and antibody reactivity. Three hundred HIV-infected men and women were included in this survey. The patients answered a standardized questionnaire, and vaccination cards were checked in order to assess hepatitis B vaccine status. A blood sample was collected for quantitative determination of antibody to hepatitis B virus surface antigen (anti-HBs). Participants were also evaluated for their CD4 cell count and HIV viral load. The overall vaccination coverage of HBV vaccination found in this study (57.4%) was lower than that was previously reported in South Brazil. Anti-HBs levels >10IU/L were observed in 47.0% of the studied population. A significant inequality in the coverage rates and antibody reactivity was found in favor of patients with better economic status. In conclusion, the results indicate the need for improvement in the HBV vaccination coverage among HIV carriers, in particular focusing on low-income individuals., (Copyright © 2015 Elsevier Editora Ltda. All rights reserved.)

Introduction: Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) infections are two of the world's most important infectious diseases. Our objective was to determine the hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) prevalences among adult HIV-infected patients and identify the associations between socio-demographic variables and these HBV infection markers., Methods: This study was performed from October 2012 to March 2013. Three hundred HIV-seropositive patients were monitored by the Clinical Analysis Laboratory of Professor Polydoro Ernani de São Thiago University Hospital, Santa Catarina, Brazil. The blood tests included HBsAg, anti-HBc immunoglobulin M (IgM) and total anti-HBc. Patients reported their HIV viral loads and CD4+ T-cell counts using a questionnaire designed to collect sociodemographic data., Results: The mean patient age was 44.6 years, the mean CD4 T-cell count was 525/mm3, the mean time since beginning antiretroviral therapy was 7.6 years, and the mean time since HIV diagnosis was 9.6 years. The overall prevalences of HBsAg and total anti-HBc were 2.3% and 29.3%, respectively. Among the individuals analyzed, 0.3% were positive for HBsAg, 27.3% were positive for total anti-HBc, and 2.0% were positive either for HBsAg or total anti-HBc and were classified as chronically HBV-infected. Furthermore, 70.3% of the patients were classified as never having been infected. Male gender, age >40 years and Caucasian ethnicity were associated with an anti-HBc positive test., Conclusions: The results showed an intermediate prevalence of HBsAg among the studied patients. Moreover, the associations between the anti-HBc marker and socio-demographic factors suggest a need for HBV immunization among these HIV-positive individuals, who are likely to have HIV/HBV coinfection.

Autonomic sympathetic nerves innervate peripheral resistance arteries, thereby regulating vascular tone and controlling blood supply to organs. Despite the fundamental importance of blood flow control, how sympathetic arterial innervation develops remains largely unknown. Here, we identified the axon guidance cue netrin-1 as an essential factor required for development of arterial innervation in mice. Netrin-1 was produced by arterial smooth muscle cells (SMCs) at the onset of innervation, and arterial innervation required the interaction of netrin-1 with its receptor, deleted in colorectal cancer (DCC), on sympathetic growth cones. Function-blocking approaches, including cell type-specific deletion of the genes encoding Ntn1 in SMCs and Dcc in sympathetic neurons, led to severe and selective reduction of sympathetic innervation and to defective vasoconstriction in resistance arteries. These findings indicate that netrin-1 and DCC are critical for the control of arterial innervation and blood flow regulation in peripheral organs.

Purpose: To identify risk groups for oropharyngeal dysphagia in hospitalized patients in a university hospital., Methods: The study was design as an exploratory cross-sectional with quantitative data analysis. The researched population consisted of 32 patients admitted to the medical clinic at the university hospital. Patient history data were collected, followed by a universal swallowing screening which included functional feeding assessment, to observe clinical signs and symptoms of dysphagia, and assessment of nutritional status through anthropometric data and laboratory tests., Results: Of the total sample, the majority of patients was male over 60 years. The most common comorbidities related to patients with signs and symptoms of dysphagia were chronic obstructive pulmonary disease, systemic arterial hypertension, congestive heart failure, diabetes mellitus and acute myocardial infarction. The food consistency that showed higher presence of clinical signs of aspiration was pudding and the predominant sign was wet voice., Conclusion: There is a high incidence of risk for oropharyngeal dysphagia in hospitalized patients and an even higher rate of hospitalized patients with nutritional deficits or already malnourished. Hospitalized patients with respiratory diseases, chronic obstructive pulmonary disease, congestive heart failure and patients with xerostomia were indicated as risk group for oropharyngeal dysphagia.

Objectives: Waist circumference (WC) is highly associated with metabolic risk factor clusters (RFC) for chronic non-communicable diseases (NCDs). In this study, we evaluated the use of WC measurements to detect hyperglycemia and dyslipidemia in children and adolescents using the WC cutoff points reported in the Bogalusa Heart study and the New Zealand study., Design and Methods: Students (n=1011; aged 6 to 14years) were enrolled in a cross-sectional study. Anthropometric indices, fasting glucose, and lipid profiles were measured. The associations between WC measures and serum parameters were investigated by logistic regression models, and the clinical accuracy of the studied parameters was assessed using receiver operating characteristic (ROC) curve analysis., Results: The prevalence of increased WC was 30.2% using the New Zealand cutoff points and 13.7% using the Bogalusa cutoff values. In general, children with increased WC exhibited higher concentrations of total cholesterol, triglycerides, LDL-cholesterol, and non-HDL-cholesterol and lower levels of HDL-cholesterol. The areas under the ROC curves (AUC) of the WC measurements were 0.770 (95% CI: 0.744-0.797) and 0.600 (95% CI: 0.569-0.631) using, respectively, the New Zealand and Bogalusa cutoff points for WC, indicating the prediction of simultaneous hyperglycemia, increased levels of non-HDL-cholesterol, and reduced HDL-cholesterol for students with increased WC. There was a significant difference between AUC values (P=0.001). Furthermore, the sensitivity of using WC for detecting RFC in students was 2.0 to 2.5-fold higher with the New Zealand study cutoff values for WC than with those from the Bogalusa study. Logistic regression analysis revealed that increased WC was associated with simultaneous hyperglycemia and dyslipidemia after controlling for differences in sex and age (P<0.01 for all)., Conclusions: Children and adolescents exhibited a high prevalence of increased WC associated with other RFCs for NCDs. Increased WC may be used to screen and identify students with elevated clusters of metabolic risk factors for NCDs., (© 2013.)

Objectives: The aim of the present study was to assess the expression profile of multidrug resistance (MDR)-related proteins ABCB1, ABCC1 and LRP in 46 patients with acute leukemia (AL)., Methods: The levels of MDR gene mRNA expression and protein expression at diagnosis were analyzed by semi-quantitative PCR and flow cytometry, respectively., Results: In the adult group, higher expression levels of abcc1 gene were associated with older age and lower levels of lactate dehydrogenase (LDH). In the pediatric group, abcc1 gene expression levels were associated with higher CD34 expression and a higher ABCB1 protein expression was correlated with high WBC counts., Discussion/conclusion: The present data indicate that abcb1 gene overexpression may be associated with a poor prognosis in adults with AL and that ABCB1 and abcc1 expression correlates with different prognostic factors in pediatric patients with AL. Our findings demonstrate that the method of choice to evaluate chemotherapy resistance-related proteins is a major variable.

Regeneration of injured tissue is a dynamic process, critically dependent on the formation of new blood vessels and restructuring of the nascent plexus. Endothelial barrier function, a functional correlate of vascular restructuring and maturation, was quantified via intravital microscopic analysis of 150 kDa FITC-dextran-perfused blood vessels within discrete wounds created in the panniculus carnosus (PC) muscle of dorsal skinfold chamber (DSC) preparations in mice. Time to recovery of half-peak fluorescence intensity (t(1/2)) within individual vessel segments in three functional regions of the wound (pre-existing vessels, angiogenic plexus and blind-ended vessels (BEVs)) was quantified using in vivo fluorescence recovery after photobleaching (FRAP) and linear regression analysis of recovery profiles. Plasma flux across the walls of new vessel segments, particularly BEVs, was greater than that of pre-existing vessels at days 5-7 after injury (P < 0.05). TNP-470 reduced the permeability of BEVs at the leading edge of the advancing vascular plexus as measured by the decrease in luminal t(1/2) (P < 0.05), confirming the utility of FRAP as a quantitative measure of endothelial barrier function. Furthermore, these data are suggestive of a role for TNP-470 in selection for less leaky vascular segments within healing wounds. Increased FITC-dextran leakage was observed from pre-existing vessels after treatment with TNP-470 (P < 0.05), consistent with induction of transient vascular damage, although the significance of this finding is unclear. Using in vivo FRAP this study demonstrates the relationship between temporal changes in microvascular macromolecular flux and the morphology of maturing vascular segments. This combination of techniques may be useful to assess the therapeutic potential of angiogenic agents in restoring pre-injury levels of endothelial barrier function, following the establishment of a functional vascular plexus such as in models of wounding or tumour development.

Objective: The most critical determinant of restoration of tissue structure during wound healing is the re-establishment of a functional vasculature, which largely occurs via angiogenesis, specifically endothelial sprouting from the pre-existing vasculature., Materials and Methods: We used confocal microscopy to capture sequential images of perfused vascular segments within the injured panniculus carnosus muscle in the mouse dorsal skin-fold window chamber to quantify a range of microcirculatory parameters during the first nine days of healing. This data was used to inform a mathematical model of sequential growth of the vascular plexus. The modeling framework mirrored the experimental circular wound domain and incorporated capillary sprouting and endothelial cell (EC) sensing of vascular endothelial growth factor gradients., Results: Wound areas, vessel densities and vessel junction densities obtained from the corresponding virtual wound were in excellent agreement both temporally and spatially with data measured during the in vivo healing process. Moreover, by perturbing the proliferative ability of ECs in the mathematical model, this leads to a severe reduction in vascular growth and poor healing. Quantitative measures from this second set of simulations were found to correlate extremely well with experimental data obtained from animals treated with an agent that targets endothelial proliferation (TNP-470)., Conclusion: Our direct combination and comparison of in vivo longitudinal analysis (over time in the same animal) and mathematical modeling employed in this study establishes a useful new paradigm. The virtual wound created in this study can be used to investigate a wide range of experimental hypotheses associated with wound healing, including disorders characterized by aberrant angiogenesis (e.g., diabetic models) and the effects of vascular enhancing/disrupting agents or therapeutic interventions such as hyperbaric oxygen., (© 2011 John Wiley & Sons Ltd.)