Mucormycosis is an aggressive and potentially devastating fungal infection which typically manifests in pulmonary, rhinocerebral, or disseminated forms in patients with hematologic malignancy. ...Mucormycosis confined to the periodontium is uncommon, and to our knowledge only 6 cases have been reported in the English-language literature. This case report describes a patient with acute leukemia and periodontal mucormycosis. Calcofluor fluorescence microscopy is also proposed as a method for establishing a prompt diagnosis and guiding extent of intraoperative surgical debridement.
Objectives
Chronic oxidative stress (OS) may play a role in cardiovascular disease in HIV‐infected patients, and increased bilirubin levels may have a beneficial role in counteracting OS. Atazanavir ...(ATV) inhibits UDP‐glucuronosyl‐transferase 1A1 (UGT1A1), thus increasing unconjugated bilirubin levels. We aimed to compare changes in OS markers in patients on ATV/ritonavir (ATV/r)‐ vs. efavirenz (EFV)‐based first‐line antiretroviral therapy (ART).
Methods
A multicentre, prospective cohort study of HIV‐infected patients who started first‐line ART with either ATV/r or EFV was conducted. Lipoprotein‐associated phospholipase A2 (Lp‐PLA2), myeloperoxidase (MPO) and oxidized low‐density lipoprotein (oxLDL) were measured for 145 patients in samples obtained at baseline and after at least 9 months of ART during which the initial regimen was maintained and the patient was virologically suppressed. The change in OS markers was modelled using multiple linear regressions adjusting for baseline values and confounders.
Results
After adjustment for baseline variables, patients on ATV/r had a significantly greater decrease in Lp‐PLA2 estimated difference −16.3; 95% confidence interval (CI) −31.4, −1.25; P = 0.03 and a significantly smaller increase in OxLDL (estimated difference −21.8; 95% CI −38.0, −5.6; P < 0.01) relative to those on EFV, whereas changes in MPO were not significantly different (estimated difference 1.2; 95% CI −14.3, 16.7; P = 0.88). Adjusted changes in bilirubin were significantly greater for the ATV/r group than for the EFV group (estimated difference 1.33 mg/dL; 95% CI 1.03, 1.52 mg/dL; P < 0.01). Changes in bilirubin and changes in OS markers were significantly correlated.
Conclusions
When compared with EFV, ATV/r‐based therapy was associated with lower levels of oxidative stress biomarkers, which was in part attributable to increased bilirubin levels.
The physico-chemical properties of manufactured nanomaterials (NMs) can be fine-tuned to obtain different functionalities addressing the needs of specific industrial applications. The ...physico-chemical properties of NMs also drive their biological interactions. Accordingly, each NM requires an adequate physico-chemical characterization and potentially an extensive and time-consuming (eco)toxicological assessment, depending on regulatory requirements. Grouping and read-across approaches, which have already been established for chemicals in general, are based on similarity between substances and can be used to fill data gaps without performing additional testing. Available data on “source” chemicals are thus used to predict the fate, toxicokinetics and/or (eco)toxicity of structurally similar “target” chemical(s). For NMs similar approaches are only beginning to emerge and several challenges remain, including the identification of the most relevant physico-chemical properties for supporting the claim of similarity. In general, NMs require additional parameters for a proper physico-chemical description. Furthermore, some parameters change during a NM's life cycle, suggesting that also the toxicological profile may change. This paper compares existing concepts for NM grouping, considering their underlying basic principles and criteria as well as their applicability for regulatory and other purposes. Perspectives and recommendations based on experiences obtained during the EU Horizon 2020 project NanoReg2 are presented. These include, for instance, the importance of harmonized data storage systems, the application of harmonized scoring systems for comparing biological responses, and the use of high-throughput and other screening approaches. We also include references to other ongoing EU projects addressing some of these challenges.
Gastroesophageal reflux can be a catastrophic illness in small animals during anesthesia since its complications can cause serious pathologies, such as esophagitis, esophageal stenosis and aspiration ...pneumonia. With an incidence from 12 to 78.5% in anesthetized dogs, gastroesophageal reflux is normally silent during anesthesia and will be notices only if regurgitation occurs and stomach acid is present in the nasal or oral cavities. In humans, gastroesophageal reflux disease (GERD) is a well-defined pathology where the lower esophageal sphincter has a sustained weakness. However, in dogs, gastroesophageal reflux disease as such is not well established, if at all; it has only been described as gastroesophagic reflux, occurring principally in anesthetized animals. There are several factors influencing the presentation of reflux in anesthetized dogs, which may be inherent to the patient (e.g. age, sex, breed, weight, or body condition), medications used prior to and during anesthesia, type of surgery or position of the animal during surgery. The objective of this review is to discuss a series of conditions that could predispose dogs to gastroesophageal reflux during anesthesia and to assist in the prevention and diagnosis of this condition.
O refluxo gastroesofágico durante a anestesia pode ser uma entidade catastrófica na clínica de pequenas espécies, já que suas complicações resultam em entidades realmente graves, como esofagite, estenose esofágica e pneumonia por aspiração. O refluxo gastroesofágico em cães anestesiados é geralmente silencioso, com uma incidência de 12 até 78.5% e só é observada quando há regurgitação e o refluxo passa até a cavidade oral ou nasal. Nos humanos, a doença pelo refluxo gastroesofágico (ERGE) é uma patologia bem definida, onde o esfíncter esofágico inferior apresenta uma debilidade continua. Porém, esta doença em cães não está bem estabelecida, pelo qual só se descreve o refluxo gastroesofágico, que ocorre principalmente em animais anestesiados. Existem diversos fatores que influenciam na apresentação do refluxo em cães anestesiados. Estes podem ser inerentes ao paciente (por exemplo: idade, sexo, raça, peso ou condição corporal), a medicamentos utilizados previamente e durante a anestesia, ao tipo de cirurgia ou a posição do animal durante a cirurgia. O objetivo da revisão foi discutir uma guia das condições que predispõem à aparição de refluxo gastroesofágico durante a anestesia em cães com o fim de facilitar o diagnóstico e a prevenção dessa condição.
El reflujo gastroesofágico durante la anestesia puede ser una entidad catastrófica en la clínica de pequeñas especies, ya que sus complicaciones derivan en entidades realmente graves como esofagitis, estenosis esofágica y neumonía por aspiración. Con una incidencia del 12 al 78.5% en perros anestesiados, el reflujo gastroesofágico durante la anestesia es generalmente silencioso y sólo se observa cuando existe regurgitación y el reflujo pasa a cavidad oral o nasal. En el humano, la enfermedad por reflujo gastroesofágico (ERGE) es una patología bien definida, donde el esfínter esofágico inferior presenta una debilidad sostenida. Sin embargo, en el perro esta enfermedad como tal no está bien establecida, si acaso se describe el reflujo gastroesofágico, que ocurre principalmente en animales anestesiados. Existen diversos factores que influyen en la presentación del reflujo en los perros anestesiados. Estos pueden ser inherentes al paciente (por ejemplo: edad, sexo, raza, peso o condición corporal), a medicamentos utilizados previamente y durante la anestesia, al tipo de cirugía o a la posición del animal durante la cirugía. El objetivo de esta revisión es discutir una guía de las condiciones que predisponen a la aparición de reflujo gastroesofágico durante la anestesia en perros con el fin de facilitar el diagnóstico y la prevención de esta condición.
The prevalence of atopic dermatitis (AD), a chronic skin disease, has increased substantially in recent decades, and different factors have been implicated in its etiology. Although dietary habits ...are being investigated, few conclusive findings have been reported. Nevertheless, increased consumption of polyunsaturated fatty acids (PUFA) and a diet poor in antioxidants have been related to AD.
The objectives of this study were to investigate the association between AD, the intake of different foods, and the effect of a Mediterranean diet among Spanish schoolchildren aged 6 to 7.
We performed a cross-sectional study with 20 106 schoolchildren aged 6-7 years from 10 different areas of Spain. The participation rate was 76.50%. The prevalence of AD was assessed using the International Study of Asthma and Allergies in Childhood questionnaire and the criteria of the Spanish Academy of Dermatology. To calculate the Mediterranean diet score, we classified food into 2 groups: Mediterranean food, including fruit, seafood, vegetables, pulses, cereals, pasta, rice, and potatoes; and non-Mediterranean food, including meat, milk, and fast food.
Milk was negatively associated with AD. Butter and nuts also were negatively associated, although statistical significance was only reached when these foods were consumed 3 or more times a week.
We found no association between the Mediterranean diet score and AD and a positive association between AD and obesity.
Attributes and predictors of long COVID Sudre, Carole H; Murray, Benjamin; Varsavsky, Thomas ...
Nature Medicine,
04/2021, Letnik:
27, Številka:
4
Journal Article, Magazine Article
Recenzirano
Odprti dostop
Reports of long-lasting coronavirus disease 2019 (COVID-19) symptoms, the so-called 'long COVID', are rising but little is known about prevalence, risk factors or whether it is possible to predict a ...protracted course early in the disease. We analyzed data from 4,182 incident cases of COVID-19 in which individuals self-reported their symptoms prospectively in the COVID Symptom Study app
. A total of 558 (13.3%) participants reported symptoms lasting ≥28 days, 189 (4.5%) for ≥8 weeks and 95 (2.3%) for ≥12 weeks. Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. Experiencing more than five symptoms during the first week of illness was associated with long COVID (odds ratio = 3.53 (2.76-4.50)). A simple model to distinguish between short COVID and long COVID at 7 days (total sample size, n = 2,149) showed an area under the curve of the receiver operating characteristic curve of 76%, with replication in an independent sample of 2,472 individuals who were positive for severe acute respiratory syndrome coronavirus 2. This model could be used to identify individuals at risk of long COVID for trials of prevention or treatment and to plan education and rehabilitation services.
To determine the evolution and trends of amoxicillin-clavulanic acid resistance among Escherichia coli isolates in Spain, we tested 9,090 blood isolates from 42 Spanish hospitals and compared ...resistance with trends in outpatient consumption. These isolates were collected by Spanish hospitals that participated in the European Antimicrobial Resistance Surveillance System network from April 2003 through December 2006.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose
Multiparametric MRI (mpMRI) improves the detection of clinically significant prostate cancer, but is limited by interobserver variation. The second version of theProstate Imaging Reporting ...and Data System (PIRADSv2) was recently proposed as a standard for interpreting mpMRI. To assess the performance and interobserver agreement of PIRADSv2 we performed a multi‐reader study with five radiologists of varying experience.
Materials and Methods
Five radiologists (n = 2 prostate dedicated, n = 3 general body) blinded to clinicopathologic results detected and scored lesions on prostate mpMRI using PIRADSv2. The endorectal coil 3 Tesla MRI included T2W, diffusion‐weighted imaging (apparent diffusion coefficient, b2000), and dynamic contrast enhancement. Thirty‐four consecutive patients were included. Results were correlated with radical prostatectomy whole‐mount histopathology produced with patient‐specific three‐dimensional molds. An index lesion was defined on pathology as the lesion with highest Gleason score or largest volume if equivalent grades. Average sensitivity and positive predictive values (PPVs) for all lesions and index lesions were determined using generalized estimating equations. Interobserver agreement was evaluated using index of specific agreement.
Results
Average sensitivity was 91% for detecting index lesions and 63% for all lesions across all readers. PPV was 85% for PIRADS ≥ 3 and 90% for PIRADS ≥ 4. Specialists performed better only for PIRADS ≥ 4 with sensitivity 90% versus 79% (P = 0.01) for index lesions. Index of specific agreement among readers was 93% for the detection of index lesions, 74% for the detection of all lesions, and 85% for scoring index lesions, and 58% for scoring all lesions.
Conclusion
By using PIRADSv2, general body radiologists and prostate specialists can detect high‐grade index prostate cancer lesions with high sensitivity and agreement.
Level of Evidence: 1
J. Magn. Reson. Imaging 2017;45:579–585.
Background The brain is increasingly being recognized as a sanctuary site for metastatic tumor cells in women with HER2-overexpressing breast cancer who receive trastuzumab therapy. There are no ...approved or widely accepted treatments for brain metastases other than steroids, cranial radiotherapy, and surgical resection. We examined the efficacy of lapatinib, an inhibitor of the epidermal growth factor receptor (EGFR) and HER2 kinases, for preventing the outgrowth of breast cancer cells in the brain in a mouse xenograft model of brain metastasis. Methods EGFR-overexpressing MDA-MB-231-BR (231-BR) brain-seeking breast cancer cells were transfected with an expression vector that contained or lacked the HER2 cDNA and used to examine the effect of lapatinib on the activation (ie, phosphorylation) of cell signaling proteins by immunoblotting, on cell growth by the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and on cell migration using a Boyden chamber assay. The outgrowth of large (ie, >50 μm2) and micrometastases was counted in brain sections from nude mice that had been injected into the left cardiac ventricle with 231-BR cells and, beginning 5 days later, treated by oral gavage with lapatinib or vehicle (n = 22–26 mice per treatment group). All statistical tests were two-sided. Results In vitro, lapatinib inhibited the phosphorylation of EGFR, HER2, and downstream signaling proteins; cell proliferation; and migration in 231-BR cells (both with and without HER2). Among mice injected with 231-BR-vector cells, those treated with 100 mg lapatinib/kg body weight had 54% fewer large metastases 24 days after starting treatment than those treated with vehicle (mean number of large metastases per brain section: 1.56 vs 3.36, difference = 1.80, 95% confidence interval CI = 0.92 to 2.68, P < .001), whereas treatment with 30 mg lapatinib/kg body weight had no effect. Among mice injected with 231-BR-HER2 cells, those treated with either dose of lapatinib had 50%–53% fewer large metastases than those treated with vehicle (mean number of large metastases per brain section, 30 mg/kg vs vehicle: 3.21 vs 6.83, difference = 3.62, 95% CI = 2.30 to 4.94, P < .001; 100 mg/kg vs vehicle: 3.44 vs 6.83, difference = 3.39, 95% CI = 2.08 to 4.70, P < .001). Immunohistochemical analysis revealed reduced phosphorylation of HER2 in 231-BR-HER2 cell–derived brain metastases from mice treated with the higher dose of lapatinib compared with 231-BR-HER2 cell–derived brain metastases from vehicle-treated mice (P < .001). Conclusions Lapatinib is the first HER2-directed drug to be validated in a preclinical model for activity against brain metastases of breast cancer.
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