Wild Artichoke (Cynara cardunculus subsp. sylvestris, Asteraceae) Leaf Extract: Phenolic Profile and Oxidative Stress Inhibitory Effects on HepG2 Cells.

Cynara cardunculus subsp. sylvestris (wild artichoke) is widespread in Sicily, where it has been used for food and medicinal purposes since ancient times; decoctions of the aerial parts of this plant have been traditionally employed as a remedy for different hepatic diseases. In this study, the phenolic profile and cell-free antioxidant properties of the leaf aqueous extract of wild artichokes grown in Sicily (Italy) were investigated. The crude extract was also tested in cells for its antioxidant characteristics and potential oxidative stress inhibitory effects. To resemble the features of the early stage of mild steatosis in humans, human HepG2 cells treated with free fatty acids at the concentration of 1.5 mM were used. HPLC-DAD analysis revealed the presence of several phenolic acids (caffeoylquinic acids) and flavonoids (luteolin and apigenin derivatives). At the same time, DPPH assay showed a promising antioxidant power (IC50 = 20.04 ± 2.52 µg/mL). Biological investigations showed the safety of the crude extract and its capacity to counteract the injury induced by FFA exposure by restoring cell viability and counteracting oxidative stress through inhibiting reactive oxygen species and lipid peroxidation and increasing thiol-group levels. In addition, the extract increased mRNA expression of some proteins implicated in the antioxidant defense (Nrf2, Gpx, and SOD1) and decreased mRNA levels of inflammatory cytokines (IL-6, TNF-α, and IL-1ß), which were modified by FFA treatment. Results suggest that the total phytocomplex contained in wild artichoke leaves effectively modulates FFA-induced hepatic oxidative stress.

Chemical, Antioxidant and Biological Studies of Brassica incana subsp. raimondoi (Brassicaceae) Leaf Extract.

Brassica incana subsp. raimondoi is an endemic taxon present in a restricted area located on steep limestone cliffs at an altitude of about 500 m a.s.l. in eastern Sicily. In this research, for the first time, studies on the phytochemical profile, the antioxidant properties in cell-free and cell-based systems, the cytotoxicity on normal and cancer cells by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay, and on Artemia salina Leach, were performed. The total phenolic, flavonoid, and condensed tannin contents of the leaf hydroalcoholic extract were spectrophotometrically determined. Ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) analysis highlighted the presence of several phenolic acids, flavonoids, and carotenoids, while High-Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD) identified various kaempferol and isorhamnetin derivatives. The extract exhibited different antioxidant properties according to the five in vitro methods used. Cytotoxicity by MTT assay evidenced no impact on normal human fibroblasts (HFF-1) and prostate cancer cells (DU145), and cytotoxicity accompanied by necrotic cell death for colon cancer cells (CaCo-2) and hepatoma cells (HepG2), starting from 100 µg/mL and 500 µg/mL, respectively. No cytotoxic effects were detected by the A. salina lethality bioassay. In the H2O2-induced oxidative stress cell model, the extract counteracted cellular reactive oxygen species (ROS) production and preserved non-protein thiol groups (RSH) affected by H2O2 exposure in HepG2 cells. Results suggest the potential of B. incana subsp. raimondoi as a source of bioactive molecules.

Advances on Natural Abietane, Labdane and Clerodane Diterpenes as Anti-Cancer Agents: Sources and Mechanisms of Action.

Extensive research over the past decades has identified numerous phytochemicals that could represent an important source of anti-cancer compounds. There is an immediate need for less toxic and more effective preventive and therapeutic strategies for the treatment of cancer. Natural compounds are considered suitable candidates for the development of new anti-cancer drugs due to their pleiotropic actions on target events with multiple manners. This comprehensive review highlighted the most relevant findings achieved in the screening of phytochemicals for anticancer drug development, particularly focused on a promising class of phytochemicals such as diterpenes with abietane, clerodane, and labdane skeleton. The chemical structure of these compounds, their main natural sources, and mechanisms of action were critically discussed.

Epidural administration of combinations of ropivacaine, morphine and xylazine in bitches undergoing total unilateral mastectomy: a randomized clinical trial.

OBJECTIVE: To investigate the epidural administration of combinations of ropivacaine, morphine and xylazine in bitches undergoing unilateral mastectomy. STUDY DESIGN: Prospective, randomized, blinded, clinical study. ANIMALS: A total of 22 bitches scheduled to undergo unilateral mastectomy for mammary tumor excision. METHODS: Dogs were anesthetized with acepromazine (0.02 mg kg-1) and morphine (0.3 mg kg-1) intramuscularly, propofol intravenously (IV) and isoflurane. Prior to the beginning of surgery, dogs were randomly administered one of three epidural treatments: ropivacaine (0.75 mg kg-1) with morphine (0.1 mg kg-1) (group RM, n = 7); ropivacaine with xylazine (0.1 mg kg-1) (group RX, n = 8); or ropivacaine with morphine and xylazine (group RMX, n = 7). Cardiopulmonary variables and the expired concentration of isoflurane (Fe'Iso) were recorded intraoperatively. Meloxicam (0.1 mg kg-1) was administered IV during skin closure. Postoperative pain scores were evaluated with the Glasgow composite measure pain scale short form for 24 hours, and rescue analgesia with morphine (0.5 mg kg-1) was administered intramuscularly when pain scores were ≥ 6/24. RESULTS: Fe'Iso was significantly higher in group RM than in groups RX and RMX. Heart rate decreased significantly in groups RX and RMX, but blood pressure remained within acceptable values. The number of dogs administered rescue analgesia within 24 hours was significantly higher in group RX (seven dogs, 87.5%) than in groups RM (one dog, 14.3%; p = 0.01) and RMX (two dogs, 28.6%; p = 0.04). Time to standing was significantly longer in group RX than in group RM. CONCLUSIONS AND CLINICAL RELEVANCE: All epidural treatments provided adequate antinociception with minimal cardiovascular adverse effects during mastectomy. The inclusion of morphine (groups RM and RMX) provided the best postoperative analgesia. Owing to the undesirable effect of xylazine on ambulation, the combination ropivacaine-morphine appeared to provide greater benefits in bitches undergoing unilateral mastectomy.

Cardiovascular morbidity and mortality is increased post-liver transplantation even in recipients with no pre-existing risk factors.

BACKGROUND/AIMS: Post-liver transplant (LT) metabolic syndrome (PTMS) and cardiovascular (CVS) mortality are becoming increasingly prevalent following sustained improvements in post-LT survival. We investigated the prevalence and predictors of PTMS and CVS complications in a cohort of consecutive LT recipients. METHODS: We reviewed prospectively collected data of patients (n = 928) who underwent LT (1995-2013) and survived at least 1-year post-LT or died before that due to a major CVS complication. RESULTS: Median follow-up was 85 months (IQR = 106). The prevalence of PTMS was 22.4% and it developed de novo in 183 recipients (19.7%). A total of 187 (20.2%) patients developed at least one CVS event post-LT within a median of 49 months (IQR = 85). Overall mortality rate was 22.6% (n = 210). Causes of death were CVS events (n = 45, 21.4%), malignancies (21%), liver-related deaths (20%) and infections (6.7%). Independent predictors of major CVS events were: documented CVS disease pre-LT (Hazard Ratio (HR) = 3.330; 95% CI = 1.620-6.840), DM (HR = 1.120; 95% CI 1.030-1.220), hypertension (HR = 1.140; 95% CI 1.030-1.270), dyslipidaemia (HR = 1.140; 95% CI 1.050-1.240) and creatinine levels at 1 year (HR = 1.010; 95% CI = 1.005-1.013). Among LT recipients without pre-LT CVS disease or MS components (n = 432), 85 recipients developed ≥1 CVS events (19.7%) with independent predictors being DM (HR = 1.150; 95% CI = 1.010-1.320), creatinine levels at 1 year (HR = 1.020; 95% CI = 1.010-1.030) and hypertension (HR = 1.190; 95% CI = 1.040-1.360). CONCLUSIONS: Post-LT patients are at increased risk of CVS morbidity even in the absence of pre-existing metabolic risk factors. Renal sparing immunosuppressive protocols might reduce CVS events post-LT.

Short and long-term mortality of patients presenting with bleeding events to the Emergency Department.

BACKGROUND: Death of patients presenting with bleeding events to the Emergency Department still represent a major problem. We sought to analyze clinical characteristics associated with worse outcomes including short- and long-term death, beyond antithombotic treatment strategy. METHODS: Patients presenting with any bleeding events during 2016-2017years were enrolled. Clinical parameters, site of bleeding, major bleeding, ongoing anti-thrombotic treatment strategy and death were collected. Hard 5:1 propensity score matching was performed to adjust dead patients in baseline characteristics. Endpoints were one-month and one-year death. RESULTS: Out of 166,000 visits to the Emergency Department, 3.050 patients (1.8%) were enrolled and eventually 429 were analyzed after propensity. Overall, anticoagulants or antiplatelets were given to 234(54%). Major bleeding account for 111(26%) patients, without differences between those taking anticoagulants or antiplatelets versus others. Death at one-month and one-year was 26(6%) and 72(17%), respectively. Independent predictors of one-month death were major bleeding (Odds Ratio, OR 26, p<0.001), female gender (OR 7, p<0.001) and white blood cells (OR 1.2, p=0.01); of one-year were major bleeding (OR 7, p<0.001), age (OR 1.1, p<0.001) and female gender (OR 2.3, p=0.043). Of note, death rate of gastrointestinal and intracranial bleeding where higher than others (p<0.001). Overall mortality was approximately 40% on one-month; 60% in older patients and 80% in female gender with CHA2D2VASC-score≥2. Receiver operator characteristics analysis showed larger areas for major bleeding and age (0.75 and 0.72, respectively) over others; p<0.05 on C-statistic. CONCLUSIONS: In patients with bleeding events, death rate was driven by major bleeding on short-term and older age on long-term. Among dead patients mortality was approximately 40% on one-month; 60% in older patients, and 80% in female gender.

Congenital cutaneous melanoma in a dog.

BACKGROUND: Melanocytic tumours are derived from melanocytes and are common in older dogs with dark pigmented skin. Primary congenital cutaneous melanoma has been described in domestic mammals although there are no reports in the dog. HYPOTHESIS/OBJECTIVE: We describe a case of canine congenital cutaneous melanoma with rapid progression to metastasis and death. ANIMAL: A male, mixed breed dog was born with a circular ulcerated lesion near the left ear. By 12 days of age the lesion had grown significantly, with multiple soft, round nodules located at the outer base of the ear. METHODS AND RESULTS: Histopathological examination showed the proliferation of round and elongated neoplastic cells with eosinophilic cytoplasm that occasionally contained granules of melanin. Immunohistochemical analysis was positive for melan A, S-100 protein, neuron-specific enolase (NSE) and vimentin, confirming the diagnosis of melanoma. The tumour progressed rapidly and at six months the dog died suddenly. Postmortem examination revealed pulmonary, cardiac and lymph node metastases. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge, this is the first report of a primary congenital melanoma in the dog. The neoplastic condition showed malignant behaviour and high metastatic potential.

High-frequency QRS analysis superior to conventional ST-segment analysis of women with chest pain.

BACKGROUND: The novel analysis of high-frequency QRS components (HF/QRS) has been proposed in patients with chest pain (CP) referred for exercise tolerance test (ex-ECG). We sought to evaluate the prognostic role of exercise high-frequency QRS-analysis (ex-HF/QRS) in patients with recent-onset stable CP, in the emergency setting. METHODS: Patients with CP underwent ex-ECG. A decrease greater than or equal to 50% of the signal of HF/QRS intensity was considered as index of ischemia as ST-segment depression greater than or equal to 2 mm or greater than or equal to 1 mm associated with CP. Exclusion criteria were QRS duration greater than or equal to 120 milliseconds and inability to exercise. Baseline characteristics were adjusted with the propensity score matching specifying nearest-neighbor matching in cardiovascular risk factors and risk scores. The primary end point was the composite of coronary stenosis greater than or equal to 70% or acute coronary syndrome, revascularization, and cardiac death on the 6-month follow-up. RESULTS: Of 589 patients, 22 achieved the end point. On the univariate analysis, known cardiovascular disease, GRACE score, and ex-HF/QRS were predictors of the end point. On the multivariate analysis, only ex-HF/QRS was predictor of the end point (odd ratio, 28; 95% confidence interval [CI], 6-120; P < .001). Overall, the ex-HF/QRS when compared to ex-ECG showed higher sensitivity (91% vs 27%; P = .02), lower specificity (74% vs 86%; P = .09), and comparable negative predictive value (99% vs 97%; P = .78). Receiver operating characteristic curve analysis showed the larger area of ex-HF/QRS (0.83; 95% CI, 0.75-0.90) over ex-ECG (0.57; CI, 0.44-0.70) and GRACE score (0.65; CI, 0.54-0.76); P < .03 on C-statistic. Women showed the largest area (0.89; CI, 0.83-0.95; P < .03) vs the other clinical data. CONCLUSIONS: In patients with CP, the novel ex-HF/QRS analysis has a valuable incremental prognostic role over ex-ECG, especially in women.

Comparison of exercise electrocardiogram and exercise echocardiography in intermediate-risk chest pain patients.

BACKGROUND: The novel exercise computer-assisted high-frequency QRS analysis (HF/QRS) has demonstrated improved sensitivity and specificity over the conventional ST/electrocardiogram-segment analysis (ST/ECG) in the detection of myocardial ischemia. The aim of the present study was to compare the diagnostic value of the validated exercise echocardiography (ex-Echo) with the novel exercise ECG (ex-ECG) including HF/QRS and ST/ECG analysis. METHODS: A prospective cohort study was conducted in the emergency department of a tertiary care teaching Hospital. Patients with chest pain (CP), normal resting ECGs, troponins, and echocardiography, labeled as "intermediate-risk" for adverse coronary events, underwent the novel ex-ECG and ex-Echo. An ST-segment depression of at least 2 mV or at least 1 mV when associated with CP was considered as an index of ischemia, as well as a decrease of at least 50% in HF/QRS intensity, or new wall motion abnormalities on ex-Echo. Exclusion criteria were QRS duration of at least 120 milliseconds, poor echo-acoustic window, and inability to exercise. Patients were followed up to 3 months. The end point was the composite of coronary stenoses of 50% or greater at angiography or acute coronary syndrome, revascularization, and cardiovascular death on the 3-month follow-up. RESULTS: Of 188 patients enrolled, 18 achieved the end point. The novel ex-ECG and ex-Echo showed comparable negative predictive value (97% vs 96%; P = .930); however, sensitivity was 83% vs 61%, respectively (P = .612), and specificity was 64% vs 92%, respectively,(P = .026). The areas on receiver operating characteristic analysis were comparable (ex-ECG: 0.734 [95% confidence interval, or CI, 0.62-0.85] vs ex-Echo: 0.767 [CI, 0.63-0.91]; C statistic, P = .167). On multivariate analysis, both ex-ECG (hazard ratio, 5; CI, 1-20; P = .017) and ex-Echo (HR, 12; CI, 4-40; P < .001) were predictors of the end point. CONCLUSIONS: In intermediate-risk CP patients, the novel ex-ECG including HF/QRS added to ST/ECG analysis was a valuable diagnostic tool and might be proposed to avoid additional imaging. However, the novel test needs additional study before it can be recommended as a replacement for current techniques.

In old anticoagulated patients with mild traumatic brain injury, a 24-h observation period should not be recommended without evidence of a clear benefit: a retrospective study of delayed hemorrhagic versus iatrogenic complications.

Mild traumatic brain injury (mTBI) is a common cause of admission to the Emergency Department (ED). Many patients are elderly on oral anticoagulant therapy (OAT) at increased risk of immediate and delayed intracranial hemorrhage (ICH). To investigate the frequency of delayed ICH (DICH) in old patients with mTBI in OAT and the occurrence of complications related to the ED stay. In this single-center retrospective study, we recruited all patients in OAT aged 65 and over, admitted for mTBI to the ED of our Hospital in Florence from March 2019 to February 2021. Clinical variables were collected and cranial computed tomography (CT) scans reviewed. The primary outcome was the frequency of DICH occurring within 30 days since the trauma after a first negative CT. Secondary outcomes included need of neurosurgical intervention and death for DICH, and hospital-related complications. Statistical analyses were conducted using IBM SPSS Statistics (version 22). Among 363 enrolled patients, there were 31 acute ICH (8.5%) at the first CT scan, while in the 316 negative included patients, 10 DICH (3.2%) were identified. Among the latter, no neurosurgical treatment, or death due to ICH occurred. Overall, 25 cases (6.9%) had iatrogenic complications during the 24-h observation period, often serious, such as respiratory failure after sedation due to restlessness, or COVID-19 infection. The low frequency of DICH and the occurrence of several iatrogenic complications suggest that the risk-benefit ratio of a 24-h ED observation is not advantageous in elderly with mTBI.

Protective Effects of Wild Sulla coronaria (Fabaceae) Flowers Phytocomplex in Human Dermal Fibroblasts Stimulated with Interleukin-1ß.

Sulla coronaria is indigenous to the Mediterranean region. It is grown as fodder in southern Italy because it contains various secondary metabolites with beneficial activities on animals. Recently, its potential use in cosmeceutical treatments for skin problems was reported. In this scenario, to contribute to a possible cosmeceutical application, we characterized the phytochemical profile of Sulla coronaria flowers' hydroalcoholic extract by HPLC-DAD, Folin-Ciocalteu, Aluminum Chloride methods, DPPH assay, and, for the first time, we evaluated the antioxidant and anti-inflammatory activities on dermal fibroblasts. The phytochemical analysis confirmed the significant content of phenolic compounds (TPC 69.8 ± 0.6 mg GAE/g extract, TFC 15.07 mg CE/g extract) and the remarkable presence of rutin, quercetin, and isorhamnetin derivatives that give to the phytocomplex a good antioxidant activity as highlighted by the DPPH assay (IC50 of 8.04 ± 0.5 µg/mL). Through the reduction in NO• and ROS levels in human dermal fibroblasts, the biological tests demonstrated both the safety of the extract and its ability to counteract the inflammatory state generated by Interleukin-1ß exposure. Our findings indicate that the antioxidant activities of the phytocomplex are strictly related to the anti-inflammatory action of the Sulla coronaria flowers extract, confirming that this plant could be a valuable source of bioactive molecules for cosmeceutical and nutraceutical applications.

Redox State Modulatory Activity and Cytotoxicity of Olea europaea L. (Oleaceae) Leaves Extract Enriched in Polyphenols Using Macroporous Resin.

The food products derived from Olea europaea are a fundamental part of the Mediterranean diet, and their health-promoting effects are well known. In this study, we analyzed the phytochemical characteristics, the redox state modulatory activity, and the cytotoxic effect of an olive leaf aqueous extract enriched by macroporous resin on different tumor and normal cell lines (LNCaP, PC3, HFF-1). HPLC-DAD analysis, the Folin-Ciocalteu and aluminum chloride methods confirmed the qualitatively and quantitatively high content of phenolic compounds (130.02 ± 2.3 mg GAE/g extract), and a DPPH assay (IC50 = 100.00 ± 1.8 µg/mL), the related antioxidant activity. The biological investigation showed a significant cytotoxic effect, highlighted by an MTT test and the evident cellular morphological changes, on two prostate cancer cell lines. Remarkably, the extract was practically non-toxic on HFF-1 at the concentrations (100, 150, 300 µg/mL) and exposure times tested. Hence, the results are selective for tumor cells. The underlying cytotoxicity was associated with the decrease in ROS production (55% PC3, 42% LNCaP) and the increase in RSH levels (>50% PC3) and an LDH release assay (50% PC3, 40% LNCaP, established necrosis as the main cell death mechanism.

Natural Compounds and Glutathione: Beyond Mere Antioxidants.

The tripeptide glutathione plays important roles in many cell processes, including differentiation, proliferation, and apoptosis; in fact, disorders in glutathione homeostasis are involved both in the etiology and in the progression of several human diseases, including cancer. Natural compounds have been found to modulate glutathione levels and function beyond their role as mere antioxidants. For example, certain compounds can upregulate the expression of glutathione-related enzymes, increase the availability of cysteine, the limiting amino acid for glutathione synthesis, or directly interact with glutathione and modulate its function. These compounds may have therapeutic potential in a variety of disease states where glutathione dysregulation is a contributing factor. On the other hand, flavonoids' potential to deplete glutathione levels could be significant for cancer treatment. Overall, while natural compounds may have potential therapeutic and/or preventive properties and may be able to increase glutathione levels, more research is needed to fully understand their mechanisms of action and their potential benefits for the prevention and treatment of several diseases. In this review, particular emphasis will be placed on phytochemical compounds belonging to the class of polyphenols, terpenoids, and glucosinolates that have an impact on glutathione-related processes, both in physiological and pathological conditions. These classes of secondary metabolites represent the most food-derived bioactive compounds that have been intensively explored and studied in the last few decades.

Vitamin E and Non-Communicable Diseases: A Review.

Vitamin E, a nutrient found in several foods, comprises eight lipophilic vitamers, the α-, ß-, γ- and δ-tocopherols and the α-, ß-, γ- and δ-tocotrienols. This vitamin is capable of exerting antioxidant and anti-inflammatory activities, and acting as immunomodulators. Despite these well-known biological activities, the findings regarding the ability of vitamin E and its serum metabolites to prevent and/or control chronic disease are often conflicting and inconsistent. In this review, we have described the metabolism of vitamin E and its interaction with the gut microbiota, considering that these factors may be partially responsible for the divergent results obtained. In addition, we focused on the correlations between vitamin E serum levels, dietary intake and/or supplementation, and the main non-communicable diseases, including diabetes mellitus, asthma, cardiovascular diseases, and the four most common cancers (breast cancer, lung cancer, colorectal cancer, and prostate cancer) with the intention of providing an overview of its health effects in the non-communicable-diseases prevention.

Point-of-care ultrasound (PoCUS) in the early diagnosis of novel coronavirus 2019 disease (COVID-19) in a first-level emergency department during a SARS-CoV-2 outbreak in Italy: a real-life analysis.

In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) spread worldwide, challenging emergency departments (EDs) with the need of rapid diagnosis for appropriate allocation in dedicated setting. Many authors highlighted the role of lung ultrasound (LUS) in management of the novel coronavirus disease 2019 (COVID-19). The study aims to analyze the performance of LUS in the early identification of COVID-19 patients in ED during a SARS-CoV-2 outbreak. We prospectively collected consecutive adult patients admitted to a first-level ED in Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation Florence with history or symptoms suggestive for COVID-19 that underwent LUS during the ED management. LUS findings were categorized in 6 discrete main etiological patterns. "A", "Cardiogenic B" and "Typical C" patterns were referred as non-COVID-19-suggestive, while "Atypical" B or C patterns, "Multiple Consolidations" pattern and "ARDS" pattern were referred as COVID-19-suggestive. The primary outcome was the diagnosis of SARS-CoV-2 infection. From 12 March to 12 May 2020, 360 patients were enrolled. COVID-19 suggestive LUS findings were significantly associated with final COVID-19 diagnosis (86% in COVID-19 vs 29% in non-COVID-19, p < 0.001). The presence in ED of at least one in positive swab OR a COVID-19-suggestive LUS showed a sensitivity of 97% and a negative predictive value (NPV) of 98%. In patients with known SARS-CoV-2 exposition in the last 14 days, a COVID-19-suggestive pattern at LUS had a positive predictive value (PPV) of 97% for COVID-19 diagnosis. Point-of-care ultrasound (PoCUS) is a valuable tool for diagnostic stratification during COVID-19 outbreaks. LUS can help physicians in identifying false-negative RT-PCR, improving its diagnostic sensitivity in ED.

Effects of Stem Density on Crown Architecture of Scots Pine Trees.

Trees adapt to their growing conditions by regulating the sizes of their parts and their relationships. For example, removal or death of adjacent trees increases the growing space and the amount of light received by the remaining trees enabling their crowns to expand. Knowledge about the effects of silvicultural practices on crown size and shape and also about the quality of branches affecting the shape of a crown is, however, still limited. Thus, the aim was to study the crown structure of individual Scots pine trees in forest stands with varying stem densities due to past forest management practices. Furthermore, we wanted to understand how crown and stem attributes and also tree growth affect stem area at the height of maximum crown diameter (SAHMC), which could be used as a proxy for tree growth potential. We used terrestrial laser scanning (TLS) to generate attributes characterizing crown size and shape. The results showed that increasing stem density decreased Scots pine crown size. TLS provided more detailed attributes for crown characterization compared with traditional field measurements. Furthermore, decreasing stem density increased SAHMC, and strong relationships (Spearman's correlations > 0.5) were found between SAHMC and crown and stem size and also stem growth. Thus, this study provided quantitative and more comprehensive characterization of Scots pine crowns and their growth potential. The combination of a traditional growth and yield study design and 3D characterization of crown architecture and growth potential can open up new research possibilities.

Genetic variability and phospholipase production of Malassezia pachydermatis isolated from dogs with diverse grades of skin lesions.

Little detailed information is available on the association of Malassezia pachydermatis genotypes and the extent of skin damage that they cause. In the present study, isolates of M. pachydermatis, recovered from the skin of healthy dogs and dogs with dermatitis in Brazil, were characterized on the basis of partial sequencing of the large subunit (LSU), first internal transcribed spacer (ITS-1) and chitin synthase 2 gene (chs-2). The determination of phospholipase production was also included in the investigations. The severity of lesions and hyperpigmentation of dogs with skin disease were evaluated. For each locus, two main sequence types were designated as genotypes A and C. Two other minor sequence types (A2(I)-C2(I)) were also recorded and defined for the ITS-1. Genotype A isolates were the most prevalent, being recovered from healthy and diseased animals. No significant difference was detected among genotypes or ITS-1 sequence types and grades of skin damage or hyperpigmentation in the dogs with skin lesions. The number of M. pachydermatis isolates that produced phospholipase was statistically higher for diseased dogs than for strains found in healthy animals. The present study reveals that multiple genetic variants of M. pachydermatis occur in dogs and that the distribution patterns of particular genotypes on the skin of dogs in Brazil might be related to environmental and ecological factors which maintain distinctive genotype assemblages in specific geographical areas.

Hemorrhagic diathesis and bone marrow aplasia secondary to lomustine overdose in a dog.

A 9-year-old mixed breed 13 kg spayed female dog was presented for evaluation of two masses in the right abdominal mammary gland region. Surgery was conducted to excise the masses. A grade I complex mammary gland carcinoma and high grade (grade III) mast cell tumor with an inguinal lymph node metastasis were diagnosed. Forty-seven days after the surgical procedure, the mast cell tumor relapsed, and neoadjuvant treatment with lomustine (81 mg/m2 ) was prescribed. Thirteen days from initiation of lomustine therapy, the dog was re-presented to the hospital with bloody diarrhea, hematemesis, epistaxis, an elevated rectal temperature, depression, severe dehydration, and marked dyspnea. The CBC showed severe thrombocytopenia and leukopenia. According to the owner, lomustine (45mg per os [PO]) was mistakenly administered daily for 10 consecutive days (total dose, 810 mg/m2 ). The dog died and a necropsy was performed. The main gross lesions consisted of severe multifocal hemorrhages in multiple organs, especially in the digestive system. Histopathologic evaluation revealed disseminated hemorrhages, as well as marked bone marrow aplasia. This report describes the clinical, hematologic, gross, and histologic findings in a fatal case of lomustine overdose in a dog.

Management of patients presenting with haemoptysis to a Tertiary Care Italian Emergency Department: the Florence Haemoptysis Score (FLHASc).

We analysed the clinical features and diagnostic workup of patients presenting with haemoptysis to an Italian teaching hospital to derive an easy-to-use clinical score to guide risk stratification and initial management in the emergency department (ED). We retrospectively reviewed clinical records of consecutive patients with haemoptysis over 1 year. A pre-specified set of variables, including demographic data, vital signs, type of expectorate (pure blood vs. blood-streaked sputum), comorbidities, and diagnostic tests and treatments was originally registered. The primary outcome was a composite of any of the following: death from any cause, invasive or non-invasive ventilation, Intensive Care Unit admission, blood transfusions or invasive haemostatic procedures. We investigated associations between the pre-specified clinical variables and the primary outcome using a logistic regression analysis. Finally, we derived a score (the Florence Haemoptysis Score, FLHASc) giving a proportional weight to each variable according to the Odds Ratios (OR). We included 197 patients with a median age of 60 years. The first radiological study was a plain chest X-ray in 128 patients (65%). For 33 (17%) patients, a chest computer tomography (CT scan) was the first radiological study. The most common diagnosis was lung malignancy (19% of cases). The diagnosis remained undetermined in one-third of patients. The primary outcome was met by 11.2% of the study population. Systolic blood pressure <100 mmHg (OR 9.7), a history of malignancy (OR 3), the expectoration of pure blood (OR 2.8), and more than 2 episodes of haemoptysis in the prior 24 h (OR 2.5) are found as independent predictors of the primary outcome. The FLHASc ranges from 0 to 6 with a prognostic accuracy of 78% (IC 95%, 68-88%). The primary outcome incidence is 2.4% (IC 95%, 0.2-8.2%) in patients with a FLHASc equal to zero (n = 85, 43%) versus 13.4% (IC 95% 7.8-21.1%) in patients with a FLHASc > 0 (p < 0.01). Among patients with a FLHASc equal to zero, a negative chest X-ray study identifies patients who may be safely discharged. Patients who presented to the ED with haemoptysis experience a heterogeneous management. We derive a simple clinical prognostic score that may rationalize their diagnostic workup.

Role of Hypertension and Other Clinical Variables in Prognostication of Patients Presenting to the Emergency Department With Major Bleeding Events.

BACKGROUND: Clinical variables including hypertension could be linked with major bleeding events and death beyond vitamin K antagonist (warfarin) or direct oral anti-coagulants (DOACs) treatment strategy. METHODS: Subgroup analysis of major bleeding (primary endpoint) associated with clinical variables, site of bleeding, ongoing antithrombotics, reversal treatment or blood transfusion, outcomes (secondary endpoints) was performed in patients with bleeding events submitted to hard 5:1 propensity-score matching for hypertension. RESULTS: Enrolled patients were 2,792 (mean age, 65.6 ± 19.9 years) during 2-year survey including 166,000 visits, of 200,000 inhabitants catchment area; 8,239 patients received warfarin and 3,797 DOACs. Hypertension account for 1,077 (39%) patients; major bleeding for 474 (17%); death for 29 (1%), and 72 (3%) on 1-month and 1-year, respectively. Hypertension, age, glucose, cancer, ischemic vascular disease, and CHA2D2VASc score were more likely to link with major bleeding. On multivariate analysis, only age (odds ratio [OR], 1.02; P < 0.001), CHA2DS2VASc score ≥ 2 (OR, 2.14; P = 0.001), and glucose (OR, 1.01; P = 0.005) were predictors of major bleeding. Kaplan-Meier analysis demonstrated patients with hypertension as compared with patients without showed 60% versus 20% death on 1-month (P < 0.001). Warfarin compared with DOACs was more likely to present with major bleeding (0.7% versus 0.2%; OR, 2.8; P = 0.005). Receiver operator characteristics analysis showed high value (0.61) of age and glucose over creatinine and systolic arterial pressure (P = NS). CONCLUSIONS: Four in 10 patients with major bleeding showed hypertension; of these 8 in 10 will die within 1 month. Warfarin compared with DOACs was more likely to present with major bleeding.