Fear of memory loss predicts increased memory failures and lower quality of life in older adults: preliminary findings from a fear-avoidance of memory loss (FAM) scale.

BACKGROUND: Few studies have measured the impact of dementia-related fear on daily functioning, despite its clinical relevance. Our aim was to determine the relationship between fear-avoidance of memory loss, perceived memory failures and self-reported quality of life in a community based sample of older adults using a novel fear of memory loss (FAM) scale. METHODS: Sixty-seven older adults (59-81 years) completed a 23-item self-report scale designed to capture multi-faceted components of fear of memory loss, known as the FAM scale. Perceived memory failures were measured using the Memory Failures Scale (MFS) and quality of life was assessed using the Older Person's Quality of Life scale (OPQOL-35). Participants also completed the Wechsler Memory Scale (WMS-IV) as a measure of objective memory performance and the Depression, Anxiety and Stress Scales (DASS) and the Geriatric Anxiety Inventory (GAI) as measures of general anxiety. RESULTS: The FAM scale demonstrated strong internal consistency (Cronbach's α = .82) and concurrent validity with the GAI (r = .47). Three latent factors were observed: (1) fear-avoidance, (2) problematic beliefs and (3) affective resilience. After adjusting for objective memory performance and general anxiety, higher fear-avoidance significantly predicted increased perceived memory failures (p = .014) and reduced quality of life (p = .033). CONCLUSIONS: Fear of memory loss predicts increased perceived memory failures and lower self-reported quality of life in a community sample of older adults. Based on these findings, we propose a preliminary fear-avoidance model that explains the development and maintenance of dementia-related functional disability in terms of psychological processes.

A comparison of resting state EEG and structural MRI for classifying Alzheimer's disease and mild cognitive impairment.

Alzheimer's disease (AD) is the leading cause of dementia, accounting for 70% of cases worldwide. By 2050, dementia prevalence will have tripled, with most new cases occurring in low- and middle-income countries. Mild cognitive impairment (MCI) is a stage between healthy aging and dementia, marked by cognitive deficits that do not impair daily living. People with MCI are at increased risk of dementia, with an average progression rate of 39% within 5 years. There is urgent need for low-cost, accessible and objective methods to facilitate early dementia detection. Electroencephalography (EEG) has potential to address this need due to its low cost and portability. Here, we collected resting state EEG, structural MRI (sMRI) and rich neuropsychological data from older adults (55+ years) with AD, amnestic MCI (aMCI) and healthy controls (~60 per group). We evaluated a range of candidate EEG markers (i.e., frequency band power and functional connectivity) for AD and aMCI classification and compared their performance with sMRI. We also tested a combined EEG and cognitive classification model (using Mini-Mental State Examination; MMSE). sMRI outperformed resting state EEG at classifying AD (AUCs â€‹= â€‹1.00 vs 0.76, respectively). However, both EEG and sMRI were only moderately good at distinguishing aMCI from healthy aging (AUCs â€‹= â€‹0.67-0.73), and neither method achieved sensitivity above 70%. The addition of EEG to MMSE scores had no added benefit relative to MMSE scores alone. This is the first direct comparison of EEG and sMRI for classification of AD and aMCI.

Fungal infections of the central nervous system and paranasal sinuses in onco-haematologic patients. Epidemiological study reporting the diagnostic-therapeutic approach and outcome in 89 cases.

Invasive fungal infections (IFI) of the Central Nervous System (IFI-CNS) and Paranasal Sinuses (IFI-PS) are rare, life-threatening infections in haematologic patients, and their management remains a challenge despite the availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohorts of patients focusing on these rare IFI are still lacking. Between January 2010 and December 2016, 89 consecutive cases of Proven (53) or Probable (36) IFI-CNS (71/89) and IFI-PS (18/89) were collected in 34 haematological centres. The median age was 40 years (range 5-79); acute leukaemia was the most common underlying disease (69%) and 29% of cases received a previous allogeneic stem cell transplant. Aspergillus spp. were the most common pathogens (69%), followed by mucormycetes (22%), Cryptococcus spp. (4%) and Fusarium spp. (2%). The lung was the primary focus of fungal infection (48% of cases). The nervous system biopsy was performed in 10% of IFI-CNS, and a sinus biopsy was performed in 56% of IFI-PS (P = 0.03). The Galactomannan test on cerebrospinal fluid has been performed in 42% of IFI-CNS (30/71), and it was positive in 67%. Eighty-four pts received a first-line antifungal therapy with Amphotericine B in 58% of cases, Voriconazole in 31% and both in 11%. Moreover, 58% of patients received 2 or more lines of therapy and 38% were treated with a combination of 2 or more antifungal drugs. The median duration of antifungal therapy was 60 days (range 5-835). A surgical intervention was performed in 26% of cases but only 10% of IFI-CNS underwent neurosurgical intervention. The overall response rate to antifungal therapy (complete or partial response) was 57%, and 1-year overall survival was 32% without significant differences between IFI-CNS and IFI-PS. The overall mortality was 69% but the IFI attributable mortality was 33%. Mortality of IFI-CNS/PS remains high but, compared to previous historical data, it seems to be reduced probably due to the availability of newer antifungal drugs. The results arising from this large contemporary cohort of cases may allow a more effective diagnostic and therapeutic management of these very rare IFI complications in haematologic patients.

Trichinella spiralis in a South American sea lion (Otaria flavescens) from Patagonia, Argentina.

Trichinella spp. from a sylvatic cycle has been found in several animal species such as pumas (Puma concolor), armadillos (Chaetophractus villosus), rats (Rattus norvegicus), and wild boars (Sus scrofa) in Argentina. Moreover, Trichinella infection has been detected in a wide range of marine mammals around the world, including polar bears (Ursus maritimus) and walruses (Odobenus rosmarus). Until the present time, Trichinella spp. infection has not been detected in marine mammals of South America. Samples from four South American sea lions (Otaria flavescens) found dead in Rio Negro, Argentina, were analyzed by artificial digestion, and in the case of one animal, Trichinella larvae were identified at the species level by nested multiplex PCR as Trichinella spiralis. This is the first report of a Trichinella species infecting marine mammals from South America.

Evaluation of the infectivity and the persistence of Trichinella patagoniensis in muscle tissue of decomposing guinea pig (Cavia porcellus).

Trichinella patagoniensis, a new species of Trichinella, is widespread in Argentina. The success of parasite transmission depends, among other factors, on the resistance of L1 larvae present in the muscle tissue (ML) of dead hosts undergoing the decomposition process in different environmental conditions. The aim of the present work was to study the infectivity of T. patagoniensis muscle larvae in Cavia porcellus and the capability of the parasite to survive in decomposed muscle tissue of guinea pigs subjected to different environmental conditions. Thirty-two female Ssi:AL guinea pigs were orally inoculated with 2000 ML of T. patagoniensis (ISS2311). All the animals were sacrificed 42 days post-infection. Twenty-six animals were eviscerated, and carcasses were placed on the surface of soil inside plastic boxes that were exposed to environmental conditions in the summer 2014-2015 and autumn of 2015 in Buenos Aires, Argentina. Carcasses from six animals were placed into a plastic box inside the refrigerator at a temperature of 4 °C. The muscle tissue samples from the carcasses were examined weekly for the presence of larvae, and the infectivity of recovered ML was tested in BALB/c mice. Our results showed for the first time the ability of T. patagoniensis to complete its life cycle in guinea pigs, thus serving as a potential natural host. Also, larvae of T. patagoniensis remained infective in muscle tissue for several weeks while undergoing decomposition under different environmental conditions.

Cardiac mesenchymal stromal cells are a source of adipocytes in arrhythmogenic cardiomyopathy.

AIM: Arrhythmogenic cardiomyopathy (ACM) is a genetic disorder mainly due to mutations in desmosomal genes, characterized by progressive fibro-adipose replacement of the myocardium, arrhythmias, and sudden death. It is still unclear which cell type is responsible for fibro-adipose substitution and which molecular mechanisms lead to this structural change. Cardiac mesenchymal stromal cells (C-MSC) are the most abundant cells in the heart, with propensity to differentiate into several cell types, including adipocytes, and their role in ACM is unknown. The aim of the present study was to investigate whether C-MSC contributed to excess adipocytes in patients with ACM. METHODS AND RESULTS: We found that, in ACM patients' explanted heart sections, cells actively differentiating into adipocytes are of mesenchymal origin. Therefore, we isolated C-MSC from endomyocardial biopsies of ACM and from not affected by arrhythmogenic cardiomyopathy (NON-ACM) (control) patients. We found that both ACM and control C-MSC express desmosomal genes, with ACM C-MSC showing lower expression of plakophilin (PKP2) protein vs. CONTROLS: Arrhythmogenic cardiomyopathy C-MSC cultured in adipogenic medium accumulated more lipid droplets than controls. Accordingly, the expression of adipogenic genes was higher in ACM vs. NON-ACM C-MSC, while expression of cell cycle and anti-adipogenic genes was lower. Both lipid accumulation and transcription reprogramming were dependent on PKP2 deficiency. CONCLUSIONS: Cardiac mesenchymal stromal cells contribute to the adipogenic substitution observed in ACM patients' hearts. Moreover, C-MSC from ACM patients recapitulate the features of ACM adipogenesis, representing a novel, scalable, patient-specific in vitro tool for future mechanistic studies.

Clinical models and biochemical predictors of VTE in lung cancer.

Venous thromboembolism (VTE) is a frequent complication of lung cancer and its treatment, especially in the advanced stages of disease. The risk of a pro-thrombotic state might increase through the activation of hemostasis, occurring both via the induction of a pro-coagulant activity and with platelet involvement, ultimately leading to the development of metastases. Despite the acknowledgement of an increased thrombophilic condition in cancer patients, and the experimental evidence that heparin compounds may have direct anticancer benefits, there is no univocal consent regarding VTE prevention in cancer outpatients receiving therapy. Thus, many authors highlighted the need for the development of stratification techniques to identify at-risk patients who might benefit from thromboprophylaxis. Clinical risk models were developed and validated, in order to assign high-risk patients to a proper thromboprophylaxis regimen that, however, might not be justified in all clusters. Besides, efforts have been devoted to identify candidate biomarkers that may be used in VTE risk assessment, although none has been recognized, so far, as a predictor for VTE in lung cancer patients. In this review, we will summarize the latest information concerning this very controversial topic, with focus on some of the proposed strategies to select the appropriate patients for prophylaxis.

Lactobacillus casei and bifidobacterium lactis supplementation reduces tissue damage of intestinal mucosa and liver after 2,4,6-trinitrobenzenesulfonic acid treatment in mice.

Probiotics (PB) are living microorganisms that act as a commensal population in normal intestines and confer numerous beneficial effects on the host. The introduction of probiotics in the treatment of inflammatory bowel disease (IBD) prolongs remission. The aim of this study was to investigate the intestinal and hepatic effects of PB supplementation in an experimental IBD model in mice induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). In the first step of the experimental procedure, CD-1 male mice, 5 to 6 weeks old, were randomly divided into 3 groups and inoculated intrarectally with, respectively, saline, alcohol, or TNBS to assess the experimental IBD model. In the second step, mice treated, or not, with TNBS inoculation, were treated with PB (Lactobacillus Casei, Bifidobacterum Lactis) for 1, 2 or 3 weeks, on a daily basis. Large bowel (colon and rectum) and liver were processed for histological alterations, according to a scoring system. Large bowel was also assessed for apoptosis by TUNEL assay. TNBS induced, as expected, severe damage and inflammation in the large bowel, including nuclear alterations and apoptosis, and, to a lesser extent, to the liver. Administration of PB determined significant reduction of both histological alterations and apoptosis. PB administration in advance protects from inflammation. In conclusion, supplementation with Lactobacillus casei, Bifidobacterum lactis PB is able to ameliorate the colitis by reversing the histological changes caused by TNBS in mice. Experimentation in human subjects in needed to prove their efficacy in reducing histological alterations that may be present in subjects with IBD.

A Toxocara cati eggs concentration method from cats' faeces, for experimental and diagnostic purposes.

Toxocariosis is a zoonotic parasite infection worldwide distributed, now considered a neglected disease associated to poverty. For experimental infection in animals and to develop the diagnosis in humans it is necessary to obtain large number of Toxocara spp. larval eggs. Toxocara cati eggs recovered percentage from faeces of infected cats was determined employing a novel egg concentration method. The McMaster egg counting technique and the concentration method were applied on 20 positive cats' sample faeces obtained from naturally infected cats. The mean percentage of eggs recovered by the concentration method was 24.37% higher than the count obtained by McMaster egg counting technique. The main advantage of this method is that it can be obtained a small final volume with a high number of recovered eggs and a good quality inoculum for experimental and diagnostic purposes.

Combination of intralesional verapamil and oral antioxidants for Peyronie's disease: a prospective, randomised controlled study.

The aim of this study was to evaluate the efficacy of the association of intralesional verapamil (ILV) injection with oral antioxidants compared with ILV monotherapy in patients with early onset of Peyronie's disease (PD) at 12-week follow-up. Group A (n = 52) received ILV 10 mg weekly for 12 weeks, while group B (n = 53) received ILV 10 mg weekly for 12 weeks + antioxidants orally one tablet once a day for 3 months. The main efficacy outcomes were the change in plaque size (PS), penile curvature (PC), visual analogue score (VAS), IIEF-15 and IIEF-15 subdomains. Both groups showed significant improvement from baseline to week 12 relative to PS and PC, while group B also in IIEF-15 score (mean difference: 5.51, P < 0.01) and VAS (mean difference: -2.71, P < 0.01). No significant differences were observed between both groups in PS and PC. Finally, both groups showed significant increase in orgasmic function (IIEF-OF) and overall satisfaction (IIEF-OS), while group B showed significant improvement also in intercourse satisfaction (IIEF-IS). Significant differences were found relative to IIEF-OF, IIEF-IS, IIEF-OS and VAS scores in the group B compared with group A. Patients affected by PD may benefit from combination treatment with ILV and oral antioxidants thanks to the improvement in IIEF-OF, IIEF-IS and IIEF-OS at 12 weeks.

New records of Trichinella patagoniensis from Argentina.

Trichinella spiralis was long considered the sole Trichinella species in Argentina. However, since 2004, various Trichinella species, including the encapsulated Trichinella patagoniensis and Trichinella britovi, as well as the unencapsulated Trichinella pseudospiralis, have been detected in the country. The present study aimed to identify Trichinella ML at the species level from cougars naturally infected from Argentina. To this end, muscle tissue samples from one cougar each from Córdoba, Neuquén, and Santa Cruz Provinces were individually analysed using the artificial digestion technique. DNA extraction and molecular identification of Trichinella species were conducted on individual muscle larvae by PCR amplification of the ESV region and subsequent PCR amplification and sequencing of the COI gene. Morphological analysis revealed muscle larvae with characteristics consistent with Trichinella genus. PCR revealed a single band of approximately 127 bp for each individual muscle larva. PCR amplification of the COI gene from each isolate generated a 309 bp band. Sequencing of the mitochondrial COI gene confirmed the identity of the parasite as T. patagoniensis. The present study documents new occurrences of T. patagoniensis in Puma concolor from Argentina, including the first detection of T. patagoniensis in Puma concolor from Córdoba and Neuquén Province. These findings expand the limited knowledge of T. patagoniensis distribution in Argentina.

Video Versus Direct Laryngoscopy for Intubation: Updated Systematic Review and Meta-Analysis.

Direct laryngoscopy (DL) is a modality commonly used in endotracheal intubation (EI). Video laryngoscopy (VL) was introduced to further facilitate the procedure with enhancement in glottic views, which captures the video image of the vocal cords to be projected onto a screen, providing enhanced visualization. This real-time video projection aids in accurately placing the endotracheal tube (ETT) through the vocal cords. In emergency and critical care settings, both laryngoscopes are used for intubations. This study assesses the efficacy of both modalities by comparing success rates in first-attempt tracheal intubation in critically ill patients.  PubMed, EMBASE, and Scopus were searched and all randomized controlled trials (RCTs) and observational studies until 2023 were included. Studies included patients in critical care settings undergoing EI under the guidance of either DL or VL. The primary outcome was the first attempt at successful tracheal intubation. The secondary outcomes assessed the comparative safety of DL and VL by comparing the rates of severe hypoxemia, severe hypotension, and cardiac arrest occurring during each modality. P-values were considered of statistical significance if below 0.05. Statistical analysis was performed using RevMan v5.4 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark). The results were displayed in the form of forest plots.  A total of eight studies were included with a total of 5348 patients, with 1780 in the DL group and 3568 in the VL group. Analysis revealed that in emergency situations, the success rate of intubation on the first attempt was significantly higher for VL than DL [81.5% vs 68%; RR= 1.19; 95% CI: 1.10, 1.29; p <0.00001; I2=70%]. There was no significant correlation between VL and severe hypoxemia [13.4% vs 11.6%; RR= 0.99; 95% CI: 0.74, 1.33; p =0.97; I2=46%], severe hypotension [6.09% vs 4.78%; RR:1.19; 95% CI: 0.83, 1.72; p =0.35, I2-15%], and cardiac arrest, [0.8% vs 0.4%; RR= 1.17; 95% CI: 0.37, 3.70]; p =0.79; I2=0%]. Our meta-analysis confirmed that VL has a higher success rate for first-pass intubation than DL. Furthermore, our analysis has shown no significant evidence linking VL to any adverse events.

TNF-α gene promoter polymorphisms and risk of venous thromboembolism in gastrointestinal cancer patients undergoing chemotherapy.

BACKGROUND: TNF-α has been proposed as a predictive factor for venous thromboembolism (VTE). Genetic polymorphisms could regulate TNF-α production. However, the relationship between TNFA gene variants and VTE is not clarified. This study aims to investigate the predictive role of five different TNFA gene promoter SNPs, or their haplotype combination(s), for a first VTE episode in gastrointestinal cancer out-patients treated with chemotherapy. PATIENTS AND METHODS: Serum TNF-α levels and TNFA -863C/A, -857C/T, -376G/A, -308G/A and -238G/A gene promoter polymorphisms were retrospectively evaluated in 314 subjects, including 157 controls and 157 Caucasian patients with histologically diagnosed GI cancers beginning chemotherapy delivery (5-fluorouracil either as monotherapy or in combination with platinum compounds or irinotecan). RESULTS: Haplotype analysis showed that a five-loci haplotype (CTGGG haplotype) has higher frequency in GI cancer patients who developed VTE (n = 15) during chemotherapy [odds ratio = 2.7, 95% confidence interval (CI) 1.04-7.11, P = 0.04]. GI patients who remained VTE-free did not differ in CTGGG haplotype frequency from controls. No association was observed between serum TNF-α levels and TNFA haplotype, but both were independent predictors of VTE. Approximately 20% of GI cancer patients carrying the CTGGG haplotype developed VTE compared with 4% of the remaining 101 patients (hazard ratio = 5.6, 95% CI 1.8-17.6, P = 0.003). CONCLUSION: These results suggest that TNFA might represent a candidate gene contributing to VTE pathogenesis in GI cancer patients and suggest that VTE risk during chemotherapy might be genetically identified. Validation studies are needed for translation into clinical practice.

Risk factors of sexual dysfunction after transurethral resection of the prostate (TURP): a 12 months follow-up.

The aim of this study was to evaluate the impact of risk factors of erectile dysfunction (ED) after transurethral resection of the prostate (TURP) in men with lower urinary tract symptoms caused by bladder outlet obstruction secondary to benign prostatic hyperplasia. The study was conducted prospectively on 178 consecutive patients (normal IIEF-5 before surgery, ≥ 22) who underwent TURP. Patients were assessed before surgery and at 12 months. At 12 months, the IIEF-5 score significantly decreased from24 to 18 (p<0.0001). No statistical associations were found between hypertension, diabetes, dyslipidemia and capsular perforation and the development of ED after TURP. Operating time, duration of catheterization, and BMI did not determine a significant decrease of the IIEF-5 score after TURP. On univariable and multivariable linear regression analysis, age was the only risk factor associated with newly-reported ED 12 months after TURP (p<0.0001). On univariable andmultivariable logistic regression analysis, patients older than 65 yr had an higher risk of developing ED after TURP (p<0.0001) and they developed a lower IIEF-5 score (p<0.0001) at followup when compared with those ≤ 65 yr. These results suggest that age of patients represents an independent risk factor of ED at 12 months follow-up after TURP.

Impact of statins on the coagulation status of type 2 diabetes patients evaluated by a novel thrombin-generation assay.

PURPOSE: Dyslipidemia is common in type 2 diabetes (T2D) and contributes to cardiovascular disease (CVD) by exacerbating atherosclerosis and hypercoagulability. Statins can stabilize atherosclerotic plaque and reduce prothrombotic status. In the present study we aimed to evaluate the coagulation activity and the effect of statins on procoagulant state of T2D patients using a novel activated protein C (APC)-dependent thrombin-generation assay. METHODS: Procoagulant status (by HemosIL ThromboPath (ThP) assay) and in vivo platelet activation (by plasma soluble (s)CD40L levels) were analyzed in a retrospective, cross-sectional study of 198 patients with long-standing T2D and 198 controls. RESULTS: Procoagulant status of T2D patients was enhanced when compared to control subjects (p < 0.0001). Similarly, sCD40L levels were increased in T2D (p < 0.0001). When testing ThP as the dependent variable in a multivariate regression model, sCD40L (p < 0.0001) and statin treatment (p = 0.019) were independent predictors of the procoagulant state of T2D patients. Subgroup analysis showed a significant improvement of coagulability in T2D patients on statins (p = 0.012). CONCLUSIONS: The use of a standardized, easy-to-run, and commercially available APC-dependent thrombin-generation assay detected the presence of a procoagulant status in a large series of patients with long-standing T2D and demonstrated a significant impact of statins in the coagulation status of patients with T2D.

Study of Trichinella patagoniensis in wild boars.

Trichinellosis is a zoonotic disease, which represents a significant public health concern in some South American countries, such as Argentina and Chile. Its impact is essentially due to absence of adequate control measures on meat from game animals, as well as the presence of illegal slaughterhouses and the trade of meat products without being tested for this parasite. In Argentina, trichinellosis is an endemic disease. At present, Trichinella spiralis, Trichinella patagoniensis, Trichinella pseudospiralis, and Trichinella britovi have been detected in animals from Argentina. Until now, T. patagoniensis had only been found in mountain cougars (Puma concolor) in Argentina but there is limited information available. The present study intends to determine susceptibility, serological response and distribution of muscle larvae in wild boars infected with T. patagoniensis, T. spiralis and T. pseudospiralis. For each of the Trichinella species five wild boars were inoculated with 20,000 muscle larvae. Except for two specimens which died during the experiment, the animals were euthanized 19 weeks post infection (pi). Blood samples were collected throughout the study in order to determine the antibody kinetics. Also, nine muscle samples from each specimen were taken and analysed for determination of larval distribution. Additionally, four muscle samples were used to obtain muscle juices. Wild boars infected with T. patagoniensis showed little to no larvae in the muscle samples analysed while animals infected with T. spiralis and T. pseudospiralis had a significantly high larval load in all the samples analysed. Optical density (OD) values remained above the cut-off value throughout the experiment. This is the first study to characterize the biological aspects of T. patagoniensis in wild boars.

Brain event-related potentials predict individual differences in inhibitory control.

Stop-signal reaction time (SSRT), the time needed to cancel an already-initiated motor response, quantifies individual differences in inhibitory control. Electrophysiological correlates of SSRT have primarily focused on late event-related potential (ERP) components over midline scalp regions from successfully inhibited stop trials. SSRT is robustly associated with the P300, there is mixed evidence for N200 involvement, and there is little information on the role of early ERP components. Here, machine learning was first used to interrogate ERPs during both successful and failed stop trials from 64 scalp electrodes at 4 ms resolution (n = 148). The most predictive model included data from both successful and failed stop trials, with a cross-validated Pearson's r of 0.32 between measured and predicted SSRT, significantly higher than null models. From successful stop trials, spatio-temporal features overlapping the N200 in right frontal areas and the P300 in frontocentral areas predicted SSRT, as did early ERP activity (<200 ms). As a demonstration of the reproducibility of these findings, the application of this model to a separate dataset of 97 participants was also significant (r = 0.29). These results show that ERPs during failed stops are relevant to SSRT, and that both early and late ERP activity contribute to individual differences in SSRT. Notably, the right lateralized N200, which predicted SSRT here, is not often observed in neurotypical adults. Both the ascending slope and peak of the P300 component predicted SSRT. These results were replicable, both within the training sample and when applied to ERPs from a separate dataset.

The soluble glycoprotein NMB (GPNMB) produced by macrophages induces cancer stemness and metastasis via CD44 and IL-33.

In cancer, myeloid cells have tumor-supporting roles. We reported that the protein GPNMB (glycoprotein nonmetastatic B) was profoundly upregulated in macrophages interacting with tumor cells. Here, using mouse tumor models, we show that macrophage-derived soluble GPNMB increases tumor growth and metastasis in Gpnmb-mutant mice (DBA/2J). GPNMB triggers in the cancer cells the formation of self-renewing spheroids, which are characterized by the expression of cancer stem cell markers, prolonged cell survival and increased tumor-forming ability. Through the CD44 receptor, GPNMB mechanistically activates tumor cells to express the cytokine IL-33 and its receptor IL-1R1L. We also determined that recombinant IL-33 binding to IL-1R1L is sufficient to induce tumor spheroid formation with features of cancer stem cells. Overall, our results reveal a new paracrine axis, GPNMB and IL-33, which is activated during the cross talk of macrophages with tumor cells and eventually promotes cancer cell survival, the expansion of cancer stem cells and the acquisition of a metastatic phenotype.

The predictive value of clinical, radiographic, echocardiographic variables and cardiac biomarkers for assessing risk of the onset of heart failure or cardiac death in dogs with preclinical myxomatous mitral valve disease enrolled in the DELAY study.

OBJECTIVES: To identify the predictive value on time to onset of heart failure (HF) or cardiac death of clinical, radiographic, and echocardiographic variables, as well as cardiac biomarkers N-terminal pro brain natriuretic peptide (NT-proBNP) and cardiac troponin I in dogs with preclinical myxomatous mitral valve disease (MMVD). ANIMALS: One hundred sixty-eight dogs with preclinical MMVD and left atrium to aortic root ratio ≥1.6 (LA:Ao) and normalized left ventricular end-diastolic diameter ≥1.7 were included. METHODS: Prospective, randomized, multicenter, single-blinded, placebo-controlled study. Clinical, radiographic, echocardiographic variables and plasma cardiac biomarkers concentrations were compared at different time points. Using receiving operating curves analysis, best cutoff for selected variables was identified and the risk to develop the study endpoint at six-month intervals was calculated. RESULTS: Left atrial to aortic root ratio >2.1 (hazard ratio [HR] 3.2, 95% confidence interval [95% CI] 1.9-5.6), normalized left ventricular end-diastolic diameter > 1.9 (HR: 6.3; 95% CI: 3.3-11.8), early transmitral peak velocity (E peak) > 1 m/sec (HR: 3.9; 95% CI: 2.3-6.7), and NT-proBNP > 1500 ρmol/L (HR: 5.7; 95% CI: 3.3-9.5) were associated with increased risk of HF or cardiac death. The best fit model to predict the risk to reach the endpoint was represented by the plasma NT-proBNP concentrations adjusted for LA:Ao and E peak. CONCLUSIONS: Logistic and survival models including echocardiographic variables and NT-proBNP can be used to identify dogs with preclinical MMVD at higher risk to develop HF or cardiac death.

Biotic and abiotic factors influencing distribution and abundance of Culicoides obsoletus group (Diptera: Ceratopogonidae) in central Italy.

In the framework of a bluetongue surveillance program including clinical, serological, and entomological activities, Culicoides biting midges were light trapped weekly in two regions of central Italy, Lazio and Tuscany. In the period January 2002 through December 2005, 3,944 collections were carried out in 189 trap sites distributed in all the provinces of the two regions. Abundance data of C. obsoletus group were analyzed in relation to trap site altitude, distance from the sea, land use, and number of farmed animals. Species seasonality and overall temporal trend were also described. C. obsoletus was distributed over the whole study area, almost in all trapping sites and with high abundances. The species group was dominant among all captured Culicoides, with higher abundances recorded inland and in areas where land cover was partially or completely natural-wooded. Adults on the wing were caught all year round, with peaks in May-June and middle October. The observed trend through years recorded a peak during autumn 2002, in concomitance with a local epidemic of bluetongue.