Noncanonical Wnt signaling promotes colon tumor growth, chemoresistance and tumor fibroblast activation.

Colon tumors of the mesenchymal subtype have the lowest overall survival. Snail1 is essential for the acquisition of this phenotype, characterized by increased tumor stemness and invasion, and high resistance to chemotherapy. Here, we find that Snail1 expression in colon tumor cells is dependent on an autocrine noncanonical Wnt pathway. Accordingly, depletion of Ror2, the co-receptor for noncanonical Wnts such as Wnt5a, potently decreases Snail1 expression. Wnt5a, Ror2, and Snail1 participate in a self-stimulatory feedback loop since Wnt5a increases its own synthesis in a Ror2- and Snail1-dependent fashion. This Wnt5a/Ror2/Snail1 axis controls tumor invasion, chemoresistance, and formation of tumor spheres. It also stimulates TGFß synthesis; consequently, tumor cells expressing Snail1 are more efficient in activating cancer-associated fibroblasts than the corresponding controls. Ror2 downmodulation or inhibition of the Wnt5a pathway decreases Snail1 expression in primary colon tumor cells and their ability to form tumors and liver metastases. Finally, the expression of SNAI1, ROR2, and WNT5A correlates in human colon and other tumors. These results identify inhibition of the noncanonical Wnt pathway as a putative colon tumor therapy.

Long-Term Protective Effects of Succinate Dehydrogenase Inhibition during Reperfusion with Malonate on Post-Infarction Left Ventricular Scar and Remodeling in Mice.

Succinate dehydrogenase inhibition with malonate during initial reperfusion reduces myocardial infarct size in both isolated mouse hearts subjected to global ischemia and in in situ pig hearts subjected to transient coronary ligature. However, the long-term effects of acute malonate treatment are unknown. Here, we investigated whether the protective effects of succinate dehydrogenase inhibition extend to a reduction in scar size and adverse left ventricular remodeling 28 days after myocardial infarction. Initially, ten wild-type mice were subjected to 45 min of left anterior descending coronary artery (LAD) occlusion, followed by 24 h of reperfusion, and were infused during the first 15 min of reperfusion with saline with or without disodium malonate (10 mg/kg/min, 120 µL/kg/min). Malonate-treated mice depicted a significant reduction in infarct size (15.47 ± 3.40% of area at risk vs. 29.34 ± 4.44% in control animals, p < 0.05), assessed using triphenyltetrazolium chloride. Additional animals were then subjected to a 45 min LAD ligature, followed by 28 days of reperfusion. Treatment with a single dose of malonate during the first 15 min of reperfusion induced a significant reduction in scar area, measured using Picrosirius Red staining (11.94 ± 1.70% of left ventricular area (n = 5) vs. 23.25 ± 2.67% (n = 9), p < 0.05), an effect associated with improved ejection fraction 28 days after infarction, as determined using echocardiography, and an attenuated enhancement in expression of the pro-inflammatory and fibrotic markers NF-κB and Smad2/3 in remote myocardium. In conclusion, a reversible inhibition of succinate dehydrogenase with a single dose of malonate at the onset of reperfusion has long-term protective effects in mice subjected to transient coronary occlusion.

Urothelial carcinoma masquerading as retroperitoneal fibrosis: A case report.

Retroperitoneal fibrosis, a rare and often idiopathic condition, poses significant diagnostic challenges. While most cases are considered idiopathic or immune-mediated, a small but important proportion are associated with malignant neoplasms, with implications for prognosis and management. The present study describes the case of a 69-year-old man who presented to the emergency department of the Virgen de las Nieves University Hospital (Granada, Spain), with a 2-week history of epigastric pain, vomiting and altered bowel habits. Laboratory investigations revealed previously undiagnosed renal insufficiency. An abdominal computed tomography (CT) scan showed extensive diffuse retroperitoneal infiltration extending from the periduodenal region to the pubic bone, resulting in gastric dilatation and hydronephrosis. A CT-guided retroperitoneal biopsy was performed and pathology confirmed the presence of urothelial carcinoma. This diagnosis led to the initiation of a chemotherapy regimen consisting of carboplatin and gemcitabine specifically designed for urothelial carcinoma. A follow-up 18F-FDG PET scan performed 6 months later showed a partial functional response. This case illustrates a rare presentation of urothelial carcinoma masked by extensive retroperitoneal fibrosis, and highlights the importance of accurate diagnosis in reducing tumor burden and improving the clinical status of patients.

Combined therapy against murine-disseminated infection by Fusarium verticillioides.

Using a murine model of disseminated infection by two strains of Fusarium verticillioides, we have evaluated the efficacy of high doses of amphotericin B (AMB) (3 mg/kg of body weight/day), voriconazole (VRC) (60 mg/kg of body weight/day), posaconazole (PSC) (100 mg/kg of body weight/day), and the combinations of AMB plus VRC or PSC. In general, our results were very modest. Neither combination was superior to the respective monotherapies. VRC alone and in combination with AMB was able to prolong survival but not to reduce tissue burden, and AMB plus PSC was able to reduce fungal load in organs but not to prolong survival.

Lifetime sexual behavior of psychiatric inpatients.

INTRODUCTION: Sexual life of psychiatric patients, including risk behaviors related to sexually transmitted diseases, remains a poorly studied area, especially in those with severe mental illnesses. AIMS: To assess some aspects of lifetime sexual behavior of psychiatric inpatients. METHODS: Patients consecutively admitted to a psychiatric unit in a general hospital were interviewed about partner-related lifetime sexual behavior. MAIN OUTCOME MEASURES: A semi-structured interview developed by the authors was used to collect information concerning their general sexual experience throughout life, homosexual and heterosexual relations, and relations with partners who were intravenous drug users (IVDU), HIV carriers or suffering from AIDS, and with sex workers. In each of these areas, time elapsed since last sexual contact; number of partners in previous year, frequency of these relations and condom use were investigated. RESULTS: Five hundred forty-six patients (306 men and 240 women) were assessed, and 87.7% of them reported sexual relations at some point during their life. Of these, 90% reported heterosexual and 10% homosexual or bisexual sexual contacts. Further, 11.06% had had at least one partner who was an IVDU; 8.1% an HIV-positive partner, and 32.4% (50% of the men) had paid for sex. Overall 49.79% of the total sample reported never using condoms in their sexual relations, with similar percentages for those with HIV-positive (46%) and IVDU (47%) partners. Of those who paid for sex, 29% never used condoms. CONCLUSIONS: Psychiatric patients admitted to a general hospital psychiatric unit have sexual experience close to the general population, with a higher percentage of homosexual contacts and lower rates of condom use, even in higher risk situations, such as men having sex with men, and partners who are HIV-positive or IVDUs. This information obliges clinicians to systematically explore the sexual behavior of psychiatric patients, evaluate risk behaviors, and adopt measures to promote safe sex practices in this population.

Telemonitoring and home hospitalization in patients with chronic obstructive pulmonary disease: study TELEPOC.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major consumer of healthcare resources, with most costs related to disease exacerbations. Telemonitoring of patients with COPD may help to reduce the number of exacerbations and/or the related costs. On the other hand, home hospitalization is a cost-saving alternative to inpatient hospitalization associated with increased comfort for patients. The results are reported regarding using telemonitoring and home hospitalization for the management of patients with COPD. METHODS: Twenty-eight patients monitored their health parameters at home for six months. A nurse remotely revised the collected parameters and followed the patients as programmed. A home care unit was dispatched to the patients' home if an alarm signal was detected. The outcomes were compared to historical data from the same patients. RESULTS: The number of COPD exacerbations during the study period did not reduce but the number of hospital admissions decreased by 60% and the number of emergency room visits by 38%. On average, costs related to utilization of healthcare resources were reduced by €1,860.80 per patient per year. CONCLUSIONS: Telemonitoring of patients with COPD combined with home hospitalization may allow for a reduction in healthcare costs, although its usefulness in preventing exacerbations is still unclear.

In vitro activity of micafungin combined with itraconazole against Candida spp.

The in vitro activity of the combination micafungin + itraconazole was evaluated against 105 strains of six species of Candida. The highest percentage of synergy was obtained against Candida albicans (50%) and the lowest against Candida tropicalis (0%).

Undertreatment of human immunodeficiency virus in psychiatric inpatients: a cross-sectional study of seroprevalence and associated factors.

BACKGROUND: The aims of this study were to evaluate the prevalence of HIV and its associated demographic and clinical factors among psychiatric inpatients of a general hospital. METHODS: This was a single-center, observational, cross-sectional study that included patients consecutively admitted to our unit aged 16 years or older and with no relevant cognitive problems. The patients were evaluated using a semistructured interview and an appropriate test for HIV infection. RESULTS: Of the 637 patients who were screened, 546 (86%) who consented to participate were included in the analyses. Twenty-five (4.6%, 95% confidence interval [CI] 3.0-6.8) patients were HIV-positive. The prevalence was higher among patients with substance misuse (17.4%, 95% CI 9.7-28.8). All except one of the 25 patients knew of their seropositive condition prior to participation in the study. Only 14 (56%) of the 25 seropositive patients had previously received pharmacological treatment for their infection. According to the multiple logistic regression analysis, the likelihood of HIV infection was lower in patients with higher levels of education and higher among patients who were single, had history of intravenous drug use, and had an HIV-positive partner, particularly if they did not use condoms. Among the patients with HIV infection, 18 (72%) had a history of suicide attempts compared with 181 (34.7%) of the patients without HIV infection (relative risk 2.1, 95% CI 1.6-2.7; P<0.001). CONCLUSION: HIV infection is highly prevalent in patients admitted to a psychiatric unit, especially those with a diagnosis of substance misuse. Seropositive patients show very poor treatment adherence. The risk of suicide seems to be very high in this population. Implementing interventions to reduce the suicide risk and improve adherence to antiretroviral therapy and psychotropic medications seems crucial.

Bladder endometriosis and endocervicosis: presentation of 2 cases with endoscopic management and review of literature.

Urinary tract endometriosis and endocervicosis are an uncommon pathologic finding, with a common embryological origin. We present 2 cases of female patients with bladder mass. The first one was a finding of a nodular formation in the bladder during study of a nonviable foetus and the second was an incidental finding of a neoformation in the fundus of the bladder during the realization of an ultrasound. In both cases, we performed a surgical management with transurethral resection. Histopathological examination revealed a bladder endometrioma in the first case and endocervicosis with associated endometriosis in the second.

Evaluation of antifungal therapy in a neutropenic murine model of Neoscytalidium dimidiatum infection.

We evaluated the efficacy of amphotericin B (1.5mg/kg/day), voriconazole (60mg/kg/day) and posaconazole (60mg/kg/day) in a murine model of systemic infection caused by Neoscytalidium dimidiatum. All the treatments were able to prolong survival and to reduce the tissue burden in the spleen and kidneys of infected mice. Neither voriconazole nor posaconazole improved the results achieved with amphotericin B.

Microvejiga tras BCG / Microbladder after the BCG therapy

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