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Background: Immune checkpoint inhibitors (ICI) have changed the therapeutic landscape of many solid tumors. Modulation of the intestinal microbiota by antibiotics (Abx) has been suggested to impact on ICI outcomes., Methods: Retrospective analysis of 475 patients with advanced solid tumors treated with ICI from 2015 to 2022. For each patient, the use of Abx was recorded from 1 month before ICI initiation until disease progression or death. The impact of Abx on objective response rates (ORR), disease control rates (DCR), progression-free survival (PFS), and overall survival (OS) was analyzed. Kaplan-Meier and log-rank tests were used to compare survival outcomes., Results: In total 475 patients with advanced solid tumors were evaluated. Median age was 67.5 years and performance status (PS) was 0-1 in 84.6%. 66.5% of patients received Abx during treatment with ICI, mainly beta-lactams (53.8%) and quinolones (35.9%). The early exposure to Abx (from 60 days before to 42 days after the first cycle of ICI) was associated with a lower ORR (27.4% vs 39.4%; P < .01), a lower DCR (37.3% vs 57.4%; P < .001), lower PFS (16.8 m vs 27.8 m; HR 0.66; P < .001]) and lower OS (2.5 m vs 6.6 m; HR 0.68; P = .001]). The negative impact of Abx on OS and PFS was confirmed by a multivariable analysis. This effect was not observed among patients receiving Abx after 6 weeks from ICI initiation., Conclusions: Our results validate the hypothesis of a detrimental effect of an early exposure to Abxon the efficacy of ICI in a multi-tumor cohort of patients., (© The Author(s) 2024. Published by Oxford University Press.)

Metastatic colorectal cancer (mCRC) with mutated BRAF exhibits distinct biological and molecular features that set it apart from other subtypes of CRC. Current standard treatment for these tumors involves a combination of chemotherapy (CT) and VEGF inhibitors. Recently, targeted therapy against BRAF and immunotherapy (IT) for cases with microsatellite instability (MSI) have been integrated into clinical practice. While targeted therapy has shown promising results, resistance to treatment eventually develops in a significant portion of responsive patients. This article aims to review the available literature on mechanisms of resistance to BRAF inhibitors (BRAFis) and potential therapeutic strategies to overcome them.

Background: Global collaboration in cardio-oncology is needed to understand the prevalence of cancer therapy-related cardiovascular toxicity in different risk groups, practice settings, and geographic locations. There are limited data on the socioeconomic and racial/ethnic disparities that may impact access to care and outcomes. To address these gaps, we established the Global Cardio-Oncology Registry, a multinational, multicenter prospective registry., Methods: We assembled cardiologists and oncologists from academic and community settings to collaborate in the first Global Cardio-Oncology Registry. Subsequently, a survey for site resources, demographics, and intention to participate was conducted. We designed an online data platform to facilitate this global initiative., Results: A total of 119 sites responded to an online questionnaire on their practices and main goals of the registry: 49 US sites from 23 states and 70 international sites from 5 continents indicated a willingness to participate in the Global Cardio-Oncology Registry. Sites were more commonly led by cardiologists (85/119; 72%) and were more often university/teaching (81/119; 68%) than community based (38/119; 32%). The average number of cardio-oncology patients treated per month was 80 per site. The top 3 Global Cardio-Oncology Registry priorities in cardio-oncology care were breast cancer, hematologic malignancies, and patients treated with immune checkpoint inhibitors. Executive and scientific committees and specific committees were established. A pilot phase for breast cancer using Research Electronic Data Capture Cloud platform recently started patient enrollment., Conclusions: We present the structure for a global collaboration. Information derived from the Global Cardio-Oncology Registry will help understand the risk factors impacting cancer therapy-related cardiovascular toxicity in different geographic locations and therefore contribute to reduce access gaps in cardio-oncology care. Risk calculators will be prospectively derived and validated., Competing Interests: Disclosures Dr Teske has received speaker fees from Philips and Abbott; consulting from Nordic Pharma. Dr Neilan reports consulting from BMS, Abbvie, Sanofi, Genentech, Roche, and C4-Therapeutics; grant funding from BMS and AZ. Dr López-Fernández has received speaker fees from Philips, Janssen, and Incyte. Dr Szmit has received speaker fees from Amgen, Angelini, Astra Zeneca, Bayer, Bristol-Myers Squibb, Gilead, and Pfizer. Dr Guha is supported by American Heart Association-Strategically Focused Research Network Grant in Disparities in Cardio-Oncology (847740 and 863620). Dr Iakobishvili has received speaker fees from AstraZeneca, Boehringer Ingelheim, Novartis, Pfizer, Novo-Nordisk, and Bayer. Dr Sverdlov is supported by the National Heart Foundation of Australia Future Leader Fellowship (Award ID 106025) and reports research grants from the Medical Research Future Fund (Australia), NSW Health (Australia), Cancer Institute NSW (Australia), Hunter Medical Research Institute (Australia), Biotronik, RACE Oncology, Bristol Myer Squibb, Roche Diagnostics, and Vifor; and personal speaker fees from Novartis, Bayer, Bristol Myer Squibb, AstraZeneca, and Boehringer Ingelheim. The other authors report no conflicts.

There is substantial heterogeneity between different subtypes of sarcoma regarding their biological behavior and microenvironment, which impacts their responsiveness to immunotherapy. Alveolar soft-part sarcoma, synovial sarcoma and undifferentiated pleomorphic sarcoma show higher immunogenicity and better responses to checkpoint inhibitors. Combination strategies adding immunotherapy to chemotherapy and/or tyrosine-kinase inhibitors globally seem superior to single-agent schemes. Therapeutic vaccines and different forms of adoptive cell therapy, mainly engineered TCRs, CAR-T cells and TIL therapy, are emerging as new forms of immunotherapy for advanced solid tumors. Tumor lymphocytic infiltration and other prognostic and predictive biomarkers are under research.

Laura Gochicoa-Rangel, Santiago C. Arce, Carlos Aguirre-Franco, Wilmer Madrid-Mejía, Mónica Gutiérrez-Clavería, Lorena Noriega-Aguirre, Patricia Schonffeldt-Guerrero, Agustín Acuña-Izcaray, Arturo Cortés-Telles, Luisa Martínez-Valdeavellano, Federico Isaac Hernández-Rocha, Omar Ceballos-Zúñiga, Rodrigo Del Rio Hidalgo, Sonia Sánchez, Erika Meneses-Tamayo, and Iván Chérrez-Ojeda; and on Behalf of the Respiratory Physiology Project in COVID-19 (FIRCOV). Effect of altitude on respiratory functional status in COVID-19 survivors: results from a Latin American Cohort-FIRCOV. High Alt Med Biol 24:37-48, 2023. Persistent symptoms and lung function abnormalities are common in COVID-19 survivors. Objectives: To determine the effect of altitude and other independent variables on respiratory function in COVID-19 survivors. Methods: Analytical, observational, cross-sectional cohort study done at 13 medical centers in Latin America located at different altitudes above sea level. COVID-19 survivors were invited to perform pulmonary function tests at least 3 weeks after diagnosis. Results: 1,368 participants (59% male) had mild (20%), moderate (59%), and severe (21%) disease. Restriction by spirometry was noted in 32%; diffusing capacity of the lung for carbon monoxide (DLCO) was low in 43.7%; and 22.2% walked less meters during the 6-minute walk test (6-MWT). In multiple linear regression models, higher altitude was associated with better spirometry, DLCO and 6-MWT, but lower oxygen saturation at rest and during exercise. Men were 3 times more likely to have restriction and 5.7 times more likely to have a low DLCO. Those who had required mechanical ventilation had lower DLCO and walked less during the 6-MWT. Conclusions: Men were more likely to have lower lung function than women, even after correcting for disease severity and other factors. Patients living at a higher altitude were more likely to have better spirometric patterns and walked farther but had lower DLCO and oxygen saturation.

Masticatory myofascial pain disorders (MMPD) are a common group of orofacial pain conditions affecting the muscles of mastication, with headache and cervical disorders as well as chronic widespread pain and psychosocial disorders being common comorbid conditions. As their pathophysiology is multifactorial in nature, a multimodal and interdisciplinary approach should be considered. Overall treatment goals include decreasing pain and disability, increasing mandibular range of motion, and improving quality of life. This article describes a complex case exhibiting common characteristics of MMPD while additionally reviewing the literature on classification, pathophysiology, and evidence-based treatment planning., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bone sarcomas are a heterogeneous group of rare tumors with a predominance in the young population. Few options of systemic treatment are available once they become unresectable and resistant to conventional chemotherapy. A better knowledge of the key role that tyrosine kinase receptors (VEGFR, RET, MET, AXL, PDGFR, KIT, FGFR, IGF-1R) may play in the pathogenesis of these tumors has led to the development of multi-target inhibitors (TKIs) that are progressively being incorporated into our therapeutic arsenal. Osteosarcoma (OS) is the most frequent primary bone tumor and several TKIs have demonstrated clinical benefit in phase II clinical trials (cabozantinib, regorafenib, apatinib, sorafenib, and lenvatinib). Although the development of TKIs for other primary bone tumors is less advanced, preclinical data and early trials have begun to show their potential benefit in advanced Ewing sarcoma (ES) and rarer bone tumors (chondrosarcoma, chordoma, giant cell tumor of bone, and undifferentiated pleomorphic sarcoma). Previous reviews have mainly provided information on TKIs for OS and ES. We aim to summarize the existing knowledge regarding the use of TKIs in all bone sarcomas including the most recent studies as well as the potential synergistic effects of their combination with other systemic therapies.

Metastatic urothelial cancer, associated with a poor prognosis, is still major cause of cancer-related death, with scarce options of effective treatment after progression to platinum-based chemotherapy and immunotherapy. The human epithelial growth factor receptor 2 (Her-2) has been identified as a new therapeutic target in medical oncology. However, despite the encouraging results in breast and gastric cancers, clinical trials with anti-Her-2 monoclonal antibodies and tyrosine-kinase inhibitors have shown limited efficacy of this strategy in urothelial tumors. Notably, more favorable data have been recently shown that antibody-drug conjugates are currently emerging as a novel promising approach for Her-2 targeted therapy in advanced urothelial cancer.

Peripheral blood polymorphonuclear neutrophils (PMNs) forming extracellular traps (NETs), as well as endothelial- and platelet-derived parameters, have been analyzed in patients with SARS-CoV-2 pneumonia, and their prognostic role has been evaluated. Eighty-seven consecutive patients hospitalized with SARS-CoV-2 pneumonia were prospectively selected. A sample of 30 healthy individuals served as the control group. Clinical and oxygenation (oxygen saturation to fraction of inspired oxygen ratio-SpO 2 /FiO 2 ) characteristics and PMNs forming NETs, serum levels of myeloperoxidase, E-selectin, vascular cell adhesion molecule 1-VCAM1-vascular endothelial growth factor, P-selectin, platelet factor 4 and plasma concentrations of D-dimer were evaluated at hospital admission, at discharge and 14 days after discharge. Intensive care unit admission or death was the primary composite endpoint. Patients showed a higher number of PMNs forming NETs than healthy controls. The absolute number of PMNs forming NETs was inversely correlated with oxygen status (SpO 2 /FiO 2 ) and positively with inflammatory (C-reactive protein, ferritin) markers and VCAM1. A decrease in, but not a normalization of NETs and endothelial-derived parameters was observed in patients who survived. In conclusion, the formation of NETs runs parallel to that of other inflammatory and endothelial activation markers, and is inverse to the oxygenation parameters, supporting a pathogenic role for PMNs in this entity.

Fear extinction is not permanent but is instead more vulnerable than the original fear memory, as traditionally shown by the return of fear phenomena. Because of this, techniques to mitigate the return of fear are needed in the clinical treatment of related psychological conditions. One promising strategy is the occasional reinforced extinction treatment, introducing a gradual and sparse number of conditioned stimulus-unconditioned stimulus (CS-US) pairings within the extinction treatment. We present the results of three experiments in which we used a threat conditioning procedure in humans. Our main aim was to evaluate whether occasional reinforced extinction could reduce two different forms of relapse: spontaneous recovery (Experiments 1 and 2) and reinstatement (Experiment 3). Contrary to our predictions and previous literature, the results indicate that an occasional reinforcement treatment did not mitigate relapse compared with standard extinction. From a theoretical standpoint, these results are more consistent with the idea that extinction entails the acquisition of new knowledge than with the idea that there are conditions in which extinction leads to a weakening of the original fear memory. These findings also question the generality of the potential benefits of using occasional reinforced extinction in clinical settings.

Objective: Spain's so-called Stroke Belt is an area with high prevalence of vascular disease. We aimed to determine the prevalence of undetected obstructive sleep apnea-hypopnea syndrome (OSAHS) among patients with acute ischemic stroke (AIS) in southern Spain., Methods: We conducted a cross-sectional study at the Virgen Macarena University Hospital Stroke Unit during 2018 to 2019. We included patients <72 hours after AIS with a neuroimaging lesion and performed sleep tests., Results: Seventy-two patients were included. The median participant age was 72 years. Mean body mass index was 27.07 kg/m 2 , and 40.28% were daily alcohol drinkers. Hypertension, atrial fibrillation, ischemic cardiomyopathy, and previous stroke were detected in 63.9%, 11.1%, 15.3%, and 17.6% of patients, respectively. Polygraphy was feasible in 91.38% of patients. The prevalence of OSAHS was 84.72% (apnea-hypopnea index ≥5). Patients with moderate and severe OSAHS were more likely to be obese and to have a larger neck circumference and facial palsy. The diagnostic criteria of central sleep apnea syndrome were met in only 1.38% of patients., Conclusions: The high prevalence of OSAHS found in the Spanish Stroke Belt justifies further investigation and development of a screening program as a strategy to identify patients with undetected OSAHS.

Radiation therapy is a cornerstone of cancer therapy, with >50% of patients undergoing therapeutic radiation. As a result of widespread use and improved survival, there is increasing focus on the potential long-term effects of ionizing radiation, especially cardiovascular toxicity. Radiation therapy can lead to atherosclerosis of the vasculature as well as valvular, myocardial, and pericardial dysfunction. We present a consensus statement from the International Cardio-Oncology Society based on general principles of radiotherapy delivery and cardiovascular risk assessment and risk mitigation in this population. Anatomical-based recommendations for cardiovascular management and follow-up are provided, and a priority is given to the early detection of atherosclerotic vascular disease on imaging to help guide preventive therapy. Unique management considerations in radiation-induced cardiovascular disease are also discussed. Recommendations are based on the most current literature and represent a unanimous consensus by the multidisciplinary expert panel., Competing Interests: Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002345 as well as by the National Institutes of Health grant R01 HL147884. Dr Mitchell has received research funding from Pfizer, Longer Life Foundation, and Children’s Discovery Institute; and is a consultant for Pfizer (modest). Dr Bergrom has received research support from the Susan G. Komen Foundation and Innovation Pathways. Dr Ferencik has received research support from the National Institutes of Health and the American Heart Association; and is a consultant for Biograph, Inc (unrelated to current work). Dr Szmit has received personal fees from Amgen, Angelini, AstraZeneca, Bayer, Berlin-Chemie, Bristol Myers Squibb, Clinigen, Janssen-Cilag, Pfizer, Polpharma, Roche, and TEVA. Dr Zaha has received support from the Cancer Prevention Research Institute of Texas (RP180404). Dr Herrmann was supported by the National Cancer Institute of the National Institutes of Health (CA233610), the Miami Heart Foundation, and the Mayo Clinic. Dr Nohria has received research funding from Amgen, Inc; and is a consultant for Takeda Oncology and AstraZeneca. Dr Lenihan has received research funding from Myocardial Solutions; and is a consultant for Lilly, Prothena, AstraZeneca, Roche, Clementia, and Eidos (all consultancy renumeration is modest). Dr Dent has received research funding from Novartis; and is a consultant for Novartis and Eli Lilly. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2021 The Authors.)

Objectives: This study's goal was to determine the perceived risks of infection as well as the perceived risks of hospitalization and death from COVID-19 in Ecuador and Kenya. It also assessed the factors associated with the risk-related perceptions., Methods: Cross-sectional studies with samples from the adult populations in both countries were conducted to assess the perceived risks of contracting COVID-19. Data were collected online using the Qualtrics platform (Qualtrics, Provo, Utah, United States) from samples of 1050 heads of households, aged 18 years or older, in each country. A total of 3 statistical analyses were conducted: summary statistics, correlation, and linear regression., Results: The average perceived risks of COVID-19 infection, hospitalization, and death in the Kenyan sample were 27.1%, 43.2%, and 17.2%, respectively, and the values for the Ecuadorian sample were 34%, 32.8%, and 23.3%, respectively. The Pearson's correlation coefficients between the risk measures in each country were less than 0.38. Risk measures were associated with several sociodemographic variables (e.g., income, gender, location), but not with age., Conclusions: The perceived risks of COVID-19 infection, hospitalization, and death in Kenya and Ecuador were significantly higher relative to the statistics reported; however, no strong association existed between perceived risk and age, which is a key factor in adverse health outcomes, including death, among COVID-19 infected individuals.

Given the poor track record to date of animal models for creating cardioprotective drugs, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have been proposed as a therapeutically relevant human platform to guide target validation and cardiac drug development. Mitogen-Activated Protein Kinase Kinase Kinase Kinase-4 (MAP4K4) is an "upstream" member of the MAPK superfamily that is implicated in human cardiac muscle cell death from oxidative stress, based on gene silencing and pharmacological inhibition in hPSC-CMs. A further role for MAP4K4 was proposed in heart muscle cell death triggered by cardiotoxic anti-cancer drugs, given its reported activation in failing human hearts with doxorubicin (DOX) cardiomyopathy, and its activation acutely by DOX in cultured cardiomyocytes. Here, we report successful protection from DOX in two independent hPSC-CM lines, using two potent, highly selective MAP4K4 inhibitors. The MAP4K4 inhibitors enhanced viability and reduced apoptosis at otherwise lethal concentrations of DOX, and preserved cardiomyocyte function, as measured by spontaneous calcium transients, at sub-maximal ones. Notably, in contrast, no intereference was seen in tumor cell killing, caspase activation, or mitochondrial membrane dissipation by DOX, in human cancer cell lines. Thus, MAP4K4 is a plausible, tractable, selective therapeutic target in DOX-induced human heart muscle cell death.

The purpose of the pilot study was twofold, seeking to investigate both the feasibility and preliminary effects of a music therapy intervention on the global cognitive state (attention, immediate and delayed memory, and executive function) and gait parameters (gait velocity, cadence, and right and left stride length) in older adults with mild cognitive impairment (MCI). Sixteen participants attended the one-hour music therapy sessions three times a week for 12 weeks. The intervention was feasible, achieving a retention rate of 84%. Significant effects were found in global cognitive state (p = .001), attention (p = .007), immediate memory (p < .001), delayed memory (p = .001), executive function (p = .002), gait velocity (p = .021), right stride length (p = .007), and left stride length (p = .014). These results suggest that music therapy intervention is a potentially innovative strategy for improving cognition and gait parameters in older adults with MCI., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of "traffic-light" nutritional labeling on the purchase of soft drinks and on their nutritional content in Ecuador., Methods: Two databases were used: the first was provided by Ecuador's National Agency for Health Regulation, Control, and Surveillance; the second was obtained from the international market research company Kantar World Panel. A before/after study was conducted of introducing traffic-light labeling, using Student's t-tests to evaluate changes in average nutritional content and the purchase of soft drinks. Multiple linear regression methods were used to evaluate changes in purchases resulting from the introduction of traffic-light labeling., Results: After labeling, average per capita consumption of soft drinks declined by 0.003 L/month--a small change with respect to average per capita consumption of 1.678 L/month. The results of the Student's t-tests indicated that this difference was not statistically significant. Furthermore, the regression analyses found no empirical evidence that traffic-light labeling affected soft drink consumption. With regard to sugar content, an average reduction of 0.93 gm/100 ml of beverage was observed., Conclusions: No empirical evidence was found that implementation of traffic-light labeling changed soft-drink purchase habits in Ecuador, but there is evidence that it reduced sugar content in carbonated beverages in the country., Competing Interests: Conflictos de interés. Los autores declaran no tener conflictos de interés

Objective: To characterize the etiologies and clinical features at diagnosis of patients with hemophagocytic lymphohistiocytosis (HLH) and correlate these baseline features with survival using an etiopathogenically guided multivariable model., Patients and Methods: The Spanish Group of Autoimmune Diseases HLH Study Group, formed in 2013, is aimed at collecting adult patients with HLH diagnosed in internal medicine departments between January 3, 2013, and October 28, 2017., Results: The cohort consisted of 151 patients (91 men; mean age, 51.4 years). After a mean follow-up of 17 months (range, 1-142 months), 80 patients died. Time-to-event analyses for death identified a worse survival curve for patients with neoplasia ( P <.001), mixed microbiological infections ( P =.02), and more than 1 infection ( P =.01) and glucocorticoid monotherapy ( P =.02). According to univariate analyses, platelets of less than 100,000/mm 3 (hazard ratio [HR], 3.39; 95% CI, 1.37-8.40), leukopenia (HR, 1.81; 95% CI, 1.01-3.23), severe hyponatremia (HR, 1.61; 95% CI, 1.02-2.54), disseminated intravascular coagulation (HR, 1.87; 95% CI, 1.05-3.34), bacterial infection (HR, 1.99; 95% CI, 1.09-3.63), mixed microbiological infections (HR, 3.42; 95% CI, 1.38-8.46), and 2 or more infectious triggers (HR, 2.95; 95% CI, 1.43-6.08) were significantly associated with death. In contrast, peripheral adenopathies (HR, 0.63; 95% CI, 0.40-0.98) and the immunosuppressive drug/intravenous immunoglobulin/biological therapies (HR, 0.44; 95% CI, 0.20-0.96) were protective against all-cause mortality. Multivariable Cox proportional hazards regression analysis identified 2 or more infectious triggers (HR, 3.14; 95% CI, 1.28-7.68) as the only variable independently associated with death., Conclusion: The mortality rate of adult patients diagnosed with HLH exceeds 50%. Infection with more than 1 microbiological agent was the only independent variable associated with mortality irrespective of the underlying disease, epidemiological profile, clinical presentation, and therapeutic management.

Introduction: Reducing the form factor of an implantable cardiac monitor (ICM) may simplify device implant. This study evaluated R-wave sensing at a range of electrode distances and a preferred device implant location without mapping., Methods: Patients scheduled for a Medtronic Reveal® ICM implant (Medtronic Inc., Minneapolis, MN, USA) underwent a preimplant pocket recording using a diagnostic recording catheter. The ICM implant location was left to the discretion of the implanting physician, but a "recommended" position spanned the V2 -V3 electrocardiogram electrode location in an oblique 45° angle. R-wave amplitudes were analyzed from ICM follow-up., Results: Seventeen of 41 subjects (15 male, age 57 ± 16 years) had the maximum surface-filtered R-wave at the recommended location. Fourteen patients underwent diagnostic recording across the range of electrode spacing. There was a strong correlation between the R-wave amplitude and electrode distance (r(2) = 0.97, P < 0.001) with an increase of 29 μV per 2.5 mm. Comparing normalized R-wave distributions between the recommended ICM implant group (Group 1, n = 19) and the remaining patients (Group 2, n = 7), the proportion of ICM R-wave counts of amplitude 0.25-1.2 mV was higher (79% vs 46%, P < 0.05). Of 17 patients in Group 1 who had ≥ 1-month ICM follow-up (79 ± 45 days), no sensing-related false arrhythmia detection was found in 16 (93%) patients., Conclusions: The subcutaneous R-wave amplitude correlates with electrode spacing in the implant zone of ICM patients. Implant locations at the V2 -V3 position at a 45° angle offer an adequate R wave for sensing. Preimplant mapping to achieve acceptable R-wave amplitude may not be necessary., (©2013 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals, Inc.)

Parkinson's disease (PD) is characterized by malfunction of dopaminergic systems, and the current symptomatic treatment is to replace lost dopamine. For investigating mechanisms of pathogenesis and alternative treatments to compensate lack of dopamine (DA) activity in PD, the 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD has been useful, these animals display apomorphine-induced contralateral rotational behavior, when they are examined after lesion. The purpose of this study was to assess Titania-dopamine (TiO2-DA) complexes implanted on the caudate nucleus for diminishing motor behavior alterations of the 6-OHDA rat model. Rats with 6-OHDA unilateral lesions received TiO2 alone or TiO2-DA implants, and were tested for open field (OF) gross motor crossing and rearing behaviors, and apomorphine-induced rotation (G) behavior. TiO2 complex have no effects on rearing OF and G behaviors, and a significant reducing effect on crossing motor behavior of normal rats compared to control non-treated rats throughout 56 days of observation. Interestingly, TiO2-DA treatment significant recovered motor crossing and rearing behaviors in 6-OHDA-lesioned rats, and diminished the G behaviors during 56 days of examination. Additionally, in the 6-OHDA-lesioned rats TiO2 treatment had a moderate recovering effect only on crossing behavior compared to lesioned non treated rats. Our results suggest that continuous release of dopamine in the caudate nucleus from TiO2-DA complex is capable of reversing gross motor deficits observed in the 6-OHDA-lesioned rat model of PD. Thistype of delivery system of DA represents a promising therapy for PD in humans.

An 87-year-old woman was admitted to our hospital with sepsis and foetid vaginal discharge. She presented an abdominal mass that had been present for the last 20 years, refused diagnostic or therapeutic procedures. A computed tomography scan detected a uterine body with multiple calcifications and an internal collection of 10 cm. No other infectious sources were apparent. A tentative diagnostic of pyometra was made and empiric antibiotic treatment was initiated. A hysteroscopy was performed with incomplete drainage of purulent material, due to important vaginal atrophy. In both blood and vaginal fluid cultures Prevotella spp. was isolated. Clinical evolution was favourable with metronidazole. The patient refused a hysterectomy or other surgical drainages, and she was discharged from hospital with oral antibiotics. The patient underwent antibiotic therapy during 1 month; 1 week after finishing this treatment, the patient died. The characteristics of clinical evolution in these last days were not known.