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1.
Braz. j. med. biol. res ; 57: e12857, fev.2024. tab, graf
Article in English | LILACS-Express | LILACS | ID: biblio-1534068

ABSTRACT

Abstract MCH1 is a synthetic macamide that has shown in vitro inhibitory activity on fatty acid amide hydrolase (FAAH), an enzyme responsible for endocannabinoid metabolism. This inhibition can modulate endocannabinoid and dopamine signaling in the nucleus accumbens (NAc), potentially having an antidepressant-like effect. The present study aimed to evaluate the effect of the in vivo administration of MCH1 (3, 10, and 30 mg/kg, ip) in 2-month-old BALB/c male mice (n=97) on forced swimming test (FST), light-dark box (LDB), and open field test (OFT) and on early gene expression changes 2 h after drug injection related to the endocannabinoid system (Cnr1 and Faah) and dopaminergic signaling (Drd1 and Drd2) in the NAc core. We found that the 10 mg/kg MCH1 dose reduced the immobility time compared to the vehicle group in the FST with no effect on anxiety-like behaviors measured in the LDB or OFT. However, a 10 mg/kg MCH1 dose increased locomotor activity in the OFT compared to the vehicle. Moreover, RT-qPCR results showed that the 30 mg/kg MCH1 dose increased Faah gene expression by 2.8-fold, and 10 mg/kg MCH1 increased the Cnr1 gene expression by 4.3-fold compared to the vehicle. No changes were observed in the expression of the Drd1 and Drd2 genes in the NAc at either MCH1 dose. These results indicated that MCH1 might have an antidepressant-like effect without an anxiogenic effect and induces significant changes in endocannabinoid-related genes but not in genes of the dopaminergic signaling system in the NAc of mice.

2.
Braz J Med Biol Res ; 57: e12857, 2024.
Article in English | MEDLINE | ID: mdl-38381881

ABSTRACT

MCH1 is a synthetic macamide that has shown in vitro inhibitory activity on fatty acid amide hydrolase (FAAH), an enzyme responsible for endocannabinoid metabolism. This inhibition can modulate endocannabinoid and dopamine signaling in the nucleus accumbens (NAc), potentially having an antidepressant-like effect. The present study aimed to evaluate the effect of the in vivo administration of MCH1 (3, 10, and 30 mg/kg, ip) in 2-month-old BALB/c male mice (n=97) on forced swimming test (FST), light-dark box (LDB), and open field test (OFT) and on early gene expression changes 2 h after drug injection related to the endocannabinoid system (Cnr1 and Faah) and dopaminergic signaling (Drd1 and Drd2) in the NAc core. We found that the 10 mg/kg MCH1 dose reduced the immobility time compared to the vehicle group in the FST with no effect on anxiety-like behaviors measured in the LDB or OFT. However, a 10 mg/kg MCH1 dose increased locomotor activity in the OFT compared to the vehicle. Moreover, RT-qPCR results showed that the 30 mg/kg MCH1 dose increased Faah gene expression by 2.8-fold, and 10 mg/kg MCH1 increased the Cnr1 gene expression by 4.3-fold compared to the vehicle. No changes were observed in the expression of the Drd1 and Drd2 genes in the NAc at either MCH1 dose. These results indicated that MCH1 might have an antidepressant-like effect without an anxiogenic effect and induces significant changes in endocannabinoid-related genes but not in genes of the dopaminergic signaling system in the NAc of mice.


Subject(s)
Amidohydrolases , Endocannabinoids , Nucleus Accumbens , Mice , Male , Animals , Endocannabinoids/metabolism , Endocannabinoids/pharmacology , Nucleus Accumbens/metabolism , Dopamine/metabolism , Dopamine/pharmacology , Antidepressive Agents/pharmacology , Gene Expression
3.
Clin Oral Implants Res ; 34(9): 987-998, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37416986

ABSTRACT

BACKGROUND: This cross-sectional study aimed to quantify the impact of implant-related complications on perceived pain, functional impairment, concern, quality of life (QoL) and confidence which were the study's primary outcomes. MATERIALS AND METHODS: Patients were recruited in five centres over 19 months. They completed a structured ad hoc questionnaire scoring pain, chewing ability, concern, QoL and confidence in future implant treatment. Some potential independent variables were also recorded. The data were analysed descriptively and with a multiple-stepwise regression model for correlations of the five primary variables with the other data. RESULTS: The sample consisted of 408 patients, with prosthesis mobility being the most common complication (40.7%). Most patients (79.2%) consulted because of a complication, while 20.8% were asymptomatic and consulted regularly. Pain was correlated with symptoms at consultation and in biological/mixed complications (p < .001; R2 = 44.8%). Chewing impairment with implant loss, prosthesis fracture and removable implant-supported or total prostheses (p < .001; R2 = 42.8%); patient concern was correlated with the clinical symptoms and removable implant-supported prostheses (p < .001; R2 = 36.1%); impact on QoL was correlated with implant loss, prosthesis fracture and removable implant-supported prostheses (p < .001; R2 = 41.1%). Patient confidence was relatively independent and only impact on quality of life significantly influenced it (r = 0.73). CONCLUSIONS: Implant-related complications moderately impaired patients' perceptions of pain, chewing ability, concern and QoL. Nevertheless, complications only slightly reduced their confidence in future implant treatment.


Subject(s)
Dental Implants , Humans , Cross-Sectional Studies , Dental Implants/adverse effects , Quality of Life , Pilot Projects , Dental Prosthesis, Implant-Supported , Pain
4.
Animal ; 17(5): 100790, 2023 May.
Article in English | MEDLINE | ID: mdl-37099893

ABSTRACT

Ruminant livestock is a large contributor of CH4 emissions globally. Assessing how this CH4 and other greenhouse gases (GHG) from livestock contribute to anthropogenic climate change is key to understanding their role in achieving any temperature targets. The climate impacts of livestock, as well as other sectors or products/services, are generally expressed as CO2-equivalents using 100-year Global Warming Potentials (GWP100). However, the GWP100 cannot be used to translate emission pathways of short-lived climate pollutants (SLCPs) emissions to their temperature outcomes. A key limitation of handling long- and short-lived gases in the same manner is revealed in the context of any potential temperature stabilisation goals: to achieve this outcome, emissions of long-lived gases must decline to net-zero, but this is not the case for SLCPs. A recent alternative metric, GWP* (so-called 'GWP-star'), has been proposed to overcome these concerns. GWP* allows for simple appraisals of warming over time for emission series of different GHGs that may not be obvious if using pulse-emission metrics (i.e. GWP100). In this article, we explore some of the strengths and limitations of GWP* for reporting the contribution of ruminant livestock systems to global temperature change. A number of case studies are used to illustrate the potential use of the GWP* metric to, for example, understand the current contribution of different ruminant livestock production systems to global warming, appraise how different production systems or mitigations compare (having a temporal element), and seeing how possible emission pathways driven by changes in production, emissions intensity and gas composition show different impacts over time. We suggest that for some contexts, particularly if trying to directly infer contributions to additional warming, GWP* or similar approaches can provide important insight that would not be gained from conventional GWP100 reporting.


Subject(s)
Greenhouse Effect , Livestock , Animals , Livestock/metabolism , Biodiversity , Temperature , Methane/metabolism , Global Warming , Gases/analysis , Nitrous Oxide/analysis , Nitrous Oxide/metabolism , Carbon Dioxide/analysis , Soil
7.
Rev. med. Chile ; 150(8): 1108-1114, ago. 2022. ilus, graf
Article in Spanish | LILACS | ID: biblio-1431863

ABSTRACT

We report 67-year-old woman with a sinus node dysfunction and diffuse conduction system disease, with a history of recurrent paroxysmal atrial fibrillation. She was admitted to the Hospital due to palpitations, dizziness, and vertigo, attributing the symptoms to the rhythm disorder described, for which the implantation of a pacemaker was indicated. With a history of tracheal cancer treated with radio and chemotherapy, and chronic steroid therapy for rheumatoid arthritis, she had an important limitation in vascular access for a conventional pacemaker, so, added to a high risk of infection, a decision was made to implant a leadless pacemaker. We discuss the electrocardiographic and clinical manifestations of sinus node disease, its relationship with oncological treatment and the indication for a permanent pacemaker, highlighting the characteristics of this new modality of artificial cardiac stimulation, for a special type of patients.


Subject(s)
Male , Female , Aged , Pacemaker, Artificial , Atrial Fibrillation , Treatment Outcome , Electrocardiography
8.
J Hosp Infect ; 126: 70-77, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35594988

ABSTRACT

BACKGROUND: The incidence of catheter-related bloodstream infections (CRBSIs) has fallen over the last decade, especially in intensive care units (ICUs). AIM: To assess the existence of concomitant trends in outcomes and to analyse the current risk factors for mortality. METHODS: A multicentre retrospective cohort study was conducted at 24 Catalan hospitals participating in the Surveillance of healthcare-associated infections in Catalonia (VINCat). All hospital-acquired CRBSI episodes diagnosed from January 2010 to December 2019 were included. A common protocol including epidemiological, clinical, and microbiological data was prospectively completed. Mortality at 30 days after bacteraemia onset was analysed using the Cox regression model. FINDINGS: Over the study period, 4795 episodes of CRBSI were diagnosed. Among them, 75% were acquired in conventional wards and central venous catheters were the most frequently involved (61%). The 30-day mortality rate was 13.8%, presenting a significant downward trend over the study period: from 17.9% in 2010 to 10.6% in 2019 (hazard ratio (HR): 0.95; 95% confidence interval (CI): 0.92-0.98). The multivariate analysis identified age (HR: 1.03; 95% CI: 1.02-1.04), femoral catheter (1.78; 1.33-2.38), medical ward acquisition (2.07; 1.62-2.65), ICU acquisition (3.45; 2.7-4.41), S. aureus (1.59; 1.27-1.99) and Candida sp. (2.19; 1.64-2.94) as risk factors for mortality, whereas the mortality rate associated with episodes originating in peripheral catheters was significantly lower (0.69; 0.54-0.88). CONCLUSION: Mortality associated with CRBSI has fallen in recent years but remains high. Intervention programmes should focus especially on ICUs and medical wards, where incidence and mortality rates are highest.


Subject(s)
Bacteremia , Catheter-Related Infections , Central Venous Catheters , Bacteremia/epidemiology , Bacteremia/microbiology , Catheter-Related Infections/microbiology , Central Venous Catheters/adverse effects , Hospitals , Humans , Incidence , Retrospective Studies , Staphylococcus aureus
9.
Rev Med Chil ; 150(8): 1108-1114, 2022 Aug.
Article in Spanish | MEDLINE | ID: mdl-37358159

ABSTRACT

We report 67-year-old woman with a sinus node dysfunction and diffuse conduction system disease, with a history of recurrent paroxysmal atrial fibrillation. She was admitted to the Hospital due to palpitations, dizziness, and vertigo, attributing the symptoms to the rhythm disorder described, for which the implantation of a pacemaker was indicated. With a history of tracheal cancer treated with radio and chemotherapy, and chronic steroid therapy for rheumatoid arthritis, she had an important limitation in vascular access for a conventional pacemaker, so, added to a high risk of infection, a decision was made to implant a leadless pacemaker. We discuss the electrocardiographic and clinical manifestations of sinus node disease, its relationship with oncological treatment and the indication for a permanent pacemaker, highlighting the characteristics of this new modality of artificial cardiac stimulation, for a special type of patients.


Subject(s)
Atrial Fibrillation , Pacemaker, Artificial , Female , Humans , Aged , Treatment Outcome , Electrocardiography
10.
J Oral Maxillofac Surg ; 80(3): 490-500, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34762850

ABSTRACT

PURPOSE: There is no agreement in the literature on whether inferior alveolar nerve block (IANB) or infiltration (INF) is the anesthetic technique of choice for placing implants in the posterior mandible. This study aimed to compare the efficacy of the 2 techniques using articaine 4% with epinephrine 1:100,000. MATERIAL AND METHODS: The trial was a comparison between 2 parallel groups of patients, who received implants distal to the mental foramen, either with IANB or INF. The anesthetic technique was the predictor variable. The primary outcome was patients' perceived pain by a numerical rating scale (NRS) in incision, osteotomy and suture. The secondary outcome, patients' satisfaction, was equally recorded 12 hours after surgery. The dataset were first analyzed by descriptive statistics. Then, Mann-Whitney test, Spearman's coefficient, and regression models were used. This trial followed the recommendations of the Consort Statement for reporting randomized controlled trials (RCTs). RESULTS: Ninety-six patients (41 men, 55 women, mean age 55.76 years) were randomly assigned to either group, IANB or INF, of 48 patients each. Only 20% of patients reported pain values >0 (range 0-4 of 10). Medians were: 0 (0-0) for both groups (P = .956, .175 and .908, incision, osteotomy and suture, respectively). Mean satisfaction was high in both groups, 9.0 ± 1.0, median 10; and 8.8 ± 1.7, median 9, for IANB and INF (P = .695). Hence, the anesthetic technique did not generate statistically significant differences. Five potential influencing variables that were measured did not significantly affect pain levels or patient satisfaction in either group. CONCLUSIONS: According to the results, an IANB might not be necessary for standard implant surgery in the posterior mandible, and infiltration of articaine 4% with epinephrine 1:100,000 appears to be sufficient. Further research is needed to check if these results are extensible to other anesthetic drugs.


Subject(s)
Anesthesia, Dental , Dental Implants , Nerve Block , Pulpitis , Anesthesia, Dental/methods , Anesthetics, Local , Carticaine , Double-Blind Method , Female , Humans , Male , Mandible/surgery , Mandibular Nerve , Middle Aged , Molar/surgery , Nerve Block/methods , Prospective Studies , Pulpitis/surgery
11.
Rev Med Chil ; 149(6): 939-944, 2021 Jun.
Article in Spanish | MEDLINE | ID: mdl-34751355

ABSTRACT

We report a 20-year-old male athlete who while running, presented a sudden death due to ventricular fibrillation. He was successfully rescued by cardiopulmonary resuscitation maneuvers and an automatic external defibrillator. Without evidence of structural heart disease, Brugada syndrome was diagnosed as the cause, after which a subcutaneous implantable cardioverter defibrillator was indicated. We discuss the subject of sudden cardiac death in athletes and its unusual relationship with exercise in this channelopathy.


Subject(s)
Brugada Syndrome , Cardiopulmonary Resuscitation , Defibrillators, Implantable , Adult , Arrhythmias, Cardiac , Brugada Syndrome/complications , Brugada Syndrome/diagnosis , Death, Sudden, Cardiac/etiology , Humans , Male , Young Adult
12.
PLoS One ; 16(10): e0255481, 2021.
Article in English | MEDLINE | ID: mdl-34673786

ABSTRACT

The aim of this study was to assess the potential use of a new advanced inertial navigation system for guiding dental implant placement and to compare this approach with standard stereolithographic template guiding. A movement processing unit with a 9-axis absolute orientation sensor was adapted to a surgical handpiece and wired to a computer navigation interface. Sixty implants were placed by 10 operators in 20 jaw models. The 30 implants of the test group were placed in 10 models guided by the new inertial navigation prototype. The 30 implants of the control group were placed in another 10 models using a CAD-CAM template. Both groups were subdivided into experienced and non-experienced operators. Pre- and postoperative computer tomography images were obtained and matched to compare the planned and final implant positions. Four deviation parameters (global, angular, depth, and lateral deviation) were defined and calculated. The primary outcome was the angular deviation between the standard stereolithographic approach and the new inertial navigation system. Results showed no significant differences between both groups, suggesting that surgical navigation based on inertial measurement units (IMUs) could potentially be useful for guiding dental implant placement. However, more studies are still needed to translate this new approach into clinical practice.


Subject(s)
Dental Implantation/methods , Dental Implants , Mandible/surgery , Models, Anatomic , Surgery, Computer-Assisted/methods , Cone-Beam Computed Tomography/methods , Dental Implantation/instrumentation , Humans , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods
13.
Rev. méd. Chile ; 149(6): 939-944, jun. 2021. ilus
Article in Spanish | LILACS | ID: biblio-1389533

ABSTRACT

We report a 20-year-old male athlete who while running, presented a sudden death due to ventricular fibrillation. He was successfully rescued by cardiopulmonary resuscitation maneuvers and an automatic external defibrillator. Without evidence of structural heart disease, Brugada syndrome was diagnosed as the cause, after which a subcutaneous implantable cardioverter defibrillator was indicated. We discuss the subject of sudden cardiac death in athletes and its unusual relationship with exercise in this channelopathy.


Subject(s)
Humans , Male , Adult , Young Adult , Cardiopulmonary Resuscitation , Defibrillators, Implantable , Brugada Syndrome/complications , Brugada Syndrome/diagnosis , Arrhythmias, Cardiac , Death, Sudden, Cardiac/etiology
14.
ESMO Open ; 6(3): 100157, 2021 06.
Article in English | MEDLINE | ID: mdl-34015642

ABSTRACT

BACKGROUND: Studies evaluating the effects of the COVID-19 pandemic on public healthcare systems are limited, particularly in cancer management. As no such studies have been carried out in Spain, our objective is to describe and quantify the impact of the COVID-19 pandemic on cancer patients in Spanish hospitals during the first wave of the pandemic. MATERIALS AND METHODS: This retrospective, multicenter, nationwide study collected information from hospital departments treating oncology patients. An electronic questionnaire comparing outcomes and management of oncohematological patients for the March-June 2019 and March-June 2020 periods was used. RESULTS: Information from 78 departments (36 tertiary hospitals) was analyzed. Forty-four departments implemented adapted protocols during March 2020. Most of these (n = 38/44; 86.4%) carried out COVID-19 triage, while 26 of 44 (59.1%) carried out onsite polymerase chain reaction tests for clinically suspected cases. A shift from in-person to telephone visits was observed in 43 of 44 (97.7%) departments. Comparing the March-June 2019 and March-June 2020 periods, the number of new patients decreased by 20.8% (from 160.2 to 126.4). Decreases were also seen in the mean number of total (2858.2 versus 1686.1) and cancer (465.5 versus 367.2) biopsies, as well as the mean number of bone marrow biopsies (30.5 versus 18.6). Concerning the number of patients visiting specific cancer care departments, a decrease from 2019 to 2020 was seen for mean number of chemotherapy treatments (712.7 versus 643.8) and radiation therapy (2169.9 versus 2139.9). Finally, a reduction from 2019 to 2020 of 12.9% (from 8.6 to 7.4) in the mean number of patients included in clinical trials was noted. CONCLUSIONS: This study provides the first comprehensive data concerning the impact of COVID-19 on cancer care in Spain. The pandemic caused a 20.8% decrease in newly diagnosed patients, which may impact future outcomes. Measures must be taken to ensure cancer management receives priority in times of healthcare emergencies.


Subject(s)
COVID-19 , Neoplasms , Humans , Pandemics , Retrospective Studies , SARS-CoV-2 , Spain
15.
Sleep Disord ; 2018: 1968985, 2018.
Article in English | MEDLINE | ID: mdl-30515336

ABSTRACT

OBJECTIVE: To determine the prevalence of respiratory complications in the early postoperative period of children with sleep apnea who required adenotonsillectomy at a tertiary pediatric hospital and to establish recommendations for postoperative monitoring. METHODS: Retrospective cohort study of children with obstructive sleep apnea (OSA) diagnosed by polysomnogram (PSG), who underwent adenotonsillectomy for treatment of OSA. The prevalence of respiratory complications in the first 24 postoperative hours was measured. Patients with craniofacial malformations, obesity, and severe cardiovascular comorbidities were excluded. The prevalence of postoperative respiratory complications was compared with the severity of OSA according to the Apnea Hypopnea Index (AHI) and NADIR. All data were taken in patients residing in Bogotá city, Colombia, at 2.640 meters above sea level (m.a.s.l). RESULTS: Between May 2014 and February 2017, 167 patients (108 males) required adenotonsillectomy for OSA, with an age range of 1 and 15 years (mean 5.3 years +/- 2.7). The prevalence of postoperative respiratory complications was 3.59% (6/167). There was a statistically significant relationship between the presence of respiratory complication and AHI greater than 44/h (p <0.04). There was an inverse correlation between the AHI and NADIR values. Risk groups of patients younger than 3 years and NADIR less than 70% had a higher prevalence of respiratory complications; however, this correlation was not statistically significant (p <0.08 and 0.89, respectively). CONCLUSIONS: The prevalence of respiratory complications in OSA patients undergoing adenotonsillectomy in high altitudes is similar to that reported in other heights. Preoperative AHI greater than 44/h could be considered a risk factor for early respiratory complication. We suggest ambulatory management after 6 hours in Postanesthetic Care Unit (PACU) observation in patients older than 3 years, with AHI less than 44/h and NADIR greater than 70% in altitudes higher than 2.500 m.a.s.l. Further research must be done to confirm this hypothesis.

16.
Case Rep Dent ; 2018: 9014372, 2018.
Article in English | MEDLINE | ID: mdl-30026988

ABSTRACT

A case of rehabilitation of the upper front teeth is presented. To prevent bone resorption following extractions, a socket-shield technique on all the extracted teeth was performed. The combination of a staged extraction approach, the sequence of provisionals together with the minimal bone loss of vestibular volume, allowed solving this high aesthetic demanding case in a satisfactory way for the patient both in duration of the treatment and in its final outcome.

17.
Eur J Clin Microbiol Infect Dis ; 35(8): 1269-76, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27180242

ABSTRACT

Switching from intravenous to oral antibiotic therapy may improve inpatient management and reduce hospital stays and the complications of intravenous treatment. We aimed to assess the effectiveness of intravenous-to-oral antibiotic switch therapy and an early discharge algorithm in hospitalized patients with gram-positive infection. We performed a prospective cohort study with a retrospective comparison cohort, recruited from eight tertiary, acute-care Spanish referral hospitals. All patients included had culture-confirmed methicillin-resistant gram-positive infection, or methicillin-susceptible gram-positive infection and beta-lactam allergy and had received intravenous treatment with glycopeptides, lipopeptides, or linezolid. The study comprised two cohorts: the prospective cohort to assess the effectiveness of a sequential intravenous-to-oral antibiotic switch algorithm and early discharge, and a retrospective cohort in which the algorithm had not been applied, used as the comparator. A total of 247 evaluable patients were included; 115 in the prospective and 132 in the retrospective cohort. Forty-five retrospective patients (34 %) were not changed to oral antibiotics, and 87 (66 %) were changed to oral antibiotics without following the proposed algorithm. The duration of hospitalization was significantly shorter in the prospective cohort compared to the retrospective group that did not switch to oral drugs (16.7 ± 18.7 vs 23 ± 13.4 days, P < 0.001). No differences were observed regarding the incidence of catheter-related bacteraemia (4.4 % vs 2.6 %, P = 0.621). Our results suggest that an intravenous-to-oral antibiotic switch strategy is effective for reducing the length of hospital stay in selected hospitalized patients with gram-positive infection.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Gram-Positive Bacterial Infections/drug therapy , Administration, Intravenous , Administration, Oral , Aged , Aged, 80 and over , Female , Gram-Positive Bacterial Infections/epidemiology , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , Spain , Treatment Outcome
18.
Prostate Cancer Prostatic Dis ; 19(1): 28-34, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26754263

ABSTRACT

BACKGROUND: Novel predictors of prognosis and treatment response for prostate cancer (PCa) are required to better individualize treatment. Single-nucleotide polymorphisms (SNPs) in four genes directly (XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5) and XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)) or indirectly (PARP1 and major vault protein (MVP)) involved in non-homologous end joining were examined in 494 Spanish PCa patients. METHODS: A total of 22 SNPs were genotyped in a Biotrove OpenArray NT Cycler. Clinical tumor stage, diagnostic PSA serum levels and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator. RESULTS: (XRCC6) rs2267437 appeared as a risk factor for developing more aggressive PCa tumors. Those patients carrying the GG genotype were at higher risk of developing bigger tumors (odds ratio (OR)=2.04, 95% confidence interval (CI) 1.26-3.29, P=0.004), present higher diagnostic PSA levels (OR=2.12, 95% CI 1.19-3.78, P=0.011), higher Gleason score (OR=1.65, 95% CI 1.01-2.68, P=0.044) and D'Amico higher risk tumors (OR=2.38, 95% CI 1.24-4.58, P=0.009) than those patients carrying the CC/CG genotypes. Those patients carrying the (MVP) rs3815824 TT genotype were at higher risk of presenting higher diagnostic PSA levels (OR=4.74, 95% CI 1.40-16.07, P=0.013) than those patients carrying the CC genotype. When both SNPs were analyzed in combination, those patients carrying the risk genotypes were at higher risk of developing D'Amico higher risk tumors (OR=3.33, 95% CI 1.56-7.17, P=0.002). CONCLUSIONS: We believe that for the first time, genetic variants at XRCC6 and MVP genes are associated with risk of more aggressive disease, and would be taken into account when assessing the malignancy of PCa.


Subject(s)
Antigens, Nuclear/genetics , DNA-Binding Proteins/genetics , Genetic Association Studies , Prostatic Neoplasms/genetics , Vault Ribonucleoprotein Particles/genetics , DNA Breaks, Double-Stranded , DNA Helicases/genetics , DNA Repair/genetics , Genetic Predisposition to Disease , Genotype , Humans , Ku Autoantigen , Male , Neoplasm Grading , Neoplasm Staging , Poly (ADP-Ribose) Polymerase-1 , Poly(ADP-ribose) Polymerases/genetics , Polymorphism, Single Nucleotide , Prostatic Neoplasms/pathology , Risk Factors
19.
BMJ Open ; 5(3): e006723, 2015 Mar 11.
Article in English | MEDLINE | ID: mdl-25762232

ABSTRACT

INTRODUCTION: Despite the availability of new antibiotics such as daptomycin, methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia continues to be associated with high clinical failure rates. Combination therapy has been proposed as an alternative to improve outcomes but there is a lack of clinical studies. The study aims to demonstrate that combination of daptomycin plus fosfomycin achieves higher clinical success rates in the treatment of MRSA bacteraemia than daptomycin alone. METHODS AND ANALYSIS: A multicentre open-label, randomised phase III study. Adult patients hospitalised with MRSA bacteraemia will be randomly assigned (1:1) to group 1: daptomycin 10 mg/kg/24 h intravenous; or group 2: daptomycin 10 mg/kg/24 h intravenous plus fosfomycin 2 gr/6 g intravenous. The main outcome will be treatment response at week 6 after stopping therapy (test-of-cure (TOC) visit). This is a composite variable with two values: Treatment success: resolution of clinical signs and symptoms (clinical success) and negative blood cultures (microbiological success) at the TOC visit. Treatment failure: if any of the following conditions apply: (1) lack of clinical improvement at 72 h or more after starting therapy; (2) persistent bacteraemia (positive blood cultures on day 7); (3) therapy is discontinued early due to adverse effects or for some other reason based on clinical judgement; (4) relapse of MRSA bacteraemia before the TOC visit; (5) death for any reason before the TOC visit. Assuming a 60% cure rate with daptomycin and a 20% difference in cure rates between the two groups, 103 patients will be needed for each group (α:0.05, ß: 0.2). Statistical analysis will be based on intention to treat, as well as per protocol and safety analysis. ETHICS AND DISSEMINATION: The protocol was approved by the Spanish Medicines and Healthcare Products Regulatory Agency (AEMPS). The sponsor commits itself to publishing the data in first quartile peer-review journals within 12 months of the completion of the study. TRIAL REGISTRATION NUMBER: NCT01898338.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Daptomycin/therapeutic use , Fosfomycin/therapeutic use , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections/drug therapy , Adolescent , Adult , Bacteremia/microbiology , Drug Combinations , Humans , Methicillin-Resistant Staphylococcus aureus/growth & development , Microbial Sensitivity Tests , Research Design , Staphylococcal Infections/microbiology , Treatment Outcome
20.
Sci Total Environ ; 505: 1191-201, 2015 Feb 01.
Article in English | MEDLINE | ID: mdl-25461117

ABSTRACT

This paper presents an alternative approach to assess the impacts of biofuel production using a method integrating the simulated values of a new semi-empirical model at the crop production stage within a life cycle assessment (LCA). This new approach enabled us to capture some of the effects that climatic conditions and crop management have on soil nitrous oxide (N2O) emissions, crop yields and other nitrogen (N) losses. This analysis considered the whole system to produce 1 MJ of biofuel (bioethanol from wheat and biodiesel from rapeseed). Non-renewable energy use, global warming potential (GWP), acidification, eutrophication and land competition are considered as potential environmental impacts. Different co-products were handled by system expansion. The aim of this study was (i) to evaluate the variability due to site-specific conditions of climate and fertiliser management of the LCA of two different products: biodiesel from rapeseed and bioethanol from wheat produced in the Basque Country (Northern Spain), and (ii) to improve the estimations of the LCA impacts due to N losses (N2O, NO3, NH3), normally estimated with unspecific emission factors (EFs), that contribute to the impact categories analysed in the LCA of biofuels at local scale. Using biodiesel and bioethanol derived from rapeseed and wheat instead of conventional diesel and gasoline, respectively, would reduce non-renewable energy dependence (-55%) and GWP (-40%), on average, but would increase eutrophication (42 times more potential). An uncertainty analysis for GWP impact showed that the variability associated with the prediction of the major contributor to global warming potential (soil N2O) can significantly affect the results from the LCA. Therefore the use of a model to account for local factors will improve the precision of the assessment and reduce the uncertainty associated with the convenience of the use of biofuels.


Subject(s)
Biofuels , Conservation of Natural Resources/methods , Crops, Agricultural/growth & development , Nitrogen , Global Warming , Greenhouse Effect , Models, Theoretical , Spain
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