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International audience; Spatial changes of fatty acids in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids, EPA-containing triglycerides, DHA-containing phospholipids, or DHA-containing triglycerides. Qualitative changes in fatty acid composition of plasma, erythrocytes and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) species in retina were determined by liquid chromatography coupled to tandem mass spectrometry and MALDI (Matrix Assisted Laser Desorption Ionization) coupled to mass spectrometry imaging. The omega-3 content in the lipids of plasma and erythrocytes suggests that phospholipids as well as triglycerides are good omega-3 carriers for retina. However, a significant increase in DHA content in retina was observed, especially molecular species as di-DHA-containing PC and PE, as well as an increase in very long chain polyunsaturated fatty acids (VLC-PUFAs, more than 28 carbons) following phospholipid-EPA and triglyceride-DHA diets only. All supplemented diets triggered spatial organization changes of DHA in the photoreceptor layer around the optic nerve. Taken together, these findings suggest that dietary omega-3 supplementation can modify the content of fatty acids in the rat retina.

BACKGROUND The diagnosis of invasive aspergillosis (IA) can be problematic in solid organ transplantation (SOT). The prognosis greatly varies according to the type of transplant, and the impact of prophylaxis is not well defined. PATIENTS AND METHODS The Diaspersot cohort analyses the impact of IA in SOT in Spain during the last 10 years. Proven and probable/putative IA was included. RESULTS We analysed 126 cases of IA. The incidences of IA were as follows: 6.5%, 2.9%, 1.8% and 0.6% for lung, heart, liver and kidney transplantation, respectively. EORTC/MSG criteria confirmed only 49.7% of episodes. Tree-in-bud sign or ground-glass infiltrates were present in 56.3% of patients, while serum galactomannan (optical density index >0.5) was positive in 50.6%. A total of 41.3% received combined antifungal therapy. Overall mortality at 3 months was significantly lower (p

Urinary tract infections (UTI) are one of the most common infections in solid organ transplant (SOT) recipients. A systematic review was performed to assess the management of UTI in SOT recipients. Recommendations are provided on the management of asymptomatic bacteriuria, and prophylaxis and treatment of UTI in SOT recipients. The diagnostic-therapeutic management of recurrent UTI and the role of infection in kidney graft rejection or dysfunction are reviewed. Finally, recommendations on antimicrobials and immunosuppressant interactions are also included.

The orbitofrontal cortex (OFC) is known to play a crucial role in learning the consequences of specific events. However, the contribution of OFC thalamic inputs to these processes is largely unknown. Using a tract-tracing approach, we first demonstrated that the submedius nucleus (Sub) shares extensive reciprocal connections with the OFC. We then compared the effects of excitotoxic lesions of the Sub or the OFC on the ability of rats to use outcome identity to direct responding. We found that neither OFC nor Sub lesions interfered with the basic differential outcomes effect. However, more specific tests revealed that OFC rats, but not Sub rats, were disproportionally relying on the outcome, rather than on the discriminative stimulus, to guide behavior, which is consistent with the view that the OFC integrates information about predictive cues. In subsequent experiments using a Pavlovian contingency degradation procedure, we found that both OFC and Sub lesions produced a severe deficit in the ability to update Pavlovian associations. Altogether, the submedius therefore appears as a functionally relevant thalamic component in a circuit dedicated to the integration of predictive cues to guide behavior, previously conceived as essentially dependent on orbitofrontal functions.SIGNIFICANCE STATEMENTIn the present study, we identify a largely unknown thalamic region, the submedius nucleus, as a new functionally relevant component in a circuit supporting the flexible use of predictive cues. Such abilities were previously conceived as largely dependent on the orbitofrontal cortex. Interestingly, this echoes recent findings in the field showing, in research involving an instrumental setup, an additional involvement of another thalamic nuclei, the parafascicular nucleus, when correct responding requires an element of flexibility (Bradfield et al., 2013a). Therefore, the present contribution supports the emerging view that limbic thalamic nuclei may contribute critically to adaptive responding when an element of flexibility is required after the establishment of initial learning.

Tuberculosis (TB) is one of the most significant infections in immunosuppressed patients due to its high frequency and high morbidity and mortality. TB is the leading cause of death among HIV-infected patients. The diagnosis and early treatment of latent tuberculosis infection is vital to preventing it progression to disease. Similarly, the early diagnosis of TB is key to improving the prognosis of patients and preventing its transmission. The clinical expression of TB in immunosuppressed patients is conditioned by the patient's degree of immunosuppression. It is important to keep this peculiarity in mind so as not to delay the diagnosis of suspected TB. TB treatment is basically the same in immunosuppressed patients as in the general population and any differences mainly derive from pharmacological interactions. We examined the diagnosis and treatment of TB and latent tuberculosis infection in immunosuppressed patients.

Objective Previous studies on monitoring of post-transplant cytomegalovirus (CMV)-specific cell-mediated immunity (CMI) are limited by single-centre designs and disparate risk categories. We aimed to assess the clinical value of a regular monitoring strategy in a large multicentre cohort of intermediate-risk kidney transplant (KT) recipients. Methods We recruited 124 CMV-seropositive KT recipients with no T-cell-depleting induction pre-emptively managed at four Spanish institutions. CMV-specific interferon-γ-producing CD4+ and CD8+ T cells were counted through the first post-transplant year by intracellular cytokine staining after stimulation with pp65 and immediate early-1 peptides (mean of six measurements per patient). The primary outcome was the occurrence of any CMV event (asymptomatic infection and/or disease). Optimal cut-off values for CMV-specific T cells were calculated at baseline and day 15. Results Twelve-month cumulative incidence of CMV infection and/or disease was 47.6%. Patients with pre-transplant CMV-specific CD8+ T-cell count Conclusions Monitoring for CMV-specific CMI in intermediate-risk KT recipients must be regular to reflect dynamic changes in overall immunosuppression and individual susceptibility. The early assessment at post-transplant day 15 remains particularly informative.

Background It is necessary to determine the incidence and risk factors for tuberculosis (TB), as well as strategies to assess and treat latent tuberculosis infection (LTBI) in lung transplant recipients. Methods A retrospective cohort study of 398 lung transplant recipients was performed. Episodes of TB were studied and the incidence rate was calculated. Logistic regression analysis was used to analyze specific variables as potential risk factors for TB. Results Median follow-up was 558 days (range 1-6636). Six cases (1.5%) of TB were documented in 398 transplant patients. The incidence density of TB was 406.3 cases/10(5) patient-years (95% confidence interval [CI] 164.7-845), which is higher than in the general population (13.10 cases/10(5) person-years). All cases occurred in the period 1993-2006, when the tuberculin skin test (TST) and treatment of LTBI in positive TST patients were not part of the protocol. Pretransplant computed tomography (CT) showed residual lesions in 50% of patients who developed TB, although the TST was negative and the chest radiograph was inconclusive. Multivariate analysis identified the presence of residual lesions in the pretransplant chest CT (odds ratio [OR] 11.5, 95% CI 1.9-69.1, P = 0.008), use of azathioprine (OR 10.6, 95% CI 1.1-99.1, P = 0.038), and use of everolimus (OR 6.7, 95% CI 1.1-39.8, P = 0.036) as independent risk factors for TB. Conclusions Residual lesions in the pretransplant chest CTs and the use of azathioprine and mTOR inhibitors are associated with the risk of TB.

A multicenter, comparative study was performed to determine the epidemiological, clinical, and prognostic differences between the diseases caused by Mycobacterium tuberculosis and Mycobacterium kansasii in human immunodeficiency virus (HIV)-infected patients. From 1 January 1995 through 31 December 1999, 25 HIV-infected patients received diagnoses of M. kansasii infection, and another 75 were selected as control subjects from among patients who had M. tuberculosis infection. Variables associated with M. tuberculosis disease in the multivariate analysis were previous intravenous drug use (odds ratio [OR], 8; 95% confidence interval [CI], 1.5-41.4) and interstitial radiologic pattern (OR, 12.7; 95% CI, 1.7-94.3). Variables associated with M. kansasii were previous diagnosis of acquired immunodeficiency syndrome (OR, 15.8; 95% CI, 4.2-59.6) and concomitant opportunistic infections (OR, 14.2; 95% CI, 2-105.7). Clinical and radiologic features were similar for both groups, but epidemiological characteristics and prognosis were different. M. kansasii disease was associated more closely with level of immunosuppression and progression of HIV infection than was disease caused by M. tuberculosis.

Background. It is necessary to develop a safe alternative to isoniazid for tuberculosis prophylaxis in liver trans-plant recipients. This study was designed to investigate the efficacy and safety of levofloxacin.Methods. An open-label, prospective, multicenter, randomized study was conducted to compare the efficacyand safety of levofloxacin (500 mg q24h for 9 months) initiated in patients awaiting liver transplantation and iso-niazid (300 mg q24h for 9 months) initiated post-transplant when liver function was stabilized. Efficacy was mea-sured by tuberculosis incidence at 18 months after transplantation. All adverse events related to the medication wererecorded.Results. CONSORT guidelines were followed in order to present the results. The safety committee suspendedthe study through a safety analysis when 64 patients had been included (31 in the isoniazid arm and 33 in the levo-floxacinarm).Thereasonforsuspensionwasanunexpectedincidenceofseveretenosynovitisinthelevofloxacinarm(18.2%). Although the clinical coursewas favorable in all cases, tenosynovitis persisted for 7 weeks in some patients.No patients treated with isoniazid, developed tenosynovitis. Only 32.2% of patients randomized to isoniazid (10/31)and 54.5% of patients randomized to levofloxacin (18/33, P=.094) completed prophylaxis. No patient developedtuberculosis during the study follow-up (median 270 days).Conclusions. Levofloxacin prophylaxis of tuberculosis in liver transplant candidates is associated with a highincidence of tenosynovitis that limits its potential utility.Keywords. tuberculosis; levofloxacin; tenosynovitis; investigator-driven clinical trial.Less than 30% of liver transplant recipients with a pos-itivetuberculinpurifiedproteinderivate(PPD)skintestcurrently receive prophylaxis with isoniazid because ofits potential hepatotoxicity [1–3],which can destabilizechronic liver diseasewhen used in the pretransplant pe-riod. For this reason some experts recommend that iso-niazid prophylaxis should not be initiated until aftertransplantation when liver function is stable [1–3].However, the prophylaxis with isoniazid is frequentlynever initiated or discontinued due to the elevation oftransaminase levels. In fact, some experts believe that,in this scenario, the risks of using isoniazid outweighits potential benefits [4]. Other alternatives [5, 6]arenot free of hepatotoxicity [2,7–11].

Background Vector-borne transmission of Trypanosoma cruzi is seen exclusively in the Americas where an estimated 8 million people are infected with the parasite. Significant research in southern Peru has been conducted to understand T. cruzi infection and vector control, however, much less is known about the burden of infection and epidemiology in northern Peru. Methodology A cross-sectional study was conducted to estimate the seroprevalence of T. cruzi infection in humans (n=611) and domestic animals [dogs (n=106) and guinea pigs (n=206)] in communities of Cutervo Province, Peru. Sampling and diagnostic strategies differed according to species. An entomological household study (n=208) was conducted to identify the triatomine burden and species composition, as well as the prevalence of T. cruzi in vectors. Electrocardiograms (EKG) were performed on a subset of participants (n=90 T. cruzi infected participants and 170 age and sex-matched controls). The seroprevalence of T. cruzi among humans, dogs, and guinea pigs was 14.9% (95% CI: 12.2 – 18.0%), 19.8% (95% CI: 12.7- 28.7%) and 3.3% (95% CI: 1.4 – 6.9%) respectively. In one community, the prevalence of T. cruzi infection was 17.2% (95% CI: 9.6 - 24.7%) among participants < 15 years, suggesting recent transmission. Increasing age, positive triatomines in a participant's house, and ownership of a T. cruzi positive guinea pig were independent correlates of T. cruzi infection. Only one species of triatomine was found, Panstrongylus lignarius, formerly P. herreri. Approximately forty percent (39.9%, 95% CI: 33.2 - 46.9%) of surveyed households were infested with this vector and 14.9% (95% CI: 10.4 - 20.5%) had at least one triatomine positive for T. cruzi. The cardiac abnormality of right bundle branch block was rare, but only identified in seropositive individuals. Conclusions Our research documents a substantial prevalence of T. cruzi infection in Cutervo and highlights a need for greater attention and vector control efforts in northern Peru., Author Summary Chagas disease causes significant morbidity and mortality throughout Central and South America. The epidemiology and control of this disease is subject to unique regional particularities, including the behavior and ecology of the local insect vector species. Significant resources have been allocated towards research and control efforts in southern Peru, yet very little is known about the prevalence and epidemiology of Trypanosoma cruzi in northern Peru. Our study highlights significant T. cruzi infection in northern Peru and is one of the first to document substantial transmission by the insect Panstrongylus lignarius. Our results illustrate major gaps in knowledge and the need for public health interventions targeted at Chagas disease in the region of Cutervo Province of northern Peru.

Visceral leishmaniasis (VL) is a rare disease in solid-organ transplant (SOT) recipients. Therefore, little is known about the risk factors and disease behavior in the transplant setting. This multicenter, matched case–control study (1:2 ratio) was designed to determine the risk factors, clinical features and outcomes of VL among this population. Control and case subjects were matched by center, transplant type and timing. Thirty-six VL cases were identified among 25 139 SOT recipients (0.1%). VL occurred 5.7-fold more frequently in Brazil than in Spain, presenting a median time of 11 months after transplantation. High-dose prednisone in the preceding 6 months was associated with VL. Patients were diagnosed over 1 month after symptom onset in 25% of cases. Thirty-one patients (86%) were febrile upon diagnosis, 81% exhibited visceromegaly and 47% showed pancytopenia. Concomitant infection was common. Parasites were identified in 89% of patients; the remaining patients were diagnosed by serology. The majority of the patients received amphotericin B. Relapses occurred in 25.7% of cases, and the crude mortality rate was 2.8%. VL after SOT is related to the VL prevalence in the general population. Delayed diagnosis frequently occurs. Liposomal amphotericin is the most commonly used therapy; mortality is low, although relapses are common.

BACKGROUND Experience with high-dose ganciclovir for the management of resistant cytomegalovirus (CMV) replication in transplant patients is limited despite its adoption as an effective therapy by some consensus documents. METHODS We studied six cases of CMV replication in solid organ transplant patients whose genotypic testing showed mutations associated with different levels of resistance to ganciclovir. All were treated with high-dose intravenous ganciclovir (7.5-10 mg/kg/12 hr) or oral valganciclovir (1350-1800 mg/12 hr) corrected according to creatinine clearance. The virologic response was considered positive if the CMV plasma viral load was undetectable. Safety was evaluated by clinical assessment, including the review of vital signs and laboratory tests. RESULTS All patients had asymptomatic replication, except one who had digestive disease. Four patients received universal prophylaxis with valganciclovir. Two patients received preemptive therapy with valganciclovir for individual episodes of replication. Two of the six patients received steroid boluses before the episode of replication by resistant CMV. All patients responded to treatment, including those with mutations associated with a high level of ganciclovir resistance. Four patients had neutropenia (

Summary Objectives The aim of this study was to determine the epidemiology and clinical impact of infections in patients awaiting heart transplantation. Methods We evaluated all patients considered for a heart transplant in our center over a period of 18 months over a period of 18 months from 2007 to 2009. The patients were followed up for 8 months or until death, transplant, or loss to follow-up. Results Ninety patients were included in the study. During follow-up, 25 infections were recorded in 22 heart transplant candidates (24.4%). Respiratory infections were the most frequent infection (12 bronchitis; 48.0%), followed by skin and soft tissue infections (four infections; 16.0%), intra-abdominal infections (four infectious diarrhea; 16.0%), bacteremia (three infections; 12.0%), and urinary tract infections (two infections; 2.0%). Age, comorbidity, sex, and diabetes were not found to be risk factors for infection. Twenty-four patients (26.7%) were transplanted during follow-up. Infection before transplantation was not associated with an increased risk of mortality or a higher rate of infection in the immediate post-transplant period. Conclusions Infections are common in heart transplant candidates, affecting almost 25% of them. Respiratory tract infections are the most frequent type of infection. However, they are not associated with increased mortality in the immediate post-transplant period.

Background Tobacco smoking is an important public health concern worldwide leading to both chronic disease and early death. In Latin America, smoking prevalence is estimated at approximately 30% and prior studies suggest that the prevalence in Peru is 22% to 38%. We sought to determine the prevalence of daily smoking in a poor peri-urban community in Lima, Peru. Methods We conducted a cross-sectional survey in a random sample of adults ≥40 years of age living in Pampas de San Juan de Miraflores, Lima, Peru. We asked participants to respond to a survey that included questions on sociodemographics, tobacco use and dependence. Results We enrolled 316 participants. Average monthly household income was ≤ 400 USD and nearly all homes had running water, sewage, and electricity. Most individuals had not completed high school. Smoking prevalence was 16% overall, yet daily smoking prevalence was 1.9%. Former daily smokers comprised 3.8% of current nonsmokers and 9.1% current occasional smokers. Average scores for the Fagerstrom Test for Nicotine Dependence for daily smokers and occasional smokers were 1.5 and 0, respectively. Conclusions Daily use of tobacco is uncommon among adults in peri-urban communities of Lima, Peru, unlike their counterparts in Lima and other Latin American capital cities. Tobacco dependence is also low. Hence, efforts aimed at primary prevention are of utmost importance in these communities. This study provides an accurate baseline using an internationally recognized assessment tool (Global Adult Tobacco Survey), allowing for accurate assessment of tobacco control interventions over time.

Candidemia is a nosocomial infection with high associated mortality. There have been changes in microbiology, epidemiology and treatment over the last few years, which has led us to analyse our own situation.Prospective, multicentre and observational study. All episodes of candidemia in adult patients seen in 17 Andalusian hospitals from 1 October 2005 to 30 September 2006 were included.Were detected 220 cases, the incidence was 0.58 cases/1,000 hospital discharges. Candida albicans was the most frecuent species (53% of cases). The majority of isolates (89%) was susceptibility to fluconazole. Sepsis was the most frequent clinical manifestation (65.7%). The treatment was inadequate in 38.7% of cases. Overall mortality was 40%. On univarite analysis death was found to be significantly associated with: aged60 years, unknown candidemia focus, Pitt score ≥ 2, APACHE II, shock at onset, persistents positive second blood cultures, non-removal of the central venous catheter and Candida species different of C. parasilopsis, among others. In the multivariate analysis death was found to be significantly associated with: aged60 years, Pitt score ≥ 2, Candida species different of C.parasilopsis and inadequate treatment.The candidemia clinical epidemiology in our region is similar to other areas and receiving inadequate treatment is the only modifiable risk factor associated with higher odds of mortality. Therefore, this modifiable factor needs to be improved to reduce the mortality.

Urinary tract infections (UTIs) are one of the most common infections in solid organ transplant (SOT) recipients.Experienced SOT researchers and clinicians have developed and implemented this consensus document in support of the optimal management of these patients. A systematic review was conducted, and evidence levels based on the available literature are given for each recommendation. This article was written in accordance with international recommendations on consensus statements and the recommendations of the Appraisal of Guidelines for Research and Evaluation II (AGREE II).Recommendations are provided on the management of asymptomatic bacteriuria, and prophylaxis and treatment of UTI in SOT recipients. The diagnostic-therapeutic management of recurrent UTI and the role of infection in kidney graft rejection or dysfunction are reviewed. Finally, recommendations on antimicrobials and immunosuppressant interactions are also included.The latest scientific information on UTI in SOT is incorporated in this consensus document.