Mortality due to visceral leishmaniasis in Brazil by municipalities, 2001-2018: a spatial-temporal analysis of estimates from the Global Burden of Disease study.

OBJECTIVES: In the American regions, Brazil accounts for 97% of visceral leishmaniasis (VL) cases, with a case fatality rate of approximately 10%. This study aimed to investigate the VL mortality distribution in Brazil and identify high-priority and high-risk areas for intervention strategies. STUDY DESIGN: This was an ecological study that analysed the spatial-temporal patterns of VL mortality in Brazilian municipalities. METHODS: Age-standardised VL mortality rates from the Global Burden of Disease study from 2001 to 2018 were used. The distribution of mortality in the municipalities was assessed, and subsequently the Local Index of Spatial Autocorrelation (LISA) analysis was conducted to identify contiguous areas with high mortality rates. Scan analysis identified clusters of high spatial-temporal risks. RESULTS: The highest mortality rates and clusters were in municipalities located in the Northeast region and in the states of Tocantins and Roraima (North region), Mato Grosso do Sul (Central-West region), and Minas Gerais (Southeast region). According to LISA, there was an increase in the number of municipalities classified as high priority from the first 3-year period (n = 434) to the last 3-year period (n = 644). The spatio-temporal analysis identified 21 high-risk clusters for VL mortality. CONCLUSION: Areas with a high risk of VL mortality should prioritise preventing transmission, invest in early diagnosis and treatment, and promote the training of healthcare professionals.

COVID-19 vaccines effectiveness against symptomatic disease and severe outcomes, 2021-2022: a test-negative case-control study.

OBJECTIVES: This study evaluated the effectiveness of COVID-19 vaccines in preventing symptomatic and severe disease. STUDY DESIGN: This was an observational test-negative case-control study. METHODS: Study participants were adults with at least one symptom included in the World Health Organization COVID-19 definition who sought health care in a public emergency department between 1 November 2021 and 2 March 2022 (corresponding with the fifth pandemic wave in Portugal dominated by the Omicron variant). This study used multivariable logistic regression models to estimate and compare the odds ratio of vaccination between test-positive cases and test-negative controls to calculate the absolute and relative vaccine effectiveness. RESULTS: The study included 1059 individuals (522 cases and 537 controls) with a median age of 56 years and 58% were women. Compared with the effectiveness of the primary vaccination scheme that had been completed ≥180 days earlier, the relative effectiveness against symptomatic infection of a booster administered between 14 and 132 days earlier was 71% (95% confidence interval [CI]: 57%, 81%; P < 0.001). The effectiveness of the primary series against symptomatic infection peaked at 85% (95% CI: 56%, 95%) between 14 and 90 days after the last inoculation and decreased to 34% (95% CI: -43%, 50%) after ≥180 days. CONCLUSIONS: Despite the known immunological evasion characteristics of the Omicron variant, results from this study show that vaccine effectiveness increases after booster administration. COVID-19 vaccine effectiveness decreases to less than 50% between 3 and 6 months after completion of the primary cycle; therefore, this would be an appropriate time to administer a booster to restore immunity.

Ecological factors associated with areas of high tuberculosis diagnosis delay.

OBJECTIVE: We aimed to identify areas of high tuberculosis (TB) diagnosis delay in mainland Portugal in 2017 and ecological factors associated with these areas. STUDY DESIGN: This was an ecological study. METHODS: We considered all notified pulmonary TB cases from the Portuguese National Tuberculosis Surveillance System in mainland Portugal. Diagnostic delays were calculated at the municipality level. Demographic variables, proxies for TB awareness, health services capacity indicators, and socio-economic variables were included and extracted from official databases, such as Statistics Portugal, Ministeries, Foreigners and Border Services. We used spatial analysis to identify areas of high delay in 2017 and logistic generalised additive models to identify ecological factors associated with the identified cluster. RESULTS: We identified an area of high delay in 2017 in the South region of the country. Overall, municipalities with a smaller population density, smaller proportion of unemployed, fewer health centres and higher old-age dependency ratio, proportion of men, TB incidence, proportion of immigrants and high school dropout had a higher probability of belonging in a high delay area. CONCLUSION: The role of primary health care in TB diagnosis should be further explored. Interventions should address factors interplaying at the local and individual levels. Policies influencing social and health conditions, leading to changes in individual behaviour, can lead to sustained improvements over time.

One-year Functional Outcomes after Holmium Laser Enucleation of the Prostate (HoLEP): Introduction of a Composite Score (Hexafecta).

OBJECTIVE: To compare the efficiency (micturition symptoms, continence, erection) and safety of Holmium Laser Enucleation of the Prostate (HoLEP) with a single composite score (the Hexafecta score) one year postprocedure. PATIENTS AND METHODS: We conducted a single-center retrospective study including all patients who had undergone HoLEP for the treatment of benign prostate hyperplasia (BPH) between May 2013 and August 2017. Data were obtained preoperatively and at the 6- and 12-month visits. We also reported all 90-day complications. The Hexafecta score included 6 criteria: peak urine flow of at least 15ml/s, 30% reduction in International Prostate Symptoms Score (IPSS) score, quality of life via the IPSS less than 2, no incontinence (International Consultation Incontinence Questionnaire), no significant change in erectile function (International Index of Erectile Function), and no grade III or more complications according to the Clavien-Dindo classification. RESULTS: Two hundred thirty-five patients were included, of whom 197 (83.8%) completed the 12-month visit. Complete data were available to assess the Hexafecta score for 178 of them (75.7%). Most of the missing data were for uroflowmetry and the erectile function assessment. Hundred three patients (58%) met all 6 criteria, while 45 (25%) met 5 of them. None were retreated for BPH in the follow-up period. The de novo incontinence rate was 4.1%. CONCLUSION: The Hexafecta score is a simple, transversal method for comprehensively evaluating functional outcomes after HoLEP surgery. Such an evaluation could be used to compare other types of procedures for BPH treatment. LEVEL OF EVIDENCE: 3.

Bioecological aspects of triatomines and marsupials as wild Trypanosoma cruzi reservoirs in urban, peri-urban and rural areas in the Western Brazilian Amazon.

In the Amazon region, Trypanosoma cruzi transmission cycles involve a great diversity of Triatominae vectors and mammal reservoirs. Some Rhodnius spp. mainly inhabit palm trees that act as microhabitats for hosts and vectors. The current study aimed to describe aspects of the bio-ecology of the vectors and reservoirs of T. cruzi in relation to human populations resident near areas with large quantities of palm trees, in rural, peri-urban and urban collection environments, located in the Western Brazilian Amazon. Rhodnius pictipes and Didelphis marsupialis were respectively the most predominant vector and reservoir, with rates of 71% for R. pictipes and 96.5% for D. marsupialis. The vast majority of T. cruzi isolates clustered with TcI. The most prevalent haplotype was TcI COII1 (69.7%). Mauritia flexuosa and Attalea phalerata were the main ecological indicators of infestation by triatomines. Birds were the most common food source (27,71%). T. cruzi isolated from R. robustus has the haplotype HUM-13, previously detected in a chronic Chagas patient living in the same area. Our results demonstrate the relevance of this study, with the occurrence of elevated infection rates in animals, and suggest the importance of the Amazon zones where there is a risk of infection in humans.

Patient and healthcare delays in critical and non-critical pulmonary tuberculosis incidence areas in Portugal: are there differences?

OBJECTIVES: To characterize patient, healthcare, and total delay in diagnosing pulmonary tuberculosis (PTB) in critical (higher PTB incidence) and non-critical (lower PTB incidence) areas and their determinants considering clinical and sociodemographic factors. STUDY DESIGN: Retrospective cohort study. METHODS: Data was retrieved from the Portuguese National Tuberculosis Surveillance System (SVIG-TB). Were included in the study all active PTB patients (n = 11,762) notified between 2008 and 2017. Spatial analysis was used to define critical and non-critical areas. Kaplan-Meier estimator, logrank test, and Cox regression were conducted, stratified by area. RESULTS: PTB cases in critical areas (n = 6594, 56.1%) presented longer patient median delay (41 vs 31days), shorter healthcare median delay (7 vs 10 days), and longer total median delay (63 vs 61days) t.han non-critical areas. Patient and total delay increased in both areas over time, while healthcare delay only increased in non-critical areas. Icn both areas, being from a high TB incidence country and alcohol abuse were associated with longer patient delays. Being female, older age, and oncologic diseases were associated with longer healthcare delays. Respiratory diseases were only associated with a longer healthcare delay in non-critical areas. Being female, older, and from a high TB incidence country were associated with a longer total delay in both areas. CONCLUSIONS: Patient delay was significantly longer in critical areas, and healthcare delay was significantly longer in non-critical areas. Several factors associated with longer delays have been identified, most of which are shared by critical and non-critical areas. Differences in patient and healthcare delay, for example, by sex, age, or country of birth, highlight the need for targeted public health interventions to help reduce these differences.

Impact of markers of endothelial injury and hypercoagulability on systemic lupus erythematosus.

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.

Sourdough bacterial dynamics revealed by metagenomic analysis in Brazil.

This study dealt with the influence of the temperature on the bacterial dynamics of two spontaneously fermented wheat sourdoughs, propagated at 21 ±â€¯1 °C (SD1) and 30 ±â€¯1 °C (SD2), during nine backslopping steps (BS1 to BS9). Proteobacteria was the only phylum found in flour. Escherichia hermannii was predominant, followed by Kosakonia cowanii, besides species belonging to the genera Pantoea and Pseudomonas. After one step of propagation, Clostridium and Bacillus cereus group became predominant. Lactobacillus curvatus was found at low relative abundance. For the second backslopping step, Clostridium was flanked by L. curvatus and Lactobacillus farciminis. From BS4 (6th day) onward, lactic acid bacteria (LAB) became predominant. L. farciminis overcame L. curvatus and remained dominant until the end of propagations for both sourdoughs. At 21 °C, Bacillus, Clostridium, Pseudomonas, and Enterobacteriaceae were gradually inhibited. At the end of propagation, SD1 harbored only LAB. Otherwise, the temperature of 30 °C favored the persistence of atypical bacteria in SD2, as Pseudomonas and Enterobacteriaceae. Therefore, the temperature of 21 °C was more suitable for sourdough propagation in Brazil. This study enhanced the knowledge of temperature's influence on microbial assembly and contributed to the elucidation of sourdough microbial communities in Brazil.

Neurorehabilitation in the times of Covid-19: insights from the Spanish Neurorehabilitation Society (SENR).

The entire world is experiencing an unprecedented global health crisis and Spain has been one of the most heavily affected countries within Europe. Unexpected rapid changes and reorganization of medical services that occurred during the pandemic lead to an impact in the practice of neurorehabilitation. The idiosyncrasies typical of neurorehabilitation management, specially in acute facilities, that makes it susceptible as a vector of dissemination of Covid but also because of the need of finding new wards and intensive care units for Covid patients, the interventions in neurorehabilitation has suffered enormous changes. There is a need for rethinking the future to treat a new wave of patients with neurorehabilitation necessities such as those recovering from Covid 19 with neurological sequelae but also of those neurorehab patients who were unable to access the health system during the locke down period. This article is intended to invite to reflect on and discuss the redesign of our current neurorehabilitation plans after the experience on the Covid 19 pandemic.

Ex vivo interaction between blood components and hormone-dependent breast cancer cells induces alterations associated with epithelial-mesenchymal transition and thrombosis.

The prevalence of breast cancer is steadily increasing with metastasis and thromboembolic complications identified as the most common causes of death. The acquisition of an aggressive phenotype by hormone-dependent breast cancers is mediated by Transforming Growth Factor Beta 1 (TGF-ß1) expression and is associated with epithelial-mesenchymal transition (EMT) and, potentially, increased propensity for thrombosis. We investigated this phenomenon by assessing the effect of platelet-rich plasma (PRP) and whole blood (WB) on parameters of EMT and hypercoagulation in vitro. MCF-7 breast cancer cells were cultured under standard conditions, followed by co-culture with PRP or WB. Cells were processed for real-time PCR (TGF-ß1 and vimentin), electron microscopy or immunocytochemistry (TGF-ß1). Micrographs were qualitatively assessed, and real-time PCR data analyzed with PAST Statistical Software. The addition of blood components heightened TGF-ß1 immunolocalization and significantly increased corresponding gene expression. Both PRP and WB significantly increased vimentin expression and induced a shape change from a typical epithelial phenotype to a spindle-shape morphology, indicative of EMT. Fibrin fiber, network and plaque formation indicated a hypercoagulatory environment. The results thus show that in preparation for hematogenous metastasis, hormone-dependent breast cancer cells assume an aggressive phenotype associated with EMT, simultaneously increasing the propensity for the formation of thrombo-emboli.

La Jument lighthouse: a real-scale laboratory for the study of giant waves and their loading on marine structures.

This paper presents results from an experiment designed to improve the understanding of the relationship between extreme breaking waves and their mechanical loading on heritage offshore lighthouses. The experiment, conducted at La Jument, an iconic French offshore lighthouse, featured several records of wave, current and structure accelerations acquired during severe storm conditions, with individual waves as high as 24 m. Data analysis focuses on a storm event marked by a strong peak in the horizontal accelerations measured inside La Jument. Thanks to stereo-video wave measurements synchronized to the acceleration record we were able to identify and describe the breaking wave responsible for this intense loading. Our observations suggest that this giant wave (19 m high) had a crest elevation high enough to directly hit the lighthouse tower, above the substructure. This paper reveals the potential for conducting ambitious field experiments from offshore lighthouses in order to collect valuable storm waves and wave loading observations. This offers a possible second service life for these heritage structures as in situ laboratories dedicated to the study of the coastal hydrodynamics and its interaction with marine structures. This article is part of the theme issue 'Environmental loading of heritage structures'.

Atherosclerotic vascular disease is more prevalent among black ESKD patients on long-term CAPD in South Africa.

BACKGROUND: Occurrence of cardiovascular disease (CVD) in the setting of chronic kidney disease (CKD) can be described as a "cruel alliance", with CVD responsible for about half of all deaths among CKD patients. Chronic kidney disease patients are more likely to die from CVD than progress to end stage kidney disease (ESKD). Dyslipidaemia, a known traditional risk factor for CVD, is highly prevalent among CKD patients and with an even higher frequency among ESKD patients on dialytic therapies. Prolonged exposure of continuous ambulatory peritoneal dialysis (CAPD) patients to high glucose concentrations in CAPD fluid have been associated with increased risk of cardiovascular events. In this study, we investigated the relationship of atherosclerotic vascular disease (AsVD) to clinical and echocardiographic parameters among black South Africans with CKD (stage 3) and ESKD on CAPD and haemodialysis (HD). METHODS: This was a cross-sectional study of 40 adult (18-65 years) non-diabetic CKD patients (kidney disease outcome quality initiative [KDOQI] stage 3), 40 ESKD patients on CAPD, 40 ESKD patients on HD and 41 age and sex-matched healthy controls. An interviewer-administered questionnaire was used to obtain information on participants' sociodemographic and cardiovascular risk factors. Anthropometric parameters were measured. Serum blood samples were analysed for creatinine, albumin and lipid profile; lipoprotein ratios, Framingham's risk score and the 10-year risk of developing coronary heart disease (CHD) were calculated. Echocardiography was performed on all patients and carotid intima media thickness (CIMT) was measured in both right and left carotid arteries at 1 cm proximal to the carotid bulb. Spearman's rank correlation and binary logistic regression were conducted to determine the relationship of AsVD to clinical and echocardiographic parameters. RESULTS: Atherosclerotic vascular disease was most prevalent among ESKD patients on CAPD (70%, n = 28/40). Chronic kidney disease and HD patients exhibited a similar prevalence (47.5%, n = 19/40), while the prevalence in controls was 17.1% (n = 7/41). Presence of AsVD was associated with significantly older age, higher waist hip ratio (WHR), left ventricular mass index (LVMI) and Framingham's 10-year risk of developing CHD. Significant differences in clinical and echocardiographic parameters were observed when the study groups were compared. Age and LVH independently predicted AsVD. CONCLUSION: Atherosclerotic vascular disease was more prevalent among CAPD patients compared to pre-dialysis CKD and HD patients. Among all lipoprotein ratios assessed, non-HDL-C showed the most consistent significant difference between the groups. Age (> 40 years) and presence of LVH were independent predictors of AsVD.

Thyroid storm and myxoedema: two reversible causes of acute heart failure.

Cardiovascular signs and symptoms can prevail in both hypothyroidism and hyperthyroidism. Case 1: 30-year-old female with acute right heart failure as first manifestation of Graves' disease. It illustrates some of its cardiovascular complications, particularly pulmonary hypertension, tricuspid regurgitation, atrial fibrillation, mitral valve prolapse and mitral regurgitation. Case 2: 83-year-old-man with a severe primary hypothyroidism/myxoedema crisis presented to emergency department with extreme bradyarrhythmia with hemodynamic impact and heart failure signs, which led to implantation of definitive pacemaker. Thyroid disorders are treatable entities and most cardiovascular changes are reversible. Early diagnosis is mandatory and can avoid severe complications and, eventually, invasive therapeutics interventions. Pulmonary hypertension and acute heart failure, especially in young adults, should be screened for underlying hyperthyroidism.

Who are the patients that default tuberculosis treatment? - space matters!

The goals of this article are: (i) to understand how individual characteristics affect the likelihood of patients defaulting their pulmonary tuberculosis (PTB) treatment regimens; (ii) to quantify the predictive capacity of these risk factors; and (iii) to quantify and map spatial variation in the risk of defaulting. We used logistic regression models and generalized additive models with a spatial component to determine the odds of default across continental Portugal. We focused on new PTB cases, diagnosed between 2000 and 2013, and included some individual information (sex, age, residence area, alcohol abuse, intravenous drug use, homelessness, HIV, imprisonment status). We found that the global default rate was 4·88%, higher in individuals with well-known risk profiles (males, immigrants, HIV positive, homeless, prisoners, alcohol and drug users). Of specific epidemiological interest was that our geographical analysis found that Portugal's main urban areas (the two biggest cities) and one tourist region have higher default rates compared to the rest of the country, after adjusting for the previously mentioneded risk factors. The challenge of treatment defaulting, either due to other individual non-measured characteristics, healthcare system failure or patient recalcitrance requires further analysis in the spatio-temporal domain. Our findings suggest the presence of significant within-country variation in the risk of defaulting that cannot be explained by these classical individual risk factors alone. The methods we advocate are simple to implement and could easily be applied to other diseases.

Water distribution in a sorption enhanced methanation reactor by time resolved neutron imaging.

Water adsorption enhanced catalysis has been recently shown to greatly increase the conversion yield of CO2 methanation. However, the joint catalysis and adsorption process requires new reactor concepts. We measured the spatial water distribution in a model fixed bed reactor using time resolved neutron imaging. Due to the high neutron attenuation coefficient of hydrogen, the absorbed water in the sorption catalyst gives a high contrast allowing us to follow its formation and map its distribution. At the same time, the product gas was analysed by FTIR-gas analysis. The measurements provided crucial insights into the future design of sorption reactors: during the sorption enhanced reaction, a reaction front runs through the reactor. Once the extension of the reaction front reaches the exhaust, the conversion rate of sorption enhanced methanation decreases. The existence of a reaction front running through the reactor is prerequisite for a high conversion rate. We give a simple model of the experimental results, in particular the conditions, under which a reaction front is established. In particular the latter effect must be taken into account for the dimensions of a large scale reactor.

Potential of Entomopathogenic Fungi as Biological Control Agents of Diamondback Moth (Lepidoptera: Plutellidae) and Compatibility With Chemical Insecticides.

The objectives were to evaluate the efficiency of entomopathogenic fungi against Plutella xylostella (L.) and the compatibility of the most virulent isolates with some of the insecticides registered for use on cabbage crops. Pathogenicity tests used isolates of Beauveria bassiana, Metarhizium rileyi, Isaria fumosorosea, Isaria sinclairii, and Lecanicillium muscarium standardized at a concentration of 10(7) conidia/ml. Cabbage leaf discs were immersed in these suspensions, and after evaporation of the excess water, were placed 10 second-instar larvae of P. xylostella, totaling 10 leaf discs per treatment. Mortality was assessed 7 d after treatment, and the isolates that caused mortality>80% were used to estimate LC50 and LT50. The compatibilities of the most virulent isolates and the insecticides were tested from the mixture of these into the culture medium, and after solidifying, the medium was inoculated with an aliquot of the isolated suspension. The following parameters were evaluated: growth of the colony, number and viability of conidia after 7 d. The isolated IBCB01, IBCB18, IBCB66, and IBCB87 of B. bassiana, LCMAP101 of M. rileyi, and ARSEF7973 of I. sinclairii caused mortality between 80 and 100%, with LC50 and LT50 between 2.504 to 6.775×10(4) conidia/ml and 52.22 to 112.13 h, respectively. The active ingredients thiamethoxam and azadirachtin were compatible with the entomopathogenic fungi. The results suggest that the use of these isolates is an important alternative in the pesticidal management of P. xylostella, with the possible exception of the associated use of chemical controls using the active ingredients thiamethoxam or azadirachtin.

[Urological complications after kidney transplantation from extended criteria donors: Ureteroneocystostomy versus pyelo-ureterostomy]. / Complications urologiques après transplantation de reins issus de donneurs à critères étendus : anastomoses urétéro-vésicales versus anastomoses pyélo-urétérales.

INTRODUCTION: The use of transplants from extended criteria donors increases the number of urological complications after renal transplantation. Two different anastomosis techniques used to restore urinary continuity are compared in this study. PATIENTS AND METHODS: Retrospective study, bi-center over a period of 5 years. One hundred and seventy six patients operated at Hospices Civils de Lyon benefited from ureteroneocystostomy according to De Campos-Freire (group 1) and 167 patients operated at the Necker Hospital in Paris had a pyelo-ureterostomy (group 2). The various urological complications (fistulas, strictures, seromas, haematomas and vesico-ureteric reflux) and their care were compared. Risk factors were sought. RESULTS: The waiting time before transplantation was longer in group 2 than in group 1 (51 and 33.84 months) as the percentage of anuric patients (52.9 % against 32.9 %) (P<0.001). The cold ischemic time was shorter in group 1 (939.3minutes on average against 1325.3minutes for group 2) (P<0.001). A double J stent was put in place in 97.6 % of cases in group 2 against 84.2 % for group 1 (P<0.001). We did not find any significant difference in the occurrence of stenosis and fistulas (major complications) between the 2 groups. There were more minor complications (hematoma, seroma and vesico-ureteric reflux) in group 1 (P=0.033). There was a difference in the treatment of these complications, especially stenosis (P=0.024) with a significantly more conservative approach in group 2. Multivariate analysis found anuria, sex of recipients and donor age as independent risk factors in the onset of complications and the double J stent as a protective factor. CONCLUSION: This study does not demonstrate the superiority of a urinary anastomosis technique. The establishment of a double J stent reduces the risk of complications. Analysis of risk factors allows to propose a decision tree to guide the surgical strategy, particularly in the population of anuric recipients. LEVEL OF EVIDENCE: 5.

Allogeneic hematopoietic stem cell transplantation in solid organ transplant recipients: a retrospective, multicenter study of the EBMT.

We conducted a questionnaire survey of the 565 European Society for Blood and Marrow Transplantation centers to analyze the outcome of allogeneic hematopoietic stem cell transplantation (alloSCT) in recipients of solid organ transplantation (SOT). We investigated 28 patients with malignant (N = 22) or nonmalignant diseases (N = 6), who underwent 31 alloSCT procedures: 12 after kidney, 13 after liver and 3 after heart transplantation. The incidence of solid organ graft failure at 60 months after first alloSCT was 33% (95% confidence interval [CI], 16-51%) for all patients, 15% (95% CI, 2-40%) for liver recipients and 50% (95% CI, 19-75%) for kidney recipients (p = 0.06). The relapse rate after alloSCT (22%) was low following transplantation for malignant disorders, despite advanced stages of malignancy. Overall survival at 60 months after first alloSCT was 40% (95% CI, 19-60%) for all patients, 51% (95% CI, 16-86%) for liver recipients and 42% (95% CI, 14-70%) for kidney recipients (p = 0.39). In summary, we show that selected SOT recipients suffering from hematologic disorders may benefit from alloSCT and experience enhanced long-term survival without loss of organ function.

A cis-acting element in the promoter of human ether à go-go 1 potassium channel gene mediates repression by calcitriol in human cervical cancer cells.

The human ether à go-go 1 potassium channel (hEAG1) is required for cell cycle progression and proliferation of cancer cells. Inhibitors of hEAG1 activity and expression represent potential therapeutic drugs in cancer. Previously, we have shown that hEAG1 expression is downregulated by calcitriol in a variety of cancer cells. Herein, we provided evidence on the regulatory mechanism involved in such repressive effect in cells derived from human cervical cancer. Our results indicate that repression by calcitriol occurs at the transcriptional level and involves a functional negative vitamin D response element (nVDRE) E-box type in the hEAG1 promoter. The described mechanism in this work implies that a protein complex formed by the vitamin D receptor-interacting repressor, the vitamin D receptor, the retinoid X receptor, and the Williams syndrome transcription factor interact with the nVDRE in the hEAG1 promoter in the absence of ligand. Interestingly, all of these transcription factors except the vitamin D receptor-interacting repressor are displaced from hEAG1 promoter in the presence of calcitriol. Our results provide novel mechanistic insights into calcitriol mode of action in repressing hEAG1 gene expression.