Renin–angiotensin–aldosterone system blockers effect in chronic kidney disease progression in hypertensive elderly patients without proteinuria: PROERCAN trial / Efecto de los bloqueantes del sistema renina-angiotensina-aldosterona en la progresión de enfermedad renal crónica en pacientes hipertensos añosos sin proteinuria: ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos

Introduction: Evidence about nefroprotective effect with RAAS blockers in elderly patients with chronic kidney disease (CKD) without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria. Materials and methods: Multicenter open-label, randomized controlled clinical trial including patients over 65 year-old with hypertension and CKD stages 3–4 without proteinuria. Patients were randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs and were followed up for three years. Primary outcome is estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcome measures include BP control, renal and cardiovascular events and mortality. Results: 88 patients were included with a mean age of 77.9±6.1 years and a follow up period of 3 years: 40 were randomized to RAAS group and 48 to standard treatment. Ethiology of CKD was: 53 vascular, 16 interstitial and 19 of unknown ethiology. In the RAAS group eGFR slope during follow up was −4.3±1.1ml/min, whereas in the standard treatment group an increase on eGFR was observed after 3 years (+4.6±0.4ml/min), p=0.024. We found no differences in blood pressure control, number of antihypertensive drugs, albuminuria, potassium serum levels, incidence of cardiovascular events nor mortality during the follow up period. Conclusions: In elderly patients without diabetes nor cardiopathy and with non proteinuric CKD the use of RAAS blockers does not show a reduction in CKD progression. The PROERCAN (PROgresión de Enfermedad Renal Crónica en ANcianos) trial (trial registration: NCT03195023). (AU)

Introducción: Actualmente no existe suficiente evidencia sobre el efecto nefroprotector de los bloqueantes del sistema renina-angiotensina-aldosterona (BSRAA) en pacientes añosos con enfermedad renal crónica (ERC) sin proteinuria y sin cardiopatía. El objetivo es evaluar el efecto de los BSRAA en la progresión de la ERC en este grupo poblacional. Métodos: Se trata de un estudio prospectivo, aleatorizado, que compara la eficacia de los BSRAA vs. otros tratamientos antihipertensivos en la progresión renal en personas mayores de 65 años con ERC estadios 3 y 4 e índice albúmina/creatinina<30mg/g. Aleatorización 1:1 BSRAA o tratamiento antihipertensivo estándar. Se recogieron cifras tensionales y parámetros analíticos de un año previo a la aleatorización y durante el seguimiento. Resultados: Se incluyeron 88 pacientes seguidos durante tres años con edad media de 77,9±6,1 años. De estos, se aleatorizaron 40 al grupo BSRAA y 48 al estándar. La etiología de ERC fue: 53 vascular, 16 intersticial y 19 no filiada. En el primer grupo se observó una progresión de la ERC con una caída del filtrado glomerular estimado (FGe) de -4,3±1,1mL/min, mientras que en el grupo estándar un aumento del FGe durante el seguimiento de 4,6±0,4mL/min, p=0,024. No se apreciaron diferencias entre ambos en el control tensional, el número de antihipertensivos, la albuminuria, los niveles de potasio, la incidencia de eventos cardiovasculares ni la mortalidad durante el seguimiento. Conclusiones: En pacientes añosos no diabéticos con ERC no proteinúrica y sin cardiopatía el uso de BSRAA no añade beneficio en la progresión de la ERC. Ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos (PROERCAN) (NCT03195023). (AU)

Renin-angiotensin-aldosterone system blockers effect in chronic kidney disease progression in hypertensive elderly patients without proteinuria: PROERCAN trial.

INTRODUCTION: Evidence about nefroprotective effect with RAAS blockers in elderly patients with chronic kidney disease (CKD) without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria. MATERIALS AND METHODS: Multicenter open-label, randomized controlled clinical trial including patients over 65 year-old with hypertension and CKD stages 3-4 without proteinuria. Patients were randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs and were followed up for three years. Primary outcome is estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcome measures include BP control, renal and cardiovascular events and mortality. RESULTS: 88 patients were included with a mean age of 77.9±6.1 years and a follow up period of 3 years: 40 were randomized to RAAS group and 48 to standard treatment. Ethiology of CKD was: 53 vascular, 16 interstitial and 19 of unknown ethiology. In the RAAS group eGFR slope during follow up was -4.3±1.1ml/min, whereas in the standard treatment group an increase on eGFR was observed after 3 years (+4.6±0.4ml/min), p=0.024. We found no differences in blood pressure control, number of antihypertensive drugs, albuminuria, potassium serum levels, incidence of cardiovascular events nor mortality during the follow up period. CONCLUSIONS: In elderly patients without diabetes nor cardiopathy and with non proteinuric CKD the use of RAAS blockers does not show a reduction in CKD progression. The PROERCAN (PROgresión de Enfermedad Renal Crónica en ANcianos) trial (trial registration: NCT03195023).

Asymmetric Wigner molecules in nanowire Y-junctions.

The possibility of crystalline states of interacting electrons, known as Wigner crystals, has been intensively studied in each of the three dimensions. One-dimensional (1D) systems, however, can be interconnected forming two-dimensional (2D) lattices, being a three-terminal Y-junction (Y-J) the simplest one. Then, even when electrons in the individual branches of the Y are confined in 1D, as the Y-J is in 2D, one could expect significant differences in the crystalline state of the electron gas in a Y-J. With the recent report of fabrication of defect-free GaAs/AlGaAs Y-Js by epitaxial methods, the study of semiconductor Y-Js acquires a special relevance due to its eventual direct exploration. Here, by considering the collective electron interactions using a Yukawa-like effective potential, we explore a two-electron distribution in nanowire Y-Js by modulating its electron density via a screening parameter. We find that the electrons changes from a quasi-continuous to a Wigner molecule-like distribution when the electron density decreases in the Y-J. In bold contrast to the strict 1D case, where equidistant distributions of equal density are obtained in the Wigner regime, in the Y-J equidistant distributions of asymmetric density are induced. We also explore the effect of an external electric field acting along the Y-axis on the asymmetric distributions.

Cancer care for Ukrainian refugees: Strategic impact assessments in the early days of the conflict.

BACKGROUND: The invasion of Ukraine by Russia in February 2022 has resulted in destruction of healthcare infrastructure and triggered the largest wave of internally displaced populations and refugees since World War Two. Conflicts in transitioned countries such as Ukraine create new non-communicable disease (NCD) challenges, especially for cancer care for refugees and humanitarian assistance in host countries. In the early days, rapid attempts were made to model possible impacts. METHODS: By evaluating open source intelligence used in the first three months of the conflict through snowball search methods, we aimed to address: (i) burden of cancer in Ukrainian population, specifically considering translating to the refugees population, and its cancer care capacity; ii) baseline capacity/strengths of cancer systems in initial host countries. Moreover, using a baseline scenario based on crude cancer incidence in Ukraine, and considering data from UNHCR, we estimated how cancer cases would be distributed across host countries. Finally, a surveillance assessment instrument was created, intersecting health system's capacity and influx of internally displaced populations and refugees. FINDINGS AND CONCLUSIONS: The total new cancer patients per month in pre-conflict Ukraine was estimated as 13,106, of which < 1 % are paediatric cases. The estimated cancer cases in the refugee population (combining prevalent and incident), assuming 7.5 million refugees by July 2022 and a female:male ratio of 9:1, was 33,121 individuals (Poland: 19284; Hungary: 3484; Moldova: 2651; Slovakia: 2421; Romania: 5281). According to our assessments, Poland is the only neighbouring country classified as green/yellow for cancer capacity, i.e. sufficient ablility to absorb additional burden into national health system; Slovakia we graded as yellow, Hungary and Romania as yellow/red and Moldova as red.

Tunneling between parallel one-dimensional Wigner crystals.

Vertically aligned arrays are a frequent outcome in the nanowires synthesis by self-assembly techniques or in its subsequent processing. When these nanowires are close enough, quantum electron tunneling is expected between them. Then, because extended or localized electronic states can be established in the wires by tuning its electron density, the tunneling configuration between adjacent wires could be conveniently adjusted by an external gate. In this contribution, by considering the collective nature of electrons using a Yukawa-like effective potential, we explore the electron interaction between closely spaced, parallel nanowires while varying the electron density and geometrical parameters. We find that, at a low-density Wigner crystal regime, the tunneling can take place between adjacent localized states along and transversal to the wires axis, which in turn allows to create two- and three-dimensional electronic distributions with valuable potential applications.

Guidelines for the Diagnosis, Treatment, and Prevention of Hand Eczema. / Guía para el diagnóstico, el tratamiento y la prevención del eccema de manos.

Hand eczema is a common condition associated with significantly impaired quality of life and high social and occupational costs. Managing hand eczema is particularly challenging for primary care and occupational health physicians as the condition has varying causes and both disease progression and response to treatment are difficult to predict. Early diagnosis and appropriate protective measures are essential to prevent progression to chronic eczema, which is much more difficult to treat. Appropriate referral to a specialist and opportune evaluation of the need for sick leave are crucial to the good management of these patients. These guidelines cover the diagnosis, prevention, and treatment of chronic hand eczema and highlight the role that primary care and occupational health physicians can play in the early management of this disease.

Guía para el diagnóstico, el tratamiento y la prevención del eccema de manos / Guidelines for the Diagnosis, Treatment, and Prevention of Hand Eczema

El eccema de manos es una patología frecuente con un fuerte impacto en la calidad de vida de los pacientes y un alto coste social y laboral. Su manejo por los médicos de atención primaria y de medicina del trabajo es complejo debido a la variedad de etiologías, la evolución difícilmente predecible de la enfermedad y la respuesta al tratamiento. El diagnóstico precoz y las medidas protectoras adecuadas son esenciales para evitar la cronificación, que es mucho más difícil de tratar. Una correcta derivación a un especialista y la valoración de una baja laboral en el momento adecuado resultan cruciales para un buen manejo de estos pacientes. En esta guía sobre el eccema crónico de manos analizamos el proceso diagnóstico, las medidas preventivas y los tratamientos, con especial énfasis en el papel del médico de atención primaria y de medicina del trabajo en los estados iniciales de su manejo

Hand eczema is a common condition associated with significantly impaired quality of life and high social and occupational costs. Managing hand eczema is particularly challenging for primary care and occupational health physicians as the condition has varying causes and both disease progression and response to treatment are difficult to predict. Early diagnosis and appropriate protective measures are essential to prevent progression to chronic eczema, which is much more difficult to treat. Appropriate referral to a specialist and opportune evaluation of the need for sick leave are crucial to the good management of these patients. These guidelines cover the diagnosis, prevention, and treatment of chronic hand eczema and highlight the role that primary care and occupational health physicians can play in the early management of this disease

Extensive pyomyositis of prevertebral muscles after acupuncture: Case report.

INTRODUCTION: Severe infectious diseases that require surgery after acupuncture therapy are quite rare. There are only a few cases of pyomyositis following acupuncture reported in the literature. This paper presents a case of cervical pyomyositis developed after such treatment. CASE PRESENTATION: A 36-year-old man presented with swelling and pain in the posterior cervical region as well as high fever and torticollis, after having received three sessions of acupuncture therapy during the preceding weeks aimed to treat his neck stiffness. Ultrasound guided fine needle aspiration (FNA) and contrast-enhanced Computed Tomography (CT) were performed, which showed a large abscess along the paraspinal muscles. The symptoms were resolved after surgical treatment and antibiotherapy. CONCLUSION: Although highly infrequent, pyomyositis is a probable complication of acupuncture. In order to minimise the risk of complications, strict hygenic precautions and knowledge of the human anatomy are mandatory to decrease the rate of complications of acupuncture.

Effect of feed intake level on the body temperature of pigs exposed to heat stress conditions.

Feed intake (FI) level affects body heat production in thermo-neutral pigs; exposure of pigs to heat stress (HS) also increases body temperature (BT). However remains unclear whether the FI level affects the heat production of HS pigs. This study analyzed the effect of FI level on BT of 9 HS pigs (46.3 ±â€¯2.6 kg body weight) implanted with a thermometer set to register the BT at 5-min intervals into the ileum. Pigs were divided in two groups randomly allotted to two FI treatments: high FI (HFI, 1.20 kg/d), and low FI (LFI, 0.96 kg/d), according to a two-period crossover experimental design. Pigs were fed 3-times a day (0600, 1200, and 2200 h), same amount each time (400 g or 320 g). Ambient temperature (AT) ranged from 29.0 to 35.4 °C. The BT of both HFI and LFI pigs followed a similar pattern along a 24-h period, but the BT of HFI pigs was higher than that of LFI pigs (P < 0.05). Postprandial afternoon and evening BT was higher than that after the morning meal (P < 0.05). The postprandial BT increment differed between meal times and AT, but not between FI levels. The BT of HFI and LFI pigs increased up to 0.18 and 0.22 °C, 0.60 and 0.61 °C, and 0.24 and 0.35 °C after the morning, afternoon, and evening meal, respectively, compared with the preprandial BT (P < 0.05). Hence, the dissipation capacity of feeding-related body heat appears to depend on the thermal load of HS pigs before consuming their meals; presumably, the thermal load during 6-h before the morning meal (AT below 32 °C) was lower than before the evening meal (AT above 32 °C). In conclusion, FI level affects the postprandial BT of HS pigs and its magnitude is larger after the evening and afternoon meals. These data suggest that HS pigs may reduce the voluntary FI during the afternoon and evening hours.

An introduction to optical super-resolution microscopy for the adventurous biologist.

Ever since the inception of light microscopy, the laws of physics have seemingly thwarted every attempt to visualize the processes of life at its most fundamental, sub-cellular, level. The diffraction limit has restricted our view to length scales well above 250 nm and in doing so, severely compromised our ability to gain true insights into many biological systems. Fortunately, continuous advancements in optics, electronics and mathematics have since provided the means to once again make physics work to our advantage. Even though some of the fundamental concepts enabling super-resolution light microscopy have been known for quite some time, practically feasible implementations have long remained elusive. It should therefore not come as a surprise that the 2014 Nobel Prize in Chemistry was awarded to the scientists who, each in their own way, contributed to transforming super-resolution microscopy from a technological tour de force to a staple of the biologist's toolkit. By overcoming the diffraction barrier, light microscopy could once again be established as an indispensable tool in an age where the importance of understanding life at the molecular level cannot be overstated. This review strives to provide the aspiring life science researcher with an introduction to optical microscopy, starting from the fundamental concepts governing compound and fluorescent confocal microscopy to the current state-of-the-art of super-resolution microscopy techniques and their applications.

Effect of feed intake level and dietary protein content on the body temperature of pigs housed under thermo neutral conditions.

Feed intake and diet composition appear to affect the body temperature of pigs. Two trials were conducted to analyse the effect of feed intake level and dietary protein content on the intestinal temperature (IT) of pigs housed under thermo neutral conditions. Ten pigs (64.1 ± 1.3 kg initial body weight) fitted with an ileal cannula were used. A thermometer set to register the IT at 5-min intervals was implanted into the ileum through the cannula. In both trials, the ambient temperature ranged from 19.1 to 21.6°C and the pigs were fed at 07:00 and 19:00 hr (same amount each time). In trial 1, the pigs were fed daily 1.2 or 1.8 kg of a wheat-soybean meal diet. The IT followed a similar pattern along a 24-hr period regardless the feed intake level. The IT rapidly increased up to 0.61 and 0.74°C after the morning meal and up to 0.53 and 0.47°C after the evening meal in pigs fed 1.2 and 1.8 kg/d respectively. The postprandial IT was higher in pigs fed 1.8 kg after each meal (p < .05). In trial 2, pigs were fed daily 1.8 kg of a low (11%) or a high (22%) crude protein diet. The IT followed a similar pattern along the 24-hr period regardless the dietary protein level. The postprandial IT did not differ between pigs fed the low protein or the high protein (p > .10). The IT rapidly increased up to 0.66 and 0.62°C after the morning meal in pigs fed the high- and low-protein diet (p < .05), but there was no change after the evening meal (p > .10). In conclusion, the feed intake level affected the IT of pigs housed under TN conditions, but the dietary protein content had no effect.

How does climate change affect regeneration of Mediterranean high-mountain plants? An integration and synthesis of current knowledge.

Mediterranean mountains are extraordinarily diverse and hold a high proportion of endemic plants, but they are particularly vulnerable to climate change, and most species distribution models project drastic changes in community composition. Retrospective studies and long-term monitoring also highlight that Mediterranean high-mountain plants are suffering severe range contractions. The aim of this work is to review the current knowledge of climate change impacts on the process of plant regeneration by seed in Mediterranean high-mountain plants, by combining available information from observational and experimental studies. We also discuss some processes that may provide resilience against changing environmental conditions and suggest some research priorities for the future. With some exceptions, there is still little evidence of the direct effects of climate change on pollination and reproductive success of Mediterranean high-mountain plants, and most works are observational and/or centred only in the post-dispersal stages (germination and establishment). The great majority of studies agree that the characteristic summer drought and the extreme heatwaves, which are projected to be more intense in the future, are the most limiting factors for the regeneration process. However, there is an urgent need for studies combining elevational gradient approaches with experimental manipulations of temperature and drought to confirm the magnitude and variability of species' responses. There is also limited knowledge about the ability of Mediterranean high-mountain plants to cope with climate change through phenotypic plasticity and local adaptation processes. This could be achieved by performing common garden and reciprocal translocation experiments with species differing in life history traits.

High speed ultra-broadband amplitude modulators with ultrahigh extinction >65 dB.

We experimentally demonstrate ultrahigh extinction ratio (>65 dB) amplitude modulators (AMs) that can be electrically tuned to operate across a broad spectral range of 160 nm from 1480 - 1640 nm and 95 nm from 1280 - 1375 nm. Our on-chip AMs employ one extra coupler compared with conventional Mach-Zehnder interferometers (MZI), thus form a cascaded MZI (CMZI) structure. Either directional or adiabatic couplers are used to compose the CMZI AMs and experimental comparisons are made between these two different structures. We investigate the performance of CMZI AMs under extreme conditions such as using 95:5 split ratio couplers and unbalanced waveguide losses. Electro-optic phase shifters are also integrated in the CMZI AMs for high-speed operation. Finally, we investigate the output optical phase when the amplitude is modulated, which provides us valuable information when both amplitude and phase are to be controlled. Our demonstration not only paves the road to applications such as quantum information processing that requires high extinction ratio AMs but also significantly alleviates the tight fabrication tolerance needed for large-scale integrated photonics.

RUNX1 amplification in AML with myelodysplasia-related changes and ring 21 chromosomes.

Ring 21 is an unstable structural abnormality of chromosome 21 that can lead to RUNX1 gene amplification. We present a unique case with a carrier patient of a constitutional ring chromosome 21 (partial monosomy and trisomy 21) with dysmorphic features and congenital malformations phenotype, who developed acute myeloid leukaemia with myelodysplasia-related changes and two ring 21 chromosomes with RUNX1 amplification. The patient's constitutional ring 21 chromosome showed alterations in tumour suppressor genes, and oncogenes, but not in RUNX1. RUNX1 gene expression at acute myeloid leukaemia diagnosis, showed no upregulation, so other genes may also be the genetic amplification targets in this patient. Copyright © 2016 John Wiley & Sons, Ltd.

Multifaceted community-based intervention reduces rate of BMI growth in obese Mexican-origin boys.

BACKGROUND: Latino children and youth have some of the highest rates of overweight and obesity. Early intervention is important to prevent future obesity and illness in this population. METHODS: A 3-year, multifaceted intervention was designed to reduce the rate of growth of body mass index (BMI) among Mexican-origin children. Two communities in California's agricultural Central Valley were targeted for intervention and comparison. To assess impact, anthropometric measures of participating children (N = 422) were collected and analysed at baseline and after 1 year of intervention. RESULTS: After 1 year of intervention, triceps skin-fold thickness in girls showed a significant decrease in unadjusted analysis between children in the two communities. In multivariate analysis, a reduction in BMI growth was seen among obese boys in the intervention community (ß-coefficient = -1.94, P = 0.05). Obese boys in the intervention community also had a smaller increase in waist circumference (ß-coefficient = -5.2, P = 0.04) than the comparison community. CONCLUSIONS: These early findings indicate the intervention's effectiveness for preventing BMI growth among obese boys. Longitudinal follow-up is needed to determine the sustainability of results and whether similar results extend to obese girls and overweight boys or girls.

An integrated diamond nanophotonics platform for quantum-optical networks.

Efficient interfaces between photons and quantum emitters form the basis for quantum networks and enable optical nonlinearities at the single-photon level. We demonstrate an integrated platform for scalable quantum nanophotonics based on silicon-vacancy (SiV) color centers coupled to diamond nanodevices. By placing SiV centers inside diamond photonic crystal cavities, we realize a quantum-optical switch controlled by a single color center. We control the switch using SiV metastable states and observe optical switching at the single-photon level. Raman transitions are used to realize a single-photon source with a tunable frequency and bandwidth in a diamond waveguide. By measuring intensity correlations of indistinguishable Raman photons emitted into a single waveguide, we observe a quantum interference effect resulting from the superradiant emission of two entangled SiV centers.

Trends and sources vs air mass origins in a major city in South-western Europe: Implications for air quality management.

This study presents a 17-years air quality database comprised of different parameters corresponding to the largest city in the south of Spain (Seville) where atmospheric pollution is frequently attributed to traffic emissions and is directly affected by Saharan dust outbreaks. We identify the PM10 contributions from both natural and anthropogenic sources in this area associated to different air mass origins. Hourly, daily and seasonal variation of PM10 and gaseous pollutant concentrations (CO, NO2 and SO2), all of them showing negative trends during the study period, point to the traffic as one of the main sources of air pollution in Seville. Mineral dust, secondary inorganic compounds (SIC) and trace elements showed higher concentrations under North African (NAF) air mass origins than under Atlantic. We observe a decreasing trend in all chemical components of PM10 under both types of air masses, NAF and Atlantic. Principal component analysis using more frequent air masses in the area allows the identification of five PM10 sources: crustal, regional, marine, traffic and industrial. Natural sources play a more relevant role during NAF events (20.6 µg · m(-3)) than in Atlantic episodes (13.8 µg · m(-3)). The contribution of the anthropogenic sources under NAF doubles the one under Atlantic conditions (33.6 µg · m(-3) and 15.8 µg · m(-3), respectively). During Saharan dust outbreaks the frequent accumulation of local anthropogenic pollutants in the lower atmosphere results in poor air quality and an increased risk of mortality. The results are relevant when analysing the impact of anthropogenic emissions on the exposed population in large cities. The increase in potentially toxic elements during Saharan dust outbreaks should also be taken into account when discounting the number of exceedances attributable to non-anthropogenic or natural origins.

In vitro and in vivo effects of lutein against cisplatin-induced ototoxicity.

INTRODUCTION: Cisplatin is a commonly prescribed drug that produces ototoxicity as a side effect. Lutein is a carotenoid with antioxidant and anti-inflammatory properties previously tested for eye, heart and skin diseases but not evaluated to date in ear diseases. AIM: To evaluate the protective effects of lutein on HEI-OC1 auditory cell line and in a Wistar rat model of cisplatin ototoxicity. MATERIALS AND METHODS: In vitro study: Culture HEI-OC1 cells were exposed to lutein (2.5-100 µM) and to 25 µM cisplatin for 24h. In vivo study: Twenty eight female Wistar rats were randomized into three groups. Group A (n=8) received intratympanic lutein (0.03 mL) (1mg/mL) in the right ear and saline solution in the left one to determine the toxicity of lutein. Group B (n=8) received also intraperitoneal cisplatin (10mg/kg) to test the efficacy of lutein against cisplatin ototoxicity. Group C (n=12) received intratympanic lutein (0.03 mL) (1mg/mL) to quantify lutein in cochlear fluids (30 min, 1h and 5 days after treatment). Hearing function was evaluated by means of Auditory Steady-State Responses before the procedure and 5 days after (groups A and B). Morphological changes were studied by confocal laser scanning microscopy. RESULTS: In vitro study: Lutein significantly reduced the cisplatin-induced cytotoxicity in the HEI-OC1 cells when they were pre-treated with lutein concentrations of 60 and 80 µM. In vivo study: Intratympanic lutein (1mg/mL) application showed no ototoxic effects. However it did not achieve protective effect against cisplatin-induced ototoxicity in Wistar rats. CONCLUSIONS: Although lutein has shown beneficial effects in other pathologies, the present study only obtained protection against cisplatin ototoxicity in culture cells, but not in the in vivo model. The large molecule size, the low dose administered, and restriction to diffusion in the inner ear could account for this negative result.

NUP98-HOXA9 bearing therapy-related myeloid neoplasm involves myeloid-committed cell and induces HOXA5, EVI1, FLT3, and MEIS1 expression.

INTRODUCTION: Chromosomal rearrangements involving NUP98 gene have been associated with human leukemias such as de novo AML, therapy-related AML (t-AML), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). Genetic fusion NUP98-HOXA9, caused by t(7;11)(p15;p15), is a recurrent cytogenetic alteration in de novo acute myeloid leukemia (AML) usually found in young Asian patients and its description in therapy-related myeloid neoplasms (t-MN) is rare. Only one Asian case with molecular demonstration of the NUP98-HOXA9 fusion has been reported in therapy-related leukemia. NUP98-HOXA9 leukemogenic mechanism is derived from the transcription factor activity of the chimeric protein, which enhances the expression of genes related to cellular differentiation arrest and proliferation. PATIENTS AND METHODS: We studied a Caucasian woman with a therapy-related acute myeloid leukemia after Ewing's sarcoma. Molecular demonstration of the genetic fusion NUP98-HOXA9 was performed by RT-PCR, and gene expression was analyzed by real-time PCR, including four AML patients with MLL rearrangements for comparative analysis. Cytologic and flow cytometric analysis was also carried out. RESULTS: After cytologic and flow cytometric analysis diagnostics was therapy-related myeloid neoplasm (t-MN). The major component of blasts in the acute leukemia was with neutrophilic differentiation, but 13% erythroid lineage blasts were also found. Cytogenetic and FISH analysis revealed t(7;11)(p15;p15) and NUP98-HOXA9 fusion gene was demonstrated. Gene expression analysis showed upregulation of EVI1 and MEIS1 in the index patient, both of them previously related to a worst outcome. CONCLUSION: In this work, we include a detailed molecular, clinical, cytological, and cytometric study of the second t-AML bearing NUP98-HOXA9 genetic fusion.