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Smart manufacturing comprises fully integrated manufacturing systems that respond in real time to meet the changing demands and conditions in industrial activities, supply networks and customer needs. A smart manufacturing environment will face new challenges, including those concerning metrological issues, i.e., analysis of large quantities of data; communication systems for digitalization; measurement standards for automated process control; digital transformation of metrological services; and simulations and virtual measurement processes for the automatic assessment of measured data. Based on the assumption that the interplay between smart manufacturing and digitalization of metrology is an emerging research field, this paper aims to present a systematic literature review (SLR) based on a bibliographic data collection of 160 scientific articles retrieved from the Web of Science and Scopus databases over the 2016-2022 time frame. The findings presented in this review and recommendations for building a research agenda can help policy makers, researchers and practitioners by providing directions for the evolution of digital metrology and its role in the digitalization of the economy and society.

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Adequately predicting overlay behaviour is essential for flexible pavement rehabilitation to reach the predicted lifespan. Reflective cracking is one of the main failure mechanisms affecting overlay performance. This failure may occur due to cracks in the lower layers that propagate to the overlay due to traffic loads, temperature variations, shrinkage cracking of cement-treated layers, and subgrade movements. This work aims to assess the reflective cracking phenomenon of asphalt rubber mixtures as an overlay through laboratory tests and numerical simulation. Four-point bending equipment and the reflective crack device were used to perform the laboratory tests. A numerical simulation through the finite element method was accomplished to estimate the von Mises strain and develop reflective cracking fatigue laws. The results showed that the asphalt rubber mixtures are suitable for extending overlay lifespan considering reflective cracking. The evaluated asphalt rubber mixtures presented reflective cracking resistance almost eight times greater than the conventional ones.

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Resumo Fundamento A pandemia de COVID-19 interferiu na prestação de atendimento a doenças cardiovasculares na América Latina. No entanto, o efeito da pandemia nos volumes de procedimentos cardíacos diagnósticos ainda não foi quantificado. Objetivo Avaliar (1) o impacto de COVID-19 nos volumes de diagnóstico cardíaco na América Latina e (2) determinar sua relação com a incidência de casos de COVID-19 e as medidas de distanciamento social. Métodos A International Atomic Energy Agency realizou uma pesquisa mundial avaliando mudanças nos volumes diagnósticos cardíacos decorrentes da COVID-19. Foram obtidos os volumes diagnósticos cardíacos dos locais participantes para março e abril de 2020 e comparados com março de 2019. Foram coletados dados de distanciamento social a partir dos Relatórios de mobilidade da comunidade de Google e a incidência de COVID-19 por país a partir de Our World in Data. Resultados Foram realizadas pesquisas em 194 centros que realizam procedimentos diagnósticos cardíacos, em 19 países da América Latina. Em comparação com o mês de março de 2019, os volumes dos procedimentos diagnósticos cardíacos diminuíram 36% em março de 2020 e 82% em abril de 2020.As maiores reduções ocorreram em relação aos testes de estresse ecocardiográfico (91%), testes ergométricos de esteira (88%) e escore de cálcio por tomografia computadorizada (87%), com pequenas variações entre as sub-regiões da América Latina. As mudanças em padrões de distanciamento social (p < 0,001) estavam mais fortemente associadas com a redução do volume do que a incidência de COVID-19 (p = 0,003). Conclusões A COVID-19 foi associada a uma redução significativa de procedimentos diagnósticos cardíacos na América Latina, a qual foi mais relacionada ao distanciamento social do que ao aumento da incidência da COVID-19. São necessários melhor equilíbrio e timing de medidas de distanciamento social e planejamento para manter o acesso ao atendimento médico durante um surto pandêmico, especialmente em regiões com alta mortalidade cardiovascular.

Abstract Background The COVID-19 pandemic has disrupted the delivery of care for cardiovascular diseases in Latin America. However, the effect of the pandemic on the cardiac diagnostic procedure volumes has not been quantified. Objective To assess (1) the impact of COVID-19 on cardiac diagnostic volumes in Latin America and (2) determine its relationship with COVID-19 case incidence and social distancing measures. Methods The International Atomic Energy Agency conducted a worldwide survey assessing changes in cardiac diagnostic volumes resulting from COVID-19. Cardiac diagnostic volumes were obtained from participating sites for March and April 2020 and compared to March 2019. Social distancing data were collected from Google COVID-19 community mobility reports and COVID-19 incidence per country from the Our World in Data. Results Surveys were conducted in 194 centers performing cardiac diagnostic procedures, in 19 countries in Latin America. Procedure volumes decreased 36% from March 2019 to March 2020, and 82% from March 2019 to April 2020. The greatest decreases occurred in echocardiogram stress tests (91%), exercise treadmill tests (88%), and computed tomography calcium scores (87%), with slight variations between sub-regions of Latin America. Changes in social distancing patterns (p < 0.001) were more strongly associated with volume reduction than COVID-19 incidence (p = 0.003). Conclusions COVID-19 was associated with a significant reduction in cardiac diagnostic procedures in Latin America, which was more related to social distancing than to the COVID-19 incidence. Better balance and timing of social distancing measures and planning to maintain access to medical care is warranted during a pandemic surge, especially in regions with high cardiovascular mortality.

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BACKGROUND: The COVID-19 pandemic has disrupted the delivery of care for cardiovascular diseases in Latin America. However, the effect of the pandemic on the cardiac diagnostic procedure volumes has not been quantified. OBJECTIVE: To assess (1) the impact of COVID-19 on cardiac diagnostic volumes in Latin America and (2) determine its relationship with COVID-19 case incidence and social distancing measures. METHODS: The International Atomic Energy Agency conducted a worldwide survey assessing changes in cardiac diagnostic volumes resulting from COVID-19. Cardiac diagnostic volumes were obtained from participating sites for March and April 2020 and compared to March 2019. Social distancing data were collected from Google COVID-19 community mobility reports and COVID-19 incidence per country from the Our World in Data. RESULTS: Surveys were conducted in 194 centers performing cardiac diagnostic procedures, in 19 countries in Latin America. Procedure volumes decreased 36% from March 2019 to March 2020, and 82% from March 2019 to April 2020. The greatest decreases occurred in echocardiogram stress tests (91%), exercise treadmill tests (88%), and computed tomography calcium scores (87%), with slight variations between sub-regions of Latin America. Changes in social distancing patterns (p < 0.001) were more strongly associated with volume reduction than COVID-19 incidence (p = 0.003). CONCLUSIONS: COVID-19 was associated with a significant reduction in cardiac diagnostic procedures in Latin America, which was more related to social distancing than to the COVID-19 incidence. Better balance and timing of social distancing measures and planning to maintain access to medical care is warranted during a pandemic surge, especially in regions with high cardiovascular mortality.

FUNDAMENTO: A pandemia de COVID-19 interferiu na prestação de atendimento a doenças cardiovasculares na América Latina. No entanto, o efeito da pandemia nos volumes de procedimentos cardíacos diagnósticos ainda não foi quantificado. OBJETIVO: Avaliar (1) o impacto de COVID-19 nos volumes de diagnóstico cardíaco na América Latina e (2) determinar sua relação com a incidência de casos de COVID-19 e as medidas de distanciamento social. MÉTODOS: A International Atomic Energy Agency realizou uma pesquisa mundial avaliando mudanças nos volumes diagnósticos cardíacos decorrentes da COVID-19. Foram obtidos os volumes diagnósticos cardíacos dos locais participantes para março e abril de 2020 e comparados com março de 2019. Foram coletados dados de distanciamento social a partir dos Relatórios de mobilidade da comunidade de Google e a incidência de COVID-19 por país a partir de Our World in Data. RESULTADOS: Foram realizadas pesquisas em 194 centros que realizam procedimentos diagnósticos cardíacos, em 19 países da América Latina. Em comparação com o mês de março de 2019, os volumes dos procedimentos diagnósticos cardíacos diminuíram 36% em março de 2020 e 82% em abril de 2020.As maiores reduções ocorreram em relação aos testes de estresse ecocardiográfico (91%), testes ergométricos de esteira (88%) e escore de cálcio por tomografia computadorizada (87%), com pequenas variações entre as sub-regiões da América Latina. As mudanças em padrões de distanciamento social (p < 0,001) estavam mais fortemente associadas com a redução do volume do que a incidência de COVID-19 (p = 0,003). CONCLUSÕES: A COVID-19 foi associada a uma redução significativa de procedimentos diagnósticos cardíacos na América Latina, a qual foi mais relacionada ao distanciamento social do que ao aumento da incidência da COVID-19. São necessários melhor equilíbrio e timing de medidas de distanciamento social e planejamento para manter o acesso ao atendimento médico durante um surto pandêmico, especialmente em regiões com alta mortalidade cardiovascular.

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Time reversal (TR) focusing of acoustical waves is a widely studied phenomenon that usually requires a chaotic cavity or disordered scattering medium to achieve spatial and frequency decorrelation of the acoustic field when using a single channel. On the other hand, sonic crystals were disregarded as scattering media for the TR process because of their periodic structure and previous results showing poor spatial focusing when compared to a disordered medium. In this paper, an experimental realization of a tunable sonic crystal, which can achieve single-channel TR focusing amplitudes in the audible range comparable to those obtained in a disordered scattering medium, is presented. Furthermore, the tunable nature of the system allows it to switch the time-reversed pulse on and off by changing its geometrical configuration. A robustness analysis with respect to the perturbations in the sonic crystal configurations is also presented, showing that the time-reversed pulses with high temporal and spatial contrasts are preserved only for configurations that are close to the original one.

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PURPOSE: To present a summary of the treatment and follow-up recommendations for the biochemical recurrence in castration-sensitive prostate cancer (PCa) acquired through a questionnaire administered to 99 PCa experts from developing countries during the Prostate Cancer Consensus Conference for Developing Countries. METHODS: A total of 27 questions were identified as related to this topic from more than 300 questions. The clinician's responses were tallied and presented in a percentage format. Topics included the use of imaging for staging biochemical recurrence, treatment recommendations for three different clinical scenarios, the field of radiation recommended, and follow-up. Each question had 5-7 relevant response options, including "abstain" and/or "unqualified to answer," and investigated not only recommendations but also if a limitation in resources would change the recommendation. RESULTS: For most questions, a clear majority (> 50%) of clinicians agreed on a recommended treatment for imaging, treatment scenarios, and follow-up, although only a few topics reached a consensus > 75%. Limited resources did affect several areas of treatment, although in many cases, they reinforced more stringent criteria for treatment such as prostate-specific antigen values > 0.2 ng/mL and STAMPEDE inclusion criteria as a basis for recommending treatment. CONCLUSION: A majority of clinicians working in developing countries with limited resources use similar cutoff points and selection criteria to manage patients treated for biochemically recurrent castration-sensitive PCa.

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Risk assessment of chemical mixtures has emerged as a focus of research efforts, but traditional toxicology testing in mammals is costly, time-consuming, and subject to ethical scrutiny in the context of recent trends to reduce reliance on animal testing. In this review, which is a summary of presentations given at a workshop in Havana, Cuba, in April 2019, we survey the utility of zebra fish as an alternative laboratory model in whole-mixture and component-based testing, as well as in vitro modeling in 3-dimensional organotypic cultures from primary human cells cultured at the air-liquid interface and organ-on-a-chip platforms. Finally, we discuss the complexities of assessing the dynamics and delivery of multispecies liquid aerosol mixtures along the human respiratory tract, with examples of alternative and computational approaches to aerosol dosimetry. The workshop contributed to the professional development of Cuban toxicologists, an underserved segment of the global scientific community, delivering a set of tools and recommendations that could potentially provide cost-effective solutions for scientists with limited research resources.

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INTRODUCTION: The aim of the study was to compare the effects of ten-week multicomponent training with different exercise frequencies on body composition (BC) and physical fitness (PF) in overweight and obese young children. METHODS: 40 children, aged 12-15 (14.77±1.49), were randomly selected and assigned to experimental groups to train three times/week (EG1) or two times/week (EG2) for 10 weeks and a CG group (no training program). RESULTS: It was shown that experimental groups (EG1 and EG2) improved similarly aerobic capacity (3.8% and 3.5%, respectively), muscular strength (29.7% and 25.2%), flexibility (6.1% and 9.9%), body mass index (5.0% and 4.6%), and body fat (6.4% and 5.6%) from pre- to post-training. CG group showed no significant improvements on BC and PF variables. CONCLUSION: Short-term multicomponent training seems to be effective on PF improvements, independently of the exercise frequency, in overweight and obese young children. However, it seems to be more effective to perform a multicomponent exercise training three times/week to improve muscular strength, body mass index, and decrease body fat percentage. This knowledge should be considered by professionals in physical education or youth sport in order to adapt practical tasks depending on the training purposes.

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Time-reversal of propagating waves has been intensely studied during the last years and successfully implemented in different experimental contexts. It has been argued that ergodic or chaotic ray dynamics improve the refocusing resolution. In this work we consider this fundamental aspect by studying the reversion of sound waves in two-dimensional reflecting cavities numerically. The boundary of the enclosure is deformed from a rectangle with regular ray dynamics to a completely chaotic hyperbolic billiard. We observed that both the regular and chaotic cases display a prominent refocusing peak, and also that in the first scenario many secondary maxima appear. We developed measures of the spatial and temporal contrasts of the reconstructed signal in order to gain insight on these phenomena and to distinguish between cases. The results obtained point to the necessity for a reconsideration of what is usually understood by successful time-reversal processes.

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In this study we evaluated whether a method of direct location is an appropriate response method for measuring auditory distance perception of far-field sound sources. We designed an experimental set-up that allows participants to indicate the distance at which they perceive the sound source by moving a visual marker. We termed this method Cross-Modal Direct Location (CMDL) since the response procedure involves the visual modality while the stimulus is presented through the auditory modality. Three experiments were conducted with sound sources located from 1 to 6 m. The first one compared the perceived distances obtained using either the CMDL device or verbal report (VR), which is the response method more frequently used for reporting auditory distance in the far field, and found differences on response compression and bias. In Experiment 2, participants reported visual distance estimates to the visual marker that were found highly accurate. Then, we asked the same group of participants to report VR estimates of auditory distance and found that the spatial visual information, obtained from the previous task, did not influence their reports. Finally, Experiment 3 compared the same responses that Experiment 1 but interleaving the methods, showing a weak, but complex, mutual influence. However, the estimates obtained with each method remained statistically different. Our results show that the auditory distance psychophysical functions obtained with the CMDL method are less susceptible to previously reported underestimation for distances over 2 m.

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In this article, we show that visual distance perception (VDP) is influenced by the auditory environmental context through reverberation-related cues. We performed two VDP experiments in two dark rooms with extremely different reverberation times: an anechoic chamber and a reverberant room. Subjects assigned to the reverberant room perceived the targets farther than subjects assigned to the anechoic chamber. Also, we found a positive correlation between the maximum perceived distance and the auditorily perceived room size. We next performed a second experiment in which the same subjects of Experiment 1 were interchanged between rooms. We found that subjects preserved the responses from the previous experiment provided they were compatible with the present perception of the environment; if not, perceived distance was biased towards the auditorily perceived boundaries of the room. Results of both experiments show that the auditory environment can influence VDP, presumably through reverberation cues related to the perception of room size.

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Previous studies on the effect of spectral content on auditory distance perception (ADP) focused on the physically measurable cues occurring either in the near field (low-pass filtering due to head diffraction) or when the sound travels distances >15 m (high-frequency energy losses due to air absorption). Here, we study how the spectrum of a sound arriving from a source located in a reverberant room at intermediate distances (1-6 m) influences the perception of the distance to the source. First, we conducted an ADP experiment using pure tones (the simplest possible spectrum) of frequencies 0.5, 1, 2, and 4 kHz. Then, we performed a second ADP experiment with stimuli consisting of continuous broadband and bandpass-filtered (with center frequencies of 0.5, 1.5, and 4 kHz and bandwidths of 1/12, 1/3, and 1.5 octave) pink-noise clips. Our results showed an effect of the stimulus frequency on the perceived distance both for pure tones and filtered noise bands: ADP was less accurate for stimuli containing energy only in the low-frequency range. Analysis of the frequency response of the room showed that the low accuracy observed for low-frequency stimuli can be explained by the presence of sparse modal resonances in the low-frequency region of the spectrum, which induced a non-monotonic relationship between binaural intensity and source distance. The results obtained in the second experiment suggest that ADP can also be affected by stimulus bandwidth but in a less straightforward way (i.e., depending on the center frequency, increasing stimulus bandwidth could have different effects). Finally, the analysis of the acoustical cues suggests that listeners judged source distance using mainly changes in the overall intensity of the auditory stimulus with distance rather than the direct-to-reverberant energy ratio, even for low-frequency noise bands (which typically induce high amount of reverberation). The results obtained in this study show that, depending on the spectrum of the auditory stimulus, reverberation can degrade ADP rather than improve it.

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ABSTRACT Trypanosomatid type I nitroreductases (NTRs), i.e., mitochondrial enzymes that metabolise nitroaromatic pro-drugs, are essential for parasite growth, infection, and survival. Here, a type I NTR of non-virulent protozoan Trypanosoma rangeli is described and compared to those of other trypanosomatids. The NTR gene was isolated from KP1(+) and KP1(-) strains, and its corresponding transcript and 5' untranslated region (5'UTR) were determined. Bioinformatics analyses and nitro-drug activation assays were also performed. The results indicated that the type I NTR gene is present in both KP1(-) and KP1(+) strains, with 98% identity. However, the predicted subcellular localisation of the protein differed among the strains (predicted as mitochondrial in the KP1(+) strain). Comparisons of the domains and 3D structures of the NTRs with those of orthologs demonstrated that the nitroreductase domain of T. rangeli NTR is conserved across all the strains, including the residues involved in the interaction with the FMN cofactor and in the tertiary structure characteristics of this oxidoreductase protein family. mRNA processing and expression were also observed. In addition, T. rangeli was shown to be sensitive to benznidazole and nifurtimox in a concentration-dependent manner. In summary, T. rangeli appears to have a newly discovered functional type I NTR.

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Trypanosomatid type I nitroreductases (NTRs), i.e., mitochondrial enzymes that metabolise nitroaromatic pro-drugs, are essential for parasite growth, infection, and survival. Here, a type I NTR of non-virulent protozoan Trypanosoma rangeli is described and compared to those of other trypanosomatids. The NTR gene was isolated from KP1(+) and KP1(-) strains, and its corresponding transcript and 5' untranslated region (5'UTR) were determined. Bioinformatics analyses and nitro-drug activation assays were also performed. The results indicated that the type I NTR gene is present in both KP1(-) and KP1(+) strains, with 98% identity. However, the predicted subcellular localisation of the protein differed among the strains (predicted as mitochondrial in the KP1(+) strain). Comparisons of the domains and 3D structures of the NTRs with those of orthologs demonstrated that the nitroreductase domain of T. rangeli NTR is conserved across all the strains, including the residues involved in the interaction with the FMN cofactor and in the tertiary structure characteristics of this oxidoreductase protein family. mRNA processing and expression were also observed. In addition, T. rangeli was shown to be sensitive to benznidazole and nifurtimox in a concentration-dependent manner. In summary, T. rangeli appears to have a newly discovered functional type I NTR.

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Proteinuria is a marker and mediator of chronic kidney disease (CKD). In clinical practice, the urinary protein-to-creatinine ratio (UP/C) is of limited usefulness, because it indicates only the magnitude of proteinuria and not the origin of the loss (glomerular or tubular). The complete assessment of proteinuria includes quantitative and qualitative evaluations, both of which are required in order to optimize the therapy. In addition to measuring the UP/C, we performed SDS-PAGE and western blotting to determine the expression of albumin, vitamin D-binding protein (VDBP), retinol-binding protein (RBP), and Tamm-Horsfall protein (THP) in urine samples of 49 dogs: healthy (control) dogs (n = 9); and dogs with CKD (n = 40), stratified by stage. In the dogs with stage 3 or 4 CKD, there was a predominance of tubular proteins. Neither VDBP nor RBP was observed in the urine of the control dogs. Among the dogs with stage 1 or 2 CKD, VDBP and RBP were detected in those without proteinuria or with borderline proteinuria. The expression of urinary albumin was significantly higher in the stage 4 group than in any other group (P ≤ 0.01). In the stage 4 group, urinary THP was either undetectable or lower than in the control group (P ≤ 0.01). In conclusion, urinary VDBP and RBP might act as early markers of kidney injury, and a decrease in urinary THP could be an indicator of CKD progression.

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Chagas disease is a chronic infection caused by Trypanosoma cruzi, an intracellular protozoan parasite. Chronic chagasic patients (CCPs) have dysfunctional CD8+ T cells that are characterized by impaired cytokine production, high coexpression of inhibitory receptors, and advanced cellular differentiation. Most patients diagnosed in the chronic phase of Chagas disease already exhibit heart involvement, and there is no vaccination that protects against the disease. Antiparasitic treatment is controversial as to its indication for this stage of the disease. There is a lack of biological markers to evaluate the effectiveness of antiparasitic treatment, and little is known about the effect of the treatment on CD8+ T cells. Thus, the aim of the current study was to analyze the early effects of antiparasitic treatment on CD8+ T cells from CCPs with asymptomatic clinical forms of disease. To evaluate the CD8+ T cell subsets, expression of inhibitory receptors, and functionality of T cells in CCPs, PBMCs were isolated. The results showed that treatment of CCPs with the asymptomatic form of the disease induces an increase in the frequency of CD8+ central memory T cells and terminal effector T cells, a decrease in the coexpression of inhibitory receptors, an improved Ag-specific CD8+ T cell response exhibited by the individual production of IFN-γ or IL-2, and a multifunctional CD8+ T cell profile of up to four functions (IFN-γ+IL-2+Perforin+Granzyme B+). These findings suggest that, in CCPs, antiparasitic treatment improved the quality of Ag-specific CD8+ T cell responses associated with a decrease in inhibitory receptor coexpression, which could serve as biomarkers for monitoring the effectiveness of antiparasitic treatment.

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BACKGROUND/AIMS: Acute activation of sympathetic activation during hemodialysis is essential to maintain blood pressure (BP), albeit long-term overactivity contributes to higher mortality. Low heart rate variability (HRV), a measure of autonomic nervous system activity, and abnormal ankle-brachial index (ABI) are associated with higher mortality in patients on hemodialysis. In this study, we assessed HRV and ABI pre and post dialysis in incident patients on hemodialysis using high (1.75mmol/l) and low (1.25mmol/l) dialysate calcium concentration (DCa). METHODS: HRV was measured as the ratio between low frequency and high frequency power (LF/HF). Thirty patients (age 47±16 years, 67% men) were studied in two consecutive mid-week hemodialysis sessions. RESULTS: Mean BP variation was positive with DCa 1.75 and negative with DCa 1.25 [4.0 (-6.0, 12.2 mmHg) vs. -3.2 (-9.8, 1.3 mmHg); p=0.050]. Reduction of ABI from pre to post HD was related to higher sympathetic activity (p=0.031). The increase in LF/HF ratio was higher with DCa 1.75 (58.3% vs. 41.7% in DCa 1.75 and 1.25, respectively, RR 2.8; p=0.026). CONCLUSION: Although higher DCa is associated with better hemodynamic tolerability during hemodialysis, this occurs at the expense of increased sympathetic activity. Higher sympathetic activity was associated with a decrease of ABI during hemodialysis.

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BACKGROUND: Approximately 10% of pancreatic neuroendocrine tumors (NET) are associated with familial syndromes, with the most common type being multiple endocrine neoplasia type 1 (MEN-1). However, the available evidence on how to treat NET comes from studies in sporadic NET. CASE REPORT: Here we report the case of a 51-year-old male patient with a metastatic MEN-1-associated pancreatic NET and hypercalcemia related to primary hyperparathyroidism and tumor-secreted parathyroid-related protein. The patient was treated with everolimus, and showed complete resolution of hypercalcemia and tumor control for 3 years when he presented with pulmonary cryptococcosis and disease progression. CONCLUSION: This case report describes the activity of everolimus in a patient with MEN-1-associated pancreatic NET, its efficacy in treating malignant hypercalcemia associated with NET and the risk of opportunistic infections with prolonged use of this agent.

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RNA helicases are ubiquitous enzymes that participate in almost all aspects of RNA processing, including RNA and RNA-protein complex remodelling. In trypanosomatids, which post-transcriptionally regulate gene expression, the formation of different kinds of ribonucleoprotein granules under stress conditions modulates the parasite's RNA metabolism. This paper describes the isolation of a putative DEVH-box RNA helicase produced by promastigotes of Leishmania braziliensis. Using a Cy3-labelled dT30 oligo, FISH showed the localization of this protein to mRNA granules under starvation stress conditions. The central region of the protein was shown to be responsible for this behaviour.

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