Given a passage, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Angiotensin II (Ang II) signaling has been implicated in cardiac arrhythmogenesis, which involves induction of reactive oxygen species (ROS). It was shown that Ang II can activate Ca/Calmodulin kinase II (CaMKII) by oxidation via a NADPH oxidase 2 (NOX2)-dependent pathway leading to increased arrhythmic afterdepolarizations. Interestingly, cAMP-dependent protein kinase A (PKA) which regulates similar targets as CaMKII has recently been shown to be redox-sensitive as well.', 'This study aims to investigate the distinct molecular mechanisms underlying Ang II-related cardiac arrhythmias with an emphasis on the individual contribution of PKA vs. CaMKII.', 'Isolated ventricular cardiac myocytes from rats and mice were used. Ang II exposure resulted in increased NOX2-dependent ROS generation assessed by expression of redox-sensitive GFP and in myocytes loaded with ROS indicator MitoSOX. Whole cell patch clamp measurements showed that Ang II significantly increased peak Ca and Na current (ICa and INa) possibly by enhancing steady-state activation of ICa and INa. These effects were absent in myocytes lacking functional NOX2 (gp91phox(-/-)). In parallel experiments using PKA inhibitor H89, the Ang II effects on peak INa and ICa were also absent. In contrast, genetic knockout of CaMKIIδ (CaMKIIδ(-/-)) did not influence the Ang II-dependent increase in peak ICa and INa. On the other hand, Ang II enhanced INa inactivation, increased late INa and induced diastolic SR (sarcoplasmic reticulum) Ca leak (confocal Ca spark measurements) in a CaMKIIδ-, but not PKA-dependent manner. Surprisingly, only the increase in diastolic SR Ca leak was absent in gp91phox(-/-)myocytes suggesting that Ang II regulates INa inactivation in a manner dependent on CaMKII- but not on NOX2. Finally, we show that Ang II increased the propensity for cellular arrhythmias, for which PKA and CaMKII contribute, both dependent on NOX2.
Does nADPH oxidase 2 mediate angiotensin II-dependent cellular arrhythmias via PKA and CaMKII?

Inadequate nutrition in very-low-birthweight (VLBW) infants is known to be associated with growth failure and poor neurological outcomes. We aimed to investigate the association of early aggressive protein and energy intakes with weight gain and 18-month neurodevelopmental outcomes in VLBW infants.', "A total of 90 infants among 129 infants who survived to discharge were included and divided into two groups (early aggressive nutrition [n = 52] vs conventional nutrition [n = 38]). Clinical findings were compared between the two groups and daily protein and energy intakes were collected for the first 4 weeks of life. Multiple regression analyses tested the association between weekly protein or energy intakes and the result of each category of the Denver Developmental Screening Test II at 18 months' corrected age or weight gain.", "The early aggressive nutrition group had higher rates of normal language development and lower rates of growth failure (<10th percentile) at both 40 weeks' and 18 months' corrected age compared to the conventional nutrition group. After controlling for the confounding variables, higher first week protein and energy intakes each independently contributed to normal language development (odds ratio [95% confidence interval]; 9.4 [1.8-49.6] per 1\u2009g/kg of protein increase and 1.7 [1.1-2.8] per 10\u2009kcal/kg of energy increase). Higher first-week protein intake was associated with a higher weight at 40 weeks' corrected age (r = 0.41, P = 0.005).
Does early aggressive nutrition enhance language development in very low-birthweight infants?

Chemotherapy is still a critical issue in the management of leishmaniasis. Until recently, pentavalent antimonials, amphotericin B or pentamidine compounded the classical arsenal of treatment. All these drugs are toxic and have to be administered by the parenteral route. Tamoxifen has been used as an antiestrogen in the treatment and prevention of breast cancer for many years. Its safety and pharmacological profiles are well established in humans. We have shown that tamoxifen is active as an antileishmanial compound in vitro, and in this paper we analyzed the efficacy of tamoxifen for the treatment of mice infected with Leishmania amazonensis, an etiological agent of localized cutaneous leishmaniasis and the main cause of diffuse cutaneous leishmaniasis in South America.', 'BALB/c mice were infected with L. amazonensis promastigotes. Five weeks post-infection, treatment with 15 daily intraperitoneal injections of 20 mg/kg tamoxifen was administered. Lesion and ulcer sizes were recorded and parasite burden quantified by limiting dilution. A significant decrease in lesion size and ulcer development was noted in mice treated with tamoxifen as compared to control untreated animals. Parasite burden in the inoculation site at the end of treatment was reduced from 10(8.5+/-0.7) in control untreated animals to 10(5.0+/-0.0) in tamoxifen-treated mice. Parasite load was also reduced in the draining lymph nodes. The reduction in parasite number was sustained: 6 weeks after the end of treatment, 10(15.5+/-0.5) parasites were quantified from untreated animals, as opposed to 10(5.1+/-0.1) parasites detected in treated mice.

Is tamoxifen effective in the treatment of Leishmania amazonensis infections in mice?