Vasopressinergic modulation of stress responses in the central amygdala of the Roman high-avoidance and low-avoidance rat

The central nucleus of the amygdala (CEA) is selectively involved in the passive component of the behavioral (immobility) and the accompanying parasympathetic response during conditioned, stressful environmental challenges. Vasopressinergic mechanisms in the brain seem to play a role in these stress responses. The effects of the neuropeptides arginine-8-vasopressin (AVP) and oxytocin (OXT) on modulating CEA activity during conditioned stress of inescapable footshock were studied in male Roman high-avoidance (RHA/Verh) and low-avoidance (RLA/Verh) rats, psychogenetically selected on the basis of shuttle-box acquisition behavior. In RLA/Verh rats, the cardiac and behavioral responses to the conditioned emotional stressor were bradycardia and immobility, suggesting an important role for the CEA in these rats. The RHA/Verh rats, however, failed to show any change in heart rate or immobility in response to a conditioned stress situation. The low dose of AVP (20 pg) in the CEA of conscious RLA/Verh rats caused an enhancement of the stress-induced bradycardiac and immobility response. However, the high dose of AVP (2 ng) and OXT (200 pg) attenuated the bradycardiac and immobility responses in the RLA/Verh rats. Infusion of AVP and OXT in the RHA/Verh rats failed to induce any change in heart rate nr immobility. Binding studies revealed that the AVP receptor selectively binds AVP with high affinity. In contrast, the OXT receptor recognizes both AVP and OXT with a similar (but lower) affinity. This suggests that the behavioral and autonomic responses of the high dose of AVP may be caused by OXT receptor stimulation. In conclusion, on the basis of the present results one may hypothesize that CEA differences in AVP and OXT innervation and/or receptor densities may contribute to the differences in coping strategy found in these animals.

Developmental Outcomes of Very Preterm Infants with Tracheostomies

Objectives To evaluate the neurodevelopmental outcomes of very preterm (<30 weeks) infants who underwent tracheostomy. Study design Retrospective cohort study from 16 centers of the NICHD Neonatal Research Network over 10 years (2001-2011). Infants who survived to at least 36 weeks (N=8,683), including 304 infants with tracheostomies, were studied. Primary outcome was death or neurodevelopmental impairment (NDI, a composite of one or more of: developmental delay, neurologic impairment, profound hearing loss, severe visual impairment) at a corrected age of 18-22 months. Outcomes were compared using multiple logistic regression. We assessed impact of timing, by comparing outcomes of infants who underwent tracheostomy before and after 120 days of life. Results Tracheostomies were associated with all neonatal morbidities examined, and with most adverse neurodevelopmental outcomes. Death or NDI occurred in 83% of infants with tracheostomies and 40% of those without [odds ratio (OR) adjusted for center 7.0 (95%CI, 5.2-9.5)]. After adjustment for potential confounders, odds of death or NDI remained higher [OR 3.3 (95%CI, 2.4-4.6)], but odds of death alone were lower [OR 0.4 (95%CI, 0.3-0.7)], among infants with tracheostomies. Death or NDI was lower in infants who received their tracheostomies before, rather than after, 120 days of life [adjusted OR 0.5 (95%CI, 0.3-0.9)]. Conclusions Tracheostomy in preterm infants is associated with adverse developmental outcomes, and cannot mitigate the significant risk associated with many complications of prematurity. These data may inform counseling about tracheostomy in this vulnerable population

Low-Level Laser Therapy Activates NF-kB via Generation of Reactive Oxygen Species in Mouse Embryonic Fibroblasts

Background Despite over forty years of investigation on low-level light therapy (LLLT), the fundamental mechanisms underlying photobiomodulation at a cellular level remain unclear. Methodology/Principal Findings In this study, we isolated murine embryonic fibroblasts (MEF) from transgenic NF-kB luciferase reporter mice and studied their response to 810 nm laser radiation. Significant activation of NF-kB was observed at fluences higher than 0.003 J/cm2 and was confirmed by Western blot analysis. NF-kB was activated earlier (1 hour) by LLLT compared to conventional lipopolysaccharide treatment. We also observed that LLLT induced intracellular reactive oxygen species (ROS) production similar to mitochondrial inhibitors, such as antimycin A, rotenone and paraquat. Furthermore, we observed similar NF-kB activation with these mitochondrial inhibitors. These results, together with inhibition of laser induced NF-kB activation by antioxidants, suggests that ROS play an important role in the laser induced NF-kB signaling pathways. However, LLLT, unlike mitochondrial inhibitors, induced increased cellular ATP levels, which indicates that LLLT also upregulates mitochondrial respiration. Conclusion We conclude that LLLT not only enhances mitochondrial respiration, but also activates the redox-sensitive NFkB signaling via generation of ROS. Expression of anti-apoptosis and pro-survival genes responsive to NFkB could explain many clinical effects of LLLT.National Institutes of Health (U.S.) (grant R01AI050875)Center for Integration of Medicine and Innovative Technology (DAMD17-02-2-0006)United States. Dept. of Defense (CDMRP Program in TBI, W81XWH-09-1-0514)United States. Air Force Office of Scientific Research (FA9950-04-1-0079

Weaning of Moderately Preterm Infants from the Incubator to the Crib: A Randomized Clinical Trial

OBJECTIVE: To assess whether length of hospital stay is decreased among moderately preterm infants weaned from incubator to crib at a lower vs higher weight. STUDY DESIGN: This trial was conducted in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants with gestational ages 29-33 weeks, birthweight <1600 g, and in an incubator were randomly assigned to a weaning weight of 1600 or 1800 g. Within 60 to 100 g of weaning weight, the incubator temperature was decreased by 1.0°C to 1.5°C every 24 hours until 28.0°C. The infants were weaned to the crib following stable temperature at 36.5°C to 37.4°C for 8 to 12 hours. Clothing and bedcoverings were standardized. The primary outcome was length of hospital stay from birth to discharge; secondary outcomes included length of stay and growth velocity from weaning to discharge. Adverse events were monitored. RESULTS: Of 1565 infants screened, 885 were eligible, and 366 enrolled-187 to the 1600-g and 179 to the 1800-g group. Maternal and neonatal characteristics did not differ among weight groups. Length of hospital stay was a median of 43 days in the lower and 41 days in the higher weight group (P = .12). Growth velocity from completion of weaning to discharge was higher in the lower weight group, 13.7 g/kg/day vs 12.8 g/kg/day (P = .005). Groups did not differ in adverse events. CONCLUSIONS: Among moderately preterm neonates, weaning from incubator to crib at a lower weight did not decrease length of stay, but was safe and was accompanied by higher weight gain after weaning

Rare non-Wilms' tumors in children

We report our institutional experience of the management of 2 cases of rare non-Wilms' tumors; a rhabdoid tumor in a 17-month old boy and a clear cell sarcoma in a 5-year old girl. The two patients were treated with ifosfamide/carboplatin/etoposide (ICE) alternating with vincristine/doxorubicin/cyclophosphamide (VDC) and cyclophosphamide/etoposide (CE) alternating with vincristine/doxorubicin/cyclophosphamide (VDC) and radiotherapy, respectively. Both patients showed full response with no significant adverse events. At 2-year follow up, they are disease and relapse free. Although contemporary treatment regimens are very promising, multicenter collaborative studies are needed in order to define a standard treatment for non-Wilms' tumors

Effect of heptavalent pneumococcal conjugate vaccination on invasive pneumococcal disease in preterm born infants

<p>Abstract</p> <p>Background</p> <p>Evidence for protection of preterm born infants from invasive pneumococcal disease (IPD) by 7-valent pneumococcal conjugate vaccination (PCV7) is relatively sparse. Data from randomized trials is based on relatively small numbers of preterm born children.</p> <p>Methods</p> <p>We report data from active prospective surveillance of IPD in children in Germany. The cohorts of preterm born children in 2000 and 2007 and the respective whole birth cohorts are compared regarding occurrence of IPD.</p> <p>Results</p> <p>After introduction of PCV7 we observed a reduction in the rate of IPD in preterm born infants comparing the 2000 and 2007 birth cohort. The rate of IPD among the whole birth cohorts was reduced from 15.0 to 8.5 notifications per 100,000 (<it>P </it>< .001). The impact among the preterm birth cohort was comparable: A reduction in notification rate from 26.1 to 16.7 per 100,000 comparing the 2000 with the 2007 preterm birth cohort (<it>P </it>= .39). Preterm born infants with IPD were either unvaccinated or vaccinated delayed or incomplete.</p> <p>Conclusions</p> <p>This adds to evidence that PCV7 also protects preterm born infants effectively from IPD. Preterm born infants should receive pneumococcal vaccination according to their chronological age.</p

How histopathological diagnosis interacts with kidney ultrasound parameters and glomerular filtration rate

The evaluation of estimated GFR (eGFR) is a pivotal staging step in patients with chronic kidney disease (CKD), and renal ultrasound plays an important role in diagnosis, prognosis and progression of CKD. The interaction between histopathological diagnosis and ultrasound parameters in eGFR determination has not been fully investigated yet. The study examined the results of native kidney biopsies performed in 48 Italian centers between 2012 and 2020. The primary goal was if and how the histopathological diagnosis influences the relationship between ultrasound parameters and eGFR. After exclusion of children, patients with acute kidney injury and patients without measure of kidney length or parenchymal thickness, 2795 patients have been selected for analysis. The median values were 52&nbsp;years for patient age, 11&nbsp;cm for bipolar kidney diameter, 16&nbsp;mm for parenchymal thickness, 2.5&nbsp;g/day for proteinuria and 70&nbsp;ml/min/1.73 m2 for eGFR. The bipolar kidney diameter and the parenchymal thickness were directly related with eGFR values (R square 0.064). Diabetes and proteinuria were associated with a consistent reduction of eGFR, improving the adjusted R square up to 0.100. Addition of histopathological diagnosis in the model increased the adjusted R square to 0.216. There is a significant interaction between histopathological diagnosis and longitudinal kidney diameter (P 0.006). Renal bipolar length and parenchymal thickness are directly related with eGFR. The magnitude of proteinuria and histopathological kidney diagnosis are associated with eGFR. The relationship between kidney length and the level of eGFR depends on the nature of the kidney disease

MYCN gene amplification is a powerful prognostic factor even in infantile neuroblastoma detected by mass screening

MYCN is the most powerful prognostic factor in cases of older children. However, how MYCN is related to the prognosis of infantile cases is not clear. A mass screening program was carried out by measuring urinary catecholamine metabolites (VMA and HVA) from 6-month-old infants. Of 2084 cases detected by the screening program, MYCN amplification (MNA) was examined by Southern blot analyses in 1533 cases from 1987 to 2000. Of the 1533 cases examined, 1500 (97.8%) showed no MNA, 20 cases (1.3%) showed MNA from three to nine copies, and 13 (0.8%) cases showed more than 10 copies. The 4-year overall survival rates of these three groups (99, 89 and 53%, respectively) were significantly different (P<0.001), indicating that MYCN copy number correlates with the prognosis. Cases with MNA more than 10 copies were more advanced than those without amplification (stage III, IV vs I, II, IVs; P<0.001). Patients with MNA more than 10 copies had significantly higher serum levels of neuron-specific-enolase (NSE) and ferritin than non-amplified patients (P=0.049, P=0.025, respectively). MYCN amplification was strongly correlated with a poor prognosis in infantile neuroblastoma cases. Therefore, for the selection of appropriate treatment, an accurate determination of MNA is indispensable

Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxel-cisplatin chemotherapy: a prospective study

<p>Abstract</p> <p>Background</p> <p>A frequent manifestation of advanced NSCLC is malnutrition, even though there are many studies which relate it with a poor survival, its relation with toxicity has not yet been consistently reported. The aim of this study was to associate malnutrition and albumin serum levels with the occurrence of chemotherapy-induced toxicity in cisplatin plus paclitaxel chemotherapy-treated NSCLC.</p> <p>Methods</p> <p>We prospectively evaluated 100 stage IV NSCLC patients treated with paclitaxel (175 mg/m²) and cisplatin (80 mg/m²). Malnutrition was assessed using SGA prior treatment. Neutrophil Lymphocyte Ratio (NLR) and the Platelet Lymphocyte Ratio (PLR) were used to determine the presence of systemic inflammatory response (SIR) and were related to the development of toxicity. Toxicity was graded according to NCI CTCAE version 3.0 after two chemotherapy cycles.</p> <p>Results</p> <p>Median age was 58 ± 10 years, 51% of patients were malnourished, 50% had albumin ≤3.0 mg/mL. NLR ≥ 5 was associated with basal hypoalbuminemia (mean ranks, 55.7 vs. 39 p = 0.006), ECOG = 2 (47.2 vs. 55.4 p = 0.026) and PLR ≥ 150 were significantly related with a basal body mass index ≤20 (56.6 vs. 43.5; p = 0.02) and hypoalbuminemia (58.9 vs. 41.3; p = 0.02). Main toxicities observed after 2 cycles of chemotherapy were alopecia (84%), nausea (49%), neuropathy (46%), anemia (33%), lymphopenia (31%), and leukopenia (30%). Patients malnourished and with hypoalbuminemia developed more chemotherapy-induced toxicity overall when compared with those without malnutrition (31 vs 22; <it>p </it>= 0.02) and normal albumin (mean ranks, 62 vs 43; <it>p </it>= 0.002), respectively. Hypoalbuminemia was associated with anemia (56 vs 47; <it>p </it>= 0.05), fatigue (58 vs 46; <it>p </it>= 0.01), and appetite loss (57.1 vs 46.7; <it>p </it>= 0.004) compared with normal albumin. PLR ≥ 150 was related with the development of toxicity grade III/IV (59.27 vs. 47.03 p = 0.008) and anemia (37.9 vs 53.8 p = 0.004).</p> <p>Conclusion</p> <p>SIR parameters were associated with malnutrition, weight loss and hypoalbuminemia. Chemotherapy-induced toxicity in NSCLC patients treated with paclitaxel and cisplatin was associated with malnutrition and hypoalbuminemia. Early nutritional assessment and support might confer beneficial effects.</p