Impact of persistent pulmonary hypertension and oxygenation on brain injury in neonates with neonatal encephalopathy treated with therapeutic hypothermia.

OBJECTIVE: To investigate the effects of persistent pulmonary hypertension (PPHN) and oxygenation on outcome of neonates with neonatal encephalopathy (NE) treated with therapeutic hypothermia (TH). STUDY DESIGN: We compared the outcome of neonates with NE treated with TH with or without PPHN. RESULTS: 384 neonates with NE were treated with TH; 24% had PPHN. The fraction of inspired oxygen was higher in the first 4 days of life (p < 0.001) in neonates with PPHN. They had a significantly lower arterial partial pressure of oxygen in the first 4 days of life (p = 0.005) and higher on days 3-4 of life (p < 0.001). They were more often intubated (p < 0.001) and more often had concomitant hypotension (p < 0.001). They had higher mortality (p = 0.009) and more often developed brain injury (p = 0.02). CONCLUSION: PPHN occurred frequently in neonates with NE treated with TH and was associated with a higher incidence of adverse outcome.

Reduction of sodium additives in cooked sausages: effect on physicochemical, sensory and microbiological characteristics.

Several efforts have been made to reduce sodium in meat products due to its demonstrated negative health effects. This study evaluated the effect on physicochemical, sensory and microbiological characteristics of cooked sausages after a simultaneous reduction of salt (2.2% and 1.8%), Na-lactate (2.8% and 1.5%) and sodium tripolyphosphate (STPP) (0.4% and 0.2%). Salt and STPP reduction affected cooking loss, while no significant differences (P > 0.05) were obtained in instrumental and sensory texture for all factors. Discrimination tests showed significant perceived differences between some pairs, however, d' values were below 0.55 in all comparisons, meaning consumer awareness of the reduction might be irrelevant in a real-life scenario. A simultaneous reduction of Na-lactate and salt did not affect microbial stability (psychrotrophic and LAB counts) of the product. Reducing sodium-containing additives might be a low cost, promising strategy to reduce total sodium content in cooked sausages with no detrimental of their physicochemical, sensory and microbiological characteristics.

A comparison of background membrane imaging versus flow technologies for subvisible particle analysis of biologics.

A recently developed high-throughput background membrane imaging (BMI) technique, the HORIZON, was assessed for its ability to quantify subvisible particulate (SVP) generated during protein therapeutic development. The HORIZON platform method was optimized and compared to three well-characterized SVP counting techniques: light obscuration, micro-flow imaging (MFI), and FlowCam®. A head-to-head comparison was performed for precision, linearity, SVP concentration, and morphological output of BMI compared to the other three techniques using two unique enzymes under investigation. We found that dilution requirements for BMI are protein-specific, and membrane coverage is the critical instrument parameter to monitor for dilution suitability. The precision of BMI ranked similarly to all other techniques. Analysis of the same sample dilution, run in triplicate, across all four techniques indicated the BMI technique provides SVP concentrations that are comparable with the flow imaging techniques. Morphological information from BMI was generally less practical when compared with flow microscopy. The major drawback of BMI was that the current software indiscriminately clips large particles, potentially resulting in a misrepresentation of SVP size distribution. Despite this phenomenon, the concentration and size data generated corresponds well with current flow imaging techniques while decreasing time, cost, and sample requirements for SVP quantification.

Impact of restricting fluid and sodium intake in term asphyxiated newborns treated with hypothermia.

Aim: To study the consequences of restricting fluid and sodium intake in asphyxiated newborns treated with hypothermia.Methods: We conducted a retrospective cohort study of asphyxiated newborns treated with hypothermia from 2009 to 2015. The fluid, parenteral nutrition, and sodium, as well as the urine produced per day, were calculated. Sodium and creatinine concentrations were recorded. The presence/severity of brain injury was scored.Results: Among the 202 newborns, 55% did not have their fluid and sodium intake restricted and 45% had their fluid and sodium intake restricted. Newborns for whom fluid and sodium was restricted had significantly lower sodium concentrations during hospitalization (p = .02) and tended to develop more often a sodium concentration lower than 125 mmol/L (p = .08). They also were more likely to experience worsening in their creatinine levels during hospitalization (p = .03) and developed more often acute kidney injury (p = .02). The incidence of severe brain injury was higher in those newborns (58 versus 43%, p = .12), although not statistically different.Conclusion: A restrictive strategy for fluid and sodium intake did not appear to be beneficial for asphyxiated newborns treated with hypothermia and might even be harmful.

Endurance training slows breast tumor growth in mice by suppressing Treg cells recruitment to tumors.

BACKGROUND: Aerobic exercise has been shown to slow tumor progression in rodents and humans, but the mechanisms behind this effect are still unclear. Here we show that aerobic exercise in the form of chronic endurance training suppresses tumor recruitment of FoxP3+ Treg cells thus enhancing antitumor immune efficiency. METHODS: Adult wild-type and athymic BALB/c female mice were endurance-trained for 8 weeks. Circulating leukocytes as well as muscle and liver mtDNA copy number were compared to aged-matched concurrent sedentary controls to establish systemic effects. 4 T1 murine mammary tumor cells were injected subcutaneously to the 4th mammary pad at the end of the training period. Tumor growth and survival rates were compared, together with antitumor immune response. RESULTS: Exercised wild-type had 17% slower growth rate, 24% longer survival, and 2-fold tumor-CD+ 8/FoxP3+ ratio than sedentary controls. Exercised athymic BALB/c females showed no difference in tumor growth or survival rates when compared to sedentary controls. CONCLUSIONS: Cytotoxic T cells are a significant factor in endurance exercise-induced suppression of tumor growth. Endurance exercise enhances antitumor immune efficacy by increasing intratumoral CD8+/FoxP3+ ratio.

Association between hypocapnia and ventilation during the first days of life and brain injury in asphyxiated newborns treated with hypothermia.

PURPOSE: Therapeutic hypothermia is the standard treatment for asphyxiated newborns. Since hypocapnia is common in these newborns, the aim of this study was to assess the association among hypocapnia, ventilation, and brain injury. METHODS: We conducted a retrospective cohort study of all asphyxiated newborns treated with hypothermia from 2008 to 2014. Partial pressure of carbon dioxide (pCO2), ventilatory status, and modes of ventilation were recorded during the first 4 days of life. Brain injury was evaluated using brain magnetic resonance imaging. Differences between intubated and nonintubated newborns and between the newborns who developed brain injury or not were assessed. RESULTS: One hundred ninety-eight asphyxiated newborns were treated with hypothermia. During the first 2 days of life, intubated newborns had consistently lower pCO2 levels (respectively, 29.01 ± 8.55, p < .001 on day 1 of life and 33.65 ± 7.12, p = .004 on day 2 of life). Fifty-nine percent of the intubated newborns developed brain injury versus only 43% of the nonintubated newborns (p = .046). The lowest pCO2 levels averaged over the first 4 days of life were significantly decreased in newborns developing brain injury (p = .02) and significantly associated with brain injury severity (p = .01). After adjusting for potential cofounders, the lowest pCO2 averaged over days 1-4 of life remained significantly associated with an increased risk of brain injury (odds ratio [95%CI]: 1.07 [1.00-1.14]; p = .04). CONCLUSIONS: Intubated and ventilated asphyxiated newborns experienced more severe hypocapnia, and had higher incidences of brain injury. Hypocapnia during the first 4 days of life was associated with an increased risk of developing (more severe) brain injury.

Illness Severity Predicts Death and Brain Injury in Asphyxiated Newborns Treated with Hypothermia.

OBJECTIVE: To determine if illness severity during the first days of life predicts adverse outcome in asphyxiated newborns treated with hypothermia. STUDY DESIGN: We conducted a retrospective cohort study of asphyxiated newborns treated with hypothermia. Illness severity was calculated daily during the first 4 days of life using the Score for Neonatal Acute Physiology II (SNAP-II score). Adverse outcome (death and/or brain injury) was recorded. Differences in SNAP-II scores between the newborns with and without adverse outcome were assessed. RESULT: 214 newborns were treated with hypothermia. The average SNAP-II score over the first 4 days of life was significantly worse in newborns developing adverse outcome. The average SNAP-II score was an excellent predictor of death (area under the curve [AUC]: 0.93; p < 0.001) and a fair predictor of adverse outcome (AUC: 0.73; p < 0.001). The average SNAP-II score remained a significant predictor of adverse outcome (odds ratio [95% confidence interval]: 1.08 [1.04-1.12]; p < 0.001), after adjusting for baseline characteristics, degree of initial asphyxial event, and initial severity of encephalopathy. CONCLUSION: In asphyxiated newborns treated with hypothermia, not only the initial asphyxial event but also the illness severity during the first days of life was a significant predictor of death or brain injury.

Hypotension and Brain Injury in Asphyxiated Newborns Treated with Hypothermia.

OBJECTIVE: This study aimed to assess the incidence of hypotension in asphyxiated newborns treated with hypothermia, the variability in treatments for hypotension, and the impact of hypotension on the pattern of brain injury. STUDY DESIGN: We conducted a retrospective cohort study of asphyxiated newborns treated with hypothermia. Mean blood pressures, lactate levels, and inotropic support medications were recorded during the hospitalization. Presence and severity of brain injury were scored using the brain magnetic resonance imaging (MRI) obtained after the hypothermia treatment was completed. RESULTS: One hundred and ninety term asphyxiated newborns were treated with hypothermia. Eighty-one percent developed hypotension. Fifty-five percent of the newborns in the hypotensive group developed brain injury compared with 35% of the newborns in the normotensive group (p = 0.04). Twenty-nine percent of the newborns in the hypotensive group developed severe brain injury, compared with only 15% in the normotensive group. Nineteen percent of the newborns presenting with volume- and/or catecholamine-resistant hypotension had near-total injury, compared with 6% in the normotensive group and 8% in the group responding to volume and/or catecholamines. CONCLUSION: Hypotension was common in asphyxiated newborns treated with hypothermia and was associated with an increased risk of (severe) brain injury in these newborns.