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Writing in Science, Al Habsi et al. show that spermidine boosts the efficacy of monoclonal antibodies targeting PD-L1 in aged tumor-bearing mice by enhancing fatty acid oxidation in CD8 T cells. These results open new therapeutic avenues to improve the effectiveness of anticancer immunotherapies in aged patients. [ABSTRACT FROM AUTHOR]

Preterm infants need the achievement of adequate lung volume. Lung recruitment maneuver (LRM) is applied during high-frequency oscillatory ventilation. We investigated the effect of an LRM with positive end-expiratory pressure (PEEP) on oxygenation and outcomes in infants conventionally ventilated for respiratory distress syndrome (RDS). Preterm infants in assisted controlled ventilationþvolume guarantee for RDS after surfactant randomly received an LRM (group A) or did not (group B). LRM entailed increments of 0.2 cm H2O PEEP every 5 minutes, until fraction of inspired oxygen (FiO2)=0.25. Then PEEP was reduced and the lung volume was set on the deflation limb of the pressure/volume curve. When saturation of peripheral oxygen fell and FiO2 rose, we reincremented PEEP until SpO2 became stable. Group A (n=10) and group B (n=10) infants were similar: gestational age 25±2 versus 2±52 weeks; body weight 747±233 versus 737±219 g; clinical risk index for babies 9.8 versus 8.1; initial FiO2 56±24 versus 52±21, respectively. LRM began at 86±69 minutes of age and lasted for 61±18 minutes. Groups A and B showed different max PEEP during the first 12 hours of life (6.1±0.3 versus 5.3±0.3 cm H2O, p=0.00), time to lowest FiO2 (94±24 versus 435±221 minutes; p=0.000) and O2 dependency (29±12 versus 45±17 days; p=0.04). No adverse events and no differences in the outcomes were observed. LRM led to the earlier lowest FiO2 of the first 12 hours of life and a shorter O2 dependency. [ABSTRACT FROM AUTHOR]

Objective To evaluate the clinical course, respiratory outcomes and markers of inflammation in preterm infants with moderate respiratory distress syndrome (RDS) assigned from birth to nasal continuous positive airway pressure (NCPAP) or bi-level NCPAP. Methods A total of 40 infants with a gestational age (GA) of 28-34 weeks (<35 weeks' GA), affected by moderate RDS, were considered eligible and were randomised to NCPAP (group A; n=20, CPAP level=6 cm H2O) or to bi-level NCPAP (group B; n=20, lower CPAP level=4.5 cm H2O, higher CPAP level=8 cm H2O), provided with variable flow devices. Inflammatory response was the primary outcome; serum cytokines were measured on days 1 and 7 of life. Length of ventilation, oxygen dependency, need for intubation and occurrence of air leaks were considered as secondary outcomes. Results Infants showed similar characteristics at birth (group A vs group B: GA 30.3±2 vs 30.2±2 weeks, birth weight 1429±545 vs 1411±560 g) and showed similar serum cytokine levels at all times. Group A underwent longer respiratory support (6.2±2 days vs 3.8±1 days, p=0.025), longer O dependency (13.8±8 days vs 6.5±4 days, p=0.027) and was discharged later (GA at discharge 36.7±2.5 weeks vs 35.6±1.2 weeks, p=0.02). All infants survived. No bronchopulmonary dysplasia (BPD) or neurological disorders occurred. Conclusions Bi-level NCPAP was associated with better respiratory outcomes versus NCPAP, and allowed earlier discharge, inducing the same changes in the cytokine levels. It was found to be well tolerated and safe in the study population. [ABSTRACT FROM AUTHOR]

Preterm birth is a significant global health issue affecting millions of infants each year, with potential implications for their developmental outcomes. This study investigated the impact of preterm birth on maternal mood states during the early postpartum period and its subsequent effects on mother–infant bonding. Mothers of 90 preterm infants were involved in the assessment of maternal mood states, examined with the Profile of Mood States (POMS) questionnaire and the evaluation of mother–infant bonding, carried out through the Postpartum Bonding Questionnaire (PBQ). Contrary to expectations, there was no significant correlation between preterm birth characteristics and maternal mood states. On the other hand, significant correlations emerged between specific maternal mood states and the quality of mother–child bonding. More specifically, regression analyses showed that feelings of tension, anger, and confusion experienced by the mother tend to negatively affect the quality of her bond with her child. These findings emphasize the crucial role of maternal mental well-being in shaping the mother–infant relationship in the early postpartum period. The study highlights the importance of identifying and addressing maternal mood disorders to promote positive mother–infant bonding and child development, further underlining the need for comprehensive support and interventions for mothers of preterm infants. [ABSTRACT FROM AUTHOR]

Caloric restriction mimetics (CRMs) are emerging as potential therapeutic agents for the treatment of cardiovascular diseases. CRMs include natural and synthetic compounds able to inhibit protein acetyltransferases, to interfere with acetyl coenzyme A biosynthesis, or to activate (de)acetyltransferase proteins. These modifications mimic the effects of caloric restriction, which is associated with the activation of autophagy. Previous evidence demonstrated the ability of CRMs to ameliorate cardiac function and reduce cardiac hypertrophy and maladaptive remodelling in animal models of ageing, mechanical overload, chronic myocardial ischaemia, and in genetic and metabolic cardiomyopathies. In addition, CRMs were found to reduce acute ischaemia–reperfusion injury. In many cases, these beneficial effects of CRMs appeared to be mediated by autophagy activation. In the present review, we discuss the relevant literature about the role of different CRMs in animal models of cardiac diseases, emphasizing the molecular mechanisms underlying the beneficial effects of these compounds and their potential future clinical application. [ABSTRACT FROM AUTHOR]

The success of chemotherapy largely depends on the anticancer immune response triggered by tumor cells that succumb to immunogenic cell death (ICD). One of the hallmarks of ICD is premortem autophagy that facilitates the release of adenosine triphosphate from dying cancer cells and acts as a chemoattractant for dendritic cell precursors. Here, we show that the immune response induced by inoculation of cancer cells undergoing ICD in response to the anthracycline mitoxantrone (MTX) can be improved by a short-term fasting regimen (48 hours of starvation) and that this effect is reversed by systemic administration of the autophagy inhibitor dimethyl α-ketoglutarate. Tumor growth reduction by MTX treatment is known to depend on autophagy induction in cancer cells as well as on an intact immune system. We compared the antitumor effects of MTX on autophagy-competent cancers implanted in wild type (WT) or partially autophagy-deficient (Becn1± or Atg4b−/-) mice. While there was no difference in the tumor growth reducing effects of MTX on tumors evolving in WT, Becn1+/- and Atg4b−/- mice, we observed an increase in the toxicity of MTX on Atg4b−/- mice. These results suggest that autophagy in cancer cells (but less so in host cells) is rate-limiting for therapeutically relevant anticancer immune responses, yet has a major role in blunting the life-threatening toxicity of chemotherapy. [ABSTRACT FROM AUTHOR]

Single-cell metabolomics has the potential to reveal unique insights into intracellular mechanisms and biological processes. However, the detection of metabolites from individual cells is challenging due to their versatile chemical properties and concentrations. Here, we demonstrate a tapered probe for pneumatically assisted nanospray desorption electrospray ionization (PA nano-DESI) mass spectrometry that enables both chemical imaging of larger cells and global metabolomics of smaller 15 μm cells. Additionally, by depositing cells in predefined arrays, we show successful metabolomics from three individual INS-1 cells per minute, which enabled the acquisition of data from 479 individual cells. Several cells were used to optimize analytical conditions, and 93 or 97 cells were used to monitor metabolome alterations in INS-1 cells after exposure to a low or high glucose concentration, respectively. Our analytical approach offers insights into cellular heterogeneity and provides valuable information about cellular processes and responses in individual cells. [ABSTRACT FROM AUTHOR]

Hypothermia is used for its neuroprotective effect in perinatal asphyxia. Mechanical ventilation is often used as a supportive therapy for severe asphyxiated infants who can present various degrees of respiratory failure. Animal studies demonstrated a protective effect of cooling on the lungs due to reduced ventilatory requirements. Even if actual knowledge on the effects of hypothermia and rewarming on respiratory parameters during mechanical ventilation is limited, nevertheless human studies seem to demonstrate that hypothermia is safe and does not cause significant changes in the level of respiratory supports. [ABSTRACT FROM AUTHOR]

Acyl-coenzyme A (CoA)–binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), is an extracellular feedback regulator of autophagy. Here, we report that injection of a monoclonal antibody neutralizing ACBP/DBI (α-DBI) protects the murine liver against ischemia/reperfusion damage, intoxication by acetaminophen and concanavalin A, and nonalcoholic steatohepatitis caused by methionine/cholinedeficient diet as well as against liver fibrosis induced by bile duct ligation or carbon tetrachloride. α-DBI downregulated proinflammatory and profibrotic genes and upregulated antioxidant defenses and fatty acid oxidation in the liver. The hepatoprotective effects of α-DBI were mimicked by the induction of ACBP/DBI-specific autoantibodies, an inducible Acbp/Dbi knockout or a constitutive Gabrg2F77I mutation that abolishes ACBP/DBI binding to the GABAA receptor. Liver-protective α-DBI effects were lost when autophagy was pharmacologically blocked or genetically inhibited by knockout of Atg4b. Of note, α-DBI also reduced myocardium infarction and lung fibrosis, supporting the contention that it mediates broad organ-protective effects against multiple insults. [ABSTRACT FROM AUTHOR]

Background: Cholestasis in extremely premature infants (EPI) constitutes a nutritional challenge and maltodextrins have been reported as a possible strategy for hypoglycaemia. We aim to describe the nutritional management of an EPI with non-syndromic bile duct paucity (NSBDP) and feeding intolerance. Case presentation: A patient, born at 27 weeks of gestational age, presented cholestatic jaundice at 20 days of life with a clinical picture of NSBDP. Patient's growth was insufficient with formula rich in medium-chain triglyceride (MCT) and branched-chain amino acids (BCAA). Due to frequent fasting hypoglicemic episodes, maltodextrins supplements were provided. He subsequently presented severe abdominal distension and painful crises, which required hospital admission and withdrawal of maltodextrins. Hypercaloric extensively hydrolysed formula provided weight gain, glycemic control, and parallel improvement in cholestasis. Conclusions: Our case suggests caution with the use of maltodextrins in infants, especially if premature. Commercial preparations for hepatopatic patients contain higher concentrations of MCTs and BCAAs, but personalized strategies must be tailored to each patient. [ABSTRACT FROM AUTHOR]

Background: Sustained lung inflation (SLI) applied at birth has been demonstrated to lead to clearance of lung fluid and achievement of a precocious functional residual capacity in animal studies. Objectives: To verify if the application of SLI in preterm infants at birth may reduce the need for mechanical ventilation and improve their respiratory outcome. Methods: We prospectively studied 89 infants with respiratory distress (gestational age (GA) 28.1 ± 2.2 weeks) treated at birth with a SLI (25 cm H2O, sustained for 15 s) in addition to AAP recommendations versus a historical control group (n = 119; GA 28.1 ± 2.0 weeks) treated without SLI with the same device (controlled positive end-expiratory pressure of 5 cm H2O). Results: The SLI group had less need for (51 vs. 76%, p < 0.0001) and shorter duration of mechanical ventilation (5 ± 11 vs. 11 ± 19 days, p = 0.008), a more frequent occurrence of exclusive nasal continuous airway pressure support (49 vs. 24%, p < 0.0001) and INtubation-SURfactant-Extubation (INSURE) treatment (16 vs. 3%, p = 0.01), less need for surfactant (45 vs. 61%, p = 0.027) and postnatal steroids (10 vs. 25%, p = 0.01), a shorter duration of oxygen therapy (21 ± 27 vs. 31 ± 31 days, p = 0.016), and, finally, a lower occurrence of bronchopulmonary dysplasia in survivors (7 vs. 25%, p = 0.004). Multiple regression analysis showed that 23-27 weeks of GA and birth weight <750 g increased the risk of mechanical ventilation, while a clinical risk index for babies (CRIB) score <3 as well as INSURE strategy and SLI treatment in the delivery room decreased it. Conclusions: The application of a SLI at birth in preterm infants with respiratory distress may decrease the need for mechanical ventilation without inducing evident adverse effects. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Spontaneous regression in the foetal period has been described for congenital hydrothorax. Hydrothorax may become larger and bilateral with hydrops and pulmonary hypoplasia. Prenatal thoracentesis and thoracoamniotic shunting of massive hydrothorax are indicated to decrease perinatal morbidity. In the neonatal period, persistent hydrothorax may require intensive care. Objective. To investigate neonatal outcome after thoracoamniotic shunting for congenital primary hydrothorax with hydrops/ polydramnios. Methods. Retrospective study on the postnatal management of a cohort of 28 congenital primary hydrothorax cases after thoracoamniotic shunting (January 2000–August 2005). Results. Congenital hydrotorax without major structural anomalies complicated by polidramnios and/or hydrops <34 weeks' gestation were the criteria accepted for thoracoamniotic shunting. There were neither pregnancy terminations nor utero deaths. Although 64% of cases were complicated by severe neonatal respiratory insufficiency, neonatal mortality rate was low (21.4%) if compared with literature. Univariate analysis identified ‘birth at gestational age (GA) <35 weeks’ and ‘time between prenatal shunting and birth’ as predictive factors for needing of ventilation. Multivariate analysis identified ‘birth at GA <35 weeks’ as the only independent predictor for needing ventilation. (OR = 0.08, CI 95% = 0.01–0.96, p = 0.046). No risk factors for death or adverse neurological outcomes were reported. Conclusions. Congenital hydrothorax although corrected by thoracoamniotic shunting is complicated by severe respiratory distress. The neonatal outcome may be improved limiting degree of prematurity; the presence of thoracoamniotic shunt is not per se an indication of premature birth, at least until GA >35 weeks and adequate pulmonary maturity is reached. [ABSTRACT FROM AUTHOR]

A noninvasive approach in the delivery room in place of intubation and mechanical ventilation can reduce rates of bronchopulmonary dysplasia and death. Nevertheless, the rate of nasal continuous positive airway pressure failure still remains high. In order to prevent lung injury and to enhance the success of continuous positive airway pressure, sustained inflation (administration by face mask or nasopharyngeal tube of a high peak pressure of 20-25 cm H2O, maintained for 10-15 s) has been recently proposed to establish an early and efficient functional residual capacity in the delivery room. Sustained inflation is an intriguing therapy, although the results of clinical trials are controversial in terms of respiratory outcomes. A critical role in the success of sustained inflation could be the presence of open or closed glottis and the contribution of spontaneous breathing that allows air to enter the lungs during the maneuver. Recent neonatal resuscitation guidelines suggest that sustained inflation may be considered in individual clinical circumstances or research settings. Respiratory distress syndrome (RDS) is the most common respiratory pathology in preterm infants and bronchopulmonary dysplasia (BPD) remains an important sequela in these patients. In the past, conventional mechanical ventilation or high-frequency oscillatory ventilation plus surfactant replacement therapy have been considered the standard approach for management of RDS. However, we know that lung injury is directly related to duration of mechanical ventilation and therefore noninvasive approaches [e.g. nasal continuous positive airway pressure (CPAP)] often associated with surfactant administration have been demonstrated to be a valid alternative [1]. Two recent meta-analyses suggest that a noninvasive approach from the delivery room instead of intubation and mechanical ventilation can reduce rates of BPD and death with a number needed to treat of 35 and 25, respectively, in very preterm infants [2, 3]. Nevertheless, the rate of CPAP failure remains high. In fact, recent randomized controlled trials (RCTs) reported that more than 50% of very low birth weight infants initially assisted in the delivery room with nasal CPAP required mechanical ventilation in the neonatal intensive care unit [4-6]. [ABSTRACT FROM AUTHOR]

BACKGROUND: To evaluate the efficacy and safety of bronchoalveolar lavage (BAL) with diluted porcine surfactant in mechanically ventilated term infants with severe acute respiratory distress syndrome (ARDS) due to meconium aspiration syndrome (MAS). METHODS: Eight consecutive mechanically ventilated term infants with severe ARDS due to MAS underwent BAL with 15 mL/kg of diluted (5.3mg phospholipid/mL) surfactant saline suspension (porcine surfactant [Curosurf®]). Treatment was administered slowly in aliquots of 2.5mL. The mean age of neonates at treatment was 3.5 (range 1-8) hours. Heart rate, systemic blood pressure and oxygen saturation were monitored continuously. Arterial blood gases were measured immediately before treatment, and again at 3 and 6 hours post-treatment. Chest x-rays were taken 6 and 24 hours after treatment. RESULTS: Radiological improvement was evident in all eight patients 6 hours post-treatment. Compared with pre-BAL values, significant improvements (p < 0.05) in mean values for partial pressure of oxygen in arterial blood, partial pressure of carbon dioxide in arterial blood, pH, arterial/alveolar O2 ratio and oxygenation index were documented at 3 and 6 hours after BAL. In all patients, tracheal fluids that had been meconium-stained prior to BAL were clear of meconium after BAL. Only one patient required nitric oxide therapy for transient pulmonary hypertension. No adverse sequelae of treatment occurred during the study. CONCLUSIONS: BAL with dilute porcine surfactant administered slowly in 2.5mL aliquots improved oxygenation and chest x-ray findings, without causing major adverse effects, in mechanically ventilated term infants with ARDS due to MAS. [ABSTRACT FROM AUTHOR]

Background: Neonatal hypoglycemia is a common disorder especially in at-risk infants and it can be associated with poor long-term neurological outcomes. Several therapeutic interventions are suggested, from the implementation of breastfeeding to the glucose intravenous administration. Oral dextrose gel massaged into the infant's inner cheek is a recent treatment option of asymptomatic hypoglycemia, after which oral feeding is encouraged. This approach seems to reduce the admission of infants to neonatal intensive care unit (NICU) so favouring maternal bonding and breastfeeding success at discharge. Methods: In our ward, we prospectively compared a group of near-term neonates, (Gr2, n = 308) at risk for hypoglycemia, treated with an innovative protocol based on the addition of 40% oral dextrose gel (Destrogel, Orsana®,Italy) administered by massaging gums and cheek with historical matching newborns (Gr1, n = 389) treated with a formerly used protocol, as control group. The primary outcome was occurrence of NICU admission and the requirement of intravenous glucose administration; while discharge with full breastfeeding was the secondary outcome. Results: In Gr1, 39/389 (10%) infants presented with asymptomatic hypoglycemia, 19/39 were transferred to the NICU, and 14/39 required intravenous glucose treatment. In Gr2, among the 30/308 infants with asymptomatic hypoglycemia managed according to the new protocol, 3/30 were transferred to the NICU and received intravenous glucose infusion. The mean duration of hospitalization respectively was 6.43 (± 6.36) and 3.73 ± 1.53 days (p < 0.001). At discharge, 7.7% of the infants in Gr1 and 30% of the infants in Gr2 were exclusively breastfed (p = 0.02). Considering Gr1 vs Gr2, the number of patients that were transferred to NICU was 19 (48.7%) vs 3 (10%) (p = 0.001) and the number of infants that needed intravenous glucose infusion was 14 (35.9%) vs 3 (10%) (p = 0.01), respectively. Conclusions: In our population of near term infants, the introduction of 40% oral dextrose gel to the protocol, helped in the safe management of asymptomatic hypoglycemia and, at the same time, implemented breastfeeding. [ABSTRACT FROM AUTHOR]

Prenatal DA closure due to early maternal intake of high‐dose paracetamol and selective serotonin reuptake inhibitors. MC twin pregnancy uncomplicated by TTTS with discordant prenatal DA closure. [ABSTRACT FROM AUTHOR]

Autophagy is a highly conserved recycling mechanism essential for maintaining cellular homeostasis. The pathophysiological role of autophagy has been explored since its discovery 50 years ago, but interest in autophagy has grown exponentially over the last years. Many researchers around the globe have found that autophagy is a critical pathway involved in the pathogenesis of cardiac diseases. Several groups have created novel and powerful tools for gaining deeper insights into the role of autophagy in the aetiology and development of pathologies affecting the heart. Here, we discuss how established and emerging methods to study autophagy can be used to unravel the precise function of this central recycling mechanism in the cardiac system. [ABSTRACT FROM AUTHOR]

We have recently shown that chemotherapy with immunogenic cell death (ICD)-inducing agents can be advantageously combined with fasting regimens or caloric restriction mimetics (CRMs) to achieve superior tumor growth control via a T cell-dependent mechanism. Here, we show that the blockade of the CD11b-dependent extravasation of myeloid cells blocks such a combination effect as well. Based on the characterization of the myeloid and lymphoid immune infiltrates, including the expression pattern of immune checkpoint proteins (and noting a chemotherapy-induced overexpression of programmed death-ligand 1, PD-L1, on both cancer cells and leukocytes, as well as a reduced frequency of exhausted CD8+ T cells positive for programmed cell death 1 protein, PD-1), we then evaluated the possibility to combine ICD inducers, CRMs and targeting of the PD-1/PD-L1 interaction. While fasting or CRMs failed to improve tumor growth control by PD-1 blockade, ICD inducers alone achieved a partial sensitization to treatment with a PD-1-specific antibody. However, definitive cure of most of the tumor-bearing mice was only achieved by a tritherapy combining (i) ICD inducers exemplified by mitoxantrone and oxaliplatin, (ii) CRMs exemplified by hydroxycitrate and spermidine and substitutable for by fasting, and (iii) immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 interaction. Altogether, these results point to the possibility of synergistic interactions among distinct classes of anticancer agents. [ABSTRACT FROM AUTHOR]

Aim:This paper aims to investigate if the dyadic interactive behaviours were influenced by parental stress and feelings both in preterm and full-term mother–child dyads. Methods:45 mothers (age = 35.29 ± 5.38) and fathers (age = 36.77 ± 6.89) of preterm infants (GA = 30.25 ± 2.95; BW = 1288.02 ± 488.76), and 36 mothers (age = 32.60 ± 4.56) and fathers (age = 35.54 ± 5.16) of full-term (GA = 39.88 ± 1.38; BW = 3156.39 ± 493.81) were involved. Parents filled out the Impact of Event Scale Revised (IES-R), Profile of Mood States (POMS) and Parenting Stress Index Short Form (PSI-SF) and interactive behaviours (Global Rating Scale) was videotaped after 3 months. Results:Mothers of preterm children showed higher level of Intrusiveness (Mpreterm = 4.07 ± .74, Mfullterm = 4.39 ± .51, t = 2.22, p = .029) and Remoteness (Mpreterm = 4.45 ± .83, Mfullterm = 4.79 ± .34, t = 2.51, p = .015) than mothers of term children. In preterm mothers’ lower levels of Sensitivity, higher levels of Intrusiveness, Remoteness and Depression are associated with the presence of negative feelings and parental stress in both parents. Moreover, higher children Distress is associated to parental negative feelings, paternal stress and post-traumatic symptoms. A higher score of parental negative feelings and parental stress predicted lower scores in Global RatingScale dimensions. Conclusions:Our results underline that preterm birth could be a risk factor for the co-construction of interactive exchanges between mother and premature baby. This study could help practitioners to better consider parental roles and to carry out specific supportive interventions for both parents and children. [ABSTRACT FROM PUBLISHER]

Background: A sustained inflation (SI) at birth in preterm babies may be ineffective unless the infants breathe. Gain in lung volume is associated with breathing during delivery room non-invasive management. Objective: To describe the breathing patterns of preterm infants during an SI and correlate to a calculated gain in lung volume. Methods: Retrospective observational study. Data collected from a respiratory function monitor during SI (25 cmH2O for 15 s then PEEP at 5 cmH2O) through a face mask in preterm infants (gestational age [GA] ≤ 31 weeks). Spontaneous breaths, inspiratory time (TI), inspiratory/expiratory tidal volume (Vti/Vte), and gain in lung volume were determined. Results: 30 SIs in 20 infants (mean GA 27 weeks; birth weight 825 g) were analysed and stratified in 2 groups according to spontaneous breathing: SIs without spontaneous breaths (apnoea: n = 11) and SIs with spontaneous breaths (breathing: n = 19). Mean GA was lower in the apnoea group versus the breathing group (25 vs. 27+5 weeks; p = 0.01). Mean birth weight was lower in the apnoea group versus the breathing group (683 vs. 860 g; p = ns). In the breathing group, the mean number of spontaneous breaths was 4 with a mean TI of 0.52 min, the mean Vti/kg was 5.9 mL/kg, and the mean Vt e was 2.7 mL/kg. The calculated mean gain in lung volume was 7.5 mL/kg in the apnoea group and 17.8 mL/kg in the breathing group (p = 0.039). Conclusions: Actively breathing infants during an SI at birth showed a gain in lung volume higher than apnoeic infants. Spontaneous breathing during SI seems to be related to GA. [ABSTRACT FROM AUTHOR]

Preterm birth is a stressful event for families. In particular, the unexpectedly early delivery may cause negative feelings in mothers and fathers. The aim of this study was to examine the relationship between preterm birth, parental stress and negative feelings, and the environmental setting of NICU. 21 mothers (age = 36.00 ± 6.85) and 19 fathers (age = 34.92 ± 4.58) of preterm infants (GA = 30.96 ± 2.97) and 20 mothers (age = 40.08 ± 4.76) and 20 fathers (age = 40.32 ± 6.77) of full-term infants (GA = 39.19 ± 1.42) were involved. All parents filled out the Parental Stressor Scale: Neonatal Intensive Care Unit, the Impact of Event Scale Revised, Profile of Mood States, the Multidimensional Scale of Perceived Social Support and the Post-Partum Bonding Questionnaire. Our data showed differences in emotional reactions between preterm and full-term parents. Results also revealed significant differences between mothers and fathers' responses to preterm birth in terms of stress, negative feelings, and perceptions of social support. A correlation between negative conditions at birth (e.g., birth weight and Neonatal Intensive Care Unit stay) and higher scores in some scales of Impact of Event Scale Revised, Profile of Mood States and Post-Partum Bonding Questionnaire were found. Neonatal Intensive Care Unit may be a stressful place both for mothers and fathers. It might be useful to plan, as soon as possible, interventions to help parents through the experience of the premature birth of their child and to begin an immediately adaptive mode of care. [ABSTRACT FROM AUTHOR]

Summary Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed. [ABSTRACT FROM AUTHOR]

One particular paradigm of anticancer immunotherapy relies on the administration of (potentially) tumor-reactive immune effector cells. Generally, these cells are obtained from autologous peripheral blood lymphocytes (PBLs) ex vivo (in the context of appropriate expansion, activation and targeting protocols), and re-infused into lymphodepleted patients along with immunostimulatory agents. In spite of the consistent progress achieved throughout the past two decades in this field, no adoptive cell transfer (ACT)-based immunotherapeutic regimen is currently approved by regulatory agencies for use in cancer patients. Nonetheless, the interest of oncologists in ACT-based immunotherapy continues to increase. Accumulating clinical evidence indicates indeed that specific paradigms of ACT, such as the infusion of chimeric antigen receptor (CAR)-expressing autologous T cells, are associated with elevated rates of durable responses in patients affected by various neoplasms. In line with this notion, clinical trials investigating the safety and therapeutic activity of ACT in cancer patients are being initiated at an ever increasing pace. Here, we review recent preclinical and clinical advances in the development of ACTbased immunotherapy for oncological indications. [ABSTRACT FROM AUTHOR]

One type of anticancer vaccine relies on the administration of DNA constructs encoding one or multiple tumor-associated antigens (TAAs). The ultimate objective of these preparations, which can be naked or vectored by non-pathogenic viruses, bacteria or yeast cells, is to drive the synthesis of TAAs in the context of an immunostimulatory milieu, resulting in the (re-)elicitation of a tumor-targeting immune response. In spite of encouraging preclinical results, the clinical efficacy of DNA-based vaccines employed as standalone immunotherapeutic interventions in cancer patients appears to be limited. Thus, efforts are currently being devoted to the development of combinatorial regimens that allow DNA-based anticancer vaccines to elicit clinically relevant immune responses. Here, we discuss recent advances in the preclinical and clinical development of this therapeutic paradigm. [ABSTRACT FROM AUTHOR]

The term “immunogenic cell death” (ICD) is now employed to indicate a functionally peculiar form of apoptosis that is sufficient for immunocompetent hosts to mount an adaptive immune response against dead cell-associated antigens. Several drugs have been ascribed with the ability to provoke ICD when employed as standalone therapeutic interventions. These include various chemotherapeutics routinely employed in the clinic (e.g., doxorubicin, epirubicin, idarubicin, mitoxantrone, bleomycin, bortezomib, cyclophosphamide and oxaliplatin) as well as some anticancer agents that are still under preclinical or clinical development (e.g., some microtubular inhibitors of the epothilone family). In addition, a few drugs are able to convert otherwise non-immunogenic instances of cell death intobona fideICD, and may therefore be employed as chemotherapeutic adjuvants within combinatorial regimens. This is the case of cardiac glycosides, like digoxin and digitoxin, and zoledronic acid. Here, we discuss recent developments on anticancer chemotherapy based on ICD inducers. [ABSTRACT FROM PUBLISHER]

Immunomodulatory monoclonal antibodies (mAbs) differ from their tumor-targeting counterparts because they exert therapeutic effects by directly interacting with soluble or (most often) cellular components of the immune system. Besides holding promise for the treatment of autoimmune and inflammatory disorders, immunomodulatory mAbs have recently been shown to constitute a potent therapeutic weapon against neoplastic conditions. One class of immunomodulatory mAbs operates by inhibiting safeguard systems that are frequently harnessed by cancer cells to establish immunological tolerance, the so-called “immune checkpoints.” No less than 3 checkpoint-blocking mAbs have been approved worldwide for use in oncological indications, 2 of which during the past 12 months. These molecules not only mediate single-agent clinical activity in patients affected by specific neoplasms, but also significantly boost the efficacy of several anticancer chemo-, radio- or immunotherapies. Here, we summarize recent advances in the development of checkpoint-blocking mAbs, as well as of immunomodulatory mAbs with distinct mechanisms of action. [ABSTRACT FROM PUBLISHER]