Behavioral arousal in newborn infants and its association with termination of apnea

Arousal is an important protective mechanism that aids in the resolution of obstructive sleep apnea in adults and children, but its role in neonatal apnea has not been investigated. The primary aim of the present study was to determine the role of arousal in the termination of apnea in preterm infants. Videorecording was used to identify spontaneous behavioral arousal in a group of healthy full-term (n = 7) and preterm (n = 10) infants before and during polygraphic monitoring of cardiorespiratory variables and in a group of preterm infants with apnea (n = 10) during similar polygraphic monitoring. Spontaneous arousal rates (mean +/- SE) in full-term infants before and during polygraphic monitoring were 0.18 +/- 0.03 and 0.23 +/- 0.07 episodes/min, respectively. Corresponding values in nonapneic preterm infants were 0.24 +/- 0.03 and 0.24 +/- 0.02 episodes/min. In apneic preterm infants, mean spontaneous arousal rate during polygraphic recording was 0.26 +/- 0.02, but it was considerably higher during apneic sleep periods (0.59 +/- 0.17) than during nonapneic sleep periods (0.25 +/- 0.01). The frequency of occurrence of arousal was significantly higher (P less than 0.005) in long vs. short apnea, mixed vs. central apnea, and severe vs. mild apnea. Although a clear association between arousal and apneic resolution was observed in preterm infants, lack of arousal responses in a large number of apneic episodes suggests that behavioral arousal is not essential for the termination of apnea in these infants.     

Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender

Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, p< 0.05–0.01. Male infants were found to begin with a low α-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother’s own breastmilk (MBM) had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion, infant postnatal age, gender and feeding type significantly contribute to the dynamic development of the gut microbiome in preterm infants.     

Oxygen-conserving effects of apnea in exercising men.

We sought to determine whether apnea-induced cardiovascular responses resulted in a biologically significant temporary O(2) conservation during exercise. Nine healthy men performing steady-state leg exercise carried out repeated apnea (A) and rebreathing (R) maneuvers starting with residual volume +3.5 liters of air. Heart rate (HR), mean arterial pressure (MAP), and arterial O(2) saturation (Sa(O(2)); pulse oximetry) were recorded continuously. Responses (DeltaHR, DeltaMAP) were determined as differences between HR and MAP at baseline before the maneuver and the average of values recorded between 25 and 30 s into each maneuver. The rate of O(2) desaturation (DeltaSa(O(2))/Deltat) was determined during the same time interval. During apnea, DeltaSaO(2)/Deltat had a significant negative correlation to the amplitudes of DeltaHR and DeltaMAP (r(2) = 0.88, P < 0.001); i.e., individuals with the most prominent cardiovascular responses had the slowest DeltaSa(O(2))/Deltat. DeltaHR and DeltaMAP were much larger during A (-44 +/- 8 beats/min, +49 +/- 4 mmHg, respectively) than during R maneuver (+3 +/- 3 beats/min, +30 +/- 5 mmHg, respectively). DeltaSa(O(2))/Deltat during A and R maneuvers was -1.1 +/- 0.1 and -2.2 +/- 0.2% units/s, respectively, and nadir Sa(O(2)) values were 58 +/- 4 and 42 +/- 3% units, respectively. We conclude that bradycardia and hypertension during apnea are associated with a significant temporary O(2) conservation and that respiratory arrest, rather than the associated hypoxia, is essential for these responses.     

Elevated temperature, per se, does not limit the ability of rainbow trout to increase stroke volume

Key questions remain about the regulation and limits of cardiac function in fish challenged with elevated temperature, and to what extent sex differences influence cardiac performance. In this study, we investigated the in vivo relationship between heart rate (f_H), stroke volume (S_V), and cardiac output (Q) in quiescent, sexually immature rainbow trout (Oncorhynchus mykiss Walbaum) when challenged with: (1) an acute increase in water temperature from 14 to 24 °C at 2 °C h⁻¹ and (2) a 50% reduction in f_H at 24 °C, achieved through the incremental administration of zatebradine hydrochloride (total dose 2 mg kg body mass⁻¹). There were no statistically significant (P<0.05) sex differences in cardiovascular function as temperature was raised to 24 °C. In males (N=10) and females (N=9), f_H increased in a linear fashion with water temperature (from ∼60 beats min⁻¹ at 14 °C to ∼125 beats min⁻¹ at 24 °C; Q₁₀=2.1), S_V was largely unchanged, and systemic blood pressure (P_DA) increased only slightly (by approx. 0.5 kPa) because the potential effect of increased Q on P_DA was mostly offset by a 35% decrease in systemic vascular resistance (R_sys). At 24 °C, zatebradine treatment halved f_H in both sexes, and yet Q was maintained at pre-treatment levels due to a doubling of S_V. Overall, these results: (1) indicate that the in vivo cardiovascular response of quiescent, immature, male and female trout to elevated temperature is similar and (2) challenge the current dogma about how temperature affects cardiac function in fishes. Specifically, unlike previous in vitro or in situ studies, our data demonstrate that fish are capable of maintaining or even increasing S_V at high temperatures. This suggests that aspects of cardiac control favor an increase in f_H as temperatures rise, or that increases in cardiac output to meet the fish’s metabolic demands at high temperatures are met solely through an increase in f_H because tachycardia is a requisite (unavoidable) physiological response.     

A respiratory sensory reflex in response to CO2 inhibits breathing in preterm infants.

Traditionally, the increase in ventilation occurring after approximately 4 s of CO2 inhalation in preterm infants has been attributed to an action at the peripheral chemoreceptors. However, on a few occasions, we have observed a short apnea (2-3 s) in response to 3-5% CO2 in these infants. To test the hypothesis that this apnea reflects a respiratory sensory reflex to CO2, we gave nine preterm infants [birth wt 1.5 +/- 0.1 (SE) kg, gestational age 31 +/- 1 wk] 7-8% CO2 while they breathed 21% O2. To study the dose-response relationship, we also gave 2, 4, 6, and 8% CO2 to another group of seven preterm infants (birth wt 1.5 +/- 0.1 kg, gestational age 31 +/- 1 wk). In the first group of infants, minute ventilation during 21% O2 breathing (0.232 +/- 0.022 l.min-1.kg-1) decreased after CO2 administration (0.140 +/- 0.022, P < 0.01) and increased with CO2 removal (0.380 +/- 0.054, P < 0.05). This decrease in ventilation was related to an apnea (12 +/- 2.6 s) occurring 7.7 +/- 0.8 s after the beginning of CO2 inhalation. There was no significant change in tidal volume. In the second group of infants, minute ventilation increased during administration of 2, 4, and 6% CO2 but decreased during 8% CO2 because of the presence of an apnea. These findings suggest that inhalation of a high concentration of CO2 (> 6%) inhibits breathing through a respiratory sensory reflex, as described in adult cats (H. A. Boushey and P. S. Richardson. J. Physiol. Lond. 228: 181-191, 1973).(ABSTRACT TRUNCATED AT 250 WORDS)     

Combined ventilatory responses to aerial hypoxia and temperature in the South American lungfish Lepidosiren paradoxa

The control of pulmonary ventilation in South American lungfish Lepidosiren paradoxa is poorly understood. Interactions between temperature and hypoxia are particularly relevant due to large seasonal variations of its habitat. Therefore, we tested the hypothesis that the ventilatory responses to aerial hypoxia of Lepidosiren are highly dependent on ambient temperature. We used a pneumotachograph to measure pulmonary ventilation (V_E), tidal volume (V_T) and respiratory frequency (f_R) during normoxic (21% O₂) and hypoxic (12%, 10% and 7% O₂) conditions at two temperatures (25 and 35 °C). Blood gases, arterial PO₂ (PaO₂), arterial PCO₂ (PaCO₂) and arterial pH (pH_a) were also evaluated. At 25 °C, V_E increased significantly at 10% and 7% hypoxic levels when compared to the control value (21% O₂). At 35 °C, all hypoxic levels elicited a significant increase of V_E relative to control values. V_E is augmented mostly by increases of respiratory frequency (f_R), and there were significant interactions (p<0.001) between aerial hypoxia and temperature. PaCO₂ increased from ∼22 mmHg (normoxic value at 25 °C) to ∼32 mmHg (normoxic value at 35 °C). Concomitantly, the pH_a decreased from 7.51 (25 °C) to 7.38 (35 °C). Hypoxia-induced hyperventilation caused a reduction in PaCO₂ and an increase in pH_a, which were more pronounced at 35 °C than at 25 °C, reflecting an increased hyperventilation under the high temperature. In conclusion, the magnitude of ventilatory response is highly temperature-dependent in L. paradoxa, which is important for an animal experiencing large seasonal variations.     

Coupling of Mitochondrial Fatty Acid Uptake to Oxidative Flux in the Intact Heart

The coordination of long chain fatty acid (LCFA) transport across the mitochondrial membrane (V_PAL) with subsequent oxidation rate through β-oxidation and the tricarboxylic acid (TCA) cycle (V_tca) has been difficult to characterize in the intact heart. Kinetic analysis of dynamic ¹³C-NMR distinguished these flux rates in isolated rabbit hearts. Hearts were perfused in a 9.4 T magnet with either 0.5 mM [2,4,6,8,10,12,14,16-¹³C₈] palmitate (n = 4), or 0.5 mM ¹³C-labeled palmitate plus 0.08 mM unlabeled butyrate (n = 4). Butyrate is a short chain fatty acid (SCFA) that bypasses the LCFA transporters of mitochondria. In hearts oxidizing palmitate alone, the ratio of V_TCA to V_PAL was 8:1. This is consistent with one molecule of palmitate yielding eight molecules of acetyl-CoA for the subsequent oxidation through the TCA cycle. Addition of butyrate elevated this ratio; V_TCA/V_PAL = 12:1 due to an SCFA-induced increase in V_TCA of 43% (p < 0.05). However, SCFA oxidation did not significantly reduce palmitate transport into the mitochondria: V_PAL = 1.0 ± 0.2 μmol/min/g dw with palmitate alone versus 0.9 ± 0.1 with palmitate plus butyrate. Thus, the products of β-oxidation are preferentially channeled to the TCA cycle, away from mitochondrial efflux via carnitine acetyltransferase.     

Extracellular Protons Inhibit Charge Immobilization in the Cardiac Voltage-Gated Sodium Channel

Low pH depolarizes the voltage-dependence of cardiac voltage-gated sodium (Na_V1.5) channel activation and fast inactivation and destabilizes the fast-inactivated state. The molecular basis for these changes in protein behavior has not been reported. We hypothesized that changes in the kinetics of voltage sensor movement may destabilize the fast-inactivated state in Na_V1.5. To test this idea, we recorded Na_V1.5 gating currents in Xenopus oocytes using a cut-open voltage-clamp with extracellular solution titrated to either pH 7.4 or pH 6.0. Reducing extracellular pH significantly depolarized the voltage-dependence of both the Q_ON/V and Q_OFF/V curves, and reduced the total charge immobilized during depolarization. We conclude that destabilized fast-inactivation and reduced charge immobilization in Na_V1.5 at low pH are functionally related effects.     

Attachment and Biofilm Forming Capabilities of Staphylococcus epidermidis Strains Isolated from Preterm Infants

Staphylococcus epidermidis, a human commensal, is an important opportunistic, biofilm-forming pathogen and the main cause of late onset sepsis in preterm infants, worldwide. In this study we describe the characteristics of S. epidermidis strains causing late onset (>72 h) bloodstream infection in preterm infants and skin isolates from healthy newborns. Attachment and biofilm formation capability were analyzed in microtiter plates and with transmission electron microscopy (TEM). Clonal relationship among strains was studied with pulsed-field gel electrophoresis. Antimicrobial susceptibility testing was performed, as well as the detection of biofilm-associated genes and of the invasiveness marker IS256 with polymerase chain reaction. Blood and skin isolates had similar attachment and biofilm-forming capabilities and biofilm formation was not related to the presence of specific genes. Filament-like membrane structures were seen by TEM early in the attachment close to the device surface, both in blood and skin strains. Nine of the ten blood isolates contained the IS256 and were also resistant to methicillin and gentamicin in contrast to skin strains. S. epidermidis strains causing bloodstream infection in preterm infants exhibit higher antibiotic resistance and are provided with an invasive genetic equipment compared to skin commensal strains. Adhesion capability to a device surface seems to involve bacterial membrane filaments.     

Monitoring Lung Aeration during Respiratory Support in Preterm Infants at Birth

Background

If infants fail to initiate spontaneous breathing, resuscitation guidelines recommend respiratory support with positive pressure ventilation (PPV). The purpose of PPV is to establish functional residual capacity and deliver an adequate tidal volume (V_T) to achieve gas exchange.

Objective

The aim of our pilot study was to measure changes in exhaled carbon dioxide (ECO₂), V_T, and rate of carbon dioxide elimination (VCO₂) to assess lung aeration in preterm infants requiring respiratory support immediately after birth.

Method

A prospective observational study was performed between March and July 2013. Infants born at <37 weeks gestational age who received continuous positive airway pressure (CPAP) or PPV immediately after birth had V_T delivery and ECO₂ continuously recorded using a sensor attached to the facemask.

Results

Fifty-one preterm infants (mean (SD) gestational age 29 (3) weeks and birth weight 1425 (592 g)) receiving respiratory support in the delivery room were included. Infants in the CPAP group (n = 31) had higher ECO₂ values during the first 10 min after birth compared to infants receiving PPV (n = 20) (ranging between 18–30 vs. 13–18 mmHg, p<0.05, respectively). At 10 min no significant difference in ECO₂ values was observed. V_T was lower in the CPAP group compared to the PPV group over the first 10 min ranging between 5.2–6.6 vs. and 7.2–11.3 mL/kg (p<0.05), respectively.

Conclusions

Immediately after birth, spontaneously breathing preterm infants supported via CPAP achieved better lung aeration compared to infants requiring PPV. PPV guided by V_T and ECO₂ potentially optimize lung aeration without excessive V_T administered.     

Lung Volume,Breathing Pattern and Ventilation Inhomogeneity in Preterm and Term Infants

Background

Morphological changes in preterm infants with bronchopulmonary dysplasia (BPD) have functional consequences on lung volume, ventilation inhomogeneity and respiratory mechanics. Although some studies have shown lower lung volumes and increased ventilation inhomogeneity in BPD infants, conflicting results exist possibly due to differences in sedation and measurement techniques.

Methodology/Principal Findings

We studied 127 infants with BPD, 58 preterm infants without BPD and 239 healthy term-born infants, at a matched post-conceptional age of 44 weeks during quiet natural sleep according to ATS/ERS standards. Lung function parameters measured were functional residual capacity (FRC) and ventilation inhomogeneity by multiple breath washout as well as tidal breathing parameters. Preterm infants with BPD had only marginally lower FRC (21.4 mL/kg) than preterm infants without BPD (23.4 mL/kg) and term-born infants (22.6 mL/kg), though there was no trend with disease severity. They also showed higher respiratory rates and lower ratios of time to peak expiratory flow and expiratory time (t _PTEF/t _E) than healthy preterm and term controls. These changes were related to disease severity. No differences were found for ventilation inhomogeneity.

Conclusions

Our results suggest that preterm infants with BPD have a high capacity to maintain functional lung volume during natural sleep. The alterations in breathing pattern with disease severity may reflect presence of adaptive mechanisms to cope with the disease process.     

Influence of the lamellar phase unbinding energy on the relative stability of lamellar and inverted cubic phases

Based on curvature energy considerations, nonbilayer phase-forming phospholipids in excess water should form stable bicontinuous inverted cubic (Q_II) phases at temperatures between the lamellar (L_α) and inverted hexagonal (H_II) phase regions. However, the phosphatidylethanolamines (PEs), which are a common class of biomembrane phospholipids, typically display direct L_α/H_II phase transitions and may form intermediate Q_II phases only after the temperature is cycled repeatedly across the L_α/H_II phase transition temperature, T_H, or when the H_II phases are cooled from T > T_H. This raises the question of whether models of inverted phase stability, which are based on curvature energy alone, accurately predict the relative free energy of these phases. Here we demonstrate the important role of a noncurvature energy contribution, the unbinding energy of the L_α phase bilayers, g_u, that serves to stabilize the L_α phase relative to the nonlamellar phases. The planar L_α phase bilayers must separate for a Q_II phase to form and it turns out that the work of their unbinding can be larger than the curvature energy reduction on formation of Q_II phase from L_α at temperatures near the L_α/Q_II transition temperature (T_Q). Using g_u and elastic constant values typical of unsaturated PEs, we show that g_u is sufficient to make T_Q > T_H for the latter lipids. Such systems would display direct L_α → H_II transitions, and a Q_II phase might only form as a metastable phase upon cooling of the H_II phase. The g_u values for methylated PEs and PE/phosphatidylcholine mixtures are significantly smaller than those for PEs and increase T_Q by only a few degrees, consistent with observations of these systems. This influence of g_u also rationalizes the effect of some aqueous solutes to increase the rate of Q_II formation during temperature cycling of lipid dispersions. Finally, the results are relevant to protocols for determining the Gaussian curvature modulus, which substantially affects the energy of intermediates in membrane fusion and fission. Recently, two such methods were proposed based on measuring T_Q and on measuring Q_II phase unit cell dimensions, respectively. In view of the effect of g_u on T_Q that we describe here, the latter method, which does not depend on the value of g_u, is preferable.     

Pharyngeal fluid clearance and aspiration preventive mechanisms in sleeping infants

We sought to characterize ventilatory and airway protective responses to pharyngeal stimulation in young infants during sleep. We studied the various responses with respect to frequency of occurrence, effect of increased stimulus intensity, and relation of stimulus fluid to laryngeal structures. Two groups of infants were studied: healthy full-term infants (n = 5) and preterm infants with a history of prolonged apnea (n = 9). We used a nasopharyngeal catheter to deliver small boluses of warm saline (0.02-0.35 ml) to the oropharynx. Responses repeatedly observed in both infant groups included swallows, obstructed respiratory efforts, brief apnea, prolonged apnea, and cough. In both infant groups, swallows and obstructed breaths occurred frequently and cough and prolonged apnea infrequently. The functional significance of some response patterns was clear, whereas that of others was obscure. Larger stimulus volumes yielded more frequent responses (P less than 0.01), and preterm infants responded much more frequently than full-term infants (P less than 0.01). Prolonged apnea was a composite of the other responses and was much more common in preterm than full-term infants (P less than 0.01). The stimulus technique was performed under direct visualization of the airway in two deceased infants. The findings suggested that the relation of the piriform fossae to the interarytenoid notch is important in determining response frequency. Implications for regulation of the removal of upper airway secretions during sleep are discussed.     

Effects of host nutritional status and seasonality on the nitrogen status of zooxanthellae in the temperate coral Plesiastrea versipora (Lamarck)

The nitrogen status of endosymbiotic dinoflagellates (zooxanthellae) in the temperate coral Plesiastrea versipora (Lamarck) was determined by measuring the extent to which ammonium (40 μM NH₄⁺) enhanced the rate of zooxanthellar dark carbon fixation above that seen in filtered seawater (FSW) alone; the enhancement ratio was expressed as [dark NH₄⁺ rate/dark FSW rate]. V_D′/V_L, a further index of nitrogen status, was also calculated where V_D′ = [dark NH₄⁺ rate − dark FSW rate] and V_L = rate of carbon fixation in the light. When corals were starved for 2-8 weeks, zooxanthellar nitrogen deficiency became apparent at ≥ 4 weeks, with NH₄⁺/FSW and V_D′/V_L averaging up to 2.08 and 0.0061, respectively. A decrease in light-saturated photosynthesis per zooxanthella also occurred, with the photosynthetic rate after 4-6 weeks being just 81% of that seen prior to starvation. In comparison, when corals were fed 5 times per week for 8 weeks the addition of ammonium had little effect, indicating nitrogen sufficiency; NH₄⁺/FSW and V_D′/V_L were 1.03 and 0.0003, respectively. Photosynthetic rates of zooxanthellae from well-fed corals were up to 1.7 times greater than those of zooxanthellae from starved corals. The nitrogen status of zooxanthellae from corals in the field exhibited seasonal differences. Autumn samples were nitrogen sufficient, with NH₄⁺/FSW = 1.003 and V_D′/V_L = 0.0001. In contrast, a small degree of nitrogen deficiency was seen in winter and spring, when NH₄⁺/FSW averaged 1.075 and 1.249, and V_D′/V_L averaged 0.0013 and 0.0014, respectively. The greatest degree of nitrogen deficiency was observed in summer, when NH₄⁺/FSW averaged 1.318 and V_D′/V_L averaged 0.0036. Given the clear links between food supply and nitrogen status seen under experimental conditions, and the likelihood that the zooxanthellae are also able to take up nutrients directly from the seawater, the fluctuations in nitrogen status may reflect temporal fluctuations in seawater nutrient concentrations and plankton abundance. The nutrient status of these temperate zooxanthellae in the field is in contrast to the marked nitrogen deficiency seen in zooxanthellae from nutrient-poor coral reef waters, and raises the possibility that temperate zooxanthellae can store nitrogen for use when exogenous nutrients and food are less readily available. This, in turn, may contribute to the considerable stability of temperate zooxanthellar populations under highly variable environmental conditions.     

DNA repair genes XPC,XPD, XRCC1, and XRCC3 are associated with risk and survival of squamous cell carcinoma of the head and neck

Head and neck squamous cell carcinomas (HNSCC) are a heterogenous group of tumors with a high rate of early recurrences, second primary tumors, and mortality. Despite advances in diagnosis and treatment over the past decades, the overall 5-year survival rate remains around 50%. Since the head-and neck-region is continuously exposed to potentially DNA-damaging exogenous and endogenous factors, it is reasonable to expect that the DNA repair genes play a part in the development, progression, and outcome of HNSCC. The aim of this study was to investigate the SNPs XPC A499V, XPD K751Q, XRCC1 R399Q, and XRCC3 T241M as potential risk factors and indicators of survival among Caucasian patients. One-hundred-sixty-nine patients as well as 344 healthy controls were included and genotyped with PCR–RFLP. We showed that XPC A499V was associated with increased risk of HNSCC, especially laryngeal carcinoma. Among women, XPD K751Q was associated with increased risk of oral SCC. Furthermore, XPD homozygous mutant individuals had the shortest survival time, a survival time that increased however after full dose radiotherapy. Wild-type individuals of XRCC3 T241M demonstrated an earlier age of onset. HPV-positive never smokers had lower frequencies of p53 mutation. Among HNSCC patients, HPV-positivity was significantly associated with XRCC1 R399Q homozygous mutant genotype. Moreover, combinations of putative risk alleles seemed to act synergistically, increasing the risk of HNSCC. In conclusion, our results suggest that SNPs of the DNA repair genes XPC, XPD, XRCC1, and XRCC3 may affect risk and survival of HNSCC.     

Metabolic responses of sand fiddler crabs, Uca pugilator, in northwest Florida to seasonal temperature change

Metabolic responses of sand fiddler crab, Uca pugilator, populations in northwest Florida are greatly influenced by seasonal temperature fluctuations. Crabs acclimated at 20 °C and immediately transferred to either 14 or 26 °C produced an acute metabolic response with respective temperature quotient (Q₁₀) values of 3.46 and 3.91. Crabs acclimated at 10 and 20 °C exhibited a Q₁₀ of 2.62 indicating a partial compensation response. A brumation (reverse) response (Q₁₀ value of 20.11) was observed for acclimated crabs between 5 and 10 °C. Brumation is advantageous during winter when food supplies are scarce and crabs must survive extensive periods of inactivity.     

Center Variation in Intestinal Microbiota Prior to Late-Onset Sepsis in Preterm Infants

Objective

Late onset sepsis (LOS) contributes to mortality and morbidity in preterm infants. We tested the hypotheses that microbes causing LOS originate from the gut, and that distortions in the gut microbial community increases subsequent risk of LOS.

Study Design

We examined the gut microbial community in prospectively collected stool samples from preterm infants with LOS and an equal number of age-matched controls at two sites (Cincinnati, OH and Birmingham, AL), by sequencing the bacterial 16S rDNA. We confirmed our findings in a subset of infants by whole genome shotgun sequencing, and analyzed the data using R and LEfSe.

Results

Infants with LOS in Cincinnati, as compared to controls, had less abundant Actinobacteria in the first samples after birth (median 18 days before sepsis onset), and less abundant Pseudomonadales in the last samples collected prior to LOS (median 8 days before sepsis onset). Infants with LOS in Birmingham, as compared to controls, had no differences identified in the first sample microbial communities, but Lactobacillales was less abundant in the last samples prior to LOS (median 4 days before sepsis onset). Sequencing identified detectable levels of the sepsis-causative organism in stool samples prior to disease onset for 82% of LOS cases.

Conclusions

Translocation of gut microbes may account for the majority of LOS cases. Distortions in the fecal microbiota occur prior to LOS, but the form of distortion depends on timing and site. The microbial composition of fecal samples does not predict LOS onset in a generalizable fashion.     

Ventilation Onset Prior to Umbilical Cord Clamping (Physiological-Based Cord Clamping) Improves Systemic and Cerebral Oxygenation in Preterm Lambs

BackgroundAs measurement of arterial oxygen saturation (SpO₂) is common in the delivery room, target SpO₂ ranges allow clinicians to titrate oxygen therapy for preterm infants in order to achieve saturation levels similar to those seen in normal term infants in the first minutes of life. However, the influence of the onset of ventilation and the timing of cord clamping on systemic and cerebral oxygenation is not known.AimWe investigated whether the initiation of ventilation, prior to, or after umbilical cord clamping, altered systemic and cerebral oxygenation in preterm lambs.MethodsSystemic and cerebral blood-flows, pressures and peripheral SpO₂ and regional cerebral tissue oxygenation (SctO₂) were measured continuously in apnoeic preterm lambs (126±1 day gestation). Positive pressure ventilation was initiated either 1) prior to umbilical cord clamping, or 2) after umbilical cord clamping. Lambs were monitored intensively prior to intervention, and for 10 minutes following umbilical cord clamping.ResultsClamping the umbilical cord prior to ventilation resulted in a rapid decrease in SpO₂ and SctO₂, and an increase in arterial pressure, cerebral blood flow and cerebral oxygen extraction. Ventilation restored oxygenation and haemodynamics by 5–6 minutes. No such disturbances in peripheral or cerebral oxygenation and haemodynamics were observed when ventilation was initiated prior to cord clamping.ConclusionThe establishment of ventilation prior to umbilical cord clamping facilitated a smooth transition to systemic and cerebral oxygenation following birth. SpO₂ nomograms may need to be re-evaluated to reflect physiological management of preterm infants in the delivery room.     

GSTM1 and GSTT1 gene polymorphisms as major risk factors for bronchopulmonary dysplasia in a Chinese Han population

Bronchopulmonary dysphasia (BPD) is a complex multifactorial disease with an obvious genetic predisposition. Oxidative stress plays an important role in its pathogenesis. Glutathione S-transferases (GSTs) detoxify metabolites produced by oxidative stress within the cell and protect the cells against injury. In the present study, the hypothesis that polymorphisms in the GSTM1 and GSTT1 genes are associated with BPD in Chinese Han infants was examined. Sixty infants with BPD and 100 gestational age and birth weight-matched preterm infants without BPD were recruited. Genotyping for GSTM1 and GSTT1 was performed by multiplex polymerase chain reaction (PCR). The GSTM1 null genotype was more prevalent in BPD infants (65.0%) than in the control subjects (48.0%), which yielded higher risk towards BPD (odds ratio (OR): 2.012, 95% confidence interval (CI) = 1.040–3.892, p = 0.037). There was no statistically significant association of GSTT1 genotype with BPD (OR: 1.691, 95% CI = 0.884–3.236, p = 0.111), although the frequency of GSTT1 null genotype was higher among the BPD subjects (60.0%) than in the control patients (47.0%). GSTM1 and GSTT1 double null genotype was also higher in BPD group (38.3%) than in controls (21.0%) with a higher risk towards BPD (OR: 2.338, 95%CI = 1.151–4.751, p = 0.017). The results suggest that null genotypes of GSTM1 and GSTT1 genes may contribute to the development of BPD in our Chinese Han population.