Lower versus higher hemoglobin threshold for transfusion in ARDS patients with and without ECMO.

BACKGROUND: Efficacy and safety of different hemoglobin thresholds for transfusion of red blood cells (RBCs) in adults with an acute respiratory distress syndrome (ARDS) are unknown. We therefore assessed the effect of two transfusion thresholds on short-term outcome in patients with ARDS. METHODS: Patients who received transfusions of RBCs were identified from a cohort of 1044 ARDS patients. After propensity score matching, patients transfused at a hemoglobin concentration of 8 g/dl or less (lower-threshold) were compared to patients transfused at a hemoglobin concentration of 10 g/dl or less (higher-threshold). The primary endpoint was 28-day mortality. Secondary endpoints included ECMO-free, ventilator-free, sedation-free, and organ dysfunction-free composites. MEASUREMENTS AND MAIN RESULTS: One hundred ninety-two patients were eligible for analysis of the matched cohort. Patients in the lower-threshold group had similar baseline characteristics and hemoglobin levels at ARDS onset but received fewer RBC units and had lower hemoglobin levels compared with the higher-threshold group during the course on the ICU (9.1 [IQR, 8.7-9.7] vs. 10.4 [10-11] g/dl, P < 0.001). There was no difference in 28-day mortality between the lower-threshold group compared with the higher-threshold group (hazard ratio, 0.94 [95%-CI, 0.59-1.48], P = 0.78). Within 28 days, 36.5% (95%-CI, 27.0-46.9) of the patients in the lower-threshold group compared with 39.5% (29.9-50.1) of the patients in the higher-threshold group had died. While there were no differences in ECMO-free, sedation-free, and organ dysfunction-free composites, the chance for successful weaning from mechanical ventilation within 28 days after ARDS onset was lower in the lower-threshold group (subdistribution hazard ratio, 0.36 [95%-CI, 0.15-0.86], P = 0.02). CONCLUSIONS: Transfusion at a hemoglobin concentration of 8 g/dl, as compared with a hemoglobin concentration of 10 g/dl, was not associated with an increase in 28-day mortality in adults with ARDS. However, a transfusion at a hemoglobin concentration of 8 g/dl was associated with a lower chance for successful weaning from the ventilator during the first 28 days after ARDS onset. TRIAL REGISTRATION: ClinicalTrials.gov NCT03871166.

Positive and negative aspects of soda/anthraquinone pulping of hardwoods.

The positive aspects of the non-sulfur soda/anthraquinone (SAQ) process are mostly tied to improved energy efficiency while lower pulp brightness after bleaching is its most significant drawback. A credible method that quantifies bleachability as well as an approach that solves the problem for SAQ pulps from hardwoods will be described. A straight line correlation (R2=0.904) was obtained between O2 kappa number and final light absorption coefficient (LAC) value after standardized OD0EpD1 bleaching of nine hardwood kraft pulps from three laboratories and one pulp mill. The bleachability of pulps from four different soda processes catalyzed by anthraquinone (AQ) and 2-methylanthraquinone (MAQ) was compared to that of conventional kraft pulps by comparing O2 kappa number decrease and final LAC values. It was observed that a mild hot water pre-hydrolysis improved the bleachability of SAQ pulps to a level equal to that of kraft.

Characterization of complementary DNA encoding the precursor for gonadotropin-releasing hormone and its associated peptide from a teleost fish.

Reproductive maturity among male African cichlids Haplochromis burtoni is cued by a series of environmental and social interactions and is mediated physiologically by GnRH. A cDNA clone encoding the precursor for GnRH was isolated from this teleost. The molecular architecture of the predicted prohormone is analogous to that of the previously characterized mammalian forms; however, the predicted sequence of the associated peptide is strikingly different. Attempts to isolate a putative second precursor using low stringency hybridization were not successful despite evidence that a second related decapeptide exists in at least some teleost species.

Primary structure of solitary form of gonadotropin-releasing hormone (GnRH) in cichlid pituitary; three forms of GnRH in brain of cichlid and pumpkinseed fish.

GnRH is a decapeptide family with at least nine distinct structures. Vertebrates, except for most placental mammals, have more than one of these GnRH forms within the brain. We report chromatographical and immunological evidence that three forms of GnRH are in the brains of both cichlid (Haplochromis burtoni) and pumpkinseed (Lepomis gibbosus) fishes. We argue that the three forms correspond to those previously described as sea bream GnRH (sbGnRH), chicken GnRH-II and salmon GnRH. In contrast, only one GnRH form was present in the pituitary of the cichlid and is identified as sbGnRH by amino acid sequence. This is the first report in which the primary structure of GnRH is determined from pituitary tissue. The N-terminus was identified by monitoring the digestion of the peptide by pyroglutamate aminopeptidase with matrix assisted laser desorption/ionization (MALDI) mass spectrometry (MS). The amidation of the C-terminus was established using an esterification procedure for monitoring with MALDI-MS. This report supports the idea that three forms of GnRH within one species is widespread in the order Perciformes. The present study establishes sbGnRH as the third GnRH form in H. burtoni and predicts that sbGnRH is synthesized in preoptic neurons, then transported to the pituitary in the preoptic-hypophyseal axons for the release of one or both gonadotropins.

Ontogeny of gonadotropin releasing hormone-containing neurons in the teleost brain.

We investigated changes in two gonadotropin releasing hormone (GnRH)-containing neuronal populations during juvenile development in the African teleost, Haplochromis burtoni. Juveniles were sampled at weekly intervals and GnRHir neurons were identified through immunocytochemistry (ICC), then counted and measured on computer-captured video images. Soma size of GnRH neurons in the preoptic area (POA), which regulate gonadotropin release from the pituitary, is socially modulated in adults. Here we show that in juveniles the soma size of these neurons increases as a linear function of body weight. Terminal nerve (TN) GnRHir neurons, in contrast, are not involved in pituitary regulation and their soma size is not socially modulated in adults. In juveniles, soma size of these neurons is a quadratic function of body size and the covariance of soma size and body size is much less than in the POA GnRHir neurons. In both populations, GnRHir neuronal number covaries with body size or age only in the earliest juvenile stages. Analysis of the development of these two distinct GnRHir neuronal populations provides insight into their functional differentiation in adults.

Unmasking affiliative behavior among juvenile Midas cichlids (Cichlasoma citrinellum).

Adults of the Midas cichlid (Cichlasoma citrinellum) are predominantly normal-colored (N) morphs, although 8% in nature are gold (G) morphs. They tend to mate assortatively by color; that behavior may be influenced by prior experience with parents or siblings or by their own color. A previous experiment indicated that juveniles respond according to a rule that they avoid and behave defensively toward G juveniles and that they consort with and behave aggressively toward N juveniles (Barlow & Siri, 1987). The fear-provoking effect of G may have interfered with more subtle aspects of choice because the 4 treatment fish in each group reacted through the glass barrier to the approach of the subject. In the present experiment such feedback was eliminated by using one-way mirrors. N juveniles reared by normal parents (N X N) differentiated between N and G treatment fish only in that they attacked significantly more toward G; thus their behavior was contrary to that predicted by the fear-provoking effect of gold. The notable effect among juveniles reared by G parents (G X G) was that N spent more time with N and avoided G treatment fish, in keeping with the fear-provoking effect of gold. The results are discussed in terms of the differences in experiences between juveniles reared N X N, all of which were themselves N, and those reared G X G, consisting of both color morphs. Despite the differences in the two experiments, the main conclusion remains in place: Affiliative responses of juveniles, as measured in these tests, do not predict choice of mate among adults.

Effect of additives on fiber yield improvement for kraft pulping of kadam (Anthocephalus chinensis).

Projected decline in future wood resources has prompted researchers to try various additives in existing pulping processes for fiber yield improvement. Many studies have been conducted in the past aimed at improving kraft pulp yield with the use of additives in the cooking liquor. In this study, the effects of anthraquinone (AQ) and 2-methylanthraquinone (MAQ) on the pulp yield of kadam (Anthocephalus chinensis) were investigated. Three different active alkali doses (14%, 16% and 19% as NaOH) along with 0.1% of AQ or MAQ on chips were used to obtain various levels of delignification of the hardwood. Addition of AQ or MAQ to kraft pulping, increased fiber yield (0.5-2.7% on chips) and improved delignification selectivity (lignin vs. carbohydrate removal). Increases in pulp yield due to AQ or MAQ were more significant at lower doses of active alkalis. The viscosities and the physical strength properties of the pulps with kappa numbers 16-19 were comparable to kraft although there was a minor decrease in tensile strength for the kraft/MAQ pulp.

Adherence to guideline-based standard operating procedures in pre-hospital emergency patients with chronic obstructive pulmonary disease.

This study investigated improvements in pre-hospital care for patients with acute exacerbated chronic obstructive pulmonary disease (aeCOPD) achieved by using a standard operating procedure (SOP). An SOP for pre-hospital treatment of patients with aeCOPD was designed based on valid national guidelines. A total of 1000 Emergency Medical Service patient care reports were analysed prospectively: 500 before and 500 after introduction of the SOP. Overall guideline adherence was 34.6% before and 53.8% after introduction of the SOP; this increase was not statistically significant. After SOP introduction, the administration of ß(2) mimetics by inhalative, intravenous and subcutaneous routes increased significantly. The level of knowledge of the national guidelines was rated at 67% by emergency physicians during self-assessment, but was only 33% when physicians were asked specific questions during interview. Introducing the SOP for patients with aeCOPD did not significantly improve adherence to valid national guidelines, but did help to improve specific elements of therapy.

Evolutionary neurobiology.

The chasm that formerly separated evolutionary biology from the research of physiologists and developmental biologists has been partially bridged in recent years. An increasing amount of research in the neurosciences makes explicit reference to issues in evolutionary biology. Much of this research is an attempt to understand structures and functions of the brain as adaptations to an animal's physical and social environment. In addition, however, some of this research at the interface of evolutionary biology and neurobiology provides information on internal evolutionary factors and the way they may constrain evolution by natural selection.

Social control of primary sex differentiation in the Midas cichlid.

Sexual differentiation in teleost fishes is characteristically labile. The most dramatic form of sexual lability is postmaturational sex change, which is common among teleosts although rare or absent in other vertebrate taxa. In many cases this process is regulated by social cues, particularly dominance interactions. Here we show that in the Midas cichlid, Cichlasoma citrinellum, these same sorts of social interactions affect much earlier stages of sexual differentiation. In this species, males are larger than females. By manipulating relative size in juveniles, we show that this sex-based size difference does not arise from endogenous factors associated with sex. Rather, sex is determined by relative size as a juvenile. We argue that this mode of sex determination, which may be common among teleosts, is a heterochronic variant of postmaturational sex change, one in which some individuals are deflected from a default female trajectory before maturation, as a result of social signals. The size-advantage model, which specifies the optimal size for sex change in hermaphroditic species, can be extended to account for the decision whether to mature as a male or a female in the Midas cichlid.

Social regulation of the brain-pituitary-gonadal axis.

Reproduction in vertebrates is regulated by the hypothalamic-pituitary-gonadal axis via neural and hormonal feedback. This axis is also subject to exogenous influences, particularly social signals. In the African cichlid fish Haplochromis burtoni, gonadal development in males is socially regulated. A small fraction of the males, which are brightly colored, maintain territories and aggressively dominate inconspicuously colored nonterritorial males. Here we show through manipulation of the social and endocrine environment that changes in social status and gonadal state are accompanied by soma size changes in a population of gonadotropin-releasing hormone-containing neurons in the ventral forebrain. In territorial males, these cells are significantly larger than in nonterritorial males. When an animal switches from being territorial to nonterritorial through a change in social situation, these cells shrink; in animals that change from nonterritorial to territorial status, the cells enlarge. These gonadotropin-releasing hormone-containing cells project to the pituitary and are ultimately responsible for regulating gonadal growth. This mechanism of socially induced cell size change provides the potential for relatively quick adaptive changes in the neuron-endocrine system without nerve cell addition or death. Since the structure of this regulatory axis is conserved among all vertebrates, other species with socially modulated reproductive physiology may exhibit a similar form of physiological regulation.

Number of preoptic GnRH-immunoreactive cells correlates with sexual phase in a protandrously hermaphroditic fish, the dusky anemonefish (Amphiprion melanopus).

The populations of gonadotropin-releasing hormone (GnRH)-producing cells within the preoptic area (POA) and terminal nerve (TN) of the brain have been suggested as the neuronal systems mediating social control of sex and gonadogenesis in sequentially hermaphroditic teleosts. In the present study, the number and soma size of GnRH-immunoreactive (GnRH-ir) cells in the POA and TN were studied in male, female and juvenile individuals of the dusky anemonefish (Amphiprion melanopus), a species which displays both male to female sex change and socially controlled sexual maturation. The results showed that the number of POA (but not TN) GnRH-ir cells differ significantly between sexual phases, with males displaying higher cell numbers than both females and juveniles. Soma sizes of POA and TN GnRH-ir cells were larger in females than in males and juveniles. However, this relationship was fully explained by differences in body size. The results indicate that high POA GnRH cell numbers are part of a masculinizing mechanism and support the hypothesis that the POA GnRH cell population plays a central role in initiating or mediating the process of socially induced gonadal and/or behavioural transformations in sequential hermaphrodites.

Effect of angiotensin II and endothelin-1 receptor blockade on the haemodynamic and hormonal changes after acute blood loss and after retransfusion in conscious dogs.

AIM: This study investigates angiotensin II and endothelin-1 mediated mechanisms involved in the haemodynamic, hormonal, and renal response towards acute hypotensive haemorrhage. METHODS: Conscious dogs were pre-treated with angiotensin II type 1 (AT1) and/or endothelin-A (ETA) receptor blockers or not. Protocol 1: After a 60-min baseline period, 25% of the dog's blood was rapidly withdrawn. The blood was retransfused 60 min later and data recorded for another hour. Protocol 2: Likewise, but preceded by AT1 blockade with i.v. Losartan. Protocol 3: Likewise, but preceded by ETA blockade with i.v. ABT-627. Protocol 4: Likewise, but with combined AT1 plus ETA blockade. RESULTS: In controls, haemorrhage decreased mean arterial pressure (MAP) by approximately 25%, cardiac output by approximately 40%, and urine volume by approximately 60%, increased angiotensin II (3.1-fold), endothelin-1 (1.13-fold), vasopressin (116-fold), and adrenaline concentrations (3.2-fold). Glomerular filtration rate and noradrenaline concentrations remained unchanged. During AT1 blockade, the MAP decrease was exaggerated (-40%) and glomerular filtration rate fell. During ETA blockade, noradrenaline increased after haemorrhage instead of adrenaline, and the MAP recovery after retransfusion was blunted. The decrease in cardiac output was similar in all protocols. CONCLUSIONS: Angiotensin II is more important than endothelin-1 for the short-term regulation of MAP and glomerular filtration rate after haemorrhage, whereas endothelin-1 seems necessary for complete MAP recovery after retransfusion. After haemorrhage, endothelin-1 seems to facilitate adrenaline release and to blunt noradrenaline release. Haemorrhage-induced compensatory mechanisms maintain blood flow more effectively than blood pressure, as the decrease in cardiac output--but not MAP--was similar in all protocols.

Androgen regulation of hypothalamic neurons containing gonadotropin-releasing hormone in a cichlid fish: integration with social cues.

Reproduction in vertebrates is regulated by internal signals such as hormone levels and by external signals such as social interactions. In an African cichlid fish, Haplochromis burtoni, the effect of social interactions is evident in the hypothalamo-pituitary-gonadal (HPG) axis of males. Territorial males, characterized by aggressive and reproductive activity, have significantly larger hypothalamic gonadotropin-releasing hormone (GnRH)-containing neurons and larger testes than nonterritorial males. Furthermore, a switch in the social status of an adult male causes a corresponding change in GnRH neuron size and testis size. Here we show that the GnRH-containing neurons in the hypothalamus of adult territorial males are also influenced by gonadal hormones. Castration of territorial males caused GnRH neurons to increase in size. This neuronal hypertrophy in castrated animals was prevented either by testosterone (T) or 11-ketotestosterone (KT) treatment. Estradiol (E2) treatment did not reduce GnRH cell size in castrated animals. These results suggest that androgens reduce the size of GnRH cells through negative feedback. Since E2 had no effect, androgen influence on GnRH cell size appears to be independent of aromatization. These data are consistent with the hypothesis that the setpoint for hypothalamic GnRH cell size is determined by social cues and that this setpoint is maintained by negative feedback from gonadal androgens.

Hypertrophy of gonadotropin releasing hormone-containing neurons after castration in the teleost, Haplochromis burtoni.

In the African cichlid fish, Haplochromis burtoni, males are either territorial or nonterritorial. Territorial males suppress reproductive function in the nonterritorial males, and have larger gonads and larger gonadotropin-releasing hormone- (GnRH) containing neurons in the preoptic area (POA). We describe an experiment designed to establish the causal relationship between large GnRH neurons and large testes in these males by determining the feedback effects of gonadal sex steroids on the GnRH neurons. Territorial males were either castrated or sham-operated, 4 weeks after which they were sacrificed. Circulating steroid levels were measured, and the GnRH-containing neurons were visualized by staining sagittal sections of the brains with an antibody to salmon GnRH. The soma areas of antibody-stained neurons were measured with a computer-aided imaging system. Completely castrated males had markedly reduced levels of circulating sex steroids [11-ketotestosterone (11KT) and testosterone (T)], as well as 17 beta-estradiol (E2). POA GnRH neurons in castrates showed a significant increase in mean soma size relative to the intact territorial males. Hence, in mature animals, gonadal steroids act as a brake on the growth of GnRH-containing neurons, and gonadal products are not responsible for the large GnRH neurons characteristic of territorial males.