What About the Little Ones? Systematic Review of Cognitive and Behavioral Outcomes Following Early TBI.

There is increasing empirical focus on the effects of early traumatic brain injuries (TBI; i.e., before the age of six years) on child development, but this literature has never been synthetized comprehensively. This systematic review aimed to document the cognitive, academic, behavioral, socio-affective, and adaptive consequences of early TBI. Four databases (Medline, PsycNET, CINAHL, PubMed) were systematically searched from 1990 to 2019 using key terms pertaining to TBI and early childhood. Of 12, 153 articles identified in the initial search, 43 were included. Children who sustain early TBI are at-risk for a range of difficulties, which are generally worse when injury is sustained at a younger age, injury severity is moderate to severe, and injury mechanisms are non-accidental. Early childhood is a sensitive period for the emergence and development of new skills and behaviors, and brain disruption during this time is not benign. Research, clinical management, intervention, and prevention efforts should be further developed with consideration of the unique characteristics of the early childhood period.

Changes in auxin response from mutations in an AUX/IAA gene.

Transcription of the AUX/IAA family of genes is rapidly induced by the plant hormone auxin, but evidence that AUX/IAA genes mediate further responses to auxin has been elusive. Changes in diverse auxin responses result from mutations in the Arabidopsis AXR3 gene. AXR3 was shown to be a member of the AUX/IAA family, providing direct evidence that AUX/IAA genes are central in auxin signaling. Molecular characterization of axr3 gain-of-function and loss-of-function mutations established the functional importance of domains conserved among AUX/IAA proteins.

Spontaneous diabetes mellitus in the Bio-Breeding/Worcester rat. Evidence in vitro for natural killer cell lysis of islet cells.

We sought direct evidence for anti-islet cellular cytotoxicity in diabetic Bio-Breeding/Worcester (BB/W) rats by comparing the effects of splenic lymphoid cells from BB/W diabetic (D), diabetes-prone (DP), and diabetes-resistant (DR) rats on the release of 51Cr from damaged islet cells in vitro. D and DP splenic lymphoid cells were cytotoxic to major histocompatibility complex (MHC)-compatible Wistar-Furth (WF) rat islet cells and also to MHC-incompatible Lewis rat islet cells and a rat islet cell line (RIN 5F), whereas WF and Lewis rat spleen cells and a rat pituitary cell line (GH3) were not lysed by lymphoid cells from D or DP rats. The cytotoxic cells were identified as natural killer (NK) cells since NK-sensitive cells (G1-TC and YAC-1 cell lines) were lysed by D and DP spleen cells, YAC-1 cells competed for the lysis of RIN islet cells by D spleen cells, lysis of RIN cells was increased by using D spleen cells from the low density fraction (large lymphocytes/monocytes) of a Percoll density gradient, and incubation of D spleen cells with an antiserum to NK cells (anti-asialo GM1 serum) and complement decreased monoclonal antibody-defined subsets containing NK cells (W3/13+ OX19- and OX8+), and this was accompanied by similar decreases in cytotoxicity to YAC-1, RIN, and WF islet cells. These studies demonstrate that NK cell activity is increased in BB/W diabetic and DP rats, and that islet cells can serve as targets for these NK cells. The findings suggest that NK cells may participate in the islet-directed cellular cytotoxic response leading to beta cell destruction and diabetes.

Lymphoid cells of BB/W diabetic rats are cytotoxic to islet beta cells in vitro.

Assays were developed to detect cell-mediated immune destruction of pancreatic islet beta cells by lymphoid cells isolated from diabetic BioBreeding/Worcester (BB/W) rats. Splenic lymphoid cells from diabetic (D), diabetes-prone (DP), and diabetes-resistant (DR) BB/W rats were incubated for 2 days with monolayer cultures of major histocompatibility complex (MHC)-compatible Wistar-Furth (WF) rat islet cells or a rat islet cell line (RIN), and islet beta cell survival was determined by measuring insulin content in the cultures. D splenic lymphoid cells significantly decreased insulin content in WF rat islet (-32%) and RIN cultures (-77%). DP cells also significantly reduced the insulin content in WF rat islet (-20%) and RIN cultures (-63%), whereas DR cells had no significant effect. Islet-directed cytotoxicity was detected also by the release of 51Cr from RIN cells incubated for 8 h with BB/W spleen cells. Cytotoxicity was linearly related to the number of effector spleen cells. At a target: effector of 1:20, lysis (mean +/- SEM) of RIN target cells by spleen cells from D rats (21.6 +/- 2.0%) and DP rats (16.5 +/- 4.1%) was significantly greater than the effect of DR spleen cells (5.4 +/- 1.0%). D and DP splenic lymphoid cells activated in vitro for 2 days with concanavalin A exhibited a doubling of cytotoxicity to RIN islet cells. These results provide direct evidence for lymphoid cell-mediated immune damage to islet beta cells in diabetic BB rats.

A prospective analysis of islet-cell cytotoxic antibodies in insulin-dependent diabetic children. Transient effects of plasmapheresis.

We determined the effects of plasmapheresis on cytotoxic antibodies to islet cells in 10 children (aged 11-16 yr) with newly diagnosed insulin-dependent diabetes mellitus (IDDM), as well as the plasma levels of antibodies over the next 30 mo and their relation to serum C-peptide concentrations. Complement-dependent, antibody-mediated cytotoxicity (C'AMC) in plasma was measured in a 51Cr release assay using monolayers of the rat islet cell line RINm5F. Cytotoxic antibodies decreased in most IDDM subjects treated by plasmapheresis four times within 2 wk of diagnosis; however, the decreases were small and lasted less than 2-3 days. Thus, both before and after plasmapheresis, 7 of the 10 IDDM children were C'AMC-positive (51Cr release greater than 2 SD above mean for 13 healthy children). After 18-30 mo, only 2 of the original 7 IDDM children with C'AMC-positive plasmas were still positive, and 1 of the original 3 IDDM children without significant cytotoxicity had become positive. Meal-stimulated serum C-peptide responses, measured from diagnosis to 18-30 mo later, did not correlate with C'AMC values. We conclude that (1) plasmapheresis has only transient effects on islet-cytotoxic antibody levels in children with IDDM; (2) these antibodies decrease in most, but not all, subjects over the first 18 mo after diagnosis; and (3) the level of cytotoxic antibodies in IDDM plasma at diagnosis has no predictive effect on residual B-cell function.

Stimulation of insulin release by repaglinide and glibenclamide involves both common and distinct processes.

The action of repaglinide, a novel insulin secretagogue, was compared with the sulfonylurea glibenclamide with regard to the hypoglycemic action in vivo, binding to betaTC-3 cells, insulin secretion from perifused mouse islets, and capacity to stimulate exocytosis by direct interaction with the secretory machinery in single voltage-clamped mouse beta-cells. Two binding sites were identified: a high-affinity repaglinide (KD = 3.6 nmol/l) site having lower affinity for glibenclamide (14.4 nmol/l) and one high-affinity glibenclamide (25 nmol/l) site having lower affinity for repaglinide (550 nmol/l). In contrast to glibenclamide, repaglinide (in concentrations as high as 5 micromol/l) lacked the ability to enhance exocytosis in voltage-clamped beta-cells. Repaglinide was more potent than glibenclamide in stimulating insulin release from perifused mouse islets (EC50 29 vs. 80 nmol/l). The greater potency of repaglinide in vitro was paralleled by similar actions in vivo. The ED50 values for the hypoglycemic action were determined to be 10.4 and 15.6 microg/kg after intravenous and oral administration, respectively. The corresponding values for glibenclamide were 70.3 microg/kg (intravenous) and 203.2 microg/kg (oral). Further, repaglinide (1 mg/kg p.o.) was effective (P < 0.001) as an insulin-releasing agent in a rat model (low-dose streptozotocin) of type 2 diabetes. These observations suggest that the insulinotropic actions of repaglinide and glibenclamide in vitro and in vivo are secondary to their binding to the high-affinity repaglinide site and that the insulinotropic action of repaglinide involves both distinct and common cellular mechanisms.

Multiple antimicrobial resistant Salmonella enterica serovar Paratyphi B variant Java in cattle: a case report.

An epidemiological investigation of a calf rearing premises and a closely associated dairy herd was carried out after the isolation of Salmonella enterica serovar Paratyphi B variant Java phage type 3b variant 2 from clinically diseased calves on the premises. The isolate was resistant to ampicillin, chloramphenicol, streptomycin, sulphonamides, tetracyclines, trimethoprim and cefoperazone. The organism was widespread on the calf unit and was also recovered from the dairy premises, mainly from groups of weaned calves. The investigation was extended to 10 epidemiologically linked farms but no S Java was isolated from any of the 40 to 60 samples collected from each premises. Molecular studies showed that the S Java isolates were genetically most similar to isolates from cases of human disease associated with ornamental fish tanks or feed. Long PCR and resistance gene profiling identified a resistance island which was indistinguishable from the human 'fish tank' strain of S Java and animal and human epidemic strains of S Typhimurium DT104. The isolates were clearly distinguished from multi-resistant S Java strains commonly associated with continental poultry. This is the first report of S Java with this resistance pattern in Great Britain.

Inhibition of insulin release after passive transfer of immunoglobulin from insulin-dependent diabetic children to mice.

We used the mouse passive transfer model to test whether islet cell antibodies affect beta-cell function. The immunoglobulin (Ig) fraction of plasma from 5 islet cell surface antibody-positive, newly diagnosed insulin-dependent diabetic children or of a pool of plasma from 12 normal subjects was injected daily (7-16 mg IgG/day) for 14 days into normal immunosuppressed BALB/c mice. Insulin secretory responses in the Ig-injected mice were then examined by perfusing the rodent pancreata in vitro. Insulin release induced by 20 mmol/liter D-glucose during 30 min of stimulation decreased from 900 ng insulin (median; range, 814-1138) from pancreata of mice injected with control Ig to 511 ng (range, 130-786) from pancreata of mice injected with diabetic Ig (P less than 0.003). Both the initial peak and the sustained second phase of glucose-stimulated insulin release were depressed in 4 of the 5 pancreata from mice injected with diabetic Ig. These results indicate that circulating antibodies in diabetic children may alter beta-cell function and possibly contribute to the pathogenesis of insulin-dependent diabetes.

Treatment with GAD65 or BSA does not protect against diabetes in BB rats.

The M(r) 65,000 isoform of glutamic acid decarboxylase (GAD65) has been implicated as the initiating islet cell antigen in the pathogenesis of diabetes, primarily based on studies in non-obese diabetic (NOD) mice. To test the role of this islet cell autoantigen in the pathogenesis of spontaneously occurring diabetes in another animal model, purified recombinant human islet GAD65 was injected i.v. at 200 micrograms/animal into 18-day-old diabetes-prone BB rats. For controls, bovine serum albumin (BSA), which has also been implicated in the pathogenesis of diabetes, or buffer alone was injected into age matched BB rats. At 210 days of age there were no differences in diabetes incidence in the 3 groups, i.e. 73% (11 of 15) in the GAD65-treated, 81% (13 of 16) in the BSA-treated and 65% (11 of 17) in the buffer-treated animals, or in the median age at onset of disease, i.e. 79 days (range 65-111), 87 days (range 60-107) and 86 days (range 74-109), respectively. The lack of protection against diabetes following GAD65 treatment could hypothetically be explained by no or by an aberrant expression of GAD in BB-rat islet cells. However, immunohistochemistry of pancreata and immunoblotting analysis of isolated islets showed that the expression of GAD65 and GAD67 was similar in BB and Lewis rats. In conclusion, these data indicate that neither GAD65 nor BSA autoimmunity is important for the development of diabetes in BB rats, in contrast to the situation in NOD mice, and further emphasizes that extrapolation from only one animal model to autoimmune diabetes in general may not be appropriate.

Incidence of infection with hepatitis B virus in 56 patients with haemophilia A 1971-1979.

During each of the four-year periods 1971-1975 and 1975-1979, the annual incidence of hepatitis B infection has been assessed in 56 patients with haemophilia A by measuring plasma HBsAg, anti-HBs and anti-HBc levels. Infection rates of 7% and 9.5% per annum respectively were observed for each four-year period despite the screening of individual blood donations for HBsAg by techniques up to the sensitivity of reversed passive haemagglutination. The highest incidence of seroconversion was amongst severe haemophiliacs many of whom had received treatment predominantly with cryoprecipitate. Of the 16 patients in whom serological evidence of hepatitis B infection was obtained only one had an accompanying clinical episode of hepatitis. We conclude that haemophiliacs are still at high risk of infection by hepatitis B virus despite the screening of individual blood donors for HBsAg.

Direct isolation of coagulase-negative staphylococci from neonatal blood samples.

Coagulase-negative staphylococci (CNS) were isolated by direct inoculation of anticoagulated whole blood onto agar from 14 (41.2%) of 34 episodes (30 neonates) of suspected bacterial infection, associated with isolation of CNS from the same blood sample by broth-dilution blood cultures. The equivalent of more than 1,000 cfu ml-1 were isolated from four samples (four neonates); the range of counts was 1-103 cfu 25 microliters-1. There was a statistically significant association between isolation of CNS by direct agar inoculation and a raised C-reactive protein level and/or a positive nitroblue tetrazolium test and with the use of an intravascular catheter when compared to those episodes where CNS were isolated from broth blood cultures only. This simple procedure provides an estimate of the number of CNS in the blood of a neonate with suspected bacteraemia and may help to corroborate a diagnosis of CNS bacteraemia.

Seasonal variation in the photoperiodic responses of a pea aphid population: evidence for long-distance movements between populations.

The purpose of the study was to quantify long distance movements in populations of pea aphid, Acyrthosiphon pisum (Harris), by estimating origins and distances travelled by immigrants into a southern Manitoba population. A strong relationship was demonstrated between latitude of origin and photoperiods at which pea aphid populations are stimulated to produce the diapause stage (Smith 1987). Therefore, the approach was to use photoperiodic response as a physiological marker to identify the source of immigrant aphids. The responses of 89 clones from Glenlea, Manitoba (49°38'N), sampled 5 times over 2 seasons, were measured. One sample of clones collected the first season had photoperiodic responses similar to those of a population about 300 km to the south, and significantly different from clones collected in spring of the same year at the same site. Weather analysis corroberates that the migrants were probably carried into Manitoba on a southerly flow of air during the previous 24 to 36 h.

Are development and growth of pea aphids, Acyrthosiphon pisum, in North America adapted to local temperatures?

Developmental rate and adult weight were studied at constant temperatures from 9.8 to 27.9°C for 18 clones from each of five populations of the pea aphid, Acyrthosiphon pisum (Harris), from locations between 39 and 53°N latitude in central North America. The response of developmental rate to temperature for each clone was accurately described by a three parameter non-linear equation. Adult weight usually decreased with increasing rearing temperature, but the shape of the response to temperature varied among clones. Variation in the developmental parameters was greater among clones within populations than among populations. No consistent trends were observed in the developmental parameters or adult weights either with latitude or the long term average temperatures at the locations. We conclude that previously reported geographic variation in the developmental threshold of this species, which was attributed to local adaptation, occurred either because the clones tested were not representative of the populations or because rearing methods differed among studies. The results are discussed in relation to the hypothesis that life history traits which are temperature sensitive are adapted to local thermal environments.

Randomised controlled double blind study of role of recombinant erythropoietin in the prevention of chronic lung disease.

AIM: To evaluate the role of recombinant human erythropoietin (R-HuEpo) in reducing iron infusion, which may exacerbate free radical damage, leading to chronic lung disease. METHODS: A multicentre, randomised, placebo controlled, double blind study was carried out in four neonatal intensive care units in Yorkshire. Infants were randomly allocated and received either R-HuEpo (480 U/kg/wk) or placebo by twice weekly subcutaneous injection. The primary outcome measure was the number of days on respiratory support and a secondary outcome the number of blood transfusions required. RESULTS: Forty two very low birthweight (VLBW) infants were randomly allocated. There was little difference in the need for respiratory support one month after randomisation, but subsequently there was a trend towards a reduction in the proportion requiring respiratory support in the R-HuEpo group (difference at three months -0.50, 95% confidence interval -1.00, 0.17). During stay in hospital, the median number of blood transfusions was lower for infants in the R-HuEpo group (difference in medians -2, 95% CI -4, 0). The study was stopped early because of failure to recruit babies at the expected rate. CONCLUSIONS: R-HuEpo seems to reduce the number of days in oxygen for ill VLBW infants. These data could be used to construct a larger multicentre study to evaluate this effect further.

Pancreatic exocrine function and necrotising enterocolitis.

Pancreatic protease deficiency may be an aetiological factor in enteritis necroticans, a disease sharing some features of necrotising enterocolitis (NEC). Using faecal chymotrypsin measurement we have prospectively studied pancreatic exocrine function in infants at risk of NEC. No significant difference was found comparing those infants who subsequently developed NEC and those who did not.

Combat-related posttraumatic stress disorder and severity of substance abuse in Vietnam veterans.

This study examined the effects of Vietnam war-zone duty and combat-related posttraumatic stress disorder (PTSD) on severity of drug- and alcohol-abuse disorders among veterans seeking treatment for substance dependence. Combat-exposed Vietnam-theater veterans (N = 108) were compared with Vietnam-era veterans without war-zone duty (N = 151) on psychometric measures of drug and alcohol abuse. There were no differences between theater and era veterans on these measures. However, Vietnam-theater veterans with PTSD experienced more severe drug- and alcohol-abuse problems than did theater veterans without PTSD and were at greater risk for having both forms of substance abuse. Further analyses showed that PTSD was significantly related to some dimensions of drug- and alcohol-abuse problems but not to other dimensions. These findings indicate that PTSD, rather than combat stress per se, is linked to severity of substance abuse. Finally, reexperiencing and avoidance/numbing components of PTSD were more strongly associated with drug abuse than alcohol abuse, but physiological arousal symptoms of PTSD were more highly correlated with alcohol abuse.

The provision of public health nursing follow-up services for postnatal clients in Ontario: a cross-sectional survey.

We did a cross-sectional survey of official health agencies in Ontario in 1990 to assess methods of providing postnatal services. The response rate was 78.6%. We found that diverse methods of postnatal follow-up are offered although home visits remain a primary mode of service delivery. There are significant differences in the timing of home and telephone visits and postnatal group sessions.

Subcutaneous emphysema and pneumomediastinum complicating labor in a twin pregnancy.

Although a rare complication of labor, subcutaneous emphysema and pneumomediastinum (Hamman's syndrome) must be considered in the parturient complaining of chest or neck pain, dysphagia, or shortness of breath. With conservative management, the prognosis is favorable. The case presented is the first of Hamman's syndrome complicating the labor of a twin gestation. The pathophysiology, symptoms, and management guidelines for the syndrome are reviewed.

Anaesthesia-related morbidity in Victoria: a report from 1990 to 2005.

This report involves a review of 736 cases of anaesthesia-related morbidity reported from 1990 to 2005 by the Victorian Consultative Council on Anaesthetic Mortality and Morbidity. Using a combination of an established classification system, emerging categorisation definitions and appropriate keywords, an analysis of the clinical issues and contributory factors was undertaken. Airway-related morbidity, respiratory complications and drug-related adverse events are the most commonly reported. Organisational issues are increasingly implicated in adverse anaesthesia outcomes.