Atypical presentation of a newborn with Apert syndrome.

INTRODUCTION: Apert syndrome is a rare syndrome characterized by a consistent phenotype including bilateral coronal suture synostosis with an enlarged anterior fontanel, midface hypoplasia, and complex symmetric syndactyly of hands and feet. CASE REPORT: We present a boy with Apert syndrome caused by the pathogenic c.755C > G p.Ser252Trp mutation in the FGFR2 gene with atypical characteristics, including premature fusion of the metopic suture with a small anterior fontanel, hypotelorism, and a massive posterior fontanel. Directly after birth, he showed papilledema, epilepsy, and central apneas. CONCLUSION: We present a newborn with Apert syndrome with atypical craniofacial presentation.

Long-tailed macaques (Macaca fascicularis) understand what conspecifics can see in a competitive situation.

Visual perspective taking (VPT), an understanding of what others can see, is a prerequisite for theory of mind (ToM). While VPT in apes is proven, its presence in monkeys is much-debated. Several different paradigms have been developed to test its existence, but all face interpretational problems since results can be explained by simpler cognitive mechanisms than VPT. Therefore, we adjusted one method where two individuals compete for access to food, visible or invisible for the dominant competitor, to preclude cognitively simpler mechanisms. The subordinate long-tailed macaques tested, selected significantly more often the food item invisible than the item visible to the dominant. In most trials, subjects retrieved only one food item and preferred the invisible food item. Surprisingly, they occasionally adopted an alternative strategy to obtain both food items, by first choosing the visible, most at risk food item. Faster animals adopted this strategy proportionally more often than slower ones. Contrary to previous research, our results cannot be explained by simpler cognitive mechanisms, since behavioural reading was prevented by a one-way mirror between the competitor and the food, and accessibility was equal to both food items. This is the first unequivocal evidence of VPT in a monkey species, suggesting that this precursor to ToM is an evolutionarily conserved capacity present in monkeys, apes and humans.

Quantified tracking and monitoring of diazepam treated socially housed cynomolgus monkeys.

Quantitative assessment of behavioural patterns is frequently used in rodent toxicity studies, however only limited approaches are available for monkeys. Often qualitative behavioural scoring using functional observation batteries (FOBs) is performed, with difficulties like poor reproducibility or lack of sensitivity. In this study, we investigated whether quantitative behavioural monitoring can be applied to group-housed cynomolgus monkeys. Video-tracking EthoVision® XT system and special analysis software were used to evaluate diazepam (i.v. 1mg/kg) related behavioural changes in group-housed animals. Recordings were made predose and at the anticipated time of maximum drug exposure (T(max)). General parameters such as distance travelled and velocity did not reveal the known sedative effects of diazepam. However, inspection of the automatically generated track images indicated that diazepam-treated animals had more a meandering movement pattern suggesting that diazepam induced a loss of balance which was regained by corrective movements. Therefore, parameters revealing specific aspects of the meandering movement pattern such as velocity profiles and turn angles have been analyzed and revealed an increase in the curvature and in the number of directional changes of the movement path.

Sneaky monkeys: an audience effect of male rhesus macaques (Macaca mulatta) on sexual behavior.

Males and females have different sexual interests and subsequently may show conflicting sexual strategies. While dominant males try to monopolize females, promiscuity benefits females and subordinate males. One way to escape monopolization by dominant males is to copulate in their absence. We tested this inhibitory effect of males on the sexual behavior of their group members in captive group-living Rhesus macaques. Copulations between females and nonalpha males almost exclusively took place when the alpha male was out of sight. Furthermore, the inhibiting effect was not unique for the alpha male. An upcoming nonalpha male also inhibited copulations of its group members, and three other nonalpha males inhibited female copulation solicitations. Females adjusted their behavior to the presence of bystander males, as they initiated and accepted initiations more often in absence than in presence of bystander males. Although not significant, in males, a similar pattern was found. The observed reduction in mating behavior in presence of bystander males is in accordance with an "audience effect," in which the behavior is modulated in relation to the presence or absence of third parties. This audience effect may serve as an important mechanism to reduce (aggressive) interruptions of subordinate male copulations.

Influence of environmental enrichment and handling on the acute stress response in individually housed mice.

In this study we investigated the effect of environmental enrichment and handling on the acute physiological stress response caused by short periods of restraint in individually housed female mice. Heart rate (HR) and body temperature (BT) were measured by radiotelemetry and compared with plasma corticosterone (pCORT) levels. Also, postmortem thymus weight and tyrosine hydroxylase (TH) activity were assessed. The acute stress response was seen in both HR and BT. Enrichment and handling were found to increase rather than decrease this stress response, but pCORT values, measured 90 min after restraint, suggested a lower stress response in the enriched groups. No effect was found with thymus weight or TH as parameters.

Novel approach to the behavioural characterization of inbred mice: automated home cage observations.

Here we present a newly developed tool for continuous recordings and analysis of novelty-induced and baseline behaviour of mice in a home cage-like environment. Aim of this study was to demonstrate the strength of this method by characterizing four inbred strains of mice, C57BL/6, DBA/2, C3H and 129S2/Sv, on locomotor activity. Strains differed in circadian rhythmicity, novelty-induced activity and the time-course of specific behavioural elements. For instance, C57BL/6 and DBA/2 mice showed a much faster decrease in activity over time than C3H and 129S2/Sv mice. Principal component analysis revealed two major factors within locomotor activity, which were defined as 'level of activity' and 'velocity/stops'. These factors were able to distinguish strains. Interestingly, mice that displayed high levels of activity in the initial phase of the home cage test were also highly active during an open-field test. Velocity and the number of stops during movement correlated positively with anxiety-related behaviour in the elevated plus maze. The use of an automated home cage observation system yields temporal changes in elements of locomotor activity with an advanced level of spatial resolution. Moreover, it avoids the confounding influence of human intervention and saves time-consuming human observations.

Effect of restraint and injection methods on heart rate and body temperature in mice.

Routine procedures in the laboratory, inducing acute stress, will have an impact on the animals and might thereby influence scientific results. In an attempt to gain more insight into quantifying this acute stress by means of the parameters heart rate (HR) and body temperature (BT), we subjected mice to different restraint and injection methods. We first compared the treatment response of HR and BT, measured by means of radiotelemetry, with the treatment response of plasma corticosterone (pCORT), a common and well-validated parameter for measuring acute stress responses. It was found that HR, and to a lesser extent also BT, parallels pCORT values after subjecting the animals to different methods of restraint. Secondly, the acute stress response caused by different injection methods was evaluated. Again, HR was found to be a more sensitive parameter than BT. We found that, in case of sham injections, the acute stress response after an intraperitoneal (i.p.) injection was more pronounced than after intramuscular (i.m.) or subcutaneous (s.c.) injections, but this difference was found to be inconsistent when saline was used as injection fluid. In a third experiment we investigated if the level of experience of the animal technician influenced the stress response after s.c. injections, but no differences were found. Overall, the results have indicated that HR might be considered as a useful parameter for measuring acute stress responses to routine procedures, but the value of BT seems to be of limited value in this respect.

Susceptibility of duck and turkey to severe hypercapnic hypoxia.

Large groups of poultry, including ducks and turkeys, are killed for disease control purposes with CO2. In this study, we examined the physiological reaction of White Pekin ducks and turkeys to increasing CO2 concentrations. Additionally, we examined the suitability of killing both species with increasing CO2 concentrations. Blood gas values showed similar reaction patterns for both species: a strong increase in pCO2 from approximately 40 to 200 mmHg, decreasing pO2 and O2 saturation, a decrease in pH from 7.4 to 6.7, and a strong shift in acid-base equilibrium (averaging 0 to -23). On the electroencephalogram, theta and sigma waves occurred at 21 to 23% CO2, and suppression to a near isoelectric electroencephalogram occurred between 41.8 and 43.4% CO2 in inhaled air. Heartbeat declined from approximately 300 beats per min (bpm) at the start to 225 bpm at loss of posture to 150 bpm at 1 min before the heartbeat ceased. During the last phase of heart activity, an irregular rhythm and fibrillation were observed in addition to a decline in bpm. Blood gas values and electrophysiological data confirmed that ducks and turkeys lose consciousness before a level of 25% CO2 in inhaled air is reached and that both ducks and turkeys die within 13 min in an environment of 45% CO2 in inhaled air.

Slaughter of poultry during the epidemic of avian influenza in the Netherlands in 2003.

During an outbreak of avian influenza in the Netherlands in spring 2003, the disease was controlled by destroying all the poultry on the infected farms and on all the farms within a radius of 3 km. In total, 30 million birds were killed on 1242 farms and in more than 8000 hobby flocks, by using mobile containers filled with carbon dioxide, mobile electrocution lines and by gassing whole poultry houses with carbon monoxide or carbon dioxide. Observations of these methods were used to compare their effectiveness and capacity, and their effects on the welfare of the birds. Gassing whole poultry houses had a much greater capacity than mobile equipment, and catching live birds to bring them to a mobile killing device caused extra stress and could cause pain due to injuries inflicted when catching and handling them. Gassing whole poultry houses with carbon monoxide requires strict safety regulations and, therefore, gassing with carbon dioxide was considered preferable. However, this method is not suited to all types of housing, and in these circumstances mobile killing devices were a useful alternative.

Abnormal transcranial Doppler cerebral blood flow velocity and blood pressure profiles in children with syndromic craniosynostosis and papilledema.

OBJECTIVE: Children with syndromic craniosynostosis are at risk of intracranial hypertension. This study aims to examine patient profiles of transcranial Doppler (TCD) cerebral blood flow velocity (CBFv) and systemic blood pressure (BP) in subjects with and without papilledema at the time of surgery, and subsequent effect of cranial vault expansion. METHODS: Prospective study of patients treated at a national referral center. Patients underwent TCD of the middle cerebral artery 1 day before and 3 weeks after surgery. Measurements included mean CBFv, peak systolic velocity, and end diastolic velocity; age-corrected resistive index (RI) was calculated. Systemic BP was recorded. Papilledema was used to indicate intracranial hypertension. RESULTS: Twelve patients (mean age 3.1 years, range 0.4-9.5) underwent TCD; 6 subjects had papilledema. Pre-operatively, patients with papilledema, in comparison to those without, had higher TCD values, RI, and BP (all p = 0.04); post-operatively, the distinction regarding BP remained (p = 0.04). There is a significant effect of time following vault surgery with a decrease in RI (p < 0.01). CONCLUSION: Patients with syndromic craniosynostosis who have papilledema have a different TCD profile with raised BP. Vault surgery results in increased CBFv and decrease in RI, however the associated systemic BP response to intracranial hypertension remained at short-term follow-up.

Place learning and hippocampal synaptic plasticity in streptozotocin-induced diabetic rats.

Moderate impairment of learning and memory has been recognized as a complication of diabetes. The present study examined behavioral and electrophysiological measures of cerebral function in streptozotocin (STZ)-induced diabetic rats. Behavioral testing consisted of a spatial learning task in a water maze. Electrophysiological testing consisted of in vitro assessment of hippocampal long-term potentiation (LTP), an activity-dependent form of synaptic plasticity, which is believed to be related to the cellular mechanisms of learning and memory. Two experiments were performed: the first with severely hyperglycemic rats and the second with moderately hyperglycemic rats. Rats were tested in the water maze 11 weeks after induction of diabetes. Next, LTP was measured in vitro in trained animals. Both spatial learning and LTP expression in the CA1 field of the hippocampus were impaired in severely hyperglycemic rats as compared with nondiabetic controls. In contrast, spatial learning and hippocampal LTP were unaffected in moderately hyperglycemic rats. The association of alterations in hippocampal LTP with specific learning impairments has previously been reported in conditions other than diabetes. Our findings suggest that changes in LTP-like forms of synaptic plasticity in the hippocampus, and possibly in other cerebral structures, are involved in learning deficits in STZ-induced diabetes. The beneficial effect of moderate glycemic control on both place learning and hippocampal LTP supports the significance of the relation between these two parameters and indicates that the development of the observed deficits may be related to the level of glycemic control.

Increased gabaergic input to ventral tegmental area dopaminergic neurons associated with decreased cocaine reinforcement in mu-opioid receptor knockout mice.

There is general agreement that dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens and prefrontal cortex play a key role in drug reinforcement. The activity of these neurons is strongly modulated by the inhibitory and excitatory input they receive. Activation of mu-opioid receptors, located on GABAergic neurons in the VTA, causes hyperpolarization of these GABAergic neurons, thereby causing a disinhibition of VTA dopaminergic neurons. This effect of mu-opioid receptors upon GABA neurotransmission is a likely mechanism for mu-opioid receptor modulation of drug reinforcement. We studied mu-opioid receptor signaling in relation to cocaine reinforcement in wild-type and mu-opioid receptor knockout mice using a cocaine self-administration paradigm and in vitro electrophysiology. Cocaine self-administration was reduced in mu-opioid receptor knockout mice, suggesting a critical role of mu-opioid receptors in cocaine reinforcement. The frequency of spontaneous inhibitory post-synaptic currents onto dopaminergic neurons in the ventral tegmental area was increased in mu-opioid receptor knockout mice compared with wild-type controls, while the frequency of spontaneous excitatory post-synaptic currents was unaltered. The reduced cocaine self-administration and increased GABAergic input to VTA dopaminergic neurons in mu-opioid receptor knockout mice supports the notion that suppression of GABAergic input onto dopaminergic neurons in the VTA contributes to mu-opioid receptor modulation of cocaine reinforcement.

Temporal and sequential structure of behavior and facility usage of laying hens in an enriched environment.

Improved housing for laying hens may start from the translation of their behavioral needs into welfare-based design parameters for laying hen houses. The objective of our research was to gain insights into the facility usage and behavioral needs of the hen over 24 h when there are no obvious restraints. Twenty ISA Brown commercial laying hens (Gallus domesticus) that were 18 wk old and not beak trimmed, were accommodated in a pen (4 x 6 m) at 19 + 2 degrees C on a light-dark cycle of 10L:14D. The pen providing nest boxes, drinkers, feeders, perches, sand, and wood shaving was designed to accommodate the hens for the experimental period. Video recordings were made for 10 d. Behavioral analyses were conducted on 5 birds for 5 d. Time spent on each behavior, log survivor analysis of events and inter-event intervals, bout analysis, diurnal pattern in events and bouts, occurrence of behavior in different segments and the corridor of the pen, and sequence analysis were performed to gain insights into the temporal and sequential structures of behavior. Hens spent 97% of the day on nest use, preening, drinking, feeding, still, walking, perching, and resting; 43% on commodity-dependent behavior; and 57% not on commodity-oriented behaviors. Behavioral events were short (around 70% event <2 min) and frequent (around 70% inter-event intervals <40s). The pen corridor was the preferred place for attack, escape, flying, resting, walking, and wing flapping. Feeding-drinking-feeding, preening-resting-preening, scratching-resting-scratching, dust bathing-resting-preening, or dust bathing-resting-wing stretching-dust bathing were the preferred sequences of behavior. Although hens interrupted ongoing behaviors and changed behaviors frequently, they nonetheless clustered behavioral events.

Tactical deception to hide sexual behaviour: macaques use distance, not visibility.

Although tactical deception (TD) may be employed to hide sexual behaviour, there is as yet no firm evidence for it. Hiding may be guided by cognitive mechanisms consistent with either no, low or high level TD, such as exploiting male peripheral positions (no TD), creating distance (TD level 1) or hiding behind screens (TD level 1.5 which involves visual perspective taking (VPT)). Macaques are capable of VPT in a food context, suggesting that they may employ TD level 1.5. We investigated, in an observational study with temporarily provided hiding screens, which strategy was used to hide sexual behaviour in captive groups of two macaque species (Macaca mulatta and Macaca fascicularis). Sexual behaviour only sporadically took place near screens, and the few copulations near screens were not systematically hidden from the alpha male, precluding TD level 1.5. Instead, both females and non-alpha males were at a larger distance from the alpha male during sexual interactions than otherwise, consistent with TD level 1. Creating peripheral locations (TD level 1) may be effective in improving sexual opportunities in many species.

Progressive decline in social attention in aging rats: an information-statistical method.

The purpose of this study was to assess the earliest signs of behavioral changes during aging. In a longitudinal setup the spontaneously displayed social behavior was observed and analyzed. Social interactions offer an appropriate paradigm for studying a gradual decrease in several categories of social behavior in aging animals. The frequencies and durations of 12 behavioral categories collected over 18 sessions yield a wealth of data, which is difficult to evaluate. Therefore, an information-statistical analysis was used, which compressed the frequencies and sequential organization of behavior into a very sensitive and meaningful index. This index expressing the predictability of behavior does not only show age-related changes but also yields an interpretation of the complex changes seen in frequency distributions. The applied analysis focuses on the predictability of behavior, which may be predominantly determined by the animal's own preceding behavior or by the behavior of its social partner. It is shown that the influence of the behavior of a partner on ongoing behavior declines age-dependently, whereas the influence of the animal's own preceding behavior increases. The simultaneous change in these two indices is interpreted as a progressive decline in social attention, which seems to be characteristic for aging rats. It is concluded that the analysis of the sequential organization of behavior offers a new tool, useful in longitudinal behavioral studies on aging.

An ACTH4-9 analog enhances social attention in aging rats: a longitudinal study.

Effect of chronic treatment of the ACTH4-9 analog, Org2766, on social attention was studied longitudinally in aging rats. A 6-week treatment temporarily enhanced specific combinations of behaviors of two interacting animals. During a 6-month treatment social attention of treated animals remained at the same level, whereas control animals showed a gradual decrease. Two months after the treatment was ceased this effect on social attention was still present; moreover, the peptide-treated animals performed better in a spatial water maze task three months after the last injection. In addition, the nerve conduction velocity of the major caudal nerves and the sciatic nerve were measured; aged, peptide-treated animals preserved their conduction velocity. The present study shows beneficial long-lasting effects of the ACTH4-9 analog in aging rats on complex behavioral indices and on a physiological measure.

Behavioral changes in ACTH-(1-24)-induced excessive grooming in aging rats.

Age-related behavioral changes are commonly associated with impaired cognitive functioning. As a result an abundance of neuropsychological tools have been developed to study learning and memory in man and animal. The combined use of ethological methods and the extensively studied measures of excessive grooming behavior in rats provides an excellent tool to study non-cognitive behavioral changes. In the present study, a sequential analysis was applied to the different grooming elements. Aged rats showed a loss in the sequential organization of their grooming behavior, which led to a decrease in the display of tail sniffing. Interestingly, the reduced display of an element which appears latest in the ontogeny of grooming is reminiscent of the Jacksonian principle of behavioral degeneration. Seemingly, this principle is not necessarily confined to learning paradigms, but may be extended to other behavioral systems as well.

Increased rigidity with age in social behavior of Java-monkeys (Macaca fascicularis).

In this study we investigated the effect of aging on the structure of behavior of socially housed Java-monkeys. Indices of the sequential structure of an animal's own ongoing behavior and of its responses to behavior of other animals were calculated using an information statistic approach. These indices reflect information-processing abilities of an animal, as they represent the ability of an animal to adjust its behavior in response to actions by interaction partners. The influence of an animal's dominance history on the age-related changes was investigated as well. In the literature social subordinance in monkeys is generally associated with elevated levels of cortisol which, in turn, have been suggested to influence information processing abilities. In this study, old animals of low dominance history became more rigid in their own ongoing behavior, whereas old animals of high dominance history did not differ from young animals. The ability of old animals to maintain normal levels of predictability during social interactions declined, but only in social interactions with unfamiliar animals, such as young or unrelated animals. These results may explain the generally found social withdrawal of old non-human primates.

Aging, dominance history, and social behavior in Java-monkeys (Macaca fascicularis).

The aim of this study was to investigate the influence of the dominance history of socially housed Java-monkeys on the aging process. In monkeys, social subordinance is generally associated with elevated levels of cortisol, which, in turn, have been suggested to influence cognitive decline. As cognitive skills are necessary for successful social life, we investigated the effect of old age in relation to the dominance history of the animals on their social behavior by comparing old females with their younger daughters. Old age, especially in combination with a history of low rank, led to a withdrawal from social interactions with unfamiliar animals and to a decrease in amounts of aggression received. Still, however, old animals showed an increase in behaviors associated with arousal. A reduced ability to deal with complex social interactions, caused by a decline in information processing abilities, is suggested as an explanation for these results.

Morphine attenuates the effects of juvenile isolation in rats.

The acute effects of juvenile isolation on sucrose intake and its long-term consequences on adult social behavior were investigated. Additionally, the role of the endogenous opioid systems was studied. Juvenile rats were housed in one of three conditions: in groups or in isolation with (partial isolation, PI) or without 30 min of daily social contact from 22 to 35 days-of-age. During this period the rats were treated daily with saline or morphine. Juvenile isolated rats showed an increased sucrose intake as compared to non-isolated controls, with PI-rats somewhere in-between, suggesting a negative correlation between the amount of social contact and sucrose consumption. Morphine treatment during the isolation period enhanced the sucrose intake in non-isolated rats, whereas it decreased sucrose consumption in (partial) isolated rats. With regard to the long-term effects, (partial) isolated rats decreased social activity as compared to non-isolated controls which was reversed by morphine treatment during the isolation period. In non-isolated rats, morphine treatment caused an opposite effect: it decreased social activity as compared to the saline treated controls. The data suggest that stimulation of endogenous opioid systems in the juvenile phase may have an important modulatory role in the expression of adult social behavior. The results are discussed in relation to a possible function of morphine as a substitute for the release of endogenous opioid peptides during social play.