Schistosomiasis in Brazil: Does social development suffice?

Up to 15 years ago, when asked to identify the major public health problems of Brazil, there would be no hesitation in naming infant diarrhoea, Chagas disease and Schistosoma mansoni. While most field workers have now eliminated schistosomiasis from the list, now certainly headed by malaria, in academic and bureaucratic circles the old priorities are still maintained.     

Electrophysiological Measurements and Analysis of Nociception in Human Infants

Pain is an unpleasant sensory and emotional experience. Since infants cannot verbally report their experiences, current methods of pain assessment are based on behavioural and physiological body reactions, such as crying, body movements or changes in facial expression. While these measures demonstrate that infants mount a response following noxious stimulation, they are limited: they are based on activation of subcortical somatic and autonomic motor pathways that may not be reliably linked to central sensory processing in the brain. Knowledge of how the central nervous system responds to noxious events could provide an insight to how nociceptive information and pain is processed in newborns.The heel lancing procedure used to extract blood from hospitalised infants offers a unique opportunity to study pain in infancy. In this video we describe how electroencephalography (EEG) and electromyography (EMG) time-locked to this procedure can be used to investigate nociceptive activity in the brain and spinal cord.This integrative approach to the measurement of infant pain has the potential to pave the way for an effective and sensitive clinical measurement tool.     

How Well Do Clinical Pain Assessment Tools Reflect Pain in Infants?

Background

Pain in infancy is poorly understood, and medical staff often have difficulty assessing whether an infant is in pain. Current pain assessment tools rely on behavioural and physiological measures, such as change in facial expression, which may not accurately reflect pain experience. Our ability to measure cortical pain responses in young infants gives us the first opportunity to evaluate pain assessment tools with respect to the sensory input and establish whether the resultant pain scores reflect cortical pain processing.

Methods and Findings

Cortical haemodynamic activity was measured in infants, aged 25–43 wk postmenstrual, using near-infrared spectroscopy following a clinically required heel lance and compared to the magnitude of the premature infant pain profile (PIPP) score in the same infant to the same stimulus (n = 12, 33 test occasions). Overall, there was good correlation between the PIPP score and the level of cortical activity (regression coefficient = 0.72, 95% confidence interval [CI] limits 0.32–1.11, p = 0.001; correlation coefficient = 0.57). Of the different PIPP components, facial expression correlated best with cortical activity (regression coefficient = 1.26, 95% CI limits 0.84–1.67, p < 0.0001; correlation coefficient = 0.74) (n = 12, 33 test occasions). Cortical pain responses were still recorded in some infants who did not display a change in facial expression.

Conclusions

While painful stimulation generally evokes parallel cortical and behavioural responses in infants, pain may be processed at the cortical level without producing detectable behavioural changes. As a result, an infant with a low pain score based on behavioural assessment tools alone may not be pain free.     

Acquired Antibiotic Resistance: Are We Born with It?

The rapid emergence of antibiotic resistance (AR) is a major public health concern. Recent findings on the prevalence of food-borne antibiotic-resistant (ART) commensal bacteria in ready-to-consume food products suggested that daily food consumption likely serves as a major avenue for dissemination of ART bacteria from the food chain to human hosts. To properly assess the impact of various factors, including the food chain, on AR development in hosts, it is important to determine the baseline of ART bacteria in the human gastrointestinal (GI) tract. We thus examined the gut microbiota of 16 infant subjects, from the newborn stage to 1 year of age, who fed on breast milk and/or infant formula during the early stages of development and had no prior exposure to antibiotics. Predominant bacterial populations resistant to several antibiotics and multiple resistance genes were found in the infant GI tracts within the first week of age. Several ART population transitions were also observed in the absence of antibiotic exposure and dietary changes. Representative AR gene pools including tet(M), ermB, sul2, and bla(TEM) were detected in infant subjects. Enterococcus spp., Staphylococcus spp., Klebsiella spp., Streptococcus spp., and Escherichia coli/Shigella spp. were among the identified AR gene carriers. ART bacteria were not detected in the infant formula and infant foods examined, but small numbers of skin-associated ART bacteria were found in certain breast milk samples. The data suggest that the early development of AR in the human gut microbiota is independent of infants' exposure to antibiotics but is likely impacted by exposure to maternal and environmental microbes during and after delivery and that the ART population is significantly amplified within the host even in the absence of antibiotic selective pressure.     

Identification of Aminoglycoside and β-Lactam Resistance Genes from within an Infant Gut Functional Metagenomic Library

The infant gut microbiota develops rapidly during the first 2 years of life, acquiring microorganisms from diverse sources. During this time, significant opportunities exist for the infant to acquire antibiotic resistant bacteria, which can become established and constitute the infant gut resistome. With increased antibiotic resistance limiting our ability to treat bacterial infections, investigations into resistance reservoirs are highly pertinent. This study aimed to explore the nascent resistome in antibiotically-naïve infant gut microbiomes, using a combination of metagenomic approaches. Faecal samples from 22 six-month-old infants without previous antibiotic exposure were used to construct a pooled metagenomic library, which was functionally screened for ampicillin and gentamicin resistance. Our library of ∼220Mb contained 0.45 ampicillin resistant hits/Mb and 0.059 gentamicin resistant hits/Mb. PCR-based analysis of fosmid clones and uncloned metagenomic DNA, revealed a diverse and abundant aminoglycoside and β-lactam resistance reservoir within the infant gut, with resistance determinants exhibiting homology to those found in common gut inhabitants, including Escherichia coli, Enterococcus sp., and Clostridium difficile, as well as to genes from cryptic environmental bacteria. Notably, the genes identified differed from those revealed when a sequence-driven PCR-based screen of metagenomic DNA was employed. Carriage of these antibiotic resistance determinants conferred substantial, but varied (2–512x), increases in antibiotic resistance to their bacterial host. These data provide insights into the infant gut resistome, revealing the presence of a varied aminoglycoside and β-lactam resistance reservoir even in the absence of selective pressure, confirming the infant resistome establishes early in life, perhaps even at birth.     

Development,validation, and application of an acetylcholinesterase-biosensor test for the direct detection of insecticide residues in infant food

A highly sensitive and rapid food-screening test based on disposable screen-printed biosensors was developed, which is suitable for monitoring infant food. The exposure of infants and children to neurotoxic organophosphates and carbamates is of particular concern because of their higher susceptibility to adverse effects. The European Union has, therefore, set a very low limit for pesticides in infant food, which must not contain concentrations exceeding 10 microg/kg for any given pesticide. The maximum residue limit (MRL) has been set to be near the determination threshold that is typically achieved for pesticides with traditional analytical methods. The biosensor method could detect levels lower than 5 microg/kg and thus clearly fulfills the demands of the EU. To substantiate these measurements, recovery rates were determined and amounted on average to 104% in food. Matrix effects were eliminated by the introduction of a special electrode treatment. The test was compared with two traditional pesticide multiresidue analysis methods (GC-MS, LC-MS) using 26 fruit and vegetable samples from local markets and 23 samples of processed infant food from Germany, Spain, Poland and USA. Three infant food samples exceeded the MRL of 10 microg/kg when analyzed by either biosensor test or multiresidue methods.     

Social withdrawal behaviour in infant: clinical and research interest

The social withdrawal behaviour concept is presented, along with its historical background and its links to infant depression. Sustained social withdrawal behaviour in infancy is observed either with attachment disorders, in autism, sensory impairment, intense and chronic pain, or in interaction disorders and as effects of maternal depression on the infant. The alarm distress baby scale (ADBB) is a 8 item-assessment scale. It has been built to help screening early withdrawal behaviour, making use for example of the routine physical examination in a Well Baby clinic. Current clinical and research application and validations of the scale are presented.     

The maternal brain and its plasticity in humans

This article is part of a Special Issue “Parental Care”.Early mother–infant relationships play important roles in infants' optimal development. New mothers undergo neurobiological changes that support developing mother–infant relationships regardless of great individual differences in those relationships. In this article, we review the neural plasticity in human mothers' brains based on functional magnetic resonance imaging (fMRI) studies. First, we review the neural circuits that are involved in establishing and maintaining mother–infant relationships. Second, we discuss early postpartum factors (e.g., birth and feeding methods, hormones, and parental sensitivity) that are associated with individual differences in maternal brain neuroplasticity. Third, we discuss abnormal changes in the maternal brain related to psychopathology (i.e., postpartum depression, posttraumatic stress disorder, substance abuse) and potential brain remodeling associated with interventions. Last, we highlight potentially important future research directions to better understand normative changes in the maternal brain and risks for abnormal changes that may disrupt early mother–infant relationships.     

Longitudinal evolution of true protein,amino acids and bioactive proteins in breast milk: a developmental perspective

The protein content of breast milk provides a foundation for estimating protein requirements of infants. Because it serves as a guideline for regulatory agencies issuing regulations for infant formula composition, it is critical that information on the protein content of breast milk is reliable. We have therefore carried out a meta-analysis of the protein and amino acid contents of breast milk and how they evolve during lactation. As several bioactive proteins are not completely digested in the infant and therefore represent “non-utilizable” protein, we evaluated the quantity, mechanism of action and digestive fate of several major breast milk proteins. A better knowledge of the development of the protein contents of breast milk and to what extent protein utilization changes with age of the infant will help improve understanding of protein needs in infancy. It is also essential when designing the composition of infant formulas, particularly when the formula uses a “staging” approach in which the composition of the formula is modified in stages to reflect changes in breast milk and changing requirements as the infant ages.     

The development of nociceptive circuits

The study of pain development has come into its own. Reaping the rewards of years of developmental and molecular biology, it has now become possible to translate fundamental knowledge of signalling pathways and synaptic physiology into a better understanding of infant pain. Research has cast new light on the physiological and pharmacological processes that shape the newborn pain response, which will help us to understand early pain behaviour and to design better treatments. Furthermore, it has shown how developing pain circuitry depends on non-noxious sensory activity in the healthy newborn, and how early injury can permanently alter pain processing.     

Infant skull and suture properties: measurements and implications for mechanisms of pediatric brain injury

The mechanical properties of the adult human skull are well documented, but little information is available for the infant skull. To determine the age-dependent changes in skull properties, we tested human and porcine infant cranial bone in three-point bending. The measurement of elastic modulus in the human and porcine infant cranial bone agrees with and extends previous published data [McPherson, G. K., and Kriewall, T. J. (1980), J. Biomech., 13, pp. 9-16] for human infant cranial bone. After confirming that the porcine and human cranial bone properties were comparable, additional tensile and three-point bending studies were conducted on porcine cranial bone and suture. Comparisons of the porcine infant data with previously published adult human data demonstrate that the elastic modulus, ultimate stress, and energy absorbed to failure increase, and the ultimate strain decreases with age for cranial bone. Likewise, we conclude that the elastic modulus, ultimate stress, and energy absorbed to failure increase with age for sutures. We constructed two finite element models of an idealized one-month old infant head, one with pediatric and the other adult skull properties, and subjected them to impact loading to investigate the contribution of the cranial bone properties on the intracranial tissue deformation pattern. The computational simulations demonstrate that the comparatively compliant skull and membranous suture properties of the infant brain case are associated with large cranial shape changes, and a more diffuse pattern of brain distortion than when the skull takes on adult properties. These studies are a fundamental initial step in predicting the unique mechanical response of the pediatric skull to traumatic loads associated with head injury and, thus, for defining head injury thresholds for children.     

Maturation of guinea pig tracheal strip stiffness

Previously, we showed the shortening velocity of guinea pig tracheal strips was the greatest in juvenile (3-wk-old) compared with infant (1-wk-old) and adult animals (3-mo-old). The greatest shortening velocity was associated with the least resistance to shortening calculated from force-velocity curves among the three age groups. It remained to be verified if the stiffness of tracheal tissue, a measure of tissue response to geometrical deformations, is different among the three age groups. We hypothesized that stiffness of intact tracheal strips is lowest in the juvenile group and that this can explain the ontogeny of airway smooth muscle resistance to shortening and shortening velocity. Static stiffness measured through stepwise deformations showed no age-related differences. Evaluation of tissue response to oscillatory deformations showed that the dynamic stiffness of unstimulated tracheal strips was 8.35 +/- 0.88, 4.15 +/- 1.09, and 8.21 +/- 1.57 kPa, and the phase angle was 10.3 +/- 2.93, 2.46 +/- 0.67, and 7.87 +/- 1.77 degrees in infant, juvenile, and adult, respectively. Unstimulated juvenile strips were significantly lower in dynamic stiffness and phase angle compared with unstimulated infant or adult strips. This maturational profile was independent of muscle strip preset length or oscillation mode/amplitude but was abolished at peak of contraction to either carbachol or electric field stimulation. These results suggest that the noncontractile components of tracheal strips are less stiff and contain fewer viscous/frictional elements in juvenile than in other age groups. This may provide a functional basis for reduced resistance to length changes in juvenile airway smooth muscle.     

Method for detecting the relationship between the initial degree of cellular resistance and its changes under the effect of the stimulants]

Methods have been elaborated for detecting the individual changes in the resistance of cells on the basis of the analysis of alcohol- and heat resistance of isolated muscles of Rana temporaria L. A correlation has been determined between the initial resistance level of cells and its change induced by experimental effects. This method allows to identify a really existing relation as opposed to the seeming one caused by random factors. The study of this makes it possible to detect the responses which fail to be found by traditional methods of statistical treatment of experimental material.     

Adaptive adjustment of offspring sex ratio and maternal reproductive effort in an iteroparous mammal

Large mammals in seasonal environments have a pattern of high-reproductive synchrony in spring, but how the timing of reproduction affects resource allocation decisions at different stages of the reproductive cycle remains largely unexplored. By manipulating the timing of conception in reindeer (Rangifer tarandus), we tested how the timing of conception affected sex ratio, gestation length and weight development of mother and offspring. Females that conceived at their first ovulation within the rut had a 60.5% probability of producing a male; in contrast, females that conceived a cycle later had a 31.3% probability of producing a male. Late conceiving females had gestation times that were 10 days shorter and the calves were 0.6 kg (9.2%) lighter at birth and 7.4 kg (14.7%) lighter in autumn. Over the year, female weight changes was similar between the groups suggesting reindeer follow a bet-hedging strategy; reducing the quality of this year's offspring to ensure their own future reproduction and survival. Harvesting is often selective leading to skewed sex ratios and age structure, which may influence the timing of reproduction due to females hesitation to mate with young males. Whenever this hesitation is strong enough to increase the frequency of recycling, harvesting is likely to have profound life history consequences.     

Delivery of a small for gestational age infant and greater maternal risk of ischemic heart disease

Background

Delivery of a small for gestational age (SGA) infant has been associated with increased maternal risk of ischemic heart disease (IHD). It is uncertain whether giving birth to SGA infant is a specific determinant of later IHD, independent of other risk factors, or a marker of general poor health. The purpose of this study was to investigate the association between delivery of a SGA infant and maternal risk for IHD in relation to traditional IHD risk factors.

Methods and Findings

Risk of maternal IHD was evaluated in a population based cross-sectional study of 6,608 women with a prior live term birth who participated in the National Health and Nutrition Examination Survey (1999–2006), a probability sample of the U.S. population. Sequence of events was determined from age at last live birth and at diagnosis of IHD. Delivery of a SGA infant is strongly associated with greater maternal risk for IHD (age adjusted OR; 95% CI: 1.8; 1.2, 2.9; p = 0.012). The association was independent of the family history of IHD, stroke, hypertension and diabetes (family history-adjusted OR; 95% CI: 1.9; 1.2, 3.0; p = 0.011) as well as other risk factors for IHD (risk factor-adjusted OR; 95% CI: 1.7; 1.1, 2.7; p = 0.025). Delivery of a SGA infant was associated with earlier onset of IHD and preceded it by a median of 30 (interquartile range: 20, 36) years.

Conclusions

Giving birth to a SGA infant is strongly and independently associated with IHD and a potential risk factor that precedes IHD by decades. A pregnancy that produces a SGA infant may induce long-term cardiovascular changes that increase risk for IHD.     

Health and fitness benefits of a resistance training intervention performed in the workplace

This study examined the effects of a workplace-based resistance training intervention on different health-, fitness-, and work-related measures in untrained men (bus drivers). The subjects were recruited from a bus company and divided into a training (n = 48) and control (n = 48) groups after initial prescreening. The training group performed a 24-week resistance training program, whereas the control group maintained their normal daily activities. Each group was assessed for body composition, blood pressure (BP), pain incidence, muscular endurance, and flexibility before and after the 24-week period. Work absenteeism was also recorded during this period and after a 12-week follow-up phase. In general, no body composition changes were identified in either group. In the training group, a significant reduction in BP and pain incidence, along with improvements in muscle endurance and flexibility were seen after 24 weeks (p < 0.05). There were no changes in these parameters in the control group, and the between-group differences were all significant (p < 0.05). A reduction in worker absenteeism rate was also noted in the training (vs. control) group during both the interventional and follow-up periods (p < 0.05). In conclusion, it was found that a periodized resistance training intervention performed within the workplace improved different aspects of health and fitness in untrained men, thereby potentially providing other work-related benefits. Thus, both employers and employees may benefit from the setup, promotion, and support of a work-based physical activity program involving resistance training.     

The gut as reservoir of antibiotic resistance: microbial diversity of tetracycline resistance in mother and infant

The microbiota in the human gastrointestinal tract (GIT) is highly exposed to antibiotics, and may be an important reservoir of resistant strains and transferable resistance genes. Maternal GIT strains can be transmitted to the offspring, and resistances could be acquired from birth. This is a case study using a metagenomic approach to determine the diversity of microorganisms conferring tetracycline resistance (Tc(r)) in the guts of a healthy mother-infant pair one month after childbirth, and to investigate the potential for horizontal transfer and maternal transmission of Tc(r) genes. Fecal fosmid libraries were functionally screened for Tc(r), and further PCR-screened for specific Tc(r) genes. Tc(r) fosmid inserts were sequenced at both ends to establish bacterial diversity. Mother and infant libraries contained Tc(r), although encoded by different genes and organisms. Tc(r) organisms in the mother consisted mainly of Firmicutes and Bacteroidetes, and the main gene detected was tet(O), although tet(W) and tet(X) were also found. Identical Tc(r) gene sequences were present in different bacterial families and even phyla, which may indicate horizontal transfer within the maternal GIT. In the infant library, Tc(r) was present exclusively in streptococci carrying tet(M), tet(L) and erm(T) within a novel composite transposon, Tn6079. This transposon belongs to a family of broad host range conjugative elements, implying a potential for the joint spread of tetracycline and erythromycin resistance within the infant's gut. In addition, although not found in the infant metagenomic library, tet(O) and tet(W) could be detected in the uncloned DNA purified from the infant fecal sample. This is the first study to reveal the diversity of Tc(r) bacteria in the human gut, to detect a likely transmission of antibiotic resistance from mother to infant GITs and to indicate the possible occurrence of gene transfers among distantly related bacteria coinhabiting the GIT of the same individual.     

Social behavior and hormonal correlates during the perinatal period in Japanese macaques

This work assessed the changes in both social interactions and estrogen metabolite excreted in feces in eight group-living Japanese macaques (Macaca fuscata). We tested the hypothesis that the social behavior of pregnant females shows significant changes during the late prepartum and early postpartum period. We also tested the hypothesis that the marked fluctuation in estrogen levels during the perinatal period is associated with the changes in social behavior. We found that pregnant females withdrew from the social life of their group in preparation for parturition and only slowly regained their normal social activity after delivery. These changes were correlated with the fluctuation in estrogen conjugate excreted in feces, giving further evidence that hormones can enhance responsiveness to the infant and may predict maternal competence in macaques. We also found that the high frequency of self-grooming by pregnant females during the perinatal period may be a functional way to improve the quality of care toward an infant by a simple shifting from the care for oneself to the care for the infant after parturition.     

Change in social status and risk of low birth weight in Denmark: population based cohort study.

OBJECTIVE: To estimate the risk of having a low birthweight infant associated with changes in social, environmental, and genetic factors. DESIGN: Population based, historical cohort study using the Danish medical birth registry and Statistic Denmark''s fertility database. SUBJECTS: All women who had a low birthweight infant (< 2500 g) (index birth) and a subsequent liveborn infant (outcome birth) in Denmark between 1980 and 1992 (exposed cohort, n = 11,069) and a random sample of the population who gave birth to an infant weighing > or = 2500 g and to a subsequent liveborn infant (unexposed cohort, n = 10,211). MAIN OUTCOME MEASURES: Risk of having a low birthweight infant in the outcome birth as a function of changes in male partner, area of residence, type of job, and social status between the two births. RESULTS: Women in the exposed cohort showed a high risk (18.5%) of having a subsequent low birthweight infant while women in the unexposed cohort had a risk of 2.8%. After adjustment for initial social status, a decline in social status increased the absolute risk of having a low birthweight infant by about 5% in both cohorts, though this was significant only in the unexposed cohort. Change of male partner did not modify the risk of low birth weight in either cohort. CONCLUSION: Having had a low birthweight infant and a decline in social status are strong risk factors for having a low birthweight infant subsequently.     

House martins respond to perceived danger

We designed a field experiment on breeding house martins (Delichon urbica) which build conspicuous nests in human structures, which require the parents to be wary of potential predators. Some birds therefore avoid entering the nest in the presence of a potential nest predator when the parent is most vulnerable when inside the nest. Therefore, the hesitation to enter the nest in the presence of a potential predator might be for the bird’s own safety. A number of species show such a hesitation in response to a human observer. Using this behaviour exhibited by the house martin, we show here that the bird appreciates the perspective of the observer and behaves as if it can understand what the observer ‘knows’.