Cognitive and brain systems underlying early mathematical development.

We review current debate regarding the core competencies that support early mathematics learning, focusing on the contributions of the inherent system for representing approximate magnitudes, and domain-general systems that facilitate learning across academic domains. The latter include the executive control system that enables explicit processing of quantitative symbols, such as Arabic numerals, and the logical problem-solving abilities (intelligence) that facilitate learning the relations among numerals. The neural systems that underlie these abilities, as related to mathematical learning, are also discussed, albeit briefly. We place the contributions of inherent quantitative abilities and domain-general mechanisms in an evolutionary context and provide some discussion as to how they interact during the learning of evolutionarily novel mathematics.

Tissue engineered constructs for peripheral nerve surgery.

BACKGROUND: Tissue engineering has been defined as "an interdisciplinary field that applies the principles of engineering and life sciences toward the development of biological substitutes that restore, maintain, or improve tissue function or a whole organ". Traumatic peripheral nerve injury resulting in significant tissue loss at the zone of injury necessitates the need for a bridge or scaffold for regenerating axons from the proximal stump to reach the distal stump. METHODS: A review of the literature was used to provide information on the components necessary for the development of a tissue engineered peripheral nerve substitute. Then, a comprehensive review of the literature is presented composed of the studies devoted to this goal. RESULTS: Extensive research has been directed toward the development of a tissue engineered peripheral nerve substitute to act as a bridge for regenerating axons from the proximal nerve stump seeking the distal nerve. Ideally this nerve substitute would consist of a scaffold component that mimics the extracellular matrix of the peripheral nerve and a cellular component that serves to stimulate and support regenerating peripheral nerve axons. CONCLUSIONS: The field of tissue engineering should consider its challenge to not only meet the autograft "gold standard" but also to understand what drives and inhibits nerve regeneration in order to surpass the results of an autograft.

Abortion Incidence and Postabortion Care in Rwanda

Abortion is illegal in Rwanda except when necessary to protect a woman's physical health or to save her life. Many women in Rwanda obtain unsafe abortions; and some experience health complications as a result. To estimate the incidence of induced abortion; we conducted a national sample survey of health facilities that provide postabortion care and a purposive sample survey of key informants knowledgeable about abortion conditions. We found that more than 16;700 women received care for complications resulting from induced abortion in Rwanda in 2009; or 7 per 1;000 women aged 15-44. Approximately 40 percent of abortions are estimated to lead to complications requiring treatment; but about a third of those who experienced a complication did not obtain treatment. Nationally; the estimated induced abortion rate is 25 abortions per 1;000 women aged 15-44; or approximately 60;000 abortions annually. An urgent need exists in Rwanda to address unmet need for contraception; to strengthen family planning services; to broaden access to legal abortion; and to improve postabortion care. (StudieS in Family Planning 2012; 43[1]: 11-20)

Cytokine levels in neonatal necrotizing enterocolitis and long-term growth and neurodevelopment.

OBJECTIVE: To investigate if circulating cytokines are related to growth and neurodevelopmental outcome following necrotizing enterocolitis (NEC). STUDY DESIGN: Pro-inflammatory cytokine levels were measured prospectively in 40 neonates and compared with neurodevelopmental outcome. Cytokine levels were measured at the onset of feeding intolerance (Group II, n = 17) or NEC (Group III, n = 10) and at weeks 2-3 in control infants (Group I, n = 13). Neurodevelopmental outcome was assessed at the age of 24-28 months. Data were analysed using descriptive statistics, non-parametric tests and Student t-test. RESULTS: Median birth weights (range) in groups I, II and III were 1120 (525-1564) g, 1068 (650-1937) g and 1145 (670-2833) g, and median gestational ages (range) were 28 (24-35) weeks 28 (24-35) weeks and 28 (25-37) weeks respectively. NEC occurred in 10 infants. Serum IL-6 (interleukin-6) was elevated in group III, (p = 0.03). Significant developmental delay was found in 12% of the infants in Group II and 20% of the infants in Group III, but no infant in group I. Five infants in group III with NEC (50%), had head ultrasound abnormalities. At 1 year of age, growth, weight and head circumference were significantly different in Group III, however, at two years of age, only height was significantly different, p < 0.02. Although there was wide variation, neonatal cytokine levels tended to be greater in the infants later found to have abnormal cognitive and psychomotor outcomes. CONCLUSION: This study suggests that increased serum levels of pro-inflammatory cytokines may play a role in the poor growth and neurodevelopment associated with this high-risk population.

Prophylactic antibiotics in the prevention of catheter-associated bloodstream bacterial infection in preterm neonates: a systematic review.

OBJECTIVE: To evaluate the efficacy of prophylactic antibiotics in preventing infection associated with central venous catheters in preterm neonates. STUDY DESIGN: The search strategy of the Cochrane Neonatal Review Group was used. The following databases were searched: Medline, Cochrane Central Register of Controlled Trials, CINAHL and EMBASE. In addition, we hand-searched abstracts of Pediatric Academic Societies annual meetings published in Pediatric Research (1990 to July 2007) and Canadian Pediatric Society annual meeting proceedings (1990 to July 2007). No language restrictions were applied. Included were randomized controlled trials of antibiotics given prophylactically to prevent infection in preterm infants (<37 completed weeks) less than 1-month old admitted to neonatal intensive care units. Both centrally or peripherally inserted central venous catheters were included. Assessment of methodological quality and extraction of data for included trials was undertaken independently by two authors. When suitable, data from trials were combined in a meta-analysis. RESULT: A total of three studies were found which addressed the role of prophylactic antibiotics to prevent catheter-related infection in neonates. Two studies used vancomycin as the prophylactic antibiotic and one study used amoxicillin. The meta-analysis of studies that used vancomycin had shown an absolute risk reduction of infection from 23 to 2.4%, which yields a number needed to treat equal to 5 (P=0.0001). Total duration of catheter stay and mortality, were both similar in the vancomycin and control groups. In the amoxicillin study, catheter-related sepsis was not significantly different between the treatment and control groups (P=0.40). The rate of colonization, however, was significantly higher in the control group (relative risk 0.48; 95% CI 0.12, 1.35). The incidence of necrotizing enterocolitis, intracranial hemorrhage, thrombosis and deaths were not statistically significant between groups. CONCLUSION: Prophylactic vancomycin appeared to be effective in preventing catheter-related sepsis in preterm neonates. The potential risks, however, of the emergence of resistance because of prophylactic antibiotics, and their continued effectiveness, need further evaluation, before routine use can be recommended.

Safety profile of morphine following surgery in neonates.

OBJECTIVE: To determine the effect of morphine on duration of mechanical ventilation, apnoea and hypotension among full-term neonates who underwent thoracic or abdominal surgery in a level III neonatal intensive care unit. METHOD: Medical records of 82 infants were reviewed retrospectively and data including patient demographics, clinical diagnosis, type of surgery, postoperative opioid administration, duration of mechanical ventilation, hypotension, apnoea and pain scores (premature infant pain profile (PIPP) score) were collected. RESULT: Sixty-two neonates (76%) received morphine following surgery as a continuous intravenous infusion during the postoperative period. Linear regression analysis showed that morphine dosage and duration were significantly associated with the duration of mechanical ventilation. An increase in morphine infusion rate by 10 microg kg(-1) h(-1) was associated with an increase in the duration of mechanical ventilation by 24 h (P<0.0001) and an increase in morphine duration of 1 hour was associated with a longer duration of mechanical ventilation by 38 min (P<0.0001). Logistic regression analysis showed no association between morphine infusion rate or duration and hypotension. Apnoea was not associated with morphine dosage or duration of infusion in neonates receiving morphine following extubation. Score on the PIPP correlated significantly with morphine infusion rate across time (r=0.47, P<0.01). CONCLUSION: Postoperative morphine dose and duration may prolong the duration of mechanical ventilation but there are no significant dose-dependent effects on other parameters including apnoea or hypotension following extubation in term neonates. More research is needed to determine the safety profile of morphine for management of pain in non-ventilated neonates.

Molecular mechanisms of spider silk.

Spiders spin high-performance silks through the expression and assembly of tissue-restricted fibroin proteins. Spider silks are composite protein biopolymers that have complex microstructures. Retrieval of cDNAs and genomic DNAs encoding silk fibroins has revealed an association between the protein sequences and structure-property relationships. However, before spider silks can be subject to genetic engineering for commercial applications, the complete protein sequences and their functions, as well as the details of the spinning mechanism, will require additional progress and collaborative efforts in the areas of biochemistry, molecular biology and material science. Novel approaches to reveal additional molecular constituents embedded in the spider fibers, as well as cloning strategies to manipulate the genes for expression, will continue to be important aspects of spider biology research. Here we summarize the molecular characteristics of the different spider fibroins, the mechanical properties and assembly process of spidroins and the advances in protein expression systems used for recombinant silk production. We also highlight different technical approaches being used to elucidate the molecular constituents of silk fibers.

Gefitinib in patients with chemo-sensitive and chemo-refractory relapsed small cell cancers: a Hoosier Oncology Group phase II trial.

BACKGROUND: Gefitinib has demonstrated activity in patients with non-small cell lung cancer (NSCLC). Clinical trials have not demonstrated a relationship between response to gefitinib and over-expression of the epidermal growth factor receptor (EGFR). Although, EGFR is not over-expressed in small cell lung cancer (SCLC), we postulated that gefitinib might affect tumor growth through other mechanisms. Agents that are active in NSCLC usually are also effective in SCLC. METHODS: The primary objective was to assess the clinical control rate: complete response (CR) partial response (PR) and stable disease (SD > 90 days), of gefitinib in patients with chemo-resistant and chemo-sensitive small cell cancers. Eligibility criteria included pathologic proof of a neuroendocrine tumor, especially small cell cancer, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2, prior treatment with one or two prior chemotherapy regimens and adequate end-organ function. Patients received gefitinib, 250 mg p.o. daily until disease progression or intolerable side effects. RESULTS: From April 2003 to March 2004, 19 patients were enrolled. Small cell lung cancer accounted for 18 of the 19 patients and one patient had metastatic Merkel cell carcinoma. Twelve patients (63%) had chemo-sensitive disease, defined as progression greater than three months from completion of prior chemotherapy; 7 (37%) had chemo-refractory disease; 13 (68%) had one prior chemotherapy regimen. Other patient characteristics: mean age 64 years (range 52-79 years); ECOG PS 0/1/2 = 7/9/3, M:F = 9:10. Grade 3 toxicities included: fatigue in three patients (15.8%), pulmonary toxicities in three (15.8%) and one patient (5.3%) each with hyperglycemia or pain. Four patients had grade four toxicities: one patient (5.3%) with fatigue and three patients (15.8%) with dyspnea. There were no patients with grade 3 or 4 rash or diarrhea. Two patients had stable disease (<90 days) and 17 had progressive disease as their best response. This study was a two-stage design and because the continuing criterion for stage one was not met, stage 2 was not performed. Median time to progression (TTP) was 50 days (95% CI = 21-58 days). One year overall survival (OS) was 21% (95% CI = 6-45.6%). CONCLUSION: Although gefitinib has activity in select patients with NSCLC, this study failed to demonstrate benefit in patients with small cell lung cancer.

Ultrastructure of lamellar bodies in congenital surfactant deficiency.

Congenital surfactant deficiency (CSD) is a newly identified neonatal lung disorder associated with a variety of molecular defects affecting surfactant synthesis and secretion in alveolar type II cells. The authors present ultrastructural findings of abnormal lamellar bodies in lung biopsies from 4 infants with CSD. All were term infants presenting shortly after birth with severe respiratory failure that was unresponsive to conventional therapy and all died within the first month of life. Lung biopsies were performed between 8 and 25 days of age. Biochemical and molecular studies in 2 unrelated male infants identified SP-B deficiency, one case with 121 ins 2 mutation and the second with a 209 + 4 A > G mutation. Light microscopy in both cases showed features of alveolar proteinosis. Ultrastructurally, alveolar type II cells lacked mature lamellar bodies, and their cytoplasm contained numerous pleomorphic inclusions with membranous and vesicular structures not seen in normal type II cells. The other 2 infants were a pair of siblings in whom molecular studies identified mutations in ABCA3 transporter gene. Light microscopy showed features of acinar dysplasia and desquamative interstitial pneumonitis. TEM studies revealed absence of mature lamellar bodies in type II cells and instead showed a mixture of cytoplasmic electron-dense inclusions with concentric membranes and distinctive electron dense aggregates. The ultrastructural changes in alveolar type II cells correlated well with specific gene defect. In SP-B deficiency, the absence of mature lamellar bodies is consistent with the postulated role for this protein in the formation of lamellar bodies. The lack of mature lamellar bodies in the ABCA3 gene mutations is due to the dysfunction of this endogenous lipid transporter that targets surfactant lipid moieties to the lamellar bodies. The findings demonstrate the importance of TEM studies of lung biopsies from infants with CSD as it is a critical adjunct in the diagnosis of neonatal lung disease and in defining the underlying cellular defects.

Prenatal ultrasonography and neonatal imaging of complete cleft sternum: a case report.

The prenatal diagnosis of a complete cleft sternum was established in a fetus of a twin pregnancy at 22 weeks' gestation. We present the prenatal imaging and correlation with postnatal magnetic resonance imaging and high-resolution ultrasonography. Thinned and depressed midline anterior chest wall transmitting the cardiac pulsation was the clue to the diagnosis, and the defective sternum could be identified on close sonographic observation. Successful surgical correction was undertaken at 2 months of age. There were no major associated abnormalities such as ectopia cordis or midline abdominal wall defects.

Selective screening for neonatal galactosemia: an alternative approach.

UNLABELLED: No universal consensus exists for population-based neonatal screening for galactosemia. In our institution, selective screening for classical galactosemia is carried out on infants under 2 wk of age and those with symptoms suggestive of this disorder. Eighteen cases were diagnosed from 25,099 tests done; 17 were symptomatic at the time of diagnosis. CONCLUSION: We suggest that improved clinical vigilance and selective screening would identify most infants with severe galactosemia as early as a population-based program.

The effect of graded intake of glycyl-L-tyrosine on phenylalanine and tyrosine metabolism in parenterally fed neonates with an estimation of tyrosine requirement.

Although tyrosine is considered indispensable during the neonatal period, its poor solubility has limited its inclusion in parenteral amino acid solutions to less than 1% of total amino acids. Dipeptides of tyrosine are highly soluble, have been shown to be well used and safe in animal models and humans, and, therefore, may be used as an effective means of providing tyrosine in the parenterally fed neonate. The goal of the present study was to determine the tyrosine requirement of the parenterally fed neonate receiving graded intakes of glycyl-L-tyrosine as a source of tyrosine. Thirteen infants receiving adequate energy (340 +/- 38 kJ. kg(-1).d(-1)) and protein (2.4 +/- 0.4 g.kg(-1).d(-1)) were randomized to receive parenteral nutrition with one of five graded levels of glycyl-L-tyrosine. The mean requirement and safe level of intake were estimated using a 1-(13)C-phenylalanine tracer and linear regression cross-over analysis that identified a break point in the response of label appearance in breath CO(2) (F(13)CO(2)) and phenylalanine oxidation to graded tyrosine intake. Based on the mean estimates of whole-body phenylalanine oxidation, the tyrosine mean requirement and safe level of intake were found to be 74 mg.kg(-1). d(-1) and 94 mg.kg(-1).d(-1), respectively. This represents 3.1 and 3.9% of total amino acids, respectively, considerably higher than levels found in present commercially available pediatric amino acid solutions. These data raise concern regarding the adequacy of aromatic amino acid intake in the parenterally fed neonate.

Deficiency of lamellar bodies in alveolar type II cells associated with fatal respiratory disease in a full-term infant.

We report a case of a full-term female infant who presented with severe respiratory distress shortly after birth and died at 23 d of age with unremitting respiratory failure. Infectious and other known causes of respiratory disease in this clinical setting were excluded. Examination of a lung biopsy showed abnormal lung parenchyma with features reminiscent of desquamative interstitial pneumonitis. Ultrastructural studies revealed that alveolar type II cells lacked cytoplasmic lamellar bodies, while other organelles appeared normal. Histochemical and immunohistochemical investigations indicated normal alveolar type II cell marker expression including surfactant proteins (SP-A, SP-B, pro-SP-B, and pro-SP-C). Mutations in the coding sequences of the SP-B gene were excluded as a cause of disease. This case appears to be a novel congenital defect affecting the pulmonary surfactant system. The cellular abnormality may involve the assembly of cytoplasmic lamellar bodies in alveolar type II cells-the principal storage site of pulmonary surfactant.

Short and long range order of the morphology of silk from Latrodectus hesperus (Black Widow) as characterized by atomic force microscopy.

The surfaces of both stretched and unstretched silk threads from the cobweb weaver, Latrodectus hesperus (Black Widow) have been examined by atomic force microscopy (AFM). AFM images of cobweb scaffolding threads show both unordered and highly ordered regions. Two types of fibers within the threads were observed: thicker (approximately 300 nm in diameter) fibers oriented parallel to the thread axis and thinner (10-100 nm) fibrils oriented across the thread axis. While regions which lacked parallel fibers or fibrils were observed on threads at all strain values, the probability of observing fibers and/or fibrils increased with strain. High-resolution AFM images show that with increasing strain, both mean fiber and fibril diameters decrease and that fibrils align themselves more closely with the thread axis. The observation of fibers and fibrils within the cobweb threads has implications for current models of the secondary and tertiary structure and organization of spider silk.

Material properties of cobweb silk from the black widow spider Latrodectus hesperus.

We present the material analysis of scaffolding silk from the cobweb of the black widow spider Latrodectus hesperus. 30 strands were tested from the webs of nine spiders. Strands were stretched at 0.211 mm/s as force and extension were recorded. Cross-sectional area was measured under 1000 x oil-immersion light microscopy. The stress strain curve shows that cobweb silk is a distinct material from other known spider silks. The average breaking point for this cobweb silk is 1.1 +/- 0.5 GPa at 0.22 +/- 0.05 strain. All samples increased stiffness as they were stretched, but to different extents. Variation in stiffness might be due to differential crystallization or alignment of the silk proteins during stretching.

Symptomatic hypoglycemia in otherwise healthy, breastfed term newborns.

Transient symptomatic neonatal hypoglycemia, a diagnosis that is made in the neonatal nursery, is not usually associated with apparently normal infants who have been discharged from hospital. We describe 3 such cases that presented at home on day 3 of life with seizures or life-threatening apneas. We postulate that early discharge of apparently normal infants with marginal nutritional or metabolic adaptation, may expose some infants to postdischarge (but still neonatal) hypoglycemia and its attendant risks.

Cutting edge: secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes.

Dendritic cells (DCs) emigrate to regional lymph nodes (LNs) during immune responses via afferent lymphatic channels. Secondary lymphoid-tissue chemokine (SLC), a CC chemokine, is expressed in secondary lymphoid organs and mediates the chemotaxis of lymphocytes and DCs via its receptor, CC chemokine receptor 7 (CCR7). By dual-label fluorescence confocal microscopy, we showed MHC class II-positive cells within SLC-staining lymphatic channels in the mouse dermis. SLC was a potent in vitro chemoattractant for cultured, migratory skin DCs, and it enhanced the emigration of MHC class II-positive DCs from mouse skin explants by an average of 2.5-fold. Mature or cytokine-activated, but not resting, Langerhans cells expressed CCR7 mRNA by RT-PCR. Anti-SLC Abs, but not control or anti-eotaxin Abs, blocked the in vivo migration of 51Cr-labeled, skin-derived DCs from footpads to draining LNs by 50% (n = 9, p < 0. 005). Thus, we provide direct evidence that SLC and CCR7 participate in the emigration of DCs from peripheral tissue to LNs via lymphatics.

Coupled ocean-atmosphere dynamics in the Indian Ocean during 1997-98.

Climate variability in the Indian Ocean region seems to be, in some aspects, independent of forcing by external phenomena such as the El Niño/Southern Oscillation. But the extent to which, and how, internal coupled ocean-atmosphere dynamics determine the state of the Indian Ocean system have not been resolved. Here we present a detailed analysis of the strong seasonal anomalies in sea surface temperatures, sea surface heights, precipitation and winds that occurred in the Indian Ocean region in 1997-98, and compare the results with the record of Indian Ocean climate variability over the past 40 years. We conclude that the 1997-98 anomalies--in spite of the coincidence with the strong El Niño/Southern Oscillation event--may primarily be an expression of internal dynamics, rather than a direct response to external influences. We propose a mechanism of ocean-atmosphere interaction governing the 1997-98 event that may represent a characteristic internal mode of the Indian Ocean climate system. In the Pacific Ocean, the identification of such a mode has led to successful predictions of El Niño; if the proposed Indian Ocean internal mode proves to be robust, there may be a similar potential for predictability of climate in the Indian Ocean region.

Phenylalanine and tyrosine metabolism in neonates receiving parenteral nutrition differing in pattern of amino acids.

Tyrosine is considered to be an indispensable dietary amino acid in the neonate, yet achieving adequate parenteral tyrosine intake is difficult due to its poor solubility. Increasing the supply of phenylalanine is the most common means of compensating for low tyrosine levels. Unfortunately, plasma phenylalanine concentrations are sometimes elevated in infants receiving high phenylalanine intake. This led us to study the phenylalanine and tyrosine metabolism in 16 neonates randomized to receive total parenteral nutrition with either a high or a moderate phenylalanine-containing amino acid solution. A primed, 24-h continuous stable isotope infusion of L-[1-13C]phenylalanine and L-[3,3-2H2]tyrosine was given to enable the measurement of phenylalanine and tyrosine kinetics. Results demonstrated that 1) phenylalanine hydroxylation was significantly greater in infants receiving high phenylalanine, 2) phenylalanine oxidation and percent dose oxidized was also significantly greater in infants receiving high phenylalanine, 3) apparent phenylalanine retention was greater in neonates receiving high phenylalanine, and 4) alternate catabolites of phenylalanine and tyrosine metabolism were significantly greater in infants receiving high phenylalanine compared with moderate phenylalanine. We conclude that neonates respond to increased parenteral phenylalanine intake by increasing their hydroxylation and oxidation rates. The greater oxidation of phenylalanine in infants receiving high phenylalanine in conjunction with the urinary excretion of alternate catabolites of phenylalanine and tyrosine suggests that the high phenylalanine intake may be in excess of needs. However, the lower apparent phenylalanine retention observed in infants receiving moderate phenylalanine suggests that the total aromatic amino acid level of moderate phenylalanine may be deficient for neonatal needs.