Cellular resolution anatomical and molecular atlases for prenatal human brains.

Increasing interest in studies of prenatal human brain development, particularly using new single-cell genomics and anatomical technologies to create cell atlases, creates a strong need for accurate and detailed anatomical reference atlases. In this study, we present two cellular-resolution digital anatomical atlases for prenatal human brain at postconceptional weeks (PCW) 15 and 21. Both atlases were annotated on sequential Nissl-stained sections covering brain-wide structures on the basis of combined analysis of cytoarchitecture, acetylcholinesterase staining, and an extensive marker gene expression dataset. This high information content dataset allowed reliable and accurate demarcation of developing cortical and subcortical structures and their subdivisions. Furthermore, using the anatomical atlases as a guide, spatial expression of 37 and 5 genes from the brains, respectively, at PCW 15 and 21 was annotated, illustrating reliable marker genes for many developing brain structures. Finally, the present study uncovered several novel developmental features, such as the lack of an outer subventricular zone in the hippocampal formation and entorhinal cortex, and the apparent extension of both cortical (excitatory) and subcortical (inhibitory) progenitors into the prenatal olfactory bulb. These comprehensive atlases provide useful tools for visualization, segmentation, targeting, imaging, and interpretation of brain structures of prenatal human brain, and for guiding and interpreting the next generation of cell census and connectome studies.

Adjuvant-induced arthritis affects testes and ventral prostate of Wistar rats.

BACKGROUND: Rheumatoid arthritis (RA) may reduce the testosterone production, thereby leading to testicular dysfunction and subfertility. OBJECTIVES: This study aimed to evaluate whether adjuvant-induced arthritis (AIA) induces histopathological and morphometric-stereological alterations on testes with repercussions on the prostate, and alternatively, verifying AIA-induced direct effects on the prostate, regardless of the testicular involvement. MATERIAL AND METHODS: Adult male Wistar rats were sham-orchiectomized or orchiectomized. Twenty days after the surgery, these animals were injected with vehicle (SHAM and ORQ groups, respectively) or adjuvant (Mycobacterium tuberculosis) to induce arthritis (AIA and ORQ/AIA groups, respectively). Forty days later, testes and ventral prostate were processed for histopathological and morphometric-stereological analyses, as well as to PCNA immunohistochemistry. Collagen deposit was evaluated in prostate. Circulating testosterone levels were determined 15 days post-AIA induction in SHAM and AIA rats and 40th day in all groups. RESULTS: In the testes, AIA promoted histopathological changes characterized by an increase in the percentage of abnormal tubules and reduction in the height of the seminiferous epithelium, daily production of spermatozoa, and cellular proliferation. In the prostate, AIA decreased the luminal volume of the secretory ducts. In condition of androgenic deprivation due to the orchiectomy, AIA induced proliferation of the prostatic epithelium. DISCUSSION: The effects of arthritis on testes and prostate were observed 40 days post-AIA induction, possibly results of the hypoandrogenism were already established on 15th day post-induction, which is related to the decline of the steroidogenesis in the Leydig cells. On the other hand, the joint inflammatory process may also have direct repercussions upon the prostate, regardless of this hypoandrogenism. CONCLUSION: AIA effects on reproductive tissues may be related to both hypoandrogenism and other direct inflammatory mechanisms. Possibly, these AIA effects on the testes and prostate occur at a stage in which the inflammatory process is most active, about 15-20 days after induction, remaining evident until the 40th day.

Comprehensive cellular-resolution atlas of the adult human brain.

Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Transcriptional landscape of the prenatal human brain.

The anatomical and functional architecture of the human brain is mainly determined by prenatal transcriptional processes. We describe an anatomically comprehensive atlas of the mid-gestational human brain, including de novo reference atlases, in situ hybridization, ultra-high-resolution magnetic resonance imaging (MRI) and microarray analysis on highly discrete laser-microdissected brain regions. In developing cerebral cortex, transcriptional differences are found between different proliferative and post-mitotic layers, wherein laminar signatures reflect cellular composition and developmental processes. Cytoarchitectural differences between human and mouse have molecular correlates, including species differences in gene expression in subplate, although surprisingly we find minimal differences between the inner and outer subventricular zones even though the outer zone is expanded in humans. Both germinal and post-mitotic cortical layers exhibit fronto-temporal gradients, with particular enrichment in the frontal lobe. Finally, many neurodevelopmental disorder and human-evolution-related genes show patterned expression, potentially underlying unique features of human cortical formation. These data provide a rich, freely-accessible resource for understanding human brain development.

Citrullination of autoantigens: upstream of TNFα in the pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by synovial inflammation and destruction of joints. Over 20 years ago, tumour necrosis factor alpha (TNFα) was identified as a key player in a cytokine network, whose multifunctional effects could account for both the inflammation and destruction in RA. The remarkable efficacy of TNF inhibitors in the treatment of RA has resulted in extensive research addressing the regulation of TNFα production responsible for this excessive production. The discovery of autoimmunity to citrullinated protein/peptide antigens (ACPA) has led the concept that ACPA may be the essential link between disease susceptibility factors and the production of TNFα, which ultimately accounts for the disease phenotype. In this review we will consider (1) the mechanisms of citrullination, both physiological and pathological, (2) how known genetic and environmental factors could drive this peculiar form of autoimmunity and (3) how the immune response could lead to excessive production of TNFα by the synovial cells and ultimately to the disease phenotype (Fig. 1).

Healthy food choices and physical activity opportunities in two contrasting Alabama cities.

Food and physical activity access and availability in two contrasting cities in Alabama were investigated. An in-outlet, observational, cross-sectional design was utilized to assess the opportunities for healthy food choices and physical activity. Thirty retail food outlets and 29 physical activity outlets were inventoried. None of the convenience stores carried frozen, low-sodium or dark-green, yellow vegetables, low-fat milk or yogurt, low-sodium and low-fat cheese, while none of the supermarkets in Tuskegee stocked low-sodium vegetables. In Tuskegee, the single public recreational area, which offered activities such as basketball, fees ranged from $25 to $35/month. Tuskegee has a shortage of "chain" supermarkets and a dominance of convenience stores which stocked few healthy foods. Overall, there are limited opportunities for healthy food and physical activity choices, which could be a barrier for chronic disease prevention efforts.

Nutritional, physical, and sensory evaluation of hydroponic carrots (Daucus carota L.) from different nutrient delivery systems.

Carrot (Daucus carota L.) has the highest carotenoid content among foods and is consumed in large quantities worldwide, while at the same time its market demand continues to increase. Carotenoids have also been associated with protective effects against cancer and other chronic diseases. The most predominant carotenoids in carrots are beta- and alpha-carotenes. Moisture, ash, fat, texture, color, carotene content, and consumer acceptance of carrots grown in a hydroponic system with nutrient film technique (NFT) and microporous tube membrane system (MTMS) were evaluated. The moisture contents of the NFT- and MTMS-grown carrots ranged from 86.8 +/- 0.13% to 92.2 +/- 2.25% and 80.9 +/- 0.31% to 91.6 +/- 1.01%, respectively. Fat and ash contents of the carrots were negligible. NFT-grown Oxheart had the most beta-carotene (9900 +/- 20 microg/100 g) while Juwaroot had the least (248 +/- 10 microg/100 g). However, the beta-carotene content of Juwaroot from the NFT batch II carrots was 3842 +/- 6 microg/100 g. MTMS-grown carrots had less variation in the total beta-carotene contents (2434 +/- 89 to 10488 +/- 8 microg/100 g) than those from NFT. Overall, Nantes Touchan (4.8 +/- 2.3) and Nevis-F (7 +/- 1.4) from NFT were the least and most preferred by consumers. Mignon was also acceptable to consumers, and significantly (P < 0.05) more preferred than the other carrots in that NFT batch. MTMS-grown Kinko and Paramex, which were significantly (P < 0.05) more preferred than Nandrin-F and the commercial field-grown carrot, were equally liked by consumers. Nevis-F, Mignon (NFT), Paramex, and Kinko (MTMS) are potentially good cultivars to be included in NASA's food system.

Predictive haptic guidance: intelligent user assistance for the control of dynamic tasks.

Intelligent systems are increasingly able to offer real-time information relevant to a user's manual control of an interactive system, such as dynamic system control space constraints for animation control and driving. However, it is difficult to present this information in a usable manner and other approaches which have employed haptic cues for manual control in "slow" systems often lead to instabilities in highly dynamic tasks. We present a predictive haptic guidance method based on a look-ahead algorithm, along with a user evaluation which compares it with other approaches (no guidance and a standard potential-field method) in a 1-DoF steered path-following scenario. Look-ahead guidance outperformed the other methods in both quantitative performance and subjective preference across a range of path complexity and visibility and a force analysis demonstrated that it applied smaller and fewer forces to users. These results (which appear to derive from the predictive guidance's supporting users in taking earlier and more subtle corrective action) suggest the potential of predictive methods in aiding manual control of dynamic interactive tasks where intelligent support is available.

Umbilical cord blood and neonatal endothelin-1 levels in preterm newborns with and without respiratory distress syndrome.

Increased pulmonary vascular resistance in preterm newborn infants with respiratory distress syndrome is suggested, and endothelin-1 plays an important role in pulmonary vascular reactivity in newborns. We determined umbilical cord blood and neonatal (second sample) levels of endothelin-1 in 18 preterm newborns with respiratory distress syndrome who had no clinical or echocardiographic diagnosis of pulmonary hypertension and 22 without respiratory distress syndrome (gestational ages: 31.4 +/- 1.6 and 29.3 +/- 2.3 weeks, respectively). Umbilical cord blood and a second blood sample taken 18 to 40 h after birth were used for endothelin-1 determination by enzyme immunoassay. Median umbilical cord blood endothelin-1 levels were similar in both groups (control: 10.9 and respiratory distress syndrome: 11.4 pg/mL) and were significantly higher than in the second sample (control: 1.7 pg/mL and respiratory distress syndrome: 3.5 pg/mL, P < 0.001 for both groups). Median endothelin-1 levels in the second sample were significantly higher in children with respiratory distress syndrome than in control infants (P < 0.001). There were significant positive correlations between second sample endothelin-1 and Score for Neonatal Acute Physiology and Perinatal Extension II (r = 0.36, P = 0.02), and duration of mechanical ventilation (r = 0.64, P = 0.02). A slower decline of endothelin-1 from birth to 40 h of life was observed in newborns with respiratory distress syndrome when compared to controls. A significant correlation between neonatal endothelin-1 levels and some illness-severity signs suggests that endothelin-1 plays a role in the natural course of respiratory distress syndrome in preterm newborns.

Umbilical cord blood and neonatal endothelin-1 levels in preterm newborns with and without respiratory distress syndrome

Increased pulmonary vascular resistance in preterm newborn infants with respiratory distress syndrome is suggested, and endothelin-1 plays an important role in pulmonary vascular reactivity in newborns. We determined umbilical cord blood and neonatal (second sample) levels of endothelin-1 in 18 preterm newborns with respiratory distress syndrome who had no clinical or echocardiographic diagnosis of pulmonary hypertension and 22 without respiratory distress syndrome (gestational ages: 31.4 ± 1.6 and 29.3 ± 2.3 weeks, respectively). Umbilical cord blood and a second blood sample taken 18 to 40 h after birth were used for endothelin-1 determination by enzyme immunoassay. Median umbilical cord blood endothelin-1 levels were similar in both groups (control: 10.9 and respiratory distress syndrome: 11.4 pg/mL) and were significantly higher than in the second sample (control: 1.7 pg/mL and respiratory distress syndrome: 3.5 pg/mL, P < 0.001 for both groups). Median endothelin-1 levels in the second sample were significantly higher in children with respiratory distress syndrome than in control infants (P < 0.001). There were significant positive correlations between second sample endothelin-1 and Score for Neonatal Acute Physiology and Perinatal Extension II (r = 0.36, P = 0.02), and duration of mechanical ventilation (r = 0.64, P = 0.02). A slower decline of endothelin-1 from birth to 40 h of life was observed in newborns with respiratory distress syndrome when compared to controls. A significant correlation between neonatal endothelin-1 levels and some illness-severity signs suggests that endothelin-1 plays a role in the natural course of respiratory distress syndrome in preterm newborns.

Physical properties and sixth graders' acceptance of an extruded ready-to-eat sweetpotato breakfast cereal.

Extruded ready-to-eat breakfast cereals (RTEBCs) were made from varying levels of sweetpotato flour (SPF), whole-wheat bran (WWB), and extrusion cooking. Moisture, protein, and ash contents were lower in the 100% SPF than the 100% WWB. Carbohydrate, beta-carotene, and ascorbic acid contents were higher in the 100% SPF. Fat, thiamin, riboflavin contents, bulk densities, and the water absorption index were similar for the cereals. However, the expansion ratio was highest in the 100% SPF cereal. The 100% WWB had the lightest color and most fibrous morphology. Extruded RTEBC containing 100% SPF and 75%/25% SPF/WWB were well-liked and acceptable to sixth graders attending an elementary school in Auburn, Alabama, but the 100% WWB was unacceptable.

Sensory characterization of a ready-to-eat sweetpotato breakfast cereal by descriptive analysis.

The sweetpotato [Ipomoea batatas (L.) Lam], an important industry in the United States, has been selected as a candidate crop to be grown on future long-duration space missions by NASA. Raw sweetpotato roots were processed into flour, which was used to formulate ready-to-eat breakfast cereal (RTEBC). Twelve trained panelists evaluated the sensory attributes of the extruded RTEBC using descriptive analysis. The samples were significantly different (P<0.05) for all attributes. Twelve perceived sensory attributes, which could be used to differentiate the appearance, texture, and flavor of sweetpotato RTEBC, were described. The data could be used to optimize the RTEBC and for designing studies to test its consumer acceptance.

Breastfeeding knowledge and beliefs among adults in eastern Tobago.

Using a cross-sectional survey, the knowledge and beliefs about breastfeeding were evaluated among adults in Eastern Tobago (N = 509). Of the respondents, 95%, 69%, and 48% indicated that a baby should be exclusively breastfed at birth, 3 months, and 6 months, respectively. The baby's mother was thought to have the greatest influence on breastfeeding decisions. Of the respondents, 63% and 80% were unaware of expressed breast milk and cup-feeding a neonate, whereas 82% believed that a solely breastfed baby should receive water. Additionally, 23% and 44% felt that breastfeeding should be terminated before 6 months and between 6 and 12 months, respectively. Inadequate maternal nutrition and employment were reported as the principal factors affecting breastfeeding. There is a lack of knowledge about the anatomy and physiology of lactation and about the benefits of exclusive breastfeeding. These findings are useful for guiding the development and implementation of interventions to promote breast-feeding in Tobago.

[The effect of recombinant human erythropoietin on the treatment of anemia of prematurity] / O efeito da eritropoetina humana recombinante no tratamento da anemia da prematuridade.

OBJECTIVE: To assess the efficacy of erythropoietin in the prevention and treatment of anemia of prematurity, correlating the use of this drug with weight gain, length, and head circumference and comparing two administration schemes of he same weekly dose: daily use and twice a week. METHODS: The study comprised 42 premature newborns with gestational age up to 33 weeks, birthweight up to 1550 g, and postnatal age between 10 and 35 days. The newborns were randomized into three groups: patients in group 1 received seven daily doses of 100 U/kg erythropoietin per week; patients in group 2 received two 350 U/kg erythropoietin doses per week; and patients in group 3 did not receive the drug. Hematologic measurements, blood transfusion requirements, and growth rates were followed during therapy. RESULTS: Cases and controls did not differ with respect to weight, length, head circumference, and total time of hospital stay. At the end of the study, no significant difference was observed in the platelet count measurement means, white blood cell count, and ferritin levels in the three groups. However, the final hematocrit and hemoglobin values of patients who did not receive erythropoietin were significantly lower than those of patients who received the drug. The absolute reticulocyte count mean was significantly higher in patients who received erythropoietin after two weeks of treatment when compared with those patients who did not receive the drug. Patients in group 1 e 2 received fewer excessive transfusions (2 or more) than patients in group 3. The administration of 700 U/kg/week erythropoietin significantly reduced the number of excessive blood transfusions. There is no significant difference in blood transfusion volume between patients who received erythropoietin on a daily basis and those who received the drug twice weekly. CONCLUSIONS: the use of erythropoietin did not influence weight gain and growth. The administration of 700 U/kg/week erythropoietin in premature infants with gestational age up to 33 weeks and birthweight up to 1550 g stimulates erythropoiesis and significantly reduces excessive blood transfusion requirements. Erythropoietin showed to be a safe and well tolerated medication, with no short-term side effects in the study population.

Iron absorption from ferrous bisglycinate and ferric trisglycinate in whole maize is regulated by iron status.

BACKGROUND: There is a need to determine whether iron absorption from iron amino acid chelates is protected from inhibition by dietary phytate and regulated normally by iron status. OBJECTIVE: The objective of this study was to compare iron absorption from ferrous sulfate, ferrous bisglycinate, and ferric trisglycinate in whole-maize meal; to determine whether iron from ferrous bisglycinate and ferrous sulfate exchanges in the intestinal pool; and to assess iron absorption from ferrous bisglycinate and ferric trisglycinate over a range of iron statuses. DESIGN: In study 1A, 10 iron-sufficient men consumed ferrous sulfate-fortified whole-maize meal porridge equilibrated with (59)Fe-sulfate on day 1 and (55)Fe-bisglycinate on day 2. In study 1B, these volunteers consumed ferrous sulfate-fortified porridge equilibrated with (59)Fe-sulfate and (55)Fe-bisglycinate simultaneously. In studies 2A and 2B, iron absorption from 3 mg Fe as (59)Fe-ascorbate, (55)Fe-bisglycinate, or (59)Fe-trisglycinate in water and in porridge was compared in 23 subjects with a range of iron statuses. Iron absorption was determined from blood radioactivity on day 16. RESULTS: In study 1A, geometric mean iron absorption from ferrous bisglycinate was 6.0% (range: 2.6-13.6%), 4 times higher than that from ferrous sulfate (1. 7%; range: 1.0-3.3%; P < 0.05). In study 1B, absorption from neither source was different from that in study 1A. In studies 2A and 2B, absorption from all sources was strongly inversely related to serum ferritin, with geometric means of 32.5% (iron ascorbate), 9.1% (bisglycinate), and 15.3% (trisglycinate). Iron from ferric trisglycinate was poorly absorbed (2.3%; range: 0.5-9.2%) from maize. CONCLUSION: In whole-maize meal, iron from ferrous bisglycinate is better absorbed than is iron from ferrous sulfate and does not exchange with iron from maize or ferrous sulfate in the intestinal pool. Absorption of iron from bisglycinate and trisglycinate is regulated normally by iron status.

Knowledge, beliefs and practices of breastfeeding among adults in Tobago East: preliminary findings - Poster abstract

OBJECTIVES: To evaluate the knowledge, beliefs and practices of breastfeeding among adults in Tobago East. DESIGN AND METHODS: A cross-sectional survey was conducted on adults aged > 18 years residing in Tobago East. All participants were interviewed using structured questionnaires. RESULTS: The study comprised 509 persons of who 312 (61 percent) were females. Ninety-five percent (95 percent), 69 percent and 48 percent of the respondents indicated that a baby should be exclusively breastfed at birth, 3 months and 6 months, respectively. The main source of information about breastfeeding was obtained from the health center (53 percent). The mother (50 percent) and both parents (29 percent) were thought to be responsible for making the decision to breastfeed. Sixty-three percent (63 percent) and 80 percent of the respondents did not know about "expressed breast milk and cup-feeding' of a new-born while 82 percent and 47 percent believed that the breastfed baby should be given water and that breastfeeding caused a woman's breast to sag. In addition, 23 percent and 44 percent felt that breastfeeding should be terminated <6 months of age and between 6 and 12 months, respectively. The respondents believed that inadequate maternal nutrition (35 percent) and maternal employment (26 percent) were the principal factors affecting breastfeeding. CONCLUSION: There is a low level of awareness among the respondents regarding the value of exclusive breastfeeding for the first six months. These findings can be used to guide the development and implementation of interventions to promote exclusive breastfeeding in Tobago.(AU)