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In this article, we describe how the "weathering hypothesis" and Adverse Childhood Experiences set the stage for higher rates of chronic disease, mental health disorders and maternal mortality seen in African American adults. We illustrate the toll that untreated and overtreated mental health disorders have on Black individuals, who have similar rates of mental health disorders as their white counterparts but have fewer outpatient mental health services and higher rates of hospitalizations. We discuss the history of Medicaid, which, while passed alongside Medicare during the Civil Rights era, was Congress's concession to Southern states unwilling to concede federal oversight and funds to the provision of equal healthcare for poor and Black people. Medicaid, which covers 33% of all Blacks in the US and suffers from chronic underfunding and state efforts to weaken it through demonstration waivers, is a second-class system of healthcare with eligibility criteria that vary by state and year. We propose the adoption of a national, single payer Medicare for All system to cover everyone equally, from conception to death. While this will not erase all structural racism, it will go a long way towards leveling the playing field and achieving greater equity in the US.

Although central Africa is classified as having a high endemicity of hepatitis B virus (HBV) and hepatitis D virus (HDV) infection, there is paucity of prevalence studies. For the first time on a country-wide level in Central Africa, we show in Gabon an overall 7.4% prevalence of Hepatitis B surface antigen (HBsAg) and that more than 25% of the HBsAg-positive population are infected by HDV. Although HBV prevalence did not differ significantly between provinces, there is a north-south split in the distribution of HDV seroprevalence, with the highest rates (>66.0%) correlating with the presence of specific ethnic groups in the northeastern provinces. Genotyping revealed high genetic diversity of the HBV and HDV strains circulating in Gabon, including many restricted to this region of the globe. This work confirmed that high exposure to HBV and HDV infection reported in selected regions of Gabon holds true across the whole country., (© 2018 John Wiley & Sons Ltd.)

Obesity, cardiovascular diseases, and diabetes are becoming leading causes of morbidity and mortality in the Eastern Caribbean countries of St. Vincent and the Grenadines, Saint Lucia, Grenada, and Dominica. To promote healthful diets and lifestyles and encourage behavioral changes, Food-Based Dietary Guidelines (FBDG) were developed for the general population in each of these countries. This paper reports on the comprehensive process of developing the guidelines through consensus building among stakeholders, technical assessments and priority setting, and use of qualitative methods to field test messages to ensure public understanding and motivation. Nutritionists in each country received training and support from the Food and Agriculture Organization and the Pan American Health Organization's nutritionists.

1 In primary unpassaged rat brain capillary endothelial cell cultures (RBECs), using reverse-transcriptase PCR with primers specific for P2Y receptor subtypes, we detected mRNA for P2Y2, P2Y4 and P2Y6, but not P2Y1 receptors. 2 None of the various nucleotides tested reduced forskolin elevated cyclic AMP levels in RBECs. ATP and ATPgammaS, as well as adenosine, enhanced cyclic AMP accumulation in the presence of forskolin. 3 Comparison of the concentration response curves to ATPgammaS with those for ATP and adenosine, at different incubation times, indicated that the response to purine nucleotides was not wholly dependent on conversion to adenosine. Adenosine deaminase abolished the response to adenosine but only reduced the response to ATP by about 50%. These results suggest the participation of a receptor responsive to nucleotides. 4 Isobutylmethylxanthine and 8-sulphophenyltheophylline prevented the cyclic AMP response, while neither 8-cyclopentyl-1, 3-dipropylxanthine nor SCH58261 were effective antagonists. 2-chloradenosine gave a robust response, but neither 2-chloro-N6-cyclopentyladenosine nor CGS 21680 were agonists. 5 These results show that adenosine and ATP can elevate the cyclic AMP levels of brain endothelial cells by acting on receptors which have a pharmacology apparently distinct from known P2Y and adenosine receptors.

1. The blood-brain barrier is formed by capillary endothelial cells and is regulated by cell-surface receptors, such as the G protein-coupled P2Y receptors for nucleotides. Here we investigated some of the characteristics of control of brain endothelial cells by these receptors, characterizing the phospholipase C and Ca2+ response and investigating the possible involvement of mitogen-activated protein kinases (MAPK). 2. Using an unpassaged primary culture of rat brain capillary endothelial cells we showed that ATP, UTP and 2-methylthio ATP (2MeSATP) give similar and substantial increases in cytosolic Ca2+, with a rapid rise to peak followed by a slower decline towards basal or to a sustained plateau. Removal of extracellular Ca2+ had little effect on the peak Ca2+-response, but resulted in a more rapid decline to basal. There was no response to alpha,beta-MethylATP (alpha,beta MeATP) in these unpassaged cells, but a response to this P2X agonist was seen after a single passage. 3. ATP (log EC50 -5.1+/-0.2) also caused an increase in the total [3H]-inositol (poly)phosphates ([3H]-InsPx) in the presence of lithium with a rank order of agonist potency of ATP=UTP=UDP>ADP, with 2MeSATP and alpha,beta MeATP giving no detectable response. 4. Stimulating the cells with ATP or UTP gave a rapid rise in the level of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), with a peak at 10 s followed by a decline to a sustained plateau phase. 2MeSATP gave no detectable increase in the level of Ins(1,4,5)P3. 5. None of the nucleotides tested affected basal cyclic AMP, while ATP and ATPgammaS, but not 2MeSATP, stimulated cyclic AMP levels in the presence of 5 microM forskolin. 6. Both UTP and ATP stimulated tyrosine phosphorylation of p42 and p44 mitogen-activated protein kinase (MAPK), while 2MeSATP gave a smaller increase in this index of MAPK activation. By use of a peptide kinase assay, UTP gave a substantial increase in MAPK activity with a concentration-dependency consistent with activation at P2Y2 receptors. 2MeSATP gave a much smaller response with a lower potency than UTP. 7. These results are consistent with brain endothelial regulation by P2Y2 receptors coupled to phospholipase C, Ca2+ and MAPK; and by P2Y1-like (2MeSATP-sensitive) receptors which are linked to Ca2+ mobilization by a mechanism apparently independent of agonist stimulated Ins(1,4,5)P3 levels. A further response to ATP, acting at an undefined receptor, caused an increase in cyclic AMP levels in the presence of forskolin. The differential MAPK coupling of these receptors suggests that they exert fundamentally distinct influences over brain endothelial function.

1. K+ conductances were characterized in isolated, identified superior colliculus-projecting (SCP) rat visual cortical neurons. SCP neurons were identified in vitro under epifluorescence illumination after in vivo retrograde labeling with rhodamine-labeled microspheres or "beads." For experiments, SCP neurons were isolated from the primary visual cortex of postnatal day 7 to 16 (P7-P16) Long Evans rat pups after bead injections into the ipsilateral superior colliculus at p5. 2. Recording conditions were optimized to allow the characterization of Ca2+ -independent K+ conductances. SCP cells that were largely devoid of processes were selected for recording, and experiments were completed 2-30 h after cell isolation. Ca2+ -independent, depolarization-activated K+ currents were routinely recorded during 200-ms voltage steps to potentials positive to -50 mV from a holding potential of -70 mV. 3. Peak outward current densities and the relative amplitudes of the peak and plateau outward currents evoked during 200-ms voltage steps varied among SCP cells. Although cells were isolated from animals at different ages (P7-P16) and maintained for varying times in vitro (2-30 h), no correlations were found between the variations in peak current densities or peak to plateau current ratios and the age of the animal from which the cell was isolated or the length of time the cell was maintained in vitro before recording. 4. Pharmacological experiments revealed the coexpression of three K+ current components in SCP cells that could be separated on the basis of differing sensitivities to the K+ channel blockers, 4-aminopyridine (4-AP) and tetraethylammonium (TEA). Varying the concentration of 4-AP, for example, facilitated the separation of two rapidly activating K+ currents similar to A (IA) and D(ID) type currents in other cells. ID in SCP neurons is blocked by micromolar concentrations of 4-AP, whereas micromolar concentrations of 4-AP are required to effect complete block of IA in these cells. The current component remaining in the presence of high concentrations (5-10 mM) of 4-AP is slowly activating outward K+ current, similar to delayed rectifier (IK) currents in other cells. IK in SCP neurons is blocked by micromolar concentrations of TEA. 5. Activation of IA, ID, and IK in SCP neurons is voltage dependent, although the three current components display distinct time- and voltage-dependent properties. For example, although both IA and ID begin to activate at approximately -50 mV, IA activates two to three times faster than ID. In addition, the threshold for activation of IK (-30 mV) is approximately 20 mV depolarized from that of IA (or ID), and the voltage dependence of IK activation is steeper than that of IA and ID.(ABSTRACT TRUNCATED AT 400 WORDS)

1. Using whole-cell and single channel recordings, we have examined the properties of acetylcholine (ACh)-activated currents in neurones from larval and pupal Drosophila melanogaster (fruit fly), larval and embryonic Musca domestica (house fly), and nymphal Schistocerca gregaria (locust). 2. In all preparations, single channel recordings revealed two major classes of ACh-activated channels, with average conductances of approximately 32 and 59 pS. 3. At ACh concentrations from 1 to 10 microM, channel activity in Drosophila larval neurones occurs in bursts with an average of 1-2 openings. Open times and burst durations are described by one or two exponentials. Burst durations for the 32 pS channel (approximately 3 ms, slow component) were longer than those for the 59 pS channel (approximately 1.0 ms). The mean open interval duration for the 32 pS channel (slow component) was also longer than that of the 59 pS channel. 4. At high ACh (20-200 microM) concentrations, bursts of the smaller conductance channel occur in clusters separated by long-lived periods without channel activity. Considerable kinetic heterogeneity was observed among clusters. 5. The whole-cell dose-response curve suggests that activation of current by ACh increases up to at least 100 microM and that multiple ligand binding steps are involved. 6. Drosophila and Musca larval neuronal ACh-activated channels show some unique features in their cholinergic pharmacological properties: (a) they are only weakly activated by the potent neuromuscular nicotinic agonist suberyldicholine, (b) hexamethonium and decamethonium are weak, but approximately equi-effective blockers, and (c) alpha- and kappa-bungarotoxin (BTX) both blocked reversibly, though alpha-BTX appears to be the more potent inhibitor.

Seventy-two women with known gestational ages underwent serial human chorionic gonadotropin (hCG) measurements and transvaginal ultrasound studies with embryonic heart rate measurements. In 53 continuing singleton pregnancies, embryonic pulse appeared between days 26 and 32, was 80 beat per minute (bpm) on day 26, and increased linearly to plateau at 160-200 bpm by day 45 (r2 = 0.72). The pulse was always seen with hCG greater than 21,000 mIU/mL; pulse rate was correlated to embryonic crown-rump length. Of the remaining 19 pregnancies, 8 were anembryonic, 10 showed heart activity but subsequently aborted, and 1 was terminated. Absence of embryonic pulse by 32 days after conception or a serum hCG greater than 21,000 mIU/mL predicts spontaneous abortion; presence of a pulse may not guarantee successful continuation of the pregnancy since incidence of spontaneous abortion after visualization of embryonic pulse may be as high as 16%.

A human endometrial tumor (Ishikawa) cell line in culture responded to estradiol stimulation, as measured by growth and alkaline phosphatase activity. These effects were similar whether the medium was enriched with serum or was serum-free. Estradiol increased placental alkaline phosphatase activity 2-3-fold over control in these Ishikawa cells. The mechanism for this increase appeared to be at the level of transcription, at least in part, since there was an increase in the concentration of placental alkaline phosphatase mRNA. The administration of tamoxifen or 4-hydroxytamoxifen was unable to antagonize the estradiol-stimulated alkaline phosphatase enzyme activity or mRNA expression. The administration of tamoxifen alone had no effect on alkaline phosphatase enzyme activity, but tamoxifen did stimulate the steady state concentration of alkaline phosphatase mRNA. In contrast, a new antiestrogen, ICI 164,384, was able to antagonize both of these estradiol-stimulated effects.

Pituitary luteinizing hormone (LH) pulse frequency and amplitude were assessed as an indirect indicator of hypothalamic luteinizing hormone-releasing hormone (LH-RH) release in women with evidence of ovarian failure. Exogenous LH-RH (20 micrograms) was administered intravenously every 2 hours for 48 hours to determine the effect on pituitary LH release and the hypothalamic pulse generator for LH-RH secretion. This study design was used to investigate the possibility of an ultrashort negative feedback of LH-RH upon the synthesis and release of endogenous LH-RH. A wide range of LH pulse frequencies (8 to 28 pulses/24 hours) was present in these women. There was no discernible inhibition of hypothalamic LH-RH pulse frequency during or following exogenous LH-RH administration. Mean peripheral LH levels were significantly increased during exogenous LH-RH administration (P = 0.0038), reflecting both an increased baseline and an augmented pituitary LH response to the exogenous LH-RH. There were no differences found in LH pulse amplitude before and after LH-RH treatment. These data indicate that pituitary LH secretion in women with ovarian failure can be further stimulated by exogenous LH-RH. However, there was no evidence for inhibition of either pituitary LH secretion or hypothalamic LH-RH release using this administration schedule of exogenous LH-RH.

Specimens of the stone crab, Menippe mercenaria, survived severe hypoxia (PO2 less than 8mm Hg) for at least 12 hr at 28-30 degrees C. During the time course of 12 hr of hypoxia, hemolymph L-lactate levels rose to 30-50 mumoles/g wet wt. There was a slight elevation of L-alanine levels, whereas succinate was found in only trace quantities in the hemolymph. Pronounced metabolic changes took place in the heart, cheliped closer, and leg socket muscles during severe hypoxia. L-lactate accumulated to levels ranging from 16-20 mumoles/g wet wt. There were pronounced changes in high-energy phosphate levels in the cheliped closer and leg socket muscles. Taking into account expected intra- and extracellular water content, the calculated intracellular lactate content in the three muscles investigated is substantially less than the hemolymph lactate concentrations. Part of this reverse concentration gradient may be accounted for by the reduction in lactate activity due to cation-lactate complex formation. Hemolymph calcium and magnesium concentrations rose considerably during severe hypoxia. During recovery from severe hypoxia, approximately 50% of the accumulated lactate in the hemolymph was cleared in 6 hr. Hemolymph lactate and alanine levels returned to near control levels after 24 hr of recovery. This study shows that the stone crab, M. mercenaria, survives severe hypoxia by a reliance on glycogen fermentation to lactate. This species is capable of tolerating high levels of accumulated lactate.

Authors studied the importance of occult bacteremia among children, under 24 months of age, presenting fever without localizing signs. 113 patients were studied, six had positive blood cultures (5.4%). Agents identified were: N. meningitidis twice, E. coli, Staphylococcus aureus, Streptococcus viridians and group B Streptococcus. Some clinical and laboratory data (body temperature, WBC count, neutrophil count and band count), were studied as predictors of bacteremia. None of these were statistically related to presence of bacteremia.