Two-dimensional amine and hydroxy functionalized fused aromatic covalent organic framework

Ordered two-dimensional covalent organic frameworks (COFs) have generally been synthesized using reversible reactions. It has been difficult to synthesize a similar degree of ordered COFs using irreversible reactions. Developing COFs with a fused aromatic ring system via an irreversible reaction is highly desirable but has remained a significant challenge. Here we demonstrate a COF that can be synthesized from organic building blocks via irreversible condensation (aromatization). The as-synthesized robust fused aromatic COF (F-COF) exhibits high crystallinity. Its lattice structure is characterized by scanning tunneling microscopy and X-ray diffraction pattern. Because of its fused aromatic ring system, the F-COF structure possesses high physiochemical stability, due to the absence of hydrolysable weak covalent bonds

Obesity and diabetes are major risk factors for epicardial adipose tissue inflammation

BACKGROUND: Epicardial adipose tissue (EAT) directly overlies the myocardium, with changes in its morphology and volume associated with myriad cardiovascular and metabolic diseases. However, EAT’s immune structure and cellular characterization remain incompletely described. We aimed to define the immune phenotype of EAT in humans and compare such profiles across lean, obese, and diabetic patients. METHODS: We recruited 152 patients undergoing open-chest coronary artery bypass grafting (CABG), valve repair/replacement (VR) surgery, or combined CABG/VR. Patients’ clinical and biochemical data and EAT, subcutaneous adipose tissue (SAT), and preoperative blood samples were collected. Immune cell profiling was evaluated by flow cytometry and complemented by gene expression studies of immune mediators. Bulk RNA-Seq was performed in EAT across metabolic profiles to assess whole-transcriptome changes observed in lean, obese, and diabetic groups. RESULTS: Flow cytometry analysis demonstrated EAT was highly enriched in adaptive immune (T and B) cells. Although overweight/obese and diabetic patients had similar EAT cellular profiles to lean control patients, the EAT exhibited significantly (P ≤ 0.01) raised expression of immune mediators, including IL-1, IL-6, TNF-α, and IFN-γ. These changes were not observed in SAT or blood. Neither underlying coronary artery disease nor the presence of hypertension significantly altered the immune profiles observed. Bulk RNA-Seq demonstrated significant alterations in metabolic and inflammatory pathways in the EAT of overweight/obese patients compared with lean controls. CONCLUSION: Adaptive immune cells are the predominant immune cell constituent in human EAT and SAT. The presence of underlying cardiometabolic conditions, specifically obesity and diabetes, rather than cardiac disease phenotype appears to alter the inflammatory profile of EAT. Obese states markedly alter EAT metabolic and inflammatory signaling genes, underlining the impact of obesity on the EAT transcriptome profile. FUNDING: Barts Charity MGU0413, Abbott, Medical Research Council MR/T008059/1, and British Heart Foundation FS/13/49/30421 and PG/16/79/32419

How Mistimed and Unwanted Pregnancies Affect Timing of Antenatal Care Initiation in three Districts in Tanzania

Early antenatal care (ANC) initiation is a doorway to early detection and management of potential complications associated with pregnancy. Although the literature reports various factors associated with ANC initiation such as parity and age, pregnancy intentions is yet to be recognized as a possible predictor of timing of ANC initiation. Data originate from a cross-sectional household survey on health behaviour and service utilization patterns. The survey was conducted in 2011 in Rufiji, Kilombero and Ulanga districts in Tanzania on 910 women of reproductive age who had given birth in the past two years. ANC initiation was considered to be early only if it occurred in the first trimester of pregnancy gestation. A recently completed pregnancy was defined as mistimed if a woman wanted it later, and if she did not want it at all the pregnancy was termed as unwanted. Chisquare was used to test for associations and multinomial logistic regression was conducted to examine how mistimed and unwanted pregnancies affect timing of ANC initiation. Although 49.3% of the women intended to become pregnant, 50.7% (34.9% mistimed and 15.8% unwanted) became pregnant unintentionally. While ANC initiation in the 1st trimester was 18.5%, so was 71.7% and 9.9% in the 2nd and 3rd trimesters respectively. Multivariate analysis revealed that ANC initiation in the 2nd trimester was 1.68 (95% CI 1.10‒2.58) and 2.00 (95% CI 1.05‒3.82) times more likely for mistimed and unwanted pregnancies respectively compared to intended pregnancies. These estimates rose to 2.81 (95% CI 1.41‒5.59) and 4.10 (95% CI 1.68‒10.00) respectively in the 3rd trimester. We controlled for gravidity, age, education, household wealth, marital status, religion, district of residence and travel time to a health facility. Late ANC initiation is a significant maternal and child health consequence of mistimed and unwanted pregnancies in Tanzania. Women should be empowered to delay or avoid pregnancies whenever they need to do so. Appropriate counseling to women, especially those who happen to conceive unintentionally is needed to minimize the possibility of delaying ANC initiation.\u

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Gene expression patterns in the hippocampus and amygdala of endogenous depression and chronic stress models

The etiology of depression is still poorly understood, but two major causative hypotheses have been put forth: the monoamine deficiency and the stress hypotheses of depression. We evaluate these hypotheses using animal models of endogenous depression and chronic stress. The endogenously depressed rat and its control strain were developed by bidirectional selective breeding from the Wistar–Kyoto (WKY) rat, an accepted model of major depressive disorder (MDD). The WKY More Immobile (WMI) substrain shows high immobility/despair-like behavior in the forced swim test (FST), while the control substrain, WKY Less Immobile (WLI), shows no depressive behavior in the FST. Chronic stress responses were investigated by using Brown Norway, Fischer 344, Lewis and WKY, genetically and behaviorally distinct strains of rats. Animals were either not stressed (NS) or exposed to chronic restraint stress (CRS). Genome-wide microarray analyses identified differentially expressed genes in hippocampi and amygdalae of the endogenous depression and the chronic stress models. No significant difference was observed in the expression of monoaminergic transmission-related genes in either model. Furthermore, very few genes showed overlapping changes in the WMI vs WLI and CRS vs NS comparisons, strongly suggesting divergence between endogenous depressive behavior- and chronic stress-related molecular mechanisms. Taken together, these results posit that although chronic stress may induce depressive behavior, its molecular underpinnings differ from those of endogenous depression in animals and possibly in humans, suggesting the need for different treatments. The identification of novel endogenous depression-related and chronic stress response genes suggests that unexplored molecular mechanisms could be targeted for the development of novel therapeutic agents

Correlates of Out-of-Pocket and Catastrophic Health Expenditures in Tanzania: Results from a National Household Survey.

Inequality in health services access and utilization are influenced by out-of-pocket health expenditures in many low and middle-income countries (LMICs). Various antecedents such as social factors, poor health and economic factors are proposed to direct the choice of health care service use and incurring out-of-pocket payments. We investigated the association of these factors with out-of-pocket health expenditures among the adult and older population in the United Republic of Tanzania. We also investigated the prevalence and associated determinants contributing to household catastrophic health expenditures. We accessed the data of a multistage stratified random sample of 7279 adult participants, aged between 18 and 59 years, as well as 1018 participants aged above 60 years, from the first round of the Tanzania National Panel survey. We employed multiple generalized linear and logistic regression models to evaluate the correlates of out-of-pocket as well as catastrophic health expenditures, accounting for the complex sample design effects. Increasing age, female gender, obesity and functional disability increased the adults' out-of-pocket health expenditures significantly, while functional disability and visits to traditional healers increased the out-of-pocket health expenditures in older participants. Adult participants, who lacked formal education or worked as manual laborers earned significantly less (p < 0.001) and spent less on health (p < 0.001), despite having higher levels of disability. Large household size, household head's occupation as a manual laborer, household member with chronic illness, domestic violence against women and traditional healer's visits were significantly associated with high catastrophic health expenditures. We observed that the prevalence of inequalities in socioeconomic factors played a significant role in determining the nature of both out-of-pocket and catastrophic health expenditures. We propose that investment in social welfare programs and strengthening the social security mechanisms could reduce the financial burden in United Republic of Tanzania

Own Song Selectivity in the Songbird Auditory Pathway: Suppression by Norepinephrine

Like human speech, birdsong is a learned behavior that supports species and individual recognition. Norepinephrine is a catecholamine suspected to play a role in song learning. The goal of this study was to investigate the role of norepinephrine in bird's own song selectivity, a property thought to be important for auditory feedback processes required for song learning and maintenance.Using functional magnetic resonance imaging, we show that injection of DSP-4, a specific noradrenergic toxin, unmasks own song selectivity in the dorsal part of NCM, a secondary auditory region.The level of norepinephrine throughout the telencephalon is known to be high in alert birds and low in sleeping birds. Our results suggest that norepinephrine activity can be further decreased, giving rise to a strong own song selective signal in dorsal NCM. This latent own song selective signal, which is only revealed under conditions of very low noradrenergic activity, might play a role in the auditory feedback and/or the integration of this feedback with the motor circuitry for vocal learning and maintenance

Relationship between birth weight and retinal microvasculature in newborn infants

Objective: The purposes of this study were to determine the normal retinal microvasculature measurements in human infants who are born at term and to determine whether birth weight influences measurements of retinal microvasculature. Study Design: Retinal arteriole and venule measurements were obtained in a cohort of 24 infants who were born at term. Digital images of both the retinas were obtained using a digital retinal camera after pupillary dilation. Result: In all, 24 newborn infants born at term (12 females and 12 males) were analyzed in this study. The measured retinal arteriole diameters were from 66.8 to 147.8 μm (mean, 94.2±19.6 μm), and the venule diameters were from 102.0 to 167.8 μm (mean, 135.2±19.1 μm). Seven babies in the sample had low birth weight (LBW), while 17 babies were born with normal weight. Babies with lower birth weights had larger arteriole (113.1±17.9 μm vs 86.4±14.4 μm; P=0.0009) and venule diameters (151.7±14.9 μm vs 128.4±16.9 μm; P=0.0040). Conclusion: Retinal venules and arterioles in LBW babies are larger compared with those of normal-birth-weight babies. We postulate that the difference observed in our study was due to in utero pathophysiological changes that occurred in the cerebral circulation of growth-restricted fetuses