Showing papers in "Annals of the New York Academy of Sciences in 2019"

Land–atmospheric feedbacks during droughts and heatwaves: state of the science and current challenges

Abstract: Droughts and heatwaves cause agricultural loss, forest mortality, and drinking water scarcity, especially when they occur simultaneously as combined events. Their predicted increase in recurrence and intensity poses serious threats to future food security. Still today, the knowledge of how droughts and heatwaves start and evolve remains limited, and so does our understanding of how climate change may affect them. Droughts and heatwaves have been suggested to intensify and propagate via land-atmosphere feedbacks. However, a global capacity to observe these processes is still lacking, and climate and forecast models are immature when it comes to representing the influences of land on temperature and rainfall. Key open questions remain in our goal to uncover the real importance of these feedbacks: What is the impact of the extreme meteorological conditions on ecosystem evaporation? How do these anomalies regulate the atmospheric boundary layer state (event self-intensification) and contribute to the inflow of heat and moisture to other regions (event self-propagation)? Can this knowledge on the role of land feedbacks, when available, be exploited to develop geo-engineering mitigation strategies that prevent these events from aggravating during their early stages? The goal of our perspective is not to present a convincing answer to these questions, but to assess the scientific progress to date, while highlighting new and innovative avenues to keep advancing our understanding in the future.

Anemia epidemiology, pathophysiology, and etiology in low- and middle-income countries

Abstract: Anemia affects a third of the world’s population and contributes to increased morbidity and mortality, decreased work productivity, and impaired neurological development. Understanding anemia’s varied and complex etiology is crucial for developing effective interventions that address the context-specific causes of anemia and for monitoring anemia control programs. We outline definitions and classifications of anemia, describe the biological mechanisms through which anemia develops, and review the variety of conditions that contribute to anemia development. We emphasize the risk factors most prevalent in low- and middle-income countries, including nutritional deficiencies, infection/inflammation, and genetic hemoglobin disorders. Recent work has furthered our understanding of anemia’s complex etiology, including the proportion of anemia caused by iron deficiency (ID) and the role of inflammation and infection. Accumulating evidence indicates that the proportion of anemia due to ID differs by population group, geographical setting, infectious disease burden, and the prevalence of other anemia causes. Further research is needed to explore the role of additional nutritional deficiencies, the contribution of infectious and chronic disease, as well as the importance of genetic hemoglobin disorders in certain populations.

Impact of Recent and Future Climate Change on Vector-Borne Diseases

Abstract: Climate change is one of the greatest threats to human health in the 21st century. Climate directly impacts health through climatic extremes, air quality, sea-level rise, and multifaceted influences on food production systems and water resources. Climate also affects infectious diseases, which have played a significant role in human history, impacting the rise and fall of civilizations and facilitating the conquest of new territories. Our review highlights significant regional changes in vector and pathogen distribution reported in temperate, peri-Arctic, Arctic, and tropical highland regions during recent decades, changes that have been anticipated by scientists worldwide. Further future changes are likely if we fail to mitigate and adapt to climate change. Many key factors affect the spread and severity of human diseases, including mobility of people, animals, and goods; control measures in place; availability of effective drugs; quality of public health services; human behavior; and political stability and conflicts. With drug and insecticide resistance on the rise, significant funding and research efforts must to be maintained to continue the battle against existing and emerging diseases, particularly those that are vector borne.

Inflammation in psychiatric disorders: what comes first?

Abstract: Neuropsychiatric disorders (i.e., mood disorders and schizophrenia) and inflammation are closely intertwined, and possibly powering each other in a bidirectional loop. Depression facilitates inflammatory reactions and inflammation promotes depression and other neuropsychiatric disorders. Patients with neuropsychiatric disorders exhibit all cardinal features of inflammation, including increased circulating levels of inflammatory inducers, activated sensors, and inflammatory mediators targeting all tissues. Inflammation may contribute to the pathophysiology and clinical progression of these disorders. Of note, proinflammatory cytokines modulate mood behavior and cognition by reducing brain monoamine levels, activating neuroendocrine responses, promoting excitotoxicity (increased glutamate levels), and impairing brain plasticity. What are the sources of this chronic inflammation? Increasing evidence indicates that changes in neuroendocrine regulation, metabolism, diet/microbiota, and negative health behaviors are important triggers of inflammation. Finally, recent data indicate that early-life stress is associated with overt inflammation prior to the development of neuropsychiatric disorders.

The effect of mindfulness meditation on sleep quality: a systematic review and meta-analysis of randomized controlled trials.

Abstract: There is a growing interest in the effectiveness of mindfulness meditation for sleep disturbed populations. Our study sought to evaluate the effect of mindfulness meditation interventions on sleep quality. To assess for relative efficacy, comparator groups were restricted to specific active controls (such as evidenced-based sleep treatments) and nonspecific active controls (such as time/attention-matched interventions to control for placebo effects), which were analyzed separately. From 3303 total records, 18 trials with 1654 participants were included. We determined the strength of evidence using four domains (risk of bias, directness of outcome measures, consistency of results, and precision of results). At posttreatment and follow-up, there was low strength of evidence that mindfulness meditation interventions had no effect on sleep quality compared with specific active controls (ES 0.03 (95% CI -0.43 to 0.49)) and (ES -0.14 (95% CI -0.62 to 0.34)), respectively. Additionally, there was moderate strength of evidence that mindfulness meditation interventions significantly improved sleep quality compared with nonspecific active controls at postintervention (ES 0.33 (95% CI 0.17-0.48)) and at follow-up (ES 0.54 (95% CI 0.24-0.84)). These preliminary findings suggest that mindfulness meditation may be effective in treating some aspects of sleep disturbance. Further research is warranted.

The challenge of converting Gram-positive-only compounds into broad-spectrum antibiotics.

Abstract: Multidrug resistant Gram-negative bacterial infections are on the rise, and there is a lack of new classes of drugs to treat these pathogens. This drug shortage is largely due to the challenge of finding antibiotics that can permeate and persist inside Gram-negative species. Efforts to understand the molecular properties that enable certain compounds to accumulate in Gram-negative bacteria based on retrospective studies of known antibiotics have not been generally actionable in the development of new antibiotics. A recent assessment of the ability of >180 diverse small molecules to accumulate in Escherichia coli led to predictive guidelines for compound accumulation in E. coli. These "eNTRy rules" state that compounds are most likely to accumulate if they contain a nonsterically encumbered ionizable Nitrogen (primary amines are the best), have low Three-dimensionality (globularity ≤ 0.25), and are relatively Rigid (rotatable bonds ≤ 5). In this review, we look back through 50+ years of antibacterial research and 1000s of derivatives and assess this historical data set through the lens of these predictive guidelines. The results are consistent with the eNTRy rules, suggesting that the eNTRy rules may provide an actionable and general roadmap for the conversion of Gram-positive-only compounds into broad-spectrum antibiotics.

The Arctic's sea ice cover: trends, variability, predictability, and comparisons to the Antarctic.

Abstract: As assessed over the period of satellite observations, October 1978 to present, there are downward linear trends in Arctic sea ice extent for all months, largest at the end of the melt season in September. The ice cover is also thinning. Downward trends in extent and thickness have been accompanied by pronounced interannual and multiyear variability, forced by both the atmosphere and ocean. As the ice thins, its response to atmospheric and oceanic forcing may be changing. In support of a busier Arctic, there is a growing need to predict ice conditions on a variety of time and space scales. A major challenge to providing seasonal scale predictions is the 7-10 days limit of numerical weather prediction. While a seasonally ice-free Arctic Ocean is likely well within this century, there is much uncertainty in the timing. This reflects differences in climate model structure, the unknown evolution of anthropogenic forcing, and natural climate variability. In sharp contrast to the Arctic, Antarctic sea ice extent, while highly variable, has increased slightly over the period of satellite observations. The reasons for this different behavior remain to be resolved, but responses to changing atmospheric circulation patterns appear to play a strong role.

Maternal hemoglobin concentrations across pregnancy and maternal and child health: a systematic review and meta-analysis

Abstract: Maternal anemia is a well-recognized global health problem; however, there remain questions on specific hemoglobin (Hb) thresholds that predict health risk or protection for mother and child. We conducted a systematic review and meta-analysis to examine the associations of maternal Hb concentrations with a range of maternal and infant health outcomes, accounting for the timing of measurement (preconception, and first, second, and third trimesters), etiology of anemia, and cutoff category. The systematic review included 272 studies and the meta-analysis included 95 studies. Low maternal Hb ( 130 g/L) was associated with increased odds of SGA, stillbirth, preeclampsia, and gestational diabetes. Relationships varied by the timing of measurement and cutoff category (stronger associations with lower cutoffs); limited data were available on anemia etiology. There were insufficient data for other maternal outcomes and long-term child health outcomes. Current data are insufficient for determining if revisions to current Hb cutoffs are required. Pooled high-quality individual-level data analyses, as well as prospective cohort studies, would be valuable to inform the reevaluation of Hb cutoffs.

Plasmid evolution in carbapenemase-producing Enterobacteriaceae: a review

Abstract: Carbapenem-resistant Enterobacteriaceae (CRE) have been listed by the WHO as high-priority pathogens owing to their high association with mortalities and morbidities. Resistance to multiple β-lactams complicates effective clinical management of CRE infections. Using plasmid typing methods, a wide distribution of plasmid replicon groups has been reported in CREs around the world, including IncF, N, X, A/C, L/M, R, P, H, I, and W. We performed a literature search for English research papers, published between 2013 and 2018, reporting on plasmid-mediated carbapenem resistance. A rise in both carbapenemase types and associated plasmid replicon groups was seen, with China, Canada, and the United States recording a higher increase than other countries. blaKPC was the most prevalent, except in Angola and the Czech Republic, where OXA-181 (n = 50, 88%) and OXA-48-like (n = 24, 44%) carbapenemases were most prevalent, respectively; blaKPC-2/3 accounted for 70% (n = 956) of all reported carbapenemases. IncF plasmids were found to be responsible for disseminating different antibiotic resistance genes worldwide, accounting for almost 40% (n = 254) of plasmid-borne carbapenemases. blaCTX-M , blaTEM , blaSHV , blaOXA-1/9 , qnr, and aac-(6')-lb were mostly detected concurrently with carbapenemases. Most reported plasmids were conjugative but not present in multiple countries or species, suggesting limited interspecies and interboundary transmission of a common plasmid. A major limitation to effective characterization of plasmid evolution was the use of PCR-based instead of whole-plasmid sequencing-based plasmid typing.

Excess iodine intake: sources, assessment, and effects on thyroid function.

Abstract: Iodine is essential for thyroid hormone synthesis. High iodine intakes are well tolerated by most healthy individuals, but in some people, excess iodine intakes may precipitate hyperthyroidism, hypothyroidism, goiter, and/or thyroid autoimmunity. Individuals with preexisting thyroid disease or those previously exposed to iodine deficiency may be more susceptible to thyroid disorders due to an increase in iodine intake, in some cases at intakes only slightly above physiological needs. Thyroid dysfunction due to excess iodine intake is usually mild and transient, but iodine-induced hyperthyroidism can be life-threatening in some individuals. At the population level, excess iodine intakes may arise from consumption of overiodized salt, drinking water, animal milk rich in iodine, certain seaweeds, iodine-containing dietary supplements, and from a combination of these sources. The median urinary iodine concentration (UIC) of a population reflects the total iodine intake from all sources and can accurately identify populations with excessive iodine intakes. Our review describes the association between excess iodine intake and thyroid function. We outline potential sources of excess iodine intake and the physiological responses and consequences of excess iodine intakes. We provide guidance on choice of biomarkers to assess iodine intake, with an emphasis on the UIC and thyroglobulin.

New pathogens, new tricks: emerging, drug-resistant fungal pathogens and future prospects for antifungal therapeutics.

Abstract: Fungal pathogens are a growing threat to public health. As human immunodeficiency becomes increasingly common, fungal infections are becoming more prevalent. The use of antifungal agents for prophylaxis and treatment of fungal infections has favored the emergence of previously rare or unidentified species of drug-resistant fungal pathogens, including several Candida and Cryptococcus species, as well as mold pathogens. As these new and increasingly drug-resistant fungal pathogens continue to emerge, novel strategies for rapid identification and treatment are necessary to combat these life-threatening infections.

Neural mechanisms of social homeostasis.

Abstract: Social connections are vital to survival throughout the animal kingdom and are dynamic across the life span. There are debilitating consequences of social isolation and loneliness, and social support is increasingly a primary consideration in health care, disease prevention, and recovery. Considering social connection as an "innate need," it is hypothesized that evolutionarily conserved neural systems underlie the maintenance of social connections: alerting the individual to their absence and coordinating effector mechanisms to restore social contact. This is reminiscent of a homeostatic system designed to maintain social connection. Here, we explore the identity of neural systems regulating "social homeostasis." We review findings from rodent studies evaluating the rapid response to social deficit (in the form of acute social isolation) and propose that parallel, overlapping circuits are engaged to adapt to the vulnerabilities of isolation and restore social connection. By considering the neural systems regulating other homeostatic needs, such as energy and fluid balance, we discuss the potential attributes of social homeostatic circuitry. We reason that uncovering the identity of these circuits/mechanisms will facilitate our understanding of how loneliness perpetuates long-term disease states, which we speculate may result from sustained recruitment of social homeostatic circuits.

Phenotypic instability of chondrocytes in osteoarthritis: on a path to hypertrophy

Abstract: Articular chondrocytes are quiescent, fully differentiated cells responsible for the homeostasis of adult articular cartilage by maintaining cellular survival functions and the fine-tuned balance between anabolic and catabolic functions. This balance requires phenotypic stability that is lost in osteoarthritis (OA), a disease that affects and involves all joint tissues and especially impacts articular cartilage structural integrity. In OA, articular chondrocytes respond to the accumulation of injurious biochemical and biomechanical insults by shifting toward a degradative and hypertrophy-like state, involving abnormal matrix production and increased aggrecanase and collagenase activities. Hypertrophy is a necessary, transient developmental stage in growth plate chondrocytes that culminates in bone formation; in OA, however, chondrocyte hypertrophy is catastrophic and it is believed to initiate and perpetuate a cascade of events that ultimately result in permanent cartilage damage. Emphasizing changes in DNA methylation status and alterations in NF-κB signaling in OA, this review summarizes the data from the literature highlighting the loss of phenotypic stability and the hypertrophic differentiation of OA chondrocytes as central contributing factors to OA pathogenesis.

The neurobiology of addiction.

Abstract: Substance and alcohol use disorders impose large health and economic burdens on individuals, families, communities, and society. Neither prevention nor treatment efforts are effective in all individuals. Results are often modest. Advances in neuroscience and addiction research have helped to describe the neurobiological changes that occur when a person transitions from recreational substance use to a substance use disorder or addiction. Understanding both the drivers and consequences of substance use in vulnerable populations, including those whose brains are still maturing, has revealed behavioral and biological characteristics that can increase risks of addiction. These findings are particularly timely, as law- and policymakers are tasked to reverse the ongoing opioid epidemic, as more states legalize marijuana, as new products including electronic cigarettes and newly designed abused substances enter the legal and illegal markets, and as "deaths of despair" from alcohol and drug misuse continue.

The neurobiology of impulsivity and substance use disorders: implications for treatment.

Abstract: Impulsivity is strongly associated with substance use disorders (SUDs). Our review discusses impulsivity as an underlying vulnerability marker for SUDs, and treatment of co-occurring impulsivity in SUDs. Three factors should be considered for the complex relationship between impulsivity and a SUD: (1) the trait effect of impulsivity, centering on decreased cognitive and response inhibition, (2) the state effect resulting from either acute or chronic substance use on brain structure and function, and (3) the genetic and environmental factors (e.g., age and sex) may influence impulsive behavior associated with SUDs. Both subjective and objective measures are used to assess impulsivity. Together, treatment developments (pharmacological, behavioral, and neurophysiological) should consider these clinically relevant dimensions assessed by a variety of measures, which have implications for treatment matching in individuals with SUD. Despite its heterogeneity, impulsivity is a marker associated with SUDs and may be understood as an imbalance of bottom-up and top-down neural systems. Further investigation of these relationships may lead to more effective SUD treatments.

Complexities in understanding antimicrobial resistance across domesticated animal, human, and environmental systems

Abstract: Antimicrobial resistance (AMR) is a significant threat to both human and animal health. The spread of AMR bacteria and genes across systems can occur through a myriad of pathways, both related and unrelated to agriculture, including via wastewater, soils, manure applications, direct exchange between humans and animals, and food exposure. Tracing origins and drivers of AMR bacteria and genes is challenging due to the array of contexts and the complexity of interactions overlapping health practice, microbiology, genetics, applied science and engineering, as well as social and human factors. Critically assessing the diverse and sometimes contradictory AMR literature is a valuable step in identifying tractable mitigation options to stem AMR spread. In this article we review research on the nonfoodborne spread of AMR, with a focus on domesticated animals and the environment and possible exposures to humans. Attention is especially placed on delineating possible sources and causes of AMR bacterial phenotypes, including underpinning the genetics important to human and animal health.

Methods and analyzers for hemoglobin measurement in clinical laboratories and field settings.

Abstract: This paper describes and compares methods and analyzers used to measure hemoglobin (Hb) in clinical laboratories and field settings. We conducted a literature review for methods used to measure Hb in clinical laboratories and field settings. We described methods to measure Hb and factors influencing results. Automated hematology analyzer (AHA) was reference for all Hb comparisons using evaluation criteria of ±7% set by College of American Pathologists (CAP) and Clinical Laboratory Improvement Amendments (CLIA). Capillary fingerprick blood usually produces higher Hb concentrations compared with venous blood. Individual drops produced lower concentrations than pooled capillary blood. Compared with the AHA: (1) overall cyanmethemoglobin (1.0-8.0 g/L), WHO Colour Scale (0.5-10.0 g/L), paper-based devices (5.0-7.0 g/L), HemoCue® Hb-201 (1.0-16.0 g/L) and Hb-301 (0.5-6.0 g/L), and Masimo Pronto® (0.3-14.0 g/L) overestimated concentrations; (2) Masimo Radical®-7 both under- and overestimated concentrations (0.3-104.0 g/L); and (3) other methods underestimated concentrations (2.0-16.0 g/L). Most mean concentration comparisons varied less than ±7% of the reference. Hb measurements are influenced by several analytical factors. With few exceptions, mean concentration bias was within ±7%, suggesting acceptable performance. Appropriate, high-quality methods in all settings are necessary to ensure the accuracy of Hb measurements.This paper describes and compares methods and analyzers used to measure hemoglobin (Hb) in clinical laboratories and field settings. With few exceptions, mean concentration bias was within ±7%, suggesting acceptable performance. Appropriate, high-quality methods in all settings are necessary to ensure the accuracy of Hb measurements.

Effects of hemoglobin levels during pregnancy on adverse maternal and infant outcomes: a systematic review and meta-analysis

Abstract: Maternal anemia affects approximately 56 million women worldwide and increases the risk of adverse pregnancy outcomes. Our study aimed to summarize the evidence for the association between maternal hemoglobin (Hb) concentrations and maternal or infant outcomes, evaluating it in a continuous manner. In this systematic review and meta-analysis, we conducted an electronic search on PubMed, Embase, CINAHL, and Web of Science from inception to April 19, 2017, and further updated to November 21, 2018, applying subject heading terms related to pregnant women with anemia. We included 117 studies with 4,127,430 pregnancies. Maternal anemia increased the risk of low birth weight (odds ratio (OR), 1.65; 95% confidence interval (CI): 1.45-1.87), preterm birth (PTB) (OR, 2.11; 95% CI: 1.76-2.53), perinatal mortality (PNM) (OR, 3.01; 95% CI: 1.92-4.73), stillbirth (OR, 1.95; 95% CI: 1.15-3.31), and maternal mortality (OR, 3.20; 95% CI: 1.16-8.85). A nonlinear relationship was found between maternal Hb and adverse maternal and infant outcomes. The OR of outcomes such as PTB, small-for-gestational age, PNM, preeclampsia, gestational hypertension, and postpartum hemorrhage was increased by two to three times. Assessing Hb as a continuous variable is important to determine the associated risk of adverse outcomes with decreasing or increasing levels.

The Wnt signaling pathway: a potential therapeutic target against cancer

Abstract: The role of the evolutionarily conserved Wnt signaling pathway is well documented in several cellular processes, such as cell proliferation, differentiation, cell motility, and maintenance of the stem cell niche. The very first indication that aberrant Wnt signaling can cause carcinogenesis came from a finding that the mutation of the adenomatous polyposis coli gene (APC) predisposes a person to colorectal carcinoma. Later, with progressing research it became clear that abnormal activation or mutation of the genes related to this pathway could drive tumorigenesis. Here, we review recent advances in research regarding Wnt signaling regulation and its role in several cancer subtypes. Additionally, the utility of Wnt pathway-targeted cancer therapy intervention is also highlighted, with an overview of current approaches to target the Wnt pathway in oncogenesis and the future scopes and challenges associated with them.

The role of the microbiome in nonhealing diabetic wounds

Abstract: Wound healing is a highly coordinated and complex process, and there can be devastating consequences if it is interrupted It is believed that, in combination with host factors, microorganisms in a wound bed can not only impair wound healing but can lead to stalled, chronic wounds It is hypothesized that the wound microbiota persists in chronic wounds as a biofilm, recalcitrant to antibiotic and mechanical intervention Cultivation-based methods are the gold standard for identification of pathogens residing in wounds However, these methods are biased against fastidious organisms, and do not capture the full extent of microbial diversity in chronic wounds Thus, the link between specific microbes and impaired healing remains tenuous This is partially because local infection and, more specifically, the formation of a biofilm, is difficult to diagnose This has led to research efforts aimed at understanding if biofilm formation delays healing and leads to persistent and chronic infection Circumventing challenges associated with culture-based estimations, advances in high-throughput sequencing analysis has revealed that chronic wounds are host to complex, diverse microbiomes comprising multiple species of bacteria and fungi Here, we discuss how the use of genomic methodologies to study wound microbiomes has advanced the current understanding of infection and biofilm formation in chronic wounds

Racial discrimination, the superwoman schema, and allostatic load: exploring an integrative stress-coping model among African American women

Abstract: Racial discrimination has been linked to allostatic load (i.e., cumulative biological stress) among African American women. However, limited attention has been given to psychosocial processes involved in the stress response-critical for understanding biological pathways to health-in studies examining racial discrimination as a social determinant of health. We examined whether the superwoman schema (SWS), a multidimensional culture-specific framework characterizing psychosocial responses to stress among African American women, modifies the association between racial discrimination and allostatic load. We used purposive sampling to recruit a community sample of African American women ages 30-50 from five San Francisco Bay Area counties (n = 208). Path analysis was used to test for interactions while accounting for the covariance among SWS subscales using both linear and quadratic models. Significant interactions were observed between racial discrimination and four of the five SWS subscales. Feeling obligated to present an image of strength and an obligation to suppress emotions were each protective whereas feeling an intense motivation to succeed and feeling an obligation to help others exacerbated the independent health risk associated with experiencing racial discrimination. Our findings affirm the need to consider individual variability in coping and potentially other psychosocial processes involved in the stress response process, and offer several insights that may help elucidate the mechanisms by which racial discrimination gets "under the skin."

Critically important antibiotics: criteria and approaches for measuring and reducing their use in food animal agriculture.

Abstract: Globally, increasing acquired antimicrobial resistance among pathogenic bacteria presents an urgent challenge to human and animal health. As a result, significant efforts, such as the One Health Initiative, are underway to curtail and optimize the use of critically important antimicrobials for human medicine in all applications, including food animal production. This review discusses the rationale behind multiple and competing "critically important antimicrobial" lists and their contexts as created by international, regional, and national organizations; identifies discrepancies among these lists; and describes issues surrounding risk management recommendations that have been made by regulatory organizations on the use of antibiotics in food animal production. A more harmonized approach to defining criticality in its various contexts (e.g., for human versus animal health, enteric diseases versus other systemic infections, and direct versus indirect selection of resistance) is needed in order to identify shared contextual features, aid in their translation into risk management, and identify the best ways to maintain the health of food animals, all while keeping in mind the wider risks of antimicrobial resistance, environmental impacts, and animal welfare considerations.

The state of the art and fundamental aspects of regional climate modeling in South America

Abstract: Regional climate models have been used since 1989 in order to improve climate simulation in regions where mesoscale forcings modulate the regional climate. These models are driven by time-dependent lateral boundary conditions from global climate models or reanalysis, and this process is called dynamical downscaling. Here, we review the evolution of regional climate modeling, as well as present the studies developed for South America.

Stress and the psyche–brain–immune network in psychiatric diseases based on psychoneuroendocrineimmunology: a concise review

Abstract: In the last decades, psychoneuroendocrineimmunology research has made relevant contributions to the fields of neuroscience, psychobiology, epigenetics, molecular biology, and clinical research by studying the effect of stress on human health and highlighting the close interrelations between psyche, brain, and bodily systems. It is now well recognized that chronic stress can alter the physiological cross-talk between brain and biological systems, leading to long-lasting maladaptive effects (allostatic overload) on the nervous, immune, endocrine, and metabolic systems, which compromises stress resiliency and health. Stressful conditions in early life have been associated with profound alterations in cortical and subcortical brain regions involved in emotion regulation and the salience network, showing relevant overlap with different psychiatric conditions. This paper provides a summary of the available literature concerning the notable effects of stress on the brain and immune system. We highlight the role of epigenetics as a mechanistic pathway mediating the influences of the social and physical environment on brain structure and connectivity, the immune system, and psycho-physical health in psychiatric diseases. We also summarize the evidence regarding the effects of stress management techniques (mainly psychotherapy and meditation practice) on clinical outcomes, brain neurocircuitry, and immune-inflammatory network in major psychiatric diseases.

Nrf2-Keap1 pathway-mediated effects of resveratrol on oxidative stress and apoptosis in hydrogen peroxide-treated rheumatoid arthritis fibroblast-like synoviocytes.

Abstract: Resveratrol (Res) is a polyphenolic compound that has a variety of biological functions and activities. This study aimed to explore the mechanisms of the antioxidant and proapoptotic effects of Res in H2 O2 -treated rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) by the Nrf2-Keap1 signaling pathway. We found that 5 µM H2 O2 promoted cell proliferation and increased intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) content in RA-FLSs. However, Res could reverse these effects in 5 µMH2O2-treated RA-FLSs by (1) promoting expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), (2) reducing expression of Kelch-like ECH-related protein 1 (Keap1), (3) inhibiting production of ROS and MDA, (4) blocking activation of nuclear factor-κB (NF-κB) p65, (5) inhibiting cell proliferation and migration, and (6) activating Bcl-2/Bax to induce apoptosis. After lentiviral silencing of Nrf2 (siNrf2) mRNA expression in RA-FLSs, Res addition did not increase the expression of Nrf2 or HO-1 to reduce the production of mitochondrial ROS caused by 5 µM H2 O2 . Res reduced the Bcl-2/Bax ratio, but siNrf2 reduced the ability of Res to promote apoptosis. We conclude that Res inhibits ROS production by activating the Nrf2 pathway, thereby inhibiting activation of NF-κB and proliferation and migration of RA-FLSs, to induce apoptosis. Targeting the Nrf2-Keap1 pathway may be a relevant aim of using Res in the treatment of RA.

Targeting LOX-1 in atherosclerosis and vasculopathy: current knowledge and future perspectives

Abstract: LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1; also known as OLR1) is the dominant receptor that recognizes and internalizes oxidized low-density lipoproteins (ox-LDLs) in endothelial cells. Several genetic variants of LOX-1 are associated with the risk and severity of coronary artery disease. The LOX-1-ox-LDL interaction induces endothelial dysfunction, leukocyte adhesion, macrophage-derived foam cell formation, smooth muscle cell proliferation and migration, and platelet activation. LOX-1 activation eventually leads to the rupture of atherosclerotic plaques and acute cardiovascular events. In addition, LOX-1 can be cleaved to generate soluble LOX-1 (sLOX-1), which is a useful diagnostic and prognostic marker for atherosclerosis-related diseases in human patients. Of therapeutic relevance, several natural products and clinically used drugs have emerged as LOX-1 inhibitors that have antiatherosclerotic actions. We hereby provide an updated overview of role of LOX-1 in atherosclerosis and associated vascular diseases, with an aim to highlighting the potential of LOX-1 as a novel theranostic tool for cardiovascular disease prevention and treatment.

Endoplasmic reticulum–mitochondria crosstalk: from junction to function across neurological disorders

Abstract: The endoplasmic reticulum (ER) and mitochondria are fundamental organelles highly interconnected with a specialized set of proteins in cells. ER-mitochondrial interconnections form specific microdomains, called mitochondria-associated ER membranes, that have been found to play important roles in calcium signaling and lipid homeostasis, and more recently in mitochondrial dynamics, inflammation, and autophagy. It is not surprising that perturbations in ER-mitochondria connections can result in the progression of disease, especially neurological disorders; hence, their architecture and regulation are crucial in determining the fate of cells and disease. The molecular identity of the specialized proteins regulating ER-mitochondrial crosstalk remains unclear. Our discussion here describes the physical and functional crosstalk between these two dynamic organelles and emphasizes the outcome of altered ER-mitochondrial interconnections in neurological disorders.

What is animal happiness

Abstract: Today, we see a growing concern for the quality of life of nonhuman animals and an accompanying call for viable means of assessing how well animals thrive. Past research focused on minimizing negatives such as stress, while more recent endeavors strive to promote positives such as happiness. But what is animal happiness? Although often mentioned, the term lacks a clear definition. With recent advances in the study of animal emotion, current interest into positive rather than negative experiences, and the call for captive and domesticated animals to have good lives, the time is ripe to examine the concept of animal happiness. We draw from the human and animal literature to delineate a concept of animal happiness and propose how to assess it. We argue that animal happiness depends on how an individual feels generally—that is, a typical level of affect.

The increase in hemoglobin concentration with altitude varies among human populations

Abstract: Decreased oxygen availability at high altitude requires physiological adjustments allowing for adequate tissue oxygenation. One such mechanism is a slow increase in the hemoglobin concentration ([Hb]) resulting in elevated [Hb] in high-altitude residents. Diagnosis of anemia at different altitudes requires reference values for [Hb]. Our aim was to establish such values based on published data of residents living at different altitudes by applying meta-analysis and multiple regressions. Results show that [Hb] is increased in all high-altitude residents. However, the magnitude of increase varies among the regions analyzed and among ethnic groups within a region. The highest increase was found in residents of the Andes (1 g/dL/1000 m), but this increment was smaller in all other regions of the world (0.6 g/dL/1000 m). While sufficient data exist for adult males and females showing that sex differences in [Hb] persist with altitude, data for infants, children, and pregnant women are incomplete preventing such analyses. Because WHO reference values were originally based on [Hb] of South American people, we conclude that individual reference values have to be defined for ethnic groups to reliably diagnose anemia and erythrocytosis in high-altitude residents. Future studies need to test their applicability for children of different ages and pregnant women.

Speech rhythm and language acquisition: an amplitude modulation phase hierarchy perspective

Abstract: Language lies at the heart of our experience as humans and disorders of language acquisition carry severe developmental costs. Rhythmic processing lies at the heart of language acquisition. Here, I review our understanding of the perceptual and neural mechanisms that support language acquisition, from a novel amplitude modulation perspective. Amplitude modulation patterns in infant- and child-directed speech support the perceptual experience of rhythm, and the brain encodes these rhythm patterns in part via neuroelectric oscillations. When brain rhythms align themselves with (entrain to) acoustic rhythms, speech intelligibility improves. Recent advances in the auditory neuroscience of speech processing enable studies of neuronal oscillatory entrainment in children and infants. The "amplitude modulation phase hierarchy" theoretical perspective on language acquisition is applicable across languages, and cross-language investigations adopting this novel perspective would be valuable for the field.