321 research outputs found

    Children’s Cancer Pain in a World of the Opioid Epidemic: Challenges and Opportunities

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    The opioid crisis in the United States has grown at an alarming rate. Children with cancer are at high risk for pain, and opioids are a first‐line treatment in this population. Accordingly, there is an urgent need to optimize pain management in children with cancer without contributing to the opioid crisis. This report details opportunities for this optimization, including clinical practice guidelines, comprehensive approaches to pain management, mobile health, and telemedicine. It is vital to balance appropriate use of analgesics with efforts to prevent misuse in order to reduce unnecessary suffering and minimize unintended harms

    Suicidal Thoughts and Behaviors Among Transgender Adults in Relation to Education, Ethnicity, and Income: A Systematic Review

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    Introduction: This systematic review assessed the impact of race/ethnicity, education, and income on transgender individual's lifetime experience of suicidal thoughts and behaviors (SITB) in gray and published literature (1997–2017). Methods: Sixty four research projects (108 articles) were identified in WorldCat, PubMed, and Google Scholar. Articles were included if they were published in Canada or the United States, included original quantifiable data on transgender SITBs, and had ≥5 participants, at least 51% of whom were ≥18 years. Results: Across all projects suicide ideation averaged 46.55% and attempts averaged 27.19%. The majority of participants were Caucasian, whereas the highest rate of suicide attempts (55.31%) was among First Nations, who accounted for <1.5% of participants. Caucasians, by contrast, had the lowest attempt rate (36.80%). More participants obtained a bachelor's degree and fewer an associate or technical degree than any other level of education. Suicide attempts were highest among those with ≤some high school (50.70%) and lowest among those with an advanced degree (30.25%). More participants made an income of 2020–50,000/year and less 1010–20,000 than any other income bracket. Conclusion: SITBs, among the transgender population, are both universally high and impacted by race/ethnicity, educational attainment, and income. These findings may be useful in creating culturally and factually informed interventions for transgender individuals experiencing SITBs and in informing future research on this topic

    Nitrogen and sulphur management: challenges for organic sources in temperate agricultural systems

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    A current global trend towards intensification or specialization of agricultural enterprises has been accompanied by increasing public awareness of associated environmental consequences. Air and water pollution from losses of nutrients, such as nitrogen (N) and sulphur (S), are a major concern. Governments have initiated extensive regulatory frameworks, including various land use policies, in an attempt to control or reduce the losses. This paper presents an overview of critical input and loss processes affecting N and S for temperate climates, and provides some background to the discussion in subsequent papers evaluating specific farming systems. Management effects on potential gaseous and leaching losses, the lack of synchrony between supply of nutrients and plant demand, and options for optimizing the efficiency of N and S use are reviewed. Integration of inorganic and organic fertilizer inputs and the equitable re-distribution of nutrients from manure are discussed. The paper concludes by highlighting a need for innovative research that is also targeted to practical approaches for reducing N and S losses, and improving the overall synchrony between supply and demand

    MTHFR polymorphisms in gastric cancer and in first-degree relatives of patients with gastric cancer

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    Two common mutations, 677 C→T and a1298 A→C, in the methylenetetrahydrofolate reductase gene (MTHFR) reduce the activity of MTHFR and folate metabolism. Familial aggregation in a variable but significant proportion of gastric cancer (GC) cases suggests the importance of genetic predisposition in determining risk. In this study, we evaluate MTHFR polymorphisms in 57 patients with a diagnosis of GC, in 37 with a history of GC in first-degree relatives (GC-relatives), and in 454 blood donors. Helicobacter pylori (HP) infection was also determined. An increased risk was found for 677TT in GC patients with respect to blood donors (odds ratio (OR) = 1.98), and statistical significance was sustained when we compared sex–age-matched GC patients and donors (OR = 2.37). The 677TT genotype association with GC was found in women (OR = 3.10), while a reduction in the 667C allele frequency was present in both the sex. No statistically significant association was detected when 677–1298 genotype was stratified by sex and age. Men of GC-relatives showed a higher 1298C allele frequency than donors (OR = 4.38). Between GC and GC-relatives, HP infection frequency was similar. In conclusion, overall findings support the hypothesis that folate plays a role in GC risk. GC-relatives evidence a similar 677TT frequency to that found in the general population

    PDFR and CRY Signaling Converge in a Subset of Clock Neurons to Modulate the Amplitude and Phase of Circadian Behavior in Drosophila

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    Background: To synchronize their molecular rhythms, circadian pacemaker neurons must input both external and internal timing cues and, therefore, signal integration between sensory information and internal clock status is fundamental to normal circadian physiology. Methodology/Principal Findings: We demonstrate the specific convergence of clock-derived neuropeptide signaling with that of a deep brain photoreceptor. We report that the neuropeptide PDF receptor and the circadian photoreceptor CRYPTOCROME (CRY) are precisely co-expressed in a subset of pacemakers, and that these pathways together provide a requisite drive for circadian control of daily locomotor rhythms. These convergent signaling pathways influence the phase of rhythm generation, but also its amplitude. In the absence of both pathways, PER rhythms were greatly reduced in only those specific pacemakers that receive convergent inputs and PER levels remained high in the nucleus throughout the day. This suggested a large-scale dis-regulation of the pacemaking machinery. Behavioral rhythms were likewise disrupted: in light:dark conditions they were aberrant, and under constant dark conditions, they were lost. Conclusions/Significance: We speculate that the convergence of environmental and clock-derived signals may produce

    Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

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    Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death
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