Antibiotic resistance, prompted by the overuse of antimicrobial agents, may arise from a variety of mechanisms, particularly horizontal gene transfer of virulence and antibiotic resistance genes, ...which is often facilitated by biofilm formation. The importance of phenotypic changes seen in a biofilm, which lead to genotypic alterations, cannot be overstated. Irrespective of if the biofilm is single microbe or polymicrobial, bacteria, protected within a biofilm from the external environment, communicate through signal transduction pathways (e.g., quorum sensing or two-component systems), leading to global changes in gene expression, enhancing virulence, and expediting the acquisition of antibiotic resistance. Thus, one must examine a genetic change in virulence and resistance not only in the context of the biofilm but also as inextricably linked pathologies. Observationally, it is clear that increased virulence and the advent of antibiotic resistance often arise almost simultaneously; however, their genetic connection has been relatively ignored. Although the complexities of genetic regulation in a multispecies community may obscure a causative relationship, uncovering key genetic interactions between virulence and resistance in biofilm bacteria is essential to identifying new druggable targets, ultimately providing a drug discovery and development pathway to improve treatment options for chronic and recurring infection.
Introduction: This is the 34th Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 January 2016, 55 of the nation's poison centers ...(PCs) uploaded case data automatically to NPDS. The upload interval was 9.50 7.33, 14.6 (median 25%, 75%) min, facilitating a near real-time national exposure and information database and surveillance system.
Methods: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure.
Results: In 2016, 2,710,042 closed encounters were logged by NPDS: 2,159,032 human exposures, 54,019 animal exposures, 490,215 information cases, 6687 human confirmed non-exposures, and 89 animal confirmed non-exposures. US PCs also made 2,718,022 follow-up calls in 2016. Total encounters showed a 2.94% decline from 2015, while health care facility (HCF) human exposure cases increased by 3.63% from 2015. All information calls decreased by 12.5% but HCF information calls increased 0.454%, and while medication identification requests (Drug ID) decreased 29.6%, human exposure cases were essentially flat, decreasing by 0.431%. Human exposures with less serious outcomes have decreased 2.59% per year since 2008 while those with more serious outcomes (moderate, major or death) have increased by 4.39% per year since 2000.
The top five substance classes most frequently involved in all human exposures were analgesics (11.2%), household cleaning substances (7.54%), cosmetics/personal care products (7.20%), sedatives/hypnotics/antipsychotics (5.84%), and antidepressants (4.74%). As a class, sedative/hypnotics/antipsychotics exposures increased most rapidly, by 10.7% per year (2088 cases/year), over the last 15 years for cases showing more serious outcomes. The top five most common exposures in children age 5 years or less were cosmetics/personal care products (13.3%), household cleaning substances (11.1%), analgesics (9.21%), foreign bodies/toys/miscellaneous (6.48%), and topical preparations (5.07%). Drug identification requests comprised 28.1% of all information calls. NPDS documented 1977 human exposures resulting in death; 1492 (75.5%) of these were judged as related (RCF of 1 - undoubtedly responsible, 2 - probably responsible, or 3 - contributory).
Conclusions: These data support the continued value of PC expertise and need for specialized medical toxicology information to manage more serious exposures, despite a decrease in cases involving less serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource for collecting and monitoring US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g. foreign body, infectious, venomous, chemical agent, or commercial product), and the identification and tracking of significant public health events. NPDS is a model system for the real-time surveillance of national and global public health.
Background: This is the 32nd Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 January 2014, 56 of the nation's poison centers ...(PCs) uploaded case data automatically to NPDS. The upload interval was 7.82 7.02, 11.17 (median 25%, 75%) minutes, creating a near real-time national exposure and information database and surveillance system.
Methodology: We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Poison center cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure to the death.
Results: In 2014, 2,890,909 closed encounters were logged by NPDS: 2,165,142 human exposures, 56,265 animal exposures, 663,305 information calls, 6,085 human confirmed nonexposures, and 112 animal confirmed nonexposures. US poison centers (PCs) also made 2,617,346 follow-up calls in 2014. Total encounters showed a 5.5% decline from 2013, while health care facility human exposure cases increased by 3.3% from 2013. All information calls decreased by 17.7% and health care facility (HCF) information calls were essentially flat, decreasing by 0.04%, medication identification requests (Drug ID) decreased 29.8%, and human exposures reported to US PCs decreased 1.1%. Human exposures with less serious outcomes have decreased 3.40% per year since 2008 while those with more serious outcomes (moderate, major or death) have increased by 4.29% per year since 2000.
The top 5 substance classes most frequently involved in all human exposures were analgesics (11.3%), cosmetics/personal care products (7.7%), household cleaning substances (7.7%), sedatives/hypnotics/antipsychotics (5.9%), and antidepressants (4.4%). Sedative/Hypnotics/Antipsychotics exposures as a class increased the most rapidly (2,368 calls (12.2%)/year) over the last 13 years for cases showing more serious outcomes. The top 5 most common exposures in children age 5 years or less were cosmetics/personal care products (14.0%), household cleaning substances (11.0%), analgesics (9.3%), foreign bodies/toys/miscellaneous (6.7%), and topical preparations (5.8%). Drug identification requests comprised 43.3% of all information calls. NPDS documented 1,835 human exposures resulting in death with 1,408 human fatalities judged related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory).
Conclusions: These data support the continued value of PC expertise and need for specialized medical toxicology information to manage more serious exposures, despite a decrease in calls involving less serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time, always current status of NPDS represents a national public health resource to collect and monitor US exposure cases and information calls. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, viral, bacterial, venomous, chemical agent, or commercial product), the identification of events of public health significance, resilience, response and situational awareness tracking. NPDS is a model system for the real-time surveillance of national and global public health.
NOTE: Comparison of exposure or outcome data from previous AAPCC Annual Reports is problematic. In particular, the identification of fatalities (attribution of a death to the exposure) differed from pre-2006 Annual Reports (see Fatality Case Review - Methods). Poison center death cases are described as all cases resulting in death and those determined to be exposure-related fatalities. Likewise, Table 22 (Exposure Cases by Generic Category) since year 2006 restricts the breakdown of included deaths to single-substance cases to improve precision and avoid misinterpretation.
As the planet warms, it is important to consider possible impacts of climate change on severe thunderstorms and tornadoes. To further that discussion, the current distribution of severe thunderstorms ...as a function of large-scale environmental conditions is presented. Severe thunderstorms are much more likely to form in environments with large values of convective available potential energy (CAPE) and deep-tropospheric wind shear. Tornadoes and large hail are preferred in high-shear environments and non-tornadic wind events in low shear. Further, the intensity of tornadoes and hail, given that they occur, tends to be almost entirely a function of the shear and only weakly depends on the thermodynamics.
Climate model simulations suggest that CAPE will increase in the future and the wind shear will decrease. Detailed analysis has suggested that the CAPE change will lead to more frequent environments favorable for severe thunderstorms, but the strong dependence on shear for tornadoes, particularly the strongest ones, and hail means that the interpretation of how individual hazards will change is open to question. The recent development of techniques to use higher-resolution models to estimate the occurrence of storms of various kinds is discussed. Given the large interannual variability in environments and occurrence of events, caution is urged in interpreting the observational record as evidence of climate change.
This is the 36
Annual Report of the American Association of Poison Control Centers' (AAPCC) National Poison Data System (NPDS). As of 1 January, 2018, 55 of the nation's poison centers (PCs) uploaded ...case data automatically to NPDS. The upload interval was 7.72 6.90, 12.0 (median 25%, 75%) minutes, creating a near real-time national exposure and information database and surveillance system.
We analyzed the case data tabulating specific indices from NPDS. The methodology was similar to that of previous years. Where changes were introduced, the differences are identified. Cases with medical outcomes of death were evaluated by a team of medical and clinical toxicologist reviewers using an ordinal scale of 1-6 to assess the Relative Contribution to Fatality (RCF) of the exposure.
In 2018, 2,530,238 closed encounters were logged by NPDS: 2,099,751 human exposures, 57,017 animal exposures, 368,025 information requests, 5,346 human confirmed nonexposures, and 99 animal confirmed nonexposures. United States PCs also made 2,621,242 follow-up calls in 2018. Total encounters showed a 2.96% decline from 2017, while health care facility (HCF) human exposure cases remained nearly steady with a slight decrease of 0.261%. All information requests decreased by 15.5%, medication identification (Drug ID) requests decreased by 30.2%, and human exposure cases decreased by 0.729%. Human exposures with less serious outcomes have decreased 2.33% per year since 2008, while those with more serious outcomes (moderate, major or death) have increased 4.45% per year since 2000.Consistent with the previous year, the top 5 substance classes most frequently involved in all human exposures were analgesics (10.8%), household cleaning substances (7.28%), cosmetics/personal care products (6.53%), sedatives/hypnotics/antipsychotics (5.53%), and antidepressants (5.22%). For cases with more serious outcomes, sedative/hypnotics/antipsychotics exposures were the class that increased most rapidly, by 1,828 cases/year (9.21%/year) over the past 18 years. Over just the past 10 years (for cases with the most serious outcomes) antidepressant exposures increased most rapidly, by 1,887 cases/year (7.02%/year).The top 5 most common exposures in children age 5 years or less were cosmetics/personal care products (12.1%), household cleaning substances (10.7%), analgesics (9.04%), foreign bodies/toys/miscellaneous (6.87%), and topical preparations (4.69%). Drug identification requests comprised 18.2% of all information requests. NPDS documented 3,111 human exposures resulting in death; 2,582 (83.0%) of these were judged as related (RCF of 1-Undoubtedly responsible, 2-Probably responsible, or 3-Contributory).
These data support the continued value of PC expertise and need for specialized medical toxicology information to manage more serious exposures. Unintentional and intentional exposures continue to be a significant cause of morbidity and mortality in the US. The near real-time status of NPDS represents a national public health resource to collect and monitor US exposure cases and information requests. The continuing mission of NPDS is to provide a nationwide infrastructure for surveillance for all types of exposures (e.g., foreign body, infectious, venomous, chemical agent, or commercial product), and the identification and tracking of significant public health events. NPDS is a model system for the near real-time surveillance of national and global public health.
Excessive adipose tissue macrophage accumulation in obesity has been implicated in mediating inflammatory responses that impair glucose homeostasis and promote insulin resistance. Colony-stimulating ...factor 1 (CSF1) controls macrophage differentiation, and here we sought to determine the effect of a CSF1 receptor inhibitor, PLX3397, on adipose tissue macrophage levels and understand the impact on glucose homeostasis in mice.
A Ten-week-old mice were fed a chow or high-fat diet for 10 weeks and then treated with PLX3397 via oral gavage (50 mg/kg) every second day for 3 weeks, with subsequent monitoring of glucose tolerance, insulin sensitivity and assessment of adipose tissue immune cells.
PLX3397 treatment substantially reduced macrophage numbers in adipose tissue of both chow and high-fat diet fed mice without affecting total myeloid cell levels. Despite this, PLX3397 did not greatly alter glucose homeostasis, did not affect high-fat diet-induced increases in visceral fat cytokine expression (Il-6 and Tnfa) and had limited effect on the phosphorylation of the stress kinases JNK and ERK and macrophage polarization.
Our results indicate that macrophage infiltration of adipose tissue induced by a high-fat diet may not be the trigger for impairments in whole body glucose homeostasis, and that anti-CSF1 therapies are not likely to be useful as treatments for insulin resistance.
An expanding body of research asserts that the gut microbiota has a role in bone metabolism and the pathogenesis of osteoporosis. This review considers the human gut microbiota composition and its ...role in osteoclastogenesis and the bone healing process, specifically in the case of osteoporosis. Although the natural physiologic processes of bone healing and the pathogenesis of osteoporosis and bone disease are now relatively well known, recent literature suggests that a healthy microbiome is tied to bone homeostasis. Nevertheless, the mechanism underlying this connection is still somewhat enigmatic. Based on the literature, a relationship between the microbiome, osteoblasts, osteoclasts, and receptor activator of nuclear factor-kappa-Β ligand (RANKL) is contemplated and explored in this review. Studies have proposed various mechanisms of gut microbiome interaction with osteoclastogenesis and bone health, including micro-RNA, insulin-like growth factor 1, and immune system mediation. However, alterations to the gut microbiome secondary to pharmaceutical and surgical interventions cannot be discounted and are discussed in the context of clinical therapeutic consideration. The literature on probiotics and their mechanisms of action is examined in the context of bone healing. The known and hypothesized interactions of common osteoporosis drugs and the human gut microbiome are examined. Since dysbiosis in the gut microbiota can function as a biomarker of bone metabolic activity, it may also be a pharmacological and nutraceutical (i.e., pre- and probiotics) therapeutic target to promote bone homeostasis.
Whether or not climate change has had an impact on the occurrence of tornadoes in the United States has become a question of high public and scientific interest, but changes in how tornadoes are ...reported have made it difficult to answer it convincingly. We show that, excluding the weakest tornadoes, the mean annual number of tornadoes has remained relatively constant, but their variability of occurrence has increased since the 1970s. This is due to a decrease in the number of days per year with tornadoes combined with an increase in days with many tornadoes, leading to greater variability on annual and monthly time scales and changes in the timing of the start of the tornado season.
This paper describes a pervasive form of psychological distress occurring among people undergoing a sudden and acute collapse of faith in the teachings of the Church of Jesus Christ of Latter-day ...Saints (aka LDS, or Mormon Church). Drawing on 18 months of fieldwork in Utah, I trace the cultural–historical etiology of this unique form of psycho-existential trauma, focusing on ex-Mormons’ narratives of ‘world collapse’—in which the all-encompassing symbolic-existential framework of reality once provided by religion disintegrated once they lost faith in the Mormon Church. Although marked by symptoms resembling depression, anxiety, dissociation and paranoia, this condition is however unlike mental health disorders described in psychiatric diagnostic manuals, and has thus been largely overlooked within the mental health professions. I thereby discuss the extent to which the distress of religious disenchantment constitutes a unique form of ‘cultural syndrome’ (Hinton and Lewis-Fernandez in Cult Med Psychiatry 34(2):209–218, 2010), reflective of complex historical, cultural, and religious transformations occurring within contemporary Utah Mormonism.
Researchers have only recently turned their attention to the study of corporate reputation.As is characteristic of many early areas of management inquiry, the field is decidedly multidisciplinary and ...disconnected. This article selectively reviews reputation research conducted mainly during the past decade. A framework is proposed that views reputation from the perspective of organizational impression management. Corporations are viewed as social actors, intent on enhancing their respectability and impressiveness in the eyes of constituents.
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