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Studies of autism spectrum disorder (ASD) related to exposure to toxic levels of dietary phosphate are lacking. Phosphate toxicity from dysregulated phosphate metabolism can negatively impact almost every major organ system of the body, including the central nervous system. The present paper used a grounded theory-literature review method to synthesise associations of dysregulated phosphate metabolism with the aetiology of ASD. Cell signalling in autism has been linked to an altered balance between phosphoinositide kinases, which phosphorylate proteins, and the counteracting effect of phosphatases in neuronal membranes. Glial cell overgrowth in the developing ASD brain can lead to disturbances in neuro-circuitry, neuroinflammation and immune responses which are potentially related to excessive inorganic phosphate. The rise in ASD prevalence has been suggested to originate in changes to the gut microbiome from increasing consumption of additives in processed food, including phosphate additives. Ketogenic diets and dietary patterns that eliminate casein also reduce phosphate intake, which may account for many of the suggested benefits of these diets in children with ASD. Dysregulated phosphate metabolism is causatively linked to comorbid conditions associated with ASD such as cancer, tuberous sclerosis, mitochondrial dysfunction, diabetes, epilepsy, obesity, chronic kidney disease, tauopathy, cardiovascular disease and bone mineral disorders. Associations and proposals presented in this paper offer novel insights and directions for future research linking the aetiology of ASD with dysregulated phosphate metabolism and phosphate toxicity from excessive dietary phosphorus intake.
This paper investigates three controversies involving potential causes and consequences of information bias in case and death definitions during the coronavirus disease (COVID-19) pandemic. First, evidence suggests China’s surveillance data were biased and misinterpreted by the World Health Organization (WHO), prompting the WHO to advise nations to copy China’s lockdowns. China appeared to use narrow diagnostic definitions that undercounted cases and deaths. Second, novel genomic data disseminated during the pandemic without adequate guidance from rigorous epidemiologic studies biased infection control policies in many countries. A novel genomic sequence of a virus is insufficient to declare new cases of a novel disease. Third, media reports of COVID-19 surveillance data in many nations appeared to be biased. Broadened surveillance definitions captured additional information, but unadjusted surveillance data disseminated to the public are not true cases and deaths. Recommendations include clarification of the proper use of diagnostic and surveillance case and death definitions to avoid information bias.
Compared with an omnivorous Western diet, plant-based diets containing mostly fruits, vegetables, grains, legumes, nuts and seeds, with restricted amounts of foods of animal origin, are associated with reduced risk and severity of COVID-19. Additionally, inflammatory immune responses and severe acute respiratory symptoms of COVID-19, including pulmonary oedema, shortness of breath, fever and nasopharyngeal infections, are associated with Na toxicity from excessive dietary Na. High dietary Na is also associated with increased risks of diseases and conditions that are co-morbid with COVID-19, including chronic kidney disease, hypertension, stroke, diabetes and obesity. This article presents evidence that low dietary Na potentially mediates the association of plant-based diets with COVID-19 prevention. Processed meats and poultry injected with sodium chloride contribute considerable amounts of dietary Na in the Western diet, and the avoidance or reduction of these and other processed foods in whole-food plant-based (WFPB) diets could help lower overall dietary Na intake. Moreover, high amounts of K in plant-based diets increase urinary Na excretion, and preagricultural diets high in plant-based foods were estimated to contain much lower ratios of dietary Na to K compared with modern diets. Further research should investigate low Na in WFPB diets for protection against COVID-19 and co-morbid conditions.
In testimony before US Congress on March 11, 2020, members of the House Oversight and Reform Committee were informed that estimated mortality for the novel coronavirus was 10-times higher than for seasonal influenza. Additional evidence, however, suggests the validity of this estimation could benefit from vetting for biases and miscalculations. The main objective of this article is to critically appraise the coronavirus mortality estimation presented to Congress. Informational texts from the World Health Organization and the Centers for Disease Control and Prevention are compared with coronavirus mortality calculations in Congressional testimony. Results of this critical appraisal reveal information bias and selection bias in coronavirus mortality overestimation, most likely caused by misclassifying an influenza infection fatality rate as a case fatality rate. Public health lessons learned for future infectious disease pandemics include: safeguarding against research biases that may underestimate or overestimate an associated risk of disease and mortality; reassessing the ethics of fear-based public health campaigns; and providing full public disclosure of adverse effects from severe mitigation measures to contain viral transmission.
OBJECTIVES/GOALS: Primary graft dysfunction (PGD) is acute lung injury in the first three days after lung transplant. Patients that experience PGD have increased mortality and an increased risk of chronic lung allograft dysfunction. The pathogenesis is thought to be an ischemia-reperfusion injury but is incompletely understood and there are no specific therapies. We investigated the role of the microbiome in PGD and associations with inflammation and markers of aspiration. METHODS/STUDY POPULATION: We collected airway lavage samples from lung transplant donors before procurement and recipients after reperfusion. We extracted DNA, amplified the bacterial 16S rRNA gene, and sequenced on the Illumina MiSeq platform. QIIME2 and Deblur were used for bioinformatic analysis. R packages were used for downstream analysis and visualizations. The host response was quantified using the Milipore 41-plex Luminex and an ELISA for pepsin. Clinical data was collected by the Penn Lung Transplant Outcomes Group. PGD was assessed by degree of hypoxemia and chest X-ray findings in the 72 hours after transplant. RESULTS/ANTICIPATED RESULTS: There was no significant difference in alpha diversity (Shannon index, p = 0.51), biomass (via comparison of 16S amplicon PicoGreen, p = 0.6), or beta diversity (Weighted UniFrac, p = 0.472, PERMANOVA) between subjects with PGD grade 3 (n = 36) and those that did not (n = 96). On taxonomic analysis, we found an enrichment of Prevotella in donor and recipient lungs that went on to develop PGD (p = 0.05). To follow up this finding we measured immune response and pepsin concentrations in recipient lungs. We found elevated levels in 35/41 cytokines measured in subjects that developed PGD as well as an elevation in pepsin and a correlation between pepsin concentration and Prevotella relative abundance (Figure 1). Additionally, Prevotella relative abundance had statistically significant positive correlations with multiple cytokines such as IL-6 (Pearson’s = 0.26, p = 0.009) and eotaxin (Pearson’s = 0.24, p = 0.016). DISCUSSION/SIGNIFICANCE OF IMPACT: There is an enrichment of oral anerobes in lung allografts that eventually develop PGD. This is associated with elevated levels of pepsin and markers of inflammation. These lines of evidence suggest aspiration contributes to priming the allograft for PGD.
Presently, evidence guiding clinicians on the optimal approach to safely screen patients for coronavirus disease 2019 (COVID-19) to a nonemergent hospital procedure is scarce. In this report, we describe our experience in screening for SARS-CoV-2 prior to semiurgent and urgent hospital procedures.
Design:
Retrospective case series.
Setting:
A single tertiary-care medical center.
Participants:
Our study cohort included patients ≥18 years of age who had semiurgent or urgent hospital procedures or surgeries.
Methods:
Overall, 625 patients were screened for SARS-CoV-2 using a combination of phone questionnaire (7 days prior to the anticipated procedure), RT-PCR and chest computed tomography (CT) between March 1, 2020, and April 30, 2020.
Results:
Of the 625 patients, 520 scans (83.2%) were interpreted as normal; 1 (0.16%) had typical features of COVID-19; 18 scans (2.88%) had indeterminate features of COVID-19; and 86 (13.76%) had atypical features of COVID-19. In total, 640 RT-PCRs were performed, with 1 positive result (0.15%) in a patient with a CT scan that yielded an atypical finding. Of the 18 patients with chest CTs categorized as indeterminate, 5 underwent repeat negative RT-PCR nasopharyngeal swab 1 week after their initial swab. Also, 1 patient with a chest CT categorized as typical had a follow-up repeat negative RT-PCR, indicating that the chest CT was likely a false positive. After surgery, none of the patients developed signs or symptoms suspicious of COVID-19 that would indicate the need for a repeated RT-PCR or CT scan.
Conclusion:
In our experience, chest CT scanning did not prove provide valuable information in detecting asymptomatic cases of SARS-CoV-2 (COVID-19) in our low-prevalence population.
− Agency is one of five core analytical problems in the Earth System Governance (ESG) Project’s research framework, which offers a unique approach to the study of environmental governance. − Agency in Earth System Governance draws lessons from ESG–Agency research through a systematic review of 322 peer-reviewed journal articles published between 2008 and 2016 and contained in the ESG–Agency Harvesting Database.− ESG–Agency research draws on diverse disciplinary perspectives with distinct clusters of scholars rooted in the fields of global environmental politics, policy studies, and socio-ecological systems. − Collectively, the chapters in Agency in Earth System Governance provide an accessible synthesis of some of the field’s major questions and debates and a state-of-the-art understanding of how diverse actors engage with and exercise authority in environmental governance.
Using data collected between 2004 and 2008 from the National Politics Studies, this study explores the impact of race on the likelihood of attending worship settings that provide supportive services for and preach sermons about immigrants. It also considers the degree to which attending such worship settings associate with the perceptions that Whites, Blacks, and Hispanics hold of immigrants. We find that while Hispanics are more likely than Whites and Blacks to attend such “immigrant-conscious” congregations, attending such congregations more strongly correlates with Whites rejecting anti-immigrant frames and accepting positive frames than is the case for Blacks and Hispanics.
δ18O values of sulfate minerals from a 186-m core (past 200,000 years) in Death Valley varied from +9 to +23‰ (V-SMOW). Sulfates that accumulated in the past ephemeral saline lake, salt pans, and mud flats have relatively low δ18O values similar to those of present-day local inflows. Sulfates that accumulated during two perennial lake intervals, however, have higher δ18O values, reflecting changes in temperature, lake water levels, and/or sulfur redox reactions. Over the same time interval, the δ18O record for sulfate had excursions that bear similarities to those found for carbonate in the Death Valley core, marine carbonate (SPECMAP), and polar ice in the Summit ice core, Greenland. The δ18O record differed considerably from the records reported for carbonate at Owens Lake and Devils Hole, which probably relates to different water sources. Death Valley, Owens Lake, and Devils Hole are responding to the same climatic changes but manifesting them differently. In Death Valley sediments, the isotopic composition of sulfate may have potential as an indicator of paleoenvironmental changes.
HIV-associated cognitive impairments are prevalent, and are consistent with injury to both frontal cortical and subcortical regions of the brain. The current study aimed to assess the association of HIV infection with functional connections within the frontostriatal network, circuitry hypothesized to be highly vulnerable to HIV infection. Fifteen HIV-positive and 15 demographically matched control participants underwent 6 min of resting-state functional magnetic resonance imaging (RS-fMRI). Multivariate group comparisons of age-adjusted estimates of connectivity within the frontostriatal network were derived from BOLD data for dorsolateral prefrontal cortex (DLPFC), dorsal caudate and mediodorsal thalamic regions of interest. Whole-brain comparisons of group differences in frontostriatal connectivity were conducted, as were pairwise tests of connectivity associations with measures of global cognitive functioning and clinical and immunological characteristics (nadir and current CD4 count, duration of HIV infection, plasma HIV RNA). HIV – associated reductions in connectivity were observed between the DLPFC and the dorsal caudate, particularly in younger participants (<50 years, N=9). Seropositive participants also demonstrated reductions in dorsal caudate connectivity to frontal and parietal brain regions previously demonstrated to be functionally connected to the DLPFC. Cognitive impairment, but none of the assessed clinical/immunological variables, was also associated with reduced frontostriatal connectivity. In conclusion, our data indicate that HIV is associated with attenuated intrinsic frontostriatal connectivity. Intrinsic connectivity of this network may therefore serve as a marker of the deleterious effects of HIV infection on the brain, possibly via HIV-associated dopaminergic abnormalities. These findings warrant independent replication in larger studies. (JINS, 2015, 21, 1–11)
Previous research suggests that many people receiving mental health treatment do not meet criteria for a mental disorder but are rather ‘the worried well’.
Aims
To examine the association of past-year mental health treatment with DSM-IV disorders.
Method
The World Health Organization's World Mental Health (WMH) Surveys interviewed community samples of adults in 23 countries(n = 62 305) about DSM-IV disorders and treatment in the past 12 months for problems with emotions, alcohol or drugs.
Results
Roughly half (52%) of people who received treatment met criteria for a past-year DSM-IV disorder, an additional 18% for a lifetime disorder and an additional 13% for other indicators of need (multiple subthreshold disorders, recent stressors or suicidal behaviours). Dose–response associations were found between number of indicators of need and treatment.
Conclusions
The vast majority of treatment in the WMH countries goes to patients with mental disorders or other problems expected to benefit from treatment.
Significant new opportunities for astrophysics and cosmology have been identified at low radio frequencies. The Murchison Widefield Array is the first telescope in the southern hemisphere designed specifically to explore the low-frequency astronomical sky between 80 and 300 MHz with arcminute angular resolution and high survey efficiency. The telescope will enable new advances along four key science themes, including searching for redshifted 21-cm emission from the EoR in the early Universe; Galactic and extragalactic all-sky southern hemisphere surveys; time-domain astrophysics; and solar, heliospheric, and ionospheric science and space weather. The Murchison Widefield Array is located in Western Australia at the site of the planned Square Kilometre Array (SKA) low-band telescope and is the only low-frequency SKA precursor facility. In this paper, we review the performance properties of the Murchison Widefield Array and describe its primary scientific objectives.