Neuropsychiatric Complications of HIV Infection: Public Policy Implications

The human immunodeficiency virus (HIV) infects the central nervous system (CNS), causing symptoms in most persons with AIDS-related complex (ARC) and AIDS, and in a significant proportion of those classified as asymptomatic seropositive. The most common clinical syndrome secondary to CNS infection is known as HIV encephalopathy. When sufficiently disabling, HIV encephalopathy is known as AIDS dementia, and must be reported to the Centers for Disease Control as a case of AIDS. AIDS dementia is a complex of cognitive, affective, behavioral, and motor symptoms which varies widely in its presentation. In some persons, cognitive impairment predominates, manifesting in a loss of intellectual capacities such as short-term memory, information processing, and abstract thinking. When mood disturbance predominates, it may present as irritability, anxiety, depression, or mania. Behavioral complications are most often due to confusion or psychosis, and may render the patient difficult for caretakers to manage. Motor impairments include slowing, gait abnormalities, incontinence, and paralysis. AIDS dementia presents a significant challenge to the public health system. Physicians, other health providers, and policymakers must be educated so that they may tackle the problems of diagnosis, acute and chronic care, and public safety which are related to this illness

Quantum cascade laser-based reflectance spectroscopy: a robust approach for the classification of plastic type

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Michel, A. P. M., Morrison, A. E., Colson, B. C., Pardis, W. A., Moya, X. A., Harb, C. C., & White, H. K. Quantum cascade laser-based reflectance spectroscopy: a robust approach for the classification of plastic type. Optics Express, 28(12), (2020): 17741-17756, doi:10.1364/OE.393231.The identification of plastic type is important for environmental applications ranging from recycling to understanding the fate of plastics in marine, atmospheric, and terrestrial environments. Infrared reflectance spectroscopy is a powerful approach for plastics identification, requiring only optical access to a sample. The use of visible and near-infrared wavelengths for plastics identification are limiting as dark colored plastics absorb at these wavelengths, producing no reflectance spectra. The use of mid-infrared wavelengths instead enables dark plastics to be identified. Here we demonstrate the capability to utilize a pulsed, widely-tunable (5.59 - 7.41 µm) mid-infrared quantum cascade laser, as the source for reflectance spectroscopy, for the rapid and robust identification of plastics. Through the application of linear discriminant analysis to the resulting spectral data set, we demonstrate that we can correctly classify five plastic types: polyethylene terephthalate (PET), high density polyethylene (HDPE), low density polyethylene (LDPE), polypropylene (PP), and polystyrene (PS), with a 97% accuracy rate.Richard Saltonstall Charitable Foundation; National Academies Keck Futures Initiative (NAKFI DBS13)

Discovery of (R)-2-Amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic Acid and Congeners As Highly Potent Inhibitors of Human Arginases I and II for Treatment of Myocardial Reperfusion Injury

Recent efforts to identify treatments for myocardial ischemia reperfusion injury have resulted in the discovery of a novel series of highly potent α,α-disubstituted amino acid-based arginase inhibitors. The lead candidate, (R)-2-amino-6-borono-2-(2-(piperidin-1-yl)ethyl)hexanoic acid, compound 9, inhibits human arginases I and II with IC50s of 223 and 509 nM, respectively, and is active in a recombinant cellular assay overexpressing human arginase I (CHO cells). It is 28% orally bioavailable and significantly reduces the infarct size in a rat model of myocardial ischemia/reperfusion injury. Herein, we report the design, synthesis, and structure−activity relationships (SAR) for this novel series of inhibitors along with pharmacokinetic and in vivo efficacy data for compound 9 and X-ray crystallography data for selected lead compounds cocrystallized with arginases I and II.Fil: Van Zandt, Michael C.. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Whitehouse, Darren L.. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Golebiowski, Adam. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Ji, Min Koo. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Zhang, Mingbao. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Beckett, R. Paul. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Jagdmann, G. Erik. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Ryder, Todd R.. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Sheeler, Ryan. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Andreoli, Monica. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Conway, Bruce. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Mahboubi, Keyvan. Institutes for Pharmaceutical Discovery; Estados UnidosFil: D’Angelo, Gerard. Institutes for Pharmaceutical Discovery; Estados UnidosFil: Mitschler, Andre. Université de Strasbourg; FranciaFil: Cousido Siah, Alexandra. Université de Strasbourg; FranciaFil: Ruiz, Frances X.. Université de Strasbourg; FranciaFil: Howard, Eduardo Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina. Université de Strasbourg; FranciaFil: Podjarny, Alberto Daniel. Université de Strasbourg; FranciaFil: Schroeter, Hagen. Mars Incorporated; Estados Unido

Fresh air funds and functional families: The enduring politics of race, family and place in juvenile justice reform

This article examines the enduring ways that racial politics are masked by discourses of place and family in the history of juvenile justice in the USA. The tropes of place and family have been invoked since the inception of the USA’s juvenile justice system and have influenced the processes of policing, removal, and return, even as the latest incarnation of reforms focus on building juvenile justice facilities and alternatives to incarceration within urban areas. By pointing to recent manifestations of this rhetoric in New York, the article identifies the thread that links these claims together: the desire by social control agents for submission by the primarily impoverished and young people of color who defy legal authority

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity.

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic

Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity

Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification