COVID-19 Self-Test Data: Challenges and Opportunities - United States, October 31, 2021-June 11, 2022.

Self-tests* to detect current infection with SARS-CoV-2, the virus that causes COVID-19, are valuable tools that guide individual decision-making and risk reduction† (1-3). Increased self-test use (4) has likely contributed to underascertainment of COVID-19 cases (5-7), because unlike the requirements to report results of laboratory-based and health care provider-administered point-of-care COVID-19 tests,§ public health authorities do not require reporting of self-test results. However, self-test instructions include a recommendation that users report results to their health care provider so that they can receive additional testing and treatment if clinically indicated.¶ In addition, multiple manufacturers of COVID-19 self-tests have developed websites or companion mobile applications for users to voluntarily report self-test result data. Federal agencies use the data reported to manufacturers, in combination with manufacturing supply chain information, to better understand self-test availability and use. This report summarizes data voluntarily reported by users of 10.7 million self-tests from four manufacturers during October 31, 2021-June 11, 2022, and compares these self-test data with data received by CDC for 361.9 million laboratory-based and point-of-care tests performed during the same period. Overall trends in reporting volume and percentage of positive results, as well as completeness of reporting demographic variables, were similar across test types. However, the limited amount and quality of data reported from self-tests currently reduces their capacity to augment existing surveillance. Self-tests provide important risk-reduction information to users, and continued development of infrastructure and methods to collect and analyze data from self-tests could improve their use for surveillance during public health emergencies.

Plasma Membrane Anchoring and Gag:Gag Multimerization on Viral RNA Are Critical Properties of HIV-1 Gag Required To Mediate Efficient Genome Packaging.

Human immunodeficiency virus type 1 (HIV-1) Gag selects and packages the HIV RNA genome during virus assembly. However, HIV-1 RNA constitutes only a small fraction of the cellular RNA. Although Gag exhibits a slight preference to viral RNA, most of the cytoplasmic Gag proteins are associated with cellular RNAs. Thus, it is not understood how HIV-1 achieves highly efficient genome packaging. We hypothesize that besides RNA binding, other properties of Gag are important for genome packaging. Many Gag mutants have assembly defects that preclude analysis of their effects on genome packaging. To bypass this challenge, we established complementation systems that separate the particle-assembling and RNA-binding functions of Gag: we used a set of Gag proteins to drive particle assembly and an RNA-binding Gag to package HIV-1 RNA. We have developed two types of RNA-binding Gag in which packaging is mediated by the authentic nucleocapsid (NC) domain or by a nonviral RNA-binding domain. We found that in both cases, mutations that affect the multimerization or plasma membrane anchoring properties of Gag reduce or abolish RNA packaging. These mutant Gag can coassemble into particles but cannot package the RNA genome efficiently. Our findings indicate that HIV-1 RNA packaging occurs at the plasma membrane and RNA-binding Gag needs to multimerize on RNA to encapsidate the viral genome. IMPORTANCE To generate infectious virions, HIV-1 must package its full-length RNA as the genome during particle assembly. HIV-1 Gag:RNA interactions mediate genome packaging, but the mechanism remains unclear. Only a minor portion of the cellular RNA is HIV-1 RNA, and most of the RNAs associated with cytoplasmic Gag are cellular RNAs. However, >94% of the HIV-1 virions contain viral RNA genome. We posited that, besides RNA binding, other properties of Gag contribute to genome packaging. Using two complementation systems, we examined features of Gag that are important for genome packaging. We found that the capacities for Gag to multimerize and to anchor at the plasma membrane are critical for genome packaging. Our results revealed that Gag needs to multimerize on viral RNA at the plasma membrane in order to package RNA genome.

Oxidative stress in the bladder of men with LUTS undergoing open prostatectomy: a pilot study

ABSTRACT Purpose: This study aims to evaluate the link between preoperative parameters and oxidative stress (OS) markers in the bladder wall of men undergoing open prostatectomy. Materials and Methods: From July 2014 to August 2016, men aged ≥ 50 years and presenting with LUTS were prospectively enrolled. Preoperative assessment included validated questionnaires (IPSS and OAB - V8), lower urinary tract ultrasound and urodynamics. Bladder biopsies were taken during open prostatectomy for determination of OS markers. Increased OS was defined by increased concentration of malondialdehyde (MDA) and / or decreased concentration of antioxidant enzymes (superoxide dismutase and / or catalase). P<0.05 was regarded as statistically significant. Results: Thirty - eight consecutive patients were included. Mean age was 66.36 ± 6.44 years, mean prostate volume was 77.7 ± 20.63 cm3, and mean IPSS was 11.05 ± 8.72 points. MDA concentration was increased in men with severe bladder outlet obstruction (BOO grade V - VI according to the Schaefer's nomogram) in comparison with BOO grade III - IV (p = 0.022). Patients with severe LUTS also had higher MDA concentration when compared to those with mild LUTS (p = 0.031). There was a statistically significant association between increased post - void residual urine (cut off ≥ 50 mL) and not only higher levels of MDA, but also reduced activity of SOD and catalase (p < 0.05). Conclusions: This pilot study showed that severity of LUTS and BOO were associated with increased MDA concentration in the bladder wall of men undergoing open prostatectomy. Further studies are still needed to assess the role of non - invasive biomarkers of OS in predicting bladder dysfunction in men with LUTS.

Oxidative stress in the bladder of men with LUTS undergoing open prostatectomy: a pilot study.

PURPOSE: This study aims to evaluate the link between preoperative parameters and oxidative stress (OS) markers in the bladder wall of men undergoing open prostatectomy. MATERIALS AND METHODS: From July 2014 to August 2016, men aged ≥ 50 years and presenting with LUTS were prospectively enrolled. Preoperative assessment included validated questionnaires (IPSS and OAB - V8), lower urinary tract ultrasound and urodynamics. Bladder biopsies were taken during open prostatectomy for determination of OS markers. Increased OS was defined by increased concentration of malondialdehyde (MDA) and / or decreased concentration of antioxidant enzymes (superoxide dismutase and / or catalase). P<0.05 was regarded as statistically significant. RESULTS: Thirty - eight consecutive patients were included. Mean age was 66.36 ± 6.44 years, mean prostate volume was 77.7 ± 20.63 cm3, and mean IPSS was 11.05 ± 8.72 points. MDA concentration was increased in men with severe bladder outlet obstruction (BOO grade V - VI according to the Schaefer's nomogram) in comparison with BOO grade III - IV (p = 0.022). Patients with severe LUTS also had higher MDA concentration when compared to those with mild LUTS (p = 0.031). There was a statistically significant association between increased post - void residual urine (cut off ≥ 50 mL) and not only higher levels of MDA, but also reduced activity of SOD and catalase (p < 0.05). CONCLUSIONS: This pilot study showed that severity of LUTS and BOO were associated with increased MDA concentration in the bladder wall of men undergoing open prostatectomy. Further studies are still needed to assess the role of non - invasive biomarkers of OS in predicting bladder dysfunction in men with LUTS.

Collagen content in the bladder of men with LUTS undergoing open prostatectomy: A pilot study.

AIMS: To evaluate the collagen content in the bladder wall of men undergoing open prostate surgery. METHODS: From July 2014 to August 2016, men aged ≥ 50 years, presenting LUTS and undergoing open prostate surgery due to benign prostatic enlargement (BPE) or prostate cancer were prospectively enrolled. Preoperative assessment included validated questionnaires (IPSS and OAB-V8), lower urinary tract ultrasound, and urodynamics. Bladder biopsies were obtained during open prostatectomy for determination of collagen content (sirius red-picric acid stain; polarized light analysis). Collagen to smooth muscle ratio (C/M) in the detrusor was measured and its relationship with preoperative parameters was investigated. The level of significance was P < 0.05. RESULTS: Thirty-eight consecutive patients were included in this pilot study. Mean age was 66.36 ± 6.44 years and mean IPSS was 11.05 ± 8.72 points. Men diagnosed with diabetes mellitus (DM2) were found to have higher collagen content in the bladder wall when compared to non-diabetic patients (17.71 ± 6.82% vs 12.46 ± 5.2%, respectively; P = 0.024). Reduced bladder compliance was also marker for higher collagen content (P = 0.042). Bladder outlet obstruction (BOO) was not a predictor of increased collagen deposition in the bladder wall (P = 0.75). Patients with PVR ≥ 200 mL showed a higher collagen to smooth muscle ratio in the bladder wall (P = 0.036). CONCLUSIONS: DM2 and urodynamic parameters, such as increased PVR and reduced bladder compliance, were associated with higher collagen content in the bladder wall of men with LUTS.

Cellular minichromosome maintenance complex component 5 (MCM5) is incorporated into HIV-1 virions and modulates viral replication in the newly infected cells.

The post-entry events of HIV-1 infection occur within reverse transcription complexes derived from the viral cores entering the target cell. HIV-1 cores contain host proteins incorporated from virus-producing cells. In this report, we show that MCM5, a subunit of the hexameric minichromosome maintenance (MCM) DNA helicase complex, associates with Gag polyprotein and is incorporated into HIV-1 virions. The progeny virions depleted of MCM5 demonstrated reduced reverse transcription in newly infected cells, but integration and subsequent replication steps were not affected. Interestingly, increased packaging of MCM5 into the virions also led to reduced reverse transcription, but here viral replication was impaired. Our data suggest that incorporation of physiological amounts of MCM5 promotes aberrant reverse transcription, leading to partial incapacitation of cDNA, whereas increased MCM5 abundance leads to reduced reverse transcription and infection. Therefore, MCM5 has the properties of an inhibitory factor that interferes with production of an integration-competent cDNA product.

Nature, nurture and HIV: The effect of producer cell on viral physiology.

Macrophages and CD4-positive T lymphocytes are the major targets and producers of HIV-1. While the molecular details underlying HIV replication in macrophages and T cells become better understood, it remains unclear whether viruses produced by these target cells differ in their biological properties. Recent reports suggest that HIV virions incorporate a large number of producer cell proteins and lipids which have an effect on subsequent viral replication in newly infected cells. The identity and abundance of these incorporated factors varies between different types of producer cells, suggesting that they may influence the replication capacity and pathogenic activity of the virions produced by T cells and macrophages.

Exosomes derived from HIV-1-infected cells contain trans-activation response element RNA.

Exosomes are nano-sized vesicles produced by healthy and virus-infected cells. Exosomes derived from infected cells have been shown to contain viral microRNAs (miRNAs). HIV-1 encodes its own miRNAs that regulate viral and host gene expression. The most abundant HIV-1-derived miRNA, first reported by us and later by others using deep sequencing, is the trans-activation response element (TAR) miRNA. In this study, we demonstrate the presence of TAR RNA in exosomes from cell culture supernatants of HIV-1-infected cells and patient sera. TAR miRNA was not in Ago2 complexes outside the exosomes but enclosed within the exosomes. We detected the host miRNA machinery proteins Dicer and Drosha in exosomes from infected cells. We report that transport of TAR RNA from the nucleus into exosomes is a CRM1 (chromosome region maintenance 1)-dependent active process. Prior exposure of naive cells to exosomes from infected cells increased susceptibility of the recipient cells to HIV-1 infection. Exosomal TAR RNA down-regulated apoptosis by lowering Bim and Cdk9 proteins in recipient cells. We found 10(4)-10(6) copies/ml TAR RNA in exosomes derived from infected culture supernatants and 10(3) copies/ml TAR RNA in the serum exosomes of highly active antiretroviral therapy-treated patients or long term nonprogressors. Taken together, our experiments demonstrated that HIV-1-infected cells produced exosomes that are uniquely characterized by their proteomic and RNA profiles that may contribute to disease pathology in AIDS.

Virus-producing cells determine the host protein profiles of HIV-1 virion cores.

BACKGROUND: Upon HIV entry into target cells, viral cores are released and rearranged into reverse transcription complexes (RTCs), which support reverse transcription and also protect and transport viral cDNA to the site of integration. RTCs are composed of viral and cellular proteins that originate from both target and producer cells, the latter entering the target cell within the viral core. However, the proteome of HIV-1 viral cores in the context of the type of producer cells has not yet been characterized. RESULTS: We examined the proteomic profiles of the cores purified from HIV-1 NL4-3 virions assembled in Sup-T1 cells (T lymphocytes), PMA and vitamin D3 activated THP1 (model of macrophages, mMΦ), and non-activated THP1 cells (model of monocytes, mMN) and assessed potential involvement of identified proteins in the early stages of infection using gene ontology information and data from genome-wide screens on proteins important for HIV-1 replication. We identified 202 cellular proteins incorporated in the viral cores (T cells: 125, mMΦ: 110, mMN: 90) with the overlap between these sets limited to 42 proteins. The groups of RNA binding (29), DNA binding (17), cytoskeleton (15), cytoskeleton regulation (21), chaperone (18), vesicular trafficking-associated (12) and ubiquitin-proteasome pathway-associated proteins (9) were most numerous. Cores of the virions from SupT1 cells contained twice as many RNA binding proteins as cores of THP1-derived virus, whereas cores of virions from mMΦ and mMN were enriched in components of cytoskeleton and vesicular transport machinery, most probably due to differences in virion assembly pathways between these cells. Spectra of chaperones, cytoskeletal proteins and ubiquitin-proteasome pathway components were similar between viral cores from different cell types, whereas DNA-binding and especially RNA-binding proteins were highly diverse. Western blot analysis showed that within the group of overlapping proteins, the level of incorporation of some RNA binding (RHA and HELIC2) and DNA binding proteins (MCM5 and Ku80) in the viral cores from T cells was higher than in the cores from both mMΦ and mMN and did not correlate with the abundance of these proteins in virus producing cells. CONCLUSIONS: Profiles of host proteins packaged in the cores of HIV-1 virions depend on the type of virus producing cell. The pool of proteins present in the cores of all virions is likely to contain factors important for viral functions. Incorporation ratio of certain RNA- and DNA-binding proteins suggests their more efficient, non-random packaging into virions in T cells than in mMΦ and mMN.

Granulomatose de Wegener: importância do diagnóstico precoce. Relato de caso / Wegener?s granulomatosas: importance of early diagnosis. Case report

JUSTIFICATIVA E OBJETIVOS: A granulomatose de Wegener (GW) é uma vasculite necrosante e granulomatosa de origem idiopática, que acomete pequenas e médias artérias das vias respiratórias altas e baixas e rins. Tem prevalência estimada em 3:100.000 habitantes, não apresenta predomínio por sexo e tem pico de incidência entre a quarta e quinta décadas de vida. O objetivo desse estudo foi relatar e discutir um caso dessa rara doença, reforçando a importância de um diagnóstico precoce, a fim de instituira terapêutica adequada e proporcionar ao paciente uma maior sobrevida. RELATO DO CASO: Paciente do sexo masculino, 55 anos, atendido no pronto-socorro com sintomas relacionados às vias aéreas associado a importante emagrecimento. Alguns achados como proteína C-reativa de 117,6 mg/L, tecido pulmonar necrótico permeado por células inflamatórias, ou até mesmo a titulação do cANCA: reagente até 1/40, mesmo que não sejam exclusivos de GW, juntos auxiliaram na conclusão do diagnóstico. Após exaustiva investigação e suspeição diagnóstica, confirmou-se a hipótese de GW, com subsequente prescrição de tratamento adequado, tendo o paciente evoluído favoravelmente, com remissão completa dos sintomas, sendo encaminhado posteriormente para acompanhamento ambulatorial. CONCLUSÃO: Devido a GW ser uma doença incomum e de difícil diagnóstico, sua hipótese deve ser aventada na presença de quadro clínico sugestivo, determinado principalmente por febre, perda de peso, dispneia, hemoptise, hematúria, poliartralgias e mialgias, com o objetivo de se realizar exames mais aprofundados em relação a essa entidade clínica e se instituir a terapêutica imunossupressora, obtendo assim, uma redução na morbimortalidade e proporcionando uma sobrevida prolongada.