The Persistence of HIV Diversity, Transcription, and Nef Protein in Kaposi's Sarcoma Tumors during Antiretroviral Therapy.

Epidemic Kaposi's sarcoma (KS), defined by co-infection with Human Herpes Virus 8 (HHV-8) and the Human Immunodeficiency Virus (HIV), is a major cause of mortality in sub-Saharan Africa. Antiretroviral therapy (ART) significantly reduces the risk of developing KS, and for those with KS, tumors frequently resolve with ART alone. However, for unknown reasons, a significant number of KS cases do not resolve and can progress to death. To explore how HIV responds to ART in the KS tumor microenvironment, we sequenced HIV env-nef found in DNA and RNA isolated from plasma, peripheral blood mononuclear cells, and tumor biopsies, before and after ART, in four Ugandan study participants who had unresponsive or progressive KS after 180-250 days of ART. We performed immunohistochemistry experiments to detect viral proteins in matched formalin-fixed tumor biopsies. Our sequencing results showed that HIV diversity and RNA expression in KS tumors are maintained after ART, despite undetectable plasma viral loads. The presence of spliced HIV transcripts in KS tumors after ART was consistent with a transcriptionally active viral reservoir. Immunohistochemistry staining found colocalization of HIV Nef protein and tissue-resident macrophages in the KS tumors. Overall, our results demonstrated that even after ART reduced plasma HIV viral load to undetectable levels and restored immune function, HIV in KS tumors continues to be transcriptionally and translationally active, which could influence tumor maintenance and progression.

A Plan for Emergency Shutdown and Reopening for a Consortium of Biobanks.

Background: The AIDS and Cancer Specimen Resource (ACSR) is a network of four regional biospecimen repositories and a technical core in the United States and South Africa. Its mission is to acquire, store, and distribute HIV-associated malignancy specimens and related clinical data to support translational research. At the outset of the COVID-19 pandemic, it became apparent that existing ACSR Standard Operating Procedures (SOPs) were not sufficient to ensure long-term maintenance and integrity of inventories during periods of extended shutdown. The ACSR needed an administrative SOP for situations pertaining to epidemics/pandemics. The ACSR Quality Working Group (QWG), comprised of representatives from each of the five ACSR sites and an external member who directs a large university medical center biorepository, addressed the issue. Methods: To understand the individual problems the sites faced, questions were developed to query each of the six QWG sites' contingency plans to cover this type of emergency, the amount of work allowed onsite and by whom, the challenges sites experienced, and the lessons learned to assist with future similar situations, while remaining consistent with the existing IRB protocols. Results: Reported challenges spanned all activities of classical biobanks and differed within the geographical locations of the sites and the local COVID-19 infection rate. Review of the responses to the questions revealed that the general shutdown of society external to the biorepositories presented them with a homogeneous collection of problems, limitations, and needs. This led to creating an SOP that addresses planning for pandemic emergencies, scaling down of activities, shutting down, and reopening plans. Conclusions: The ACSR QWG sites now have a structured response SOP for their sites, including guidance on how to develop and implement an emergency shutdown and reopening plan. The complete SOP is publicly available on the ACSR website.

Graphene Oxide: An All-in-One Processing Additive for 3D Printing.

Many 3D printing technologies are based on the development of inks and pastes to build objects through droplet or filament deposition (the latter also known as continuous extrusion, robocasting, or direct ink writing). Controlling and tuning rheological behavior is key for successful manufacturing using these techniques. Different formulations have been proposed, but the search continues for approaches that are clean, flexible, robust and that can be adapted to a wide range of materials. Here, we show how graphene oxide (GO) enables the formulation of water-based pastes to print a wide variety of materials (polymers, ceramics, and steel) using robocasting. This work combines flow and oscillatory rheology to provide further insights into the rheological behavior of suspensions combining GO with other materials. Graphene oxide can be used to manipulate the viscoelastic response, enabling the formulation of pastes with excellent printing behavior that combine shear thinning flow and a fast recovery of their elastic properties. These inks do not contain other additives, only GO and the material of interest. As a proof of concept, we demonstrate the 3D printing of additive-free graphene oxide structures as well as polymers, ceramics, and steel. Due to its amphiphilic nature and 2D structure, graphene oxide plays multiple roles, behaving as a dispersant, viscosifier, and binder. It stabilizes suspensions of different powders, modifies the flow and viscoelasticity of materials with different chemistries, particle sizes and shapes, and binds the particles together, providing green strength for manual handling. This approach enables printing complex 3D ceramic structures using robocasting with similar properties to alternative formulations, thus demonstrating the potential of using 2D colloids in materials manufacturing.

Seasonality of primary care utilization for respiratory diseases in Ontario: a time-series analysis.

BACKGROUND: Respiratory diseases represent a significant burden in primary care. Determining the temporal variation of the overall burden of respiratory diseases on the health care system and their potential causes are keys to understanding disease dynamics in populations and can contribute to the rational management of health care resources. METHODS: A retrospective, cross-sectional time series analysis was used to assess the presence and strength of seasonal and temporal patterns in primary care visits for respiratory diseases in Ontario, Canada, for a 10-year period from January 1, 1992 to December 31, 2002. Data were extracted from the Ontario Health Insurance Plan database for people who had diagnosis codes for chronic obstructive pulmonary disease, asthma, pneumonia, or upper respiratory tract infections. RESULTS: The results illustrate a clear seasonal pattern in visits to primary care physicians for all respiratory conditions, with a threefold increase in visits during the winter. Age and sex-specific rates show marked increases in visits of young children and in female adults. Multivariate time series methods quantified the interactions among primary care visits, and Granger causality criterion test showed that the respiratory syncytial virus (RSV) and influenza virus influenced asthma (p = 0.0060), COPD (p = 0.0038), pneumonia (p = 0.0001), and respiratory diseases (p = 0.0001). CONCLUSION: Primary care visits for respiratory diseases have clear predictable seasonal patterns, driven primarily by viral circulations. Winter visits are threefold higher than summer troughs, indicating a short-term surge on primary health service demands. These findings can aid in effective allocation of resources and services based on seasonal and specific population demands.

Localized purpura associated with lamotrigine.

Antiepileptic drug hypersensitivity syndrome consists of fever, rash, and internal organ involvement and usually occurs within the first 2 months of initiation of therapy. This report describes a 13-year-old female with a right frontal high-grade glioma and complex partial seizures who developed localized purpura after 23 months of lamotrigine monotherapy. This case study is the second report of localized purpura after prolonged lamotrigine treatment suggesting this may be an atypical lamotrigine-induced drug reaction.

Time series analysis of age related cataract hospitalizations and phacoemulsification.

BACKGROUND: Cataract surgery remains a commonly performed elective surgical procedure in the aging and the elderly. The purpose of this study was to utilize time series methodology to determine the temporal and seasonal variations and the strength of the seasonality in age-related (senile) cataract hospitalizations and phacoemulsification surgeries. METHODS: A retrospective, cross-sectional time series analysis was used to assess the presence and strength of seasonal and temporal patterns of age-related cataract hospitalizations and phacoemulsification surgeries from April 1, 1991 to March 31, 2002. Hospital admission rates for senile cataract (n = 70,281) and phacoemulsification (n = 556,431) were examined to determine monthly rates of hospitalization per 100,000 population. Time series methodology was then applied to the monthly aggregates. RESULTS: During the study period, age-related cataract hospitalizations in Ontario have declined from approximately 40 per 100,000 to only one per 100,000. Meanwhile, the use of phacoemulsification procedures has risen dramatically. The study found evidence of biannual peaks in both procedures during the spring and autumn months, and summer and winter troughs. Statistical analysis revealed significant overall seasonal patterns for both age-related cataract hospitalizations and phacoemulsifications (p < 0.01). CONCLUSION: This study illustrates the decline in age-related cataract hospitalizations in Ontario resulting from the shift to outpatient phacoemulsification surgery, and demonstrates the presence of biannual peaks (a characteristic indicative of seasonality), in hospitalization and phacoemulsification during the spring and autumn throughout the study period.