Multidrug-resistant HIV viral rebound during early syphilis: a case report

Background Syphilis has been associated with an increase in HIV RNA and a temporary decline in CD4 T cell counts in people living with HIV who are not receiving antiretroviral treatment (ART), and may be associated with a transient HIV RNA rebound in those who are receiving ART. Our case is the first to highlight the risk of a multidrug-resistant HIV viral rebound during the course of early syphilis even if antiretroviral drug concentrations are within the therapeutic range. Case presentation This 50-year-old HIV-1-positive male patient with concomitant early syphilis presented with an HIV RNA rebound (8908 copies/mL) during a scheduled visit to our clinic. He was receiving a stable ART regimen consisting of darunavir/cobicistat plus dolutegravir, and had a 15-year history of viral suppression. Good short-term drug adherence could be inferred as liquid chromatography tandem mass spectrometry showed that his trough antiretroviral drug concentrations were within the therapeutic range: darunavir 2353 ng/mL (minimum effective concentration > 500 ng/mL) and dolutegravir 986 ng/mL (minimum effective concentration > 100 ng/mL). A plasma RNA genotype resistance test revealed wild-type virus in the integrase region and protease region (PR), but extensive resistance in the reverse transcriptase (RT) region (M41L, E44D, D67N, K70R, M184V, L210W and T215Y). Phylogenetic analysis of next-generation sequences (used to investigate the presence of minor viral variants), the PR and RT sequences from plasma HIV RNA and pro-viral DNA extracted from peripheral blood mononuclear cells during the viral rebound, and a Sanger sequence obtained during a previous virological failure suggested clonal viral expression because the previous PR resistance mutations had been lost or had not been archived in pro-viral DNA. Conclusions This case shows that early syphilis may cause an HIV RNA rebound in patients under stable virological control with the potential of transmitting an extensively drug-resistant virus

Hand Rehabilitation and Telemonitoring through Smart Toys

We describe here a platform for autonomous hand rehabilitation and telemonitoring of young patients. A toy embedding the electronics required to sense fingers pressure in different grasping modalities is the core element of this platform. The system has been realized following the user-centered design methodology taking into account stakeholder needs from start: clinicians require reliable measurements and the ability to get a picture remotely on rehabilitation progression; children have asked to interact with a pleasant and comfortable object that is easy to use, safe, and rewarding. These requirements are not antithetic, and considering both since the design phase has allowed the realization of a platform reliable to clinicians and keen to be used by young children

Favorable therapeutic response with an antiretroviral salvage regimen in an HIV-1-positive subject infected with a CRF11-cpx virus

HIV drug resistance still represents a crucial problem in antiretroviral therapy. We report a case of a naive patient, harboring a CRF11-cpx virus, which showed drug resistance mutations in the reverse transcriptase. Drug resistance genotyping test was performed for pol (protease, reverse transcriptase, and integrase) and V3 regions. The initial clinical parameters results showed a 4 logs level of HIV-RNA (12,090 cp/mL) and a very low CD4+ cell count (35 cells/\ub5L). We designed an initial HAART regimen including 3TC+ABC+DRV/r. The virus resulted highly resistant to all NRTIs and NNRTIs except to ABC, TDF, and EFV and susceptible to all PIs and INIs. A salvage regimen including RAL+DRV/r was started. Ten months after, the immuno-virological status shows CD4+ 142/\ub5L and HIV-RNA <37 cp/mL. Our results demonstrate the effectiveness of a treatment combination that includes RAL+DRV/r in a patient infected with a complex X4-tropic CRF11-cpx virus

The interactions of Cobalt(II) with mitochondria from rat liver

The interactions of Co2+ with mitochondria have been investigated. The results indicate that Co2+ inhibits ATP synthesis. Further investigations into ATP synthesis mechanisms indicated that inhibition is due to the opening of a transmembrane pore. The opening of this pore causes the collapse of the high-energy intermediate where, under a pH and a potential gradient, the energy is stored and subsequently utilized to form ATP from ADP

Bidirectional fluxes of spermine across the mitochondrial membrane.

The polyamine spermine is transported into the mitochondrial matrix by an electrophoretic mechanism having as driving force the negative electrical membrane potential (DW). The presence of phosphate increases spermine uptake by reducingDpH and enhancingDW. The transport system is a specific uniporter constituted by a protein channel exhibiting two asymmetric energy barriers with the spermine binding site located in the energy well between the two barriers. Although spermine transport is electrophoretic in origin, its accumulation does not follow the Nernst equation for the presence of an efflux pathway. Spermine efflux may be induced by different agents, such as FCCP, antimycin A and mersalyl, able to completely or partially reduce theDWvalue and, consequently, suppress or weaken the force necessary to maintain spermine in the matrix. However this efflux may also take place in normal conditions when the electrophoretic accumulation of the polycationic polyamine induces a sufficient drop inDWable to trigger the efflux pathway. The release of the polyamine is most probably electroneutral in origin and can take place in exchange with protons or in symport with phosphate anion. The activity of both the uptake and efflux pathways induces a continuous cycling of spermine across the mitochondrial membrane, the rate of which may be prominent in imposing the concentrations of spermine in the inner and outer compartment. Thus, this event has a significant role on mitochondrial permeability transition modulation and consequently on the triggering of intrinsic apoptosis

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Multi-Squint Analysis to Separate Geometric and Atmospheric Phase Artifacts in Spaceborne InSAR

The main issue during phase calibration of spaceborne SAR system is to properly identify and separate different contributions to the interferometric phase. In this paper we suggest to exploit the Multi-Squint (MS) interferometric phase in order to remove InSAR fringes due to a linear orbital error, under the key assumption that the MS phase is very poorly affected by contributions from the atmospheric delay. Preliminary results obtained by processing TerraSAR-X stripmap data appear to confirm the validity of this assumption, and suggest that MS processing can be operationally employed for the calibration of spaceborne InSAR datastacks