Visible-Light-Activated Molecular Machines Kill Fungi by Necrosis Following Mitochondrial Dysfunction and Calcium Overload.

Invasive fungal infections are a growing public health threat. As fungi become increasingly resistant to existing drugs, new antifungals are urgently needed. Here, it is reported that 405-nm-visible-light-activated synthetic molecular machines (MMs) eliminate planktonic and biofilm fungal populations more effectively than conventional antifungals without resistance development. Mechanism-of-action studies show that MMs bind to fungal mitochondrial phospholipids. Upon visible light activation, rapid unidirectional drilling of MMs at ≈3 million cycles per second (MHz) results in mitochondrial dysfunction, calcium overload, and ultimately necrosis. Besides their direct antifungal effect, MMs synergize with conventional antifungals by impairing the activity of energy-dependent efflux pumps. Finally, MMs potentiate standard antifungals both in vivo and in an ex vivo porcine model of onychomycosis, reducing the fungal burden associated with infection.

Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil.

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

Teleneuropsychology for Monolingual and Bilingual Spanish-Speaking Adults in the Time of COVID-19: Rationale, Professional Considerations, and Resources.

OBJECTIVE: Neuropsychological assessments with monolingual Spanish and bilingual Spanish/English-speaking adults present unique challenges. Barriers include, but are not limited to, the paucity of test norms, uncertainty about the equivalence of translated neuropsychological tests, and limited proficiency in the provision of culturally competent services. Similar issues generalize to telephone- and video-based administration of neuropsychological tests or teleneuropsychology (TeleNP) with Hispanics/Latinos (as), and few studies have examined its feasibility and validity in this group. The sudden onset of the COVID-19 pandemic prompted neuropsychologists to identify alternative ways to provide equitable care. Clinicians providing TeleNP to this population during (and after) the pandemic must consider safety, professional factors, and systemic barriers to accessing and benefitting from virtual modalities. METHOD: This clinical process manuscript describes how cross-cultural neuropsychologists across five U.S. academic institutions serving Hispanics/Latinos (as) developed TeleNP models of care during the pandemic. RESULTS: Workflows, test batteries, and resources for TeleNP assessment with monolingual and bilingual Spanish-speaking patients are included. Factors guiding model development and informing decisions to incorporate virtual administration of neuropsychological tests into their practice are also discussed. CONCLUSIONS: Provision of TeleNP is a promising modality. Additional research in this area is warranted with focus on cultural and contextual factors that support or limit the use of TeleNP with this community.

Light-based technologies for management of COVID-19 pandemic crisis.

The global dissemination of the novel coronavirus disease (COVID-19) has accelerated the need for the implementation of effective antimicrobial strategies to target the causative agent SARS-CoV-2. Light-based technologies have a demonstrable broad range of activity over standard chemotherapeutic antimicrobials and conventional disinfectants, negligible emergence of resistance, and the capability to modulate the host immune response. This perspective article identifies the benefits, challenges, and pitfalls of repurposing light-based strategies to combat the emergence of COVID-19 pandemic.