This study aimed to address knowledge gaps related to the prevention and management of mental health responses among those with a condition that presents risk of severe COVID-19 infection. A scoping review that mapped English and Chinese-language studies (2019–2020) located in MEDLINE (Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo, Sociological Abstracts, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Airiti Library was undertaken. Search terms related to COVID-19, mental health, and physical health were used and articles that included all three of these factors were extracted (n = 77). With the exception of one hospital-based pilot study, there were no intervention studies targeting mental health in those at risk of severe COVID-19 infection. Promising practices such as integrated care models that appropriately screen for mental health issues, address health determinants, and include use of digital resources were highlighted. Patient navigator programs, group online medical visits, peer support, and social prescribing may also support those with complex needs. Future policies need to address digital health access inequities and the implementation of multi-integrated health and social care. Furthermore, research is needed to comprehensively assess multi-integrated interventions that are resilient to public health crises.

Bacteria produce a variety of nucleotide second messengers to adapt to their surroundings. Although chemically similar, the nucleotides guanosine penta- and tetraphosphate [(p)ppGpp] and adenosine penta- and tetraphosphate [(p)ppApp] have distinct functions in bacteria. (p)ppGpp mediates survival under nutrient-limiting conditions and its intracellular levels are regulated by synthetases and hydrolases belonging to the RelA-SpoT homolog (RSH) family of enzymes. By contrast, (p)ppApp is not known to be involved in nutrient stress responses and is synthesized by RSH-resembling toxins that inhibit the growth of bacterial cells. However, it remains unclear whether there exists a family of hydrolases that specifically act on (p)ppApp to reverse its toxic effects. Here, we present the structure and biochemical characterization of adenosine 3′-pyrophosphohydrolase 1 (Aph1), the founding member of a monofunctional (p)ppApp hydrolase family of enzymes. Our work reveals that Aph1 adopts a histidine-aspartate (HD)-domain fold characteristic of phosphohydrolase metalloenzymes and its activity mitigates the growth inhibitory effects of (p)ppApp-synthesizing toxins. Using an informatic approach, we identify over 2,000 putative (p)ppApp hydrolases that are widely distributed across bacterial phyla and found in diverse genomic contexts, and we demonstrate that 12 representative members hydrolyze ppApp. In addition, our in silico analyses reveal a unique molecular signature that is specific to (p)ppApp hydrolases, and we show that mutation of two residues within this signature broadens the specificity of Aph1 to promiscuously hydrolyze (p)ppGpp in vitro. Overall, our findings indicate that like (p)ppGpp hydrolases, (p)ppApp hydrolases are widespread in bacteria and may play important and underappreciated role(s) in bacterial physiology.

Type VI secretion systems (T6SSs) are cell envelope‐spanning protein complexes that Gram‐negative bacteria use to inject a diverse arsenal of antibacterial toxins into competitor cells. Recently, Wang et al. reported that the H2‐T6SS of Pseudomonas aeruginosa delivers the peptidoglycan recycling amidase, AmpDh3, into the periplasm of recipient cells where it is proposed to act as a peptidoglycan degrading toxin. They further reported that PA0808, the open reading frame downstream of AmpDh3, encodes an immunity protein that localizes to the periplasm where it binds to and inactivates intercellularly delivered AmpDh3, thus protecting against its toxic activity. Given that AmpDh3 has an established role in cell wall homeostasis and that no precedent exists for cytosolic enzymes moonlighting as T6SS effectors, we attempted to replicate these findings. We found that cells lacking PA0808 are not susceptible to bacterial killing by AmpDh3 and that PA0808 and AmpDh3 do not physically interact in vitro or in vivo. Additionally, we found no evidence that AmpDh3 is exported from cells, including by strains with a constitutively active H2‐T6SS. Finally, subcellular fractionation experiments and a 1.97 Å crystal structure reveal that PA0808 does not contain a canonical signal peptide or localize to the correct cellular compartment to confer protection against a cell wall targeting toxin. Taken together, these results cast doubt on the assertion that AmpDh3‐PA0808 constitutes an H2‐T6SS effector–immunity pair.

Tau and beta-amyloid in Alzheimer’s disease: Theories, treatments strategies, and future directions

As undergraduate students in a Health Sciences Program we were selected as teaching assistants (TAs) in a freshman introductory Cellular and Molecular Biology course that we had all taken in a standard format. The course was tightly focused on cell communication (Adv Physiol Educ 36: 13–19, 2012, Biochem Mol Biol Educ. 2013 May‐Jun;41(3):145‐55). The new version was offered synchronously on‐line to 273 students who were in different time zones (within Canada and abroad, Africa, Asia). Didactic sessions (both flipped/non‐flipped) were followed by TA sessions (60‐90 mins.) designed to help students consolidate content and prepare them for active assessments used (The FASEB Journal, 31: 575.2‐575.2.). Each tutorial Group had on the average, twenty students. For the tutorials, we met them in virtual break‐out rooms where we had considerable flexibility to organize our sessions. Larger groups were reconvened to meet the instructors either on the same day or on a separate session. These sessions served to further consolidate their learning. In addition, we had the options of organizing office hours on our own to deal with our students. We were taking several of our own on‐line courses in parallel. These dual obligations as teachers in one course and learners for several others posed many challenges. As teachers, we had to foster engagement, promote interactions, gauge comprehension, maintain enthusiasm, identify individual learning needs despite lack of verbal, non‐verbal cues as many students remained both silent and invisible and also deal with technical glitches. To prepare for our own courses we faced similar technical issues, maintained enthusiasm, battled online fatigue, engaged with our Professors and TAs, dealt with conflicting schedules, found resources, remained flexible, and stayed focused as the lack of a distinct campus environment blurred boundaries between home and academia. We adapted rapidly to cope with these concurrent contrary demands.