Tuberculosis is the leading killer among infectious diseases worldwide. Increasing multidrug resistance has prompted new approaches for tuberculosis drug development, including targeted inhibition of virulence determinants and of signaling cascades that control many downstream pathways. We used a multisystem approach to determine the effects of a potent small-molecule inhibitor of the essential Mycobacterium tuberculosis Ser/Thr protein kinases PknA and PknB. We observed differential levels of phosphorylation of many proteins and extensive changes in levels of gene expression, protein abundance, cell wall lipids, and intracellular metabolites. The patterns of these changes indicate regulation by PknA and PknB of several pathways required for cell growth, including ATP synthesis, DNA synthesis, and translation. These data also highlight effects on pathways for remodeling of the mycobacterial cell envelope via control of peptidoglycan turnover, lipid content, a SigE-mediated envelope stress response, transmembrane transport systems, and protein secretion systems. Integrated analysis of phosphoproteins, transcripts, proteins, and lipids identified an unexpected pathway whereby threonine phosphorylation of the essential response regulator MtrA decreases its DNA binding activity. Inhibition of this phosphorylation is linked to decreased expression of genes for peptidoglycan turnover, and of genes for mycolyl transferases, with concomitant changes in mycolates and glycolipids in the cell envelope. These findings reveal novel roles for PknA and PknB in regulating multiple essential cell functions and confirm that these kinases are potentially valuable targets for new antituberculosis drugs. In addition, the data from these linked multisystems provide a valuable resource for future targeted investigations into the pathways regulated by these kinases in the M. tuberculosis cell.

Objective: To identify the environmental factors essential for infection control in senior-living facilities. Background: In the COVID-19 pandemic, older adults are more likely to be infected and develop serious outcomes than young people. Worldwide, senior-living facilities face a battle to protect their residents. Compared with age-related declines, the built environment is more modifiable and can be used for infection control. Methods: This research conducted content analysis of the guidelines on COVID-19 control issued by the State Council of China in February 2020 for senior-living facilities. Six senior-living facility managers in China were interviewed and shared their experiences using these guidelines. Quantitative and qualitative analyses were conducted to identify the essential environmental factors for infection control. Results: Environmental factors suggested in the guidelines were analyzed for three groups of infection-control strategies: keep COVID-19 from entering the facility, prevent COVID-19 spread in the facility, and manage infection and illness. Key topics of experience using the guidelines were identified, including residents’ needs for social interaction and the difficulties of providing dedicated air-conditioning and circulation systems. Based on these analyses, from the perspective of environmental design, environmental factors essential for COVID-19 control in senior-living facilities were summarized at the site, building, and room levels. Conclusion: Proper planning and design of the built environment promote strategies for infection control in senior-living facilities. Findings can be used to guide the new design, renovation, and modification of senior-living facilities for COVID-19 control and future public health emergencies.

More than 50% of cancer patients receive chemotherapy by infusion, which is typically delivered in ambulatory healthcare settings. Influences of the built environment on inpatient care are well documented, but environmental research focusing on ambulatory healthcare is lacking. This empirical research focuses on cancer infusion environments and reveals important patient needs linking the built environment to infusion care. A survey of 166 patients and observations of 252 patients were conducted in an academic cancer center to explore patient preferences on private, semiopen, or open environments for infusion treatment and the reasons for their preferences. The observations investigated patient interactions with the environments during infusion treatment. Findings from qualitative and quantitative data analyses showed that private, semiopen, or open spaces were generally equally popular among patient participants. Needs for high-level privacy, quiet places to nap or sleep, social interaction, patient-nurse access, sunshine, and views to the outside were identified as major reasons for patient preferences. Items important to patients during treatment included patient chair tablets, guest chairs, personal televisions, nap blankets, food or beverages, window views, and sunshine. Participants with access to positive window views reported significantly lower levels of stress and greater hope for successful treatment than their counterparts (p < .05). Findings suggest that important environmental features of ambulatory healthcare settings are both similar to and different from that of inpatient environments in the way they significantly impact the quality and experience of care.

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Multiple types of treatment environments should be provided in chemotherapy care to incorporate varied user needs. Privacy, social interaction, patient-nurse access, and access to nature should be considered during the design of environments for cancer chemotherapy.