Extraneous Load, Patient Census, and Patient Acuity Correlate With Cognitive Load During ICU Rounds.

BACKGROUND: Cognitive load theory asserts that learning and performance degrade when cognitive load exceeds working memory capacity. This is particularly relevant in the learning environment of ICU rounds, when multidisciplinary providers integrate complex decision-making and teaching in a noisy, high-stress environment prone to cognitive distractions. RESEARCH QUESTION: What features of ICU rounds correlate with high provider cognitive load? STUDY DESIGN AND METHODS: This was an observational, multisite study of multidisciplinary providers during ICU rounds. Investigators recorded rounding characteristics and hourly extraneous cognitive load events during rounds (defined as distractions, episodes of split-attention or repetition, and deviations from standard communication format). After rounds, investigators measured each provider's cognitive load using the provider task load (PTL), an instrument derived from the National Aeronautics and Space Administration Task Load Index survey that assesses perceived workload associated with complex tasks. Relationships between rounding characteristics, extraneous load, and PTL score were evaluated using mixed-effects modeling. RESULTS: A total of 76 providers were observed during 32 rounds from December 2020 to May 2021. The mean rounding census ± SD was 12.5 ± 2.9 patients. The mean rounding time ± SD was 2 h 17 min ± 49 min. The mean extraneous load ± SD was 20.5 ± 4.5 events per hour, or one event every 2 min 51 s. This included 8.6 ± 3.4 distractions, 8.2 ± 4.2 communication deviations, 1.9 ± 1.4 repetitions, and 1.8 ± 1.3 episodes of split-attention per hour. Controlling for covariates, the hourly extraneous load events, number of new patients, and number of higher acuity patients were each associated with increased PTL score (slope, 2.40; 95% CI, 0.76-4.04; slope, 5.23; 95% CI, 2.02-8.43; slope, 3.35; 95% CI, 1.34-5.35, respectively). INTERPRETATION: Increased extraneous load, new patients, and patient acuity were associated with higher cognitive load during ICU rounds. These results can help direct how the ICU rounding structure may be modified to reduce workload and optimize provider learning and performance.

Childcare Stress, Burnout, and Intent to Reduce Hours or Leave the Job During the COVID-19 Pandemic Among US Health Care Workers.

Importance: Childcare stress (CCS) is high during the COVID-19 pandemic because of remote learning and fear of illness transmission in health care workers (HCWs). Associations between CCS and burnout, intent to reduce (ITR) hours, and intent to leave (ITL) are not known. Objective: To determine associations between CCS, anxiety and depression, burnout, ITR in 1 year, and ITL in 2 years. Design, Setting, and Participants: This survey study, Coping with COVID, a brief work-life and wellness survey of US HCWs, was conducted between April and December 2020, assessing CCS, burnout, anxiety, depression, workload, and work intentions. The survey was distributed to clinicians and staff in participating health care organizations with more than 100 physicians. Data were analyzed from October 2021 to May 2022. Main Outcomes and Measures: The survey asked, "due to…COVID-19, I am experiencing concerns about childcare," and the presence of CCS was considered as a score of 3 or 4 on a scale from 1, not at all, to 4, a great extent. The survey also asked about fear of exposure or transmission, anxiety, depression, workload, and single-item measures of burnout, ITR, and ITL. Results: In 208 organizations, 58 408 HCWs (15 766 physicians [26.9%], 11 409 nurses [19.5%], 39 218 women [67.1%], and 33 817 White participants [57.9%]) responded with a median organizational response rate of 32%. CCS was present in 21% (12 197 respondents) of HCWs. CCS was more frequent among racial and ethnic minority individuals and those not identifying race or ethnicity vs White respondents (5028 respondents [25.2%] vs 6356 respondents [18.8%]; P < .001; proportional difference, -7.1; 95% CI, -7.8 to -6.3) and among women vs men (8281 respondents [21.1%] vs 2573 respondents [17.9%]; odds ratio [OR], 1.22; 95% CI, 1.17 to 1.29). Those with CCS had 115% greater odds of anxiety or depression (OR, 2.15; 95% CI, 2.04-2.26; P < .001), and 80% greater odds of burnout (OR, 1.80; 95% CI, 1.70-1.90; P < .001) vs indidivuals without CCS. High CCS was associated with 91% greater odds of ITR (OR, 1.91; 95% CI, 1.76 to 2.08; P < .001) and 28% greater odds of ITL (OR, 1.28; 95% CI, 1.17 to 1.40; P < .001). Conclusions and Relevance: In this survey study, CCS was disproportionately described across different subgroups of HCWs and was associated with anxiety, depression, burnout, ITR, and ITL. Addressing CCS may improve HCWs' quality of life and HCW retention and work participation.

Synthesis and biological evaluation of tetrahydroisoquinoline-derived antibacterial compounds.

Antibiotic resistance is one of the greatest threats to modern medicine. Drugs that were once routinely used to treat infections are being rendered ineffective, increasing the demand for novel antibiotics with low potential for resistance. Here we report the synthesis of 18 novel cationic tetrahydroisoquinoline-triazole compounds. Five of the developed molecules were active against S. aureus at a low MIC of 2-4 µg/mL. Hit compound 4b was also found to eliminate M. tuberculosis H37Rv at MIC of 6 µg/mL. This potent molecule was found to eliminate S. aureus effectively, with no resistance observed after thirty days of sequential passaging. These results identified compound 4b and its analogues as potential candidates for further drug development that could help tackle the threat of antibiotic resistance.

Understanding Perceived Appreciation to Create a Culture of Wellness.

OBJECTIVE: To fully address physician burnout, academic medical centers need cultures that promote well-being. One observed driver of a culture of wellness is perceived appreciation. The authors identified several contributors to perceived appreciation among faculty at a large, metropolitan academic institution through use of a novel survey. METHODS: The authors surveyed clinical faculty in five departments: psychiatry, emergency medicine, internal medicine, thoracic surgery, and radiology. Two open-ended response questions assessed sources of perceived and lack of perceived appreciation in narrative form. The authors also collected data on gender and department identity. Grounded theory methodology was used to analyze the narrative responses and design thinking to brainstorm specific recommendations based on the main themes identified. RESULTS: A total of 179 faculty respondents filled out the survey for an overall response rate of 29%. Major drivers of perceived appreciation were patient and families (42%); physician, trainee and non-physician colleagues (32.7%); chairs (10%); and compensation (3.3%). Major drivers of perceived lack of appreciation were disrespect for time and skill level, including inadequate staffing (30%); devaluation by a physician colleague, chief of one's service or the chair (29%); poor communication and transparency (13%); and patient and family anger (6%). CONCLUSIONS: Opportunities to improve perceived appreciation include structured communication of patient gratitude, community building programs, top of licensure initiatives and accountability for physician wellness, and inclusivity efforts from organizational leaders.

Synthesis and biological evaluation of 3,5-substituted pyrazoles as possible antibacterial agents.

The emergence of multi-drug resistant bacteria has increased the need for novel antibiotics to help overcome what may be considered the greatest threat to modern medicine. Here we report the synthesis of fifteen novel 3,5-diaryl-1H- pyrazoles obtained via one-pot cyclic oxidation of a chalcone and hydrazine-monohydrate. The synthesised pyrazoles were then screened against Staphylococcus aureus and Escherichia coli to determine their antibacterial potential. The results show that compound 7p is bacteriostatic at MIC 8 µg/mL. The compound is non-toxic against healthy mammalian cells, 3T3-L1 at the highest test concentration 50 µg/mL. Furthermore, compound 7p significantly affected bacterial morphogenesis before cell lysis in Bacillus subtilis when treated above the MIC concentration. From the results, a promising lead compound was identified for future development.

Contributors to Gender Differences in Burnout and Professional Fulfillment: A Survey of Physician Faculty.

BACKGROUND: This study was conducted to describe gender differences in physician burnout and professional fulfillment and to explore their potential contributors. METHODS: This was a single-center, cross-sectional survey study of physician faculty at Brigham and Women's Hospital, an academic medical center in Boston. The population included all physician faculty who practiced clinical medicine in 2017 (n = 2,388). The study was conducted using the Stanford Physician Wellness Survey. Burnout and professional fulfillment were the main outcome measures assessed. Other variables assessed included ratings of culture of wellness, personal resilience, and efficiency of practice factors associated with physician experience. RESULTS: The study population consisted of 1,066 faculty, of whom 46.4% were female and 59.8% were younger than 50. Female physicians reported significantly higher rates of burnout (42.4% vs. 34.4%, p = 0.01) and lower rates of professional fulfillment (35.1% vs. 50.4%, p < 0.01) than male physicians. Female physicians reported lower ratings for self-compassion and multiple culture of wellness factors. After adjusting for demographic factors and academic rank, the study team identified multiple culture of wellness factors (perceived appreciation, schedule control, work environment diversity and inclusion) and self-compassion as attenuating the significant relationship between gender and burnout. Only perceived appreciation attenuated the significant relationship between gender and professional fulfillment. CONCLUSION: This study demonstrated higher rates of burnout and lower rates of professional fulfillment among female vs. male physician faculty. Culture of wellness factors and self-compassion may contribute to gender differences in burnout and professional fulfillment and potentially represent modifiable targets for efforts seeking to eliminate gender disparities in physicians' workplace experiences.

Contingency planning for health care worker masks in case of medical supply chain failure: Lessons learned in novel mask manufacturing from COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic placed unprecedented strain on the medical supply chain. Early in the pandemic, uncertainty regarding personal protective equipment (PPE) was high. Protecting health care workers from contracting illness is critical to preserve trust and workforce capacity. METHODS: We describe an initiative to design and manufacture a novel, re-usable, half-face respirator in case conventional medical supply chain failed to meet demand. It required new collaboration between the hospital, physicians, the medical school, and the school of engineering. We describe organizational priorities, constraints, and process of design, testing and approval as the health system engaged for the first time directly with the design and manufacturing process for PPE. RESULTS: An original mask design was developed, and the University Hospital had an initial batch of this novel mask manufactured during the first wave of the SARS-COV-2 pandemic. These masks, and the die necessary to produce more, are in reserve in case of depletion of stores of conventionally sourced PPE. CONCLUSIONS: The COVID-19 pandemic demonstrated fragility of medical supply chain. Organizations considering similar efforts should anticipate constraints on raw material supply chain and be flexible, adaptive, and fast. The incident command structure was vital to identifying priority areas needing alternative approaches, creating connections, and providing rapid approvals. We found organizational value in demonstrating commitment to assuring PPE supplies for health care worker safety.

Factors affecting the production and measurement of hydrogen peroxide in honey samples.

Many Australian native honeys possess significant antimicrobial properties due to the production of hydrogen peroxide (H2O2) by glucose oxidase, an enzyme derived from the honeybee. The level of H2O2 produced in different honey samples is highly variable, and factors governing its production and stability are not well understood. In this study, highly active Australian honeys that had been stored for >10 years lost up to 54 % of their antibacterial activity, although almost all retained sufficient activity to be considered potentially therapeutically useful. We used a simple colourimetric assay to quantify H2O2 production. Although we found a significant correlation between H2O2 production and antibacterial activity across diverse honey samples, variation in H2O2 only explained 47 % of the variation observed in activity, limiting the assay as a screening tool and highlighting the complexity of the relationship between H2O2 and the killing power of honey. To further examine this, we tested whether H2O2 detection in honey was being inhibited by pigmented compounds and if H2O2 might be directly degraded in some honey samples. We found no correlation between H2O2 detection and honey colour. Some honey samples rapidly lost endogenous and spiked H2O2, suggesting that components in honey, such as catalase or antioxidant polyphenols, may degrade or quench H2O2. Despite this rapid loss of H2O2, these honeys had significant peroxide-based antibacterial activity, indicating a complex relationship between H2O2 and other honey components that may act synergistically to augment activity.

A newly identified prophage-encoded gene, ymfM, causes SOS-inducible filamentation in Escherichia coli.

Rod-shaped bacteria such as Escherichia coli can regulate cell division in response to stress, leading to filamentation, a process where cell growth and DNA replication continues in the absence of division, resulting in elongated cells. The classic example of stress is DNA damage which results in the activation of the SOS response. While the inhibition of cell division during SOS has traditionally been attributed to SulA in E. coli, a previous report suggests that the e14 prophage may also encode an SOS-inducible cell division inhibitor, previously named SfiC. However, the exact gene responsible for this division inhibition has remained unknown for over 35 years. A recent high-throughput over-expression screen in E. coli identified the e14 prophage gene, ymfM, as a potential cell division inhibitor. In this study, we show that the inducible expression of ymfM from a plasmid causes filamentation. We show that this expression of ymfM results in the inhibition of Z ring formation and is independent of the well characterised inhibitors of FtsZ ring assembly in E. coli, SulA, SlmA and MinC. We confirm that ymfM is the gene responsible for the SfiC phenotype as it contributes to the filamentation observed during the SOS response. This function is independent of SulA, highlighting that multiple alternative division inhibition pathways exist during the SOS response. Our data also highlight that our current understanding of cell division regulation during the SOS response is incomplete and raises many questions regarding how many inhibitors there actually are and their purpose for the survival of the organism.Importance:Filamentation is an important biological mechanism which aids in the survival, pathogenesis and antibiotic resistance of bacteria within different environments, including pathogenic bacteria such as uropathogenic Escherichia coli Here we have identified a bacteriophage-encoded cell division inhibitor which contributes to the filamentation that occurs during the SOS response. Our work highlights that there are multiple pathways that inhibit cell division during stress. Identifying and characterising these pathways is a critical step in understanding survival tactics of bacteria which become important when combating the development of bacterial resistance to antibiotics and their pathogenicity.

Inhibition of Dermatophyte Fungi by Australian Jarrah Honey.

Superficial dermatophyte infections, commonly known as tineas, are the most prevalent fungal ailment and are increasing in incidence, leading to an interest in alternative treatments. Many floral honeys possess antimicrobial activity due to high sugar, low pH, and the production of hydrogen peroxide (H2O2) from the activity of the bee-derived enzyme glucose oxidase. Australian jarrah (Eucalyptus marginata) honey produces particularly high levels of H2O2 and has been found to be potently antifungal. This study characterized the activity of jarrah honey on fungal dermatophyte species. Jarrah honey inhibited dermatophytes with minimum inhibitory concentrations (MICs) of 1.5-3.5% (w/v), which increased to ≥25% (w/v) when catalase was added. Microscopic analysis found jarrah honey inhibited the germination of Trichophyton rubrum conidia and scanning electron microscopy of mature T. rubrum hyphae after honey treatment revealed bulging and collapsed regions. When treated hyphae were stained using REDOX fluorophores these did not detect any internal oxidative stress, suggesting jarrah honey acts largely on the hyphal surface. Although H2O2 appears critical for the antifungal activity of jarrah honey and its action on fungal cells, these effects persisted when H2O2 was eliminated and could not be replicated using synthetic honey spiked with H2O2, indicating jarrah honey contains agents that augment antifungal activity.

The Burden of Opioid-Related Adverse Drug Events on Hospitalized Previously Opioid-Free Surgical Patients.

OBJECTIVE: Opioid analgesics are a mainstay for acute pain management, but postoperative opioid administration has risks. We examined the prevalence, risk factors, and consequences of opioid-related adverse drug events (ORADEs) in a previously opioid-free surgical population. METHODS: A retrospective, observational, cohort study using administrative, billing, clinical, and medication administration data from two hospitals. Data were collected for all adult patients who were opioid-free at admission, underwent surgery between October 1, 2015, and September 30, 2016, and received postoperative opioids. Potential ORADEs were determined based on inpatient billing codes or postoperative administration of naloxone. We determined independent predictors of ORADE development using multivariable logistic regression. We measured adjusted inpatient mortality, hospital costs, length of hospital stay, discharge destination, and readmission within 30 days for patients with and without ORADEs. RESULTS: Among 13,389 hospitalizations where opioid-free patients had a single qualifying surgery, 12,218 (91%) received postoperative opioids and comprised the study cohort. Of these, we identified 1111 (9.1%) with a potential ORADE. Independent predictors of ORADEs included older age, several markers of disease severity, longer surgeries, and concurrent benzodiazepine use. Opioid-related adverse drug events were strongly associated with the route and duration of opioids administered postoperatively: 18% increased odds per day on intravenous opioids. In analyses adjusted for several covariates, presence of an ORADE was associated with 32% higher costs of hospitalization, 45% longer postoperative length of stay, 36% lower odds of discharge home, and 2.2 times the odds of death. CONCLUSIONS: We demonstrate a high rate and severe consequences of potential ORADEs in previously opioid-free patients receiving postoperative opioids. Knowledge of risk factors and predictors of ORADEs can help develop targeted interventions to minimize the development of these potentially dangerous and costly events.

Cataloguing the small RNA content of honey using next generation sequencing.

Honey adulteration is a problem that effects the global honey industry and specifically, has been discovered in the Australian market. Common methods of adulteration include dilution with sugar syrup substitutes and the mislabelling of the floral and geographic origin(s) of honey. Current authentication tools rely on the molecular variability between different honeys, identifying unique chemical profiles and/or DNA signatures characteristic of a particular honey. Honey is known to contain plant miRNAs derived from its floral source. To explore the composition and variability of honey RNA molecules, this is the first study to catalogue the small RNA content of Australian polyfloral table honey and New Zealand Leptospermum scoparium honey using next generation sequencing. The data shows that in addition to miRNAs, honey contains a variety of small non-coding RNAs including tRNA-derived fragments. Moreover, the honey small RNAs are derived from a range of phylogenetic sources, including from plant, invertebrate, and prokaryotic species. The data indicates that different honeys contain unique small RNA profiles, which suggests a novel avenue in developing molecular-based honey authentication tools.

Physician Task Load and the Risk of Burnout Among US Physicians in a National Survey.

BACKGROUND: Cognitive task load can affect providers' ability to perform their job well and may contribute to burnout. METHODS: The researchers evaluated whether task load, measured by the National Aeronautics and Space Administration (NASA) Task Load Index (TLX), correlated with burnout scores in a large national study of US physicians between October 2017 and March 2018 with a 17.1% response rate. Burnout was measured using the Emotional Exhaustion and Depersonalization scales of the Maslach Burnout Inventory, and a high score on either score was considered a manifestation of professional burnout. The NASA-TLX was chosen to evaluate physician task load (PTL) due to its robust validation and use across many industries, including health care, over the past 30 years. The domains included in the PTL were mental, physical, and temporal demands, and perception of effort. RESULTS: Mean score in task load dimension varied by specialty. In aggregate, high emotional exhaustion, depersonalization, and one symptom of burnout was seen in 38.8%, 27.4%, and 44.0% of participants, respectively. The mean PTL score was 260.9/400 (standard deviation = 71.4). The specialties with the highest PTL score were emergency medicine, urology, anesthesiology, general surgery subspecialties, radiology, and internal medicine subspecialties. A dose response relationship between PTL and burnout was observed. For every 40-point (10%) decrease in PTL there was 33% lower odds of experiencing burnout (odds ratio = 0.67, 95% confidence interval = 0.65-0.70, p < 0.0001). CONCLUSION: The relationship between PTL and burnout may suggest areas of particular focus to improve the practice environment and reduce physician burnout.

Perceived Electronic Health Record Usability as a Predictor of Task Load and Burnout Among US Physicians: Mediation Analysis.

BACKGROUND: Electronic health record (EHR) usability and physician task load both contribute to physician professional burnout. The association between perceived EHR usability and workload has not previously been studied at a national level. Better understanding these interactions could give further information as to the drivers of extraneous task load. OBJECTIVE: This study aimed to determine the relationship between physician-perceived EHR usability and workload by specialty and evaluate for associations with professional burnout. METHODS: A secondary analysis of a cross-sectional survey of US physicians from all specialties was conducted from October 2017 to March 2018. Among the 1250 physicians invited to respond to the subsurvey analyzed here, 848 (67.8%) completed it. EHR usability was assessed with the System Usability Scale (SUS; range: 0-100). Provider task load (PTL) was assessed using the mental demand, physical demand, temporal demand, and effort required subscales of the National Aeronautics and Space Administration Task Load Index (range: 0-400). Burnout was measured using the Maslach Burnout Inventory. RESULTS: The mean scores were 46.1 (SD 22.1) for SUS and 262.5 (SD 71.7) for PTL. On multivariable analysis adjusting for age, gender, relationship status, medical specialty, practice setting, hours worked per week, and number of nights on call per week, physician-rated EHR usability was associated with PTL, with each 1-point increase in SUS score (indicating more favorable) associated with a 0.57-point decrease in PTL score (P<.001). On mediation analysis, higher SUS score was associated with lower PTL score, which was associated with lower odds of burnout. CONCLUSIONS: A strong association was observed between EHR usability and workload among US physicians, with more favorable usability associated with less workload. Both outcomes were associated with the odds of burnout, with task load acting as a mediator between EHR usability and burnout. Improving EHR usability while decreasing task load has the potential to allow practicing physicians more working memory for medical decision making and patient communication.

Rapid Antibacterial Activity of Cannabichromenic Acid against Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) has proven to be an imminent threat to public health, intensifying the need for novel therapeutics. Previous evidence suggests that cannabinoids harbour potent antibacterial activity. In this study, a group of previously inaccessible phytocannabinoids and synthetic analogues were examined for potential antibacterial activity. The minimum inhibitory concentrations and dynamics of bacterial inhibition, determined through resazurin reduction and time-kill assays, revealed the potent antibacterial activity of the phytocannabinoids against gram-positive antibiotic-resistant bacterial species, including MRSA. One phytocannabinoid, cannabichromenic acid (CBCA), demonstrated faster and more potent bactericidal activity than vancomycin, the currently recommended antibiotic for the treatment of MRSA infections. Such bactericidal activity was sustained against low-and high-dose inoculums as well as exponential- and stationary-phase MRSA cells. Further, mammalian cell viability was maintained in the presence of CBCA. Finally, microscopic evaluation suggests that CBCA may function through the degradation of the bacterial lipid membrane and alteration of the bacterial nucleoid. The results of the current study provide encouraging evidence that cannabinoids may serve as a previously unrecognised resource for the generation of novel antibiotics active against MRSA.

Characterizing the Mechanism of Action of an Ancient Antimicrobial, Manuka Honey, against Pseudomonas aeruginosa Using Modern Transcriptomics.

Manuka honey has broad-spectrum antimicrobial activity, and unlike traditional antibiotics, resistance to its killing effects has not been reported. However, its mechanism of action remains unclear. Here, we investigated the mechanism of action of manuka honey and its key antibacterial components using a transcriptomic approach in a model organism, Pseudomonas aeruginosa We show that no single component of honey can account for its total antimicrobial action, and that honey affects the expression of genes in the SOS response, oxidative damage, and quorum sensing. Manuka honey uniquely affects genes involved in the explosive cell lysis process and in maintaining the electron transport chain, causing protons to leak across membranes and collapsing the proton motive force, and it induces membrane depolarization and permeabilization in P. aeruginosa These data indicate that the activity of manuka honey comes from multiple mechanisms of action that do not engender bacterial resistance.IMPORTANCE The threat of antimicrobial resistance to human health has prompted interest in complex, natural products with antimicrobial activity. Honey has been an effective topical wound treatment throughout history, predominantly due to its broad-spectrum antimicrobial activity. Unlike traditional antibiotics, honey-resistant bacteria have not been reported; however, honey remains underutilized in the clinic in part due to a lack of understanding of its mechanism of action. Here, we demonstrate that honey affects multiple processes in bacteria, and this is not explained by its major antibacterial components. Honey also uniquely affects bacterial membranes, and this can be exploited for combination therapy with antibiotics that are otherwise ineffective on their own. We argue that honey should be included as part of the current array of wound treatments due to its effective antibacterial activity that does not promote resistance in bacteria.

The novel E. coli cell division protein, YtfB, plays a role in eukaryotic cell adhesion.

Characterisation of protein function based solely on homology searches may overlook functions under specific environmental conditions, or the possibility of a protein having multiple roles. In this study we investigated the role of YtfB, a protein originally identified in a genome-wide screen to cause inhibition of cell division, and has demonstrated to localise to the Escherichia coli division site with some degree of glycan specificity. Interestingly, YtfB also shows homology to the virulence factor OapA from Haemophilus influenzae, which is important for adherence to epithelial cells, indicating the potential of additional function(s) for YtfB. Here we show that E. coli YtfB binds to N'acetylglucosamine and mannobiose glycans with high affinity. The loss of ytfB results in a reduction in the ability of the uropathogenic E. coli strain UTI89 to adhere to human kidney cells, but not to bladder cells, suggesting a specific role in the initial adherence stage of ascending urinary tract infections. Taken together, our results suggest a role for YtfB in adhesion to specific eukaryotic cells, which may be additional, or complementary, to its role in cell division. This study highlights the importance of understanding the possible multiple functions of proteins based on homology, which may be specific to different environmental conditions.