Like-minded sources on Facebook are prevalent but not polarizing.

Many critics raise concerns about the prevalence of 'echo chambers' on social media and their potential role in increasing political polarization. However, the lack of available data and the challenges of conducting large-scale field experiments have made it difficult to assess the scope of the problem1,2. Here we present data from 2020 for the entire population of active adult Facebook users in the USA showing that content from 'like-minded' sources constitutes the majority of what people see on the platform, although political information and news represent only a small fraction of these exposures. To evaluate a potential response to concerns about the effects of echo chambers, we conducted a multi-wave field experiment on Facebook among 23,377 users for whom we reduced exposure to content from like-minded sources during the 2020 US presidential election by about one-third. We found that the intervention increased their exposure to content from cross-cutting sources and decreased exposure to uncivil language, but had no measurable effects on eight preregistered attitudinal measures such as affective polarization, ideological extremity, candidate evaluations and belief in false claims. These precisely estimated results suggest that although exposure to content from like-minded sources on social media is common, reducing its prevalence during the 2020 US presidential election did not correspondingly reduce polarization in beliefs or attitudes.

Dermatology medications with the highest cost burden on Medicare Part D: Potential implications of the Inflation Reduction Act.

Signed into law in August 2022, the Inflation Reduction Act includes provisions requiring the federal government to negotiate prices for medications covered under Medicare Part D. Initial negotiations will target drugs with the highest total spending and price increases relative to inflation. In this study, we identify dermatology prescriptions with the highest cost burden on Medicare Part D and analyze recent trends in total spending and unit costs.

Bilateral epidural D-wave monitoring during resection of an eccentric cervical astrocytoma with evidence of asymmetrical corticospinal desynchronization.

BACKGROUND AND IMPORTANCE: The surgical management of intramedullary spinal cord tumours (IMSCT) poses inherent risk to neurologic function. Direct-wave (D-wave) monitoring is routinely reported to be a robust prognostic measure of spinal cord function via midline recording within the epidural or intradural space in a cranial-caudal montage. We explored the feasibility of bilateral epidural D-wave monitoring with routine evoked potentials in promoting safe and maximal resection in a patient with diminished midline D-wave baselines associated with an eccentric intramedullary cervical astrocytoma. CLINICAL PRESENTATION: We describe the presentation, surgical management, electrophysiological findings and post-operative outcome of a 46 year-old female patient who underwent two resections for an eccentric intramedullary cervical astrocytoma. During the first procedure we encountered clinically significant motor evoked potential signal change and discontinuation of resection pending further review. Midline D-wave signals showed no change, however peak amplitude was diminutive (7 uV) and overall morphology was characteristic of corticospinal desynchronization. Post-operatively the patient experienced significant but transient left sided weakness. A subsequent revision procedure incorporating ipsilesional and contralesional D-wave monitoring in addition to routinely incorporated evoked potentials was proposed in order to facilitate a safer resection. The ipsilesional D-wave response was considerably lower in amplitude (2.5 uV) in contrast to the contralesional D-wave (20 uV). CONCLUSION: To the authors' knowledge this is the first description of bilateral D-wave monitoring as an adjunct to cranial-caudal D-wave montages during IMSCT surgery. In patients with corticospinal desynchronization evidenced by abnormal midline D-wave morphology, bilateral D-wave monitoring in conjunction with routine evoked potentials may be clinically indicated for preservation of motor function and promotion of safe and maximal resection.

Promoting new users' online health consultation services usage behavior strategically.

Online consultation services have the potential to reduce the workload of healthcare staff, provide timely care to patients, and improve doctor-patient relationships. The COVID-19 pandemic has accelerated the development of these services and platforms, but it remains to be seen whether the general public will continue to use them after the pandemic is under control. This research proposes a framework to examine the factors contributing to UK adults' continued usage of online healthcare consultation services after COVID-19 restrictions have been lifted. A total of 430 new users completed surveys, and the results indicate that expectation confirmation, system quality, and information quality can positively impact users' self-efficacy toward using online consultation services. This, in turn, can influence their continued usage behavior. Furthermore, the results suggest that participants' perception of health risks can moderate the relationship between self-efficacy and continued usage behavior. The strategic implications of these findings are discussed.

Integrating statistical and visual analytic methods for bot identification of health-related survey data.

OBJECTIVE: In recent years, we have increasingly observed issues concerning quality of online information due to misinformation and disinformation. Aside from social media, there is growing awareness that questionnaire data collected using online recruitment methods may include suspect data provided by bots. Issues with data quality can be particularly problematic in health and/or biomedical contexts; thus, developing robust methods for suspect data identification and removal is of paramount importance in informatics. In this study, we describe an interactive visual analytics approach to suspect data identification and removal and demonstrate the application of this approach on questionnaire data pertaining to COVID-19 derived from different recruitment venues, including listservs and social media. METHODS: We developed a pipeline for data cleaning, pre-processing, analysis, and automated ranking of data to address data quality issues. We then employed the ranking in conjunction with manual review to identify suspect data and remove them from subsequent analyses. Last, we compared differences in the data before and after removal. RESULTS: We performed data cleaning, pre-processing, and exploratory analysis on a survey dataset (N = 4,163) collected using multiple recruitment mechanins using the Qualtrics survey platform. Based on these results, we identified suspect features and used these to generate a suspect feature indicator for each survey response. We excluded survey responses that did not fit the inclusion criteria for the study (n = 29) and then performed manual review of the remaining responses, triangulating with the suspect feature indicator. Based on this review, we excluded 2,921 responses. Additional responses were excluded based on a spam classification by Qualtrics (n=13), and the percentage of survey completion (n=328), resulting in a final sample size of 872. We performed additional analyses to demonstrate the extent to which the suspect feature indicator was congruent with eventual inclusion, as well as compared the characteristics of the included and excluded data. CONCLUSION: Our main contributions are: 1) a proposed framework for data quality assessment, including suspect data identification and removal; 2) the analysis of potential consequences in terms of representation bias in the dataset; and 3) recommendations for implementation of this approach in practice.

Emergency department visits associated with wildfire smoke events in California, 2016-2019.

Wildfire smoke has been associated with adverse respiratory outcomes, but the impacts of wildfire on other health outcomes and sensitive subpopulations are not fully understood. We examined associations between smoke events and emergency department visits (EDVs) for respiratory, cardiovascular, diabetes, and mental health outcomes in California during the wildfire season June-December 2016-2019. Daily, zip code tabulation area-level wildfire-specific fine particulate matter (PM2.5) concentrations were aggregated to air basins. A "smoke event" was defined as an air basin-day with a wildfire-specific PM2.5 concentration at or above the 98th percentile across all air basin-days (threshold = 13.5 µg/m3). We conducted a two-stage time-series analysis using quasi-Poisson regression considering lag effects and random effects meta-analysis. We also conducted analyses stratified by race/ethnicity, age, and sex to assess potential effect modification. Smoke events were associated with an increased risk of EDVs for all respiratory diseases at lag 1 [14.4%, 95% confidence interval (CI): (6.8, 22.5)], asthma at lag 0 [57.1% (44.5, 70.8)], and chronic lower respiratory disease at lag 0 [12.7% (6.2, 19.6)]. We also found positive associations with EDVs for all cardiovascular diseases at lag 10. Mixed results were observed for mental health outcomes. Stratified results revealed potential disparities by race/ethnicity. Short-term exposure to smoke events was associated with increased respiratory and schizophrenia EDVs. Cardiovascular impacts may be delayed compared to respiratory outcomes.

Clinical characteristics and outcome in 15 dogs treated with transsphenoidal hypophysectomy for nonfunctional sellar masses.

OBJECTIVE: To characterize the clinical features, neurological examination findings, diagnostic imaging results, histopathological findings, and outcome following transsphenoidal hypophysectomy (TSH) in dogs with nonfunctional sellar masses (NFSM). STUDY DESIGN: Multi-institutional retrospective study. METHODS: Medical records of dogs that underwent TSH for a NFSM were reviewed for clinical signs, physical and neurological examination findings, diagnostic imaging results, endocrine testing, surgery reports, and outcome. Magnetic resonance (MR) imaging was rereviewed, and tumors were classified using the previously described system according to pituitary tumor extension and vascular involvement. Owners of dogs that survived to discharge were contacted. RESULTS: The majority of dogs presented for mentation change (12/15). The mean pituitary to brain ratio (P/B ratio) was 1.05 (0.6-1.4). Eight dogs had a tumor imaging classification of 5B. Eleven dogs were diagnosed with a nonfunctional pituitary adenoma (NFPA). Perioperative mortality was 33% (5/15). The median survival for all dogs was 232 days (0-1658). When dogs that did not survive to discharge were excluded, the median survival time was 708 days. Seven of 10 dogs that survived the perioperative period received adjunctive therapy. Owner assessment of outcome was excellent (6/7) to good (1/7). CONCLUSION: The common presenting complaint for dogs with large NFSM causing mass effect was mentation changes. Dogs with NFPA that survived to discharge and received adjunctive therapy had good to excellent outcomes. CLINICAL SIGNIFICANCE: Transsphenoidal debulking with adjunctive therapy can be considered for the treatment of NFSM causing clinical signs of mass effect in dogs. Successful long-term outcomes are possible.

Examining Engagement and Usability in an Online Discussion Platform for Older Adults: Findings From Pilot Studies.

Social media may facilitate older adults' ability to engage socially and explore health information, but it can present difficulties for older adults. Therefore, it is important to explore older adults' experience of usability and user engagement. We conducted two rounds of pilot studies where we used Facebook to engage older adults. We performed a mixed-methods evaluation of user engagement and usability. A directed content analysis of qualitative data from the pilot studies was used to explore engagement and perceived usability, and the Mann-Whitney U test was used to examine differences in feature usage and engagement. We analyzed qualitative data from 13 participants. Qualitative data analysis yielded themes pertaining to three main domains: user engagement , usability , and usability related to aging-related changes . In terms of user engagement and usability, participants in both pilot studies reported positive feedback on felt involvement and endurability, and the second pilot group reported more positive comments regarding perceived usefulness compared with the first pilot group. There was no statistically significant difference in usage over the two studies. The findings of this study suggest opportunities to improve older adults' experience of online discussion platforms. Considering changes that improve perceived aesthetic appeal and focused attention will be helpful.

MRI and CT characteristics of a grade I meningioma with concurrent cribriform plate lysis in a dog.

A 6-year-old female spayed German Shepherd mixed-breed dog was presented for treatment of a frontal lobe mass diagnosed on MRI, after an acute onset of generalized seizures and behavior changes. Computed tomography of the head was performed for radiation therapy planning and revealed concurrent cribriform plate lysis without nasal sinus invasion, and focal lysis of the left ventrolateral cranial fossa. Histopathology of the mass obtained via surgical excision was consistent with a grade I fibrous meningioma. The dog had a good outcome following surgery and radiation therapy.

An algorithm for optimal testing in co-segregation analysis.

Clinical genetic sequencing tests often identify variants of uncertain significance. One source of data that can help classify the pathogenicity of variants is familial cosegregation analysis. Identifying and genotyping relatives for cosegregation analysis can be time consuming and costly. We propose an algorithm that describes a single measure of expected variant information gain from genotyping a single additional relative in a family. Then we explore the performance of this algorithm by comparing actual recruitment strategies used in 35 families who had pursued cosegregation analysis with synthetic pedigrees of possible testing outcomes if the families had pursued an optimized testing strategy instead. For each actual and synthetic pedigree, we calculated the likelihood ratio of pathogenicity as each successive test was added to the pedigree. We analyzed the differences in cosegregation likelihood ratio over time resulting from actual versus optimized testing approaches. Employing the testing strategy indicated by the algorithm would have led to maximal information more rapidly in 30 of the 35 pedigrees (86%). Many clinical and research laboratories are involved in targeted cosegregation analysis. The algorithm we present can facilitate a data driven approach to optimal relative recruitment and genotyping for cosegregation analysis and more efficient variant classification.

Initial experience using the Axonics sacral neuromodulation system in patients with multiple sclerosis.

INTRODUCTION: Sacral neuromodulation (SNM) is third-line therapy approved for urge urinary incontinence (UUI) and urgency, and nonobstructive urinary retention. Multiple sclerosis (MS) patients often suffer from neurogenic lower urinary tract dysfunction (NLUTD). The utility of SNM in the MS population is limited by magnetic resonance imaging (MRI) incompatibility as routine MRIs to evaluate for disease progression are required. The Axonics System is the first Food and Drug Administration-approved SNM device that is 1.5/3 T full-body MRI-conditionally safe. This study seeks to investigate the symptomatic improvement in MS patients after implantation of the Axonics System. METHODS: All MS patients who elected for Axonics SNM from December 2019 to January 2021 were included. Demographics and scores were queried for urogenital distress inventory (UDI-6), incontinence impact questionnaire (IIQ-7), and global response assessment (GRA). RESULTS: Fifteen MS patients with UUI were included. The time to follow-up averaged 121 days. On UDI-6, 12 patients reported improvement, 1 worsening, and 2 no change. Average UDI-6 scores before and after implantation were 56.6 and 25.2 (p < 0.0001). Improvements were significant for all questions under stress urinary incontinence, UUI, and voiding difficulty subcategories. On IIQ-7, 14 patients reported improvement and 1 reported worsening. Average IIQ-7 scores before and after implantation were 59.0 and 22.2 (p < 0.001). Improvements were significant for travel, social, and emotional subcategories, but not for physical activity. The average GRA score was 6 ("moderately improved"). CONCLUSION: The majority of MS patients reported significant initial improvement in UUI and associated quality of life measures on validated questionnaires after implantation of the Axonics System. Future studies are needed to determine the long-term outcomes and durability of this MRI full-body conditionally-safe system.

Urodynamic autonomic bladder dysfunction in women with complex chronic pelvic pain is associated with small fiber polyneuropathy.

AIMS: Small fiber neuropathy/polyneuropathy (SFN) has been found to be present in 64% of complex (refractory or multisystem) chronic pelvic pain (CPP) patients. The small fiber dysfunction seen in SFN can negatively impact autonomic control of micturition in addition to pain. This study investigated the clinical association of autonomic dysfunction (detrusor underactivity and primary bladder neck obstruction [BNO]) on video urodynamics (VUDS) with SFN in patients with CPP. METHODS: This was a retrospective observational study, querying data from patients with complex CPP. Inclusion criteria were: the presence of complex (refractory or multisystem) CPP, and completion of both (1) subspecialty autonomic neurology evaluation for SFN and (2) high-quality VUDS performed according to ICS standards. Autonomic bladder dysfunction (BNO or detrusor underactivity) on VUDS was compared to the presence of SFN. RESULTS: Thirty-two female patients with complex CPP met criteria. Of the 32, 23 (72%) were found to have SFN. Patient with autonomic bladder dysfunction (BNO or detrusor underactivity) were more likely to have SFN (OR = 9.5 [95% CI: 1.641, 55.00], p = 0.007). Post-void residual volume was higher in the SFN group (p = 0.011 [95% CI: 13.12, 94.0]) and symptoms of urge urinary incontinence were more likely to be present (p = 0.000 [95% CI: -3.4, -1.25]). CONCLUSIONS: Patients with complex CPP with autonomic bladder dysfunction are more likely to have SFN. This suggests patients with complex CPP should be considered for diagnosis and treatment of SFN, particularly if BNO or detrusor underactivity is noted on VUDS evaluation.

A Review of Mentorship in Urology: Are We Satisfied?

PURPOSE OF REVIEW: To evaluate the state of mentorship in the field of urology. RECENT FINDINGS: Mentorship has been shown to decrease burnout, increase recruitment of underrepresented minority groups, and have a positive influence on the career trajectory of mentees. Approximately half of surgical residency programs have mentorship programs. The current literature supports the idea that formal mentorship programs are successful based on level 1 satisfaction scores. However, studies are sparse and of low quality. Mentorship program success is rarely objectively measured. Structured mentorship programs appear to be beneficial, but require serious planning, evaluation, and ongoing support without which the programs can fail. Future research should be focused on objective and measurable metrics of success.

Characterizing uncertainty in goals-of-care discussions among black and white patients: a qualitative study.

BACKGROUND: Uncertainty has been associated with distress and poorer quality of life in patients with advanced cancer. Prior studies have focused on prognostic uncertainty; little is known about other types of uncertainty that patients and family members experience when discussing goals of care. Understanding the types of uncertainty expressed and differences between Black and White patients can inform the development of uncertainty management interventions. METHODS: This study sought to characterize the types of uncertainty expressed by Black and White patients and family members within the context of information needs during inpatient goals-of-care discussions. We performed a secondary analysis of transcripts from 62 recorded goals-of-care discussions that occurred between 2012 and 2014 at an urban, academic medical center in the United States. We applied an adapted taxonomy of uncertainty to data coded as describing information needs and used an inductive qualitative analysis method to analyze the discussions. We report the types of uncertainty expressed in these discussions. RESULTS: Fifty discussions included patient or family expressions of information needs. Of these, 40 discussions (n=16 Black and n=24 White) included statements of uncertainty. Black and White patients and families most frequently expressed uncertainty related to processes and structures of care (system-centered uncertainty) and to treatment (scientific uncertainty). Statements of prognostic uncertainty focused on quantitative information among Whites and on qualitative information and expectations for the future among Blacks. CONCLUSIONS: Black and White patients and families frequently expressed system-centered uncertainty, suggesting this may be an important target for intervention. Addressing other sources of uncertainty, such as prognostic uncertainty, may need more tailored approaches.

Behavioral Change Factors and Retention in Web-Based Interventions for Informal Caregivers of People Living With Dementia: Scoping Review.

BACKGROUND: Web-based interventions aimed at supporting informal caregivers of people living with dementia have the potential to improve caregivers' well-being and psychological health. However, few interventions are widely implemented for this population, and none of the prior reviews have systematically examined the use of behavior change techniques (BCTs), theories, and agents in web-based interventions for informal caregivers of people living with dementia. To better understand this implementation gap, we reviewed the literature to map behavioral factors (BCTs, theories, and agents) deployed in the studies. Furthermore, because there is an emerging consensus that retention could be shaped by participant characteristics and behavioral factors, we explored relationships between these features and retention rates across studies. OBJECTIVE: We pursued 3 objectives: to map behavioral factors involved in the web-based interventions for informal caregivers of people living with dementia; to examine the relationship between behavioral change elements and retention in the studies; and to examine the relationship between participant characteristics (gender, age, and spouse or adult children caregiver proportion) and study retention. METHODS: We conducted a literature review using the following keywords and their corresponding Medical Subject Headings terms: dementia, caregivers, and web-based intervention. The time limits were January 1998 to March 2022. Using the BCTv1 taxonomy, which specifies active behavioral components in interventions, 2 coders collected, summarized, and analyzed the frequency distributions of BCTs. Similarly, they abstracted and analyzed participant characteristics, behavior change theories, behavior change agents, and retention rates in the studies. RESULTS: The average age was 61.5 (SD 7.4) years, and the average proportion of spousal informal caregivers, adult children informal caregivers, and retention rates were 51.2% (SD 24.8%), 44.8% (SD 22%), and 70.4% (SD 17%), respectively. Only 53% (17/32) of the studies used behavior change theories, but 81% (26/32) included behavior change agents. The most common BCTv1 clusters were shaping knowledge and social support. The median number of BCTv1 clusters was 5 (IQR 3). We observed a negative correlation between the proportion of spousal informal caregivers and the retention rate (r=-0.45; P=.02) and between the number of BCTv1 clusters and retention rates (r=-0.47; P=.01). We also found that the proportion of adult children informal caregivers in the study was significantly and positively correlated with the retention rate (r=0.5; P=.03). No other participant characteristics or behavioral factors were associated with retention rates. CONCLUSIONS: We found that almost half of the studies were not informed by behavior change theories. In addition, spousal involvement and a higher number of BCTs were each associated with lower retention rates, while the involvement of adult children caregivers in the study was associated with higher retention. In planning future studies, researchers should consider matching participant characteristics with their intended intervention as the alignment might improve their retention rates.

Depressive Symptoms among US Adults during the Great Recession and Economic Recovery.

BACKGROUND AND AIMS: We study the trajectory of depressive symptoms among US adults before, during, and after the 2008/2009 Great Recession. METHODS: We use repeated cross-sectional surveys of the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2018. Mental health is assessed with the Patient Health Questionnaire-9 (PHQ-9), with the following categorization for depressive symptoms: none or mild (score 0-9), moderate or severe (score 10-27). A parallel time series was calculated from the Behavioral Risk Factor Surveillance System (BRFSS) on self-reported number of days with poor mental health. RESULTS: NHANES data show a statistically significant increase in depressive symptoms from 2005/2006 to 2007/2008 (the beginning of the Great Recession), but there were no significant or consistent changes after 2007/2008. In particular, the deterioration in the adjusted predicted PHQ-9 scores occurred prior to the large increase in unemployment rate (2009/2010). As the macroeconomic situations improved and unemployment rates recovered, mental health did not return to the previous level. In the latest wave of NHANES (2017/2018), unemployment rates were at the lowest level over the analysis period; however, the adjusted predicted PHQ-9 scores were higher than that at the beginning of the Great Recession. Trends of PHQ-9 scores were similar across income groups - all groups had an increase in depressive symptoms after 2005/2006 and PHQ-9 scores were still high in 2017/2018 after controlling for sociodemographic status. Group with the lowest income had higher levels of depressive symptoms at every time point. BRFSS data shows no consistent changes in the number of days with poor mental health that parallel economic conditions. DISCUSSION: Depressive symptoms at the population level did not match the economic cycle before, during and after the Great Recession. Future research is needed to better understand the lack of correlation between population mental health and macroeconomic conditions.

Cranial and vertebral osteosarcoma commonly has T2 signal heterogeneity, contrast enhancement, and osteolysis on MRI: A case series of 35 dogs.

Magnetic resonance imaging (MRI) is commonly used to evaluate the central nervous system (CNS) in dogs; however, published studies describing the MRI appearance of cranial and vertebral osteosarcoma are scarce. In this multicenter, retrospective, case series study, MRI studies of 35 dogs with cranial or vertebral osteosarcoma were prospectively scored by consensus of two veterinary radiologists. Recorded characteristics were location, signal intensity (compared to gray matter), homogeneity, contrast enhancement, margin delineation, local invasion, osteolysis, osteosclerosis, zone of transition, periosteal proliferation, pathological fracture, meningeal/CNS involvement, and presence of metastatic disease. Locations included the parietal bone (n = 1), occipital bone (n = 2), or cervical (n = 5), thoracic (n = 17), lumbar (n = 7), or sacral vertebrae (n = 3). Common features included signal heterogeneity in T2-weighted (T2W) images (n = 35), contrast enhancement (in all 34 dogs with postcontrast MRI), osteolysis (n = 34), compression of the CNS or cauda equina (n = 33), an associated soft tissue mass (n = 33), a long zone of transition (n = 30), osteosclerosis (n = 28), signal isointensity to normal-appearing gray matter in T1-weighted images (T1W, n = 26), and T2W hyperintensity of adjacent brain or spinal cord (n = 23). Other findings included periosteal proliferation (n = 18), meningeal contrast enhancement (n = 17), T1W and T2W hypointense foci in the soft tissue mass (n = 14), invasion into adjacent bones (n = 10), pathological vertebral fractures (n = 7), regional lymphadenopathy (n = 6), skip metastases (n = 2), lung nodule (n = 1), diaphragmatic nodule (n = 1), and brain invasion (n = 1). Contrast enhancement was typically strong and heterogeneous. Magnetic resonance imaging features of cranial and vertebral osteosarcoma were analogous to those previously reported for other imaging modalities. Osteosarcoma should be a differential diagnosis for compressive, contrast-enhancing, osteolytic lesions of the cranium or vertebrae.

The use of visual methods to support communication with older adults with cognitive impairment: A scoping review.

Older adults with cognitive impairment often face difficulties with comprehension and communication, which can impact other cognitive processes such as decision-making. This scoping review investigates how visual methods can support older adults with cognitive impairment. The review involved querying four databases. From these databases, eleven articles fit inclusion criteria. This paper examines the purposes, use contexts, types, and effectiveness of the visual methods described in each study. The two major use contexts were elicitation of thoughts, feelings, and preferences in everyday life and health/healthcare related uses. Studies that used visual methods for eliciting preferences generally employed static visualizations. Health-related contexts employed more complex and interactive visualizations. Three studies used visual tools to support older adults in understanding; six, communication; and three, decision-making. None addressed all three outcomes of interest. This study provides recommendations and future directions for visual communication research with older adults with cognitive impairment.

Effects of Regulatory Network Organization and Environment on PmrD Connector Activity and Polymyxin Resistance in Klebsiella pneumoniae and Escherichia coli.

Polymyxins are a class of cyclic peptides with antimicrobial activity against Gram-negative bacteria. In Enterobacteriaceae, the PhoQ/PhoP and PmrB/PmrA two-component systems regulate many genes that confer resistance to both polymyxins and host antimicrobial peptides. The activities of these two-component systems are modulated by additional proteins that are conserved across Enterobacteriaceae, such as MgrB, a negative regulator of PhoQ, and PmrD, a "connector" protein that activates PmrB/PmrA in response to PhoQ/PhoP stimulation. Despite the conservation of many protein components of the PhoQ/PhoP-PmrD-PmrB/PmrA network, the specific molecular interactions and regulatory mechanisms vary across different genera. Here, we explore the role of PmrD in modulating this signaling network in Klebsiella pneumoniae and Escherichia coli We show that in K. pneumoniae, PmrD is not required for polymyxin resistance arising from mutation of mgrB-the most common cause of spontaneous polymyxin resistance in this bacterium-suggesting that direct activation of polymyxin resistance genes by PhoQ/PhoP plays a critical role in this resistance pathway. However, for conditions of low pH or intermediate iron concentrations, both of which stimulate PmrB/PmrA, we find that PmrD does contribute to resistance. We further show that in E. coli, PmrD functions as a connector between PhoQ/PhoP and PmrB/PmrA, in contrast with previous reports. In this case, activity also depends on PmrB/PmrA stimulation, or on very high activation of PhoQ/PhoP. Our results indicate that the importance of the PmrD connector in modulating the polymyxin resistance network depends on both the network organization and on the environmental conditions associated with PmrB stimulation.