For ∼30 years, two distinct groups of clinical isolates of Klebsiella pneumoniae have been recognized. Classical strains (cKp) are typically isolated from patients with some degree of ...immunocompromise and are not virulent in mouse models of infection whereas hypervirulent strains (hvKp) are associated with community acquired invasive infections and are highly virulent in mouse models of infection. Hyperproduction of capsule and a hypermucoviscous colony phenotype have been strongly associated with the hypervirulence of hvKp strains. Recent studies have begun to elucidate the relationship between capsule gene expression, hypermucoviscosity and hypervirulence. Additionally, genes associated with hyperproduction of capsule and hypermucoviscosity in hvKp strains have been identified in a few cKp isolates. However, it is not clear how the acquisition of these genes impacts the virulence of cKp isolates. A better understanding of the potential risks of these strains is particularly important given that many of them are resistant to multiple antibiotics, including carbapenems.
The COVID-19 pandemic is shining a light on altruistic behaviors needed to prevent the spread of the virus. This short essay presents a personal experience of altruism during the COVID-19 pandemic ...and its resulting motivation to leverage it in health behavior change strategies for vaccination and other pandemic protective behaviors.
has a remarkable ability to cause a wide range of human diseases. It is divided into two broad classes: classical strains that are a notable problem in health care settings due to multidrug ...resistance, and hypervirulent (hv) strains that are historically drug sensitive but able to establish disease in immunocompetent hosts. Alarmingly, there has been an increased frequency of clinical isolates that have both drug resistance and hv-associated genes. One such gene,
, encodes a transcriptional regulator required for maximal capsule (
) gene expression and confers hypermucoviscosity (HMV). This link has resulted in the assumption that HMV is caused by elevated capsule production. However, we recently reported a new
regulator, RmpC, and Δ
mutants have reduced
expression but retain HMV, suggesting that capsule production and HMV may be separable traits. Here, we report the identification of a small protein, RmpD, that is essential for HMV but does not impact capsule. RmpD is 58 residues with a putative N-terminal transmembrane domain and highly positively charged C-terminal half, and it is conserved among other hv
strains. Expression of
in
complements both Δ
and Δ
mutants for HMV, suggesting that RmpD is the key driver of this phenotype. The
gene is located between
and
, within an operon regulated by RmpA. These data, combined with our previous work, suggest a model in which the RmpA-associated phenotypes are largely due to RmpA activating the expression of
to produce HMV and
to stimulate
expression.
Capsule is a critical virulence factor in
, in both antibiotic-resistant classical strains and hypervirulent strains. Hypervirulent strains usually have a hypermucoviscosity (HMV) phenotype that contributes to their heightened virulence capacity, but the production of HMV is not understood. The transcriptional regulator RmpA is required for HMV and also activates capsule gene expression, leading to the assumption that HMV is caused by hyperproduction of capsule. We have identified a new gene (
) required for HMV but not for capsule production. This distinction between HMV and capsule production will promote a better understanding of the mechanisms of hypervirulence, which is in great need given the alarming increase in clinical isolates with both drug resistance and hypervirulence traits.
Despite a growing understanding of the importance of provider HPV recommendation on parental acceptance, U.S. HPV vaccination rates remain suboptimal. Given the prevalence and use of the media for ...health decisions, this study examined the relationship between the media and provider HPV recommendation on maternal HPV vaccine hesitancy.
Thirty individual interviews with HPV vaccine-accepting mothers in the Midwest U.S. were conducted to examine their feelings of hesitancy around the decision to accept HPV vaccination at the time of provider recommendation and their suggestions for improving the recommendation experience by addressing media concerns.
Media exposure was an antecedent to hesitancy for three main vaccination concerns: safety, protection/efficacy and sexual stigma. Although mothers accepted vaccination, they continued to feel confused and hesitant about HPV vaccination. They had several recommendations for how providers could combat hesitancy to improve confidence in HPV vaccine acceptance.
Providers' approach to HPV vaccination recommendation must consider concerns reported in the media with delivery techniques modified to adjust to maternal fears absorbed from adverse media information.
During the COVID-19 pandemic, antivaccination social media accounts are proliferating online, threatening to further escalate vaccine hesitancy related to the COVID-19 vaccine. This commentary seeks ...to alert and encourage the health care provider community, including health care professionals and academic organizations, to engage in social media to counter the mounting vaccine-related infodemic. To validate our recommendation for engagement, the authors describe preliminary findings using a mixed methods approach of quantitative Twitter-based ranking algorithms of networks and users with qualitative content analysis of 1 million tweets related to COVID-19 vaccine conversations. Results show highly polarized and active antivaccine conversations that were primarily influenced by political and nonmedical Twitter users. In contrast, less than 10% of the tweets stemmed from the medical community, demonstrating a lack of active health care professional connectivity in addressing COVID-19 misinformation. The authors introduce the concept of Health Care Provider Social Media Hesitancy to refer to the public health threat of health care providers' nonaction in providing pro-vaccine and scientific information about the vaccine on social media. The authors conclude by describing multilevel strategies for encouraging health care providers and the medical community to effectively "Tweet up" to combat the mounting threat of vaccine misinformation and hesitancy.
Vaccine hesitancy is a top ten global health threat that can negatively impact COVID-19 vaccine uptake. It is assumed that vaccine refusers hold deep, negative beliefs, while acceptors hold strong, ...positive beliefs. However, vaccine hesitancy exists along a continuum and is multidimensional, varying by time, place, vaccine, subgroup, and person. Guided by the Health Belief Model and vaccine hesitancy frameworks, the study purpose was to qualitatively explore maternal COVID-19 threat perceptions and willingness to accept a COVID-19 vaccine in light of their expressed vaccine hesitancy toward past school required and routinely recommended vaccines and the HPV vaccine for their children. Researchers conducted twenty-five interviews with US Midwestern mothers during the early COVID-19 pandemic months. Mothers were grouped by vaccine hesitancy categories and thematic analysis was used to analyze the data within and across categories. Results showed that prior vaccine hesitancy attitudes and behavior did not fully capture maternal acceptance of COVID-19 vaccine or perception of COVID-19 threat. Perceptions of COVID-19 threat did influence mothers' decisions about COVID-19 protective behaviors (e.g., handwashing, mask wearing, and distancing). However, mothers were hesitant to accept the COVID-19 vaccine across vaccine hesitancy categories, primarily citing concerns about safety, efficacy, and confusion over conflicting information as barriers to immediate COVID-19 vaccine acceptance. Findings indicate that mothers cannot be grouped together based on hesitancy about, or acceptance of, other vaccines for purposes of assuming COVID-19 preventive behavior adherence or anticipated COVID-19 vaccine acceptance.
To examine the effectiveness of Mind Over Matter (MOM), a group psychosocial intervention based on CBT, ACT, and mind-body interventions, from data collected during a quality improvement project. MOM ...was offered in person prior to COVID-19 and via telehealth after COVID-19 began.
Distress, as measured by anxiety, depression, the severity of physical symptoms and the impact of physical symptoms on daily functioning, was measured pre- and post-MOM.
The sample included 46 participants with an experience of cancer ranging in age from 31 to 75.
Overall, there were significant differences in anxiety, depression, and physical symptom severity and interference pre and post MOM. The in-person intervention showed significant differences in anxiety, depression, and physical symptom interference. There were significant differences in anxiety and physical symptom severity reported in the telehealth groups.
MOM may be an effective psychosocial intervention for addressing cancer-related physical and emotional challenges making it a valuable resource for institutions trying to meet needs identified by distress screenings.
Parental vaccine hesitancy is a significant contributor to low adolescent HPV vaccination. Shared HPV vaccination decision-making among adolescents and parents is an important determinant of ...vaccination uptake. We performed a scoping review to identify studies that used parent-adolescent dyads in HPV vaccination research.
We searched peer-reviewed articles in PubMed, Embase, and PsychInfo from 2012 to 2023. Randomized or observational studies with parent-adolescent dyads related to HPV vaccination were eligible for inclusion. Articles were coded for the main themes related to use of parent-adolescent dyads in HPV vaccination research.
Fifteen articles met the inclusion criteria and were categorized into two main themes: qualitative decision-making and quantitative vaccination intentions. Dyad members reported substantially different roles, barriers, and facilitators of HPV vaccine decisions and intentions. Dyad members disagreed on who made the final decision. Provider recommendation style and content were important to parental confidence in the vaccine decision.
The recent evidence for parent-adolescent HPV vaccination dyad research is sparse but indicates that factors that account for dyad vaccination decisions and intentions often differ between dyad members.
Practice Implications: Studies in this review support ongoing research with parent-adolescent dyads to target HPV vaccine interventions at individual dyad members to increase HPV vaccination.
•There is minimal research with parent-adolescent dyads to understand HPV vaccination.•Dyads hold varying perceptions about facilitators of and barriers to HPV vaccination.•Providers do not always clearly communicate the HPV vaccine.•Dyad members often do not agree on who makes the final HPV vaccination decision.•Provider HPV recommendation should be aimed at both parent and adolescent concerns.
The polysaccharide capsule is an essential virulence factor for
in both community-acquired hypervirulent strains as well as health care-associated classical strains that are posing significant ...challenges due to multidrug resistance. Capsule production is known to be transcriptionally regulated by a number of proteins, but very little is known about how these proteins collectively control capsule production. RmpA and RcsB are two known regulators of capsule gene expression, and RmpA is required for the hypermucoviscous (HMV) phenotype in hypervirulent
strains. In this report, we confirmed that these regulators performed their anticipated functions in the ATCC 43816 derivative, KPPR1S:
and
mutants are HMV negative and have reduced capsule gene expression. We also identified a novel transcriptional regulator, RmpC, encoded by a gene near
The Δ
strain has reduced capsule gene expression but retains the HMV phenotype. We further showed that a regulatory cascade exists in which KvrA and KvrB, the recently characterized MarR-like regulators, and RcsB contribute to capsule regulation through regulation of the
promoter and through additional mechanisms. In a murine pneumonia model, the regulator mutants have a range of colonization defects, suggesting that they regulate virulence factors in addition to capsule. Further testing of the
and
mutants revealed that they have distinct and overlapping functions and provide evidence that HMV is not dependent on overproduction of capsule. This distinction will facilitate a better understanding of HMV and how it contributes to enhanced virulence of hypervirulent strains.
continues to be a substantial public health threat due to its ability to cause health care-associated and community-acquired infections combined with its ability to acquire antibiotic resistance. Novel therapeutics are needed to combat this pathogen, and a greater understanding of its virulence factors is required for the development of new drugs. A key virulence factor for
is the capsule, and community-acquired hypervirulent strains produce a capsule that causes hypermucoidy. We report here a novel capsule regulator, RmpC, and provide evidence that capsule production and the hypermucoviscosity phenotype are distinct processes. Infection studies showing that this and other capsule regulator mutants have a range of phenotypes indicate that additional virulence factors are in their regulons. These results shed new light on the mechanisms controlling capsule production and introduce targets that may prove useful for the development of novel therapeutics for the treatment of this increasingly problematic pathogen.
Cancer-induced immune responses affect tumour progression and therapeutic response. In multiple murine models and clinical datasets, we identified large variations of neutrophils and macrophages that ...define 'immune subtypes' of triple-negative breast cancer (TNBC), including neutrophil-enriched (NES) and macrophage-enriched subtypes (MES). Different tumour-intrinsic pathways and mutual regulation between macrophages (or monocytes) and neutrophils contribute to the development of a dichotomous myeloid compartment. MES contains predominantly macrophages that are CCR2-dependent and exhibit variable responses to immune checkpoint blockade (ICB). NES exhibits systemic and local accumulation of immunosuppressive neutrophils (or granulocytic myeloid-derived suppressor cells), is resistant to ICB, and contains a minority of macrophages that seem to be unaffected by CCR2 knockout. A MES-to-NES conversion mediated acquired ICB resistance of initially sensitive MES models. Our results demonstrate diverse myeloid cell frequencies, functionality and potential roles in immunotherapies, and highlight the need to better understand the inter-patient heterogeneity of the myeloid compartment.
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