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Background Cytochrome bd complexes are respiratory oxidases found exclusively in prokaryotes that are important during infection for numerous bacterial pathogens. Methods In silico docking was employed to screen approved drugs for their ability to bind to the quinol site of Escherichia coli cytochrome bd -I. Respiratory inhibition was assessed with oxygen electrodes using membranes isolated from E. coli and methicillin-resistant Staphylococcus aureus strains expressing single respiratory oxidases (ie, cytochromes bd , bo ′, or aa 3). Growth/viability assays were used to measure bacteriostatic and bactericidal effects. Results The steroid drugs ethinylestradiol and quinestrol inhibited E. coli bd -I activity with median inhibitory concentration (IC50) values of 47 ± 28.9 µg/mL (158 ± 97.2 µM) and 0.2 ± 0.04 µg/mL (0.5 ± 0.1 µM), respectively. Quinestrol inhibited growth of an E. coli " bd -I only" strain with an IC50 of 0.06 ± 0.02 µg/mL (0.2 ± 0.07 µM). Growth of an S. aureus " bd only" strain was inhibited by quinestrol with an IC50 of 2.2 ± 0.43 µg/mL (6.0 ± 1.2 µM). Quinestrol exhibited potent bactericidal effects against S. aureus but not E. coli. Conclusions Quinestrol inhibits cytochrome bd in E. coli and S. aureus membranes and inhibits the growth of both species, yet is only bactericidal toward S. aureus. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is one of the greatest threats to human health. Gram-positive methicillin resistant Staphylococcus aureus (MRSA), in both its planktonic and biofilm form, is of particular concern. Herein we identify the hydrogelation properties for a series of intrinsically fluorescent, structurally related supramolecular self-associating amphiphiles and determine their efficacy against both planktonic and biofilm forms of MRSA. To further explore the potential translation of this hydrogel technology for real-world applications, the toxicity of the amphiphiles was determined against the eukaryotic multicellular model organism, Caenorhabditis elegans. Due to the intrinsic fluorescent nature of these supramolecular amphiphiles, material characterisation of their molecular self-associating properties included; comparative optical density plate reader assays, rheometry and widefield fluorescence microscopy. This enabled determination of amphiphile structure and hydrogel sol dependence on resultant fibre formation. [ABSTRACT FROM AUTHOR]

Objective Acculturation has been linked to health outcomes in Hispanics/Latinos (H/Ls). However, there is equivocal evidence of a relationship between acculturation and neuropsychological outcomes. Various factors limit the ability to subject the evidence to systematic/meta-analytic review. We sought to examine the current state of the literature in the context of H/Ls and neuropsychology and describe the various limitations of measuring acculturation across the lifespan. Method Applying a scoping review approach, we identified unique stand-alone (e.g. questionnaires) measures of acculturation. We focused on psychometric (e.g. internal consistency) and other characteristics (e.g. language, structure/format) and description of the validation samples (e.g. cultural background/country of origin). Results A total of 40 unique acculturation measures were identified. Measures spanned various domains (e.g. language proficiency, food preference, music choice), and relied heavily on linguistic behavioral characteristics. Internal consistency varied from unacceptable to clinically acceptable ranges. Variable approaches to development and validation were reported. Validation samples varied from 22 to 2,048 respondents (median = 380), most of which represented a general adult population. Only eight measures were validated for use in pediatric populations; none were developed specifically for use with older adults. Conclusions Published measures are outdated, evidence highly variable psychometric and methodological weaknesses, and lack a lifespan perspective. Several themes in the types of items considered elemental to the acculturative process are revealed and findings are summarized via an "ABC" framework, categorizing items as antecedents, behaviors, and consequent acculturative changes, that lends itself to clinical and research settings. [ABSTRACT FROM AUTHOR]

Objective To assemble a comprehensive neuropsychological battery appropriate for differential diagnosis of dementia in Farsi-speaking Iranian adults in the United States. Method Systematic searches of PubMed, PsychInfo, and Google Scholar databases were conducted to obtain test instruments relevant to Farsi speakers in consultation with a Farsi-speaking cultural broker. Results A proposed battery assessing the domains of attention, executive function, verbal and visual episodic memory, language, visuospatial/visuoconstruction abilities, and mood/anxiety was assembled that includes core measures developed, either specifically for a Farsi-speaking Iranian population or validated/normed with a Farsi-speaking Iranian sample. Though not ideal, additional measures were selected that can be administered using translated instructions with English normative data to supplement the limited tests available for use in this population. The rationale for test selection and caveats for their clinical use are presented along with a case study. Conclusions The number of neuropsychological measures available in Farsi and/or with normative data for Farsi speakers is extremely limited. Cognitive tests either developed for or validated with a bilingual Farsi-English sample also represent a significant gap in the literature. Appropriate measures for these populations are urgently needed to provide a culturally competent assessment of a growing older adult segment of an underserved community. [ABSTRACT FROM AUTHOR]

Objective A brain health equity neuropsychology research framework (NRF) is crucial to the anti-racist movement in cognitive assessments. Universalist interpretation of neuropsychological tools contributes to systemic disparities, and there is a need for a clear conceptual framework for disentangling the direct and indirect impact of social determinants of health (SDH) on brain-behavior relationships and neuropsychological performance. The aim of this paper is to present a NRF anchored in the principles of brain health and health equity that is inclusive, and can be implemented across racially and ethnically diverse communities. Methods The Re-engaging Individuals and societies for Structural Evolution (RISE) NRF aims to address this via a two-pronged approach: 1. Focusing on community engagement and recruitment and retention of individuals and societies typically not equitably represented in brain health studies, and 2. Integrating the conceptual structure of individual, community, and SDH, while considering the broader historical and current structures that differentially shape these. Results The proposed RISE NRF is dynamic and multidirectional. It identifies barriers and proposes strategies to engage communities and diversify recruitment. It identifies evidence-based guidance on non-cognitive determinants of health to include, consider or explore in brain health research. Conclusion The RISE NRF can guide the development of culturally and linguistically responsive methodologies and assist with clearly conceptualized and contextualized interpretation of neuropsychological tools to foment a transformative science that benefits the brain health of marginalized communities. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are cytotoxic lymphocytes that accumulate within the tumor microenvironment and are generally considered to be antitumorigenic. Using single-cell RNA sequencing and functional analysis of multiple triple-negative breast cancer (TNBC) and basal tumor samples, we observed a unique subcluster of Socs3highCD11b−CD27− immature NK cells that were present only in TNBC samples. These tumor-infiltrating NK cells expressed a reduced cytotoxic granzyme signature and, in mice, were responsible for activating cancer stem cells through Wnt signaling. NK cell–mediated activation of these cancer stem cells subsequently enhanced tumor progression in mice, whereas depletion of NK cells or Wnt ligand secretion from NK cells by LGK-974 decreased tumor progression. In addition, NK cell depletion or inhibition of their function improved anti–programmed cell death ligand 1 (PD-L1) antibody or chemotherapy response in mice with TNBC. Furthermore, tumor samples from patients with TNBC and non-TNBC revealed that increased numbers of CD56bright NK cells were present in TNBC tumors and were correlated to poor overall survival in patients with TNBC. Together, our findings identify a population of protumorigenic NK cells that may be exploited for both diagnostic and therapeutic strategies to improve outcomes for patients with TNBC. Immature NK cells aid cancer: Natural Killer (NK) cells are generally thought to be an effective contributor to antitumor immune responses. However, not all NK cells are created equal. Here, Thacker et al. demonstrated that Socs3highCD11b–CD27– immature NK cells were present in samples from patients with triple negative breast cancer (TNBC) and correlated with worse prognosis. The authors further showed that this population of NK cells promoted, rather than inhibited, tumor progression in mice. Depletion of this population of NK cells or inhibition of Wnt ligand secretion prevented this effect, suggesting that these immature NK cells may represent a therapeutic target for TNBC. —CM [ABSTRACT FROM AUTHOR]

Herein, we present the synthesis of two novel adamantane appended supramolecular self-associating amphiphiles. The antimicrobial efficacy of these compounds is determined against both clinically relevant Gram-positive methicillin-resistant Staphylococcus aureus and Gram-negative Escherichia coli. We also explore the self-associative properties of these amphiphiles in both polar organic DMSO-d6 0.5% H2O and H2O (D2O)/EtOH 19:1 solutions, confirming aggregate stability through the determination of zeta potential values, aggregate size through a combination of 1H NMR DOSY and dynamic light scattering studies as appropriate, and critical aggregate concentration through the derivation of concentration-dependent surface tension values. We also perform a variety of 1H NMR dilution studies and in-silico modelling to further explore the roles of intermolecular hydrogen bonding and lipophilicity within aggregate formation and antimicrobial efficacy. Finally, we perform haemolysis and Galleria mellonella toxicity assays to establish the potential of these compounds to undergo further development as antibiotic agents. [ABSTRACT FROM AUTHOR]

Objective: To investigate differences in performance on a widely used cognitive screener between community-dwelling older adults from two disparate socioeconomic groups. Participants and Methods: Participants were part of a larger study of cognitive screening in healthy older adults. The total sample (N=79, 69.6% female, 19% White/Caucasian, 12.7% Asian, 43% Latino/a, 25.3% Black/African-American) consisted of community-dwelling adults (M age=73.1 years [SD =7.2] and M education=14.3 years [SD =2.6]) who were initially recruited via social media, flyers, and general community announcements. A lack of ethnic minority participants resulted in a two-year commitment to reach communities of color via visits and provision of health literacy to local religious and community programs. Continuous contact with leaders/gatekeepers helped establish research study credibility and forge a stronger sense of trust among ethnically diverse participants in the greater Houston, TX, area. Testing was initially conducted at the clinical study site. Due to low participation rates among people of color, greater effort was placed on tailored strategies to overcome economic and time constraints (i.e., schedule/time conflicts, lack of transportation, inability to pay for parking). To fit the priorities and needs of the participants, testing was also conducted at their homes (25.3%) and nearby religious and community centers (22.8%). Participants identifying as Latino/a or Black were predominantly recruited and tested at their local community center (as requested by gatekeepers/participants) to increase access to the study, in contrast to Caucasian participants. Median income estimates were used to stratify participants by socioeconomic status (SES) based on zip codes into low SES (L-SES) or high SES (H-SES) groups. Results: Participants from the L-SES group had significantly lower total scores on the MoCA than their H-SES counterparts, t (77 J =2.837, p =0.003, g =0.696. The average MoCA total score for participants from the L-SES group was 2.64 points lower. The observed differences in MoCA total score when stratifying by ethnicity may be attributable to differences in education level and SES, which are known risk factors for cognitive impairment and will be further examined upon recruitment completion. Conclusions: Studies have found that ethnically diverse older adults not only encounter more barriers to accessing quality health care but also experience disparities in brain health research. Communities of color comprise a sizeable portion of our older adults but have been traditionally underrepresented in clinical research, limiting the generalizability of research findings to clinical treatment. Socioeconomic deprivation has been identified as one of several barriers to research engagement for people of color, placing ethnic communities at increased risk for under- or misdiagnosis and limited access to medical intervention. Preliminary findings have implications for the recruitment of ethnically diverse groups in clinical research. Given the growing racial and ethnic diversity among the United States population, we must do our due diligence to increase understanding of participation and recruitment barriers for racial/ethnic individuals. Tailored community outreach and engagement strategies may be effective in improving the inclusion of ethnically diverse populations and facilitating recruitment and retention in clinical research studies. [ABSTRACT FROM AUTHOR]

Objective: To investigate the latent factor structure and construct validity of the Verbal Series Attention Test (VSAT) across clinical patient populations. Participants and Methods: Participants included a consecutive series of clinical patients presenting with a primary memory complaint. Each patient underwent a comprehensive neuropsychological assessment and provided informed consent to allow their clinical data to be used for research. Groups formed included 1) No Neurocognitive Disorder [NoND, N=262, mean age=68.8, mean education=16.2, mean MMSE=28.3], 2) Mild Neurocognitive Disorder [MildND, N=337, mean age=72.3, mean education=15.4, mean MMSE=28.7], and 3) Major Neurocognitive Disorder [MajorND, N=524, mean age=76.5, mean education=14.5, mean MMSE=19.0] with etiologies including suspected Alzheimer's disease and/or vascular pathology. Latent factors were investigated using exploratory factor analysis (EFA). Results: EFA was conducted using SAS 9.4 software and the promax (oblique) rotation to reveal the latent factors of the eight timed items of the VSAT in each of the three clinical groups. The structure was essentially identical in all three groups with two primary factors consistently emerging identified as 1-Complex Attention and 2-Simple Attention. Each factor had four items loading with a correlation range of > 0.37 x < 0.92. The internal consistency (Cronbach's alpha) for the VSAT total score in each group was excellent (NoND a=0.83, MildND a=0.81, and MajorND a=0.84). To investigate construct validity, the VSAT items were entered into factor analysis with measures of attention and executive function (i.e., Digit Span [forward, backward, sequence], Trail Making Test A & B, semantic fluency (animals), Controlled Oral Word Association Test [COWAT, FAS]). All three patient groups were combined (N=950) given the VSAT's consistent factor structure. Using the same EFA procedure as before, two main factors emerged with the VSAT Complex Attention variables loading on a general complex attention/working memory factor including Trails B, semantic fluency, and Digit Span subtests. The VSAT Simple Attention items loaded on a general attention factor with the VSAT Simple Attention variables and Trails A. COWAT did not load significantly on either factor. Conclusions: The latent factor structure of the VSAT was consistent across patient populations with excellent internal consistency in each clinical group. The Complex and Simple Attention factors of the VSAT loaded on factors with similar variables identifying the anticipated latent factor structure demonstrating the construct validity of the VSAT across a wide spectrum of cognitive impairment in patients with primary memory complaints ranging from NoND to MajorND. This supports the use of the VSAT in patients across neurocognitive severity. Future studies will further explore additional psychometric properties of this instrument. [ABSTRACT FROM AUTHOR]

Objective: Poor mood and quality of life is common among patients with medically intractable seizures. Many of these patients are not candidates for seizure focus resection and continue to receive standard medical care. Responsive neurostimulation (RNS) has been an effective approach to reduce seizure frequency for nonsurgical candidates. Previous research using RNS clinical trial participants has demonstrated improved mood and quality of life when patients received RNS-implantation earlier in their medically resistant epilepsy work-up (Loring et al., 2021). We aimed to describe the level of depression and quality of life in adults with medical resistant epilepsy, treated with RNS, presenting to an outpatient clinic. Participants and Methods: This pilot study was conducted among 11 adult epilepsy patients treated with RNS at the epilepsy specialty clinic at Baylor College of Medicine. Ages of participants ranged from 18-56 (M=32.01, SD=12.37) with a mean education of 12.43 (SD=0.85). The majority of the participants identified as White (White=72.2%; Hispanic/Latino/a=14.3%, Other=7.1%). We also present pre- and post-RNS preliminary results of a subset of 4 patients for whom pre and post implantation data was available. Depression symptoms were assessed through the Beck Depression Inventory, 2nd Edition (BDI-II) and quality of life was determined using the Quality of Life in Epilepsy (QoLiE-31). Results: Patients reported minimal symptoms of depression (M=5.45, SD=4.03) and good overall quality of life (M=71.18, SD=14.83) after RNS. Participants' scores on their overall quality of life ranged from 50 to 95 (100=better quality of life). The QoLiE-31 showed high scores on emotional wellbeing (M=69.45, SD=14.56) and cognitive functioning (M=65.36, SD=16.66) domains. Post-hoc analysis revealed a significant difference in the cognitive functioning domain of QoLiE-31 before (M=44.75, SD=12.58) and after (M=51.0, SD=11.58) RNS implantation(t(3)=-3.78, p=0.016. Additionally, overall QoLiE score approached statistical significance when comparing pre-RNS (M=44.75 SD=9.29) to post-RNS (M=49.75 SD=11.62; t(3)=-2.01, p = 0.069). No significant differences were evident on seizure worry, energy/fatigue, medication effects, and social functioning domains of QoLiE-31 before and after RNS treatment. Conclusions: These pilot study results suggest low levels of depression with this population post-RNS implantation. Additionally, there is preliminary evidence to suggest improved patient-rated cognitive functioning and overall quality of life. While this is a small study population, the results have important implications for patients with intractable epilepsy, even with those form who surgical resection may not be possible. Future studies with large enough samples to examine moderating and mediating factors to mood and quality of life changes post-RNS will be important. [ABSTRACT FROM AUTHOR]

Background: Executive function (EF) is associated with obesity development and self‐management. Individuals who demonstrate or self‐report poorer EF performance tend to have poorer short‐term outcomes in obesity treatment. There may be distinct behavioral self‐management strategies and EF domains related to initial weight loss as compared to weight loss maintenance. Objective: To characterize EF in individuals who achieved clinically significant weight loss via behavioral intervention and examine potential differences in EF between those who maintained versus regained lost weight. Methods: Participants who previously achieved ≥5% weight loss via lifestyle intervention were included (N = 44). "Maintainers" (n = 16) maintained this minimum level of weight loss for ≥1 year. "Regainers" (n = 28) regained some or all initially lost weight. Performance‐based EF, intelligence quotient, health literacy, depression, anxiety, binge eating, demographics, and medical/weight history were assessed using a cross‐sectional design. Descriptive statistics and age‐, gender‐, education‐adjusted reference ranges were used to characterize EF. Analyses of covariance were conducted to examine EF differences between maintainers and regainers. Results: The sample consisted primarily of females with obesity over age 50. Approximately half self‐identified as African–American. Decision‐making performance was better in maintainers than regainers (p = 0.003, partη2 = 0.19). There were no differences between maintainers and regainers in inhibitory control, verbal fluency, planning/organization, cognitive flexibility, or working memory (ps > 0.05, partη2s = 0.003–0.07). At least 75% of the sample demonstrated average‐above average EF test performance, indicated by scaled scores ≥13 or t‐scores > 60. Conclusions: Most individuals with obesity who achieved clinically significant weight loss via behavioral intervention had average to above average EF. Individuals who maintained (vs. regained) their lost weight performed better on tests of decision‐making. [ABSTRACT FROM AUTHOR]

Women in rural settings are at increased risk for adverse pregnancy outcomes. One potential way to improve pregnancy outcomes in rural settings is through physical activity promotion. However, given the disparities in prenatal care, women in rural areas may not receive information from their health care provider regarding physical activity during pregnancy. Therefore, the purpose of this study was to examine patient and provider communication in a rural setting (both patients' and providers' perspectives) regarding physical activity during pregnancy. A mixed methods study was performed among patients and providers in an obstetrical practice in a rural setting. During early pregnancy, patients were asked questions about their current physical activity levels and intentions for physical activity during their pregnancy. During late pregnancy, patients completed a survey regarding communication from their obstetric provider about exercise during pregnancy. Providers responsible for the patients' prenatal care were surveyed regarding communication with patients about physical activity. Seventy-one pregnant women and five providers participated. 58.2% of patients reported their provider did not discuss physical activity during pregnancy with them at all. Meanwhile, all providers (100%) reported discussing physical activity with all of their patients. Similarly, only 21.8% of patients reported their provider discussed the benefits of exercise during pregnancy, while 100% of providers reported telling their patients about the benefits of exercise during pregnancy. Our study suggests ineffective patient-provider communication regarding physical activity during pregnancy in a rural setting. Improved communication strategies could reduce disparities in health outcomes among pregnant women in rural settings. [ABSTRACT FROM AUTHOR]