Chlorophyllin Supplementation of Medicated or Unmedicated Swine Diets Impact on Fecal Escherichia coli and Enterococci.

Considering that certain catabolic products of anaerobic chlorophyll degradation inhibit efflux pump activity, this study was conducted to test if feeding pigs a water-soluble chlorophyllin product could affect the antibiotic resistance profiles of select wild-type populations of fecal bacteria. Trial 1 evaluated the effects of chlorophyllin supplementation (300 mg/meal) on fecal E. coli and enterococcal populations in pigs fed twice daily diets supplemented without or with ASP 250 (containing chlortetracycline, sulfamethazine and penicillin at 100, 100 and 50 g/ton, respectively). Trial 2, conducted similarly, evaluated chlorophyllin supplementation in pigs fed diets supplemented with or without 100 g tylosin/ton. Each trial lasted 12 days, and fecal samples were collected and selectively cultured at 4-day intervals to enumerate the total numbers of E. coli and enterococci as well as populations of these bacteria phenotypically capable of growing in the presence of the fed antibiotics. Performance results from both studies revealed no adverse effect (p > 0.05) of chlorophyllin, antibiotic or their combined supplementation on average daily feed intake or average daily gain, although the daily fed intake tended to be lower (p = 0.053) for pigs fed diets supplemented with tylosin than those fed diets without tylosin. The results from trial 1 showed that the ASP 250-medicated diets, whether without or with chlorophyllin supplementation, supported higher (p < 0.05) fecal E. coli populations than the non-medicated diets. Enterococcal populations, however, were lower, albeit marginally and not necessarily significantly, in feces from pigs fed the ASP 250-medicated diet than those fed the non-medicated diet. Results from trial 2 likewise revealed an increase (p < 0.05) in E. coli and, to a lesser extent, enterococcal populations in feces collected from pigs fed the tylosin-medicated diet compared with those fed the non-medicated diet. Evidence indicated that the E. coli and enterococcal populations in trial 1 were generally insensitive to penicillin or chlortetracycline, as there were no differences between populations recovered without or with antibiotic selection. Conversely, a treatment x day of treatment interaction observed in trial 2 (p < 0.05) provided evidence, albeit slight, of an enrichment of tylosin-insensitive enterococci in feces from the pigs fed the tylosin-medicated but not the non-medicated diet. Under the conditions of the present study, it is unlikely that chlorophyllin-derived efflux pump inhibitors potentially present in the chlorophyllin-fed pigs were able to enhance the efficacy of the available antibiotics. However, further research specifically designed to optimize chlorophyll administration could potentially lead to practical applications for the swine industry.

Alternative TSS use is widespread in Cryptococcus fungi in response to environmental cues and regulated genome-wide by the transcription factor Tur1.

Alternative transcription start site (TSS) usage regulation has been identified as a major means of gene expression regulation in metazoans. However, in fungi, its impact remains elusive as its study has thus far been restricted to model yeasts. Here, we first re-analyzed TSS-seq data to define genuine TSS clusters in 2 species of pathogenic Cryptococcus. We identified 2 types of TSS clusters associated with specific DNA sequence motifs. Our analysis also revealed that alternative TSS usage regulation in response to environmental cues is widespread in Cryptococcus, altering gene expression and protein targeting. Importantly, we performed a forward genetic screen to identify a unique transcription factor (TF) named Tur1, which regulates alternative TSS (altTSS) usage genome-wide when cells switch from exponential phase to stationary phase. ChiP-Seq and DamID-Seq analyses suggest that at some loci, the role of Tur1 might be direct. Tur1 has been previously shown to be essential for virulence in C. neoformans. We demonstrated here that a tur1Δ mutant strain is more sensitive to superoxide stress and phagocytosed more efficiently by macrophages than the wild-type (WT) strain.

Global cancer stigma research: a U.S. National Cancer Institute workshop report.

Stigma is a social process characterized by negative beliefs, attitudes, and stereotypes associated with a specific attribute or characteristic that leads to discrimination and social exclusion. Stigma manifests across the cancer control continuum and remains a key challenge for cancer prevention and control worldwide. In this commentary, we provide an overview of the U.S. National Cancer Institute's (NCI) Global Cancer Stigma Research Workshop, a multi-disciplinary international conference held virtually in September 2022, which focused on the intersection of cancer and stigma. The meeting was unique in its convening of researchers, advocates, clinicians, and non-governmental and governmental organizations, who-as a collective-provided overarching topics, cross-cutting considerations, and future directions for the cancer stigma research community to consider, which we describe herein. In summary, studying cancer stigma comprehensively requires a holistic, adaptive, and multifaceted approach-and should consider interrelated factors and their intersection within diverse cultural and social contexts worldwide. Collectively, there was a call for: an inclusive approach, encouraging researchers and practitioners to identify and measure cancer stigma as a driver for cancer health inequities globally; an expansion of existing research methodology to include diversity of experiences, contexts, and perspectives; and collaborations among diverse stakeholders to develop more effective strategies for reducing stigma and improving cancer outcomes. Such efforts are essential to cultivating effective and equitable approaches to preventing and treating cancer worldwide.

Disparities in Telehealth Offer and Use among U.S. Adults: 2022 Health Information National Trends Survey.

Objective: Understanding the sources of telehealth disparities can inform efforts to ensure equity. This study examines disparities in telehealth offer and use to understand the role of health care providers in increasing telehealth access. Methods: This cross-sectional analysis of the 2022 Health Information National Trends Survey (n = 5,295) used survey-weighted proportions to characterize telehealth use and multivariable logistic regressions to test associations of sociodemographic and social determinants with (1) telehealth offer and (2) use among those offered the option. Results: Among U.S. adults, 57% were offered telehealth, 80% of whom used it. Technology difficulties and privacy concerns were barriers for 15%-20% of U.S. adults. Compared to telehealth users, most nonusers preferred in-person care (25% versus 84%). Age, education, geographic location, and broadband internet access were related to telehealth offer, whereas no significant disparities emerged in telehealth use. Conclusions: Telehealth use is widespread, but structural and provider-level engagement are needed to achieve equity.

National Cancer Institute-funded grants focused on synchronous telehealth cancer care delivery: a portfolio analysis.

BACKGROUND: Telehealth use increased during the COVID-19 pandemic and remains a complementary source of cancer care delivery. Understanding research funding trends in cancer-related telehealth can highlight developments in this area of science and identify future opportunities. METHODS: Applications funded by the US National Cancer Institute (NCI) between fiscal years 2016 and 2022 and focused on synchronous patient-provider telehealth were analyzed for grant characteristics (eg, funding mechanism), cancer focus (eg, cancer type), and study features (eg, type of telehealth service). Of 106 grants identified initially, 60 were retained for coding after applying exclusion criteria. RESULTS: Almost three-quarters (73%) of telehealth grants were funded during fiscal years 2020-2022. Approximately 67% were funded through R01 or R37 mechanism and implemented as randomized controlled trials (63%). Overall, telehealth grants commonly focused on treatment (30%) and survivorship (43%); breast cancer (12%), hematologic malignancies (10%), and multiple cancer sites (27%); and health disparity populations (ie, minorities, rural residents) (73%). Both audio and video telehealth were common (65%), as well as accompanying mHealth apps (20%). Telehealth services centered on psychosocial care, self-management, and supportive care (88%); interventions were commonly delivered by mental health professionals (30%). CONCLUSION: NCI has observed an increase in funded synchronous patient-provider telehealth grants. Trends indicate an evolution of awards that have expanded across the cancer control continuum, applied rigorous study designs, incorporated additional digital technologies, and focused on populations recognized for disparate cancer outcomes. As telehealth is integrated into routine cancer care delivery, additional research evidence will be needed to inform clinical practice.

Disparities in cancer clinical trials information-seeking: Findings from the National Cancer Institute's Cancer Information Service.

OBJECTIVE: To better understand cancer clinical trials (CCT) information-seeking, a necessary precursor to patient and provider engagement with CCT. METHODS: Data from the National Cancer Institute's Cancer Information Service (CIS) were used to examine CCT information-seeking patterns over a 5-year period. Descriptive and logistic regression analyses were conducted to examine characteristics of CIS inquiries and their associations with having a CCT discussion. RESULTS: Between September 2018 - August 2023, 117,016 CIS inquiries originated from cancer survivors, caregivers, health professionals, and the general public; 27.5 % of these inquiries included a CCT discussion (n = 32,160). Among CCT discussions, 35.5 % originated from survivors, 53.5 % from caregivers, 6.1 % from the public, and 4.9 % from health professionals. Inquiries in Spanish had lower odds of a CCT discussion (OR=.26, [.25-.28]), whereas inquiries emanating from the CIS instant messaging (OR=2.29, [2.22-2.37]) and email (OR=1.24, [1.18-1.30]) platforms were associated with higher odds of discussing CCT compared to the telephone. Individuals who were male, younger, insured, and had higher income and education had significantly higher odds of a CCT discussion while those who were non-Hispanic Black and living in rural locales had significantly lower odds. CONCLUSIONS: Disparities in CCT information-seeking may contribute to downstream CCT participation. PRACTICE IMPLICATIONS: Quality, language-concordant health information is needed to enable equitable awareness of - and ultimately engagement in - CCT.

Selection for high and low antibody responses to sheep red blood cells influences cytokine and chemokine expression in chicken peripheral blood leukocytes and splenic tissue.

White Leghorn chickens from a common founder population have been divergently selected for high (HAS) or low (LAS) antibody responses to sheep red blood cells (SRBC) for 49 generations resulting in 2 diverse lines for this trait. Much has been studied in these two lines; however, the impact of these selection pressures on cytokine and chemokine expression is not fully understood. The purpose of this study is to determine if selection for antibody response to SRBC impacts cytokine and chemokine expression in peripheral blood leukocytes (PBL) and spleen from HAS and LAS chickens. Total RNA was isolated from PBL and spleen after which mRNA expression of cytokines (IL4, IL6, IL10, TGF-ß4) and chemokines (CXCL8, CCL4) were determined by quantitative real-time RT-PCR (qRT-PCR). The data were analyzed using Student's t test comparing HAS and LAS (P < 0.05) and are reported as corrected 40-CT. PBL and spleen samples were analyzed separately. With respect to PBL, expression of IL6 was higher (P < 0.05) in PBL isolated from LAS chickens compared to those from the HAS line whereas there were no differences (P > 0.05) in IL4, IL10, CXCL8, CCL4, or TGF-ß4. The cytokine and chemokine mRNA expression profiles were different in the spleen between the two lines. IL4 and CXCL8 expression were higher (P < 0.05) in spleen samples from HAS chickens than LAS. The expression of IL6, IL10, CCL4, or TGF-ß4 in the spleens did not differ (P > 0.05) between the lines. The data indicate that selection for specific antibody responses to SRBC impacts the cytokine and chemokine expression profile in PBL and spleens but in different ways in HAS and LAS. These studies provide insight into the influence that selection pressures for antibody responses have on different immune response components, specifically cytokines and chemokines typically involved in the innate response.

The kinematics of false intent Conveyed by deceptive sidestep actions.

Researchers have identified kinematic differences between deceptive and non-deceptive rugby reorientation actions. However, the honest and deceptive signals corresponded to 'deception detection' (accuracy increasing) rather than signals that caused deception (accuracy decreasing). In this study, statistical parametric mapping and multilevel modelling were applied to examine the kinematic differences between sidestep and non-deceptive actions during the time window of deception. The analysis compared three-dimensional motion capture data from 144 deceptive actions and 144 genuine actions performed by six high-skilled rugby players. Results indicated that the kinematics of deceptive actions were characterized by a combination of exaggerated head roll, outside foot and centre-of-mass displacement, and attenuated thorax roll and yaw relative to genuine actions. These are candidate sources for the cause of deception, either individually or in combination with other sources. Furthermore, the results indicate that previously identified 'honest' signals may not be reliable sources of information earlier in the action sequence.

Are alcohol-related attentional biases and holistic perception independent processes?

Excessive alcohol consumption is associated with the development of attentional biases for alcohol-related cues and their prioritization in heavy drinkers. Recently, it has been hypothesized that holistic processing may also play a role in this prioritization, with higher alcohol consumers exhibiting stronger holistic perception for alcohol cues. However, it is unclear how processing stimuli holistically may be related to attentional biases. We explored potential relationships between attentional biases, holistic processing, and alcohol consumption in a sample of drinkers using two tasks. In the first, a visual probe task replicated previous findings by showing an increased attentional bias for alcohol-related stimuli in individuals with higher alcohol consumption. Surprisingly, using an inversion paradigm to measure holistic perception in our second task, we showed reduced holistic processing for both alcohol and nonalcohol cues in higher alcohol consumers compared to light alcohol consumers. Although alcohol consumption was positively associated with attentional biases and negatively associated with holistic processing, these cognitive processes were not associated with each other. This study supports a model of visual perception in which attentional biases and holistic processing are independently linked with alcohol use. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

PARP14 is pro- and anti-viral host factor that promotes IFN production and affects the replication of multiple viruses.

PARP14 is a 203 kDa multi-domain protein that is primarily known as an ADP-ribosyltransferase, and is involved in a variety of cellular functions including DNA damage, microglial activation, inflammation, and cancer progression. In addition, PARP14 is upregulated by interferon (IFN), indicating a role in the antiviral response. Furthermore, PARP14 has evolved under positive selection, again indicating that it is involved in host-pathogen conflict. We found that PARP14 is required for increased IFN-I production in response to coronavirus infection lacking ADP-ribosylhydrolase (ARH) activity and poly(I:C), however, whether it has direct antiviral function remains unclear. Here we demonstrate that the catalytic activity of PARP14 enhances IFN-I and IFN-III responses and restricts ARH-deficient murine hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication. To determine if PARP14's antiviral functions extended beyond CoVs, we tested the ability of herpes simplex virus 1 (HSV-1) and several negative-sense RNA viruses, including vesicular stomatitis virus (VSV), Ebola virus (EBOV), and Nipah virus (NiV), to infect A549 PARP14 knockout (KO) cells. HSV-1 had increased replication in PARP14 KO cells, indicating that PARP14 restricts HSV-1 replication. In contrast, PARP14 was critical for the efficient infection of VSV, EBOV, and NiV, with EBOV infectivity at less than 1% of WT cells. A PARP14 active site inhibitor had no impact on HSV-1 or EBOV infection, indicating that its effect on these viruses was independent of its catalytic activity. These data demonstrate that PARP14 promotes IFN production and has both pro- and anti-viral functions targeting multiple viruses.

Perceptions of HPV-Linked Oropharyngeal Cancer Risk Messages Among a Sample of Young Adult Men in the US: A Pilot Study.

Awareness of risk for oropharyngeal cancer from oral human papillomavirus (HPV) infection is low among men in the United States. This pilot study tested messages communicating oral HPV and oropharyngeal cancer risk among a sample of U.S. young adult men (aged 18-26). Six oral HPV and cancer risk messages were tested in an online survey. Participants (N = 68) were randomly assigned to one of two message sets, each containing three unique text-based messages. Participants evaluated messages separately based on various measures (e.g., perceived message effectiveness [PME], novelty). One-way repeated measures ANOVAs were used to assess evaluation differences within message sets. Participants provided open-ended feedback about each message, which were synthesized into overarching themes. Participants were receptive to the risk messages, rating them high on PME (mean range = 3.72-4.25 out of 5) and other measures. Analyses identified three high-performing messages. For example, participants rated a message about HPV-linked oropharyngeal cancer risk rates in men versus women higher on attention and novelty than two other messages in the same set (both ps < .05). Participants were shown three messages (instead of all six) in each message set to minimize survey fatigue. Common themes from open-ended feedback were that participants liked the short-form structure of the messages and that the messages used gender-tailored language. In conclusion, oral HPV and oropharyngeal cancer risk messages may be useful for increasing risk awareness among men in the U.S. Further work should test such messages in rigorous experimental contexts to assess their efficacy in modifying other health outcomes, such as HPV vaccination behaviors.

GRP94 is an IGF-1R chaperone and regulates beta cell death in diabetes.

High workload-induced cellular stress can cause pancreatic islet ß cell death and dysfunction, or ß cell failure, a hallmark of type 2 diabetes mellitus. Thus, activation of molecular chaperones and other stress-response genes prevents ß cell failure. To this end, we have shown that deletion of the glucose-regulated protein 94 (GRP94) in Pdx1+ pancreatic progenitor cells led to pancreas hypoplasia and reduced ß cell mass during pancreas development in mice. Here, we show that GRP94 was involved in ß cell adaption and compensation (or failure) in islets from leptin receptor-deficient (db/db) mice in an age-dependent manner. GRP94-deficient cells were more susceptible to cell death induced by various diabetogenic stress conditions. We also identified a new client of GRP94, insulin-like growth factor-1 receptor (IGF-1R), a critical factor for ß cell survival and function that may mediate the effect of GRP94 in the pathogenesis of diabetes. This study has identified essential functions of GRP94 in ß cell failure related to diabetes.

Short-term air pollution levels and sickle cell disease hospital encounters in South Carolina: A case-crossover analysis.

BACKGROUND: Sickle cell disease (SCD) is a genetic disorder and symptoms may be sensitive to environmental stressors. Although it has been hypothesized that exposure to outdoor air pollution could trigger acute SCD events, evidence is limited. METHODS: We obtained SCD administrative data on hospital encounters in South Carolina from 2002 to 2019. We estimated outdoor air pollutant (particulate matter<2.5 µm (PM2.5), ozone (O3), and PM2.5 elemental carbon (EC) concentrations at residential zip codes using spatio-temporal models. Using a random bi-directional, fixed-interval case-crossover study design, we investigated the relationship between air pollution exposure over 1-, 3-, 5-, 9-, and14-day periods with SCD hospital encounters. RESULTS: We studied 8410 patients with 144,129 hospital encounters. We did not observe associations among all patients with SCD and adults for PM2.5, O3, and EC. We observed positive associations among children for 9- and 14-day EC (OR: 1.05 (95% confidence interval (CI): 1.02, 1.08) and OR: 1.05 (95% CI: 1.02, 1.09), respectively) and 9- and 14-day O3 (OR: 1.04 (95%CI: 1.00, 1.08)) for both. CONCLUSIONS: Our findings suggest that short-term (within two-weeks) levels of EC and O3 and may be associated with SCD hospital encounters among children. Two-pollutant model results suggest that EC is more likely responsible for effects on SCD than O3. More research is needed to confirm our findings.

Gender differences in the associations of psychosocial trauma and acute medical stressors with immune system activation and dementia risk.

Objective: The purpose of this article is to provide a narrative review synthesizing the literature on differences between women and men in relationships among certain stressors associated with immune system activation and their relationship to cognitive dysfunction and dementia. Method: We review the cycle of stress leading to neuroinflammation via cortisol and neurochemical alterations, cell-mediated immune system activation, and pro-inflammatory cytokines, and how this is implicated in the development of dementia. We follow this by discussing sex differences in stress physiology and immune function. We then review the work on early life adversity (ELA) and adverse childhood experiences (ACEs), post-traumatic stress disorder, acute medical stressors, and their associations with cognitive dysfunction and dementia. Throughout, we emphasize women's presentations and issues unique to women (e.g. trauma disorder prevalence). Conclusions: There is a need for more mechanistic and longitudinal studies that consider trauma accumulation, both physical and emotional, as well as a greater focus on traumas more likely to occur in women (e.g. sexual abuse), and their relationship to early cognitive decline and dementia.

Dynamics and prognostic value of serum neurofilament light chain in Guillain-Barré syndrome.

BACKGROUND: Neurofilament light chain (NfL) is a biomarker for axonal damage in several neurological disorders. We studied the longitudinal changes in serum NfL in patients with Guillain-Barré syndrome (GBS) in relation to disease severity, electrophysiological subtype, treatment response, and prognosis. METHODS: We included patients with GBS who participated in a double-blind, randomised, placebo-controlled trial that evaluated the effects of a second course of intravenous immunoglobulin (IVIg) on clinical outcomes. Serum NfL levels were measured before initiation of treatment and at one, two, four, and twelve weeks using a Simoa HD-X Analyzer. Serum NfL dynamics were analysed using linear mixed-effects models. Logistic regression was employed to determine the associations of serum NfL with clinical outcome and the prognostic value of serum NfL after correcting for known prognostic markers included in the modified Erasmus GBS Outcome Score (mEGOS). FINDINGS: NfL levels were tested in serum from 281 patients. Serum NfL dynamics were associated with disease severity and electrophysiological subtype. Strong associations were found between high levels of serum NfL at two weeks and inability to walk unaided at four weeks (OR = 1.74, 95% CI = 1.27-2.45), and high serum NfL levels at four weeks and inability to walk unaided at 26 weeks (OR = 2.79, 95% CI = 1.72-4.90). Baseline serum NfL had the most significant prognostic value for ability to walk, independent of predictors included in the mEGOS. The time to regain ability to walk unaided was significantly longer for patients with highest serum NfL levels at baseline (p = 0.0048) and week 2 (p < 0.0001). No differences in serum NfL were observed between patients that received a second IVIg course vs. IVIg and placebo. INTERPRETATION: Serum NfL levels are associated with disease severity, axonal involvement, and poor outcome in GBS. Serum NfL potentially represents a biomarker to monitor neuronal damage in GBS and an intermediate endpoint to evaluate the effects of treatment. FUNDING: Prinses Beatrix Spierfonds W.OR19-24.

Autoimmunity-associated allele of tyrosine phosphatase gene PTPN22 enhances anti-viral immunity.

The 1858C>T allele of the tyrosine phosphatase PTPN22 is present in 5-10% of the North American population and is strongly associated with numerous autoimmune diseases. Although research has been done to define how this allele potentiates autoimmunity, the influence PTPN22 and its pro-autoimmune allele has in anti-viral immunity remains poorly defined. Here, we use single cell RNA-sequencing and functional studies to interrogate the impact of this pro-autoimmune allele on anti-viral immunity during Lymphocytic Choriomeningitis Virus clone 13 (LCMV-cl13) infection. Mice homozygous for this allele (PEP-619WW) clear the LCMV-cl13 virus whereas wildtype (PEP-WT) mice cannot. This is associated with enhanced anti-viral CD4 T cell responses and a more immunostimulatory CD8α- cDC phenotype. Adoptive transfer studies demonstrated that PEP-619WW enhanced anti-viral CD4 T cell function through virus-specific CD4 T cell intrinsic and extrinsic mechanisms. Taken together, our data show that the pro-autoimmune allele of Ptpn22 drives a beneficial anti-viral immune response thereby preventing what is normally a chronic virus infection.