Search

Abstract Aim Illicitly manufactured fentanyl and its analogs are the primary drivers of opioid overdose deaths in the United States (U.S.). People who use drugs may be exposed to fentanyl or its analogs intentionally or unintentionally. This study sought to identify strategies used by rural people who use drugs to reduce harms associated with unintentional fentanyl exposure. Methods This analysis focused on 349 semi-structured qualitative interviews across 10 states and 58 rural counties in the U.S conducted between 2018 and 2020. Interview guides were collaboratively standardized across sites and included questions about drug use history (including drugs currently used, frequency of use, mode of administration) and questions specific to fentanyl. Deductive coding was used to code all data, then inductive coding of overdose and fentanyl codes was conducted by an interdisciplinary writing team. Results Participants described being concerned that fentanyl had saturated the drug market, in both stimulant and opioid supplies. Participants utilized strategies including: (1) avoiding drugs that were perceived to contain fentanyl, (2) buying drugs from trusted sources, (3) using fentanyl test strips, 4) using small doses and non-injection routes, (5) using with other people, (6) tasting, smelling, and looking at drugs before use, and (7) carrying and using naloxone. Most people who used drugs used a combination of these strategies as there was an overwhelming fear of fatal overdose. Conclusion People who use drugs living in rural areas of the U.S. are aware that fentanyl is in their drug supply and use several strategies to prevent associated harms, including fatal overdose. Increasing access to harm reduction tools (e.g., fentanyl test strips, naloxone) and services (e.g., community drug checking, syringe services programs, overdose prevention centers) should be prioritized to address the polysubstance-involved overdose crisis. These efforts should target persons who use opioids and other drugs that may contain fentanyl.

Abstract CD4+ T cells recognising citrullinated self-epitopes presented by HLA-DRB1 bearing the shared susceptibility epitope (SE) are implicated in rheumatoid arthritis (RA). However, the underlying T cell receptor (TCR) determinants of epitope specificity towards distinct citrullinated peptide antigens, including vimentin-64cit59-71 and α-enolase-15cit10-22 remain unclear. Using HLA-DR4-tetramers, we examine the T cell repertoire in HLA-DR4 transgenic mice and observe biased TRAV6 TCR gene usage across these two citrullinated epitopes which matches with TCR bias previously observed towards the fibrinogen β−74cit69-81 epitope. Moreover, shared TRAV26-1 gene usage is evident in four α-enolase-15cit10-22 reactive T cells in three human samples. Crystal structures of mouse TRAV6+ and human TRAV26-1+ TCR-HLA-DR4 complexes presenting vimentin-64cit59-71 and α-enolase-15cit10-22, respectively, show three-way interactions between the TCR, SE, citrulline, and the basis for the biased selection of TRAV genes. Position 2 of the citrullinated epitope is a key determinant underpinning TCR specificity. Accordingly, we provide a molecular basis of TCR specificity towards citrullinated epitopes.

Introduction: To expand access to naloxone, the state of Illinois implemented a standing order allowing registered pharmacies to dispense the drug without an individual prescription. To participate under the standing order, pharmacies were required to opt in through a formal registration process. In our study we aimed to evaluate the availability and price of naloxone at registered pharmacies. Methods: This was a prospective, de-identified, cross-sectional telephone survey. Trained interviewers posed as potential customers and used a standardized script to determine the availability of naloxone between February–December, 2019. The primary outcome was defined as a pharmacy indicating it carried naloxone, currently had naloxone in stock, and was able to dispense it without an individual prescription. Results: Of 948 registered pharmacies, 886 (93.5%) were successfully contacted. Of those, 792 (83.4%) carried naloxone, 659 (74.4%) had naloxone in stock, and 472 (53.3%) allowed purchase without a prescription. Naloxone nasal spray (86.4%) was the formulation most commonly stocked. Chain pharmacies were more likely to carry naloxone (adjusted odds ratio [aOR] 3.16, 95% confidence interval [CI] 1.97–5.01, P

Abstract Background Accurate prevalence estimates of drug use and its harms are important to characterize burden and develop interventions to reduce negative health outcomes and disparities. Lack of a sampling frame for marginalized/stigmatized populations, including persons who use drugs (PWUD) in rural settings, makes this challenging. Respondent-driven sampling (RDS) is frequently used to recruit PWUD. However, the validity of RDS-generated population-level prevalence estimates relies on assumptions that should be evaluated. Methods RDS was used to recruit PWUD across seven Rural Opioid Initiative studies between 2018-2020. To evaluate RDS assumptions, we computed recruitment homophily and design effects, generated convergence and bottleneck plots, and tested for recruitment and degree differences. We compared sample proportions with three RDS-adjusted estimators (two variations of RDS-I and RDS-II) for five variables of interest (past 30-day use of heroin, fentanyl, and methamphetamine; past 6-month homelessness; and being positive for hepatitis C virus (HCV) antibody) using linear regression with robust confidence intervals. We compared regression estimates for the associations between HCV positive antibody status and (a) heroin use, (b) fentanyl use, and (c) age using RDS-1 and RDS-II probability weights and no weights using logistic and modified Poisson regression and random-effects meta-analyses. Results Among 2,842 PWUD, median age was 34 years and 43% were female. Most participants (54%) reported opioids as their drug of choice, however regional differences were present (e.g., methamphetamine range: 4-52%). Many recruitment chains were not long enough to achieve sample equilibrium. Recruitment homophily was present for some variables. Differences with respect to recruitment and degree varied across studies. Prevalence estimates varied only slightly with different RDS weighting approaches, most confidence intervals overlapped. Variations in measures of association varied little based on weighting approach. Conclusions RDS was a useful recruitment tool for PWUD in rural settings. However, several violations of key RDS assumptions were observed which slightly impacts estimation of proportion although not associations.

Abstract People who nonmedically use drugs (PWUD) face intricate social issues that suppress self-actualization, communal integration, and overall health and wellness. “Strengths-based” approaches, an under-used pedagogy and practice in addiction medicine, underscore the significance of identifying and recognizing the inherent and acquired skills, attributes, and capacities of PWUD. A strengths-based approach engenders client affirmation and improves their capacity to reduce drug use-related harms by leveraging existing capabilities. Exploring this paradigm, we conducted and analyzed interviews with 46 PWUD who were clients at syringe services programs in New York City and rural southern Illinois, two areas with elevated rates of opioid-related morbidity and mortality, to assess respondents’ perceived strengths. We located two primary thematic modalities in which strengths-based ethos is expressed: individuals (1) being and advocate and resource for harm reduction knowledge and practices and (2) engaging in acts of continuous self-actualization. These dynamics demonstrate PWUD strengths populating and manifesting in complex ways that both affirm and challenge humanist and biomedical notions of individual agency, as PWUD refract enacted, anticipated, and perceived stigmas. In conclusion, programs that blend evidence-based, systems-level interventions on drug use stigma and disenfranchisement with meso and micro-level strengths-based interventions that affirm and leverage personal identity, decision-making capacity, and endemic knowledge may help disrupt health promotion cleavages among PWUD.

This study explores the advantages of employing an unmanned aerial vehicle (UAV) in a massive multiple-input multiple-output (MIMO) network with zero-forcing processing at the base station (BS). Considering potential inaccuracies in channel estimation, we derive a closed-form expression for lower bounds on spectral efficiency in the massive MIMO system, utilizing the UAV as an aerial relay. Subsequently, we formulate a comprehensive optimization problem that encompasses UAV placement and user power allocation in the downlink network, aiming to maximize the data rate for terrestrial users. To address the optimization problem, we propose a novel deep learning-based algorithm that jointly optimizes UAV positioning and power allocation. Finally, we present numerical results that not only validate our theoretical framework and but also demonstrates the effectiveness of the proposed approach.

Background This review aimed to quantify the impact of socioeconomic status on functional outcomes from stroke and identify the socioeconomic status indicators that exhibit the highest magnitude of association. Methods and Results We performed a systematic literature search across Medline and Embase from inception to May 2022, to identify observational studies (n≥100, and in English). Risk of bias was assessed using the modified Newcastle Ottawa Scale. Random effects meta‐analysis was used to pool data. We included 19 studies (157 715 patients, 47.7% women) reporting functional outcomes measured with modified Rankin Scale or Barthel index, with 10 assessed as low risk of bias. Measures of socioeconomic status reported were education (11 studies), income (8), occupation (4), health insurance status (3), and neighborhood socioeconomic deprivation (3). Pooled data suggested that low socioeconomic status was significantly associated with poor functional outcomes, including incomplete education or below high school level versus high school attainment and above (odds ratio [OR], 1.66 [95% CI, 1.40–1.95]), lowest income versus highest income (OR, 1.36 [95% CI, 1.02–1.83]), a manual job/being unemployed versus a nonmanual job/working (OR, 1.62 [95% CI, 1.29–2.02]), and living in the most disadvantaged socioeconomic neighborhood versus the least disadvantaged (OR, 1.55 [95% CI, 1.25–1.92]). Low health insurance status was also associated with an increased risk of poor functional outcomes (OR, 1.32 [95% CI, 0.95–1.84]), although this was association was not statistically significant. Conclusions Despite great strides in stroke treatment in the past decades, social disadvantage remains a risk factor for poor functional outcome after an acute stroke. Further research is needed to better understand causal mechanisms and disparities.

Abstract Background Research conducted in urban areas has highlighted the impact of housing instability on people who inject drugs (PWID), revealing that it exacerbates vulnerability to drug-related harms and impedes syringe service program (SSP) use. However, few studies have explored the effects of houselessness on SSP use among rural PWID. This study examines the relationship between houselessness and SSP utilization among PWID in eight rural areas across 10 states. Methods PWID were recruited using respondent-driven sampling for a cross-sectional survey that queried self-reported drug use and SSP utilization in the prior 30 days, houselessness in the prior 6 months and sociodemographic characteristics. Using binomial logistic regression, we examined the relationship between experiencing houselessness and any SSP use. To assess the relationship between houselessness and the frequency of SSP use, we conducted multinomial logistic regression analyses among participants reporting any past 30-day SSP use. Results Among 2394 rural PWID, 56.5% had experienced houselessness in the prior 6 months, and 43.5% reported past 30-day SSP use. PWID who had experienced houselessness were more likely to report using an SSP compared to their housed counterparts (adjusted odds ratio [aOR] = 1.24 [95% confidence intervals [CI] 1.01, 1.52]). Among those who had used an SSP at least once (n = 972), those who experienced houselessness were just as likely to report SSP use two (aOR = 0.90 [95% CI 0.60, 1.36]) and three times (aOR = 1.18 [95% CI 0.77, 1.98]) compared to once. However, they were less likely to visit an SSP four or more times compared to once in the prior 30 days (aOR = 0.59 [95% CI 0.40, 0.85]). Conclusion This study provides evidence that rural PWID who experience houselessness utilize SSPs at similar or higher rates as their housed counterparts. However, housing instability may pose barriers to more frequent SSP use. These findings are significant as people who experience houselessness are at increased risk for drug-related harms and encounter additional challenges when attempting to access SSPs.

There is a growing demand for the consumption of medicinal mushrooms and their products. Ganoderma lucidum and Cordyceps militaris are two important medicinal mushrooms with significant pharmacological activities. In this study, we aim to develop a preparation of the extracts of these two mushrooms, and investigate its composition, antioxidant activities, and protective effects against oxidative damage. Liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (LC-QTOF MS) was employed to analyze the chemical profiles of the mixture. A total of 94 compounds were identified as belonging to phenolic acids, flavonoids, triterpenes, and nucleosides. In addition, HPLC-DAD was used to quantify major compounds. Ferulic and cinnamic acids were predominant in the phenolic acid groups, with corresponding concentrations of 0.41 and 0.29 mg/g. The concentration of ganoderic acid A was 0.08 mg/g, and the contents of adenosine and cordycepin were 0.53 and 0.14 mg/g, respectively. The mixture could scavenge free radicals and reduce ferric ions in vitro. The preparation also showed nontoxic but proliferative effects on human fibroblast cells. In addition, it could protect fibroblasts against oxidative stress, reducing 21–22% of cell death in the presence of H2O2. These findings provide more information on the applications of medicinal mushrooms in the functional food and pharmaceutical industries.

Abstract The majority of adoptive cellular therapies are produced from peripheral mononuclear cells obtained via leukapheresis and further enriched for the cells of interest (e.g., T cells). Here, we present a first‐of‐its‐kind closed system, which effectively removes ~85% of monocytes and ~88% of platelets, while recovering ~88% of concentrated T cells in a separate output stream, as the leukapheresis sample flows through a microfluidic device at 5 mL/min. The system is driven by a common peristaltic pump, enabled by a novel pressure wave dampener, and operates in a closed bag‐to‐bag configuration, without requiring any specialized, dedicated equipment. When compared to standard density gradient centrifugation on paired samples, the new system demonstrated a 1.5‐fold increase in T cell recovery and a 2‐fold reduction in inter‐sample variability for this separation outcome. The T cell‐to‐monocyte ratio of the leukapheresis sample was increased to 20:1, whereas with density gradient processing it decreased to 2:1. As a result of superior purity and/or gentler processing, T cells enriched by the system showed a 2.7‐times higher fold expansion during subsequent culture, and an overall 3.5‐times higher cumulative yield. This centrifugation‐free and label‐free closed system for enriching lymphocytes could significantly simplify and standardize the manufacturing of life‐saving cellular therapies.

African swine fever virus is a complex DNA virus that causes high fatality in pigs and wild boar and has a great socio-economic impact. An attenuated genotype II strain was constructed by replacing the gene for wildtype CD2v protein with versions in which single or double amino acid substitutions were introduced to reduce or abrogate the binding to red blood cells and reduce virus persistence in blood. The mutant CD2v proteins were expressed at similar levels to the wildtype protein on the surface of infected cells. Three recombinant viruses also had K145R, EP153R, and in one virus DP148R genes deleted. Following immunization of pigs, the virus with a single amino acid substitution in CD2v, Q96R, induced moderate levels of replication, and 100% protection against virulent ASFV. Two additional recombinant viruses had two amino acid substitutions in CD2v, Q96R, and K108D, and induced no binding to red blood cells in vitro. In immunized pigs, reduced levels of virus in blood and strong early ASFV-specific antibody and cellular responses were detected. After challenge low to moderate replication of challenge virus was observed. Reduced clinical signs post-challenge were observed in pigs immunized with the virus from which DP148R gene was deleted. Protection levels of 83–100% were maintained across a range of doses. Further experiments with virus GeorgiaΔDP148RΔK145RΔEP153R-CD2v_mutantQ96R/K108D showed low levels of virus dissemination in tissue and transient clinical signs at high doses. The results support further evaluation of GeorgiaΔDP148RΔK145RΔEP153R-CD2v_mutantQ96R/K108D as a vaccine candidate.

Abstract Breast and gynaecological cancer (BGC) patients receiving chemotherapy may experience high levels of stress during the COVID-19 pandemic. Music interventions may be effective in lowering their stress levels. This study explored stressors, coping strategies, and the feasibility of music interventions among BGC patients in Vietnam. An exploratory qualitative study with individual face-to-face semi-structured interviews was conducted. A convenience sample of BGC patients receiving chemotherapy was recruited from the oncology centre of a public hospital in Vietnam. Twenty patients were interviewed with open-ended questions developed based on the transactional model of stress and coping to explore stress-causing factors and coping strategies and based on guidelines for music therapy practice to explore their music preferences and perceptions. Field notes and interview transcripts were analysed following the qualitative content analysis approach. Two stressor themes were identified: undesirable experiences during treatment and patients’ inability to fulfil their own roles and responsibilities. Our findings revealed a new coping strategy—self-realisation of responsibilities towards the family—that is not listed in the transactional model of stress and coping. Future psychological interventions for stress management among BGC patients should focus on raising the patients’ awareness of their values and responsibilities towards their families. Three categories of preferred music genres for stress reduction were identified: religious, softly melodic, and revolutionary music. The patients were aware of the positive effects of music and had different musical preferences. This study also explored the acceptance of music interventions and facilitators and barriers to implementing them among BGC patients in Vietnam. The findings suggest that before implementing music interventions, the musical preferences, religions, and beliefs of each individual should be considered to achieve desirable results. Music interventions for BGC patients receiving chemotherapy in Vietnam are feasible. Further intervention studies are needed to evaluate their effectiveness.

Abstract Background Chronic health conditions associated with long-term drug use may pose additional risks to people who use drugs (PWUD) when coupled with COVID-19 infection. Despite this, PWUD, especially those living in rural areas, may be less likely to seek out health services. Previous research has highlighted the increased disease burden of COVID-19 among PWUD. Our manuscript supplements this literature by exploring unique attitudes of PWUD living in rural areas toward the pandemic, COVID-19 vaccination, and the role of harm reduction (HR) organizations in raising health awareness among PWUD. Methods Semi-structured interviews were conducted with 20 PWUD living in rural southern Illinois. Audio recordings were professionally transcribed. A preliminary codebook was created based on interview domains. Two trained coders conducted iterative coding of the transcripts, and new codes were added through line-by-line coding and thematic grouping. Results Twenty participants (45% female, mean age of 38) completed interviews between June and November 2021. Participants reported negative impacts of the pandemic on mental health, financial wellbeing, and drug quality. However, the health impacts of COVID-19 were often described as less concerning than its impacts on these other aspects of life. Many expressed doubt in the severity of COVID-19 infection. Among the 16 unvaccinated participants who reported receiving most of their information from the internet or word of mouth, uncertainty about vaccine contents and distrust of healthcare and government institutions engendered wariness of the vaccination. Distrust of healthcare providers was related to past stigmatization and judgement, but did not extend to the local HR organization, which was unanimously endorsed as a positive institution. Among participants who did not access services directly from the HR organization, secondary distribution of HR supplies by other PWUD was a universally cited form of health maintenance. Participants expressed interest in low-threshold healthcare, including COVID-19 vaccination, should it be offered in the local HR organization’s office and mobile units. Conclusion COVID-19 and related public health measures have affected this community in numerous ways. Integrating healthcare services into harm reduction infrastructures and mobilizing secondary distributors of supplies may promote greater engagement with vaccination programs and other healthcare services. Trial number NCT04427202.

Abstract Objective To characterize and address the opioid crisis disproportionately impacting rural U.S. regions. Methods The Rural Opioid Initiative (ROI) is a two-phase project to collect and harmonize quantitative and qualitative data and develop tailored interventions to address rural opioid use. The baseline quantitative survey data from people who use drugs (PWUD) characterizes the current opioid epidemic (2018–2020) in eight geographically diverse regions. Results Among 3,084 PWUD, 92% reported ever injecting drugs, 86% reported using opioids (most often heroin) and 74% reported using methamphetamine to get high in the past 30 days; 53% experienced homelessness in the prior 6 months; and 49% had ever overdosed. Syringe service program use varied by region and 53% had ever received an overdose kit or naloxone prescription. Less than half (48%) ever received medication for opioid use disorder (MOUD). Conclusions The ROI combines data across eight rural regions to better understand drug use including drivers and potential interventions in rural areas with limited resources. Baseline ROI data demonstrate extensive overlap between opioid and methamphetamine use, high homelessness rates, inadequate access to MOUD, and other unmet needs among PWUD in the rural U.S. By combining data across studies, the ROI provides much greater statistical power to address research questions and better understand the syndemic of infectious diseases and drug use in rural settings including unmet treatment needs.

Abstract Background Drug overdose rates in the United States have been steadily increasing, particularly in rural areas. The COVID-19 pandemic and associated mitigation strategies may have increased overdose risk for people who use drugs by impacting social, community, and structural factors. Methods The study included a quantitative survey focused on COVID-19 administered to 50 people who use drugs and semi-structured qualitative interviews with 17 people who use drugs, 12 of whom also participated in the quantitative survey. Descriptive statistics were run for the quantitative data. Qualitative coding was line-by-line then grouped thematically. Quantitative and qualitative data were integrated during analysis. Results Findings demonstrate how COVID-19 disruptions at the structural and community level affected outcomes related to mental health and drug use at the individual level. Themes that emerged from the qualitative interviews were (1) lack of employment opportunities, (2) food and housing insecurity, (3) community stigma impacting health service use, (4) mental health strains, and (5) drug market disruptions. Structural and community changes increased anxiety, depression, and loneliness on the individual level, as well as changes in drug use patterns, all of which are likely to increase overdose risk. Conclusion The COVID-19 pandemic, and mitigation strategies aimed at curbing infection, disrupted communities and lives of people who use drugs. These disruptions altered individual drug use and mental health outcomes, which could increase risk for overdose. We recommend addressing structural and community factors, including developing multi-level interventions, to combat overdose. Trial registration Clinicaltrails.gov: NCT04427202. Registered June 11, 2020: https://clinicaltrials.gov/ct2/show/NCT04427202?term=pho+mai&draw=2&rank=3

Tissue engineering has driven significant research in the strive to create a supply of tissues for patient treatment. Cell integration into engineered tissues maximizes functional capabilities, however, issues of rejection remain. Autologous cell sources able to solve this issue are difficult to identify for tissue engineering purposes. Here, we present the efficacy of patient-sourced cells derived from adipose (adipose-derived stem cells, ASCs) and skin tissue (dermal fibroblasts, PtFibs) to build a combined engineered tunica media and adventitia graft, respectively. Patient cells were integrated into our lab's vascular tissue engineering technique of forming vascular rings that are stacked into a tubular structure to create the vascular graft. For the media layer, ASCs were successfully differentiated into the smooth muscle phenotype using angiotensin II followed by culture in smooth muscle growth factors, evidenced by significantly increased expression of αSMA and myosin light chain kinase. Engineered media vessels composed of differentiated ASCs (ASC-SMCs) exhibited an elastic modulus (45.2 ± 18.9 kPa) between that of vessels of undifferentiated ASCs (71.8 ± 35.3 kPa) and control human aortic smooth muscle cells (HASMCs; 18.7 ± 5.49 kPa) (p

Background: Acute kidney injury remains a common complication with a poor prognosis, and is a significant predictor of mortality in cirrhosis patients. We aimed to determine the percentage of acute kidney injury in decompensated cirrhosis patients and evaluate the treatment results of acute kidney injury as well as several factors related to the mortality of decompensated cirrhosis patients. Methods: A prospective study was conducted on decompensated cirrhosis patients in Can Tho City, Vietnam, from 2019 to 2020. Decompensated cirrhosis patients were found to have acute kidney injury on admission by a blood creatinine test. They were treated according to ICA 2015 standards, after which they were monitored and evaluated for treatment outcomes during hospitalization. Results: Of 250 decompensated cirrhosis patients, 64 (25.6%) had acute kidney injury and 37.5% died. Several factors were associated with mortality in decompensated cirrhosis patients, such as Child–Pugh C (p = 0.02; OR = 3, 95% CI 1.5–6.3), acute kidney injury (p < 0.0001; OR = 9.5, 95% CI 4.3–21.1), hyponatremia (p = 0.01; OR = 2.5, 95% CI 1.2–5.1), elevated total bilirubin > 51 µmol/L (p = 0.03; OR = 2.2, 95% CI 1.1–4.6), and prothrombin < 70% (p = 0.03; OR = 6.8, 95% CI 1–51.6). Hypoalbuminemia was unrelated to mortality in these patients (p = 0.8; OR = 1.2, 95% CI 0.5–2.7), but gastrointestinal bleeding significantly increased mortality in these patients up to 2.3 times (p = 0.03; OR = 2.3, 95% CI 1.1–4.9). Three independent factors regarding mortality in decompensated cirrhosis patients included acute kidney injury, hepatic encephalopathy, and gastrointestinal bleeding. The rate of acute kidney injury in patients with decompensated cirrhosis was 25.6%; the mortality rate was 37.5%. Conclusions: Acute kidney injury was a valuable predictor of mortality in Vietnamese patients with decompensated cirrhosis.

This study investigates the integration of an intelligent reflecting surface (IRS) into an unmanned aerial vehicle (UAV) platform to utilize the advantages of these leading technologies for sixth-generation communications, e.g., improved spectral and energy efficiency, extended network coverage, and flexible deployment. In particular, we investigate a downlink IRS–UAV system, wherein single-antenna ground users (UEs) are served by a multi-antenna base station (BS). To assist the communication between UEs and the BS, an IRS mounted on a UAV is deployed, in which the direct links are obstructed owing to the complex urban channel characteristics. The beamforming at the BS, phase shift at the IRS, and the 3D placement of the UAV are jointly optimized to maximize the sum rate. Because the optimization variables, particularly the beamforming and IRS phase shift, are highly coupled with each other, the optimization problem is naturally non-convex. To effectively solve the formulated problem, we propose an iterative algorithm that employs block coordinate descent and inner approximation methods. Numerical results demonstrate the effectiveness of our proposed approach for a UAV-mounted IRS system on the sum rate performance over the state-of-the-art technology using the terrestrial counterpart.

This study investigates a combined system comprising non-orthogonal multiple access (NOMA) and beamforming in a downlink network. To fully exploit the advantages of NOMA, user (UE) pairing and beamforming design are jointly optimized via a generalized model for UE association, subject to energy efficiency maximization. Owing to the combination of binary variables and nonconvex constraints, the resulting optimization problem belongs to the class of mixed-integer nonconvex programming. An innovative algorithm, integrating the inner-approximation and Dinkelbach methods, is proposed herein to address a nonconvex fractional function. By introducing a pairing matrix and relaxing the binary variables into continuous ones, our approach is capable of reaching an optimal solution, where two arbitrary UEs are optimally paired regardless of geographical or spatial constraints. For practical scenarios, we further propose a robust design to manage the effect of channel estimation errors under settings involving channel uncertainty. Numerical results show that our proposed designs, even with the presence of the imperfect channel state information at the base station, significantly outperform the conventional beamforming and existing pairing schemes.

Abstract Glioblastoma (GBM) tumor cells are found in the perivascular niche microenvironment and are believed to associate closely with the brain microvasculature. However, it is largely unknown how the resident cells of the perivascular niche, such as endothelial cells, pericytes, and astrocytes, influence GBM tumor cell behavior and disease progression. A 3D in vitro model of the brain perivascular niche developed by encapsulating brain‐derived endothelial cells, pericytes, and astrocytes in a gelatin hydrogel is described. It is shown that brain perivascular stromal cells, namely pericytes and astrocytes, contribute to vascular architecture and maturation. Cocultures of patient‐derived GBM tumor cells with brain microvascular cells are used to identify a role for pericytes and astrocytes in establishing a perivascular niche environment that modulates GBM cell invasion, proliferation, and therapeutic response. Engineered models provide unique insight regarding the spatial patterning of GBM cell phenotypes in response to a multicellular model of the perivascular niche. Critically, it is shown that engineered perivascular models provide an important resource to evaluate mechanisms by which intercellular interactions modulate GBM tumor cell behavior, drug response, and provide a framework to consider patient‐specific disease phenotypes.

Epitopes formed by fusion of more than one self peptide, such as proinsulin and other β cell proteins, can result in the formation of non-self hybrid peptides that can potentially trigger autoimmune responses. Here the authors show how TRBV5 + T cell receptors are geared towards recognition of HLA-DQ8 bound hybrid peptides in patients with type 1 diabetes.

Jiansheng Cai,1,2,&ast; Shuzhen Liu,1,&ast; You Li,3,&ast; Qiumei Liu,1 Min Xu,1 Chunbao Mo,3 Tingyu Mai,3 Xia Xu,1 Xu Tang,1 Quanhui Chen,1 Chuntao Nong,1 Huaxiang Lu,1,3 Haoyu He,1,4 Jiexia Tang,5 Junling Zhang,1 Chunmei Wei,1 Dechan Tan,3 Jian Qin,1 Zhiyong Zhang1,3 1Department of Environmental and Occupational Health, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi Province, People’s Republic of China; 2Guangxi Key Laboratory of Tumor Immunology and Microenvironmental Regulation, Guilin Medical University, Guilin, People’s Republic of China; 3Department of Environmental Health and Occupational Medicine, School of Public Health, Guilin Medical University, Guilin, People’s Republic of China; 4Quality Management Department, the Affiliated Hospital of Stomatology, Guangxi Medical University, Nanning, People’s Republic of China; 5Guangxi Center for Disease Prevention and Control, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Qin; Zhiyong ZhangDepartment of Environmental and Occupational Health, School of Public Health, Guangxi Medical University, Shuangyong Road No. 22, Nanning, 530021, Guangxi Province, People’s Republic of ChinaTel +86-771-5358124Fax +86-771-5358124Email qinjian@gxmu.edu.cn; rpazz@163.comBackground: Animal experiments have found that oil tea reduces body weight and improves blood lipid levels. However, the effect of oil tea on human health has not been confirmed yet. This study aims to explore the relationship between oil tea consumption and obesity and dyslipidemia.Methods: In a cross-sectional population study in Guangxi, China, a semi-quantitative questionnaire was used to investigate the oil tea consumed and food consumption frequency in adults aged 30 years and over. Anthropometric variables and serum biochemical indicators were measured. A total of 2001 adults were divided into five groups based on their non-consumption status and quartile of consumption (groups non-drink oil tea, Q1–Q4).Results: The risk of abdominal obesity tended to decrease significantly with increasing consumption of oil tea (P for trend< 0.05) in the overall participants (Q3 group, OR = 0.545, 95% CI = 0.336– 0.884; Q4 group, OR = 0.520, 95% CI = 0.311– 0.871) and in women (Q2 group, OR = 0.502, 95% CI = 0.274– 0.920; Q3 group, OR = 0.397, 95% CI = 0.213– 0.740; Q4 group, OR = 0.421, 95% CI = 0.228– 0.780). Oil tea consumption Q1, Q2, Q3 and Q4 group significantly reduced the risk of abnormal HDL-cholesterol (P < 0.05). Oil tea consumption Q2 group significantly increased the risk of abnormal LDL-cholesterol (OR = 2.600, 95% CI = 1.033– 6.546) in women. Oil tea consumption Q1 (OR = 0.081, 95% CI =0.008– 0.864) and Q3 (OR = 0.057, 95% CI = 0.004– 0.913) groups significantly reduced the risk of abnormal HDL-cholesterol in women.Conclusion: Oil tea consumption may be associated with a low risk of abdominal obesity. High-dose oil tea consumption may be associated with a low risk of abnormal HDL-cholesterol. Prospective studies with large sample sizes would be required to further investigate this association.Keywords: abdominal obesity, blood lipid, HDL-C

This article describes a state-supported, multiuniversity, interdisciplinary effort to address unmet disaster recovery needs identified by six hard-hit, low-capacity North Carolina communities following Hurricane Matthew. At the request of the director of the North Carolina Division of Emergency Management and the state governor, university officials created a team of faculty, practitioners, and students called the Hurricane Matthew Disaster Recovery and Resilience Initiative (HMDRRI). This 2-year program delivered research, teaching, and engagement activities of the sort that are not typically undertaken by federal or state emergency management agencies, insurance providers, or nonprofit organizations. HMDRRI also offered graduate students in land-use planning, landscape architecture, and architecture opportunities to help provide community assistance under the supervision and mentoring of faculty and practitioners. An overarching goal of the program was to help build greater rural resilience, an outcome that has received inadequate attention from academics and practitioners.

Tissue engineering has the advantage of replicating soft tissue mechanics to better simulate and integrate into native soft tissue. However, soft tissue engineering has been fraught with issues of insufficient tissue strength to withstand physiological mechanical requirements. This factor is due to the lack of strength inherent in cell-only constructs and in the biomaterials used for soft tissue engineering and limited extracellular matrix (ECM) production possible in cell culture. To address this issue, we explored the use of an ECM-based hydrogel coating to serve as an adhesive tool, as demonstrated in vascular tissue engineering. The efficacy of cells to supplement mechanical strength in the coating was explored. Specifically, selected coatings were applied to an engineered artery tunica adventitia to accurately test their properties in a natural tissue support structure. Multiple iterations of three primary hydrogels with and without cells were tested: fibrin, collagen, and gelatin hydrogels with and without fibroblasts. The effectiveness of a natural crosslinker to further stabilize and strengthen the hydrogels was investigated, namely genipin extracted from the gardenia fruit. We found that gelatin crosslinked with genipin alone exhibited the highest tensile strength; however, fibrin gel supported cell viability the most. Overall, fibrin gel coating without genipin was deemed optimal for its balance in increasing mechanical strength while still supporting cell viability and was used in the final mechanical and hydrodynamic testing assessments. Engineered vessels coated in fibrin hydrogel with cells resulted in the highest tensile strength of all hydrogel-coated groups after 14 d in culture, demonstrating a tensile strength of 11.9 ± 2.91 kPa, compared to 5.67 ± 1.37 kPa for the next highest collagen hydrogel group. The effect of the fibrin hydrogel coating on burst pressure was tested on our strongest vessels composed of human aortic smooth muscle cells. A significant increase from our previously reported burst pressure of 51.3 ± 2.19 mmHg to 229 ± 23.8 mmHg was observed; however, more work is needed to render these vessels compliant with mechanical and biological criteria for blood vessel substitutes.

Abstract Background Empiric antibiotics for community acquired bacterial pneumonia (CABP) are often prescribed to patients with COVID-19, despite a low reported incidence of co-infections. Stewardship interventions targeted at facilitating appropriate antibiotic prescribing for CABP among COVID-19 patients are needed. We developed a guideline for antibiotic initiation and discontinuation for CABP in COVID-19 patients. The purpose of this study was to assess the impact of this intervention on the duration of empiric CABP antibiotic therapy among patients with COVID-19. Methods This was a single-center, retrospective, quasi-experimental study of adult patients admitted between 3/1/2020 to 4/25/2020 with COVID-19 pneumonia, who were initiated on empiric CABP antibiotics. Patients were excluded if they were initiated on antibiotics > 48 h following admission or if another source of infection was identified. The primary outcome was the duration of antibiotic therapy (DOT) prior to the guideline (March 1 to March27, 2020) and after guideline implementation (March 28 to April 25, 2020). We also evaluated the clinical outcomes (mortality, readmissions, length of stay) among those initiated on empiric CABP antibiotics. Results A total of 506 patients with COVID-19 were evaluated, 102 pre-intervention and 404 post-intervention. Prior to the intervention, 74.5% (n = 76) of patients with COVID-19 received empiric antibiotics compared to only 42% of patients post-intervention (n = 170), p

Abstract Nanostructured cathode materials based on Mn-doped olivine LiMnxFe1−xPO4 (x = 0, 0.1, 0.2, and 0.3) were successfully synthesized via a hydrothermal route. The field-emission scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) analyzed results indicated that the synthesized LiMnxFe1−xPO4 (x = 0, 0.1, 0.2, and 0.3) samples possessed a sphere-like nanostructure and a relatively homogeneous size distribution in the range of 100–200 nm. Electrochemical experiments and analysis showed that the Mn doping increased the redox potential and boosted the capacity. While the undoped olivine (LiFePO4) had a capacity of 169 mAh g−1 with a slight reduction (10%) in the initial capacity after 50 cycles (150 mAh g−1), the Mn-doped olivine samples (LiMnxFe1−xPO4) demonstrated reliable cycling tests with negligible capacity loss, reaching 151, 147, and 157 mAh g−1 for x = 0.1, 0.2, and 0.3, respectively. The results from electrochemical impedance spectroscopy (EIS) accompanied by the galvanostatic intermittent titration technique (GITT) have resulted that the Mn substitution for Fe promoted the charge transfer process and hence the rapid Li transport. These findings indicate that the LiMnxFe1−xPO4 nanostructures are promising cathode materials for lithium ion battery applications.

Abstract The ideal engineered vascular graft would utilize human-derived materials to minimize foreign body response and tissue rejection. Current biological engineered blood vessels (BEBVs) inherently lack the structure required for implantation. We hypothesized that an ECM material would provide the structure needed. Skin dermis ECM is commonly used in reconstructive surgeries, is commercially available and FDA-approved. We evaluated the commercially-available decellularized skin dermis ECM Alloderm for efficacy in providing structure to BEBVs. Alloderm was incorporated into our lab’s unique protocol for generating BEBVs, using fibroblasts to establish the adventitia. To assess structure, tissue mechanics were analyzed. Standard BEBVs without Alloderm exhibited a tensile strength of 67.9 ± 9.78 kPa, whereas Alloderm integrated BEBVs showed a significant increase in strength to 1500 ± 334 kPa. In comparison, native vessel strength is 1430 ± 604 kPa. Burst pressure reached 51.3 ± 2.19 mmHg. Total collagen and fiber maturity were significantly increased due to the presence of the Alloderm material. Vessels cultured for 4 weeks maintained mechanical and structural integrity. Low probability of thrombogenicity was confirmed with a negative platelet adhesion test. Vessels were able to be endothelialized. These results demonstrate the success of Alloderm to provide structure to BEBVs in an effective way.

In the present study, the photocatalytic activity of Ti-SBA-15/C3N4 catalysts was investigated to degrade 2,4-Dichlorophenoxyacetic acid (2,4-D) herbicides in water under visible light irradiation. The catalysts were synthesized via a simple hydrothermal method and characterized by various analytical techniques, including SAXS, N2 adsorption-desorption isotherms, Zeta potential, PL, FT-IR, XRF, TGA, and UV-DRS. Our study indicated that the 2.5Ti-SBA-15/C3N4 had higher efficiency in the degradation of 2,4-D than Ti-SBA-15 and C3N4. The decomposition of 2,4-D reached 60% under 180 minutes of visible light irradiation at room temperature on 2.5Ti-SBA-15/C3N4. Moreover, the degradation of 2,4-D on Ti-SBA-15/C3N4 was pseudo-first-order kinetics with the highest rate constant (0.00484 min−1), which was much higher than that obtained for other photocatalysts reported recently. Furthermore, the catalyst can be reused at least two times for photodegradation of 2,4-D solution under visible light irradiation within a slight decrease in catalytic activity.

Background With the influence of Confucian culture, sex is often considered a taboo subject in Vietnam. This study aimed to examine the prevalence of exposure to sexually explicit Internet material (SEIM) among adolescents in Vi-etnam, as well as the factors affecting exposure to SEIM. Participants and procedure The sample consisted of 886 Vietnamese adolescents (58.10% female) aged 15 to 18 years (M = 16.72, SD = 0.72). The survey was adapted from the study of Van Ouytsel, Ponnet and Walrave to assess the frequen-cy of exposure to SEIM. Several measurement scales of factors affecting exposure to SEIM among adoles-cents were used including the Perceived Realism of SEIM, the Sexual Sensation Seeking Scale, the Family Cohesion and the Parental Monitoring Scale. Results The overall prevalence of exposure to SEIM was 84.10%, with a gender difference: 89.80% in males and 80.00% in females. The prevalence of passive exposure to SEIM was 58.30%, higher than 41.70% for active exposure. Perceived realism of SEIM, sexual sensation seeking and Internet usage time for entertainment are factors affecting frequencies of exposure to SEIM among adolescents, with β coefficient values of .29, .18 and .16 respectively. Conclusions The majority of children in this study reported SEIM exposure. Parents, schools and other stakeholders should pay attention to sex education for children early on, diversifying forms and subjects of sex education. The con-tent of sex education should emphasize the responsibility in the decisions made by children related to sex.

Introduction Opioid overdose education and naloxone distribution (OEND) for use by laypersons are safe and effective at preventing deaths from opioid overdose, but emergency department (ED) implementation is challenging. Curricula addressing OEND could enable students to serve in value-added roles on the clinical team, overcome challenges of naloxone distribution, and improve patient care. Methods We created a 1-hour didactic session on opioid use disorder and OEND for first-year medical students in the emergency medicine elective. During two clinical shifts, students used this knowledge to perform screenings to identify patients at high risk of overdose. If a patient screened positive, students performed patient education and then notified the physician, who ordered a naloxone kit. Results Thirty students received the didactic and conducted screening shifts. Of 147 patients screened, 40% (n = 59) were positive for naloxone eligibility, 21% (n = 31) reported that someone close to them used opioids, 18% (n = 26) had witnessed an opioid overdose, 12% (n = 17) had previously overdosed themselves, and 12% (n = 18) previously knew what naloxone was. Fifty-nine naloxone kits were distributed over the 3-month pilot versus 13 naloxone prescriptions for patients discharged from the ED the prior year. Discussion Through didactic training and structured patient engagement, medical students gained knowledge of and hands-on experience with addiction medicine, discussed sensitive topics with patients, and identified a high volume of patients eligible to receive naloxone. Medical student screening for OEND in ED patients is feasible and adds significant value to the clinical team.

Endovenous laser ablation (EVLA) is a minimally invasive surgical procedure, often guided by ultrasound (US) imaging, for treating venous insufficiencies. US imaging limitations in accurately visualizing the catheter and the lack of a temperature monitoring system can lead to sub-optimal outcomes. An integrated photoacoustic (PA)-guided EVLA system has been previously developed and reported to overcome the shortcomings of US-guided procedure. In this study, we further characterized the system and tested the in vivo utility. In addition, PA thermometry was further explored by compensating the variation of PA signal with temperature with respect to the temperature-dependent absorption of blood and water. In vivo imaging results indicated that the PA-guided EVLA system can provide high contrast and accurate images of the ablation catheter tip overlaid on US images of the background tissue. Additionally, absorption-compensated PA signal amplitudes over a relevant range of temperature were measured and demonstrated.

Summary: Current single-cell RNA sequencing (scRNA-seq) protocols are limited by the number of cells that can be simultaneously sequenced, restricting the ability to resolve heterogeneity of rare cell types. We describe here a protocol for rapid isolation of myeloid cells from tumor-harboring mouse cerebellum without cell sorting to minimize cell damage for scRNA-seq. This protocol includes the procedures for further enrichment of myeloid cells using CD11b+ magnetic beads, followed by the generation of scRNA library and sequencing analysis.For complete details on the use and execution of this protocol, please refer to Dang et al. (2021).

Background: The efficacy of Helicobacter pylori (H. pylori) eradication therapy for children is currently low, and antibiotic resistance is a significant cause of treatment failure. The purpose of this study was to evaluate the H. pylori eradication efficacy of therapy based on antimicrobial susceptibility in pediatric patients with gastritis and peptic ulcer. Methods: This study was conducted at Can Tho Children’s Hospital and Can Tho University of Medicine and Pharmacy Hospital between March 2019 and April 2022. We performed an upper gastrointestinal endoscopy, cultured H. pylori from biopsies of gastric mucosa, determined antibiotic sensitivities to H. pylori by the E-test method, and treated eradication based on the antibiotic susceptibilities of bacteria. After at least 4 weeks of eradication therapy, we assessed the effectiveness of treatment with a breath test. Results: Among 237 children recruited in this study, 48.9% were boys and 51.1% were girls, and the mean age was 10.03 ± 2.53 years. We determined that 80.6% of H. pylori were resistant to clarithromycin, as well as amoxicillin, metronidazole, levofloxacin, and tetracycline, at 71.7%, 49.4%, 45.1%, and 11.4%, respectively. The overall eradication rate of H. pylori was 83.1% (172/207). Among therapies tailored to antimicrobial susceptibility, the bismuth quadruple regimen achieved the greatest success, but the efficacy of triple therapy with esomeprazole + AMX + CLR/MTZ was low. Conclusions: Tailored eradication therapy was highly successful in our study but did not achieve over 90%. We recommend that in countries with a high prevalence of antibiotic resistance in H. pylori strains, particularly where the amoxicillin-resistance rate of H. pylori is high, therapy tailored to antimicrobial susceptibility should be used as first-line therapy, and bismuth and tetracycline should be added to enhance the eradication efficacy in children.

Neurological disorders including traumatic brain injury, stroke, primary and metastatic brain tumors, and neurodegenerative diseases affect millions of people worldwide. Disease progression is accompanied by changes in the brain microenvironment, but how these shifts in biochemical, biophysical, and cellular properties contribute to repair outcomes or continued degeneration is largely unknown. Tissue engineering approaches can be used to develop in vitro models to understand how the brain microenvironment contributes to pathophysiological processes linked to neurological disorders and may also offer constructs that promote healing and regeneration in vivo. In this Perspective, we summarize features of the brain microenvironment in normal and pathophysiological states and highlight strategies to mimic this environment to model disease, investigate neural stem cell biology, and promote regenerative healing. We discuss current limitations and resulting opportunities to develop tissue engineering tools that more faithfully recapitulate the aspects of the brain microenvironment for both in vitro and in vivo applications.

The current opioid crisis and the increase in injection drug use (IDU) have led to outbreaks of HIV in communities across the country. These outbreaks have prompted country and statewide examination into identifying factors to determine areas at risk of a future HIV outbreak. Based on methodology used in a prior nationwide county-level analysis by the US Centers for Disease Control and Prevention (CDC), we examined Illinois at the ZIP code level (n = 1,383). Combined acute and chronic hepatitis C virus (HCV) infection among persons

Introduction: To expand access to naloxone, the state of Illinois implemented a standing order allowing registered pharmacies to dispense the drug without an individual prescription. To participate under the standing order, pharmacies were required to opt in through a formal registration process. In our study we aimed to evaluate the availability and price of naloxone at registered pharmacies.Methods: This was a prospective, de-identified, cross-sectional telephone survey. Trained interviewers posed as potential customers and used a standardized script to determine the availability of naloxone between February–December, 2019. The primary outcome was defined as a pharmacy indicating it carried naloxone, currently had naloxone in stock, and was able to dispense it without anindividual prescription.Results: Of 948 registered pharmacies, 886 (93.5%) were successfully contacted. Of those, 792 (83.4%) carried naloxone, 659 (74.4%) had naloxone in stock, and 472 (53.3%) allowed purchase without a prescription. Naloxone nasal spray (86.4%) was the formulation most commonly stocked. Chain pharmacies were more likely to carry naloxone (adjusted odds ratio [aOR] 3.16, 95% confidence interval [CI] 1.97–5.01, P < 0.01) and have naloxone in stock (aOR 2.72, 95% CI 1.76–4.20, P < 0.01), but no more likely to dispense it without a prescription. Pharmacies in higher population areas (aOR 0.99, 95% CI 0.99–0.99, P < 0.05) and rural areas adjacent to metropolitan areas (aOR 0.5, 95% CI 025–0.98, P < 0.05) were less likely to have naloxone available without a prescription. Associations of naloxone availability based on other urbanicity designations, overdose count, and overdose rate were not significant.Conclusion: Among pharmacies in Illinois that formally registered to dispense naloxone without a prescription, the availability of naloxone remains limited. Additional interventions may be needed to maximize the potential impact of a statewide standing order.

Summary: Tumor-associated macrophages (TAMs) play an important role in tumor immunity and comprise of subsets that have distinct phenotype, function, and ontology. Transcriptomic analyses of human medulloblastoma, the most common malignant pediatric brain cancer, showed that medulloblastomas (MBs) with activated sonic hedgehog signaling (SHH-MB) have significantly more TAMs than other MB subtypes. Therefore, we examined MB-associated TAMs by single-cell RNA sequencing of autochthonous murine SHH-MB at steady state and under two distinct treatment modalities: molecular-targeted inhibitor and radiation. Our analyses reveal significant TAM heterogeneity, identify markers of ontologically distinct TAM subsets, and show the impact of brain microenvironment on the differentiation of tumor-infiltrating monocytes. TAM composition undergoes dramatic changes with treatment and differs significantly between molecular-targeted and radiation therapy. We identify an immunosuppressive monocyte-derived TAM subset that emerges with radiation therapy and demonstrate its role in regulating T cell and neutrophil infiltration in MB.

Background: Increased drug use has disproportionately impacted rural areas across the U.S. People who use drugs are at risk of overdose and other medical complications, including infectious diseases. Understanding barriers to healthcare access for this often stigmatized population is key to reducing morbidity and mortality, particularly in rural settings where resources may be limited.Methods: We conducted 20 semi-structured interviews with people who use drugs, including 17 who inject drugs, in rural southern Illinois between June 2018 and February 2019. Interviews were analyzed using a modified grounded theory approach where themes are coded and organized as they emerge from the data.Results: Participants reported breaches of trust by healthcare providers, often involving law enforcement and Emergency Medical Services, that dissuaded them from accessing medical care. Participants described experiences of mistreatment in emergency departments, with one account of forced catheterization. They further recounted disclosures of protected health information by healthcare providers, including communicating drug test results to law enforcement and sharing details of counseling sessions with community members without consent. Participants also described a hesitancy common among people who use drugs to call emergency medical services for an overdose due to fear of arrest.Conclusion: Breaches of trust by healthcare providers in rural communities discouraged people who use drugs from accessing medical care until absolutely necessary, if at all. These experiences may worsen healthcare outcomes and further stigmatize this marginalized community. Structural changes including reforming and clarifying law enforcement's role in Emergency Departments as well as instituting diversion policies during arrests may help rebuild trust in these communities. Other possible areas for intervention include stigma training and harm reduction education for emergency medicine providers, as well as developing and implementing referral systems between Emergency Departments and local harm reduction providers and medically assisted drug treatment programs.

Summary: Activated macrophages must carefully calibrate their inflammatory responses to balance efficient pathogen control with inflammation-mediated tissue damage, but the molecular underpinnings of this “balancing act” remain unclear. Using genetically engineered mouse models and primary macrophage cultures, we show that Toll-like receptor (TLR) signaling induces the expression of the transcription factor Spic selectively in patrolling monocytes and tissue macrophages by a nuclear factor κB (NF-κB)-dependent mechanism. Functionally, Spic downregulates pro-inflammatory cytokines and promotes iron efflux by regulating ferroportin expression in activated macrophages. Notably, interferon-gamma blocks Spic expression in a STAT1-dependent manner. High levels of interferon-gamma are indicative of ongoing infection, and in its absence, activated macrophages appear to engage a “default” Spic-dependent anti-inflammatory pathway. We also provide evidence for the engagement of this pathway in sterile inflammation. Taken together, our findings uncover a pathway wherein counter-regulation of Spic by NF-κB and STATs attune inflammatory responses and iron metabolism in macrophages.

Abstract Efforts for tissue engineering vascular grafts focuses on the tunica media and intima, although the tunica adventitia serves as the primary structural support for blood vessels. In surgery, during endarterectomies, surgeons can strip the vessel, leaving the adventitia as the main strength layer to close the vessel. Here, we adapted our recently developed technique of forming vascular tissue rings then stacking the rings into a tubular structure, to accommodate human fibroblasts to create adventitia vessels in 8 days. Collagen production and fibril cross-linking was augmented with TGF-β and ascorbic acid, significantly increasing tensile strength to 57.8 ± 3.07 kPa (p = 0.008). Collagen type I gel was added to the base fibrin hydrogel to further increase strength. Groups were: Fibrin only; 0.7 mg/ml COL; 1.7 mg/ml COL; and 2.2 mg/ml COL. The 0.7 mg/ml collagen rings resulted in the highest tensile strength at 77.0 ± 18.1 kPa (p = 0.015). Culture periods of 1–2 weeks resulted in an increase in extracellular matrix deposition and significantly higher failure strength but not ultimate tensile strength. Histological analysis showed the 0.7 mg/ml COL group had significantly more, mature collagen. Thus, a hydrogel of 0.7 mg/ml collagen in fibrin was ideal for creating and strengthening engineered adventitia vessels.

Abstract Background Application of cardiac stem cells combined with biomaterial scaffold is a promising therapeutic strategy for heart repair after myocardial infarction. However, the optimal cell types and biomaterials remain elusive. Methods In this study, we seeded Isl1+ embryonic cardiac progenitor cells (CPCs) into decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM) to assess the therapeutic potential of Isl1+ CPCs and the biocompatibility of SIS-ECM with these cells. Results We observed that SIS-ECM supported the viability and attachment of Isl1+ CPCs. Importantly, Isl1+ CPCs differentiated into cardiomyocytes and endothelial cells 7 days after seeding into SIS-ECM. In addition, SIS-ECM with CPC-derived cardiomyocytes showed spontaneous contraction and responded to β-adrenergic stimulation. Next, patches of SIS-ECM seeded with CPCs for 7 days were transplanted onto the outer surface of infarcted myocardium in mice. Four weeks after transplantation, the patches were tightly attached to the surface of the host myocardium and remained viable. Transplantation of patches improved cardiac function, decreased the left ventricular myocardial scarring area, and reduced fibrosis and heart failure. Conclusions Transplantation of Isl1+ CPCs seeded in SIS-ECM represents an effective approach for cell-based heart therapy.

Background: Inappropriate antibiotic use among outpatients is recognized as the primary driver of antibiotic resistance. A proper understanding of appropriate antibiotic usage and associated factors helps to determine and limit inappropriateness. We aimed to identify the rate of appropriate use of antibiotics and identify factors associated with the inappropriate prescriptions. Methods: We conducted a cross-sectional descriptive study in outpatient antibiotic use at a hospital in Can Tho City, Vietnam, from August 1, 2019, to January 31, 2020. Data were extracted from all outpatient prescriptions at the Medical Examination Department and analyzed by SPSS 18 and Chi-squared tests, with 95% confidence intervals. The rationale for antibiotic use was evaluated through antibiotic selection, dose, dosing frequency, dosing time, interactions between antibiotics and other drugs, and general appropriate usage. Results: A total of 420 prescriptions were 51.7% for females, 61.7% with health insurance, and 44.0% for patients with one comorbid condition. The general appropriate antibiotic usage rate was 86.7%. Prescriptions showed that 11.0% and 9.5% had a higher dosing frequency and dose than recommended, respectively; 10.2% had an inappropriate dosing time; 3.1% had drug interactions; and only 1.7% had been prescribed inappropriate antibiotics. The risk of inappropriate antibiotic use increased in patients with comorbidities and antibiotic treatment lasting >7 days (p < 0.05). Conclusions: The study indicated a need for more consideration when prescribing antibiotics to patients with comorbidities or using more than 7 days of treatment.

We describe the epidemiological characteristics, pattern of circulation, and geographical distribution of influenza B viruses and its lineages using data from the Global Influenza B Study. We included over 1.8 million influenza cases occurred in thirty-one countries during 2000-2018. We calculated the proportion of cases caused by influenza B and its lineages; determined the timing of influenza A and B epidemics; compared the age distribution of B/Victoria and B/Yamagata cases; and evaluated the frequency of lineage-level mismatch for the trivalent vaccine. The median proportion of influenza cases caused by influenza B virus was 23.4%, with a tendency (borderline statistical significance, p = 0.060) to be higher in tropical vs. temperate countries. Influenza B was the dominant virus type in about one every seven seasons. In temperate countries, influenza B epidemics occurred on average three weeks later than influenza A epidemics; no consistent pattern emerged in the tropics. The two B lineages caused a comparable proportion of influenza B cases globally, however the B/Yamagata was more frequent in temperate countries, and the B/Victoria in the tropics (p = 0.048). B/Yamagata patients were significantly older than B/Victoria patients in almost all countries. A lineage-level vaccine mismatch was observed in over 40% of seasons in temperate countries and in 30% of seasons in the tropics. The type B virus caused a substantial proportion of influenza infections globally in the 21st century, and its two virus lineages differed in terms of age and geographical distribution of patients. These findings will help inform health policy decisions aiming to reduce disease burden associated with seasonal influenza.

The efficacy of T cells expressing chimeric antigen receptors (CARs) for solid tumors has been limited by insufficient CAR T cell expansion and persistence. The use of virus-specific T cells (VSTs) as carriers for CARs may overcome this limitation since CAR-VSTs can be boosted by viral vaccines or oncolytic viruses. However, there is limited understanding of the optimal combination of endodomains and their influence on the native T cell receptor (TCR) in VSTs. We therefore compared the function of GD2.CARs expressing the TCR zeta chain (ζ) alone or combined with endodomains from CD28 and 4-1BB in varicella zoster virus-specific (VZV) T cells. VZVSTs expressing GD2-CARs recognized VZV-derived peptides and killed GD2-expressing tumor cells. However, after repeated stimulation through their native TCR, the expansion of GD2-CAR.CD28ζ-VZVSTs was 3.3-fold greater (p < 0.001) than non-transduced VZVSTs, whereas GD2-CARζ- and GD2-CAR.41BBζ inhibited VZVST expansion (p < 0.01). Compared to control VZVSTs, GD2-CAR.ζ VZVSTs showed a greater frequency of apoptotic (p < 0.01) T cells, whereas prolonged downregulation of the native αβ TCR was observed in GD2-CAR.41BBζ VZVSTs (p < 0.001). We confirmed that CD28ζ can best maintain TCR function by expressing GD2.CARs in Epstein-Barr virus-specific T cells and CD19-CARs in VZVSTs. In response to CAR stimulation VSTs with CD28ζ endodomains also showed the greatest expansion (6 fold > GD2-CAR.41BBζ VZVSTs (p < 0.001), however anti-tumor efficacy was superior in GD2-CAR.41BBζ-VZVSTs. These findings demonstrate that CAR signaling domains can enhance or diminish the function of the native TCR and indicate that only CD28ζ may preserve the function of the native TCR in tonically signaling CAR-VSTs.

Previously, we noted that carboxylated multi-walled carbon nanotubes (cMWNTs) coated with Pluronic® F-108 (PF108) bound to and were accumulated by macrophages, but that pristine multi-walled carbon nanotubes (pMWNTs) coated with PF108 were not (Wang et al., Nanotoxicology2018, 12, 677). Subsequent studies with Chinese hamster ovary (CHO) cells that overexpressed scavenger receptor A1 (SR-A1) and with macrophages derived from mice knocked out for SR-A1 provided evidence that SR-A1 was a receptor of PF108-cMWNTs (Wang et al., Nanomaterials (Basel) 2020, 10, 2417). Herein, we replaced the PF108 coat with bovine serum albumin (BSA) to investigate how a BSA corona affected the interaction of multi-walled carbon nanotubes (MWNTs) with cells. Both BSA-coated cMWNTs and pMWNTs bound to and were accumulated by RAW 264.7 macrophages, although the cells bound two times more BSA-coated cMWNT than pMWNTs. RAW 264.7 cells that were deleted for SR-A1 using CRISPR-Cas9 technology had markedly reduced binding and accumulation of both BSA-coated cMWNTs and pMWNTs, suggesting that SR-A1 was responsible for the uptake of both MWNT types. Moreover, CHO cells that ectopically expressed SR-A1 accumulated both MWNT types, whereas wild-type CHO cells did not. One model to explain these results is that SR-A1 can interact with two structural features of BSA-coated cMWNTs, one inherent to the oxidized nanotubes (such as COOH and other oxidized groups) and the other provided by the BSA corona; whereas SR-A1 only interacts with the BSA corona of BSA-pMWNTs.

This paper considers a non-orthogonal multiple access (NOMA) downlink network, where a hybrid of NOMA and beamforming designs is developed to enhance the channel capacity. We aim to improve the system performance in terms of rate fairness and power consumption. Hence, a multi-objective problem with a joint optimization of user equipment pairing, power control, and quality-of-service requirements is addressed. To efficiently solve the problem, we propose two low-complexity algorithms based on the inner-approximation method, with the first algorithm using the relaxation method and the second one using graph theory. Numerical results are provided to demonstrate the effectiveness of the two proposed algorithms in comparison with the exhaustive search and existing methods.