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Medical implant-associated infections (IAI) is a growing threat to patients undergoing implantation surgery. IAI prevention typically relies on medical implants endowed with bactericidal properties achieved through surface modifications with antibiotics. However, the clinical efficacy of this traditional paradigm remains suboptimal, often necessitating revision surgery and posing potentially lethal consequences for patients. To bolster the existing anti-IAI arsenal, we propose herein a chitosan-based bioactive coating, i.e., ChitoAntibac, which exerts bacteria-inhibitory effects either through immune modulation or phage-directed microbial clearance, without relying on conventional antibiotics. The immuno-stimulating effects and phage-induced bactericidal properties can be tailored by engineering the loading dynamic of macrophage migration inhibitory factor (MIF), which polarizes macrophages towards the proinflammatory subtype (M1) with enhanced bacterial phagocytosis, and Staphylococcal Phage K, resulting in rapid and targeted pathogenic clearance (>99.99%) in less than 8 h. Our innovative antibacterial coating opens a new avenue in the pursuit of effective IAI prevention through immuno-stimulation and phage therapeutics.

Latino children of Migrant and Seasonal Farmworkers (MSFWs) with asthma are at risk for poor health outcomes due to medical access barriers. We compared differences in acute care utilization for asthma exacerbations among migrant and non-migrant Latino and non-Hispanic white (NHW) children at U.S. community health centers.A retrospective observational study utilizing electronic health record data from the ADVANCE Clinical Research Network of United States community health centers included 13,423 children ages 3–17 with a primary care visit between 2005 and 2017 from eight states. Emergency department (ED) and hospitalization data came from Oregon Medicaid claims. Outcomes included acute clinic visits, ED visits, and hospitalizations for asthma exacerbation. Regression analyses adjusted for patient-level covariates.Latino children had higher odds of acute clinic visits for asthma exacerbation compared to NHW children (MSFW odds ratio [OR] = 1.17, 95 % CI = 1.03–1.33; without migrant status OR = 1.13, 95 % CI = 1.03–1.23). MSFW children using Oregon Medicaid had fewer ED visits (rate ratio [RR] = 0.72, 95 % CI = 0.52–0.99) and hospitalizations (RR = 0.47, 95 % CI = 0.26–0.86) compared to NHW children.Increased community health center visits may help mitigate disparities in acute asthma care for MSFW children.

Heteromorphic sex chromosomes are usually thought to have originated from a pair of autosomes that acquired a sex-determining locus and subsequently stopped recombining, leading to degeneration of the sex-limited chromosome. The majority of nematode species lack heteromorphic sex chromosomes and determine sex using an X-chromosome counting mechanism, with males being hemizygous for one or more X chromosomes (XX/X0). Some filarial nematode species, including important parasites of humans, have heteromorphic XX/XY karyotypes. It has been assumed that sex is determined by a Y-linked locus in these species. However, karyotypic analyses suggested that filarial Y chromosomes are derived from the unfused homologue of an autosome involved in an X-autosome fusion event. Here, we generated a chromosome-level reference genome for Litomosoides sigmodontis, a filarial nematode with the ancestral filarial karyotype and sex determination mechanism (XX/X0). By mapping the assembled chromosomes to the rhabditid nematode ancestral linkage (or Nigon) elements, we infer that the ancestral filarial X chromosome was the product of a fusion between NigonX (the ancestrally X-linked element) and NigonD (ancestrally autosomal). In the two filarial lineages with XY systems, there have been two independent X-autosome chromosome fusion events involving different autosomal Nigon elements. In both lineages, the region shared by the neo-X and neo-Y chromosomes is within the ancestrally autosomal portion of the X, confirming that the filarial Y chromosomes are derived from the unfused homologue of the autosome. Sex determination in XY filarial nematodes therefore likely continues to operate via the ancestral X-chromosome counting mechanism, rather than via a Y-linked sex-determining locus.

The search for the chiral magnetic effect (CME) in heavy-ion collisions has been impeded by the significant background arising from the anisotropic particle emission pattern, particularly elliptic flow. To alleviate this background, the event shape selection (ESS) technique categorizes collision events according to their shapes and projects the CME observables to a class of events with minimal flow. In this study, we explore two event shape variables to classify events and two elliptic flow variables to regulate the background. Each type of variable can be calculated from either single particles or particle pairs, resulting in four combinations of event shape and elliptic flow variables. By employing a toy model and the realistic event generator, event-by-event anomalous-viscous fluid dynamics (EBE-AVFD), we discover that the elliptic flow of resonances exhibits correlations with both the background and the potential CME signal, making the resonance flow unsuitable for background control. Through the EBE-AVFD simulations of Au+Au collisions at sNN=200 GeV with various input scenarios, we ascertain that the optimal ESS strategy for background control entails utilizing the single-particle elliptic flow in conjunction with the event shape variable based on particle pairs.

With growing mental health concerns among college students, they need to effectively develop skills to alleviate stress amidst the demands of university life. Teaching mindfulness skills to engineering students early in their programs, such as during introductory courses, may provide students with the tools they need to effectively cope with academic stressors, support well-being, and mitigate mental health concerns. This study aimed to understand the variation in experiences of engineering students who participated in weekly mindfulness meditation during a first-year cornerstone engineering course. This study used a thematic analysis approach to analyze students’ in-class, weekly reflections from eight meditation exercises across two course sections. The frequency of codes and themes were then analyzed across meditation types to identify trends in student experiences. Our results show that the most common student experience from engaging in mindfulness meditation was feeling less stressed, calmer, and more relaxed. Other positive experiences include feeling more energized and focused. Some students, however, did report some negative experiences, such as distress and tiredness. The Dynamic Breathing exercise, in particular, showed higher rates of negative experiences than other meditation types. The results also demonstrate that different types of meditations produce different student experiences. Meditation exercises with open monitoring components showed higher rates of insight/awareness and difficulty focusing attention than focused attention meditations. These findings indicate that utilizing weekly mindfulness exercises in introductory engineering courses can benefit students’ overall mental health and well-being when adequately implemented.

Microbial resistance to current antibiotics therapies is a major cause of implant failure and adverse clinical outcomes in orthopaedic surgery. Recent developments in advanced antimicrobial nanotechnologies provide numerous opportunities to effective remove resistant bacteria and prevent resistance from occurring through unique mechanisms. With tunable physicochemical properties, nanomaterials can be designed to be bactericidal, antifouling, immunomodulating, and capable of delivering antibacterial compounds to the infection region with spatiotemporal accuracy. Despite its substantial advancement, an important, but under-explored area, is potential microbial resistance to nanomaterials and how this can impact the clinical use of antimicrobial nanotechnologies. This review aims to provide a better understanding of nanomaterial-associated microbial resistance to accelerate bench-to-bedside translations of emerging nanotechnologies for effective control of implant associated infections.

Abstract Background Residential treatment is a common approach for treating opioid use disorder (OUD), however, few studies have directly compared it to outpatient treatment. The objective of this study was to compare OUD outcomes among individuals receiving residential and outpatient treatment. Methods A retrospective cohort study used linked data from a state Medicaid program, vital statistics, and the Substance Abuse and Mental Health Services Administration (SAMHSA) Treatment Episodes Dataset (TEDS) to compare OUD-related health outcomes among individuals treated in a residential or outpatient setting between 2014 and 2017. Multivariable Cox proportional hazards and logistic regression models examined the association between treatment setting and outcomes (i.e., opioid overdose, non-overdose opioid-related and all-cause emergency department (ED) visits, hospital admissions, and treatment retention) controlling for patient characteristics, co-morbidities, and use of medications for opioid use disorders (MOUD). Interaction models evaluated how MOUD use modified associations between treatment setting and outcomes. Results Of 3293 individuals treated for OUD, 957 (29%) received treatment in a residential facility. MOUD use was higher among those treated as an outpatient (43%) compared to residential (19%). The risk of opioid overdose (aHR 1.39; 95% CI 0.73–2.64) or an opioid-related emergency department encounter or admission (aHR 1.02; 95% CI 0.80–1.29) did not differ between treatment settings. Independent of setting, MOUD use was associated with a significant reduction in overdose risk (aHR 0.45; 95% CI 0.23–0.89). Residential care was associated with greater odds of retention at 6-months (aOR 1.71; 95% CI 1.32–2.21) but not 1-year. Residential treatment was only associated with improved retention for individuals not receiving MOUD (6-month aOR 2.05; 95% CI 1.56–2.71) with no benefit observed in those who received MOUD (aOR 0.75; 95% CI 0.46–1.29; interaction p = 0.001). Conclusions Relative to outpatient treatment, residential treatment was not associated with reductions in opioid overdose or opioid-related ED encounters/hospitalizations. Regardless of setting, MOUD use was associated with a significant reduction in opioid overdose risk.

Background: The COVID-19 pandemic presents challenges in participant recruitment strategies for clinical research involving people with opioid use disorders recently engaged in treatment. We describe challenges to participant recruitment in a trial comparing virtual buprenorphine treatment platform to office-based buprenorphine treatment. Methods: The parent study was a cohort trial of telehealth delivered buprenorphine treatment compared to office-based buprenorphine treatment, however, due to the pandemic potential participant recruitment for both arms became virtual. Between 9/27/2021 and 7/11/2022, telephone, email, flyers, and word-of-mouth were used to recruit study participants from each treatment setting. Recruitment tracking documents recorded the primary outcomes: number of outreach attempts and most effective contact methods. Results: Treatment settings provided contact information for 1485 potential study participants. Information was incorrect or disconnected for 282 (19%) individuals, 695 (47%) did not respond to outreach, and 508 (34%) responded to outreach. Of these responders, 369 were interested in study participation, 259 completed the online informed consent and screening assessment, and 148 met eligibility criteria and enrolled in the study. A total of 3804 virtual outreach attempts across 1485 potential participants were made, resulting in an average of 2.7 attempts per contact and a mean of 25.7 attempts per enrolled participant (n = 148). Conclusion: Conducting research during the COVID-19 pandemic required shifting from in-person to virtual recruitment strategies to contact and engage potential study participants. Virtual recruitment for this population during a pandemic appears to be less efficient and hindered efforts to meet recruitment goals.

BackgroundDespite the fact that direct oral anticoagulants (DOACs) are favoured over warfarin for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), physicians need to maintain competence in using and monitoring warfarin since many patients have contraindications or other barriers to using DOACs. Unlike DOACs, warfarin therapy requires regular blood testing to ensure that it is within a target range to ensure efficacy and safety. There is limited real-world data on the adequacy of warfarin control and the cost and burden of monitoring warfarin therapy in Canadian NVAF patients.ObjectivesIn a large cohort of Canadian patients with NVAF on warfarin we assessed time in therapeutic range (TTR), determinants of TTR, process of care, direct costs, health related quality of life and loss of work time and productivity related to warfarin therapy.MethodsFive hundred and fifty one patients with NVAF, either newly initiated or stable on warfarin were prospectively enrolled across 9 Canadian provinces from primary care practices and anticoagulant clinics. Participating physicians provided baseline demographic and medical information. Patients completed diaries for 48 weeks, capturing information about International Normalized Ratio (INR) test results, test locations, process of INR monitoring, direct costs of travel, health-related quality of life and work productivity measures. TTR was estimated using linear interpolation of INR results and linear regression used to investigate associations between TTR and factors (defined a priori).ResultsFour hundred and eighty (87.1%) patients had complete follow-up with an overall TTR of 74.4% based on 7,175 physician-reported INR values from 501 patients. 88% of this cohort were monitored through routine medical care (RMC). The average number of INRs per patient during the 48-week period was 14.1 (standard deviation (SD) = 8.3) tests with a mean duration of 23.8 (SD = 11.1) days between tests. We did not find a relationship between TTR and age, sex, presence of major comorbidities, patient's province of residence or rural vs. urban residence. 12% of patients monitored through anticoagulant clinics had significantly better TTR than patients monitored through RMC (82% vs. 74%; 95% confidence interval: -13.8, -1.2; p = 0.02). Health related quality of life utility values were high and remained consistent throughout the study. The majority of patients reported no impact on either work productivity or impairment of regular activities due to being on long-term warfarin treatment.ConclusionsWe showed excellent overall TTR in an observed Canadian cohort, with monitoring through a dedicated anticoagulant clinic being associated with a statistically and clinically significant improvement in TTR. The burden of warfarin therapy on patients' health related quality of life or daily work and activities was low.

Introduction Glaucoma is a progressive, chronic condition that can have a significant impact on a patient’s health-related quality of life (HRQoL). Validated, disease-specific HRQoL tools such as the Health Utility for Glaucoma (HUG-5) tool and the Glaucoma Quality of Life Questionnaire (GlauQoL-17) can be used to monitor a patient’s quality of life. However, the utility of these tools in outpatient clinic practice is not well established. The primary objective of this study is to characterise the feasibility of administering periodic HRQoL questionnaires in glaucoma using a semi-automated workflow.Methods and analysis This study will be a single-centre, unblinded, randomised, parallel-group study with an exploratory data analysis framework. We aim to determine the feasibility of administering the HUG-5 in an outpatient clinic using a semi-automated workflow and determine patient engagement through email and telephone contact methods. We will also be investigating the association of the HUG-5 and GlauQoL-17 with patient visual field testing and visual acuity. Mean differences between groups will be tested with analysis of variance to determine if the frequency of calls affects burden, satisfaction and perceived value of information.Ethics and dissemination This study has been approved by the Hamilton Integrated Research Ethics board (ID: 13046) and will be conducted within Canadian Tri-Council Statement policy. Personal information of the study’s participants will be anonymised with identification codes and data will be kept on an encrypted server. Results of this study will be disseminated through peer-reviewed journals, conferences and internal meetings.

Transitional care interventions have the potential to optimize continuity of care, improve health outcomes and enhance quality of life for adolescents and young adults living with chronic childhood-onset disabilities, including neurodevelopmental disorders, as they transition to adult health and social care services. The paucity of research in this area poses challenges in identifying and implementing interventions for research, evaluation and implementation. The purpose of this project was to advance this research agenda by identifying the transitional care interventions from the scientific literature and prioritize interventions for study. A modified-Delphi approach involving two rounds of online surveys followed by a face-to-face consensus meeting with knowledge users, researchers and clinician experts in transitional care (n = 19) was used. A subsequent virtual meeting concluded the formulation of next steps. Experts rated 16 categories of interventions, derived from a systematic review, on importance, impact, and feasibility. Seven of the 16 interventions categories received a mean score rating of ≥7 (out of 10) on all three rating categories. Participants then rank ordered the reduced list of seven interventions in order of priority and the top four ranked interventions advanced for further discussion at a consensus meeting. Using the Template for Intervention Description and Replication (TIDieR) checklist as a guide, the participants identified that a study of a peer system navigator was worthy of future evaluation. This study highlighted that transitional care interventions are complex and multifaceted. However, the presence of a peer to support system navigation, advocacy and individual and family education was considered the most ideal intervention addressing the current gap in care. Future research, which aims to engage patients and families in a co-design approach, is recommended to further develop this intervention.

Abstract Background Early readmission amongst older safety-net hospitalized adults is costly. Interventions to prevent early readmission have had mixed success. The role of perceived social support is unclear. We examined the association of perceived social support in 30-day readmission or death in older adults admitted to a safety-net hospital. Methods This is an observational cohort study derived from the Support From Hospital to Home for Elders (SHHE) trial. Participants were community-dwelling English, Spanish and Chinese speaking older adults admitted to medicine wards at an urban safety-net hospital in San Francisco. We assessed perceived social support using the Multidimensional Scale of Perceived Social Support (MSPSS). We defined high social support as the highest quartile of MSPSS. We ascertained 30-day readmission and mortality based on a combination of participant self-report, hospital and death records. We used multiple/multivariable logistic regression to adjust for patient demographics, health status, and health behaviors. We tested for whether race/ethnicity modified the effect high social support had on 30-day readmission or death by including a race-social support interaction term. Results Participants (n = 674) had mean age of 66.2 (SD 9.0), with 18.8% White, 24.8% Black, 31.9% Asian, and 19.3% Latino. The 30-day readmission or death rate was 15.0%. Those with high social support had half the odds of readmission or death than those with low social support (OR = 0.47, 95% CI 0.26–0.88). Interaction analyses revealed race modified this association; higher social support was protective against readmission or death among minorities (AOR = 0.35, 95% CI 0.16–0.76) but increased likelihood of readmission or death among Whites (AOR = 3.7, 95% CI 1.07–12.9). Conclusion In older safety-net patients nearing discharge, high perceived social support may protect against 30-day readmission or death among minorities. Assessing patients’ social support may aid targeting of transitional care resources and intervention design. How perceived social support functions across racial/ethnic groups in health outcomes warrants further study. Trial registration NIH trials registry number ClinicalTrials.gov: NCT01221532.

Abstract Background Monoclonal antibodies against calcitonin gene-related peptide (CGRP) or its receptor are efficacious for the prevention of migraine headaches. The downstream molecular mechanisms following ligand-receptor blockade by which these antibodies prevent CGRP signaling through CGRP receptors have not been demonstrated. Methods Here we produced tool monoclonal functional antagonist antibodies against CGRP and its canonical receptor and developed a novel cellular model using fluorogen-activated protein technology that allows detection of CGRP receptor internalization by flow cytometry and, for an extended time course, visualization by confocal microscopy. Results Using this cell model we showed that these antagonist antibodies block both CGRP-induced cAMP signaling and CGRP receptor internalization. At least 10-fold higher concentrations of either antibody are necessary to block CGRP receptor internalization compared with cAMP accumulation in our cell model. Conclusion These data reinforce our understanding of how monoclonal functional antagonist antibodies interfere with CGRP signaling.

Abstract Background Medically complex urban patients experiencing homelessness comprise a disproportionate number of high-cost, high-need patients. There are few studies of interventions to improve care for these populations; their social complexity makes them difficult to study and requires clinical and research collaboration. We present a protocol for a trial of the streamlined unified meaningfully managed interdisciplinary team (SUMMIT) team, an ambulatory ICU (A-ICU) intervention to improve utilization and patient experience that uses control populations to address limitations of prior research. Methods/design Participants are patients at a Federally Qualified Health Center in Portland, Oregon that serves patients experiencing homelessness or who have substance use disorders. Participants meet at least one of the following criteria: > 1 hospitalization over past 6 months; at least one medical co-morbidity including uncontrolled diabetes, heart failure, chronic obstructive pulmonary disease, liver disease, soft-tissue infection; and 1 mental health diagnosis or substance use disorder. We exclude patients if they have

Abstract Background Dysnatremias are associated with increased mortality in critically ill patients. Hypernatremia in burn patients is also associated with poor survival. Based on these findings, we hypothesized that high plasma sodium variability is a marker for increased mortality in severely burn-injured patients. Methods We performed a retrospective review of adult burn patients with a burn injury of 15% total body surface area (TBSA) or greater from 2010 to 2014. All patients included in the study had at least three serum sodium levels checked during admission. We used multivariate logistic regression analysis to determine if hypernatremia, hyponatremia, or sodium variability independently increased the odds ratio (OR) for death. Results Two hundred twelve patients met entry criteria. Mean age and %TBSA for the study was 45 ± 18 years and 32 ± 19%. Twenty-nine patients died for a mortality rate of 14%. Serum sodium was measured 10,310 times overall. The median number of serum sodium measurements per patient was 22. Non-survivors were older (59 ± 19 vs. 42 ± 16 years) and suffered from a more severe burn injury (50 ± 25% vs. 29 ± 16%TBSA). While mean sodium was significantly higher for non-survivors (138 ± 3 milliequivalents/liter (meq/l)) than for survivors (135 ± 2 meq/l), mean sodium levels remained within the laboratory reference range (135 to 145 meq/l) for both groups. Non-survivors had a significantly higher median number of hypernatremic (> 145 meq/l) measurements (2 vs. 0). Coefficient of variation (CV) was significantly higher in non-survivors (2.85 ± 1.1) than survivors (2.0 ± 0.7). Adjusting for TBSA, age, ventilator days, and intensive care unit (ICU) stay, a higher CV of sodium measurements was associated with mortality (OR 5.8 (95% confidence interval (CI) 1.5 to 22)). Additionally, large variation in sodium ranges in the first 10 days of admission may be associated with increased mortality (OR 1.35 (95% CI 1.06 to1.7)). Conclusions Increased variability in plasma sodium may be associated with death in severely burned patients.

Both intrinsic and external signals regulate stem cell fate. Here, the authors perform a genome-wide RNAi screen to identify regulators of testis germline stem cells (GSC) in Drosophila, finding more than half of the genes were external regulators and heterochromatin/cytokinesis proteins mediated GSC fate.

Non-medical prescription opioid use is a growing public health concern. Social media is an emerging tool to understand health attitudes, beliefs, and behaviors.We retrieved a sample of publicly available Twitter messages in early 2014, using common opioid medication names and slang search terms. We used content analysis to code messages by user, context of message (personal vs general experiences), and key content themes.We reviewed 540 messages, of which 375 (69%) messages were related to opioid behaviors. Of these, 316 (84%) originated from individual user accounts; 125 messages expressed personal experience with opioids. The majority of personal messages referenced using opioids to obtain a "high", use for sleep, or other non-intended use (87,70%). General attitudes regarding opioid use included positive sentiment (52, 27%), comments on others peoples opioid use (57, 30%), and messages containing public health information or links (48, 25%).In a sample of social media messages mentioning opioid medications, the most common theme amongst English users related to various forms of opioid misuse. Social media can provide insights into the types of misuse of opioids that might aid public health efforts to reduce non-medical opioid use.

The active loop extrusion hypothesis proposes that chromatin threads through the cohesin protein complex into progressively larger loops until reaching specific boundary elements. We build upon this hypothesis and develop an analytical theory for active loop extrusion which predicts that loop formation probability is a nonmonotonic function of loop length and describes chromatin contact probabilities. We validate our model with Monte Carlo and hybrid Molecular Dynamics-Monte Carlo simulations and demonstrate that our theory recapitulates experimental chromatin conformation capture data. Our results support active loop extrusion as a mechanism for chromatin organization and provide an analytical description of chromatin organization that may be used to specifically modify chromatin contact probabilities. [ABSTRACT FROM AUTHOR]

Identification of small and large molecule pain therapeutics that target the genetically validated voltage-gated sodium channel Na V1.7 is a challenging endeavor under vigorous pursuit. The monoclonal antibody SVmab1 was recently published to bind the Na V1.7 DII voltage sensor domain and block human Na V1.7 sodium currents in heterologous cells. We produced purified SVmab1 protein based on publically available sequence information, and evaluated its activity in a battery of binding and functional assays. Herein, we report that our recombinant SVmAb1 does not bind peptide immunogen or purified Na V1.7 DII voltage sensor domain via ELISA, and does not bind Na V1.7 in live HEK293, U-2 OS, and CHO-K1 cells via FACS. Whole cell manual patch clamp electrophysiology protocols interrogating diverse Na V1.7 gating states in HEK293 cells, revealed that recombinant SVmab1 does not block Na V1.7 currents to an extent greater than observed with an isotype matched control antibody. Collectively, our results show that recombinant SVmab1 monoclonal antibody does not bind Na V1.7 target sequences or specifically inhibit Na V1.7 current.

The adoption of Sustainable Land Management (SLM) practices among smallholder farmers remains low, particularly among women farmers. Understanding the relationship between assets, gender, and SLM adoption and how their interaction impinges on household food self-sufficiency and livelihoods is essential for developing gender-responsive SLM programmes that effectively promote sustainable livelihoods and address household food insecurity. This study examines the effects of asset type on SLM practices adoption, women farmers, and their implications on household incomes and food self-sufficiency. Data was collected through a cross-sectional survey of 761 households selected from 11 chiefdoms across six districts in Eastern Zambia. Analysis involved Structural Equation System framework and Propensity Score Matching techniques to examine relationships between SLM adoption, food self-sufficiency, and household incomes, considering various socio-economic factors. Results showed marital status and household size as significant demographics, with education positively correlating with household income and SLM participation (p