Short peptides based on the conserved regions of MIEN1 protein exhibit anticancer activity by targeting the MIEN1 signaling pathway.

Migration and invasion enhancer 1 (MIEN1) overexpression characterizes several cancers and facilitates cancer cell migration and invasion. Leveraging conserved immunoreceptor tyrosine-based activation motif and prenylation motifs within MIEN1, we identified potent anticancer peptides. Among them, bioactive peptides LA3IK and RP-7 induced pronounced transcriptomic and protein expression changes at sub-IC50 concentrations. The peptides effectively inhibited genes and proteins driving cancer cell migration, invasion, and epithelial-mesenchymal transition pathways, concurrently suppressing epidermal growth factor-induced nuclear factor kappa B nuclear translocation in metastatic breast cancer cells. Specifically, peptides targeted the same signal transduction pathway initiated by MIEN1. Molecular docking and CD spectra indicated the formation of MIEN1-peptide complexes. The third-positioned isoleucine in LA3IK and CVIL motif in RP-7 were crucial for inhibiting breast cancer cell migration. This is evident from the limited migration inhibition observed when MDA-MB-231 cells were treated with scrambled peptides LA3IK SCR and RP-7 SCR. Additionally, LA3IK and RP-7 effectively suppressed tumor growth in an orthotopic breast cancer model. Notably, mice tolerated high intraperitoneal (ip) peptide doses of 90 mg/Kg well, surpassing significantly lower doses of 5 mg/Kg intravenously (iv) and 30 mg/Kg intraperitoneally (ip) used in both in vivo pharmacokinetic studies and orthotopic mouse model assays. D-isomers of LA3IK and RP-7 showed enhanced anticancer activity compared to their L-isomers. D-LA3IK remained stable in mouse plasma for 24 h with 75% remaining, exhibiting superior pharmacokinetic properties over D/L-RP-7. In summary, our findings mark the first report of short peptides based on MIEN1 protein sequence capable of inhibiting cancer signaling pathways, effectively impeding cancer progression both in vitro and in vivo.

Patient-reported symptoms after minimally invasive hysterectomy and association with postoperative complications.

OBJECTIVE: To describe patient-reported postoperative symptoms and to evaluate the use of digital symptom tracking and alerts to detect postoperative complications. METHODS: We retrospectively reviewed patients who underwent a minimally invasive hysterectomy and enrolled in our Recovery Tracker program from 4/5/17-12/31/21. The Recovery Tracker is an at-home virtual tool used to track patient-reported postoperative symptoms for 10 days. Predefined thresholds for "red" and "yellow" alerts are based on symptom severity and timing. Data on patient demographics, surgery, and postoperative course were collected to evaluate the association of alerts with complications and compare outcomes of patients who did/did not enroll in the program. RESULTS: Of 2362 eligible patients, 1694 (71.7%) enrolled in the Recovery Tracker program. Pain was the most severe symptom, followed by fatigue. Eighty-seven patients experienced 102 complications (5.1% complication rate) and 32 experienced 39 grade ≥ 2 complications (1.9% severe complication rate). Excluding complications that occurred prior to Recovery Tracker use, 1673 patients experienced 28 grade ≥ 2 complications. Of 345 patients (20.6%) who triggered a red alert, 13 (3.8%) had a grade ≥ 2 complication. Of 1328 patients (79.4%) with no red alerts, 15 (1.13%) had a grade ≥ 2 complication. Relative risk of a grade ≥ 2 complication if a red alert was triggered was 3.25 (95% CI: 1.6-6.9, P = .002). Rate of severe complications was significantly higher among patients who did not use the tool (3.3% vs 1.9%; P = .04). CONCLUSIONS: The Recovery Tracker tool may assist in early identification of postoperative symptoms after minimally invasive hysterectomy.

A comparison of brief versus explicit descriptors for verbal rating scales: interrupted time series design.

BACKGROUND: Verbal rating scales (VRS) are widely used in patient-reported outcome (PRO) measures. At our institution, patients complete an online instrument using VRSs with a five-point brief response scale to assess symptoms as part of routine follow-up after ambulatory cancer surgery. We received feedback from patients that the brief VRS descriptors such as "mild" or "somewhat" were vague. We added explicit descriptors to our VRSs, for instance, "Mild: I can generally ignore my pain" for pain severity or "Somewhat: I can do some things okay, but most of my daily activities are harder because of fatigue" for fatigue interference. We then compared responses before and after this change was made. METHODS: The symptoms investigated were pain, fatigue and nausea. Our hypothesis was that the explicit descriptors would reduce overall variance. We therefore compared the coefficient of variation of scores and tested the association between symptoms scores and known predictors thereof. We also compared time to completion between questionnaires with and without the additional descriptors. RESULTS: A total of 17,500 patients undergoing 21,497 operations were assigned questionnaires in the period before the descriptors were added; allowing for a short transition period, 1,417 patients having 1436 operations were assigned questionnaires with the additional descriptors. Symptom scores were about 10% lower with the additional descriptors but the coefficient of variation was slightly higher. Moreover, the only statistically significant difference between groups for association with a known predictor favored the item without the additional language for nausea severity (p = 0.004). Total completion time was longer when the instrument included the additional descriptors, particularly the first and second time that the questionnaire was completed. CONCLUSIONS: Adding descriptors to a VRS of post-operative symptoms did not improve scale properties in patients undergoing ambulatory cancer surgery. We have removed the additional descriptors from our tool. We recommend further comparative psychometric research using data from PROs collected as part of routine clinical care.

Protecting healthcare workers and patients during the COVID-19 pandemic: a comparison of baseline and follow-up infection prevention and control needs in Nigerian military healthcare facilities delivering HIV services.

BACKGROUND: Protecting the HIV health workforce is critical for continuity of services for people living with HIV, particularly during a pandemic. Early in the COVID-19 pandemic, the Nigerian Ministry of Defence, in partnership with the US Military HIV Research Program, took steps to improve infection prevention and control (IPC) practices among staff working in select PEPFAR-supported Nigerian military health facilities. METHODS: We identified a set of IPC activities a priori for implementation at four Nigerian military hospitals in HIV and related departments in early 2021, including continuous medical masking, physical distancing, placement of additional hand washing stations and hand sanitizers throughout facilities, and training. We fine-tuned planned intervention activities through a baseline needs assessment conducted in December 2020 that covered eight IPC components: 'IPC program structure, funding and leadership engagement'; 'IPC policies, guidelines and standard operating procedures (SOPs)'; 'infrastructure'; 'triage and screening'; 'training, knowledge and practice'; 'personal protective equipment (PPE) materials, availability and adequacy'; 'biosafety and waste management'; and 'monitoring and remediation' prior to implementation. Baseline results were compared with those of a follow up assessment administered in August 2021, following intervention implementation. RESULTS: IPC readiness remained high at both baseline and follow-up assessments for 'IPC guidelines, policies, and SOPs' (96.7%). The components 'infrastructure' and 'monitoring and remediation', which needed improvement at baseline, saw modest improvements at follow-up, by 2% and 7.5%, respectively. At follow-up, declines from high scoring at baseline were seen in 'IPC program structure, funding and leadership engagement', 'training, knowledge and practice', and 'biosafety and waste management'. 'PPE materials availability and adequacy' improved to 88.9% at follow-up. Although unidirectional client flow was newly implemented, the score for 'triage and screening' did not change from baseline to follow-up (73%). CONCLUSION: Variability in IPC component readiness and across facilities highlights the importance of building resilience and employing a quality improvement approach to IPC that includes regular monitoring, re-assessment and re-training at set intervals. Results can be used to encourage solutions-oriented dialogue between staff and leadership, determine needs and implement action plans to protect staff and people with HIV.

Prevalence and Correlates of Viral Load Suppression and Human Immunodeficiency Virus (HIV) Drug Resistance Among Children and Adolescents in South Rift Valley and Kisumu, Kenya.

BACKGROUND: Children and adolescents living with HIV (CALHIV) face unique challenges, including poorer treatment outcomes, risk for drug-resistance mutations (HIVDRMs), and limited drug formulations. We estimated viral suppression (VS) prevalence and evaluated predictors of VS and HIVDRMs in Kenya. METHODS: From 2018-2020, CALHIV 1-19 years on antiretroviral therapy (ART) >6 months were enrolled in this cross-sectional study. Participants underwent viral load (VL) testing; those with VL ≥1000 copies/mL had HIVDRM testing. Sociodemographic questionnaires and medical record abstraction were completed. VS prevalence (VL <1000 copies/mL) was estimated; robust Poisson regression models were used to estimate prevalence ratios (PRs) and 95% CIs for associations between potential predictors of VS. RESULTS: Nine hundred and sixty-nine participants were enrolled. VS prevalence was .80 (95% CI: .78-.83). Being on ART >24 months (adjusted PR [aPR]: 1.22; 95% CI: 1.06-1.41), an integrase strand transfer inhibitor-containing regimen (1.13; 1.02-1.26), and attending a level 3 health facility (1.23; 1.11-1.36) were associated with VS. Missing ≥3 doses of ART in the past month (aPR: .73; 95% CI: .58-.92), having a viremic mother with HIV (.72; .53-.98), and having 3-7 (.90; .83-.97), 8-13 (.89; .82-.97), or ≥14 (.84; .77-.92) compared with <2 adherence counseling referrals were inversely associated with VS. A high proportion (n = 119, 81.5%) of unsuppressed participants had evidence of any major HIVDRM. CONCLUSIONS: HIV treatment programs should target interventions for pediatric patients at risk for treatment failure-namely, those with a caregiver with failed VS and those struggling with adherence.

Characterization of Symptoms after Radical Prostatectomy and Their Relation to Postoperative Complications.

PURPOSE: Many patients will experience symptoms in the initial days after radical prostatectomy (RP), but early patient-reported symptoms have not been well characterized. Our objective was to illustrate the pattern of symptoms experienced after RP and the relation of severe symptoms to postoperative complications. MATERIALS AND METHODS: In 2016, electronic patient-reported symptom monitoring began at our institution's ambulatory surgery center. We retrospectively reviewed patients treated with minimally invasive RP who were sent a daily questionnaire completed using a web interface until postoperative day 10. Severe symptoms automatically generate a "yellow alert," which messages the clinic, while very severe symptoms generate a "red alert," additionally prompting the patient to call. We summarized rates of moderate-to-very severe symptoms and fit local polynomial regressions. We compared rates of 30-day or 90-day complications (grade ≥2) based on the presence of alert symptoms. RESULTS: Of 2,266 men undergoing RP, 1,942 (86%) completed surveys. Among moderate-to-very severe symptom levels, pain (72%) and dyspnea (11%) were most common. Pain, nausea and dyspnea consistently decreased over time; fever and vomiting had a flat pattern. In patients experiencing red-alert symptoms, we observed a higher risk of 30-day complications, but rates were low and differences between groups were nonsignificant (2.9% vs 1.9%; difference 1.1%; 95% CI -1.3-3.5; p=0.3). Results were similar examining 90-day complications. CONCLUSIONS: While symptoms are common after RP, substantial improvements occur over the first 10 days. Severe or very severe symptoms conferred at most a small absolute increase in complication risk, which should be reassuring to patients and clinicians.

Benefits and Harms of Prescription Drugs and Supplements for Treatment of Clinical Alzheimer-Type Dementia.

BACKGROUND: Effects of drug treatment of clinical Alzheimer-type dementia (CATD) are uncertain. PURPOSE: To summarize evidence on the effects of prescription drugs and supplements for CATD treatment. DATA SOURCES: Electronic bibliographic databases (inception to November 2019), ClinicalTrials.gov (to November 2019), and systematic review bibliographies. STUDY SELECTION: English-language trials of prescription drug and supplement treatment in older adults with CATD that report cognition, function, global measures, behavioral and psychological symptoms of dementia (BPSD), or harms. Minimum treatment was 24 weeks (≥2 weeks for selected BPSD). DATA EXTRACTION: Studies with low or medium risk of bias (ROB) were analyzed. Two reviewers rated ROB. One reviewer extracted data; another verified extraction accuracy. DATA SYNTHESIS: Fifty-five studies reporting non-BPSD outcomes (most ≤26 weeks) and 12 reporting BPSD (most ≤12 weeks) were analyzed. Across CATD severity, mostly low-strength evidence suggested that, compared with placebo, cholinesterase inhibitors produced small average improvements in cognition (median standardized mean difference [SMD], 0.30 [range, 0.24 to 0.52]), no difference to small improvement in function (median SMD, 0.19 [range, -0.10 to 0.22]), no difference in the likelihood of at least moderate improvement in global clinical impression (median absolute risk difference, 4% [range, 2% to 4%]), and increased withdrawals due to adverse events. In adults with moderate to severe CATD receiving cholinesterase inhibitors, low- to insufficient-strength evidence suggested that, compared with placebo, add-on memantine inconsistently improved cognition and improved global clinical impression but not function. Evidence was mostly insufficient about prescription drugs for BPSD and about supplements for all outcomes. LIMITATION: Most drugs had few trials without high ROB, especially for supplements, active drug comparisons, BPSD, and longer trials. CONCLUSION: Cholinesterase inhibitors and memantine slightly reduced short-term cognitive decline, and cholinesterase inhibitors slightly reduced reported functional decline, but differences versus placebo were of uncertain clinical importance. Evidence was mostly insufficient on drug treatment of BPSD and on supplements for all outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018117897).

Does Cognitive Training Prevent Cognitive Decline?: A Systematic Review.

Background: Structured activities to stimulate brain function-that is, cognitive training exercises-are promoted to slow or prevent cognitive decline, including dementia, but their effectiveness is highly debated. Purpose: To summarize evidence on the effects of cognitive training on cognitive performance and incident dementia outcomes for adults with normal cognition or mild cognitive impairment (MCI). Data Sources: Ovid MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and PsycINFO through July 2017, supplemented by hand-searches. Study Selection: Trials (published in English) lasting at least 6 months that compared cognitive training with usual care, waitlist, information, or attention controls in adults without dementia. Data Extraction: Single-reviewer extraction of study characteristics confirmed by a second reviewer; dual-reviewer risk-of-bias assessment; consensus determination of strength of evidence. Only studies with low or medium risk of bias were analyzed. Data Synthesis: Of 11 trials with low or medium risk of bias, 6 enrolled healthy adults with normal cognition and 5 enrolled adults with MCI. Trainings for healthy older adults were mostly computer based; those for adults with MCI were mostly held in group sessions. The MCI trials used attention controls more often than trials with healthy populations. For healthy older adults, training improved cognitive performance in the domain trained but not in other domains (moderate-strength evidence). Results for populations with MCI suggested no effect of training on performance (low-strength and insufficient evidence). Evidence for prevention of cognitive decline or dementia was insufficient. Adverse events were not reported. Limitation: Heterogeneous interventions and outcome measures; outcomes that mostly assessed test performance rather than global function or dementia diagnosis; potential publication bias. Conclusion: In older adults with normal cognition, training improves cognitive performance in the domain trained. Evidence regarding prevention or delay of cognitive decline or dementia is insufficient. Primary Funding Source: Agency for Healthcare Research and Quality.

Physical Activity Interventions in Preventing Cognitive Decline and Alzheimer-Type Dementia: A Systematic Review.

Background: The prevalence of cognitive impairment and dementia is expected to increase dramatically as the population ages, creating burdens on families and health care systems. Purpose: To assess the effectiveness of physical activity interventions in slowing cognitive decline and delaying the onset of cognitive impairment and dementia in adults without diagnosed cognitive impairments. Data Sources: Several electronic databases from January 2009 to July 2017 and bibliographies of systematic reviews. Study Selection: Trials published in English that lasted 6 months or longer, enrolled adults without clinically diagnosed cognitive impairments, and compared cognitive and dementia outcomes between physical activity interventions and inactive controls. Data Extraction: Extraction by 1 reviewer and confirmed by a second; dual-reviewer assessment of risk of bias; consensus determination of strength of evidence. Data Synthesis: Of 32 eligible trials, 16 with low to moderate risk of bias compared a physical activity intervention with an inactive control. Most trials had 6-month follow-up; a few had 1- or 2-year follow-up. Evidence was insufficient to draw conclusions about the effectiveness of aerobic training, resistance training, or tai chi for improving cognition. Low-strength evidence showed that multicomponent physical activity interventions had no effect on cognitive function. Low-strength evidence showed that a multidomain intervention comprising physical activity, diet, and cognitive training improved several cognitive outcomes. Evidence regarding effects on dementia prevention was insufficient for all physical activity interventions. Limitation: Heterogeneous interventions and cognitive test measures, small and underpowered studies, and inability to assess the clinical significance of cognitive test outcomes. Conclusion: Evidence that short-term, single-component physical activity interventions promote cognitive function and prevent cognitive decline or dementia in older adults is largely insufficient. A multidomain intervention showed a delay in cognitive decline (low-strength evidence). Primary Funding Source: Agency for Healthcare Research and Quality.

Evidence-based approaches to reduce cancer health disparities: Discover, develop, deliver, and disseminate.

The Texas Center for Health Disparities (TCHD) at the University of North Texas Health Science Center is a National Institute on Minority Health and Health Disparities-funded, specialized center of excellence for health disparities. TCHD organized its 12th annual conference focusing on "Evidence-Based Approaches to Reduce Cancer Health Disparities: Discover, Develop, Deliver, and Disseminate." At this conference, experts in health care, biomedical sciences, and public health gathered to discuss the current status and strategies for reducing cancer health disparities. The meeting was conducted in three sessions on breast cancer, prostate cancer, and colorectal cancer disparities, in addition to roundtable discussions and a poster session. Each session highlighted differences in the effects of cancer, based on factors such as race/ethnicity, gender, socioeconomic status, and geographical location. In each session, expert speakers presented their findings, and this was followed by a discussion panel made up of experts in that field and cancer survivors, who responded to questions from the audience. This article summarizes the approaches to fundamental, translational, clinical, and public health issues in cancer health disparities discussed at the conference.

Sialic acid attenuates puromycin aminonucleoside-induced desialylation and oxidative stress in human podocytes.

Sialoglycoproteins make a significant contribution to the negative charge of the glomerular anionic glycocalyx-crucial for efficient functioning of the glomerular permselective barrier. Defects in sialylation have serious consequences on podocyte function leading to the development of proteinuria. The aim of the current study was to investigate potential mechanisms underlying puromycin aminonucleosisde (PAN)-induced desialylation and to ascertain whether they could be corrected by administration of free sialic acid. PAN treatment of podocytes resulted in a loss of sialic acid from podocyte proteins. This was accompanied by a reduction, in the expression of sialyltransferases and a decrease in the key enzyme of sialic acid biosynthesis N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). PAN treatment also attenuated expression of the antioxidant enzyme superoxide dismutase (mSOD) and concomitantly increased the generation of superoxide anions. Sialic acid supplementation rescued podocyte protein sialylation and partially restored expression of sialyltransferases. Sialic acid also restored mSOD mRNA expression and quenched the oxidative burst. These data suggest that PAN-induced aberrant sialylation occurs as a result of modulation of enzymes involved sialic acid metabolism some of which are affected by oxidative stress. These data suggest that sialic acid therapy not only reinstates functionally important negative charge but also acts a source of antioxidant activity.

Patient-Centered Clinical Decision Support-Where Are We and Where to Next?

Patient-centered clinical decision support (PC CDS) includes digital health tools that support patients, caregivers, and care teams in healthcare decisions that incorporate patient-centered factors related to four components: knowledge, data, delivery, and use. This paper explores the current state of each factor and how each promotes patient-centeredness in healthcare. We conducted a literature review, reviewing 175 peer-reviewed and grey literature, and eighteen key informant interviews. Findings show a need for more research on how to incorporate patient input into the guideline selection and prioritization for PC CDS, development and implementation of PC CDS tools, technical challenges for capturing patient contributed data, and optimizing PC CDS across various settings to meet patient and caregiver needs. While progress is being made in each of the four components of PC CDS, critical gaps remain.

Bedside ultrasonographic evaluation of optic nerve sheath diameter for monitoring of intracranial pressure in traumatic brain injury patients: a cross sectional study in level II trauma care center in India.

BACKGROUND: Optic nerve sheath diameter (ONSD) is an emerging non-invasive, easily accessible, and possibly useful measurement for evaluating changes in intracranial pressure (ICP). The utilization of bedside ultrasonography (USG) to measure ONSD has garnered increased attention due to its portability, real-time capability, and lack of ionizing radiation. The primary aim of the study was to assess whether bedside USG-guided ONSD measurement can reliably predict increased ICP in traumatic brain injury (TBI) patients. METHODS: A total of 95 patients admitted to the trauma intensive care unit was included in this cross sectional study. Patient brain computed tomography (CT) scans and Glasgow Coma Scale (GCS) scores were assessed at the time of admission. Bedside USG-guided binocular ONSD was measured and the mean ONSD was noted. Microsoft Excel was used for statistical analysis. RESULTS: Patients with low GCS had higher mean ONSD values (6.4±1.0 mm). A highly significant association was found among the GCS, CT results, and ONSD measurements (P<0.001). Compared to CT scans, the bedside USG ONSD had 86.42% sensitivity and 64.29% specificity for detecting elevated ICP. The positive predictive value of ONSD to identify elevated ICP was 93.33%, and its negative predictive value was 45.00%. ONSD measurement accuracy was 83.16%. CONCLUSIONS: Increased ICP can be accurately predicted by bedside USG measurement of ONSD and can be a valuable adjunctive tool in the management of TBI patients.

Evaluation of Immunoexpression of AJUBA Protein in Normal Oral Mucosa and Oral Squamous Cell Carcinoma.

AJUBA is multifunctional scaffold protein which belongs to Zyxin family of proteins. It is known to have dual role in cancer as a tumor promoter and tumor suppressor. AJUBA has a key role in systemic malignancies like esophageal squamous cell carcinoma, colorectal cancer, cervical, breast, prostate cancer, etc. But there is very sparse literature available regarding its expression profile in oral squamous cell carcinoma (OSCC) and moreover its expression has not been observed in normal oral mucosa (NOM). Thus, the aim of this research is to explore the expression profile of AJUBA by immunohistochemical method in NOM and OSCC. Furthermore, we also evaluated the association of AJUBA expression with clinicopathologic parameters. A total of 84 samples of formalin fixed paraffin embedded tissue blocks comprising of 42 cases each of NOM and OSCC were subjected to detect immunoexpression of AJUBA. We found enhanced intense immune-expression of AJUBA in OSCC cases than compared with NOM and found to be statistically significant. The parameters specific to histologic tumor grade and inflammatory response in OSCC also found to have statistically significant with AJUBA expression. Our study is first of its kind to reveal AJUBA expression in basal and suprabasal layer of NOM suggestive of its definitive role in differentiation and stratification process. We also observed its intense expression in peripheral cell of tumor islands of OSCC cases, which can suggest its possible role in tumor growth and progression.

A Unique Presentation of Nelson Syndrome Due to Partial Adrenal Insufficiency Without Bilateral Adrenalectomy.

Nelson syndrome is a rare disorder, characterized by clinical features arising from an adrenocorticotropic hormone (ACTH)-secreting pituitary macroadenoma after bilateral adrenalectomy. Common symptoms of Nelson syndrome include weight gain, vision problems, and skin hyperpigmentation, among many others. In this case report, a 58-year-old Asian female who displayed clinical features akin to Nelson syndrome despite not undergoing bilateral adrenalectomy is investigated. The patient has a past history of an ACTH-secreting pituitary macroadenoma, for which a transsphenoidal resection was performed along with radiation therapy. A year following this, she displayed severe facial and neck hyperpigmentation. According to the laboratory results obtained, the patient displayed initial high ACTH levels and low-normal AM cortisol levels, which are signs of partial adrenal insufficiency. A brain MRI was performed, which confirmed stable residual tumor tissue in the cavernous sinus. The results pointed to the adrenal glands as the cause of the hyperpigmentation, and the patient was diagnosed with primary adrenal insufficiency. To bring her ACTH levels and low-normal AM cortisol into the proper range, she was given low-dose hydrocortisone and monitored for five years. Over this time period, her hyperpigmentation improved significantly and eventually resolved entirely, and her ACTH levels were lowered, indicating that hydrocortisone was the appropriate treatment for normalizing ACTH levels. In this case, it was determined that unresponsive adrenal glands lead to high ACTH levels, which resulted in an atypical case of Nelson syndrome and the physical symptom of hyperpigmentation.

Cabazitaxel-Loaded Nanoparticles Reduce the Invasiveness in Metastatic Prostate Cancer Cells: Beyond the Classical Taxane Function.

Bone-metastatic prostate cancer symbolizes the beginning of the later stages of the disease. We designed a cabazitaxel-loaded, poly (lactic-co-glycolic acid) (PLGA) nanoparticle using an emulsion-diffusion-evaporation technique. Bis (sulfosuccinimidyl) suberate (BS3) was non-covalently inserted into the nanoparticle as a linker for the conjugation of a bone-targeting moiety to the outside of the nanoparticle. We hypothesized that the nanoparticles would have the ability to inhibit the epithelial-to-mesenchymal transition (EMT), invasion, and migration in prostate cancer cells. Targeted, cabazitaxel-loaded nanoparticles attenuated the EMT marker, Vimentin, and led to an increased E-cadherin expression. These changes impart epithelial characteristics and inhibit invasive properties in cancer progression. Consequently, progression to distant sites is also mitigated. We observed the reduction of phosphorylated Src at tyrosine 416, along with increased expression of phosphorylated cofilin at serine 3. These changes could affect migration and invasion pathways in cancer cells. Both increased p-120 catenin and inhibition in IL-8 expression were seen in targeted, cabazitaxel-loaded nanoparticles. Overall, our data show that the targeted, cabazitaxel-loaded nanoparticles can act as a promising treatment for metastatic prostate cancer by inhibiting EMT, invasion, and migration, in prostate cancer cells.

Lessons Learned from a National Initiative Promoting Publicly Available Standards-Based Clinical Decision Support.

BACKGROUND: Clinical decision support (CDS), which provides tools to assist clinical decision-making, can improve adherence to evidence-based practices, prevent medical errors, and support high-quality and patient-centered care delivery. Publicly available CDS that uses standards to express clinical logic (i.e., standards-based CDS) has the potential to reduce duplicative efforts of translating the same clinical evidence into CDS across multiple health care institutions. Yet development of such CDS is relatively new and its potential only partially explored. OBJECTIVES: This study aimed to describe lessons learned from a national initiative promoting publicly available, standards-based CDS resources, discuss challenges, and report suggestions for improvement. METHODS: Findings were drawn from an evaluation of the Agency for Healthcare Research and Quality Patient-Centered Outcomes Research CDS Initiative, which aimed to advance evidence into practice through standards-based and publicly available CDS. Methods included literature and program material reviews, key informant interviews, and a web-based survey about a public repository of CDS artifacts and tools for authoring standards-based CDS. RESULTS: The evaluation identified important lessons for developing and implementing standards-based CDS through publicly available repositories such as CDS Connect. Trust is a critical factor in uptake and can be bolstered through transparent information on underlying evidence, collaboration with experts, and feedback loops between users and developers to support continuous improvement. Additionally, while adoption of standards among electronic health record developers will make it easier to implement standards-based CDS, lower-resourced health systems will need extra support to ensure successful implementation and use. Finally, although we found the resources developed by the Initiative to offer valuable prototypes for the field, health systems desire more information about patient-centered, clinical, and cost-related outcomes to help them justify the investment required to implement standards-based, publicly available CDS. CONCLUSION: While the standards and technology to publicly share standards-based CDS have increased, broad dissemination and implementation remain challenging.

A lifecycle framework illustrates eight stages necessary for realizing the benefits of patient-centered clinical decision support.

The design, development, implementation, use, and evaluation of high-quality, patient-centered clinical decision support (PC CDS) is necessary if we are to achieve the quintuple aim in healthcare. We developed a PC CDS lifecycle framework to promote a common understanding and language for communication among researchers, patients, clinicians, and policymakers. The framework puts the patient, and/or their caregiver at the center and illustrates how they are involved in all the following stages: Computable Clinical Knowledge, Patient-specific Inference, Information Delivery, Clinical Decision, Patient Behaviors, Health Outcomes, Aggregate Data, and patient-centered outcomes research (PCOR) Evidence. Using this idealized framework reminds key stakeholders that developing, deploying, and evaluating PC-CDS is a complex, sociotechnical challenge that requires consideration of all 8 stages. In addition, we need to ensure that patients, their caregivers, and the clinicians caring for them are explicitly involved at each stage to help us achieve the quintuple aim.

Implementation and evaluation of an electronic health record-integrated app for postpartum monitoring of hypertensive disorders of pregnancy using patient-contributed data collection.

Remote monitoring of women experiencing hypertensive disorders of pregnancy (HDP) can provide timely life-saving data, particularly if these data are integrated into existing patient and clinical workflows. This pilot intervention of a smartphone application (app) for postpartum monitoring of hypertensive disorders integrates patient-contributed data into electronic health records (EHRs) to support monitoring and clinical decision-making. Results from the evaluation of the pilot highlight the resources needed when implementing the app, challenges for integrating an app into the EHR, and the usability and utility of the HDP monitoring app for patient and clinician users. The implementation team's key observations included the importance of a local clinical champion, more robust patient involvement and support for the remote patient monitoring program, an impetus for EHR developers to adopt data integration standards, and a need to expand the capabilities of the standards to support interventions using patient-contributed data.