CD151 Maintains Endolysosomal Protein Quality to Inhibit Vascular Inflammation.

BACKGROUND: Tetraspanin CD151 is highly expressed in endothelia and reinforces cell adhesion, but its role in vascular inflammation remains largely unknown. METHODS: In vitro molecular and cellular biological analyses on genetically modified endothelial cells, in vivo vascular biological analyses on genetically engineered mouse models, and in silico systems biology and bioinformatics analyses on CD151-related events. RESULTS: Endothelial ablation of Cd151 leads to pulmonary and cardiac inflammation, severe sepsis, and perilous COVID-19, and endothelial CD151 becomes downregulated in inflammation. Mechanistically, CD151 restrains endothelial release of proinflammatory molecules for less leukocyte infiltration. At the subcellular level, CD151 determines the integrity of multivesicular bodies/lysosomes and confines the production of exosomes that carry cytokines such as ANGPT2 (angiopoietin-2) and proteases such as cathepsin-D. At the molecular level, CD151 docks VCP (valosin-containing protein)/p97, which controls protein quality via mediating deubiquitination for proteolytic degradation, onto endolysosomes to facilitate VCP/p97 function. At the endolysosome membrane, CD151 links VCP/p97 to (1) IFITM3 (interferon-induced transmembrane protein 3), which regulates multivesicular body functions, to restrain IFITM3-mediated exosomal sorting, and (2) V-ATPase, which dictates endolysosome pH, to support functional assembly of V-ATPase. CONCLUSIONS: Distinct from its canonical function in strengthening cell adhesion at cell surface, CD151 maintains endolysosome function by sustaining VCP/p97-mediated protein unfolding and turnover. By supporting protein quality control and protein degradation, CD151 prevents proteins from (1) buildup in endolysosomes and (2) discharge through exosomes, to limit vascular inflammation. Also, our study conceptualizes that balance between degradation and discharge of proteins in endothelial cells determines vascular information. Thus, the IFITM3/V-ATPase-tetraspanin-VCP/p97 complexes on endolysosome, as a protein quality control and inflammation-inhibitory machinery, could be beneficial for therapeutic intervention against vascular inflammation.

Predictors and benefits of multiagent chemotherapy for pancreatic adenocarcinoma: Timing matters.

INTRODUCTION: Adjuvant (A) multiagent chemotherapy (MC) is the standard of care for patients with pancreatic adenocarcinoma (PDAC). Tolerating MC following a morbid operation may be difficult, thus neoadjuvant (NA) treatment is preferable. This study examined how the timing of chemotherapy was related to the regimen given and ultimately the overall survival (OS). METHODS: The National Cancer Database was queried from 2006 to 2017 for nonmetastatic PDAC patients who underwent surgical resection and received MC or single-agent chemotherapy (SC) pre- or postresection. Predictors of receiving MC were determined using multivariable logistic regression. Five-year OS was evaluated using the Kaplan-Meier and Cox proportional hazards model. RESULTS: A total of 12,440 patients (NA SC, n = 663; NA MC, n = 2313; A SC, n = 6152; A MC, n = 3312) were included. MC utilization increased from 2006-2010 to 2011-2017 (33.1%-49.7%; odds ratio [OR]: 0.59; p < 0.001). Younger age, fewer comorbidities, higher clinical stage, and larger tumor size were all associated with receipt of MC (all p < 0.001), but NA treatment was the greatest predictor (OR 5.18; 95% confidence interval [CI]: 4.63-5.80; p < 0.001). MC was associated with increased median 5-year OS (26.0 vs. 23.9 months; hazard ratio [HR]: 0.92; 95% CI: 0.88-0.96) and NA MC was associated with the highest survival (28.2 months) compared to NA SC (23.3 months), A SC (24.0 months), and A MC (24.6 months; p < 0.001). CONCLUSION: Use and timing of MC contribute to OS in PDAC with an improved 5-year OS compared to SC. The greatest predictor of receiving MC was being given as NA therapy and the greatest survival benefit was the NA MC subgroup. Randomized studies evaluating the timing of effective MC in PDAC are needed.

The benefit of adjuvant chemotherapy following pancreaticoduodenectomy for pancreatic adenocarcinoma depends on response to neoadjuvant therapy.

BACKGROUND: The benefit of adjuvant therapy (AT) remains unclear in pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT) and surgical resection. METHODS: The 2019 National Cancer Database was queried for patients with non-metastatic PDAC who received NAT followed by pancreaticoduodenectomy. Only patients with data regarding receipt of AT were included. Patients were classified if they had nodal down-staging specifically, or any downstaging (Tumor, Nodal, or overall). Propensity score matching (PSM) adjusted for pretreatment covariate imbalance between groups. The weighted Kaplan-Meier method and log-rank test were used to estimate the cumulative survival. RESULTS: After exclusion criteria and PSM, a total of 2784 patients remained; 1689 (60.7%) received AT and 1095 (39.3%) did not receive AT. Among all, those with additional AT had a significantly improved overall survival (OS) (p < 0.001). Upon evaluation of patients without downstaging after NAT, those who received AT had improved OS (no nodal downstaging or any downstaging; p = 0.002; p = 0.001). When evaluating patients with downstaging after NAT, those receiving AT did not have improved OS (nodal downstaging or any downstaging: p = 0.352; p = 0.99). CONCLUSION: Response to NAT appears to correlate with the benefit of AT following pancreaticoduodenectomy; patients who have a favorable response to NAT may not benefit from AT.

Exploring the Gut-Mitochondrial Axis: p66Shc Adapter Protein and Its Implications for Metabolic Disorders.

This review investigates the multifaceted role of the p66Shc adaptor protein and the gut microbiota in regulating mitochondrial function and oxidative stress, and their collective impact on the pathogenesis of chronic diseases. The study delves into the molecular mechanisms by which p66Shc influences cellular stress responses through Rac1 activation, Forkhead-type transcription factors inactivation, and mitochondria-mediated apoptosis, alongside modulatory effects of gut microbiota-derived metabolites and endotoxins. Employing an integrative approach, the review synthesizes findings from a broad array of studies, including molecular biology techniques and analyses of microbial metabolites' impacts on host cellular pathways. The results underscore a complex interplay between microbial metabolites, p66Shc activation, and mitochondrial dysfunction, highlighting the significance of the gut microbiome in influencing disease outcomes through oxidative stress pathways. Conclusively, the review posits that targeting the gut microbiota-p66Shc-mitochondrial axis could offer novel therapeutic strategies for mitigating the development and progression of metabolic diseases. This underscores the potential of dietary interventions and microbiota modulation in managing oxidative stress and inflammation, pivotal factors in chronic disease etiology.

Divergent clinical outcomes in a phase 2B trial of the TLPLDC vaccine in preventing melanoma recurrence and the impact of dendritic cell collection methodology: a randomized clinical trial.

BACKGROUND: A randomized, double-blind, placebo-controlled phase 2b trial of the tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine was conducted in patients with resected stage III/IV melanoma. Dendritic cells (DCs) were harvested with and without granulocyte-colony stimulating factor (G-CSF). This analysis investigates differences in clinical outcomes and RNA gene expression between DC harvest methods. METHODS: The TLPLDC vaccine is created by loading autologous tumor lysate into yeast cell wall particles (YCWPs) and exposing them to phagocytosis by DCs. For DC harvest, patients had a direct blood draw or were pretreated with G-CSF before blood draw. Patients were randomized 2:1 to receive TLPLDC or placebo. Differences in disease-free survival (DFS) and overall survival (OS) were evaluated. RNA-seq analysis was performed on the total RNA of TLPLDC + G and TLPLDC vaccines to compare gene expression between groups. RESULTS: 144 patients were randomized: 103 TLPLDC (47 TLPLDC/56 TLPLDC + G) and 41 placebo (19 placebo/22 placebo + G). Median follow-up was 27.0 months. Both 36-month DFS (55.8% vs. 24.4% vs. 30.0%, p = 0.010) and OS (94.2% vs. 69.8% vs. 70.9%, p = 0.024) were improved in TLPLDC compared to TLPLDC + G or placebo, respectively. When compared to TLPLDC + G vaccine, RNA-seq from TLPLDC vaccine showed upregulation of genes associated with DC maturation and downregulation of genes associated with DC suppression or immaturity. CONCLUSIONS: Patients receiving TLPLDC vaccine without G-CSF had improved OS and DFS. Outcomes remained similar between patients receiving TLPLDC + G and placebo. Direct DC harvest without G-CSF had higher expression of genes linked to DC maturation, likely improving clinical efficacy.

Outcomes of Partial Versus Total Colectomy in Ulcerative Colitis: A Propensity Score-Matched Analysis.

INTRODUCTION: Total abdominal colectomy (TAC) with ileostomy is the standard treatment for severe ulcerative colitis (UC). Partial colectomy (PC) with colostomy may present a less morbid treatment option. METHODS: The 2012-19 ACS-NSQIP database was queried to assess 30-day outcomes among patients undergoing TAC versus PC for UC, utilizing propensity score matching (PSM) techniques to account for differences in disease severity, patient selection, and presentation acuity. RESULTS: Before matching (n = 9888), patients undergoing PC were older, had more comorbidities, and experienced higher complication and 30-day mortality rates (P < 0.001). After matching (n = 1846), patients undergoing TAC experienced higher 30-day overall complications (41.9% versus 36.5%, P = 0.017) and serious complications (37.2% versus 31.5%, P = 0.011). Sensitivity analyses of older patients and those undergoing nonemergency surgery demonstrated higher overall rates of complications for patients receiving TAC. However, among patients undergoing emergency surgery only, no differences in complications were seen between the two surgical approaches. CONCLUSIONS: PC with colostomy in the setting of ulcerative colitis has similar 30-day outcomes to TAC with ileostomy. PC may be an acceptable surgical alternative to TAC in select patients. Studies investigating longer-term outcomes are necessary to further investigate this option.

Topical Synthetic Platelets Loaded With Gentamicin Decrease Bacteria in Deep Partial-Thickness Burns.

INTRODUCTION: Prolonged inflammation and infection in burns may cause inadequate healing. Platelet granules contain anti-inflammatory mediators that impact wound healing. Synthetic platelets (SPs) avoid portability and storage difficulties of natural platelets and can be loaded with bioactive agents. We evaluated wound healing outcomes in deep partial-thickness (DPT) burns treated topically with SP loaded with antibiotics. MATERIALS AND METHODS: Thirty DPT burns were created on the dorsum of two Red Duroc hybrid pigs. Six wounds were randomized into five groups: SP alone, SP loaded with gentamicin vesicles, SP with gentamicin mixture, vehicle control (saline), or dry gauze. Wounds were assessed from postburn days 3-90. Primary outcome was re-epithelialization percentage at postburn day 28. Secondary outcomes included wound contraction percentage, superficial blood flow relative to normal skin controls, and bacterial load score. RESULTS: Results showed that re-epithelialization with the standard of care (SOC) was 98%, SP alone measured 100%, SP loaded with gentamicin vesicles was 100%, and SP with gentamicin mixture was 100%. Wound contraction was 5.7% in the SOC and was ∼10% in both the SP loaded with gentamicin vesicles and SP with gentamicin mixture groups. Superficial blood flow in the SOC was 102.5%, SP alone was 170%, the SP loaded was 155%, and gentamicin mixture 162.5%. Bacterial load score in the SOC was 2.2/5.0 and was significantly less at 0.8/5.0 in SP loaded with gentamicin vesicles (P > 0.05). SP and gentamicin mixture scored 2.7 and 2.3/5.0. CONCLUSIONS: Topical SP treatment did not significantly improve outcomes. However, SP loaded with gentamicin-infused vesicles decreased bacterial load.

Unraveling the Mechanisms of Fe Oxidation and Mn Reduction on Mn Indicators of Reduction in Soil (IRIS) Films.

Indicators of reduction in soil (IRIS) devices are low-cost soil redox sensors coated with Fe or Mn oxides, which can be reductively dissolved from the device under suitable redox conditions. Removal of the metal oxide coating from the surface, leaving behind the white film, can be quantified and used as an indicator of reducing conditions in soils. Manganese IRIS, coated with birnessite, can also oxidize Fe(II), resulting in a color change from brown to orange that complicates the interpretation of coating removal. Here, we studied field-deployed Mn IRIS films where Fe oxidation was present to unravel the mechanisms of Mn oxidation of Fe(II) and the resulting minerals on the IRIS film surface. We observed reductions in the Mn average oxidation state when Fe precipitation was evident. Fe precipitation was primarily ferrihydrite (30-90%), but lepidocrocite and goethite were also detected, notably when the Mn average oxidation state decreased. The decrease in the average oxidation state of Mn was due to the adsorption of Mn(II) to the oxidized Fe and the precipitation of rhodochrosite (MnCO3) on the film. The results were variable on small spatial scales (<1 mm), highlighting the suitability of IRIS in studying heterogeneous redox reactions in soil. Mn IRIS also provides a tool to bridge lab and field studies of the interactions between Mn oxides and reduced constituents.

Community-Based Surveillance and Geographic Information System‒Linked Contact Tracing in COVID-19 Case Identification, Ghana, March‒June 2020.

In response to the COVID-19 pandemic, Ghana implemented various mitigation strategies. We describe use of geographic information system (GIS)‒linked contact tracing and increased community-based surveillance (CBS) to help control spread of COVID-19 in Ghana. GIS-linked contact tracing was conducted during March 31-June 16, 2020, in 43 urban districts across 6 regions, and 1-time reverse transcription PCR testing of all persons within a 2-km radius of a confirmed case was performed. CBS was intensified in 6 rural districts during the same period. We extracted and analyzed data from Surveillance Outbreak Response Management and Analysis System and CBS registers. A total of 3,202 COVID-19 cases reported through GIS-linked contact tracing were associated with a 4-fold increase in the weekly number of reported SARS-CoV-2 infected cases. CBS identified 5.1% (8/157) of confirmed cases in 6 districts assessed. Adaptation of new methods, such as GIS-linked contact tracing and intensified CBS, improved COVID-19 case detection in Ghana.

Immunologic and dose dependent effects of rapamycin and its evolving role in chemoprevention.

Rapamycin inhibits the mechanistic (formally mammalian) target of rapamycin (mTOR), an evolutionarily conserved intracellular kinase that influences activation of growth signaling pathways and immune responses to malignancy. Rapamycin has been found to have both immunosuppressant and immunostimulatory effects throughout the innate and adaptive responses based on the inhibition of mTOR signaling. While the immunosuppressant properties of rapamycin and mTOR inhibition explain rapamycin's success in the prevention of transplant rejection, the immunostimulatory characteristics are likely partially responsible for rapamycin's anti-neoplastic effects. The immunologic response to rapamycin is at least partially dependent on the dose and administration schedule, with lower doses inducing immunostimulation and intermittent dosing promoting immune function while limiting metabolic and immunosuppressant toxicities. In addition to its FDA-approved application in advanced malignancies, rapamycin may be effective as a chemopreventive agent, suspending progression of low-grade cancers, preventing invasive conversion of in situ malignancy, or delaying malignant transformation of established pre-malignant conditions.

Guaranteeing dignity and decent work for migrant nurses and health care workers beyond the COVID-19 pandemic.

AIM(S): The main aim of this article is to outline the devastating aftereffects of COVID-19 in terms of ethical recruitment and the respect of dignity of nurses and health care professionals. BACKGROUND: Nations experience the ominous impacts of the COVID-19 pandemic in terms of an exacerbated shortage of nurses worldwide. In this situation, migration flows of nurses are skyrocketing and the respect of the migrant nurses' dignity as human beings should be guaranteed. EVALUATION: Data from reports elaborated by the International Centre on Nurse Migration (ICNM) were examined and outlined the central role of the respect of dignity of every nurse to prevent unethical exploitation of them. KEY ISSUE(S): The respect of human dignity is a complex concept. Human dignity denotes the inner nature of human beings but also their rights at work. CONCLUSION(S): In a post-COVID-19 world with increased flows of nurse migration, it is crucial to guarantee dignity at work for migrant nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse leaders should prioritize the ethical recruitment of health care workers and give a prominent role to the WHO 'Code of Practice on the International Recruitment of Health Personnel' which recognizes the ethical bedrocks of employment.

Care of the Patient With Acute Ischemic Stroke (Endovascular/Intensive Care Unit-Postinterventional Therapy): Update to 2009 Comprehensive Nursing Care Scientific Statement: A Scientific Statement From the American Heart Association.

Ischemic stroke remains the fifth leading cause of death in the United States. Nurses play a pivotal role in the care of patients throughout the continuum. With the advances in stroke care, including mechanical thrombectomy, the American Heart Association/American Stroke Association charged the writing panel to complement the 2009 clinical practice guideline, "Comprehensive Overview of Nursing and Interdisciplinary Care of the Acute Ischemic Stroke Patient," with current evidence-based nursing care. This update is 1 of a 3-part series focusing on emergency medical services/emergency care, endovascular/intensive care unit care, and postacute care. The aim of this scientific statement is to review and present current evidence, complications, best practices, and clinical practice strategies to provide current comprehensive scientific information for nursing care in the neuroendovascular area and intensive care unit in conjunction with medical treatments, including intravenous thrombolysis and mechanical thrombectomy.

Ehrlichia type IV secretion system effector Etf-2 binds to active RAB5 and delays endosome maturation.

Ehrlichia chaffeensis, an obligatory intracellular bacterium, infects monocytes/macrophages by sequestering a regulator of endosomal traffic, the small GTPase RAB5, on its membrane-bound inclusions to avoid routing to host-cell phagolysosomes. How RAB5 is sequestered on ehrlichial inclusions is poorly understood, however. We found that native Ehrlichia translocated factor-2 (Etf-2), a previously predicted effector of the Ehrlichia type IV secretion system, and recombinant Etf-2 (cloned into the Ehrlichia genome) are secreted into the host-cell cytoplasm and localize to ehrlichial inclusions. Ectopically expressed Etf-2-GFP also localized to inclusions and membranes of early endosomes marked with RAB5 and interacted with GTP-bound RAB5 but not with a GDP-bound RAB5. Etf-2, although lacking a RAB GTPase-activating protein (GAP) Tre2-Bub2-Cdc16 (TBC) domain, contains two conserved TBC domain motifs, namely an Arg finger and a Gln finger, and site-directed mutagenesis revealed that both Arg188 and Gln245 are required for Etf-2 localization to early endosomes. The yeast two-hybrid assay and microscale thermophoresis revealed that Etf-2 binds tightly to GTP-bound RAB5 but not to GDP-bound RAB5. However, Etf-2 lacks RAB5-specific GAP activity. Etf-2 localized to bead-containing phagosomes as well as endosomes containing beads coated with the C-terminal fragment of EtpE (entry-triggering protein of Ehrlichia), an Ehrlichia outer-membrane invasin, and significantly delayed RAB5 dissociation from and RAB7 localization to phagosomes/endosomes and RABGAP5 localization to endosomes. Thus, binding of Etf-2 to RAB5-GTP appears to delay RAB5 inactivation by impeding RABGAP5 localization to endosomes. This suggests a unique mechanism by which RAB5 is sequestered on ehrlichial inclusions to benefit bacterial survival and replication.

BH3-in-groove dimerization initiates and helix 9 dimerization expands Bax pore assembly in membranes.

Pro-apoptotic Bax induces mitochondrial outer membrane permeabilization (MOMP) by forming oligomers through a largely undefined process. Using site-specific disulfide crosslinking, compartment-specific chemical labeling, and mutational analysis, we found that activated integral membrane Bax proteins form a BH3-in-groove dimer interface on the MOM surface similar to that observed in crystals. However, after the α5 helix was released into the MOM, the remaining interface with α2, α3, and α4 helices was rearranged. Another dimer interface was formed inside the MOM by two intersected or parallel α9 helices. Combinations of these interfaces generated oligomers in the MOM. Oligomerization was initiated by BH3-in-groove dimerization, without which neither the other dimerizations nor MOMP occurred. In contrast, α9 dimerization occurred downstream and was required for release of large but not small proteins from mitochondria. Moreover, the release of large proteins was facilitated by α9 insertion into the MOM and localization to the pore rim. Therefore, the BH3-in-groove dimerization on the MOM nucleates the assembly of an oligomeric Bax pore that is enlarged by α9 dimerization at the rim.

A Link Between Alzheimer's and Type II Diabetes Mellitus? Ca+2 -Mediated Signal Control and Protein Localization.

We propose protein localization dependent signal activation (PLDSA) as a model to describe pre-existing protein partitioning between the cytosol, and membrane surface, as a means to modulate signal activation, specificity, and robustness. We apply PLDSA to explain possible molecular links between type II diabetes mellitus (T2DM) and Alzheimer's disease (AD) by describing Ca+2 -mediated interactions between the Src non-receptor tyrosine kinase and p52Shc adaptor protein. We suggest that these interactions may serve as a contributing factor to disease development and progression. In particular, we propose that signaling response is regulated, in part, by Ca+2 -mediated partitioning of lipid-bound and soluble forms of Src and p52shc. Thus, protein-protein interactions that drive signaling in response to extracellular ligand binding are also mediated by partitioning of signaling proteins between membrane-bound and soluble populations. We propose that PLDSA effects may explain, in part, the evolutionary basis of promiscuous protein interaction domains and their importance in cellular function.

Color constancy and color term knowledge are positively related during early childhood.

The ability to keep perception constant despite environmental changes of illumination, viewing angle, or distance is a key feature of perception. Here, we investigated how "perceptual constancy" relates to language learning by investigating the relationship between color constancy and color term knowledge in 3- and 4-year-old children. We used a novel method to test color constancy where children are required to match colored stimuli under different illuminations. We found a positive relationship between color constancy and color term knowledge; children who knew more color words also had better color constancy. The relationship remained even when accounting for the effect of age and ability to discriminate colors. The findings have implications for understanding the development of perceptual constancy, language learning, and the link between perceptual processing and cognitive development.

Nurse and health professional migration during COVID-19.

The COVID-19 pandemic has exposed the vulnerabilities of nursing supply flows, domestically and internationally. Its impact at the country-level has further highlighted preexisting nurse supply gaps and the effect of staffing shortages. Internationally, the pandemic has disrupted global supply chains. The world has witnessed the closing of borders, the interruption of travel, and, in some countries, the restriction of outflows. The State of the World's Nursing Report (SOWN) (WHO, 2020) noted a shortfall of almost six million nurses immediately pre-COVID-19, a shortage suffered particularly by low- and middle-income countries. This is of major concern given that increased international outflows of nurses in the new post-COVID era could undermine, even more than before, the readiness of those countries to meet healthcare demands (ICN, 2020). In this default scenario, some, but not all, highincome destination countries will continue to rely on international inflow of nurses to a significant extent, as they did pre-COVID- 19, further exacerbating the suffering of poor countries. Put simply, without country-level policy changes related to the nursing workforce and backed by international organisations, pre-COVID-19 trends of increased nurse flows from low- to high-income countries will likely continue. In this scenario, the iniquitous maldistribution of nurses may become more pronounced. This "do nothing" option risks undermining both country-level progress towards the attainment of Universal Health.

Intraarterial Thrombolysis as Rescue Therapy for Large Vessel Occlusions.

Background and Purpose- Mechanical thrombectomy (MT) devices have led to improved reperfusion and clinical outcomes in acute ischemic stroke patients with emergent large vessel occlusions; however, less than one-third of patients achieve complete reperfusion. Use of intraarterial thrombolysis in the context of MT may provide an opportunity to enhance these results. Here, we evaluate the use of intraarterial rtPA (recombinant tissue-type plasminogen activator) as rescue therapy (RT) after failed MT in the North American Solitaire Stent-Retriever Acute Stroke registry. Methods- The North American Solitaire Stent-Retriever Acute Stroke registry recruited sites within North America to submit data on acute ischemic stroke patients treated with the Solitaire device. After restricting the population of 354 patients to use of RT and anterior emergent large vessel occlusions, we compared patients who were treated with and without intraarterial rtPA after failed MT. Results- A total of 37 and 44 patients was in the intraarterial rtPA RT and the no intraarterial rtPA RT groups, respectively. Revascularization success (modified Thrombolysis in Cerebral Infarction ≥2b) was achieved in more intraarterial rtPA RT patients (61.2% versus 46.6%; P=0.13) with faster times to recanalization (100±85 versus 164±235 minutes; P=0.36) but was not statistically significant. The rate of symptomatic intracranial hemorrhage (13.9% versus 6.8%; P=0.29) and mortality (42.9% versus 44.7%; P=0.87) were similar between the groups. Good functional outcome (modified Rankin Scale score of ≤2) was numerically higher in intraarterial rtPA patients (22.9% versus 18.4%; P=0.64). Further restriction of the RT population to M1 occlusions only and time of onset to groin puncture ≤8 hours, resulted in significantly higher successful revascularization rates in the intraarterial rtPA RT cohort (77.8% versus 38.9%; P=0.02). Conclusions- Intraarterial rtPA as RT demonstrated a similar safety and clinical outcome profile, with higher reperfusion rates achieved in patients with M1 occlusions. Prospective studies are needed to delineate the role of intraarterial thrombolysis in MT.

Evolution of Care and Nursing: Moving With the Patients.

Health care costs are growing exponentially. They will continue to erode disposable income, especially among those most in need of health care-the poor and elderly. As the baby boomer generation ages, we will see dramatic growth in health care spending, which will influence the health care market in new ways. Increased government intervention and technological advancements will only further this shift. Factors driving the need for health care transformation include fragmentation, access problems, unsustainable costs, suboptimal outcomes, and disparities of care. Nurses now have more tools (ie, mHealth, telemedicine, and electronic health records) that they can use to provide assistance to their practices outside of acute care settings. These realities are all contributors to an evolving trend: retail health.