Accuracy of Flash Glucose Monitoring in Hemodialysis Patients With and Without Diabetes Mellitus.

AIMS: Glucose and insulin metabolism are altered in hemodialysis patients, and diabetes management is difficult in these patients. We aimed to validate flash glucose monitoring (FGM) in hemodialysis patients with and without diabetes mellitus as an attractive option for glucose monitoring not requiring regular self-punctures. METHODS: We measured interstitial glucose using a FreeStyle Libre device in eight hemodialysis patients with and seven without diabetes mellitus over 14 days and compared the results to simultaneously performed self-monitoring of capillary blood glucose (SMBG). RESULTS: In 720 paired measurements, mean flash glucose values were significantly lower than self-measured capillary values (6.17±2.52 vs. 7.15±2.41 mmol/L, p=1.3 E-86). Overall, the mean absolute relative difference was 17.4%, and the mean absolute difference was 1.20 mmol/L. The systematic error was significantly larger in patients without vs. with diabetes (- 1.17 vs. - 0.82 mmol/L) and on dialysis vs. interdialytic days (-1.09 vs. -0.90 mmol/L). Compared to venous blood glucose (72 paired measurements), the systematic error of FGM was even larger (5.89±2.44 mmol/L vs. 7.78±7.25 mmol/L, p=3.74E-22). Several strategies to reduce the systematic error were evaluated, including the addition of +1.0 mmol/L as a correction term to all FGM values, which significantly improved accuracy. CONCLUSIONS: FGM systematically underestimates blood glucose in hemodialysis patients but, taking this systematic error into account, the system may be useful for glucose monitoring in hemodialysis patients with or without diabetes.

Serious Illness Discussion in Palliative Care-A Case Study Approach in an African American Patient with Cancer.

Medicare's new focus on end-of-life care has driven nurses and other clinicians to re-examine when advanced care planning should begin, and serious illness discussions should be conducted. This article will address barriers to, cultural influences on, framing of, and documentation of serious illness discussions using a case study approach.

The role of the endolithic alga Ostreobium spp. during coral bleaching recovery.

In this study, we explore how the Caribbean coral Orbicella faveolata recovers after bleaching, using fragments from 13 coral colonies exposed to heat stress (32 °C) for ten days. Biological parameters and coral optical properties were monitored during and after the stress. Increases in both, the excitation pressure over photosystem II (Qm) and pigment specific absorption (a*Chla) were observed in the stressed corals, associated with reductions in light absorption at the chlorophyll a red peak (De675) and symbiont population density. All coral fragments exposed to heat stress bleached but a fraction of the stressed corals recovered after removing the stress, as indicated by the reductions in Qm and increases in De675 and the symbiont population observed. This subsample of the experimentally bleached corals also showed blooms of the endolithic algae Ostreobium spp. underneath the tissue. Using a numerical model, we quantified the amount of incident light reflected by the coral, and absorbed by the different pigmented components: symbionts, host-tissue and Ostreobium spp. Our study supports the key contribution of Ostreobium spp. blooms near the skeletal surface, to coral recovery after bleaching by reducing skeleton reflectance. Endolithic blooms can thus significantly alleviate the high light stress that affects the remaining symbionts during the stress or when the coral has achieved the bleached phenotype.

Implementation of a Protocol for Peripheral Intravenous Norepinephrine: Does It Save Central Line Insertion, Is It Safe?

BACKGROUND: Central venous catheters (CVC) are generally recommended for norepinephrine administration due to risk of tissue ischemia. Early resuscitation, leading to decreased infusion duration, may minimize the need for CVCs if norepinephrine can be administered safely through a peripheral intravenous catheter (PIV). OBJECTIVE: A protocol was developed for peripheral administration. Safety, CVC placement, and adherence with protocol elements were evaluated. METHODS: A single-center, prospective, observational pilot was conducted for patients receiving norepinephrine in the Medical Intensive Care Unit (MICU). Patients were considered for PIV administration of low dose norepinephrine for less than 24 hours based on clinical status and anticipated short-term use. Protocolized interventions for PIV's included criteria for gauge, number, and site as well as visual inspection and evaluation every 2 hours. Data was collected on protocol elements to evaluate safety and effectiveness of the protocol. RESULTS: There were 316 occurrences of norepinephrine infusions including 92 via PIV (patients may have received multiple treatments). 34% (31/92) did not require a CVC. 3 had infiltrated PIV's without tissue injury. Maximum dose adherence was 73%. 97% of infusions ran less than 24 hours. Nursing adherence included: 91% gauge, 65% proper site, 99% adequate number, 49% blood return on initiation, 55% ongoing blood return, and 61% IV site checked. CONCLUSION: Our results suggest that norepinephrine is safe to administer through a PIV at low doses for less than 24 hours using a protocol. Prevention of unnecessary CVC insertion is beneficial by minimizing the risk of central line complications thus improving patient morbidity.

Complex Oncologic Surgeries and Implications for the Intensive Care Unit Nurse.

There are many challenges in caring for the postsurgical patient in the intensive care unit. When the postsurgical patient has an active malignancy, this can make the intensive care unit care more challenging. Nutrition, infection, and the need for postoperative mechanical ventilatory support for the patient with cancer present challenges that may increase the patient's length of stay in the intensive care unit. Critical care nurses must be aware of these challenges as they provide care to this patient population.

Approach for tuberculosis-associated immune reconstitution inflammatory syndrome in an HIV-negative patient.

A male refugee from the Middle East was diagnosed with pulmonary tuberculosis and Pott's disease with paravertebral abscess. After starting the standard regimen, the sputum culture converted to negative and the patient's general condition improved. Six weeks later, the patient presented with clinical worsening of known symptoms, new appearance of focal neurological deficits and progress of radiological features showing progression of the paravertebral abscess. Immune reconstitution inflammatory syndrome with Mycobacterium tuberculosis (TB-IRIS) was presumed, and treatment with high-dose steroids was started. Due to recurrent relapses while tapering, corticosteroids had to be given over a prolonged period. After treatment completion, the patient was in a good general condition, abscesses had decreased and neurological deficits were in complete remission. This case presents the rare manifestation of TB-IRIS in HIV-negative patients and its management in a high-income country.

The Impact of the Electronic Health Record on Moving New Evidence-Based Nursing Practices Forward.

BACKGROUND: Anecdotal reports from across the country highlight the fact that nurses are facing major challenges in moving new evidence-based practice (EBP) initiatives into the electronic health record (EHR). PURPOSE: The purpose of this study was to: (a) learn current processes for embedding EBP into EHRs, (b) uncover facilitators and barriers associated with rapid movement of new evidence-based nursing practices into the EHR and (c) identify strategies and processes that have been successfully implemented in healthcare organizations across the nation. METHODS: A qualitative study design was utilized. Purposive sampling was used to recruit nurses from across the country (N = 29). Nine focus group sessions were conducted. Semistructured interview questions were developed. Focus groups were conducted by video and audio conferencing. Using an inductive approach, each transcript was read and initial codes were generated resulting in major themes and subthemes. RESULTS: Five major themes were identified: (a) barriers to advancing EBP secondary to the EHR, (b) organizational structure and governing processes of the EHR, (c) current processes for prioritization of EHR changes, (d) impact on ability of clinicians to implement EBP and (e) wait times and delays. LINKING EVIDENCE TO ACTION: Delays in moving new EBP practice changes into the EHR are significant. These delays are sources of frustration and job dissatisfaction. Our results underscore the importance of a priori planning for anticipated changes and building expected delays into the timeline for EBP projects. Moreover, nurse executives must advocate for greater representation of nursing within informatics technology governance structures and additional resources to hire nurse informaticians.

Outcomes of an Oral Care Protocol in Postmechanically Ventilated Patients.

BACKGROUND: Oral care is standard practice to prevent hospital-associated infections while patients are intubated and in the intensive care unit. Following extubation and transfer, infections remain an important risk for patients, but less attention is paid to oral care. Few studies have assessed the impact of oral care in recently extubated acutely ill patients. AIMS: To develop an evidence-based oral care protocol for hospitalized patients and determine the impact of this protocol on health outcomes in recently extubated patients. METHODS: In this randomized controlled trial, subjects were randomized to usual care or an intervention protocol that included tooth brushing, tongue scraping, flossing, mouth rinsing, and lip care. Major outcome measures were the revised THROAT (R-THROAT; oral cavity assessment) and overall prevalence of methicillin-sensitive Staphylococcus aureus and methicillin-resistant S. aureus on oral cultures. RESULTS: Seventy-four subjects were randomized. As measured by the R-THROAT, oral cavity health improved over time in both groups, but the intervention group demonstrated significantly more improvement than the control group (R-THROAT score improved by 1.97 intervention vs. 0.87 control; p = .04). Two categories, tongue and mouth comfort, demonstrated the most significant improvement. There was no difference in MSSA/MRSA colonization between the groups at the conclusion of the study. Overall, subjects in the intervention group were more satisfied with their protocol than subjects in the usual care group. LINKING EVIDENCE TO ACTION: This study offers an important evaluation of an oral care protocol after extubation. Results demonstrated improvement in the oral cavity assessment with the designed oral care protocol. Patients expressed a preference for the intervention protocol, which included a battery-operated toothbrush, higher-quality toothpaste and mouth rinse, tongue scraper, floss, and lip balm. The implementation of an oral care protocol specifically addressing patients in the immediate postintubation is essential.

Melting barriers to faunal exchange across ocean basins.

Accelerated loss of sea ice in the Arctic is opening routes connecting the Atlantic and Pacific Oceans for longer periods each year. These changes may increase the ease and frequency with which marine birds and mammals move between the Pacific and Atlantic Ocean basins. Indeed, recent observations of birds and mammals suggest these movements have intensified in recent decades. Reconnection of the Pacific and Atlantic Ocean basins will present both challenges to marine ecosystem conservation and an unprecedented opportunity to examine the ecological and evolutionary consequences of interoceanic faunal exchange in real time. To understand these changes and implement effective conservation of marine ecosystems, we need to further develop modeling efforts to predict the rate of dispersal and consequences of faunal exchange. These predictions can be tested by closely monitoring wildlife dispersal through the Arctic Ocean and using modern methods to explore the ecological and evolutionary consequences of these movements.

Coral transcriptome and bacterial community profiles reveal distinct Yellow Band Disease states in Orbicella faveolata.

Coral diseases impact reefs globally. Although we continue to describe diseases, little is known about the etiology or progression of even the most common cases. To examine a spectrum of coral health and determine factors of disease progression we examined Orbicella faveolata exhibiting signs of Yellow Band Disease (YBD), a widespread condition in the Caribbean. We used a novel combined approach to assess three members of the coral holobiont: the coral-host, associated Symbiodinium algae, and bacteria. We profiled three conditions: (1) healthy-appearing colonies (HH), (2) healthy-appearing tissue on diseased colonies (HD), and (3) diseased lesion (DD). Restriction fragment length polymorphism analysis revealed health state-specific diversity in Symbiodinium clade associations. 16S ribosomal RNA gene microarrays (PhyloChips) and O. faveolata complimentary DNA microarrays revealed the bacterial community structure and host transcriptional response, respectively. A distinct bacterial community structure marked each health state. Diseased samples were associated with two to three times more bacterial diversity. HD samples had the highest bacterial richness, which included components associated with HH and DD, as well as additional unique families. The host transcriptome under YBD revealed a reduced cellular expression of defense- and metabolism-related processes, while the neighboring HD condition exhibited an intermediate expression profile. Although HD tissue appeared visibly healthy, the microbial communities and gene expression profiles were distinct. HD should be regarded as an additional (intermediate) state of disease, which is important for understanding the progression of YBD.

Langerhans cell maturation is accompanied by induction of N-cadherin and the transcriptional regulators of epithelial-mesenchymal transition ZEB1/2.

Langerhans cells (LCs) are a unique subset of dendritic cells (DCs) that express epithelial adhesion molecules, allowing them to form contacts with epithelial cells and reside in epidermal/epithelial tissues. The dynamic regulation of epithelial adhesion plays a decisive role in the life cycle of LCs. It controls whether LCs remain immature and sessile within the epidermis or mature and egress to initiate immune responses. So far, the molecular machinery regulating epithelial adhesion molecules during LC maturation remains elusive. Here, we generated pure populations of immature human LCs in vitro to systematically probe for gene-expression changes during LC maturation. LCs down-regulate a set of epithelial genes including E-cadherin, while they upregulate the mesenchymal marker N-cadherin known to facilitate cell migration. In addition, N-cadherin is constitutively expressed by monocyte-derived DCs known to exhibit characteristics of both inflammatory-type and interstitial/dermal DCs. Moreover, the transcription factors ZEB1 and ZEB2 (ZEB is zinc-finger E-box-binding homeobox) are upregulated in migratory LCs. ZEB1 and ZEB2 have been shown to induce epithelial-to-mesenchymal transition (EMT) and invasive behavior in cancer cells undergoing metastasis. Our results provide the first hint that the molecular EMT machinery might facilitate LC mobilization. Moreover, our study suggests that N-cadherin plays a role during DC migration.

Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells.

Podoplanin, a mucin-like plasma membrane protein, is expressed by lymphatic endothelial cells and responsible for separation of blood and lymphatic circulation through activation of platelets. Here we show that podoplanin is also expressed by thymic fibroblastic reticular cells (tFRC), a novel thymic medulla stroma cell type associated with thymic conduits, and involved in development of natural regulatory T cells (nTreg). Young mice deficient in podoplanin lack nTreg owing to retardation of CD4(+)CD25(+) thymocytes in the cortex and missing differentiation of Foxp3(+) thymocytes in the medulla. This might be due to CCL21 that delocalizes upon deletion of the CCL21-binding podoplanin from medullar tFRC to cortex areas. The animals do not remain devoid of nTreg but generate them delayed within the first month resulting in Th2-biased hypergammaglobulinemia but not in the death-causing autoimmune phenotype of Foxp3-deficient Scurfy mice.

Live cell imaging of chemotactic dendritic cell migration in explanted mouse ear preparations.

Leukocyte migration through the interstitial space is crucial for the maintenance of tolerance and immunity. The main cues for leukocyte trafficking are chemokines thought to directionally guide these cells towards their targets. However, model systems that facilitate quantification of chemokine-guided leukocyte migration in vivo are uncommon. Here we describe an ex vivo crawl-in assay using explanted mouse ears that allows the visualization of chemokine-dependent dendritic cell (DC) motility in the dermal interstitium in real time. We present methods for the preparation of mouse ear sheets and their use in multidimensional confocal imaging experiments to monitor and analyze the directional migration of fluorescently labelled DCs through the dermis and into afferent lymphatic vessels. The assay provides a more physiological approach to study leukocyte migration than in vitro three-dimensional (3D) or 2-dimensional (2D) migration assays such as collagen gels and transwell assays.

Interstitial dendritic cell guidance by haptotactic chemokine gradients.

Directional guidance of cells via gradients of chemokines is considered crucial for embryonic development, cancer dissemination, and immune responses. Nevertheless, the concept still lacks direct experimental confirmation in vivo. Here, we identify endogenous gradients of the chemokine CCL21 within mouse skin and show that they guide dendritic cells toward lymphatic vessels. Quantitative imaging reveals depots of CCL21 within lymphatic endothelial cells and steeply decaying gradients within the perilymphatic interstitium. These gradients match the migratory patterns of the dendritic cells, which directionally approach vessels from a distance of up to 90-micrometers. Interstitial CCL21 is immobilized to heparan sulfates, and its experimental delocalization or swamping the endogenous gradients abolishes directed migration. These findings functionally establish the concept of haptotaxis, directed migration along immobilized gradients, in tissues.

The Occurrence of Mixed Infections of Symbiodinium (Dinoflagellata) within Individual Hosts.

Coral reef ecosystems depend on symbiosis between dinoflagellates of the genus Symbiodinium Freudenthal and their various hosts. The physiological characteristics associated with a particular lineage or species of Symbiodinium can determine a host's susceptibility to harmful bleaching. Therefore, the threat posed by global climate change on a host may be reduced if it can switch or shuffle its dominant algal symbiont type. An important prerequisite to this potential to switch or shuffle is the ability to host multiple alternative dominant symbiont genotypes. To examine the distribution of this trait, we review reports of mixed Symbiodinium infections in corals and nonscleractinian hosts from a phylogenetic perspective. Hosts showing evidence of mixed infection are broadly distributed across the most deeply divergent host lineages, including foraminifera, mollusks, sponges, and cnidarians. The occurrence of mixed infections is also broadly distributed across most clades of scleractinian corals. Individual colonies of certain well-studied cosmopolitan coral genera, such as Acropora, Montastraea, and Pocillopora, yield many reports of mixed infection, while other genera, such as Porites, do not. We further discuss mixed Symbiodinium infections in the context of evolutionary ecology theory. Selection pressures that affect the prevalence of mixed infection may be exerted by variation in host environment, host ontogeny, symbiont transmission strategy, host regulation of symbiont populations, availability of free-living symbiont lineages, competition between symbiont lineages, and niche partitioning of the internal host environment.

The membrane skeleton controls diffusion dynamics and signaling through the B cell receptor.

Early events of B cell activation after B cell receptor (BCR) triggering have been well characterized. However, little is known about the steady state of the BCR on the cell surface. Here, we simultaneously visualize single BCR particles and components of the membrane skeleton. We show that an ezrin- and actin-defined network influenced steady-state BCR diffusion by creating boundaries that restrict BCR diffusion. We identified the intracellular domain of Igbeta as important in mediating this restriction in diffusion. Importantly, alteration of this network was sufficient to induce robust intracellular signaling and concomitant increase in BCR mobility. Moreover, by using B cells deficient in key signaling molecules, we show that this signaling was most probably initiated by the BCR. Thus, our results suggest the membrane skeleton plays a crucial function in controlling BCR dynamics and thereby signaling, in a way that could be important for understanding tonic signaling necessary for B cell development and survival.

Adaptive force transmission in amoeboid cell migration.

The leading front of a cell can either protrude as an actin-free membrane bleb that is inflated by actomyosin-driven contractile forces, or as an actin-rich pseudopodium, a site where polymerizing actin filaments push out the membrane. Pushing filaments can only cause the membrane to protrude if the expanding actin network experiences a retrograde counter-force, which is usually provided by transmembrane receptors of the integrin family. Here we show that chemotactic dendritic cells mechanically adapt to the adhesive properties of their substrate by switching between integrin-mediated and integrin-independent locomotion. We found that on engaging the integrin-actin clutch, actin polymerization was entirely turned into protrusion, whereas on disengagement actin underwent slippage and retrograde flow. Remarkably, accelerated retrograde flow was balanced by an increased actin polymerization rate; therefore, cell shape and protrusion velocity remained constant on alternating substrates. Due to this adaptive response in polymerization dynamics, tracks of adhesive substrate did not dictate the path of the cells. Instead, directional guidance was exclusively provided by a soluble gradient of chemoattractant, which endowed these 'amoeboid' cells with extraordinary flexibility, enabling them to traverse almost every type of tissue.

Serotype distribution and antibiotic resistance of Streptococcus pneumoniae strains isolated from adults in France: evolution between 2001 and 2003.

Antibiotic-resistant Streptococcus pneumoniae (Sp) are described around the world. The present national surveillance study report analyzes more than 6000 Sp strains, isolated from adults across France in 2001 and 2003, from blood cultures (3086 in 2001 and 3164 in 2003), cerebrospinal fluid (respectively, 238 and 240), or middle ear fluid (respectively, 110 and 100). The proportion of isolates with reduced susceptibility to penicillin fell significantly between 2001 and 2003 from 46.5% to 43.9%. The proportion of high-level resistant strains to penicillin minimal inhibitory concentrations (MIC > 1 mg/L), amoxicillin, and cefotaxime (MIC > 2 mg/L) slightly decreased but remained low: 10.6%, 1.2%, and 0.2% in 2003. Resistance to other antibiotics (erythromycin, cotrimoxazole, tetracycline, and chloramphenicol) also decreased. Decrease in prevalence of penicillin-resistant Sp varied according to specimen source. The proportion of penicillin nonsusceptible pneumococci decreased in blood cultures and middle ear fluids between 2001 and 2003 but increased in cerebrospinal fluid (43.4% and 46.5%, respectively). Serotypes covered by the heptavalent vaccine accounted for 42.4% of all isolates recovered in 2001 and 46.1% in 2003. Prevalence of antibiotic-resistant Sp decreased in 2003 in France.

Early events of B cell activation by antigen.

The activation of B cells confers long-lasting protection from a plethora of infectious diseases through the generation of plasma cells that produce high-affinity antibodies and memory cells. Engagement of the B cell receptor (BCR) with cognate antigen initiates intracellular signaling and subsequent internalization of antigen. Membrane-bound antigens are now considered the predominant forms that initiate B cell activation in vivo. We have shown that upon recognition of antigen on the surface of a presenting cell, the B cell undergoes a dramatic change in morphology characterized by rapid spreading followed by more prolonged contraction along the presenting surface. This two-phase response increases the amount of antigen that the B cell accumulates, internalizes, and subsequently presents to T cells. Thus, the spreading and contraction response shapes the outcome of B cell activation. We used a combination of planar lipid bilayers and total internal reflection fluorescence microscopy to investigate the early events that occur after engagement of the BCR and before B cell spreading. We observed the rapid formation of BCR-antigen microclusters, which we redefine as "microsignalosomes" because they mediate the coordinated recruitment of intracellular effectors, such as the kinases Lyn and Syk, the adaptor Vav, and phospholipase C-gamma2 (PLC-gamma2). We identified an essential role for the co-receptor CD19 in mediating spreading, and thus B cell activation, in response to membrane-bound antigen. Preliminary evidence suggests that the cellular morphology changes described in vitro are likely to occur upon recognition of antigen presented on the surface of macrophages in lymph nodes in vivo.