Effectiveness of telepharmacy diabetes services: A systematic review and meta-analysis.

PURPOSE: Although pharmacist-provided diabetes services have been shown to be effective, the effectiveness of telepharmacy (TP) in diabetes management has not been clearly established. This systematic review and meta-analysis aims to evaluate the effectiveness of diabetes TP services. METHODS: PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched (from inception through September 2021) to identify published studies that evaluated the effect of TP services in patients with diabetes mellitus and reported either glycosylated hemoglobin (HbA1c) or fasting blood glucose (FBG) outcomes. Mean difference (MD), weighted mean difference (WMD), relative risk (RR), and 95% confidence intervals were calculated using the DerSimonian and Laird random-effects model. RESULTS: 36 studies involving 13,773 patients were included in the systematic review, and 23 studies were included in the meta-analysis. TP was associated with a statistically significant decrease in HbA1c (MD, -1.26%; 95% CI, -1.69 to -0.84) from baseline. FBG was not significantly affected (MD, -25.32 mg/dL; 95% CI, -57.62 to 6.98). Compared to non-TP service, TP was associated with a lower risk of hypoglycemia (RR, 0.48; 95% CI, 0.30-0.76). In a subset of studies that compared TP to face-to-face (FTF) pharmacy services, no significant difference in HbA1c lowering was seen between the 2 groups (WMD, -0.09%; 95% CI, -1.07 to 0.90). CONCLUSION: Use of TP was associated with reduction of HbA1c and the risk of hypoglycemia in patients with diabetes mellitus. High-quality randomized controlled trials are needed to validate the effectiveness of diabetes TP services relative to FTF services.

Students' perceptions of a new transitions of care elective course in the pharmacy curriculum.

BACKGROUND AND PURPOSE: The purpose of the new transitions of care (TOC) elective to the pharmacy curriculum is to train pharmacy students to address TOC medication-related problems, assess students' knowledge and perceptions of the TOC pharmacist's role, and explore the impact on interest in post-graduate career planning. EDUCATIONAL ACTIVITY AND SETTING: Third-year pharmacy students were enrolled in the two-credit TOC elective course. The course was designed to include relevant TOC concepts and application of the Pharmacists' Patient Care Process. The pre- and post-assessment surveys were distributed at the beginning and end of the course by a staff administrator to eliminate survey bias. Students were asked to anonymously respond to nine survey questions using a five-point Likert scale (strongly disagree = 1, strongly agree = 5). FINDINGS: Ninety-two percent (n = 23) of the pharmacy students responded to the pre- and post-assessment surveys, and results were subsequently analyzed. Statistically significant responses existed to eight of nine questions regarding students' perceptions of increased knowledge of the TOC concepts and pharmacists' role, communication skills, confidence in providing comprehensive patient care, and interest in recommending the TOC elective course to their peers. There was interest in pursuing additional training opportunities, such as post-graduate residency or fellowship training, but the survey item was not statistically significant. SUMMARY: The TOC elective course provides an opportunity for pharmacy students to learn about the TOC pharmacist's role, improve knowledge on the TOC patient care process, develop practical skills, and engage with clinical pharmacists.

Effectiveness of Telepharmacy Versus Face-to-Face Anticoagulation Services in the Ambulatory Care Setting: A Systematic Review and Meta-analysis.

BACKGROUND: Effectiveness of anticoagulation services managed via telepharmacy (TP) has not been clearly demonstrated. OBJECTIVE: This systematic review and meta-analysis compares the effectiveness of TP anticoagulation services to face-to-face (FTF) anticoagulation services in the ambulatory care setting. METHODS: A literature search for studies assessing the effectiveness of TP services was conducted using PubMed, EMBASE, and Cochrane Central databases, from inception through November 18, 2020. Studies that compared TP with FTF anticoagulation services in the ambulatory care setting were included. Outcomes of interest included thromboembolic events, major bleeding, minor bleeding, any bleeding, warfarin international normalized ratio (INR) time in therapeutic range (TTR), frequency of extreme INR, anticoagulation-related emergency department visits, anticoagulation-related hospitalization, any hospitalization, and mortality. Relative risk (RR) and weighted mean difference were calculated using the DerSimonian and Laird random-effects model. RESULTS: Overall, 11 studies involving 8395 patients were included in the systematic review, and 9 studies were included in the pooled meta-analysis. Compared with FTF service, TP was associated with a lower risk of any bleeding and any hospitalization, with RRs of 0.65 (95% CI = 0.47 to 0.90; P = 0.01) and 0.59 (95% CI = 0.39 to 0.87; P = 0.01), respectively. There was no statistically significant difference in TTR or the risk of extreme supratherapeutic INR, major bleeding, minor bleeding, or thromboembolic events between the 2 groups. CONCLUSIONS: TP appears to be at least as effective as FTF anticoagulation services. Findings from this study support the utilization of TP practice models in ambulatory care anticoagulation management.

The Role of a Simulation-Based Activity on Student Perceptions of Parenteral Nutrition Education.

Introduction: Parenteral nutrition (PN) education in pharmacy schools and postgraduate programs may not sufficiently prepare future pharmacists for clinical practice. Limited data exist regarding innovative teaching strategies in the area of PN. The purpose of this study was to identify students' perceptions of a simulated PN activity in a pharmacotherapeutics course. Methods: Second-year Doctor of Pharmacy (PharmD) students from two cohorts (N = 84 for both cohorts) completed a PN assignment using simulated PN materials, which resembled those seen in clinical practice. Before and after the activity, students completed identical surveys about their perceived competence and interest in PN, which were analyzed using Wilcoxon signed-rank tests. Results: Following the simulation, the percentage of students affirming their perceived competence (selecting strongly agree or agree in the survey) in their ability to describe the process of combining ingredients to make a PN admixture (45.2% vs. 83.3%, p < 0.001) and calculate PN-related problems (58.3% vs. 83.3%, p < 0.001) improved. The proportion of students expressing interest in PN increased after the simulation (78.6% vs. 86.9%, p < 0.001). Conclusion: A simulated practicum experience in PN was viewed positively by PharmD students at this university, and may be a valuable active learning experience to incorporate in a PharmD curriculum.

Comparison of the Efficacy of Posaconazole Delayed Release Tablets and Suspension in Pediatric Hematology/Oncology Patients.

OBJECTIVES: Posaconazole is effective in preventing invasive fungal infections in neutropenic pediatric patients. The oral suspension has challenges in administration and absorption that are theorized to be minimized with delayed release tablets. However, this has not been validated in the pediatric population. This study was conducted to compare the efficacy and safety of posaconazole suspension and delayed release tablets in pediatric hematology/oncology patients. METHODS: A retrospective chart review in pediatric hematology/oncology patients was conducted from February 2013 to February 2017. Data collected include patient demographic data; posaconazole formulation, dose, and serum concentrations; and adverse events. RESULTS: Sixty-five patients with 353 serum posaconazole concentrations were included; 51.6% of concentrations drawn while patients were receiving posaconazole suspension were therapeutic, whereas 62.5% of concentrations drawn while patients were receiving posaconazole delayed release tablets were therapeutic (p = 0.035). Serum concentrations drawn while taking acid suppression (histamine receptor antagonists or proton pump inhibitors) and posaconazole suspension were less likely to be therapeutic (p < 0.0001) compared with those taken while receiving delayed release tablets. Adverse event profiles were similar between both formulations. CONCLUSIONS: Delayed release tablets proved more effective in achieving therapeutic serum posaconazole concentrations than posaconazole suspension, with minimal difference in adverse events, in pediatric hematology/oncology patients.

Use of Arginine Hydrochloride in the Treatment of Metabolic Alkalosis or Hypochloremia in Pediatric Patients.

OBJECTIVES: Dosing of arginine for treatment of hypochloremia or metabolic alkalosis is laborious and has inherent variability in dose selection. The primary objective of this study was to determine the efficacy of arginine in the treatment of metabolic alkalosis and hypochloremia. Secondary objectives were to determine an optimal dose, route, and frequency for arginine administration in the treatment of these conditions. METHODS: This single center, retrospective, descriptive study was conducted in children who received arginine for treatment of hypochloremia or metabolic alkalosis. Treatment success was assessed by measuring serum chloride and bicarbonate concentrations after arginine administration. RESULTS: Of the 464 orders analyzed, 177 met inclusion criteria in 82 unique patients. Fifty percent (n = 81) of arginine administrations used to manage hypochloremia saw normalization of abnormal chloride levels, and 83% (n = 62) of arginine administrations used to treat metabolic alkalosis saw normalization of abnormal bicarbonate levels. Patients who received arginine to resolve hypochloremia were statistically significantly more likely to have their hypochloremia resolve if they used alternative dosing methods compared to established dosing methods (76 vs. 5, p = 0.001). However, this relationship was not seen for patients with metabolic alkalosis (11 vs. 51, p = 1.000). The median percentage of calculated daily dose of arginine needed for resolution of hypochloremia was 59% and was 35% for metabolic alkalosis. CONCLUSIONS: Arginine is effective to improve metabolic alkalosis and hypochloremia. Established dosing methods are not more effective than other methods in resolving metabolic alkalosis or hypochloremia. Further prospective studies are warranted to validate these results.

The Effect of a BSA Conjugate of a Synthetic Hexasaccharide Related to the Fragment of Capsular Polysaccharide of Streptococcus pneumoniae Type 14 on the Activation of Innate and Adaptive Immune Responses.

We report the effect of a bovine serum albumin (BSA) conjugate of a synthetic hexasaccharide (HS) related to the fragment of the capsular polysaccharide (PS) of Streptococcus pneumoniae type 14 on the stimulation of innate immune system and the subsequent development of a PS-specific antibody response. Glycoconjugate (GC) in the presence (GC + AL) or absence of aluminum hydroxide was administered to mice twice. GC increased the number of TLR2-expressing cells and induced the maturation of dendritic cells (CD11c(+), CD80(+) and, MHCII(+)), which secreted IL-1ß, IL-6, and TNFα into the culture medium. The level of IL-1ß, IL-10, IFNγ, and TNFα in the blood increased within 24 h after the single GC administration to mice. On day 7, the numbers of splenic CD4(+) and CD8(+) T lymphocytes and B lymphocytes increased. After the second immunization, the levels of CD4(+) and CD8(+) T lymphocytes were lower than in the control, whereas the B cell, NK cell, and MHC class II-expressing cell numbers remained enhanced. However, of the presence of anti-PS, IgG antibodies were not detected. The addition of aluminum hydroxide to GC stimulated the production of GM-CSF, IL-1ß, IL-5, IL-6, IL-10, IL-17, IFNγ, and TNFα. Anti-PS IgG1 antibody titers 7 days after the second immunization were high. During that period, normal levels of splenic CD4(+) T lymphocytes were maintained, whereas reduced CD8(+) T lymphocyte numbers and increased levels of B lymphocytes, NK cells, and MHC class II-expressing cell numbers were observed. Anti-PS IgG levels diminished until day 92. A booster immunization with GC + AL stimulated the production of anti-PS IgG memory antibodies, which were determined within 97 days. The elucidation of specific features of the effect of the synthetic HS conjugate on the stimulation of innate, cell-mediated immunity, and antibody response can favor the optimization of GC vaccine design.

Filamin A Is Involved in HIV-1 Vpu-mediated Evasion of Host Restriction by Modulating Tetherin Expression.

Tetherin, also known as bone marrow stromal antigen 2 (BST-2), inhibits the release of a wide range of enveloped viruses, including human immunodeficiency virus, type 1 (HIV-1) by directly tethering nascent virions to the surface of infected cells. The HIV-1 accessary protein Vpu counteracts tetherin restriction via sequestration, down-regulation, and/or displacement mechanisms to remove tetherin from sites of virus budding. However, the exact mechanism of Vpu-mediated antagonism of tetherin restriction remains to be fully understood. Here we report a novel role for the actin cross-linking regulator filamin A (FLNa) in Vpu anti-tetherin activities. We demonstrate that FLNa associates with tetherin and that FLNa modulates tetherin turnover. FLNa deficiency was found to enhance cell surface and steady-state levels of tetherin expression. In contrast, we observed that overexpression of FLNa reduced tetherin expression levels both on the plasma membrane and in intracellular compartments. Although FLNb shows high amino acid sequence similarity with FLNa, we reveal that only FLNa, but not FLNb, plays an essential role in tetherin turnover. We further showed that FLNa deficiency inhibited Vpu-mediated enhancement of virus release through interfering with the activity of Vpu to down-regulate cellular tetherin. Taken together, our studies suggest that Vpu hijacks the FLNa function in the modulation of tetherin to neutralize the antiviral factor tetherin. These findings may provide novel strategies for the treatment of HIV-1 infection.

Solvent Effects on the UV-Vis Absorption Properties and Tautomerism of N-Confused Tetraphenylporphyrin.

The two tautomeric forms of N-confused tetraphenylporphyrin (NCTPP) show distinctly different absorption spectra. The existence of each tautomer in solution has been shown to be strongly solvent-dependent. In the present work, we have studied the tautomerization using absorption spectroscopy in 15 different solvents. While changes in the two tautomers are not large in the Soret band region, the distinct spectral changes between the two tautomers in the Q-band region provide a convenient way to measure the concentration of each tautomer. The resulting data shows a strong correlation between the tautomer and the H-bond accepting ability of the solvent. The anomaly in this data is for the alcoholic solvents ethanol and methanol, for which we observe evidence for H-bonding, presumably between the exterior N2 nitrogen of the NCTPP and the O-H proton of the solvent.

Surface APRIL Is Elevated on Myeloid Cells and Is Associated with Disease Activity in Patients with Rheumatoid Arthritis.

OBJECTIVE: To assess surface APRIL (a proliferation-inducing ligand; CD256) expression by circulating myeloid cells in rheumatoid arthritis (RA) and to determine its relationship to disease activity. METHODS: Peripheral blood mononuclear cells (PBMC) and plasma were obtained from patients with RA and healthy donors. PBMC were stained for flow cytometry to detect surface APRIL and blood cell markers to identify circulating myeloid cell subsets. Based on CD14 and CD16 phenotypes, monocyte subsets described as classical (CD14+CD16-), intermediate (CD14+CD16+), and nonclassical (CD14loCD16+) were identified. Levels of surface APRIL expression were measured by flow cytometry and median fluorescence intensity was used for comparisons. Levels of soluble APRIL in the plasma were determined by ELISA. Disease activity was measured by the Disease Activity Score in 28 joints. RESULTS: In patients with RA, total myeloid cells showed expression of surface APRIL that correlated with disease activity and with plasma APRIL levels observed in these patients. In healthy donors, classical monocytes were composed of > 80% of circulating monocytes. However, in patients with RA, the intermediate and nonclassical subsets were elevated and made up the majority of circulating monocytes. In contrast to healthy donors, where high levels of surface APRIL were only observed in nonclassical monocytes, patients with RA showed high levels of surface APRIL expression by all circulating monocyte subsets. CONCLUSION: Surface APRIL is elevated in circulating myeloid cells in patients with RA where it is highly correlated with disease activity. Patients with RA also showed skewing of monocytes toward subsets associated with secretion of tumor necrosis factor-α and/or interleukin 1ß.

Kinematic and kinetic analysis of the inter- and intra-applicator assessment of the Babinski reflex.

AIMS OF THE STUDY: The first aim was to quantify variability in the mechanical technique used by neurologists to elicit the Babinski reflex. The second aim of the study was to assess if the mechanical technique is an important determinant of the subsequent reflex response. MATERIALS AND METHODS: In this study, twelve neurologists elicited the Babinski reflex five times on the same foot of the same participant using a special reflex hammer which recorded the force and duration of the stroke. Hallux movement, tibialis anterior maximum EMG amplitude and pain felt by the participant for each stroke were recorded. RESULTS: A large inter- and intra-applicator variability was shown amongst the neurologists. The change in hallux angle was significantly correlated with the duration of the stroke (R(2)=0.18, P<0.01), maximum (R(2)=0.14, P=0.01) and average (R(2)=0.17, P<0.01) force used to elicit the reflex. No correlations were shown between the hammer forces and duration and the maximum amplitude of the tibialis anterior. Significant correlations were shown between the pain score and the maximum (R(2)=0.15, P<0.01) and average (R(2)=0.17, P=0.001) force used to elicit the Babinski reflex. CONCLUSION: These results indicate that there was substantial variation when performing the Babinski reflex test within and between neurologists which could lead to differences in the resultant reflex and therefore may affect subsequent diagnoses.

Single-Molecule Fluorescence Using Nucleotide Analogs: A Proof-of-Principle.

Fluorescent nucleotide analogues, such as 2-aminopurine (2AP) and pyrrolo-C (PyC), have been extensively used to study nucleic acid local conformational dynamics in bulk experiments. Here we present a proof-of-principle approach using 2AP and PyC fluorescence at the single-molecule level. Our data show that ssDNA, dsDNA, or RNA containing both 2AP and PyC can be monitored using single-molecule fluorescence and a click chemistry immobilization method. We demonstrate that this approach can be used to monitor DNA and RNA in real time. This is the first reported assay using fluorescent nucleotide analogs at the single-molecule level. We anticipate that single 2AP or PyC fluorescence will have numerous applications in studies of DNA and RNA, including protein-induced base-flipping dynamics in protein-nucleic acid complexes.

Activation of innate immunity by bacterial ligands of toll-like receptors.

Tγδ and B1 lymphocytes are essential components of the mucosal immune system, activated directly by different bacterial and viral ligands without additional costimulatory signals and preprocessing of other immune effectors. This ability enables the immune system to provide rapid protection against pathogens and contributes to the decoding mechanism of the sensitizing activity of mucosal antigens. The early interaction of these cells results in the production of antibodies of immunoglobulin M (IgM) and IgA isotypes, but not immunoglobulin E (IgE). We studied the subcutaneous, intranasal, and oral delivery as three major routes of potential entry for antigens of opportunistic microorganisms, using the immunomodulator Immunovac-VP-4, which is able to activate Tγδ and B1 lymphocytes. The subcutaneous and intranasal routes produced a significant increase of these cells in lymph nodes associated with the nasal cavity (NALT) and in those associated with bronchial tissue (BALT). The oral route significantly increased levels of these cells in the spleen, in NALT, BALT, and in nodes associated with the gut (GALT). We found that mucosal application of Immunovac-VP-4, which contains antigens of conditionally pathogenic microorganisms, in conjunction with the activation of Tγδ and B1, induces adaptive immune mechanisms not only in the lymphoid formations associated with the respiratory system and with GALT, but also in the spleen [increased expression of cluster of differentiation 3 (CD3), CD4, CD8, CD19, and CD25]. This indicates that there is migration of lymphoid cells from the regional lymph nodes and mucosal lymphoid tissues via the lymph and blood to distant organs, resulting in lymphoid development, and both local and systemic immunity. Mucosal application of Immunovac-VP-4 in mice potentiates the cytotoxic activity of NK cells in the NALT, BALT, and GALT. The highest cytotoxicity was observed in cells, derived from lymphoid tissue of the intestine after oral immunization. Although we found that cytokine production was increased by all three immunization routes, it was most intensive after subcutaneous injection. Our findings confirm that there is an intensive exchange of lymphocytes not only between lymphoid formations in the mucous membranes of the respiratory tract and of GALT, but also with the spleen, which means that if effective mucosal vaccines are developed, they can induce both local and systemic immunity.

A multidisciplinary atrial fibrillation clinic.

BACKGROUND: Reports in the literature indicate that specialty clinics focusing on management of patients with specific chronic disorders have a significant positive impact on patient outcomes. Atrial fibrillation (AF), one of the most common forms of cardiac arrhythmia, affects millions of patients. Outcome data regarding the impact of managing patients with AF are limited. We established a specialty clinic focusing on management of patients with AF. The objective of our study was to evaluate the outcomes of treating AF patients in this clinic. METHODS: A team consisting of electrophysiologists and pharmacists designed a specific plan for managing and educating patients. This plan consisted of evaluation, implementation of an individualized treatment plan, patient education, medication management, and follow-up care. We reviewed the outcomes of patients who had clinic visits between November 2011 and March 2012. The primary outcome was the incidence of AF-related hospitalizations and stroke. RESULTS: Seventy one patients were included in the analysis. Out of 71 patients, we identified 17 (23.9%) patients who were hospitalized. Two of these 17 hospitalized patients had ischemic stroke events. CONCLUSION: When compared to published data in the existing literature, managing AF patients in specialty clinics reduces the incidence of AF-related hospitalizations and stroke.

Filamin A protein interacts with human immunodeficiency virus type 1 Gag protein and contributes to productive particle assembly.

HIV-1 Gag precursor directs virus particle assembly and release. In a search for Gag-interacting proteins that are involved in late stages of the HIV-1 replication cycle, we performed yeast two-hybrid screening against a human cDNA library and identified the non-muscle actin filament cross-linking protein filamin A as a novel Gag binding partner. The 280-kDa filamin A regulates cortical actin network dynamics and participates in the anchoring of membrane proteins to the actin cytoskeleton. Recent studies have shown that filamin A facilitates HIV-1 cell-to-cell transmission by binding to HIV receptors and coreceptors and regulating their clustering on the target cell surface. Here we report a novel role for filamin A in HIV-1 Gag intracellular trafficking. We demonstrate that filamin A interacts with the capsid domain of HIV-1 Gag and that this interaction is involved in particle release in a productive manner. Disruption of this interaction eliminated Gag localization at the plasma membrane and induced Gag accumulation within internal compartments. Moreover, blocking clathrin-dependent endocytic pathways did not relieve the restriction to particle release induced by filamin A depletion. These results suggest that filamin A is involved in the distinct step of the Gag trafficking pathway. The discovery of the Gag-filamin A interaction may provide a new therapeutic target for the treatment of HIV infection.

Spectroscopy of free-base N-confused tetraphenylporphyrin radical anion and radical cation.

The radical anions and radical cations of the two tautomers (1e and 1i) of 5,10,15,20-tetraphenyl N-confused free-base porphyrin have been studied using a combination of cyclic voltammetry, steady state absorption spectroscopy, and computational chemistry. N-Confused porphyrins (NCPs), alternatively called 2-aza-21-carba-5,10,15,20-tetraphenylporphyrins or inverted porphyrins, are of great interest for their potential as building blocks in assemblies designed for artificial photosynthesis, and understanding the absorption spectra of the corresponding radical ions is paramount to future studies in multicomponent arrays where electron-transfer reactions are involved. NCP 1e was shown to oxidize at a potential of E(ox) 0.65 V vs Fc(+)|Fc in DMF and reduce at E(red) -1.42 V, while the corresponding values for 1i in toluene were E(ox) 0.60 V and E(red) -1.64 V. The geometries of these radical ions were computed at the B3LYP/6-31+G(d)//B3LYP/6-31G(d) level in the gas phase and in solution using the polarizable continuum model (PCM). From these structures and that of H(2)TPP and its corresponding radical ions, the computed redox potentials for 1e and 1i were calculated using the Born-Haber cycle. While the computed reduction potentials and electron affinities were in excellent agreement with the experimental reduction potentials, the calculated oxidation potentials displayed a somewhat less ideal relationship with experiment. The absorption spectra of the four radical ions were also measured experimentally, with radical cations 1e(•+) and 1i(•+) displaying significant changes in the Soret and Q-band regions as well as new low energy absorption bands in the near-IR region. The changes in the absorption spectra of radical anions 1e(•-) and 1i(•-) were not as dramatic, with the changes occurring only in the Soret and Q-band regions. These results were favorably modeled using time-dependent density functional calculations at the TD-B3LYP/6-31+G(d)//B3LYP/6-31G(d) level. These results were also compared to the existing data of free base tetraphenylporphyrin and free base tetraphenylchlorin.

Synthesis and magnetic properties of Gd doped EuS nanocrystals with enhanced Curie temperatures.

EuS nanocrystals (NCs) were doped with Gd resulting in an enhancement of their magnetic properties. New EuS and GdS single source precursors (SSPs) were synthesized, characterized, and employed to synthesize Eu(1-x)Gd(x)S NCs by decomposition in oleylamine and trioctylphosphine at 290 °C. The doped NCs were characterized using X-ray diffraction, transmission electron microscopy, and scanning transmission electron microscopy, which support the uniform distribution of Gd dopants through electron energy loss spectroscopy (EELS) mapping. X-ray absorption spectroscopy (XAS) revealed the dopant ions in Eu(1-x)Gd(x)S NCs to be predominantly Gd(3+). NCs with a variety of doping ratios of Gd (0 ≤ x < 1) were systematically studied using vibrating sample magnetometry and the observed magnetic properties were correlated with the Gd doping levels (x) as quantified with ICP-AES. Enhancement of the Curie temperature (T(C)) was observed for samples with low Gd concentrations (x ≤ 10%) with a maximum T(C) of 29.4 K observed for NCs containing 5.3% Gd. Overall, the observed T(C), Weiss temperature (θ), and hysteretic behavior correspond directly to the doping level in Eu(1-x)Gd(x)S NCs and the trends qualitatively follow those previously reported for bulk and thin film samples.

The nonsense-mediated decay pathway maintains synapse architecture and synaptic vesicle cycle efficacy.

A systematic Drosophila forward genetic screen for photoreceptor synaptic transmission mutants identified no-on-and-no-off transient C (nonC) based on loss of retinal synaptic responses to light stimulation. The cloned gene encodes phosphatidylinositol-3-kinase-like kinase (PIKK) Smg1, a regulatory kinase of the nonsense-mediated decay (NMD) pathway. The Smg proteins act in an mRNA quality control surveillance mechanism to selectively degrade transcripts containing premature stop codons, thereby preventing the translation of truncated proteins with dominant-negative or deleterious gain-of-function activities. At the neuromuscular junction (NMJ) synapse, an extended allelic series of Smg1 mutants show impaired structural architecture, with decreased terminal arbor size, branching and synaptic bouton number. Functionally, loss of Smg1 results in a ~50% reduction in basal neurotransmission strength, as well as progressive transmission fatigue and greatly impaired synaptic vesicle recycling during high-frequency stimulation. Mutation of other NMD pathways genes (Upf2 and Smg6) similarly impairs neurotransmission and synaptic vesicle cycling. These findings suggest that the NMD pathway acts to regulate proper mRNA translation to safeguard synapse morphology and maintain the efficacy of synaptic function.

Laser-assisted single-molecule refolding (LASR).

To assemble into functional structures, biopolymers search for global minima through their folding potential energy surfaces to find the native conformation. However, this process can be hindered by the presence of kinetic traps. Here, we present a new single-molecule technique, termed laser-assisted single-molecule refolding (LASR), to characterize kinetic traps at the single-molecule level. LASR combines temperature-jump kinetics and single-molecule spectroscopy. We demonstrate the use of LASR to measure single-molecule DNA melting curves with ∼1°C accuracy and to determine the activation barrier of a model kinetic trap. We also show how LASR, in combination with mutagenesis, can be used to estimate the yields of competing pathways, as well as to generate and characterize transient, unstable complexes.

Complications associated with outpatient parenteral antibiotic therapy in children.

BACKGROUND: The authors sought to determine the prevalence, risk factors, and clinical impact of complications associated with outpatient parenteral antimicrobial therapy (OPAT) in children. METHODS: A cohort of patients ≤18 years old with infections, who received OPAT were evaluated retrospectively. Antibiotic-associated complications (AACs), catheter-associated complications (CACs), and unplanned medical care visits were the main outcome measures. RESULTS: Overall, 36 complications (25 CACs and 11 AACs) occurred in 32 of 98 patients. Mean age of patients, race, gender, and infecting organism did not differ between study groups. The use of OPAT for osteomyelitis was associated with complications (odds ratio = 2.69; 95% confidence interval = 0.99-7.35; P = .05). All patients, except for 4 who had complications, clinically improved by the end of OPAT. Unplanned medical visits occurred in 17 patients, 15 of which were because of CACs. CONCLUSION: Complications occurred commonly in children receiving OPAT and resulted in unplanned medical visits.