Two-photon absorption properties of BODIPY-like compounds based on BF2-naphthyridine complexes.

Boron dipyrromethene type molecules (BODIPYs) are versatile molecules which have been used for applications ranging from photodynamic therapy to solar cells (DSSC). However, these molecules usually do not present high two-photon absorption cross-sections, limiting their use in nonlinear optical applications. Herein, we study a series of BF2-naphthyridine based boron-complexes with electron-donating and withdrawing groups to increase their two-photon absorption. We have found two-photon absorption cross-sections up to approximately 270 GM, which corresponds to an increase of approximately five times in comparison to the average cross-section value reported for molecules with similar conjugation length, indicating such compounds as potential materials for nonlinear applications in both the visible and infrared spectral regions.

The Use of Aromatherapy in Postoperative Nausea and Vomiting: A Systematic Review.

PURPOSE: To evaluate the following question: In adult surgical patients, does the use of aromatherapy affect the incidence of nausea and vomiting postoperatively? DESIGN: Systematic review of research focusing on aromatherapy and the effect on postoperative nausea and vomiting (PONV) in adult surgical patients. METHODS: A search of Medline, PubMed, Cumulative Index of Nursing and Allied Literature, and Cochrane Database of Systematic Reviews using specific inclusion and exclusion criteria yielded five randomized controlled trials. FINDINGS: The overall synthesis of evidence supports the use of aromatherapy in PONV. Aromatherapy has a positive effect on PONV, and therefore should be considered as a complementary therapy or as an adjunct to antiemetic medications. CONCLUSIONS: Aromatherapy is one modality that should be considered as treatment for PONV in adult surgical patients. More research should be conducted to provide additional support in the use of aromatherapy for PONV. Future research could aim at standardizing a nausea scale that would provide more reliable and valid results in studies that research PONV.

Helicenes Grafted with 1,1,4,4-Tetracyanobutadiene Moieties: π-Helical Push-Pull Systems with Strong Electronic Circular Dichroism and Two-Photon Absorption.

Enantiopure P- and M-carbo[6]helicenes substituted with one or two tetracyanobutadiene moieties at positions 2 and 15 have been prepared. Grafting of these electron-accepting groups onto the π-helical core resulted in strong charge-transfer effects, which greatly affected the UV/Vis, electronic circular dichroism (ECD), and two-photon absorption (TPA) responses. The ECD signal was found to be reversibly switched by applying a redox stimulus.

Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol.

BACKGROUND: Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease. METHODS/DESIGN: We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance. DISCUSSION: Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials. TRIAL REGISTRATION: Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.

Direct to OR resuscitation of abdominal trauma: An NTDB propensity matched outcomes study.

BACKGROUND: Direct to operating room resuscitation (DOR) is used by some trauma centers for severely injured trauma patients as an approach to minimize time to hemorrhage control. It is unknown whether this strategy results in favorable outcomes. We hypothesized that utilization of an emergency department operating room (EDOR) for resuscitation of patients with abdominal trauma at an urban Level I trauma center would be associated with decreased time to laparotomy and improved outcomes. METHODS: We included patients 15 years or older with abdominal trauma who underwent emergent laparotomy within 120 minutes of arrival both at our institution and within a National Trauma Data Bank sample between 2007 to 2019 and 2013 to 2016, respectively. Our institutional sample was matched 1:1 to an American College of Surgeons National Trauma Databank sample using propensity score matching based on age, sex, mechanism of injury, and abdominal Abbreviated Injury Scale score. The primary outcome was time to laparotomy incision. Secondary outcomes included blood transfusion requirement, intensive care unit (ICU) length of stay (LOS), ventilator days, hospital LOS, and in-hospital mortality. RESULTS: Two hundred forty patients were included (120 institutional, 120 national). Both samples were well balanced, and 83.3% sustained penetrating trauma. There were 84.2% young adults between the ages of 15 and 47, 91.7% were male, 47.5% Black/African American, with a median Injury Severity Score of 14 (interquartile range [IQR], 8-29), Glasgow Coma Scale score of 15 (IQR, 13-15), 71.7% had an systolic blood pressure of >90 mm Hg, and had a shock index of 0.9 (IQR, 0.7-1.1) which did not differ between groups (p > 0.05). Treatment in the EDOR was associated with decreased time to incision (25.5 minutes vs. 40 minutes; p ≤ 0.001), ICU LOS (1 vs. 3.1 days; p < 0.001), transfusion requirement within 24 hours (3 units vs. 5.8 units packed red blood cells; p = 0.025), hospital LOS (5 days vs. 8.5 days, p = 0.014), and ventilator days (1 day vs. 2 days; p ≤ 0.001). There were no significant differences in in-hospital mortality (22.5% vs. 15.0%; p = 0.14) or outcome-free days (4.9 days vs. 4.5 days, p = 0.55). CONCLUSION: The use of an EDOR is associated with decreased time to hemorrhage control as evidenced by the decreased time to incision, blood transfusion requirement, ICU LOS, hospital LOS, and ventilator days. These findings support DOR for patients sustaining operative abdominal trauma. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level III.

Geriatric patients on antithrombotic therapy as a criterion for trauma team activation leads to over triage.

BACKGROUND: Our institution amended its trauma activation criteria to require a Level II activation for patients ≥65 years old on antithrombotic medication presenting with suspected head trauma. METHODS: Our institutional trauma registry was queried for geriatric patients on antithrombotic medication in the year before and after this criteria change. Demographics, presentation metrics, level of activation, and outcomes were compared between groups. RESULTS: After policy change, a greater proportion of patients received a trauma activation (19.9 vs. 74.9%, P < 0.001) and a greater proportion of these patients were discharged directly home without injury (4.3 vs. 44%, P < 0.001). However, a smaller proportion of patients with a critical Emergency Department disposition or traumatic intracranial hemorrhage failed to receive a trauma activation (65.1 vs. 23.5%, P < 0.001; 70.7% vs. 27.3%, P < 0.001). There was no change in mortality (4.3 vs. 2.0%, P = 0.21). CONCLUSIONS: Implementing new criteria increased overtriage, decreased undertriage, and had little effect on mortality.

Lopinavir cerebrospinal fluid steady-state trough concentrations in HIV-infected adults.

BACKGROUND: The central nervous system may act as a sanctuary site for viral replication in the setting of low antiretroviral penetration. Data on lopinavir cerebrospinal fluid (CSF) trough concentration (C(trough)) values have yet to be reported. OBJECTIVE: To describe lopinavir CSF C(trough) values and compare them with a measure of HIV susceptibility. METHODS: In a prospective, open-label design, HIV-infected adults whose regimen included lopinavir/ritonavir 400/100-mg soft-gel capsules twice daily for at least 4 weeks were enrolled. Each subject had 8 plasma lopinavir concentrations determined over a 12-hour dosing interval and 1 CSF lopinavir C(trough) value determined at the end of the study. Linear regression methods tested for associations between CSF or CSF to plasma concentration ratio and covariates including pharmacokinetic parameters and CSF protein. RESULTS: Ten patients (7 male; median [range] +/- SD age 45.3 +/- 2.8 y) completed the study. Median (intraquartile range [IQR]) lopinavir plasma 0- to 12-hour area under the curve (AUC(0-12)) and minimum concentrations were 71.3 h x microg/mL (48.4-87.6) and 3.82 microg/mL (2.76-5.34). Median (IQR) CSF C(trough), paired plasma concentration, and time since last dose were 11,200 pg/mL (6760-16,400), 5.42 microg/mL (3.88-5.85), and 9.9 hours (9.7-10.2), respectively. Median (IQR) CSF to plasma concentration ratio was 0.225% (0.194-0.324). Lopinavir CSF C(trough) was above the median 50% inhibitory concentration (IC(50)) for wild-type HIV-1 (wtHIV-1) (1900 pg/mL) in all subjects. Lopinavir plasma AUC(0-12) (r(2) = 0.65; p = 0.009) and CSF protein (r(2) = 0.26; p = 0.006) were associated with lopinavir CSF concentration, while CSF protein (r(2) = 0.66; p = 0.008) was associated with CSF to plasma concentration ratio. CONCLUSIONS: Lopinavir CSF C(trough) was above the median IC(50) for wtHIV-1 replication in all patients receiving lopinavir/ritonavir 400/100-mg soft-gel capsules twice daily.

Simultaneous analysis of cyclophosphamide, doxorubicin and doxorubicinol by liquid chromatography coupled to tandem mass spectrometry.

A method for the simultaneous determination of cyclophosphamide (CP), doxorubicin (dox), and doxorubicinol (dol) was developed and validated to analyze 400 microL of plasma from patients receiving chemotherapeutic treatment with CP and dox. Final calibration ranges for the analytes were 0.440-60.0 microg/mL for cyclophosphamide, 7.20-984 ng/mL for dox and 3.04-104 ng/mL for dol. The samples were prepared using solid phase extraction and analyzed using a gradient separation over a Waters Symmetry C18, 2.1 by 30 mm (Milford, MA) column. Detection was achieved in positive mixed reaction monitoring mode on a triple quadrupole mass spectrometer.

Simultaneous determination of cortisol, dexamethasone, methylprednisolone, prednisone, prednisolone, mycophenolic acid and mycophenolic acid glucuronide in human plasma utilizing liquid chromatography-tandem mass spectrometry.

Chronic combination immunosuppressive regimens are commonly prescribed to renal transplant recipients. To develop an assay method for pharmacokinetic studies and therapeutic drug monitoring of multiple immunosuppressives, a liquid chromatography-tandem mass spectrometry (LC/MS/MS) approach for the simultaneous analysis of several glucocorticoids, mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG) was investigated. The resultant method utilized a gradient reverse phase separation over a Symmetry C18 column using an ammonium acetate-methanol mobile phase at pH 3.5. The analytes were detected by coupling the chromatography system via electrospray to a triple quadrupole mass spectrometer. Multiple-reaction monitoring in the negative mode ion (MH-/product) was employed selecting MPA at 319.1/190.9, MPAG at 495.1/191.0, dexamethasone at 391.0/361.0, hydrocortisone at 361.1/331.1, methylprednisolone at 373.1/343.1, prednisone at 357.1/327.2, and prednisolone at 359.1/329.1. The calibration curve concentrations ranged from 3.60 ng/mL to 50 microg/mL with the lowest limit of quantitation for corticosteroids being 3.60-7.20 ng/mL and 0.656-6.75 microg/mL for MPA and MPAG, respectively. The relative standard deviation for quality control intraday variation and interday variation was between 0.76% and 9.57% for all analytes. This assay offers a versatile, unique method for multi-analyte immunosuppressive determinations during combination immunosuppression.

Determination of lopinavir cerebral spinal fluid and plasma ultrafiltrate concentrations by liquid chromatography coupled to tandem mass spectrometry.

A method for the determination of lopinavir (LPV) concentrations in cerebral spinal fluid (CSF) and plasma ultrafiltrate (UF) was developed and validated to analyze clinical specimens from patients receiving antiretroviral treatment with lopinavir/ritonavir. The CSF (400 microL sample volume) final calibration range for LPV was 0.313-25.0 ng/mL. The final calibration range for UF (50 microL sample volume) was 1.25-100 ng/mL. The samples were prepared using liquid-liquid extraction, concentrated, and analyzed using a reversed phase isocratic separation. Detection was achieved in positive mixed reaction monitoring mode on a triple quadrupole mass spectrometer. Isolation of LPV through chromatographic separation and proper selection of calibration matrix were important factors in achieving accurate results. Plasma UF was found to be an equivalent calibration matrix to CSF whereas plasma matrix produced a positive bias in samples with unknown concentrations. Artificial CSF media prepared chemically were biased and less superior than UF. Sources of plasma for the UF did not affect accuracy. Several CSF sources were tested for specificity of the method and LPV concentrations were accurately produced with atmospheric pressure chemical ionization source producing more accurate results than the electrospray source. The method successfully measured LPV concentrations in CSF that were previously undetectable by HPLC as well as UF from protein binding studies.

Buprenorphine assay and plasma concentration monitoring in HIV-infected substance users.

The availability of buprenorphine (BUP) provides an alternative approach to the treatment of opioid addiction with methadone, an agent that has many drug-drug interactions when combined with antiretroviral therapy (ART). However, due to limited long-term pharmacokinetic studies in HIV-infected patients, the clinical use of BUP, a CYP450-3A4 substrate, will require that studies be conducted to examine safety, tolerability and pharmacokinetics when these drugs are taken for chronic treatment. One clinical approach could include plasma concentration monitoring to avoid under- or overdosing BUP secondary to drug interactions with ART. The measurement of BUP and its active metabolite, norbuprenorphine (NBUP) facilitates the addition of BUP to ART in an attempt to avoid drug toxicity as described in a recent report by Bruce et al. Therefore, our objective was to validate a BUP assay and integrate its application into an ongoing antiretroviral (ARV) plasma concentration monitoring program. A chromatographic method for monitoring BUP and its active metabolite, NBUP was investigated. An assay was developed that would facilitate BUP and ARV measurement from a single 3 mL blood sample (0.75 mL plasma required) in conjunction with a previously validated multiple ARV HPLC method. The method measures BUP and NBUP over the range from 0.25 to 50 ng/mL with mass spectrometry detection. Inter- and intra-assay variation was

Reflections on play: recollections from a mother and her son with Asperger syndrome.

This is a personal account of the play behaviors of an individual who has autism as remembered by himself and his mother. Jean-Paul Bovee explains the activities that were enjoyable for him and which were his play, although they were unusual and may not fit the typical definition of play. His mother, Dr Julie A. Donnelly, tells of her attempts to involve Jean-Paul in typical play and how important play is as a bridge to social skills and involvement with peers. Jean-Paul concludes that his play is a part of the unique individual he has become.