Air Versus Ground Transport Times in an Urban Center.

PURPOSE: Given that the benefits of helicopter transport vary with geography and healthcare systems, we assessed transport times for rotor wing versus ground transport over a 10 year period in an urban setting. MATERIALS AND METHODS: All completed transports from 153 sending hospitals in New England from 2009 through 2018 to 8 local tertiary care centers were extracted from an administrative database. The primary outcome of interest was patient-loaded transport time for rotor wing versus ground transports. Overall, 25,483 patient transports met the inclusion criteria and were included in this study. We assessed patient-loaded transport time for all transports, and determined mean time to arrive at the scene, scene to patient time, the bedside time, and distance at which the patient-loaded transport time was faster for rotor wing than for ground transport. We also performed subgroup analyses, evaluating transport times by time of day, day of the week, and destination. RESULTS: The most common indication for transport was adult trauma, (n = 6,008, 23.6%) followed by adult cardiac (n = 4359, 17.1%), adult neuro (3729 14.6%), and adult medical (n = 3691, 14.5%). The median miles traveled for all transports was 26.0, IQR 14-38, ranging from 1 to 264 miles. The median patient-loaded transport time was 27 min (IQR 15-40) for all transports. Nearly all time intervals were shorter for rotor wing versus ground transports, and patient-loaded transport time was significantly shorter at 15 minutes compared to 38 minutes (IQR 12-22 vs 28-33, p < 0.001). There was no distance at which the patient-loaded transport time was faster for ground transport than for rotor wing. CONCLUSIONS: In over 25,000 transports over 10 years, in a compact metropolitan area with relatively short transport distances and times, the use of the helicopter was associated with substantial time savings.

Application of Immunocompetent Microphysiological Systems in Drug Development: Current Perspective and Recommendations.

Immune responses are heavily involved in the regulation and pathogenesis of human diseases, including infectious diseases, inflammatory and autoimmune conditions, cancer, neurological disorders, and cardiometabolic syndromes. The immune system is considered a double-edged sword serving as a powerful host defense mechanism against infection and cancerous cells and causing detrimental tissue damage when the immune response is exaggerated or uncontrollable. One of the challenges in studying the efficacy and toxicity of drugs that target or modulate the immune system is the lack of suitable preclinical human models that are predictive of human response. Recent advancements in human microphysiological systems (MPS) have provided a promising in vitro platform to evaluate the response of immune organs ex vivo, to investigate the interaction of immune cells with non-lymphoid tissue cells, and to reduce the reliance on animals in preclinical studies. The development, regulation, trafficking, and responses of immune cells have been extensively studied in preclinical animal models and clinically, providing a wealth of knowledge by which to evaluate new in vitro models. Therefore, the application of immunocompetent MPS in drug discovery and development should first verify that the immune response in an MPS model recapitulates the complexity of the human immune physiology. This manuscript reviews biological functions of immune organ systems and tissue-resident immune cells and discusses contexts-of-use for commonly used immunocompetent and immune organ MPS models. Current perspective and recommendations are provided to guide the continued development of immune organ and immunocompetent MPS models and their application in drug discovery and development.

Usability of Electronic Health Record-Generated Discharge Summaries: Heuristic Evaluation.

BACKGROUND: Obtaining accurate clinical information about recent acute care visits is extremely important for outpatient providers. However, documents used to communicate this information are often difficult to use. This puts patients at risk of adverse events. Elderly patients who are seen by more providers and have more care transitions are especially vulnerable. OBJECTIVE: This study aimed to (1) identify the information about elderly patients' recent acute care visits needed to coordinate their care, (2) use this information to assess discharge summaries, and (3) provide recommendations to help improve the quality of electronic health record (EHR)-generated discharge summaries, thereby increasing patient safety. METHODS: A literature review, clinician interviews, and a survey of outpatient providers were used to identify and categorize data needed to coordinate care for recently discharged elderly patients. Based upon those data, 2 guidelines for creating useful discharge summaries were created. The new guidelines, along with 17 previously developed medical documentation usability heuristics, were applied to assess 4 simulated elderly patient discharge summaries. RESULTS: The initial research effort yielded a list of 29 items that should always be included in elderly patient discharge summaries and a list of 7 "helpful, but not always necessary" items. Evaluation of 4 deidentified elderly patient discharge summaries revealed that none of the documents contained all 36 necessary items; between 14 and 18 were missing. The documents each had several other issues, and they differed significantly in organization, layout, and formatting. CONCLUSIONS: Variations in content and structure of discharge summaries in the United States make them unnecessarily difficult to use. Standardization would benefit both patients, by lowering the risk of care transition-related adverse events, and outpatient providers, by helping reduce frustration that can contribute to burnout. In the short term, acute care providers can help improve the quality of their discharge summaries by working with EHR vendors to follow recommendations based upon this study. Meanwhile, additional human factors work should determine the most effective way to organize and present information in discharge summaries, to facilitate effective standardization.

ECMO and Right Ventricular Failure: Review of the Literature.

Right ventricular (RV) failure is the inability of the RV to maintain sufficient cardiac output in the setting of adequate preload, due to either intrinsic injury to the RV or increased afterload. Medical treatment of RV failure should include optimizing preload, augmenting contractility with vasopressors and inotropes, and considering inhaled pulmonary vasodilators. However, when medical therapies are insufficient, mechanical circulatory support (MCS) is needed to maintain systemic and RV perfusion. The data on MCS for isolated RV failure are limited, but extracorporeal membrane oxygenation (ECMO) appears to be the most efficient and effective modality. For patients with isolated RV failure from acute hypoxemic respiratory failure, veno-venous (VV) ECMO is an appropriate initial configuration, even if the patient is in shock. With primary RV injury or RV failure with concomitant left ventricle (LV) failure, however, venoarterial (VA) ECMO is indicated. Both modalities provide indirect support to the RV by reducing preload, reducing RV wall tension, and delivering oxygenated blood to the coronary circulation. Peripheral cannulation is required in VV-ECMO and is most commonly used in VA-ECMO, allowing for rapid cannulation even in emergencies. Changes in pulsatility on an arterial catheter waveform can indicate changes in clinical status including changes in myocardial function, inadequate preload, worsening RV failure, and excessive VA-ECMO support leading to an elevated LV afterload. Myocardial function may be improved by titration of inotropes or vasodilators, utilization of an Impella or an intra-aortic balloon counterpulsation support devices, or by changes in VA-ECMO support.

ECMO Transport without Physicians or Additional Clinicians.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has accelerated rapidly for patients in severe cardiac or respiratory failure. As a result, ECMO networks are being developed across the world using a "hub and spoke" model. Current guidelines call for all patients transported on ECMO to be accompanied by a physician during transport. However, as ECMO centers and networks grow, the increasing number of transports will be limited by this mandate. OBJECTIVES: The aim of this study was to compare rates of adverse events occurring during transport of ECMO patients with and without an additional clinician, defined as a physician, nurse practitioner (NP), or physician assistant (PA). METHODS: This is a retrospective cohort study of all adults transported while cannulated on ECMO from 2011-2018 via ground and air between 21 hospitals in the northeastern United States, comparing transports with and without additional clinicians. The primary outcome was the rate of major adverse events, and the secondary outcome was minor adverse events. RESULTS: Over the seven-year study period, 93 patients on ECMO were transported. Twenty-three transports (24.7%) were accompanied by a physician or other additional clinician. Major adverse events occurred in 21.5% of all transports. There was no difference in the total rate of major adverse events between accompanied and unaccompanied transports (P = .91). Multivariate analysis did not demonstrate any parameter as being predictive of major adverse events. CONCLUSIONS: In a retrospective cohort study of transports of ECMO patients, there was no association between the overall rate of major adverse events in transport and the accompaniment of an additional clinician. No variables were associated with major adverse events in either cohort.

Feasibility and Safety of Prone Position Transport for Severe Hypoxemic Respiratory Failure Due to Coronavirus Disease 2019.

OBJECTIVES: To assess the safety and feasibility of a new protocol for interhospital critical care transport of mechanically ventilated patients in the prone position during the coronavirus disease 2019 pandemic by nurse and paramedic critical care transport teams. DESIGN: Retrospective observational study. SETTING: Single critical care transport agency serving multiple centers in the greater Boston area. PATIENTS: All transports of intubated patients in the prone position with severe hypoxemic respiratory failure secondary to coronavirus disease 2019. INTERVENTIONS: Records were reviewed for patients transported in the prone position. Major adverse events in transport, defined as severe hypoxemia (oxygen saturation < 80% or an absolute decrease in oxygen saturation > 10%), hypotension (mean arterial pressure < 65 mm Hg) not responsive to vasopressors or inotropes, endotracheal tube or vascular catheter dislodgement, and cardiac arrest, were recorded. MEASUREMENTS AND MAIN RESULTS: A total of 25 patients were transported in prone position. The mean Pao2:Fio2 ratio in the group was 101.3 mm Hg, and 76% (n = 19) were on vasopressors. Fourteen patients (56%) had hypotension with at least one episode of mean arterial pressure less than 65 mm Hg en route, and seven (28%) had an episode of oxygen desaturation less than 88%. Only one major adverse event of severe hypoxemia (oxygen saturation < 80%) was noted. CONCLUSIONS: Critical care transport of severe hypoxemic respiratory failure patients with coronavirus disease 2019 in the prone position is safe when performed by a dedicated team of critical care nurse and paramedics with an established protocol.

Amending HIV Drugs: A Novel Small-Molecule Approach To Target Lupus Anti-DNA Antibodies.

Systemic lupus erythematosus is an autoimmune disease that can affect numerous tissues and is characterized by the production of nuclear antigen-directed autoantibodies (e.g., anti-dsDNA). Using a combination of virtual and ELISA-based screens, we made the intriguing discovery that several HIV-protease inhibitors can function as decoy antigens to specifically inhibit the binding of anti-dsDNA antibodies to target antigens such as dsDNA and pentapeptide DWEYS. Computational modeling revealed that HIV-protease inhibitors comprised structural features present in DWEYS and predicted that analogues containing more flexible backbones would possess preferred binding characteristics. To address this, we reduced the internal amide backbone to improve flexibility, producing new small-molecule decoy antigens, which neutralize anti-dsDNA antibodies in vitro, in situ, and in vivo. Pharmacokinetic and SLE model studies demonstrated that peptidomimetic FISLE-412,1 a reduced HIV protease inhibitor analogue, was well-tolerated, altered serum reactivity to DWEYS, reduced glomeruli IgG deposition, preserved kidney histology, and delayed SLE onset in NZB/W F1 mice.

Ultrafast shock compression of an oxygen-balanced mixture of nitromethane and hydrogen peroxide.

We apply ultrafast optical interferometry to measure the Hugoniot of an oxygen-balanced mixture of nitromethane and hydrogen peroxide (NM/HP) and compare with Hugoniot data for pure nitromethane (NM) and a 90% hydrogen peroxide/water mixture (HP), as well as theoretical predictions. We observe a 2.1% percent mean pairwise difference between the measured shockwave speed (at the measured piston speed) in unreacted NM/HP and the corresponding "universal" liquid Hugoniot, which is larger than the average standard deviation of our data, 1.4%. Unlike the Hugoniots of both HP and NM, in which measured shock speeds deviate to values greater than the unreacted Hugoniot for piston speeds larger than the respective reaction thresholds, in the NM/HP mixture we observe shock speed deviations to values lower than the unreacted Hugoniot well below the von Neumann pressure (≈28 GPa). Although the trend should reverse for high enough piston speeds, the initial behavior is unexpected. Possible explanations range from mixing effects to a complex index of refraction in the reacted solution. If this is indeed a signature of chemical initiation, it would suggest that the process may not be kinetically limited (on a ~100 ps time scale) between the initiation threshold and the von Neumann pressure.

Salicylate prevents virus-induced type 1 diabetes in the BBDR rat.

Epidemiologic and clinical evidence suggests that virus infection plays an important role in human type 1 diabetes pathogenesis. We used the virus-inducible BioBreeding Diabetes Resistant (BBDR) rat to investigate the ability of sodium salicylate, a non-steroidal anti-inflammatory drug (NSAID), to modulate development of type 1 diabetes. BBDR rats treated with Kilham rat virus (KRV) and polyinosinic:polycytidylic acid (pIC, a TLR3 agonist) develop diabetes at nearly 100% incidence by ~2 weeks. We found distinct temporal profiles of the proinflammatory serum cytokines, IL-1ß, IL-6, IFN-γ, IL-12, and haptoglobin (an acute phase protein) in KRV+pIC treated rats. Significant elevations of IL-1ß and IL-12, coupled with sustained elevations of haptoglobin, were specific to KRV+pIC and not found in rats co-treated with pIC and H1, a non-diabetogenic virus. Salicylate administered concurrently with KRV+pIC inhibited the elevations in IL-1ß, IL-6, IFN-γ and haptoglobin almost completely, and reduced IL-12 levels significantly. Salicylate prevented diabetes in a dose-dependent manner, and diabetes-free animals had no evidence of insulitis. Our data support an important role for innate immunity in virus-induced type 1 diabetes pathogenesis. The ability of salicylate to prevent diabetes in this robust animal model demonstrates its potential use to prevent or attenuate human autoimmune diabetes.

Testing agents for prevention or reversal of type 1 diabetes in rodents.

We report the results of an independent laboratory's tests of novel agents to prevent or reverse type 1 diabetes (T1D) in the non-obese diabetic (NOD) mouse, BioBreeding diabetes prone (BBDP) rat, and multiple autoimmune disease prone (MAD) rat models. Methods were developed to better mimic human clinical trials, including: prescreening, randomization, blinding, and improved glycemic care of the animals. Agents were suggested by the research community in an open call for proposals, and selected for testing by an NIDDK appointed independent review panel. Agents selected for testing to prevent diabetes at later stages of progression in a rodent model were a STAT4 antagonist (DT22669), alpha1 anti-trypsin (Aralast NP), celastrol (a natural product with anti-inflammatory properties), and a Macrophage Inflammatory Factor inhibitor (ISO-092). Agents tested for reversal of established T1D in rodent models were: alpha1 anti-trypsin (Aralast NP), tolerogenic peptides (Tregitopes), and a long-acting formulation of GLP-1 (PGC-GLP-1). None of these agents were seen to prevent or reverse type 1 diabetes, while the positive control interventions were effective: anti-CD3 treatment provided disease reversal in the NOD mouse, dexamethasone prevented T1D induction in the MAD rat, and cyclosporin prevented T1D in the BBDP rat. For some tested agents, details of previous formulation, delivery, or dosing, as well as laboratory procedure, availability of reagents and experimental design, could have impacted our ability to confirm prior reports of efficacy in preclinical animal models. In addition, the testing protocols utilized here provided detection of effects in a range commonly used in placebo controlled clinical trials (for example, 50% effect size), and thus may have been underpowered to observe more limited effects. That said, we believe the results compiled here, showing good control and repeatability, confirm the feasibility of screening diverse test agents in an independent laboratory.

Experimental and TD-DFT study of optical absorption of six explosive molecules: RDX, HMX, PETN, TNT, TATP, and HMTD.

Time dependent density function theory (TD-DFT) has been utilized to calculate the excitation energies and oscillator strengths of six common explosives: RDX (1,3,5-trinitroperhydro-1,3,5-triazine), ß-HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine), TATP (triacetone triperoxide), HMTD (hexamethylene triperoxide diamine), TNT (2,4,6-trinitrotoluene), and PETN (pentaerythritol tetranitrate). The results were compared to experimental UV-vis absorption spectra collected in acetonitrile. Four computational methods were tested including: B3LYP, CAM-B3LYP, ωB97XD, and PBE0. PBE0 outperforms the other methods tested. Basis set effects on the electronic energies and oscillator strengths were evaluated with 6-31G(d), 6-31+G(d), 6-31+G(d,p), and 6-311+G(d,p). The minimal basis set required was 6-31+G(d); however, additional calculations were performed with 6-311+G(d,p). For each molecule studied, the natural transition orbitals (NTOs) were reported for the most prominent singlet excitations. The TD-DFT results have been combined with the IPv calculated by CBS-QB3 to construct energy level diagrams for the six compounds. The results suggest optimization approaches for fluorescence based detection methods for these explosives by guiding materials selections for optimal band alignment between fluorescent probe and explosive analyte. Also, the role of the TNT Meisenheimer complex formation and the resulting electronic structure thereof on of the quenching mechanism of II-VI semiconductors is discussed.

Development of standardized insulin treatment protocols for spontaneous rodent models of type 1 diabetes.

Standardized protocols for maintaining near-normal glycemic levels in diabetic rodent models for testing therapeutic agents to treat disease are unavailable. We developed protocols for 2 common models of spontaneous type 1 diabetes, the BioBreeding diabetes-prone (BBDP) rat and nonobese diabetic (NOD) mouse. Insulin formulation, dose level, timing of dose administration, and delivery method were examined and adjusted so that glycemic levels remained within a normal range and fluctuation throughout feeding and resting cycles was minimized. Protamine zinc formulations provided the longest activity, regardless of the source of insulin. Glycemic control with few fluctuations was achieved in diabetic BBDP rats through twice-daily administration of protamine zinc insulin, and results were similar regardless of whether BBDP rats were acutely or chronically diabetic at initiation of treatment. In contrast, glycemic control could not be attained in NOD mice through administration of insulin twice daily. However, glycemic control was achieved in mice through daily administration of 0.25 U insulin through osmotic pumps. Whereas twice-daily injections of protamine zinc insulin provided glycemic control with only minor fluctuations in BBDP rats, mice required continuous delivery of insulin to prevent wide glycemic excursions. Use of these standard protocols likely will aid in the testing of agents to prevent or reverse diabetes.

TGF-ß signaling is altered in the peripheral blood of subjects with multiple sclerosis.

Multiple sclerosis (MS) is a central nervous system inflammatory disorder with evidence of peripheral immune dysregulation. Abnormalities of the immune suppressive cytokine TGF-ß have been reported, but not fully defined, in MS. Through a pathway-focused expression profiling of the peripheral blood, we found abnormalities of TGF-ßRII, SMAD4 and SMAD7 expression in subjects with MS, and reduction in the levels of TGF-ß regulated genes, indicating an overall reduction in TGF-ß signaling in MS. The response to exogenous TGF-ß was intact, however, indicating an extrinsic defect of TGF-ß signaling in MS. These results indicate that TGF-ß control is diminished in MS.

Nanosecond time-resolved and steady-state infrared studies of photoinduced decomposition of TATB at ambient and elevated pressure.

The time scale and/or products of photoinduced decomposition of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) were investigated at ambient pressure and compared with products formed at 8 GPa. Ultrafast time-resolved infrared and steady-state Fourier transform IR (FTIR) spectroscopies were used to probe TATB and its products after photoexcitation with a 5 ns pulse of 532 nm light. At ambient pressure, transient spectra of TATB indicate that the molecule has significantly decomposed within 60 ns; transient spectra also indicate that formation of CO(2), an observed decomposition product, is complete within 30-40 mus. Proof of principle time-resolved experiments at elevated pressures were performed and are discussed briefly. Comparison of steady-state FTIR spectra obtained at ambient and elevated pressure (ca. 8 GPa) indicate that the decomposition products vary with pressure. We find evidence for water as a decomposition product only at elevated pressure.

Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.

BACKGROUND: Human T-cell leukemia virus-associated adult T-cell leukemia-lymphoma (ATLL) has a very poor prognosis, despite trials of a variety of different treatment regimens. Virus expression has been reported to be limited or absent when ATLL is diagnosed, and this has suggested that secondary genetic or epigenetic changes are important in disease pathogenesis. METHODS AND FINDINGS: We prospectively investigated combination chemotherapy followed by antiretroviral therapy for this disorder. Nineteen patients were prospectively enrolled between 2002 and 2006 at five medical centers in a phase II clinical trial of infusional chemotherapy with etoposide, doxorubicin, and vincristine, daily prednisone, and bolus cyclophosphamide (EPOCH) given for two to six cycles until maximal clinical response, and followed by antiviral therapy with daily zidovudine, lamivudine, and alpha interferon-2a for up to one year. Seven patients were on study for less than one month due to progressive disease or chemotherapy toxicity. Eleven patients achieved an objective response with median duration of response of thirteen months, and two complete remissions. During chemotherapy induction, viral RNA expression increased (median 190-fold), and virus replication occurred, coincident with development of disease progression. CONCLUSIONS: EPOCH chemotherapy followed by antiretroviral therapy is an active therapeutic regimen for adult T-cell leukemia-lymphoma, but viral reactivation during induction chemotherapy may contribute to treatment failure. Alternative therapies are sorely needed in this disease that simultaneously prevent virus expression, and are cytocidal for malignant cells.

Anomalous photoluminescence in CdSe quantum-dot solids at high pressure due to nonuniform stress.

The application of static high pressure provides a means to precisely control and investigate many fundamental and unique properties of nanoparticles. CdSe is a model quantum-dot system, the behavior of which under high pressure has been extensively studied; however, the effect of nonuniform stresses on this system has not been fully appreciated. Photoluminescence data obtained from CdSe quantum-dot solids in different stress environments varying from purely uniform to highly nonuniform are presented. Small deviations from a uniform stress distribution profoundly affect the electronic properties of this system. In nonuniform stress environments, a pronounced flattening of the photoluminescence enegy is observed above 3 GPa. The observations are validated with theoretical calculations obtained using an all-atom semiempirical pseudopotential technique. This effect must be considered when investigating other potentially pressure-mediated phenomena.

Retrovirally induced CTL degranulation mediated by IL-15 expression and infection of mononuclear phagocytes in patients with HTLV-I-associated neurologic disease.

CD8(+) T cells contribute to central nervous system inflammation in human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). We analyzed CD8(+) T-cell dysfunction (degranulation and IFN-gamma production) and have demonstrated that CD8(+) T cells of patients with HAM/TSP (HAM/TSP patients) spontaneously degranulate and express IFN-gamma in ex vivo unstimulated culture. CD8(+) T cells of HTLV-I asymptomatic carriers and healthy donors did not. Spontaneous degranulation was detected in Tax11-19/HLA-A*201 tetramer(+) cells, but not in CMV pp65 tetramer(+) cells. Interestingly, degranulation and IFN-gamma production in CD8(+) T cells was induced by coculture with autologous CD14(+) cells, but not CD4(+) T cells, of HAM/TSP patients, which correlated with proviral DNA load in CD14(+) cells of infected patients. Moreover, the expression of IL-15, which induced degranulation and IFN-gamma production in infected patients, was enhanced on surface of CD14(+) cells in HAM/TSP patients. Blockade of MHC class I and IL-15 confirmed these results. Thus, CD8(+) T-cell dysregulation was mediated by both virus infection and enhanced IL-15 on CD14(+) cells in HAM/TSP patients. Despite lower viral expression than in CD4(+) T cells, HTLV-I-infected or -activated CD14(+) cells may be a heretofore important but under recognized reservoir particularly in HAM/TSP patients.

Dysregulation of TGF-beta signaling and regulatory and effector T-cell function in virus-induced neuroinflammatory disease.

We previously demonstrated that CD4(+)CD25(+) T regulatory cells (Tregs), important for the maintenance of immune tolerance and prevention of autoimmune disease, from patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) exhibit reduced Foxp3 expression and Treg suppressor function compared with healthy donors. Since TGF-beta signaling has been previously reported to be critical for both Foxp3 expression and Treg function, we examined whether this signaling pathway was dysregulated in patients with HAM/TSP. Levels of TGF-beta receptor II (TGF-betaRII) as well as Smad7 (a TGF-beta-inducible gene) were significantly reduced in CD4(+) T cells in patients with HAM/TSP compared with healthy donors, and the expression of TGF-betaRII inversely correlated with the HTLV-I tax proviral load. Importantly, both CD4(+)CD25(+) and CD4(+)CD25(-) T cells from HAM/TSP patients exhibited reduced TGF-betaRII expression compared with healthy donors, which was associated with functional deficits in vitro, including a block in TGF-beta-inducible Foxp3 expression that inversely correlated with the HTLV-I tax proviral load, loss of Treg suppressor function, and escape of effector T cells from Treg-mediated control. This evidence suggests that a virus-induced breakdown of immune tolerance affecting both regulatory and effector T cells contributes to the pathogenesis of HAM/TSP.

Effect of treatment of Strongyloides infection on HTLV-1 expression in a patient with adult T-cell leukemia.

Human T-cell leukemia virus type 1 (HTLV-1) is associated with adult T-cell leukemia-lymphoma (ATLL) in about 5% of infected individuals. Coinfection by Strongyloides stercoralis has been suggested to be a cofactor for development of ATLL. We describe a patient who presented with HTLV-1-associated chronic ATLL and Strongyloides infection. Studies of this patient's viral RNA levels demonstrated stimulation of HTLV-1 replication by Strongyloides, which resolved with anti-helminthic therapy. This case provides support for the hypothesis that Strongyloides is a cofactor for ATLL via T-cell stimulation.

Ultrafast structural rearrangements in the MLCT excited state for copper(I) bis-phenanthrolines in solution.

Ultrafast excited-state structural dynamics of [Cu(I)(dmp)(2)](+) (dmp = 2,9-dimethyl-1,10-phenanthroline) have been studied to identify structural origins of transient spectroscopic changes during the photoinduced metal-to-ligand charge-transfer (MLCT) transition that induces an electronic configuration change from Cu(I) (3d(10)) to Cu(II) (3d(9)). This study has important connections with the flattening of the Franck-Condon state tetrahedral geometry and the ligation of Cu(II)* with the solvent observed in the thermally equilibrated MLCT state by our previous laser-initiated time-resolved X-ray absorption spectroscopy (LITR-XAS) results. To better understand the structural photodynamics of Cu(I) complexes, we have studied both [Cu(I)(dmp)(2)](+) and [Cu(I)(dpp)(2)](+) (dpp = 2,9-diphenyl-1,10-phenanthroline) in solvents with different dielectric constants, viscosities, and thermal diffusivities by transient absorption spectroscopy. The observed spectral dynamics suggest that a solvent-independent inner-sphere relaxation process is occurring despite the large amplitude motions due to the flattening of the tetrahedral coordinated geometry. The singlet fluorescence dynamics of photoexcited [Cu(I)(dmp)(2)](+) were measured in the coordinating solvent acetonitrile, using the fluorescence upconversion method at different emission wavelengths. At the bluest emission wavelengths, a prompt fluorescence lifetime of 77 fs is attributed to the excited-state deactivation processes due to the internal conversion and intersystem crossing at the Franck-Condon state geometry. The differentiation between the prompt fluorescence lifetime with the tetrahedral Franck-Condon geometry and that with the flattened tetrahedral geometry uncovers an unexpected ultrafast flattening process in the MLCT state of [Cu(I)(dmp)(2)](+). These results provide guidance for future X-ray structural studies on ultrafast time scale, as well as for synthesis toward its applications in solar energy conversion.