A Nationwide Survey of Educational Resource Utilization and Perception Among Internal Medicine Residents.

BACKGROUND: New virtual resources ("novel resources") have been incorporated into medical education. No recent large studies about their use and perception among internal medicine (IM) residents exist. OBJECTIVE: Characterize the use and perceived helpfulness of educational resources. DESIGN: Nationwide survey from December 2019 to March 2020. PARTICIPANTS: IM residents in the USA. MAIN MEASURES: Residents were surveyed on their use and their perceived helpfulness of resources for both attaining general medical knowledge and for point-of-care (POC) learning. Traditional resources included board review resources, clinical experience, digital clinical resources (e.g., UpToDate), journal articles, pocket references, professional guidelines, textbooks, and residency curricula. Novel resources included Twitter, video streaming platforms (e.g., YouTube), online blogs, podcasts, and Wikipedia. KEY RESULTS: We had 662 respondents from 55 residency programs across 26 states. On average, residents used 9 total resources (7 traditional and 2 novel). Digital clinical resources and clinical experience were used by all residents and found helpful by the highest percentage of residents (96% and 94%, respectively). Journal articles were next (used by 90%), followed by board review resources and residency curricula (both used by 85%). Their perceived helpfulness varied, from 90% for board review resources, to 66% for journal articles and 64% for residency curricula, the lowest perceived helpfulness of any traditional resource. Podcasts and video streaming platforms were used as frequently as textbooks (58-59%), but were rated as helpful more frequently (75% and 82% vs 66%, respectively). CONCLUSIONS: Digital clinical resources, video streaming platforms, and podcasts were perceived as helpful, underscoring the importance of ensuring their integration into medical education to complement clinical experience and other traditional resources which remain highly valued by residents. IMPORTANCE: Our findings can inform residency programs as they transition to virtual curricula in the wake of the COVID-19 pandemic.

Client and provider factors associated with integration of family planning services among maternal and reproductive health clients in Kigoma Region, Tanzania: a cross-sectional study, April-July 2016.

BACKGROUND: Integration of family planning (FP) services into non-FP care visits is an essential strategy for reducing maternal and neonatal mortality through reduction of short birth intervals and unplanned pregnancies. METHODS: Cross-sectional surveys were conducted across 61 facilities in Kigoma Region, Tanzania, April-July 2016. Multilevel, mixed effects logistic regression analyses were conducted on matched data from providers (n = 330) and clients seeking delivery (n = 935), well-baby (n = 272), pregnancy loss (PL; n = 229), and other routine (postnatal, HIV/STI, other; n = 69) services. Outcomes of interest included receipt of FP information and a modern FP method (significance level p < 0.05). RESULTS: Clients had significantly greater odds of receiving FP information if the primary reason for seeking care was for PL versus (vs) any other types of care (aOR 1.97), had four or more pregnancies vs fewer (aOR 1.78), and had had a FP discussion with their partner vs no FP discussion (aOR 1.73). Clients had lower odds of receiving FP information if they were aged 40-49 vs 15-19 (aOR 0.50) and reported attending religious services at least weekly vs less frequently (aOR 0.61). Clients of providers who perceived that in-service training had helped vs had not helped job performance (aOR 2.27), and clients of providers having high vs low recent FP training index scores (aOR 1.58) had greater odds of receiving FP information. Clients had greater odds of receiving a modern method when they received information on two or more vs fewer methods (aOR 7.13), had had a FP discussion with their partner vs no discussion (aOR 5.87), if the primary reason for seeking care was for PL vs any other types of care (aOR 4.08), had zero vs one or more live births (aOR 3.92), made their own FP decisions vs not made own FP decisions (aOR 3.17), received FP information from two or more vs fewer sources (aOR 3.12), and were in the middle or high vs the low wealth tercile (aOR 1.99 and 2.30, respectively). Well-baby care clients, Other routine services clients, and married clients had significantly lower odds of receiving a method (aOR 0.14; aOR 0.08; and aOR 0.41, respectively) compared to their counterparts. CONCLUSIONS: Strategies that better integrate FP into routine care visits, encourage women to have FP discussions with their partners and providers, increase FP training among providers, and expand FP options and sources of information may help reduce the unmet need for FP, and ultimately lower maternal and neonatal mortality.

Obesity, but not metabolic syndrome, negatively affects outcome in bipolar disorder.

OBJECTIVE: Examine the effects of obesity and metabolic syndrome on outcome in bipolar disorder. METHOD: The Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar Disorder (Bipolar CHOICE) study randomized 482 participants with bipolar disorder in a 6-month trial comparing lithium- and quetiapine-based treatment. Baseline variables were compared between groups with and without obesity, with and without abdominal obesity, and with and without metabolic syndrome respectively. The effects of baseline obesity, abdominal obesity, and metabolic syndrome on outcomes were examined using mixed effects linear regression models. RESULTS: At baseline, 44.4% of participants had obesity, 48.0% had abdominal obesity, and 27.3% had metabolic syndrome; neither obesity, nor abdominal obesity, nor metabolic syndrome were associated with increased global severity, mood symptoms, or suicidality, or with poorer functioning or life satisfaction. Treatment groups did not differ on prevalence of obesity, abdominal obesity, or metabolic syndrome. By contrast, among the entire cohort, obesity was associated with less global improvement and less improvement in total mood and depressive symptoms, suicidality, functioning, and life satisfaction after 6 months of treatment. Abdominal obesity was associated with similar findings. Metabolic syndrome had no effect on outcome. CONCLUSION: Obesity and abdominal obesity, but not metabolic syndrome, were associated with less improvement after 6 months of lithium- or quetiapine-based treatment.

A Mentoring Network for Diversity in Dental, Oral, and Craniofacial Research.

The American Association for Dental, Oral, and Craniofacial Research (AADOCR) has developed a national and sustainable mentoring and mentor training network titled AADOCR Mentoring an Inclusive Network for a Diverse Workforce of the Future (AADOCR MIND the Future). This program is instrumental in fostering a diverse group of early-career investigators in dental, oral, and craniofacial (DOC) research. The network's principal purpose has been to establish a robust and enduring national mentoring program centrally managed by AADOCR. The overarching goal is to develop a sustainable, nationally recognized mentoring network that enhances the career development of early-career DOC researchers from diverse backgrounds. The program aligns with the National Institute of Dental and Craniofacial Research Strategic Plan and aims to cultivate a robust pipeline of future DOC researchers who can address critical scientific challenges. AADOCR MIND the Future guides mentors and mentees in individual career development as well as improving the quality of mentoring at the home institution through dissemination of lessons learned by mentors and mentees in the program. As science practices have evolved, investigators have moved from isolated individual projects to interactive multidisciplinary teams. Within this research framework, AADOCR MIND the Future offers the global infrastructure and the variety of scientists/AADOCR members. While most institutional mentoring efforts have been developed using conventional single mentor-mentee pairs, the AADOCR MIND the Future program supplements this model with additional group mentoring (mentors-mentees) and peer mentoring (interactions between just the mentees). Mentees commit to 12 mo of programming devoted to enhancing research career development through intensive hands-on work, distance-learning components, and engagement in a mentored grant-writing experience. Mentees are strongly encouraged to remain engaged with the program beyond the initial 12-mo period. Years 1 to 3 alumni (cohorts 1 to 3) mentees continue to participate in a meaningful way, and after the completion of the program, it is envisioned these alumni will become mentors for another generation.

Nonadiabatic decomposition of gas-phase RDX through conical intersections: an ONIOM-CASSCF study.

Topographical exploration of nonadiabatically coupled ground- and excited-electronic-state potential energy surfaces (PESs) of the isolated RDX molecule was performed using the ONIOM methodology: Computational results were compared and contrasted with the previous experimental results for the decomposition of this nitramine energetic material following electronic excitation. One of the N-NO(2) moieties of the RDX molecule was considered to be an active site. Electronic excitation of RDX was assumed to be localized in the active site, which was treated with the CASSCF algorithm. The influence of the remainder of the molecule on the chosen active site was calculated by either a UFF MM or RHF QM method. Nitro-nitrite isomerization was predicted to be a major excited-electronic-state decomposition channel for the RDX molecule. This prediction directly corroborates previous experimental results obtained through photofragmentation-fragment detection techniques. Nitro-nitrite isomerization of RDX was found to occur through a series of conical intersections (CIs) and was finally predicted to produce rotationally cold but vibrationally hot distributions of NO products, also in good agreement with the experimental observation of rovibrational distributions of the NO product. The ONIOM (CASSCF:UFF) methodology predicts that the final step in the RDX dissociation occurs on its S(0) ground-electronic-state potential energy surface (PES). Thus, the present work clearly indicates that the ONIOM method, coupled with a suitable CASSCF method for the active site of the molecule, at which electronic excitation is assumed to be localized, can predict hitherto unexplored excited-electronic-state PESs of large energetic molecules such as RDX, HMX, and CL-20. A comparison of the decomposition mechanism for excited-electronic-state dimethylnitramine (DMNA), a simple analogue molecule of nitramine energetic materials, with that for RDX, an energetic material, was also performed. CASSCF pure QM calculations showed that, following electronic excitation of DMNA to its S(2) surface, decomposition of this molecule occurs on its S(1) surface through a nitro-nitrite isomerization producing rotationally hot and vibrationally cold distributions of the NO product.

GlideScope® vs flexible fibreoptic scope for elective intubation in obese patients.

We hypothesised that in obese patients, tracheal intubation with the GlideScope® would be advantageous compared with flexible fibreoptic intubation. Seventy-five anaesthetised obese patients were randomly assigned to oral intubation by either GlideScope or flexible fibreoptic bronchoscope. We compared the two devices for time to intubate (p = 0.19), difficulty of intubation (p = 0.58), successful intubation on first attempt (p = 0.29), number of attempts (p = 0.24), incidence of hypoxaemia (p = 0.57), amount of post-intubation bleeding (p = 0.79) and sore throat (p = 0.82). None differed significantly. Median (IQR [range]) time to intubation was 37 (25-48 [19-81]) s and 95% of the first attempts were successful with the GlideScope, vs 43 (35-58 [26-96]) s and an 86% first-attempt success rate with the flexible fibreoptic bronchoscope. For experienced users, the time required to intubate the trachea in anaesthetised obese patients is similar with the GlideScope and a flexible bronchoscope.

Experimental and theoretical studies of reactions of neutral vanadium and tantalum oxide clusters with NO and NH3.

Reactions of neutral vanadium and tantalum oxide clusters with NO, NH(3), and an NO/NH(3) mixture in a fast flow reactor are investigated by time of flight mass spectrometry and density functional theory (DFT) calculations. Single photon ionization through a 46.9 nm (26.5 eV) extreme ultraviolet (EUV) laser is employed to detect both neutral cluster distributions and reaction products. Association products VO(3)NO and V(2)O(5)NO are detected for V(m)O(n) clusters reacting with pure NO, and reaction products, TaO(3,4)(NO)(1,2), Ta(2)O(5)NO, Ta(2)O(6)(NO)(1-3), and Ta(3)O(8)(NO)(1,2) are generated for Ta(m)O(n) clusters reacting with NO. In both instances, oxygen-rich clusters are the active metal oxide species for the reaction M(m)O(n)+NO→M(m)O(n)(NO)(x). Both V(m)O(n) and Ta(m)O(n) cluster systems are very active with NH(3). The main products of the reactions with NH(3) result from the adsorption of one or two NH(3) molecules on the respective clusters. A gas mixture of NO:NH(3) (9:1) is also added into the fast flow reactor: the V(m)O(n) cluster system forms stable, observable clusters with only NH(3) and no V(m)O(n)(NO)(x)(NH(3))(y) species are detected; the Ta(m)O(n) cluster system forms stable, observable mixed clusters, Ta(m)O(n)(NO)(x)(NH(3))(y), as well as Ta(m)O(n)(NO)(x) and Ta(m)O(n)(NH(3))(y) individual clusters, under similar conditions. The mechanisms for the reactions of neutral V(m)O(n) and Ta(m)O(n) clusters with NO/NH(3) are explored via DFT calculations. Ta(m)O(n) clusters form stable complexes based on the coadsorption of NO and NH(3). V(m)O(n) clusters form weakly bound complexes following the reaction pathway toward end products N(2)+H(2)O without barrier. The calculations give an interpretation of the experimental data that is consistent with the condensed phase reactivity of V(m)O(n) catalyst and suggest the formation of intermediates in the catalytic chemistry.

Skin replication procedure for the scanning electron microscope.

Ani improved method for preparing polyethylene replicas of skin from silicone rubber molds was developed for examination in the scanning electron microscope. Electro micrographs of the replicas compare favorably to those of fixed tissues from the same animal. Because of the great depth of field of the scanning electron microscope, both loosely attached epidermal cells and the background epidermal surface can be seen simultaneously in sharp focus, thus providing, a more complete picture of the topography of skin.

Experimental and theoretical exploration of the initial steps in the decomposition of a model nitramine energetic material: dimethylnitramine.

Decomposition of dimethylnitramine (DMNA, (CH(3))(2)NNO(2)) has been studied extensively over the past decades. Although several different mechanisms have been proposed for the initial decomposition of DMNA, the dominant decomposition channel is still far from fully understood. In this report, we collect all the results reported in the literature, along with our new experimental and theoretical results, into a single reference for a sensible comparison in order to reach a general conclusion on DMNA decomposition. In this effort, nanosecond laser, energy resolved spectroscopy and complete active space self-consistent field (CASSCF) calculations are employed. The parent DMNA molecule is electronically excited using two different UV excitation wavelengths, 226 and 193 nm, to initiate the decomposition process. The NO molecule is observed as a major decomposition product with relatively hot (120 K) rotational and cold vibrational distributions by both time-of-flight mass spectrometry and laser induced fluorescence spectroscopy. On the basis of the experimental observations, a nitro-nitrite isomerization mechanism is predicted to be the major channel of decomposition of DMNA in the excited electronic state with a minor contribution from the HONO elimination mechanism. The branching ratio between nitro-nitrite isomerization and HONO elimination channels is estimated to be approximately 1:0.04. CASSCF calculations show that surface crossing (conical intersection) between upper and lower electronic states along the nitro-nitrite isomerization reaction coordinate plays an important role in the overall decomposition of DMNA. Presence of such an (S(2)/S(1))(CI) conical intersection in the nitro-nitrite isomerization reaction coordinate provides a direct nonadiabatic decomposition pathway from the Franck-Condon point of the S(2) surface, which is experimentally accessed by 226 nm photoexcitation. This excited state isomerization takes place through a loose geometry for which the NO(2) moiety interacts with the (CH(3))(2)N moiety from a long distance (approximately 2.8 A); however, in the ground electronic state, a similar (S(1)/S(0))(CI) conical intersection in this nitro-nitrite isomerization reaction coordinate hinders the isomerization exit channel, rendering NO(2) elimination as the major thermal decomposition channel of DMNA.

Photodissociation dynamics of nitromethane at 226 and 271 nm at both nanosecond and femtosecond time scales.

Photodissociation of nitromethane has been investigated for decades both theoretically and experimentally; however, as a whole picture, the dissociation dynamics for nitromethane are still not clear, although many different mechanisms have been proposed. To make a complete interpretation of these different mechanisms, photolysis of nitromethane at 226 and 271 nm under both collisional and collisionless conditions is investigated at nanosecond and femtosecond time scales. These two laser wavelengths correspond to the pi* <-- pi and pi* <-- n excitations of nitromethane, respectively. In nanosecond 226 nm (pi* <-- pi) photolysis experiments, CH(3) and NO radicals are observed as major products employing resonance enhanced multiphoton ionization techniques and time-of-flight mass spectrometry. Additionally, OH and CH(3)O radicals are weakly observed as dissociation products employing laser induced fluorescence spectroscopy; the CH(3)O product is only observed under collisional conditions. In femtosecond 226 nm experiments, CH(3), NO(2), and NO products are observed. These results confirm that rupture of C-N bond should be the main primary process for the photolysis of nitromethane after the pi* <-- pi excitation at 226 nm, and the NO(2) molecule should be the precursor of the observed NO product. Formation of the CH(3)O radical after the recombination of CH(3) and NO(2) species under collisional conditions rules out a nitro-nitrite isomerization mechanism for the generation of CH(3)O and NO from pi pi* CH(3)NO(2). The OH radical formation for pi pi* CH(3)NO(2) should be a minor dissociation channel because of the weak OH signal in both nanosecond and femtosecond (nonobservable) experiments. Single color femtosecond pump-probe experiments at 226 nm are also employed to monitor the dynamics of the dissociation of nitromethane after the pi* <-- pi excitation. Because of the ultrafast dynamics of product formation at 226 nm, the pump-probe transients for the three dissociation products are measured as an autocorrelation of the laser pulse, indicating the dissociation of nitromethane in the pi pi* excited state is faster than the laser pulse duration (180 fs). In nanosecond 271 nm (pi* <-- n) photolysis experiments, pump-probe experiments are performed to detect potential dissociation products, such as CH(3), NO(2), CH(3)O, and OH; however, none of them is observed. In femtosecond 271 nm laser experiments, the nitromethane parent ion is observed with major intensity, together with CH(3), NO(2), and NO fragment ions with only minor intensities. Pump-probe transients for both nitromethane parent and fragment ions at 271 nm excitation and 406.5 nm ionization display a fast exponential decay with a constant time of 36 fs, which we suggest to be the lifetime of the excited n pi* state of nitromethane. Combined with the 271 nm nanosecond pump-probe experiments, in which none of the CH(3), NO(2), CH(3)O, or OH fragment is observed, we suggest that all the fragment ions generated in 271 nm femtosecond laser experiments are derived from the parent ion, and dissociation of nitromethane from the n pi* excited electronic state does not occur in a supersonic molecular beam under collisionless conditions.

Unimolecular decomposition of tetrazine-N-oxide based high nitrogen content energetic materials from excited electronic states.

Unimolecular excited electronic state decomposition of novel high nitrogen content energetic molecules, such as 3,3(')-azobis(6-amino-1,2,4,5-tetrazine)-mixed N-oxides (DAATO(3.5)), 3-amino-6-chloro-1,2,4,5-tetrazine-2,4-dioxide (ACTO), and 3,6-diamino-1,2,4,5-tetrazine-1,4-dioxde (DATO), is investigated. Although these molecules are based on N-oxides of a tetrazine aromatic heterocyclic ring, their decomposition behavior distinctly differs from that of bare tetrazine, in which N(2) and HCN are produced as decomposition products through a concerted dissociation mechanism. NO is observed to be an initial decomposition product from all tetrazine-N-oxide based molecules from their low lying excited electronic states. The NO product from DAATO(3.5) and ACTO is rotationally cold (20 K) and vibrationally hot (1200 K), while the NO product from DATO is rotationally hot (50 K) and vibrationally cold [only the (0-0) vibronic transition of NO is observed]. DAATO(3.5) and ACTO primarily differ from DATO with regard to molecular structure, by the relative position of oxygen atom attachment to the tetrazine ring. Therefore, the relative position of oxygen in tetrazine-N-oxides is proposed to play an important role in their energetic behavior. N(2)O is ruled out as an intermediate precursor of the NO product observed from all three molecules. Theoretical calculations at CASMP2/CASSCF level of theory predict a ring contraction mechanism for generation of the initial NO product from these molecules. The ring contraction occurs through an (S(1)/S(0))(CI) conical intersection.

The pulsed-dye laser for treatment of cutaneous conditions.

The concept of selective photothermolysis simply states that if one heats target tissue with a laser that is selectively absorbed by that tissue, heat should last sufficiently enough to cause damage to the target tissue, but not so long for the heat to spread to the surrounding tissue. The pulsed-dye laser (PDL) was the first laser to utilize the concept of selective photothermolysis to treat dermatologic conditions. The first application of this concept was directed at treating port-wine stain birthmarks (PWSs). A myriad of conditions that were previously only marginally treated by earlier-generation PDLs could be addressed, increasing by a factor of many thousand the number of potential patients for PDL treatment. Rosacea, scars, red striae, some lower-extremity spider veins, and photodamage could now be easily treated in addition to PWSs, nevus araneuses, cherry hemangioma, and verrucae. Finally, the latest advances in PDL technology have maximized the ability to treat linear vessels such as lower-extremity spider veins, and linear facial vessels associated with rosacea, photodamage or simply heredity, as well as improving the ability to treat diffuse erythema such as the facial redness of rosacea, PWSs, scars and striae with less risk of epidermal damage and hyperpigmentation. Final advances aim to reduce side-effects of both types of vascular lasers while potentially increasing benefits by allowing the delivery of higher fluencies. Cooling the surface of the skin protects melanin pigment while allowing the delivery of light to the dermis to remove unwanted blood vessels and potentially stimulate dermal remodeling.

Expression of fibrinolytic genes in atherosclerotic abdominal aortic aneurysm wall. A possible mechanism for aneurysm expansion.

Expansion of atherosclerotic abdominal aortic aneurysm (AAA) has been attributed to remodeling of the extracellular matrix by active proteolysis. We used in situ hybridization to analyze the expression of fibrinolytic genes in aneurysm wall from eight AAA patients. All specimens exhibited specific areas of inflammatory infiltrates with macrophage-like cells expressing urokinase-type plasminogen activator (u-PA) and tissue-type PA (t-PA) mRNA. Type 1 PA inhibitor (PAI-1) mRNA was expressed at the base of the necrotic atheroma of all specimens and also within some of the inflammatory infiltrates where it frequently colocalized in regions containing u-PA and t-PA mRNA expressing cells. However, in these areas, the cellular distribution of the transcripts for t-PA and u-PA extended far beyond the areas of PAI-1 expression. These observations suggest a local ongoing proteolytic process, one which is only partially counteracted by the more restricted expression of PAI-1 mRNA. An abundance of capillaries was also obvious in all inflammatory infiltrates and may reflect local angiogenesis in response to active pericellular fibrinolysis. The increased fibrinolytic capacity in AAA wall may promote angiogenesis and contribute to local proteolytic degradation of the aortic wall leading to physical weakening and active expansion of the aneurysm.

Photic signaling by cryptochrome in the Drosophila circadian system.

Oscillations of the period (per) and timeless (tim) gene products are an integral part of the feedback loop that underlies circadian behavioral rhythms in Drosophila melanogaster. Resetting this loop in response to light requires the putative circadian photoreceptor cryptochrome (CRY). We dissected the early events in photic resetting by determining the mechanisms underlying the CRY response to light and by investigating the relationship between CRY and the light-induced ubiquitination of the TIM protein. In response to light, CRY is degraded by the proteasome through a mechanism that requires electron transport. Various CRY mutant proteins are not degraded, and this suggests that an intramolecular conversion is required for this light response. Light-induced TIM ubiquitination precedes CRY degradation and is increased when electron transport is blocked. Thus, inhibition of electron transport may "lock" CRY in an active state by preventing signaling required either to degrade CRY or to convert it to an inactive form. High levels of CRY block TIM ubiquitination, suggesting a mechanism by which light-driven changes in CRY could control TIM ubiquitination.

First Report of Sudden Death Syndrome of Soybean in Wisconsin.

In August of 2006, soybean (Glycine max (L.) Merr.) plants collected from Columbia, Dane, Green Lake, Walworth, Jefferson, and Waushara counties in southern Wisconsin exhibited symptoms typical of sudden death syndrome (SDS) caused by Fusarium virguliforme O'Donnell & Aoki [synonym F. solani (Mart.) Sacc. f. sp. glycines] (1). Foliar symptoms ranged from chlorotic spots to severe interveinal chlorosis and necrosis. Taproots of symptomatic plants were necrotic and stunted and stems exhibited a light tan discoloration, but never the dark brown discoloration typical for brown stem rot, a disease with similar foliar symptoms. Isolations from root and crown tissue of symptomatic plants were made using one-quarter-strength potato dextrose agar (PDA) amended with 100 ppm of streptomycin. Slow-growing, white-to-cream fungal colonies with blue and turquoise sporodochia were observed. Spores produced in sporodochia grown on PDA ranged in size from 32.5 to 70 µm long (average 53.1 µm) and 3 to 6 µm wide (average 4.4 µm) and with 3-5 septa (mode of 3). Isolates were characteristic of F. virguliforme based on colony morphology, spore morphology and size, and the absence of microconidia (3). The identity of F. virguliforme was confirmed by PCR amplification and DNA sequencing of the ITS, BT1, Act, and EF1B regions. All isolate sequences exhibited single nucleotide polymorphisms that matched the sequences of these regions of F. virguliforme. Koch's postulates were conducted to confirm that the causal agent of the observed symptoms was F. virguliforme. Inoculum of single-spore isolates was produced on sterilized sorghum seed. After 14 days of incubation at 20 to 22°C and a 12-h photoperiod, the sorghum seed was assayed to determine colonization incidence by transferring seeds to PDA. In all trials, sorghum seed was 100% infested. Infested sorghum seeds (35) were placed in potting soil at 2 cm beneath each seed of the susceptible soybean cv. Williams 82 (4). Noninfested sorghum seed was used for a noninoculated control. Three trials were performed, each using 15 replicates of several fungal isolates and 15 replicates of the noninoculated control. Plants were grown in water baths located in a greenhouse (trial 1) and in a growth chamber (trial 2) and both maintained at an average temperature of 25°C with a 14-h photoperiod (2). The third trial was conducted in the growth chamber without a water bath with the same temperature and light regimen. In all environments, inoculated plants developed chlorotic spots 14 days after planting. After 21 days, symptoms progressed to a range of chlorotic mottling to interveinal chlorosis and necrosis. Foliar and root symptoms that resembled those on the original plant samples infected with F. virguliforme appeared on 88% of inoculated plants. Isolates that resembled the original F. virguliforme were recovered from 75% of inoculated plants and from 88% of plants showing symptoms. No symptoms were observed and no isolates were recovered from noninoculated plants. There was a statistically significant difference between inoculated and control plants (P < 0.001) based on the presence of symptoms and isolation success using the Goodman χ2 analysis. The confirmation of the presence of SDS in five counties suggests that the disease is widespread in Wisconsin and could become a serious threat to soybean production in the future. References: (1) T. Akoi et al. Mycoscience 46:162, 2005. (2) R. Y. Hashmi et al. Online publication. doi:10.1094/PHP-2005-0906-01-RS. Plant Health Progress, 2005. (3) K. W. Roy et al. Plant Dis. 81:259, 1997. (4) J. C. Rupe et al. Can. J. Bot. 79:829, 2001.

Multiple G protein-coupled receptors initiate protein kinase C redistribution of GABA transporters in hippocampal neurons.

Neurotransmitter transporters function in synaptic signaling in part through the sequestration and removal of neurotransmitter from the synaptic cleft. A recurring theme of transporters is that many can be functionally regulated by protein kinase C (PKC); some of this regulation occurs via a redistribution of the transporter protein between the plasma membrane and the cytoplasm. The endogenous triggers that lead to PKC-mediated transporter redistribution have not been elucidated. G-protein-coupled receptors that activate PKC are likely candidates to initiate transporter redistribution. We tested this hypothesis by examining the rat brain GABA transporter GAT1 endogenously expressed in hippocampal neurons. Specific agonists of G-protein-coupled acetylcholine, glutamate, and serotonin receptors downregulate GAT1 function. This functional inhibition is dose-dependent, mimicked by PKC activators, and prevented by specific receptor antagonists and PKC inhibitors. Surface biotinylation experiments show that the receptor-mediated functional inhibition correlates with a redistribution of GAT1 from the plasma membrane to intracellular locations. These data demonstrate (1) that endogenous GAT1 function can be regulated by PKC via subcellular redistribution, and (2) that signaling via several different G-protein-coupled receptors can mediate this effect. These results raise the possibility that some effects of G-protein-mediated alterations in synaptic signaling might occur through changes in the number of transporters expressed on the plasma membrane and subsequent effects on synaptic neurotransmitter levels.

Oscillation and light induction of timeless mRNA in the mammalian circadian clock.

Circadian rhythms in Drosophila melanogaster depend on a molecular feedback loop generated by oscillating products of the period (per) and timeless (tim) genes. In mammals, three per homologs are cyclically expressed in the suprachiasmatic nucleus (SCN), site of the circadian clock, and two of these, mPer1 and mPer2, are induced in response to light. Although this light response distinguishes the mammalian clock from its Drosophila counterpart, overall regulation, including homologous transcriptional activators, appears to be similar. Thus, the basic mechanisms used to generate circadian timing have been conserved. However, contrary to expectations, the recently isolated mammalian tim homolog was reported not to cycle. In this study, we examined mRNA levels of the same tim homolog using a different probe. We observed a significant (approximately threefold) diurnal variation in mTim expression within mouse SCN using two independent methods. Peak levels were evident at the day-to-night transition in light-entrained animals, and the oscillation persisted on the second day in constant conditions. Furthermore, light pulses known to induce phase delays caused significant elevation in mTim mRNA. In contrast, phase-advancing light pulses did not affect mTim levels. The mTim expression profile and the response to nocturnal light are similar to mPer2 and are delayed compared with mPer1. We conclude that temporal ordering of mTim and mPer2 parallels that of their fly homologs. We predict that mTIM may be the preferred functional partner for mPER2 and that expression of mTim and mPer2 may, in fact, be driven by mPER1.

ATP-loaded liposomes effectively protect mechanical functions of the myocardium from global ischemia in an isolated rat heart model.

ATP-loaded liposomes (ATP-L) infused into Langendorff-instrumented isolated rat hearts protect the mechanical functions of the myocardium during ischemia/reperfusion. The left ventricular developed pressure (LVDP) at the end of the reperfusion in the ATP-L group recovered to 72% of the baseline (preservation of the systolic function) compared to 26%, 40%, and 51% in the groups treated with Krebs-Henseleit (KH) buffer, empty liposomes (EL), and free ATP (F-ATP), respectively. The ATP-L-treated group also showed a significantly lower left ventricular end diastolic pressure (LVEDP; better preservation of the diastolic function) after ischemia/reperfusion than controls. After incubating the F-ATP and ATP-L with ATPase, the protective effect of the F-ATP was completely eliminated because of ATP degradation, while the protective effect of the ATP-L remained unchanged. Fluorescence microscopy confirmed the accumulation of liposomes in ischemic areas, and the net ATP in the ischemic heart increased with ATP-L. Our results suggest that ATP-L can effectively protect myocardium from ischemic/reperfusion damage.

Stability of insulin lispro in insulin infusion systems.

OBJECTIVE: To test stability of insulin lispro in two insulin infusion systems over 48 h. RESEARCH DESIGN AND METHODS: We used reverse-phase and size-exclusion high-performance liquid chromatography (HPLC) to determine the purity, potency, and degree of polymerization of U100 insulin lispro (Humalog) after 24- and 48-h pump cycles conducted at 37 degrees C in five Disetronic H-TRON V100 and five MiniMed 504 pumps. Pumps were set to deliver a basal rate of 0.5 U/h and 6-U boluses at t = 0, 4, 8, 24, 24.5, 28.5, 32.5, and 48 h during each cycle. The effluent was collected into 1-ml vials, pooled at 24 or 48 h, and stored at 4 degrees C until assay. After each 48-h run period of insulin delivery, assays for potency, polymer, and purity were performed on the pooled samples from each individual cycle. m-cresol content and the pooled reservoir content were assayed in the 48-h pooled samples. RESULTS: Insulin lispro retained full HPLC potency (delta < or = 4%) at 48 h, with no degradation of insulin lispro to des-amidoinsulin forms (24 or 48 h). No increase in pumped insulin polymer concentration was observed following 24 h of pump flow. Nonsignificant increases of < or =0.09% (Disetronic) and < or =0.15% (MiniMed) from initial concentrations of 0.18% (polymer divided by total insulin) were detected in three of five pump cycles at 48 h when compared with 37 degrees C paired controls. Nonsignificant decreases (<5 and 10%, Disetronic and MiniMed, respectively) of m-cresol content occurred in both systems following 48 h storage in each device, but sterility was not compromised by this decrease (initial m-cresol concentration, 3.15 mg/ml). Pump performance was without mechanical or electrical fault throughout the study Basal and bolus insulin delivery was evaluated three times daily and remained as expected. Occlusion of catheters by insulin precipitation did not occur, and no change in pH was observed following delivery. CONCLUSIONS: We conclude that insulin lispro is suitable for prolonged infusion in these two medical devices when syringes and catheters are replaced at 48-h intervals.

Destruction of serotonergic neurons in the median raphe nucleus blocks circadian rhythm phase shifts to triazolam but not to novel wheel access.

Systematic treatment of hamsters with triazolam (TRZ) or novel wheel (NW) access will yield PRCs similar to those for neuropeptide Y. Both TRZ and NW access require an intact intergeniculate leaflet (IGL) to modulate circadian rhythm phase. It is commonly suggested that both stimulus types influence rhythm phase response via a mechanism associated with drug-induced or wheel access-associated locomotion. Furthermore, there have been suggestions that one or both of these stimulus conditions require an intact serotonergic system for modulation of rhythm phase. The present study investigated these issues by making serotonin neuron-specific neurotoxic lesions of the median or dorsal raphe nuclei and evaluating phase response of the hamster circadian locomotor rhythm to TRZ treatment or NW access. The expected effect of TRZ injected at CT 6 h on the average phase advance was virtually eliminated by destruction of serotonin neurons in the median, but not the dorsal, raphe nucleus. No control or lesioned animal engaged in substantial wheel running in response to TRZ. By contrast, all median raphe-lesioned hamsters that engaged in substantial amounts of running when given access to a NW had phase shifts comparable to control or dorsal raphe-lesioned animals. The results demonstrate that serotonergic neurons in the median raphe nucleus contribute to the regulation of rhythm phase response to TRZ and that it is unlikely that these neurons are necessary for phase response to NW access. The data further suggest the presence of separate pathways mediating phase response to the two stimulus conditions. These pathways converge on the IGL, a nucleus afferent to the circadian clock, that is necessary for the expression of phase response to each stimulus type.