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El trauma abierto es una de las principales urgencias que se presentan en el servicio de Ortopedia y trauma. Dentro de este campo y cuando hay progresión a infección, usualmente existe un grupo de microorganismos a tener en cuenta de acuerdo con la epidemiología local; sin embargo, la presencia de material vegetal, común en agricultores y militares, orienta a considerar microorganismos diferentes. Dentro de ellos se encuentra Pantoea spp causante comúnmente de artritis séptica, pero, sin relación clara con osteomielitis y/o infección periprotésica, más comúnmente se ha documentado por este microorganismo endocarditis infecciosa, sepsis asociada a catéter y neumonía asociada a ventilador, entre otras. A continuación, se presenta el caso de un paciente de 21 años de edad con antecedente de osteosíntesis en radio y cúbito del antebrazo derecho, quien después de una fractura abierta se aisla este microorganismo y requiere de terapia dirigida, se presenta su diagnóstico y evolución.

The Pseudomonas syringae DC3000 type III effector HopAM1 suppresses plant immunity and contains a Toll/interleukin-1 receptor (TIR) domain homologous to immunity-related TIR domains of plant nucleotide-binding leucine-rich repeat receptors that hydrolyze nicotinamide adenine dinucleotide (NAD+ ) and activate immunity. In vitro and in vivo assays were conducted to determine if HopAM1 hydrolyzes NAD+ and if the activity is essential for HopAM1's suppression of plant immunity and contribution to virulence. HPLC and LC-MS were utilized to analyze metabolites produced from NAD+ by HopAM1 in vitro and in both yeast and plants. Agrobacterium-mediated transient expression and in planta inoculation assays were performed to determine HopAM1's intrinsic enzymatic activity and virulence contribution. HopAM1 is catalytically active and hydrolyzes NAD+ to produce nicotinamide and a novel cADPR variant (v2-cADPR). Expression of HopAM1 triggers cell death in yeast and plants dependent on the putative catalytic residue glutamic acid 191 (E191) within the TIR domain. Furthermore, HopAM1's E191 residue is required to suppress both pattern-triggered immunity and effector-triggered immunity and promote P. syringae virulence. HopAM1 manipulates endogenous NAD+ to produce v2-cADPR and promote pathogenesis. This work suggests that HopAM1's TIR domain possesses different catalytic specificity than other TIR domain-containing NAD+ hydrolases and that pathogens exploit this activity to sabotage NAD+ metabolism for immune suppression and virulence.

Cancer cells often display impaired mitochondrial function, reduced oxidative phosphorylation, and augmented aerobic glycolysis (Warburg effect) to fulfill their bioenergetic and biosynthetic needs. Caveolin-1 (CAV1) is a scaffolding protein that promotes cancer cell migration, invasion, and metastasis in a manner dependent on CAV1 phosphorylation on tyrosine-14 (pY14). Here, we show that CAV1 expression increased glycolysis rates, while mitochondrial respiration was reduced by inhibition of the mitochondrial complex IV. These effects correlated with increased reactive oxygen species (ROS) levels that favored CAV1-induced migration and invasion. Interestingly, pY14-CAV1 promoted the metabolic switch associated with increased migration/invasion and augmented ROS-inhibited PTP1B, a phosphatase that controls pY14 levels. Finally, the glycolysis inhibitor 2-deoxy-D-glucose reduced CAV1-enhanced migration in vitro and metastasis in vivo of murine melanoma cells. In conclusion, CAV1 promotes the Warburg effect and ROS production, which inhibits PTP1B to augment CAV1 phosphorylation on tyrosine-14, thereby increasing the metastatic potential of cancer cells.

The Pseudomonas syringae DC3000 type III effector HopAM1 suppresses plant immunity and contains a Toll/interleukin-1 receptor (TIR) domain homologous to immunity-related TIR domains of plant nucleotide-binding leucine-rich repeat receptors that hydrolyze nicotinamide adenine dinucleotide (NAD

We have used experimental studies and DFT calculations to investigate the IrIII‐catalyzed isomerization of allylic alcohols into carbonyl compounds, and the regiospecific isomerization–chlorination of allylic alcohols into α‐chlorinated carbonyl compounds. The mechanism involves a hydride elimination followed by a migratory insertion step that may take place at Cβ but also at Cα with a small energy‐barrier difference of 1.8 kcal mol−1. After a protonation step, calculations show that the final tautomerization can take place both at the Ir center and outside the catalytic cycle. For the isomerization–chlorination reaction, calculations show that the chlorination step takes place outside the cycle with an energy barrier much lower than that for the tautomerization to yield the saturated ketone. All the energies in the proposed mechanism are plausible, and the cycle accounts for the experimental observations., Experimental and DFT calculations have been used to understand the mechanism of the IrIII‐catalyzed isomerization of allylic alcohols into carbonyl compounds, and the regiospecific isomerization–chlorination of allylic alcohols into α‐chlorinated carbonyl compounds. The results presented, point to the importance of using an experimental–computational approach to comprehend the mechanisms of complex reactions (see scheme).

The effect of thermal annealing at low temperature (≤200°C) on some structural, optical, and electrical properties of tin (Sn) layers, deposited at room temperature by direct current magnetron sputtering in an argon and oxygen reactive plasma, was studied to obtain tin monoxide (SnO). The Sn layers were 70±5 nm thick. The oxygen partial pressure (OPP) was fixed at 7% or 9%. Subsequently, deposited films were thermally annealed (TA) for 1 hour at temperatures between 160° C and 200° C in air environment. X-ray diffraction patterns of films deposited at 7% and 9% of OPP showed a dominant Sn phase oriented to different crystallographic planes. Once the deposited films were annealed at 200° C, a phase of polycrystalline SnO became predominant for the deposition process at 9% of OPP. The optical bandgap energy, the refractive index and the extinction coefficient of the annealed layers varied with the TA temperature. Finally, four-point-probe measurements showed the resistivity variation of the films from as-deposited to thermally annealed up to 200° C.

We have used experimental studies and DFT calculations to investigate the IrIII -catalyzed isomerization of allylic alcohols into carbonyl compounds, and the regiospecific isomerization-chlorination of allylic alcohols into α-chlorinated carbonyl compounds. The mechanism involves a hydride elimination followed by a migratory insertion step that may take place at Cβ but also at Cα with a small energy-barrier difference of 1.8 kcal mol-1 . After a protonation step, calculations show that the final tautomerization can take place both at the Ir center and outside the catalytic cycle. For the isomerization-chlorination reaction, calculations show that the chlorination step takes place outside the cycle with an energy barrier much lower than that for the tautomerization to yield the saturated ketone. All the energies in the proposed mechanism are plausible, and the cycle accounts for the experimental observations.

An efficient method for the synthesis of alpha-iodoketones from allylic alcohols and elemental iodine is reported. We show in this paper that the isomerization of allylic alcohols catalyzed by iridium(III) complexes can be combined with an aerobic oxidative iodination protocol, resulting in a straightforward method for the synthesis of a wide range of alpha-iodoketones as single constitutional isomers and in high yields under mild reaction conditions.

Mesoporous silica nanomaterials have emerged as promising vehicles in controlled drug delivery systems due to their ability to selectively transport, protect, and release pharmaceuticals in a controlled and sustained manner. One drawback of these drug delivery systems is their preparation procedure that usually requires several steps including the removal of the structure-directing agent (surfactant) and the later loading of the drug into the porous structure. Herein, we describe the preparation of mesoporous silica nanoparticles, as drug delivery systems from structure-directing agents based on the kidney-protector drug cilastatin in a simple, fast, and one-step process. The concept of drug-structure-directing agent (DSDA) allows the use of lipidic derivatives of cilastatin to direct the successful formation of mesoporous silica nanoparticles (MSNs). The inherent pharmacological activity of the surfactant DSDA cilastatin-based template permits that the MSNs can be directly employed as drug delivery nanocarriers, without the need of extra steps. MSNs thus synthesized have shown good sphericity and remarkable textural properties. The size of the nanoparticles can be adjusted by simply selecting the stirring speed, time, and aging temperature during the synthesis procedure. Moreover, the release experiments performed on these materials afforded a slow and sustained drug release over several days, which illustrates the MSNs potential utility as drug delivery system for the cilastatin cargo kidney protector. While most nanotechnology strategies focused on combating the different illnesses this methodology emphasizes on reducing the kidney toxicity associated to cancer chemotherapy.

The first method to access unsymmetrical aliphatic acyloins is presented. The method relies on a fast 1,3-hydride shift mediated by an Ir

2,2-Diiodo-5,5-dimethylcyclohexane-1,3-dione is reported as a new electrophilic iodinating agent that selectively iodinates electron-rich aromatics. In contrast to other common electrophilic iodinating reagents, its mild nature allows it to be used for the selective synthesis of alpha-iodinated carbonyl compounds from allylic alcohols through a 1,3-hydrogen shift/iodination process catalyzed by iridium(III) complexes.

Allergic transfusion reactions (ATRs) are a common complication of blood transfusions. Advances in transfusion medicine have significantly decreased the incidence of ATRs; however, ATRs continue to be burdensome for patients and problematic for providers who regularly order packed red blood cells and platelet transfusions. To further decrease the frequency of ATRs, routine premedication with diphenhydramine is common practice and is part of "transfusion culture" in a majority of institutions. In this article, we review the history, practice, and literature of transfusion premedication, specifically antihistamines given the adverse-effect profile. We discuss the rationale and original academic studies, which have supported the use of premedication for transfusions for decades. However, despite the common use of premedication to prevent ATRs, recent literature has not conclusively validated its use. In addition, the existing premedication that is routinely prescribed often causes a number of adverse effects. These findings have motivated the Moores Cancer Center (University of California, San Diego) to change its current transfusion premedication practices, particularly with regard to ATRs and first-generation antihistamines. We outline the preliminary development of an evidence-based and patient-specific approach to transfusion premedication, including the challenges and steps taken to revise inpatient premedication protocols. We plan to expand this protocol to the outpatient setting at a later date. Future efforts require a prospective validation of our presented transfusion premedication guidelines.

A mild base-catalyzed strategy for the isomerization of allylic alcohols and allylic ethers has been developed. Experimental and computational investigations indicate that transition metal catalysts are not required when basic additives are present. As in the case of using transition metals under basic conditions, the isomerization catalyzed solely by base also follows a stereospecific pathway. The reaction is initiated by a rate-limiting deprotonation. Formation of an intimate ion pair between an allylic anion and the conjugate acid of the base results in efficient transfer of chirality. Through this mechanism, stereochemical information contained in the allylic alcohols is transferred to the ketone products. The stereospecific isomerization is also applicable for the first time to allylic ethers, yielding synthetically valuable enantioenriched (up to 97% ee) enol ethers.

The new accelerographic network of Santa Fe de Bogota is composed of 29 three-component stations with sensors at the surface and three additional six-component borehole stations with three sensors at the surface and three at depth (115, 126 and 184 m). In total, 32 stations have been operative in the metropolitan area of Bogota since 1999. During this period of time, a significant number of weak motion are recorded and used for a preliminary analysis of local site effects. Using the SH-wave response spectra we verify the behavior of the different seismic zones proposed by the previous microzonation study of the city. A comparison between normalized SH-wave response spectra and the normalized design spectra for each zone clearly depicts that parts of the design spectra should be revised, as well as the boundaries between different zones may require some changes. The spectral amplification levels reach up to a factor of 5. The predominant periods obtained by the amplification spectra in different stations in the city, show variability from 0.3 to 3.0 s. A comparison is also made between the predominant periods obtained using H/V spectral ratios of microtremors and those using weak motion. In general, microtremors tend to predict slightly lower values of dominant periods than those calculated by the weak motion spectra. However, there is a general correlation between the two data sets. Using the data recorded by one of the borehole station, an equivalent linear seismic response analysis was conducted. The modeled and recorded response spectra show similarities in period peaks, however, the modeled soil amplification is underestimated for periods less than 0.8 s. Since the available record is weak motion which represents mostly the linear response of the soils, further analysis is required.

Body size is associated with menarche and ovarian function, but the relationship to first conception is rarely examined. We conducted a longitudinal investigation of rhesus macaques, Macaca mulatta, to determine the effect of differences in body weight on both the age at first conception and survivorship of first progeny. Young females who became pregnant weighed significantly more than peers who remained barren, with weight changes for females who successfully raised offspring no different than those for females who did not produce offspring. Infant mortality among primiparae was not significantly greater than that among multiparae, although nearly twice as high. First-born males tended to have lower survivorship than first-born female offspring. We suggest that reproductive costs encountered by primiparous females are more likely to be modulated by immature neuroendocrine function than by inexperience, small body size, or infant suckling patterns. We conclude that body size influences probability of first conception, socioendocrine factors mediate the likelihood of infant survival, and primiparous production of male progeny seems to exert a greater reproductive cost than does production of female progeny.

Pentavalent antimony, the generally accepted treatment for leishmaniasis, is given parenterally, and it is expensive and not readily available in developing countries. An inexpensive, orally administered compound would be a substantial advance in treatment. Previous studies in vitro have shown synergism between allopurinol and pentavalent antimony in tissue-culture systems. We designed this clinical study to determine whether synergism could be demonstrated in patients.We performed a randomized, controlled study of the efficacy of allopurinol plus meglumine antimoniate (Glucantime), as compared with meglumine antimoniate alone, in patients with cutaneous leishmaniasis, who were recruited from a village in southeastern Colombia. In addition, those who declined injections were treated with allopurinol alone, and those who declined any treatment were considered controls. All the patients were followed for one year after the completion of treatment. Lesions that healed completely at three months and remained healed during follow-up were considered to be cured.The cure rate for patients treated with meglumine antimoniate was 36 percent; the addition of allopurinol increased the rate to 74 percent (P less than 0.001). Treatment with allopurinol alone yielded a cure rate of 80 percent (P less than 0.001). There were no cures among the untreated patients. There was no significant difference between the cure rate with allopurinol plus meglumine antimoniate and that with allopurinol alone. No major toxic effects were observed.For the treatment of American cutaneous leishmaniasis, the combination of allopurinol and meglumine antimoniate is significantly more effective than meglumine antimoniate alone, probably because of the efficacy of allopurinol alone, which appears to be as good as the combination.

A regioselective protocol for the synthesis of substituted allylic chlorides, bromides, and fluorides has been established. Remarkably, the method can be applied to the enantioselective synthesis of challenging chiral allylic chlorides. When the allylic halides are treated with the base triazabicyclodecene as the catalyst, a [1,3]-proton shift takes place, giving the corresponding vinyl halides in excellent yields with excellent Z:E ratios. Furthermore, the [1,3]-proton shift takes place with an outstanding level of chirality transfer from chiral allylic alcohols (≤98%) to give chiral trifluoromethylated vinyl chlorides.

We have developed a simple and reproducible system for infecting a human macrophage cell line (U937) with stationary-phase Leishmania donovani promastigotes. Four days after infection, greater than 90% of the promastigotes had transformed to amastigotes. The antileishmanial agents allopurinol riboside, formycin B, 9-deazainosine, and sodium stibogluconate effectively inhibited the growth of L. donovani amastigotes in this cell line. To study the capability of amastigotes in the U937 cell line to carry out biochemical reactions that could be monitored experimentally, we incubated the cells with radiolabeled 9-deazainosine. This purine analogue underwent metabolism in the amastigote phase similar to that occurring in the promastigote phase. This cell line should be useful for studies of parasite maturation and differentiation, parasite-human interactions, and antiparasitic drugs.

Pyrazolopyrimidines, particularly allopurinol, allopurinol riboside, and other purine analogues, show promise as experimental therapeutic compounds for the treatment of leishmaniasis. The combination of these agents with pentostam may produce an improved therapeutic effect. We report here on strong synergistic activity between pyrazolopyrimidines and pentavalent antimonials in a human macrophage tissue culture system infected with Leishmania donovani and L. braziliensis.