Emergency General Surgery in the Elderly: Too Old or Too Frail?
Assessment of operative risk in geriatric patients undergoing emergency general surgery (EGS) is challenging. Frailty is an established measure for risk assessment in elective surgical cases. Emerging literature suggests the superiority of frailty measurements to chronological age in predicting outcomes. The aim of this study was to assess the outcomes in elderly patients undergoing EGS using an established Rockwood frailty index. We prospectively measured preadmission frailty in all geriatric (aged 65 years and older) patients undergoing EGS at our institution during a 2-year period. Frailty index (FI) was calculated using the modified 50-variable Rockwood Preadmission FI. Frail patients were defined by FI ≥ 0.25. Outcomes measures were in-hospital complications, development of major complications, and mortality. Multivariate regression analysis was performed. A total of 220 patients were enrolled, of which 82 (37%) were frail. Frailty index score did not correlate with age (R = 0.64; R(2) = 0.53; p = 0.1) and poorly correlated with American Society of Anesthesiologists score (R = 0.51; R(2) = 0.44; p = 0.045). Thirty-five percent (n = 77) of patients had postoperative complications and 19% (n = 42) had major complications. Frailty index was an independent predictor for development of in-hospital complications (odds ratio = 2.13; 95% CI, 1.09-4.16; p = 0.02) and major complications (odds ratio = 3.87; 95% CI, 1.69-8.84; p = 0.001). Age and American Society of Anesthesiologists score were not predictive of postoperative and major complications. Our FI model had 80% sensitivity, 72% specificity, and area under the curve of 0.75 in predicting complications in geriatric patients undergoing EGS. The overall mortality rate was 3.2% (n = 7) and all patients who died were frail. Frailty index independently predicts postoperative complications, major complications, and hospital length of stay in elderly patients undergoing emergency general surgery. Use of FI will provide insight into the hospital course of elderly patients, allowing for identification of patients in need and more efficient allocation of hospital resources.


Bone tissue response to commercially pure titanium implants blasted with fine and coarse particles of aluminum oxide.
The present study compares the bone response to commercially pure titanium screws with two different degrees of surface roughness. Implants blasted with 25- and 250-micron particles of aluminum oxide were placed in rabbit tibiae after the surface roughness of the implants had been measured. After 4 weeks, there was a significantly higher bone-to-metal contact for implants blasted with 25-micron particles compared to those blasted with 250-micron particles. The present study indicates that a highly increased surface roughness compared to a moderately increased one is a short-term disadvantage for bone tissue.


Solvation dynamics of dipolar probes in dipolar room temperature ionic liquids: separation of ion-dipole and dipole-dipole interaction contributions.
Recent solvation dynamics experiments with common dipolar solvation probes in imidazolium room temperature ionic liquids (RTIL) have revealed large dynamic Stokes' shifts and biphasic solvation energy relaxations. Because of the dipolar nature of the imidazolium cations, the solute-cation (dipole-dipole) interaction may, in addition to the ion-solute (ion-dipole) interaction, contribute significantly to the observed Stokes' shift and its dynamics. Conventional time-resolved measurements, however, cannot separate out these contributions. A simple semimolecular theory is described here which, upon separation of the dipolar part of the solvation energy from the ion-dipole part, allows estimation of these two components in the measured shifts. While the sum-total of these separated out components agree well with experiments, the ion-dipole interaction is found to contribute approximately 60% of the measured shift in each of these dipolar RTILs. In addition, the calculated solvation response functions, as observed in experiments, are characterized by a fast exponential component (approximately 15-20%) with a time constant in the subpicosecond regime and a slow nonexponential component with a time constant in the subnanosecond regime. Interestingly, the present theory finds that the fast component of the solvation response function in imidazolium ionic liquids originates from the rapid orientational relaxation involving the dipolar species in these liquids, whereas the relaxation of the ion dynamic structure factor via ion translation produces the observed slow nonexponential component. In addition, calculations presented here explain why the continuum model based theories of solvation dynamics do not work for these liquids. For alkylphosphonium ionic liquids, the ion-dipole interaction accounts for nearly 75% of the measured shifts. The present theory also explains why the experimentally observed solvation response function in these liquids does not contain any subpicosecond component and decays nonexponentially with only a single relaxation time constant.


Urgent-Start Peritoneal Dialysis: The First Year of Brazilian Experience.
This study aimed to evaluate mechanical and infectious complications associated with urgent-start peritoneal dialysis (PD) and patients and technique survival in the first 180 days. It was a prospective study that evaluated chronic patients who started unplanned PD using high-volume PD (HVPD) right after (<72 h) PD catheter placement. After hospital discharge, patients were treated with intermittent PD on alternate days in a dialysis unit until family training was provided. Fifty-one patients fulfilling the following criteria were included: age was 62.1 ± 15 years, with diabetes as the main etiology of end-stage renal disease (39%), and uremia as the main dialysis indication (76%). Metabolic and fluid controls were achieved after 3 sessions of HVPD, and patients remained in intermittent PD for 23.2 ± 7.2 days. Mechanical complications occurred in 25.7% and peritonitis rate was 0.5 episode/patient-year. In the first 6 months, technique and patients survival rates were 86 and 82.4% respectively. The PD modality was a feasible and safe alternative to hemodialysis in the urgent-start dialysis.


Coherent anti-Stokes Raman scattering in a high-finesse microcavity.
We report the measurement of degenerate coherent anti-Stokes Raman scattering (CARS) in a high-finesse optical microcavity, with an atmospheric gas as the nonlinear medium. Unlike the well-known bulk process in which index-dispersion compensation is required for phase-matching, efficient microcavity CARS involves a resonant coupling at the Stokes, pump, and anti-Stokes frequencies which can be described using coupled-mode analysis. We show how the interaction is thereby dramatically enhanced in a microscopic sample volume and illustrate the technique for the measurement of CO₂ in air.


Community-based use of the larvivorous fish Poecilia reticulata to control the dengue vector Aedes aegypti in domestic water storage containers in rural Cambodia.
A community-based study of the distribution of larvivorous fish, Poecilia reticulata (common name: guppy), in water storage containers for dengue control was undertaken in 14 villages and approximately 1,000 households in Cambodia. Community volunteers reared guppies and distributed them in water jars and tanks in households for which they were responsible. A nearby control area received no intervention. One year after project commencement, 56.9% of eligible containers contained guppies and there was a 79.0% reduction in Aedes infestation in the intervention community compared with the control. Smaller or discarded containers unsuitable for guppy distribution in the intervention area also had 51% less infestation than those in the control area, suggesting a "community-wide" protective effect. In addition, there was less infestation in villages with higher rates of fish uptake, suggesting that the presence of fish was responsible for a reduction in Aedes infestation. This applied vector control model was well-accepted, effective, efficient, and shows promise as a sustainable community-based, non-insecticidal intervention for dengue vector control in large domestic water storage containers in rural Cambodia and elsewhere.


Defining "mutation" and "polymorphism" in the era of personal genomics.
The growing advances in DNA sequencing tools have made analyzing the human genome cheaper and faster. While such analyses are intended to identify complex variants, related to disease susceptibility and efficacy of drug responses, they have blurred the definitions of mutation and polymorphism. In the era of personal genomics, it is critical to establish clear guidelines regarding the use of a reference genome. Nowadays DNA variants are called as differences in comparison to a reference. In a sequencing project Single Nucleotide Polymorphisms (SNPs) and DNA mutations are defined as DNA variants detectable in >1 % or <1 % of the population, respectively. The alternative use of the two terms mutation or polymorphism for the same event (a difference as compared with a reference) can lead to problems of classification. These problems can impact the accuracy of the interpretation and the functional relationship between a disease state and a genomic sequence. We propose to solve this nomenclature dilemma by defining mutations as DNA variants obtained in a paired sequencing project including the germline DNA of the same individual as a reference. Moreover, the term mutation should be accompanied by a qualifying prefix indicating whether the mutation occurs only in somatic cells (somatic mutation) or also in the germline (germline mutation). We believe this distinction in definition will help avoid confusion among researchers and support the practice of sequencing the germline and somatic tissues in parallel to classify the DNA variants thus defined as mutations.


Hydrolysis of alanine oligomers and of elastin by P. aeruginosa proteinases and thermolysin.
The hydrolysis of alanine oligomers by P. aeruginosa proteinases, thermolysin and porcine pancreatic elastase was studied. The concentrations of substrates and cleavage products were determined using reverse phase high pressure liquid chromatography. Tetraalanine was the shortest oligomer for which we could demonstrate hydrolysis by all the proteinases, except for porcine pancreatic elastase which only significantly hydrolyzed peptides longer than hexaalanine. Porcine pancreatic elastase hydrolyzes hexaalanine at a single site, whereas the other enzymes may split it either into two trialanine molecules, or into di- and tetraalanine, the latter being further cleavable to dialanine. A kinetic model based on first-order kinetic rate constants is proposed and the individual constants determined. Although P. aeruginosa elastase and thermolysin are closely similar in structure, they have shown a marked difference in their hydrolysis of either elastin or tetraalanine. Elastolytic activity of thermolysin was higher than that of elastase but tetraalanine was hydrolyzed more slowly by thermolysin.


Carbon Assimilation in Photoheterotrophic Cells of Peanut (Arachis hypogaea L.) Grown in Still Nutrient Medium.
The relative transport of photosynthetic and dark carboxylation products in photoheterotrophic cells of Arachis hypogaea L. var. TMV-3 at varied phases of growth were determined. Despite the presence of an equally competent photosynthetic apparatus as determined from (14)CO(2) incorporation rates in the dark and light, pulse-chase experiments revealed little or no change in the radioactivity of the C(3) intermediates but rapid disappearance of label from the dark carbon assimilates (malate and other tricarboxylic acid cycle intermediates) with a simultaneous increase in the aminoacid pool in early log-phase (10 days old) cells. However, significant flow of carbon through the photosynthetic intermediates resulting in the accumulation of sugars occurred in the late log-phase (34 days old) cells. Limitation of exogenous sugar in the nutrient milieu and depletion of reserve carbohydrates stored in starch of the chloroplasts of the cells were considered as the decisive factors in promoting transport of C(3) cycle intermediates through the reductive pentose phosphate pathway in photoheterotrophic cells. The observed drain of radioactivity even from the small amounts of tricarboxylic acid cycle intermediates synthesized during photosynthesis into glutamate indicated that the transport of carbon through the nonautotrophic pathway is not controlled by these factors.


Effects of immunosuppression on West Nile virus infection in hamsters.
A research study, comparing the pathogenesis of experimental West Nile virus (WNV) infection in immunocompetent and immunosuppressed golden hamsters, is described. Cyclophosphamide was used to immunosuppress the animals. The immunosuppressed hamsters had a prolonged period of viremia, depressed humoral immune response, more extensive and severe pathology, and higher fatality rate than the untreated immunocompetent animals. Histopathological and immunohistochemical studies of tissues from the two groups showed that pathologic changes in the untreated infected animals were confined to the brain and spinal cord, whereas the histopathological changes and WNV antigen distribution in the immunosuppressed animals were much more extensive and diffuse, involving the adrenal, kidney, heart and lung, and brain and spinal cord. Results of this study in the hamster model provide insight into the increased severity of WNV infection observed in immunosuppressed people.


[Ruptured cerebral aneurysm associated with chronic renal failure: case report and evaluation of dialysis].
Two cases of ruptured cerebral aneurysm with chronic renal failure were successfully treated by selecting an appropriate dialysis during the pre- and postoperative period. Case 1; a 41-year-old male, who had been receiving hemodialysis for 4 years, complained of sudden onset of headache, and his consciousness deteriorated abruptly afterwards. A ruptured basilar-left superior cerebellar artery aneurysm was diagnosed, and an external ventricular drainage device was installed. The patient slowly recovered consciousness and was scheduled for delayed operation. During this period hemodialysis was suspended and continuous ambulatory peritoneal dialysis (CAPD) was performed instead. On the 24th day, the aneurysm was clipped, and CAPD switched to ordinary hemodialysis three days after the operation. However, consciousness deteriorated and CT scan showed diffuse cerebral swelling due to disequilibrium syndrome. The patient recovered consciousness 24 hours after hemodialysis. Frequent short-term dialysis eventually eliminated this syndrome. Case 2; a 60-year-old male, who had been receiving hemodialysis for 6 years, complained of a sudden severe headache, and a ruptured anterior communicating artery aneurysm was diagnosed. Emergency clipping of the aneurysm was performed and, except for mild vasospasm on the seventh day, the patient's recovery was uneventful postoperatively, with non-anticoagulative agent hemodialysis. These two cases demonstrate that chronic renal failure of a ruptured cerebral aneurysm patient can, with good prognosis, be treated by CAPD preoperatively, and non-anticoagulative agent hemodialysis postoperatively, followed by ordinary dialysis carefully avoiding the disequilibrium syndrome.


[Non-pharmacological, non-conventional therapy of chronic refractory angina pectoris].
Chronic refractory angina pectoris is a clinical entity characterized by a persistent thoracic pain, despite pharmacological therapy (Canadian Cardiovascular Society functional class 3-4); the patients show a severe, diffuse coronary atherosclerosis not amenable to myocardial revascularization at coronary angioplasty or bypass grafting. This clinical entity which is becoming ever more frequent is a cause of a poor quality of life necessitating repeated hospitalization. Many therapeutic alternatives have been proposed for the treatment of these patients, but results were inconclusive. In this review their pathophysiological background, clinical efficacy, safety and complications are analyzed. Data concerning spinal cord stimulation, upper thoracic sympathectomy, high thoracic epidural analgesia, chronic-intermittent urokinase administration, enhanced external counterpulsation and transmyocardial laser revascularization are presented. Finally, the main research directions in this particular field are reported.


CO sniffing through heme-based sensor proteins.
O(2), NO, and CO are substrates, products, and/or modulators in many enzymatic reactions including O(2) respiration, denitrification, N(2) fixation, and methanogenesis. Over the last decade, O(2), NO, and CO have been reported to act as signaling molecules in the control of several distinct biological functions. Here, the heme-based mechanisms of CO sensing by the bacterial homodimeric CooA and the mammalian heterodimeric NPAS2-BMAL1 transcriptional factors are reviewed, and the signal transduction pathways are discussed.


Glutaraldehyde degradation in hospital wastewater by photoozonation.
In this paper, we assessed aqueous solutions of glutaraldehyde (GA), a chemical used for the disinfection of hospital materials, using advanced oxidative processes, O3, and UV, and the combination of the latter two. Assays with different ozone concentrations at distinct pH levels were conducted to determine the best treatment process. GA concentrations before and after each treatment were measured by spectrophotometry. The best treatment was that which combined O3 and UV, yielding a degradation of 72.0-75.0% in relation to the initial concentration with pH between 4 and 9. Kinetics demonstrated that GA degradation is not dependent on pH, as there was a first-order reaction with a rate constant of k = 0.0180 min(-1) for initial pH 9 and of k = 0.0179 min(-1) for initial pH 7, that is, the values are virtually the same. Secondary wastewater samples were also analysed using the septic tank/filter system of a regional hospital in Vale do Rio Pardo, state of Rio Grande do Sul, southern Brazil. In this case, the characteristics of the wastewater were described and, after treatment, a GA degradation rate of 23.3% was noted, with reductions of 75% for chemical oxygen demand, 81% for biochemical oxygen demand, 68% for turbidity, 70% for surfactants and total disinfection in terms of thermotolerant coliforms.


Capturing Turbulent Dynamics and Statistics in Experiments with Unstable Periodic Orbits.
In laboratory studies and numerical simulations, we observe clear signatures of unstable time-periodic solutions in a moderately turbulent quasi-two-dimensional flow. We validate the dynamical relevance of such solutions by demonstrating that turbulent flows in both experiment and numerics transiently display time-periodic dynamics when they shadow unstable periodic orbits (UPOs). We show that UPOs we computed are also statistically significant, with turbulent flows spending a sizable fraction of the total time near these solutions. As a result, the average rates of energy input and dissipation for the turbulent flow and frequently visited UPOs differ only by a few percent.


Musculo-skeletal pain among 40- and 45-year olds in Oslo: differences between two socioeconomically contrasting areas, and their possible explanations.
BACKGROUND: The objective of the study was to compare the prevalence and severity of musculo-skeletal pain between two socioeconomically contrasting areas in Oslo, Norway, and to explore possible explanatory factors. METHODS: Questionnaire survey, carried out as part of The Oslo Health Study in 2000-2001. Data from 821 persons (40 and 45 year old) living in a less affluent inner city area (called east) were compared with 854 persons living in an affluent area of the city (called west). Bivariate comparisons (chi square test) and multiple regression analyses were performed to investigate differences between the samples. RESULTS: 61 % in east and 56 % in west (p < 0.05) reported pain/stiffness in muscles/joints during the last four weeks. 30 % in east versus 19 % in west (p < 0.001) reported extensive pain. The between area difference in extensive pain was partially explained by physical inactivity, mental health problems and being of non-Western origin. CONCLUSION: Musculo-skeletal pain is reported by 55-60 % of middle aged persons in Oslo during a four week period, and must be considered a normal phenomenon. Poor social conditions, inactivity, mental health problems and being an immigrant imply increased risk of more severe symptoms with a concomitant demand of health care.


Creatine supplementation--part II: in vivo magnetic resonance spectroscopy.
Our purpose was to study effects of creatine (Cr) supplementation on muscle metabolites noninvasively by means of magnetic resonance spectroscopy (MRS) before and after supplementation with Cr or placebo. 1H-MRS was used in a comprehensive, double-blind, cross-over study in 10 volunteers to measure Cr in m. tibialis anterior and m. rectus femoris at rest. PCr/ATP was observed in m. quadriceps femoris by 31P-MRS at rest and after exercise. A significant increase in total Cr was observed with Cr intake in m. tibialis anterior (+9.6 +/- 1.7%, P = 0.001) and in m. rectus femoris (+18.0 +/- 1.8%, P < 0.001). PCr/ATP showed a significant increase (+23.9 +/- 2.3%, P < 0.001) in m. quadriceps femoris at rest with Cr supplementation. Post-Cr supplementation recovery rates from exercise were significantly lower (k = 0.029 s(-1), P < 0.01) compared with postplacebo consumption (k = 0.034 s(-1)) and presupplementation (k = 0.037 s(-1)). However, higher levels of PCr/ATP at rest compensate for this reduction of the recovery rate after Cr supplementation. The increase of PCr/ATP determined by 31P-MRS correlates with the increase of Cr observed by 1H-MRS (r = 0.824, P < 0.001). Noninvasive observation of Cr and PCr after Cr supplementation shows an increase in a muscle specific manner. Higher preexercise levels of PCr/ATP at rest compensate for significantly slower recovery rates of PCr/ATP after Cr supplementation.


Use of granulocyte-macrophage colony-stimulating factor (GM-CSF) in combination with hydroxyurea as post-transplant therapy in chronic myelogenous leukemia patients autografted with unmanipulated hematopoietic cells.
Allogeneic bone marrow transplantation remains the only potentially curative treatment for CML, but more than 70% of patients will be ineligible for allogeneic marrow transplant either because they do not have a suitable HLA-matched related or unrelated donor or because they are more than 50 years old. Several experimental and clinical findings support a role for autologous stem cell transplantation (ASCT) in CML. It has been suggested that in the early phase following autografting the Ph-negative clone has a proliferative advantage over the Ph-positive clone. We hypothesized that post-transplant GM-CSF administration could reactivate the functional activity of quiescent normal progenitors and prolong the duration of the post-transplant proliferative advantage of Ph-negative over Ph-positive progenitors. In order to evaluate the effect of post-transplant GM-CSF administration, a pilot clinical study was performed in which CML patients resistant to IFN-alpha therapy were autografted with unmanipulated marrow or blood cells and given prolonged GM-CSF therapy post-transplant. Five adult CML patients conditioned with the BAVC regimen were reinfused with either marrow (n = 2) or blood (n = 3) cells and given granulocyte-macrophage colony-stimulating factor (GM-CSF). Recombinant GM-CSF was initially administered at standard dosage (5 micrograms/kg/day) until a white blood cell count > or = 2 x 10(9)/L was achieved on two consecutive examinations, and thereafter at a low dose (1 microgram/kg/day) for 5 to 9 months. On a weekly basis, GM-CSF was discontinued and hydroxyurea (1,000 mg/d) was given for two days. Evidence of trilineage engraftment was observed in all cases. At autografting, 3 out of the 5 patients revealed 8-9% Ph-negative metaphases. During the initial phase of hematopoietic regeneration, direct cytogenetic analysis revealed 81% and 100% Ph-negative metaphases in two cases; nonleukemic hematopoiesis progressively decreased and was no longer detectable at +9 months. One patient showed cyclic Ph-negative hematopoiesis that appeared 3 months following autografting and peaked at +4 and +8 months. The fourth patient showed a low percentage (20%) of Ph-negative metaphases 1 month after ASCT, followed by a significant expansion of nonleukemic hematopoiesis, which could be detected up to month +13. No evidence of Ph-negative hematopoiesis could be detected in one patient. Three patients are in chronic phase 28, 30 and 31 months after autografting, respectively, and two patients evolved into blast crisis. This pilot study demonstrates that combined GM-CSF and hydroxyurea therapy seems to be effective in inducing and/or prolonging a transient period of Ph-negative hematopoiesis. The late appearance of Ph-negative hematopoiesis detected in two patients suggests an antileukemic activity of the combined GM-CSF/hydroxyurea therapy rather than an antileukemic effect of the conditioning regimen.


Plant Derived Silver Nanoparticles and their Therapeutic Applications.
Nanotechnology involves the synthesis of materials that are in nanometre sizes (1 to 100 nm). Nanotechnology has appeared as a new area of fundamental science and is getting worldwide consideration due to its extensive applications. They have exceptional physicochemical properties due to their unique size, shape and size distribution. Conventionally, nanoparticles were synthesized using physical and chemical methods. These methods have various disadvantages; therefore, biological methods possess great interest. Biological synthesis uses bacteria, fungi, algae and plants. Biosynthesis of nanoparticles using plants emerges as nanofactories as they offer nontoxic, clean and eco-friendly methods with various physicochemical properties. Out of all the nanoparticles, silver nanoparticles gain special attention due to their various therapeutical and environmental applications. In this review, a summary of various reports within the last ten years where plants were utilized for silver nanoparticle synthesis has been discussed. Further mechanisms involving synthesis, factors affecting the process of synthesis and therapeutical applications have been discussed.


Can invasive thymomas be resected by video-assisted thoracoscopic surgery?
Although video-assisted thoracic surgery can be used for well-encapsulated thymomas, its role in invasive thymomas remains controversial. Between 1998 and 2009, 77 patients aged 22-76 years underwent thymomectomy by video-assisted thoracic surgery. Tumors <5 cm without major invasion on preoperative computed tomography were selected. There were 13 invasive thymomas (Masaoka stage III and IV). A modified dissection technique was employed to prevent breaching the tumor capsule and risking tumor seedling. Limited resection of the phrenic nerve, pericardium, perithymic fat, and a wedge of lung was performed en bloc with the tumor. The mean duration of surgery was 138 min. Hospital stay was 3.6 days. Eleven patients had associated myasthenia gravis. There was 1 case of wound infection and no operative mortality. The mean size of the thymomas was 34 mm (range, 23-55 mm). All patients had adjuvant radiotherapy. During follow-up of 4.9 years (range, 1-10 years), there was one local recurrence. With the modified video-assisted thoracic surgery technique, selected invasive thymomas detected during surgery can be removed safely without resorting to sternotomy.


The fine structure of macrophages in lysolecithin-induced demyelination: a freeze-fracture study.
Focal injection of lysolecithin into the thoracic spinal cord was used to induce experimental demyelination in rats. The macrophages which invaded the demyelinating area to phagocytose the myelin breakdown products were examined by electron microscopy using conventional thin-section and freeze-fracture techniques. The cells had the typical foamy cytoplasm characteristic of lipid macrophages. In freeze-fracture preparations, the P-face of the plasmalemma had scattered 10-18 nm round to oval or elongate particles. The cytoplasm was filled with phagocytic vacuoles containing myelin debris. Occasionally, membranous connections could be demonstrated between lysosomes and phagocytic vacuoles. The debris in the vacuoles varied in structure from material with a normal myelin periodicity to partially digested lamellated structures and pseudocrystalline structures to homogeneous-like, lipid-filled vacuoles. These patterns appeared to represent successive stages in the digestion of the ingested myelin.


Kegel or cut? Variations on his theme.
Pelvic floor muscle training has long been recognized as a beneficial treatment for urinary incontinence. This paper discusses the concepts of muscle grading facilitation and training. Individually designed programs, suitable for the patient's current status, are critical to success. It may be tempting to operate, but it takes a dedicated health care provider to manage incontinence nonsurgically.


The Yucatan minipig model: A new preclinical model of malnutrition induced by a low-calorie/low-protein diet.
Severe malnutrition exposes patients to adverse outcomes and a higher mortality risk. The Yucatan minipig, closer to human physiology than murine models could be a pertinent and innovative experimental model for studying the physiopathology and consequences of severe malnutrition. The present study aimed to determine whether a low calorie/low protein diet (LC/LP) can reproduce marasmus malnutrition in minipigs, and to characterize body composition, gut microbiota, malnutrition-related blood parameters, and histological and molecular skeletal muscle patterns. Eleven Yucatan minipigs were subjected to two different diets: a standard control diet (ST) (n = 5) and a LC/LP diet (n = 6). LC/LP animals daily received 50% of an isocaloric low-protein diet (10.37 MJ/kg, 8.6% protein). Body composition was measured by computed tomography (CT-scan) before (T0) and after 8 weeks of diet (T8). Trapezius and biceps femoris muscles were sampled at the end of protocol to perform histological and molecular analyses. Gut microbiota composition were was also analyzed at T0 and T8 in fecal samples. Eight weeks of LC/LP diet significantly reduced body weight (-12.3 ± 9.5%, P = 0.03) and gut microbiota richness (i.e. number of observed species) (-10.4 ± 8.3%, P = 0.014) compared to baseline. After 8 weeks, LC/LP animals exhibited a significant reduction of retroperitoneal fat and skeletal muscle surface areas (P = 0.03 and P = 0.047, respectively), whereas these parameters remained unchanged in ST animals. These reductions were associated with lower muscle fiber cross-sectional area (CSA) in trapezius (P < 0.001) and biceps femoris (P = 0.003) in LC/LP animals compared to ST. LC/LP diet promoted an increase of AMP kinase phosphorylation in trapezius and biceps femoris (P = 0.05), but did not affect cytochrome c and COX IV protein content, markers of mitochondrial content. Gene and proteins involved in ubiquitin-proteasome system and apoptosis remained unchanged after 8 weeks of LC/LP diet both in trapezius and biceps femoris. All these findings support that this experimental minipig model of severe malnutrition is valid to mimic pathophysiological changes occurring in human protein-energy marasmus malnutrition and muscle atrophy associated with malnutrition, as observed in patients with secondary sarcopenia.


The cytosolic phosphoprotein stathmin is expressed in the olfactory system of the adult rat.
Stathmin is a cytosolic protein expressed particularly in the developing nervous system, whose phosphorylation is correlated with the action of multiple extracellular stimuli regulating cell proliferation and differentiation. In this study, we used an antibody that specifically recognizes the carboxyterminal region of stathmin to analyze the distribution of this protein in the olfactory system of adult rats, and found a high and selective immunoreactivity in immature olfactory receptors of the olfactory neuroepithelium and in cells of the rostral migratory stream. These results reveal an expression of stathmin in regions of the adult nervous system characterized by striking structural plasticity and cell renewal, suggesting that this protein could play a role in the differentiation of newly generated cell populations.


[Injuries and seat belts].
The effectiveness of the seat belt in reduction of road fatalities and injuries is well known. Nevertheless, improper or incorrectly wearing of the seat belt can induce specific cervical, thoracic or abdominal lesions. With reference to the literature and clinical reports, the authors describe the specific lesions of the seat belt syndrome. Superficial lesions are frequently associated with underlying deep lesions.


Iridium-Catalyzed Aerobic Coupling of Salicylaldehydes with Alkynes: A Remarkable Switch of Oxacyclic Product.
The iridium(III)/copper(II)-catalyzed dehydrogenative coupling of salicylaldehydes with internal alkynes proceeds efficiently under atmospheric oxygen through aldehyde C-H bond cleavage and decarbonylation. A variety of benzofuran derivatives can be synthesized by the environmentally benign procedure. DFT calculations suggest that this unique transformation involves the facile deinsertion of CO in the key metallacycle intermediate, which is in marked contrast to the corresponding rhodium(III) catalysis that leads to CO-retentive chromone derivatives.


A clinical trial in oral surgery of the analgesic efficacy of a suprofen/codeine combination.
Suprofen as well as codeine have been shown to be effective analgesics. In this study, a 200-mg suprofen/60-mg codeine dose is scored for analgesic efficacy and safety compared to suprofen (200 mg), codeine (60 mg), and placebo. One hundred sixty-five healthy, adult patients were asked to rate degree of pain experienced over a six-hour period after medication. The combination treatment was found to offer maximum pain relief. Dentists should be aware that flank pain and renal function abnormalities have been reported in postmarketing surveillance.


Lymphocyte DNA adducts and polymorphism in the DNA repair enzyme XPD.
The effect of genetic polymorphism of DNA repair enzyme on the DNA adduct levels was evaluated in this study. We explored the relationship between polymorphism in the nucleotide excision repair enzyme XPD and DNA adduct levels in lymphocytes. Lymphocyte DNA adducts were measured by a (32.)


Linkage analysis of sex determination in Bracon sp. near hebetor (Hymenoptera: Braconidae).
To test whether sex determination in the parasitic wasp Bracon sp. near hebetor (Hymenoptera: Braconidae) is based upon a single locus or multiple loci, a linkage map was constructed using random amplified polymorphic DNA (RAPD) markers. The map includes 71 RAPD markers and one phenotypic marker, blonde. Sex was scored in a manner consistent with segregation of a single "sex locus" under complementary sex determination (CSD), which is common in haplodiploid Hymenoptera. Under haplodiploidy, males arise from unfertilized haploid eggs and females develop from fertilized diploid eggs. With CSD, females are heterozygous at the sex locus; diploids that are homozygous at the sex locus become diploid males, which are usually inviable or sterile. Ten linkage groups were formed at a minimum LOD of 3.0, with one small linkage group that included the sex locus. To locate other putative quantitative trait loci (QTL) for sex determination, sex was also treated as a binary threshold character. Several QTL were found after conducting permutation tests on the data, including one on linkage group I that corresponds to the major sex locus. One other QTL of smaller effect had a segregation pattern opposite to that expected under CSD, while another putative QTL showed a female-specific pattern consistent with either a sex-differentiating gene or a sex-specific deleterious mutation. Comparisons are made between this study and the in-depth studies on sex determination and sex differentiation in the closely related B. hebetor.


Quality of Reduction Influences Outcome After Locked-Plate Fixation of Proximal Humeral Type-C Fractures.
The aim of this study was to determine if fracture reduction, fracture pattern, and patient-related factors influence clinical outcome after locked-plate fixation of displaced proximal humeral fractures. Ninety-eight patients (mean age, 61.1 ± 11.2 years) with a proximal humeral fracture involving the anatomical neck (type C according to the OTA/AO classification system) were included. Clinical outcome was determined by age and sex-adjusted Constant score (CS%) and the Disabilities of the Arm, Shoulder and Hand (DASH) score. Fracture reduction was quantitatively determined by 3 parameters (head-shaft displacement, head-shaft alignment, and cranialization of the greater tuberosity), and patients were divided into groups according to anatomical reduction, acceptable reduction, or malreduction. Relative risk (RR) for complications, revision surgery, and inferior clinical outcome (CS of <50%) was determined according to the quality of fracture reduction and fracture pattern (disruption of the medial hinge; type-C3 fracture) and patient-related factors (age; comorbidities). After a mean of 3.1 ± 1.5 years, the mean CS% and DASH score were 54.8% ± 28.0% and 31.9 ± 24.8, respectively. The complication rate was 32.7% (n = 32), and 27 patients (27.6%) required revision surgery. Anatomical or acceptable fracture reduction was achieved in 40 (40.8%) of the patients. This resulted in a significantly lower complication rate (20.0% compared with 41.4% among the patients with malreduction; p = 0.027), a trend of lower revision rate (20% compared with 32.8%; p = 0.165), and better clinical outcome (mean CS% of 65.4% ± 28.2% compared with 47.6% ± 25.7%; p = 0.002) without a higher risk for osteonecrosis of the humeral head (5% compared with 10.3%). Cranialization of the greater tuberosity of >5 mm (n = 25), head-shaft displacement of >5 mm (n = 50), and valgus head-shaft alignment (n = 12) all increased the RR for inferior clinical outcome by twofold to threefold. Conversely, a patient age of >65 years (n = 31) and an OTA/AO type-C3 fracture pattern (n = 38) were not significantly associated with complications and inferior clinical outcome (RR, 0.9 to 1.8). Anatomical fracture reduction with a locked plate significantly improved the clinical outcome of unstable and displaced proximal humeral fractures involving the anatomical neck. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


A Bayesian approach to jointly estimate centre and treatment by centre heterogeneity in a proportional hazards model.
When multicentre clinical trial data are analysed, it has become more and more popular to look for possible heterogeneity in outcome between centres. However, beyond the investigation of such heterogeneity, it is also interesting to consider heterogeneity in treatment effect over centres. For time-to-event outcomes, this may be investigated by including a random centre effect and a random treatment by centre interaction in a Cox proportional hazards model. Assuming independence between the random effects, we propose a Bayesian approach to fit our proposed model. The parameters of interest are the variance components sigma(0) (2) and sigma(1) (2) of these random effects, which can be interpreted as a measure of centre and treatment effect over centres heterogeneity of the hazard. These variance components are estimated from their marginal posterior density after integrating out the fixed treatment effect and the random effects. As this integration cannot be performed analytically, the marginal posterior density is approximated using the Laplace integration technique. Statistical inference is then based on the characteristics of the posterior marginal density, such as the mode and the standard deviation. We demonstrate the proposed technique using data from a pooled database of seven EORTC bladder cancer clinical trials. Substantial centre and treatment effect over centres heterogeneity in disease-free interval was found.


Modulation of Replicative Lifespan in Cryptococcus neoformans: Implications for Virulence.
The fungal pathogen, Cryptococcus neoformans, has been shown to undergo replicative aging. Old cells are characterized by advanced generational age and phenotypic changes that appear to mediate enhanced resistance to host and antifungal-based killing. As a consequence of this age-associated resilience, old cells accumulate during chronic infection. Based on these findings, we hypothesized that shifting the generational age of a pathogenic yeast population would alter its vulnerability to the host and affect its virulence. SIR2 is a well-conserved histone deacetylase, and a pivotal target for the development of anti-aging drugs. We tested its effect on C. neoformans' replicative lifespan (RLS). First, a mutant C. neoformans strain (sir2Δ) was generated, and confirmed a predicted shortened RLS in sir2Δ cells consistent with its known role in aging. Next, RLS analysis showed that treatment of C. neoformans with Sir2p-agonists resulted in a significantly prolonged RLS, whereas treatment with a Sir2p-antagonist shortened RLS. RLS modulating effects were dependent on SIR2 and not observed in sir2Δ cells. Because SIR2 loss resulted in a slightly impaired fitness, effects of genetic RLS modulation on virulence could not be compared with wild type cells. Instead we chose to chemically modulate RLS, and investigated the effect of Sir2p modulating drugs on C. neoformans cells in a Galleria mellonella infection model. Consistent with our hypothesis that shifts in the generational age of the infecting yeast population alters its vulnerability to host cells, we observed decreased virulence of C. neoformans in the Galleria host when RLS was prolonged by treatment with Sir2p agonists. In contrast, treatment with a Sir2p antagonist, which shortens RLS enhanced virulence in Galleria. In addition, combination of Sir2p agonists with antifungal therapy enhanced the antifungal's effect. Importantly, no difference in virulence was observed with drug treatment when sir2Δ cells were used for infection, which confirmed target specificity and ruled out non-specific effects of the drugs on the Galleria host. Thus, this study suggests that RLS modulating drugs, such as Sir2p agonists, shift lifespan and vulnerability of the fungal population, and should be further investigated as a potential class of novel antifungal drug targets that can enhance antifungal efficacy.


Urine Monocyte Chemoattractant Protein-1(UMCP-1) as a Biomarker of Renal Involvement in Systemic Lupus Erythematosus.
Lupus nephritis (LN) is frequently associated with a poor long-term prognosis. Renal biopsy is the diagnostic method of choice in this condition. Urine biomarkers have been mentioned in the diagnosis of LN. The study(,)s purpose was to evaluate the performance of urinary monocyte chemoattractant protein 1(UMCP-1) as a biomarker of renal involvement in systemic lupus erythematosus. Forty-one recently diagnosed systemic lupus erythematosus patients (8 male and 33 female) without renal involvement (group 1) and twenty six patients (8 male and 18 female) with LN (group 2), proven by biopsy, were recruited to this study. UMCP-1 sensitivity and specificity for identifying biopsy-proven nephritis were calculated, and a receiver operating characteristic (ROC) curve was constructed to quantify how definitely UMCP-1 distinguishes between patients with and without LN. The mean value of UMCP-1 levels were 733.07 pg/ml ± 1282.54 and 144.16 pg/ml ± 137.90 in patients with and without LN respectively. The UMCP-1 level was significantly higher in group 2 than group 1. There was no significant correlation between UMCP-1 and 24-hour urine protein (r = 0.031, P= 0.874). The area under the ROC curve was 0.727 with a CI 95% of 0.597 to 0.857 (P=0.002). Using a cut-off value of 82 pg/ml,UMCP-1 had a sensitivity of 88.5% and a specificity of 46.3% for identifying LN. UMCP-1 can serve as a biomarker of LN although further longitudinal studies of these biomarkers are required in LN.


Inhibitory activity of Socheongryong‑tang and its constituent components against the production of RANTES, eotaxin, eotaxin‑3 and MMP‑9 from BEAS‑2B cells.
Socheongryeong‑tang (SCRT) is a herbal formula previously used to treat pulmonary diseases primarily caused by the common cold virus, including airway inflammation, asthma and allergy. The aim of the present study was to investigate the inhibitory effect of SCRT water extract and its 13 constituent components on chemokine and enzyme production in the human bronchial epithelium cell line BEAS‑2B when induced by tumor necrosis factor‑α and interleukin‑4. The chemokines examined included regulated on activation of normal T‑cell‑expressed‑and‑secreted (RANTES), eotaxin and eotaxin‑3. The SCRT water extract demonstrated a dose‑dependent inhibition of RANTES, eotaxin, eotaxin‑3 and matrix metalloproteinase‑9 (MMP‑9) in BEAS‑2B cells. The 13 constituent compounds of SCRT water extract were quantitatively determined, and it was found that gallic acid, 6‑gingerol and methyl eugenol produced the most potent inhibition of RANTES, eotaxin and eotaxin‑3 as well as MMP‑9 activity regardless of their concentration in SCRT water extract. Principal component analysis and hierarchical clustering analysis revealed that the inhibitory effect of these three compounds contributed to that of SCRT water extract. In conclusion, the results of the present study indicated that the inhibitory effects of SCRT on chemokine and enzyme production in BEAS‑2B cells was associated with three of its constituent compounds, gallic acid, 6‑gingerol and methyl eugenol. This therefore suggested the potential use of these compounds as anti‑inflammatory agents.


Near infrared reflectance of colored fruits.
The near ir (NIR) spectral properties of colored fruits were measured and showed a wide variation between species. Within a species, NIR reflectance was found to vary with the degree of ripeness of the fruit, particularly for the softer fruits. Extreme values of NIR reflectances were 75% for unripe pears and 21% for the red-ripe tomatoes. This variation is considerably larger than would have been expected from similar studies with leaves and grains. Solar reflectances were calculated for the NIR region for possible use in subsequent energy balance studies. Results from this study indicate that soft fruits will have a solar energy input 10-20% greater than for hard fruits, due to a 20-40% difference in NIR spectral properties. Softening accompanying ripening of tomatoes increases solar heat input by up to 10%.


Enhanced expression of MYF5 and MYOD1 in fibroblast cells via the forced expression of bos taurus MYF5.
The formation of vertebrate skeletal muscles widely thought to be under the control of hierarchy of regulatory genes. MYF5 is one of the myogenic determination gene expressed in the developing mouse dermomyotome which control skeletal muscle differentiation. In the current work, we had obtained the cDNA sequence including the full coding region of the bos taurus myogenic factor MYF5 by reverse transcription polymerase chain reaction. Furthermore, we examined whether fibroblast cell derived from mouse and bos taurus can be transduced using plasmid vectors carrying bos taurus MYF5. Bos taurus MYF5 activates MYF5 and MYOD1 expression after 1 day culture. The concerted upregulation of the myogenic regulatory factors enhanced myosin (skeletal fast) expression. These observation show that MYF5 is essential for myogenic differentiation and provides candidates for regulation bos taurus skeletal muscle development.


Locating arbitrarily time-dependent sound sources in three dimensional space in real time.
This paper presents a method for locating arbitrarily time-dependent acoustic sources in a free field in real time by using only four microphones. This method is capable of handling a wide variety of acoustic signals, including broadband, narrowband, impulsive, and continuous sound over the entire audible frequency range, produced by multiple sources in three dimensional (3D) space. Locations of acoustic sources are indicated by the Cartesian coordinates. The underlying principle of this method is a hybrid approach that consists of modeling of acoustic radiation from a point source in a free field, triangulation, and de-noising to enhance the signal to noise ratio (SNR). Numerical simulations are conducted to study the impacts of SNR, microphone spacing, source distance and frequency on spatial resolution and accuracy of source localizations. Based on these results, a simple device that consists of four microphones mounted on three mutually orthogonal axes at an optimal distance, a four-channel signal conditioner, and a camera is fabricated. Experiments are conducted in different environments to assess its effectiveness in locating sources that produce arbitrarily time-dependent acoustic signals, regardless whether a sound source is stationary or moves in space, even toward behind measurement microphones. Practical limitations on this method are discussed.


Evaluation of Parental Nasomaxillary Asymmetry as a Risk Factor for Development of Palatal Clefts in their Offsprings.
Background and Objectives : It has been suggested previously that increased width of midfacial structure is associated with the development of palatal clefting. One of the most important heritable characteristics predisposing towards the development of orofacial clefting in an embryo is craniofacial morphology. The aim of the study was to compare nasomaxillary width of parents of children with unilateral complete cleft lip alveolus and palate with parents of noncleft children. Methods : 25 biologic parent sets of children with unilateral complete cleft lip alveolus and palate and 25 biologic parents of noncleft children were included in this study for PA cephalometric analysis. Results : There was no statistically significant difference between study and control groups. An association was found between the side of the cleft in the affected children and the parents in the same side with narrower nasomaxillary width. Interpretation and conclusion : The result of this study was in contrast with other previous studies. We observed a narrower nasomaxillary width, which suggested that this feature may be of morphogenetic importance in the etiopathogenesis of orofacial clefting in this geographic and ethnic group.


Measurement of pO2 by luminescence lifetime spectroscopy: A comparative study of the phototoxicity and sensitivity of [Ru(Phen)3 ]2+ and PdTCPP in vivo.
Dysfunctions in tissue metabolism can be detected at early stages by oxygen partial pressure (pO2 ) measurement. The measurement of emission lifetimes offers very promising and non-invasive approach to estimate pO2 in vivo. This study compares two extensively used oxygen sensors and assesses their in vivo oxygen sensitivity and phototoxic effect. Luminescence lifetime of Ru-polypyridyl complex and of Pd-porphyrin is measured in the Chick's Chorioallantoic Membrane (CAM) model with a dedicated optical fiber-based, time-resolved spectrometer. The Pd-porphyrin luminescence lifetimes measured in the CAM model exposed to different pO2 levels are longer and have a broader dynamic range (10-100 μs) than those of Ru-polypyridyl complex (0.6-1 μs). The combined statistical analysis based on an estimate of the kurtosis and skewness, bootstrapping method and routine normality tests is performed. The indicators of the averages and signal to noise ratio stability are also calculated. The combination of several data processing allows selection of the better sensor for a given application. In particular, it is found that the advantage of Ru-polypyridyl complex over Pd-porphyrin is two-fold: i) Ru-polypyridyl complex datasets have consistently better statistical characteristics, ii) Ru-polypyridyl exhibits lower cytotoxicity.


The elderly patient and informed consent. Empirical findings.
Informed consent with the elderly patient and the competency of this patient population have been neglected issues in medicine and law. Particularly, the competency of the elderly patient has received little empirical investigation. The present study examines the capacity of geriatric patients to consent to research participation. Competency is investigated through the use of hypothetical consent information on three dimensions: comprehension of consent material, quality of reasoning about the decision to participate or not participate in research, and reasonable choice regarding participation. The results indicate that elderly patients' choices about those projects in which participation is "reasonable" do not differ, by and large, from younger patients. However, the elderly show significantly poorer comprehension of consent information. Thus, screening for competency and providing special instructions may become an important part of the research process when the elderly are participants.


Physical Activity Recommendations in the Context of New Calls for Change in Physical Education.
The current social, health, and educational changes in society require an adequate response in school-based physical activity (PA), including physical education (PE) lessons. The objective of this study was to identify the real average step counts of Czech and Polish adolescents during PE lessons, and propose recommendations for improving PE programs. This research was carried out in 143 Czech and 99 Polish schools. In the research, a total of 4911 adolescents aged 12-18 years were analyzed as part of teaching practice and 1827 in the context of habitual school practice. Steps were monitored using pedometers. The average step count per PE lesson was 2390 in Czech and Polish boys, while girls achieved 1851 steps. In both countries, boys were subject to greater physical strain in PE lessons compared to girls, both in teaching practice (F(4088,3) = 154.49, p < 0.001, ηp2 = 0.102) and school practice (F(1552,3) = 70.66, p < 0.001, ηp2 = 0.103). Therefore, the priority in PE lessons is to increase the amount of PA for girls, achieve the objectives of PE during PA, and use wearables to improve awareness of PA and improve physical literacy, as well as to support hybrid and online PE as a complement to traditional PE.


Ca2+ activates glycogenolysis in isolated mantle storage cells of Mytilus galloprovincialis Lmk.
Glycogenolytic activity (GA) in isolated mantle storage cells (MSC) from Mytilus galloprovincialis was studied, while glycogen and free-glucose content, as well as glucose released from cells were tested. In the period studied (November-December), the glucose releasing activity measured can be considered as an output of GA. In both, whole cells system (WCS) and crude cell-free system (CFS), a non-stimulated GA was detected. In WCS, dopamine and 5-hydroxytryptamine (5-HT) stimulated glycogenolysis, while epinephrine, norepinephrine and isoproterenol did not show any effect. Furthermore, mellitin and the Ca(2+)-ionophore, A23187, had a stimulating effect on the GA. In CFS, the absence of Ca2+ ions was a sufficient condition to depress GA. These and other findings suggest that: 1) GA in MSC may be stimulated by dopamine and 5-HT and not by adrenergic agonists; 2) cytosolyc Ca2+ signalling may have become an absolute requirement for activation of the glycogenolytic cascade in MSC; 3) a rapid high-affinity glucose transport may occur in these cells.


Crystal structure of (E)-2-[(2S,5R)-2-isopropyl-5-methyl-cyclo-hexyl-idene]hydrazine-1-carbo-thio-amide.
The title compound, C11H21N3S, consists of a menthone moiety attached to an extended thio-semicarbazone group with the N-N-C-N torsion angle being 11.92 (16)°. The cyclo-hexane ring has a chair conformation and the conformation about the C=N bond is E. In the crystal, mol-ecules are linked via pairs of N-H⋯S hydrogen bonds, forming chains along the a axis. The absolute structure could be assigned with reference to the starting material, i.e. enanti-opure (-)-menthone [Flack parameter = 0.05 (5)].


A unique epigenetic signature is associated with active DNA replication loci in human embryonic stem cells.
The cellular epigenetic landscape changes as pluripotent stem cells differentiate to somatic cells or when differentiated cells transform to a cancerous state. These epigenetic changes are commonly correlated with differences in gene expression. Whether active DNA replication is also associated with distinct chromatin environments in these developmentally and phenotypically diverse cell types has not been known. Here, we used BrdU-seq to map active DNA replication loci in human embryonic stem cells (hESCs), normal primary fibroblasts and a cancer cell line, and correlated these maps to the epigenome. In all cell lines, the majority of BrdU peaks were enriched in euchromatin and at DNA repetitive elements, especially at microsatellite repeats, and coincided with previously determined replication origins. The most prominent BrdU peaks were shared between all cells but a sizable fraction of the peaks were specific to each cell type and associated with cell type-specific genes. Surprisingly, the BrdU peaks that were common to all cell lines were associated with H3K18ac, H3K56ac, and H4K20me1 histone marks only in hESCs but not in normal fibroblasts or cancer cells. Depletion of the histone acetyltransferases for H3K18 and H3K56 dramatically decreased the number and intensity of BrdU peaks in hESCs. Our data reveal a unique epigenetic signature that distinguishes active replication loci in hESCs from normal somatic or malignant cells.


Simultaneous PLK1 inhibition improves local tumour control after fractionated irradiation.
Polo-like kinase 1 (PLK1) plays an important role in mitotic progression, is frequently overexpressed and associated with a poor prognosis of cancer patients, thus providing a promising target in anticancer treatment. Aim of the current project was to evaluate the effect of the novel PLK1 inhibitor BI 6727 in combination with irradiation. In vitro proliferation and radiation cell survival assays as well as in vivo local tumour control assays after single treatment and combined radiation and drug application were carried out using the squamous cell carcinoma models A431 and FaDu. In addition, cell cycle phases were monitored in vitro and in vivo. BI 6727 showed a dose-dependent antiproliferative effect and an increase in the mitotic fraction. BI 6727 alone reduced clonogenic cell survival, while radiosensitivity in vitro (SF2) and in vivo (single-dose TCD(50) under clamped hypoxia) was not affected. In contrast, local tumour control was significantly improved after application of BI 6727 simultaneously to fractionated irradiation (A431: TCD(50) = 60.5 Gy [95% C.I. 57; 63] after IR alone and <30 Gy after combined treatment; FaDu: 49.5 Gy [43; 56 Gy] versus 32.9 Gy [26; 40]). Despite the lack of direct cellular radiosensitisation, PLK1 inhibition with BI 6727 during fractionated irradiation significantly improves local tumour control when compared to irradiation alone. This result is likely explained by a considerable effect on cell cycle and an independent cytotoxic potential of BI 6727.


A case of breast angiosarcoma: diagnostic imaging and review of the literature.
Primary angiosarcoma of the breast is a rare tumor, with approximately 170 cases reported in the literature (1-3, 10, 11, 15). Reports on the imaging characteristics of these tumors have been occasional until a recent review by Liberman et al. (11). Diagnostic imaging of the masses include mammographic and ultrasound examinations (5): the imaging characteristics of the tumor can be nonspecific and sometimes heterogeneous (11). Only recently was one case evaluated with magnetic resonance imaging (11). We present the mammographic and sonographic features of a case of primary angiosarcoma of the breast with an inflammatory appearance.


[Guizhou planned parenthood].
Since launching planned parenthood work in 1975 in Guizhou, the birth rate has begun to decrease each year. In the past 6 years, 1.66 million births were prevented. Some 8 years ago, the natural population growth rate in the province was as high as 31/1000. According to statistics, in 1980, of the 87 counties, municipalities and districts in the province, 66 had reduced the natural population growth rate from that of 1979, including 25 which had reduced the rate to 5/1000. During the same period, the natural population growth rate in Guiyang Municipality was reduced to 4.3/1000, while in Zunyi Prefecture, the rate was reduced from 14/1000 in 1979 to 10.9/1000. The population in this prefecture accounted for 1/4 of the total population in the province.


Role of Metabolites in the Reversible Light Activation of Pyruvate, Orthophosphate Dikinase in Zea mays Mesophyll Cells in Vivo.
Whole leaf and mesophyll cell concentrations of pyruvate, phosphoenolpyruvate (PEP), ATP, and ADP were determined in Zea mays during the reversible light activation of pyruvate, orthophosphate dikinase in vivo. Mesophyll cell levels of the four metabolites were estimated by extrapolation from values in freeze-quenched leaf samples that were fractionated by differential filtration through nylon mesh nets (adapted from M Stitt, HW Heldt [1985] Planta 164: 179-188). During the 3 minutes required for complete light activation of dikinase, pyruvate levels in the mesophyll cell decreased (from 166 +/- 15 to 64 +/- 10 nanomoles per milligram of chlorophyll [nmol/mg Chl]) while PEP levels increased (from 31 +/- 4 to 68 +/- 4 nmol/mg Chl, with a transient burst of 133 +/- 16 nmol/mg Chl at 1 minute). Mesophyll cell levels of ATP increased (from 22 +/- 4 to 48 +/- 3 nmol/mg Chl) and ADP levels decreased (from 16 +/- 4 to 7 +/- 6 nmol/mg Chl) during the first minute of illumination. Upon darkening of the leaf and inactivation of dikinase, pyruvate levels initially increased in the mesophyll (from 160 +/- 30 to a maximum of 625 +/- 40 nmol/mg Chl), and then slowly decreased to about the initial value in the light over an hour. PEP levels dropped (from 176 +/- 5 to 47 +/- 3 nmol/mg Chl) in the first 3 minutes and remained low for the remainder of the dark period. Mesophyll levels of ATP and ADP rapidly decreased and increased, respectively, about twofold upon darkening. The trends observed for these metabolite levels in the mesophyll cell during the light/dark regulation of pyruvate, orthophosphate dikinase activity suggest that pyruvate and PEP do not play a major role in vivo in regulating the extent of light activation (dephosphorylation) or dark inactivation (ADP-dependent threonyl phosphorylation) of dikinase by its bifunctional regulatory protein. While the changes in ADP levels appear qualitatively consistent with a regulatory role for this metabolite in the light activation and dark inactivation of dikinase, they are not of a sufficient magnitude to account completely for the tenfold change in enzyme activity observed in vivo.


Immune Status and SARS-CoV-2 Viral Dynamics.
Immunocompromised individuals are disproportionately affected by severe coronavirus disease 2019, but immune compromise is heterogenous, and viral dynamics may vary by the degree of immunosuppression. In this study, we categorized ACTIV-2/A5401 participants based on the extent of immunocompromise into none, mild, moderate, and severe immunocompromise. Moderate/severe immunocompromise was associated with higher nasal viral load at enrollment (adjusted difference in means: 0.47 95% confidence interval, .12-.83 log10 copies/mL) and showed a trend toward higher cumulative nasal RNA levels and plasma viremia compared to nonimmunocompromised individuals. Immunosuppression leads to greater viral shedding and altered severe acute respiratory syndrome coronavirus 2 viral decay kinetics. Clinical Trials Registration. NCT04518410.


Predicting children's presurgical anxiety and subsequent behavior changes.
Addressed, in two studies, issues of children's medical anxiety having implications for efficient psychological preparation. Study 1 assessed behavioral distress and physiological arousal of 4- to 10-year-old, unprepared, nonsedated children (N = 50) as they separated from parents, waited in the operating room, and were given general anesthesia for minor surgery. Anxiety intensity varied widely among children and was most intense at mask presentation. Mother's prediction of uncooperative behavior and a history of prior surgery were the best predictors. Study 2 examined anxiety of 37 children prior to surgery and behavior changes 2 weeks later. At follow-up, minor or transient problems were common; 4 children developed significant problems. Elevated presurgical anxiety predicted later problems, but only among children hospitalized after surgery. Findings suggest that presurgical anxiety and later behavior problems are partially predictable.


Chemical characterization and bioactive properties of two aromatic plants: Calendula officinalis L. (flowers) and Mentha cervina L. (leaves).
The chemical composition and bioactive properties of two plants (Calendula officinalis L. and Mentha cervina L.) were studied. Their nutritional value revealed a high content of carbohydrates and low fat levels, and very similar energy values. However, they presented different profiles in phenolic compounds and fatty acids; C. officinalis presented mainly glycosylated flavonols and saturated fatty acids, while M. cervina presented mainly caffeoyl derivatives and polyunsaturated fatty acids. M. cervina showed the highest concentration of phenolic compounds while C. officinalis presented higher amounts of sugars, organic acids and tocopherols. The highest antioxidant and cytotoxic activities were obtained for the hydromethanolic extract of M. cervina, which presented the lowest values of EC50 and exhibited cytotoxicity against the four tumor cell lines tested. Infusions showed no cytotoxicity for the tumor cell lines, and none of the extracts showed toxicity against non-tumor cells. This study contributes to expand the knowledge on both natural sources and therefore their use.


Improving T-DNA Transfer to Tamarix hispida by Adding Chemical Compounds During Agrobacterium tumefaciens Culture.
Agrobacterium tumefaciens-mediated gene transfer is the most commonly used method for plant genetic engineering. However, during the period of A. tumefaciens culture, the effects of Agrobacterium culture before inoculation on genetic transformation are poorly understood. In the present study, we investigated the factors that affect the genetic transformation efficiency during Agrobacterium culture using Tamarix hispida as transgenic plant material. Agrobacterium treatment with spermidine (Spe), azacitidine (5-AzaC), dithiothreitol (DTT), or acetosyringone (AS) alone all significantly improved the efficiency of T-DNA transfer. Treatment with 5-AzaC reduced DNA methylation in Agrobacterium to induce the expression of virulence (vir) family genes, including virA, virB1, virC1, virD2, virD4 virE2, and virG. Spe treatment significantly induced the expression of all the studied genes, including virA, virB1, virC1, virD1, virD2, virD4, virE2, and virG. DTT treatment decreased reactive oxygen species accumulation. AS treatment activated the expression of the genes virA, virB1, virC1, virD1, virD2, virD4 and virG. All these effects resulted in increased T-DNA transfer. Additionally, combined Spe, 5-AzaC, DTT, and AS treatment improve Agrobacterium infection to a greater extent compared with their use alone, increasing T-DNA transfer by more than 8-fold relative to no treatment. Therefore, to improve genetic transformation, pretreatment of Agrobacterium during the culture period is important for improving genetic transformation efficiency.


Unusual weak magnetic exchange in two different structure types: YbPt2Sn and YbPt2In.
We present the structural, magnetic, thermodynamic and transport properties of the two new compounds YbPt(2)Sn and YbPt(2)In. X-ray powder diffraction shows that they crystallize in different structure types, the hexagonal ZrPt(2)Al and the cubic Heusler type, respectively. Despite quite different lattice types, both compounds present very similar magnetic properties: a stable trivalent Yb(3+), no evidence for a sizeable Kondo interaction and very weak exchange interactions with a strength below 1 K as deduced from specific heat C(T). Broad anomalies in C(T) suggest short range magnetic ordering at about 250 mK and 180 mK for YbPt(2)Sn and YbPt(2)In, respectively. The weak exchange and the low ordering temperature result in a large magnetocaloric effect as deduced from the magnetic field dependence of C(T), making these compounds interesting candidates for magnetic cooling. In addition we found in YbPt(2)In evidences for a charge density wave transition at about 290 K. The occurrence of such transitions within several RET2X compound series (RE = rare earth, T = noble metal, X = In, Sn) is analyzed.


[Endoscopic Dilation to Treat One Case of Severe Intestinal Stenosis Caused by Endometriosis].
A 46-year-old woman was admitted for repeated abdominal distention and constipation for more than 10 years and further deterioration for 5 years. Colonoscopy showed, in the sigmoid colon, nodular neoplasm protruding into the cavity, resulting in local intestinal stenosis, through which the endoscopy could not pass. Pathological findings of the biopsy sample revealed changes caused by intestinal endometriosis. The patient underwent multiple endoscopic dilatation treatments in our hospital and the interval between recurrences of intestinal stenosis was extended from 6 months to 4 years. Intestinal endometriosis can cause repeated intractable stenosis caused by the infiltration of ectopic glands in the intestinal wall, which usually requires surgical intervention. Herein, we report a case of severe intestinal stenosis caused by endometriosis in the sigmoid colon. Good results have been achieved through endoscopic dilatation treatment. This case suggests that endoscopic dilation has good application value in the treatment of this kind of disease, which needs further exploration and promotion.


A comparison between ultrasonography and laparoscopy in localising the impalpable undescended testis.
In 11 boys, 3 of whom had bilateral and 8 unilateral impalpable testes, ultrasonography was used to identify the location of the testes. The results of ultrasonography are compared with those of laparoscopy in the same patients. The testes were absent in two instances. The remaining 12 testes were accurately located by laparoscopy. Ultrasonography demonstrated the testes in only two cases.


Global analysis of Saccharomyces cerevisiae growth in mucin.
Metagenomic profiling of the human gut microbiome has discovered DNA from dietary yeasts like Saccharomyces cerevisiae. However, it is unknown if the S. cerevisiae detected by common metagenomic methods are from dead dietary sources, or from live S. cerevisiae colonizing the gut similar to their close relative Candida albicans. While S. cerevisiae can adapt to minimal oxygen and acidic environments, it has not been explored whether this yeast can metabolize mucin, the large, gel-forming, highly glycosylated proteins representing a major source of carbon in the gut mucosa. We reveal that S. cerevisiae can utilize mucin as their main carbon source, as well as perform both a transcriptome analysis and a chemogenomic screen to identify biological pathways required for this yeast to grow optimally in mucin. In total, 739 genes demonstrate significant differential expression in mucin culture, and deletion of 21 genes impact growth in mucin. Both screens suggest that mitochondrial function is required for proper growth in mucin, and through secondary assays we determine that mucin exposure induces mitogenesis and cellular respiration. We further show that deletion of an uncharacterized ORF, YCR095W-A, led to dysfunction in mitochondrial morphology and oxygen consumption in mucin. Finally, we demonstrate that Yps7, an aspartyl protease and homolog to mucin-degrading proteins in C. albicans, is important for growth on mucin. Collectively, our work serves as the initial step toward establishing how this common dietary fungus can survive in the mucus environment of the human gut.


Fludarabine phosphate in refractory hairy cell leukemia.
Our experience suggests a potential role of fludarabine phosphate in the management of hairy cell leukemia. On the basis of this experience, the activity of F-AMP needs to be further evaluated in this disease.


Combined culture and metagenomic analyses reveal significant shifts in the composition of the cutaneous microbiome in psoriasis.
The treatment of psoriasis has been revolutionized by the development of biologic therapies. However, the pathogenesis of psoriasis, in particular the role of the cutaneous microbiome, remains incompletely understood. Moreover, skin microbiome studies have relied heavily on 16S rRNA sequencing data in the absence of bacterial culture. To characterize and compare the cutaneous microbiome in 20 healthy controls and 23 patients with psoriasis using metagenomic analyses and to determine changes in the microbiome during treatment. Swabs from lesional and nonlesional skin from patients with psoriasis, and from controls matched for site and skin microenvironment, were analysed using both 16S rRNA sequencing and traditional culture combined with mass spectrometry (MALDI-TOF) in a prospective study. Psoriasis was associated with an increased abundance of Firmicutes and a corresponding reduction in Actinobacteria, most marked in lesional skin, and at least partially reversed during systemic treatment. Shifts in bacterial community composition in lesional sites were reflected in similar changes in culturable bacteria, although changes in the microbiota over repeated swabbing were detectable only with sequencing. The composition of the microbial communities varied by skin site and microenvironment. Prevotella and Staphylococcus were significantly associated with lesional skin, and Anaerococcus and Propionibacterium with nonlesional skin. There were no significant differences in the amount of bacteria cultured from the skin of healthy controls and patients with psoriasis. Shifts in the cutaneous microbiome in psoriasis, particularly during treatment, may shed new light on the pathogenesis of the disease and may be clinically exploited to predict treatment response. What's already known about this topic? Alterations in the composition of the cutaneous microbiome have been described in psoriasis, although methodological differences in study design prevent direct comparison of results. To date, most cutaneous microbiome studies have focused on 16S rRNA sequencing data, including both living and dead bacteria. What does this study add? This prospective observational study confirms that changes in the composition of the cutaneous microbiome, detected by 16S rRNA sequencing, are consistent with those identified by bacterial culture and mass spectrometry. The changes in the microbiome during antipsoriasis therapy should be further investigated to determine whether these represent potential novel biomarkers of treatment response. What is the translational message? Characterization of cutaneous microbiota may ultimately move into the clinic to help facilitate treatment selection, not only by optimizing currently available treatments, but also by identifying new therapeutic targets.


[Medical adverse effects of chemoprevention: the example of tamoxifen].
Tamoxifen, a synthetic antiestrogen widely used for the treatment of breast cancer, is also being proposed for the prevention of this cancer among women at high risk for the disease. Such an approach requires an objective and accurate evaluation, not only of the expected beneficial effects, but also of the potential iatrogenic side effects which could result from the administration of this drug to a population of healthy women. The present article summarizes our present knowledge which results from studies, all carried out on women with breast cancer: we review the side effects on the female genital apparatus, the ovarian and non ovarian endocrine side effects, the effects on cardio-vascular and thromboembolic risks, on bone metabolism and on ocular and hepatic side effects. The potential carcinogenic role is only briefly mentioned since it has already been the subject of a publication in this journal.


Characterizing blood glucose variability using new metrics with continuous glucose monitoring data.
Glycemic variability contributes to oxidative stress, which has been linked to the pathogenesis of the long-term complications of diabetes. Currently, the best metric for assessing glycemic variability is mean amplitude of glycemic excursion (MAGE); however, MAGE is not in routine clinical use. A glycemic variability metric in routine clinical use could potentially be an important measure of overall glucose control and a predictor of diabetes complication risk not detected by glycosylated hemoglobin (A1C) levels. This study aimed to develop and evaluate new automated metrics of glycemic variability that could be routinely applied to continuous glucose monitoring (CGM) data to assess and enhance glucose control. Individual 24 h CGM tracings from our clinical diabetes research database were scored for MAGE and two additional metrics designed to compensate for aspects of variability not captured by MAGE: (1) number of daily glucose fluctuations >75 mg/dl that leave the normal range (70-175 mg/dl), or excursion frequency, and (2) total daily fluctuation, or distance traveled. These scores were used to train machine learning algorithms to recognize excessive variability based on physician ratings of daily CGM charts, producing a third metric of glycemic variability: perceived variability. Finger stick A1C (average) and serum 1,5-anhydroglucitol (postprandial) levels were used as clinical markers of overall glucose control for comparison. Mean amplitude of glycemic excursion, excursion frequency, and distance traveled did not adequately quantify the glycemic variability visualized by physicians who evaluated the daily CGM plots. A naive Bayes classifier was developed that characterizes CGM tracings based on physician interpretations of tracings. Preliminary results suggest that the number of excessively variable days, as determined by this naive Bayes classifier, may be an effective way to automatically assess glycemic variability of CGM data. This metric more closely reflects 90-day changes in serum 1,5-anhydroglucitol levels than does MAGE. We have developed a new automated metric to assess overall glycemic variability in people with diabetes using CGM, which could easily be incorporated into commercially available CGM software. Additional work to validate and refine this metric is underway. Future studies are planned to correlate the metric with both urinary 8-iso-prostaglandin F2 alpha excretion and serum 1,5-anhydroglucitol levels to see how well it identifies patients with high glycemic variability and increased markers of oxidative stress to assess risk for long-term complications of diabetes.


Discovery process and pharmacological characterization of 2-(S)-(4-fluoro-2-methylphenyl)piperazine-1-carboxylic acid [1-(R)-(3,5-bis-trifluoromethylphenyl)ethyl]methylamide (vestipitant) as a potent, selective, and orally active NK1 receptor antagonist.
In an effort to discover novel druglike NK(1) receptor antagonists a new series of suitably substituted C-phenylpiperazine derivatives was identified by an appropriate chemical exploration of related N-phenylpiperazine analogues, with the specific aim to maximize their in vitro affinity and optimize in parallel their pharmacokinetic profile. Among the compounds synthesized, 2-(S)-(4-fluoro-2-methylphenyl)piperazine-1-carboxylic acid [1-(R)-(3,5-bis-trifluoromethylphenyl)ethyl]methylamide (vestipitant) was identified as one of the most in vitro potent and selective NK(1) receptor antagonists ever discovered, showing appropriate pharmacokinetic properties and in vivo activity. On the basis of its preclinical profile, this compound was selected as a drug candidate.


Seroprevalence of canine herpesvirus-1 in the Belgian dog population in 2000.
Canine herpesvirus-1 (CHV-1) is known to be associated with fertility and fecundity disorders as well as neonatal mortality in puppies of less than 3 weeks of age. The virus is presumed to be enzootic in dogs all over the world and recent studies in several European countries suggest a high seroprevalence among the dog population. In the year 2000, a total of 647 Belgian canine sera from 102 privately owned patients and 545 breeding dogs were analysed with an enzyme-linked immunosorbent assay (ELISA). Furthermore 77 of the samples were submitted to two serum neutralization (SN) tests for comparison. An overall CHV-1 seroprevalence of 45.75% was observed in the Belgian dog population. No significant differences could be observed based on breeding status, reason for consultation or sex. The correlation between the ELISA and both SN tests appeared to be moderate with a significantly greater sensitivity of the ELISA. This study also demonstrated that the CHV-1 seroprevalence in the Belgian dog population is similar to that in other recently investigated European countries and that the incidence in breeding units is not necessarily higher than in non-breeding dogs.


Effects of Moringa oleifera Leaf Extracts on Xanthomonas campestris pv. campestris.
Xanthomonas campestris pv. campestris (Xcc) is a Gram-negative bacterium belonging to the Xanthomonodaceae family, causing black rot in crucifers. To control this pathogen, the study investigated the effect of different leaves extracts of Moringa oleifera Lam., a tropical plant, well known for its food properties and with countless applications in many different fields, from nutraceutical (hypoglycemic) to the cosmetic (sunscreen) properties. Nevertheless, several studies pointed to its antibacterial action against both Gram-negative and Gram-positive bacteria. Many bioactive compounds, including flavonoids, phenolic acids, alkaloids, isothiocyanates, tannins and saponins, contained in these extracts, are responsible for its countless activities. The analyses carried out in this study show that the methanolic, hydroalcoholic and hydroalcoholic maltodextrin extracts have both bacteriostatic and bactericidal effects at concentrations of 0.5, 0.5 and 0.1 mg/mL respectively. In particular, the study shows how all extracts can alter membrane permeability, to adversely affect swarming motility, and to alter biofilm formation in Xcc. The in planta experiments showed a reduction of the necrosis area in the infected radishes, although the ability of the extracts to be absorbed by root systems is yet to be understood, in order to reach the target point.


Different ataxin-2 antibodies display different immunoreactive profiles.
We have developed a monoclonal antibody (4A7) directed against the C-terminus of the ataxin-2 protein that is involved in the polyglutamine neurodegenerative disorder spinocerebellar ataxia type 2. Comparison with other ataxin-2 antibodies showed that 4A7 specifically recognized ataxin-2. In contrast, a previously reported ataxin-2 antibody (15F6) did not appear to recognize full-length ataxin-2 in our systems. Immunocytochemical and subcellular fractionation studies using 4A7 confirmed previous reports that ataxin-2 is localized to both the cytoplasm and the trans-Golgi network in rat PC12 cells and rat brain tissue. In contrast, 4A7 failed to label the trans-Golgi network in the three primate cell lines examined. Cytoplasmic ataxin-2 was not associated with mitochondria, lysosomes, endoplasmic reticulum, peroxisomes, proteasomes, clathrin-coated pits or vesicles, or F-actin. Ataxin-2 was found to be phosphorylated but not glycosylated, and exhibited an estimated half-life of not less than 21 h. Interestingly, another commercially available ataxin-2 antibody did not detect ataxin-2 localized to the trans-Golgi network. This antibody was also found to immunoprecipitate fewer proteins/protein partners than 4A7. Although cross-reactivity of the 4A7 antibody with other protein(s) cannot be ruled out, it appears likely that the interaction of ataxin-2 with other cell components is dependent on both the host cell type and its subsequent subcellular localization.


Our experience with secondary reconstruction of external rotation in obstetrical brachial plexus palsy.
Restoration of shoulder external rotation is very important for upper extremity function. The purpose of this study was to present the authors' experience with secondary restoration of external rotation in patients with obstetrical brachial plexus palsy. From 1978 to 2002, 46 children underwent secondary surgery for restoration of external rotation. Outcomes were analyzed in relation to various factors, including the type of procedure, muscle transfer only versus nerve reconstruction and muscle transfer, denervation time, type of injury (Erb versus global palsy), and severity score. In addition, the effect of restoration of external rotation on the final outcome of shoulder abduction was assessed. There was significant improvement in every case (p < 0.01) between preoperatively and postoperatively. The overall mean postoperative Mallet score for the group undergoing muscle transfer only was 3.95, whereas in the nerve reconstruction and muscle transfer group, the score was 3.88 (p >0.05). The resulting gain in external rotation was 99 degrees versus 93.8 degrees. In both populations, a very significant improvement (p <0.0001) was identified in the final outcome of shoulder abduction (109 degrees after muscle transfer versus 48.3 degrees before muscle transfer, and 112 degrees postoperatively after neurotization and muscle transfer versus 43.8 degrees before any surgery). Patients with Erb palsy had a better but not significant result (p >0.05; p = 0.94), compared with those with global palsy in both Mallet score (3.77 versus 3.76) and final active external rotation (81.7 degrees versus 77.6 degrees). Secondary surgery for the restoration of external rotation is a rewarding procedure, which also significantly improves the final outcome of shoulder abduction.


Effects of revascularisation and contractile reserve on left ventricular remodelling in patients with impaired left ventricular function.
We sought to define the influence of revascularisation and contractile reserve on left ventricular (LV) remodelling in patients with LV dysfunction after myocardial infarction. Revascularisation of viable myocardium is associated with improved regional function, but the effect on remodelling is undefined. We studied 70 patients with coronary artery disease and LV dysfunction, 31 of whom underwent revascularisation. A standard dobutamine stress echocardiogram (DbE) was carried out. All patients underwent standard medical treatment; the decision to revascularise was made clinically, independent of this study. LV volumes and ejection fraction were measured by 3D echocardiography at baseline and after an average of 40 weeks. There was no significant difference in baseline ejection fraction or volumes between patients who underwent revascularisation and the remainder. Compared to medically treated patients, revascularised patients had significant improvements in ejection fraction and end-systolic volume in follow-up. The impact of baseline variables on remodelling was assessed by dividing patients into tertiles of LV ejection fraction and volumes. Revascularised patients in the lowest tertile of ejection fraction at baseline (<38%) had a significant improvement in end-systolic volume and ejection fraction, larger than obtained in medically treated patients with low ejection fraction. Revascularised patients with an ejection fraction >38% did not show significant improvement in volumes compared to baseline. Revascularised patients in the largest tertiles of end-systolic (>88 ml) or end-diastolic volume (>149 ml) at baseline had a significant improvement in end-systolic volume. Remodeling appears to occur independent of the presence of regional contractile reserve but does correlate with the volume response to low-dose dobutamine.


Chinese medicine Yu-Ping-Feng-San attenuates allergic inflammation by regulating epithelial derived pro-allergic cytokines.
This study aimed to investigate the mechanisms of Yu-Ping-Feng-San (YPFS) on attenuating allergic inflammation in the initial stage of atopic dermatitis (AD). AD mouse model was established with fluorescein isothiocyanate (FITC) sensitization and elicitation. Epithelial barrier structure was observed with transmission electron microscope. The populations of dendritic cells (DCs) and group 2 innate lymphoid cells (ILC2s) were detected by flow cytometry. Human immortalized keratinocyte (HaCaT) cells were stimulated with Poly(I:C)/TNF-α in vitro to assessthymic stromal lymphopoietin (TSLP), interleukin (IL)-33 and nuclear factor-κB (NF-κB) levels or expressions by immunofluorescence, enzyme linked immunosorbent assay (ELISA) and western blot. In the initial stage of AD, ear swelling and infiltration of inflammatory cells in ear tissues were markedly attenuated with YPFS treatments. The damaged structures of ear epithelium and the increased levels of Th2-cytokines induced by FITC were significantly rescued in YPFS-treated mice. The production of pro-allergic cytokines, TSLP and IL-33, as well as the cell populations of their target cells DCs and ILC2s were decreased in AD model, respectively. Likewise, the levels of TSLP and IL-33 in Poly(I:C)/TNF-α-stimulated HaCaT cells showed the same results. Lower levels of p-NF-κB were detected with YPFS treatment, and the expressions of TSLP and IL-33 could be further decreased with inhibiting of NF-κB. Therefore, YPFS attenuates allergic inflammation in the initial stage of AD probably through regulating NF-κB-TSLP/IL-33 pathway, which may provide a novel effective target for the prevention and treatment of allergic diseases.


Flavonoids Accumulation in Fruit Peel and Expression Profiling of Related Genes in Purple (Passiflora edulis f. edulis) and Yellow (Passiflora edulis f. flavicarpa) Passion Fruits.
Flavonoids play a key role as a secondary antioxidant defense system against different biotic and abiotic stresses, and also act as coloring compounds in various fruiting plants. In this study, fruit samples of purple (Passiflora edulis f. edulis) and yellow (Passiflora edulis f. flavicarpa) passion fruit were collected at five developmental stages (i.e., fruitlet, green, veraison, maturation, and ripening stage) from an orchard located at Nanping, Fujian, China. The contents of flavonoid, anthocyanin, proanthocyanin, and their metabolites were determined using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), activities of key enzymes involved in flavonoid metabolism were measured, and expression profiling of related genes was done using quantitative real-time PCR (qRT-PCR). The results revealed that total flavonoids, anthocyanins, and procyanidins were found to be increased in the fruit peel of both cultivars with fruit maturity. Total flavonoids, anthocyanins, procyanidins, flavonoid metabolites (i.e., rutin, luteolin, and quercetin), and anthocyanin metabolites (i.e., cyanidin-3-O-glucoside chloride, peonidin-3-O-glucoside, and pelargonidin-3-O-glucoside) were found abundant in the peel of purple passion fruit, as compared to yellow passion fruit. Principle component analysis showed that the enzymes, i.e., C4H, 4CL, UFGT, and GST were maybe involved in the regulation of flavonoids metabolism in the peel of passion fruit cultivars. Meanwhile, PePAL4, Pe4CL2,3, PeCHS2, and PeGST7 may play an important role in flavonoid metabolism in fruit peel of the passion fruit. This study provides new insights for future elucidation of key mechanisms regulating flavonoids biosynthesis in passion fruit.


Vitamin D3 and ceramide reduce the invasion of tumor cells through extracellular matrix components by elevating protein phosphatase-2A.
Increasing phosphorylation reactions by protein kinase A (PKA) or reducing dephosphorylation reactions of protein phosphatase-2A (PP-2A) increases the invasiveness of Lewis lung carcinoma (LLC) cells, as measured by their capacity to traverse extracellular matrix (ECM)-coated filters. Metastatic LLC-LN7 variants have reduced PP-2A activity when compared to nonmetastatic LLC-C8 variants. Immunoblotting showed that this reduced level of PP-2A activity was not due to reduced levels of the PP-2A catalytic (C) subunit. The cellular PP-2A activity could be stimulated by addition of C2-ceramide to LLC-LN7 lysates, or by incubating cells with either C2-ceramide or with a noncalcemic analog of vitamin D3, which has previously been shown to stimulate the release of ceramide. These treatments to elevate PP-2A activity in metastatic LLC-LN7 cells resulted in a decline in their capacity to invade through select (ECM) components, particularly through vitronectin and laminin. Underscoring the importance of PP-2A in limiting the invasiveness of tumor cells was the demonstration that LLC-LN7 cell transfectants overexpressing the PP-2A C alpha subunit were less invasive through ECM components than the wild-type cells. Invasion by these cells was further reduced by additionally increasing PP-2A activity by incubation with C2-ceramide or the vitamin D3 analog. These results suggest a role of a vitamin D3/ceramide/PP-2A pathway in limiting the invasiveness of tumor cells through select ECM components.


HIV-free survival and morbidity among formula-fed infants in a prevention of mother-to-child transmission of HIV program in rural Haiti.
Partners In Health (PIH) works with the Ministry of Health to provide comprehensive health services in Haiti. Between 1994 and 2009, PIH recommended exclusive formula feeding in the prevention of mother-to-child transmission (PMTCT) of HIV program and provided support to implement this strategy. We conducted this study to assess HIV-free survival and prevalence of diarrhea and malnutrition among infants in our PMTCT program in rural Haiti where exclusive formula feeding was supported. We reviewed medical charts of PMTCT mother-infant pairs at PIH between November 2004 and August 2006 through a retrospective longitudinal study and cross-sectional survey. We performed household surveys for each pair and at control households matched by infant's age and gender. 254 mother-infant pairs were included. 15.3% of infants were low birth weight; most births occurred at home (68.8%). 55.9% of households had no latrine; food insecurity was high (mean score of 18; scale 0-27, SD = 5.3). HIV-free survival at 18 months was 90.6%. Within the cohort, 9 children (3.5%) were HIV-infected and 17 (6.7%) died. Community controls were more likely to be breastfed (P = 0.003) and more likely to introduce food early (P = 0.003) than PMTCT-program households. There was no difference in moderate malnutrition (Z score ≤ 2 SD) between PMTCT and community groups after controlling for guardian's education, marital status, and food insecurity (OR = 1.05; 95% CI: 0.67, 1.64; P = 0.84). Diarrhea was 2.9 times more prevalent among community children than PMTCT infants (30.3% vs. 12.2%; P < 0.0001). In a PIH-supported program in rural Haiti that addressed socioeconomic barriers to ill-health, breast milk substitution was safe, acceptable and feasible for PMTCT for HIV-infected women choosing this option.


Interviewers' perceptions of persons-organization fit and organizational selection decisions.
A model of person-organization fit and organizational hiring decisions is developed and tested, using data from 38 interviewers making hiring decisions about 93 applicants. Results suggest that interviewers can assess applicant-organization values congruence with significant levels of accuracy and that interviewers compare their perceptions of applicants' values with their organizations' values to assess person-organization fit. Results also suggested that interviewers' subjective person-organization fit assessments have large effects on their hiring recommendations relative to competing applicant characteristics, and that interviewers' hiring recommendations directly affect organizations' hiring decisions (e.g., job offers).


Adrenal Insufficiency in Pediatric Eosinophilic Esophagitis Patients Treated with Swallowed Topical Steroids.
Swallowed topical steroids (STS) are the only effective pharmacological therapy for eosinophilic esophagitis (EoE). Thus far, studies of small populations of EoE patients have reported conflicting results in relation to adrenal insufficiency (AI). We sought to measure AI in a clinical setting in children taking STS for EoE. We performed a quality improvement study of pediatric EoE patients seen in a multidisciplinary clinic, who were treated with STS for at least 3 months. Two hundred twenty-five patients completed questionnaires to assess for signs of AI. All patients were requested to have fasting morning cortisol levels completed and if abnormal (<5 μg/dL or 139 nmol/L) twice, endocrinology consultation, and low-dose adrenocorticotropic hormone stimulation test were performed. A peak stimulated cortisol level of <18 μg/dL or 500 nmol/L was diagnostic of AI. Five of 106 STS-treated EoE patients who had morning cortisol levels drawn had AI. All 5 of these patients had asthma and were on additional topical steroid treatments. The number of steroid modalities and dose of steroid were not significant risk factors. Despite this low percentage, the life-threatening potential of AI warrants patient screening, as patients with iatrogenic AI are typically asymptomatic until an emergency triggers adrenal crisis. Further multicenter studies are needed to better define the risk attributable to STS alone, particularly in patients receiving combined steroid modalities.