Phonon dispersion in two-dimensional solids from atomic probability distributions.

We propose a harmonic linear response (HLR) method to calculate the phonon dispersion relations of two-dimensional layers from equilibrium simulations at finite temperatures. This HLR approach is based on the linear response of the system, as derived from the analysis of its centroid density in equilibrium path integral simulations. In the classical limit, this approach is closely related to those methods that study vibrational properties by the diagonalization of the covariance matrix of atomic fluctuations. The validity of the method is tested in the calculation of the phonon dispersion relations of a graphene monolayer, a graphene bilayer, and graphane. Anharmonic effects in the phonon dispersion relations of graphene are demonstrated by the calculation of the temperature dependence of the following observables: the kinetic energy of the carbon atoms, the vibrational frequency of the optical E2g mode, and the elastic moduli of the layer.

Communication: Critical behavior in graphene: Spinodal instability at room temperature.

At a critical spinodal in-plane stress τC, a planar crystalline graphene layer becomes mechanically unstable. We present a model of the critical behavior of the membrane area near τC and show that it is in complete agreement with path-integral simulations and with recent experiments based on interferometric profilometry and Raman spectroscopy. Close to the critical stress, τC, the in-plane strain behaves as τC-τ1/2 for τ < τC.

Randomised crossover trial showed that using breast milk or sucrose provided the same analgesic effect in preterm infants of at least 28 weeks.

AIM: Repeated, ongoing exposure to pain influences the growth, cognitive and motor functions, behaviour, personality and neurodevelopment of preterm infants. We compared the analgesic effects of expressed breast milk (EBM) and 24% oral sucrose on preterm neonates during venipuncture. METHODS: This multicentre randomised, noninferiority, crossover trial focused on five neonatal university units in Madrid, Spain, from October 2013 to October 2014. It comprised 66 preterm infants born at less than 37 weeks and randomly split into two groups. They received either EBM or sucrose two minutes before venepuncture, together with nonnutritive sucking and swaddling, then the opposite procedure at a later point. Pain was measured with the premature infant pain profile (PIPP) and crying was also measured. RESULTS: There were no statistically significant differences between the groups. The PIPP scores were seven (4-9) with breast milk and six (4-8.25) with sucrose (p = 0.28). The 11 infants born at under 28 weeks of age showed higher median scores of nine (9-14) for breast milk and four (4-7) for sucrose (p = 0.009). CONCLUSION: EBM and 24% sucrose had the same analgesic effect during venipuncture in most of the preterm neonates, but sucrose worked better in extremely preterm infants.

Percutaneous sclerotherapy of pediatric lymphatic malformations: experience and outcomes according to the agent used. / Tratamiento percutáneo de las malformaciones linfáticas en edad pediátrica: experiencia y resultados según el esclerosante empleado.

OBJECTIVE: Analyze statistically the success, number of sessions required and complete duration of treatment of agents used in pediatric percutaneous sclerotherapy of lymphatic malformations, to determine the most suitable. MATERIAL AND METHODS: Retrospective study based on outcomes from percutaneous sclerotherapy performed on lymphatic malformations of 56 patients conducted by pediatric interventional radiologist for 14 years. As first approach, the procedure consists of ultrasound-guided introduction of sclerosing agent. Sessions were repeated until clinical resolution. Success, number of sessions and the duration of treatment were recorded and statistical treatment of the data was performed to obtain further conclusions. RESULTS: Lost patients in follow up and other minority agents used were excluded from the data. Eventually, 52 patients treated with OK432 (n=29), Ethibloc (n=5) and combination therapy (n=18) were included. The average number of sessions and duration in months of treatment was respectively 2.38 and 8.6 for OK432, 1.4 and 5.6 for Ethibloc, and 1.83 and 2.30 for dual therapy. The results were statistically significant for the difference in duration between OK432 and dual therapy. Also, 60-80% of patients reached proper results related to success, but the difference was no significant among the agents. Other demographic and anatomical variables were analyzed, not showing any difference, which supports the homogeneity of the sample. CONCLUSIONS: Despite of no significant difference in success and number of sessions among agents, longer duration of treatment with OK432 than dual therapy could mean greater health costs and probably greater disturb for patient and family.

High order harmonic generation from SF6: Deconvolution of macroscopic effects.

We measure high order harmonics from the molecule SF6 over a large range of phase matching conditions and observe several features in the harmonics that are largely independent of such macroscopic conditions. The experimental data are then compared to the quantitative rescattering theory for the generation of harmonics from three orbitals. With this comparison, we are able to assign spectroscopic features in the harmonics to contributions from 1t1g (HOMO) and 5t1u (HOMO-1) orbitals.

Comparison of two different strategies of treatment with zoledronate in HIV-infected patients with low bone mineral density: single dose versus two doses in 2 years.

OBJECTIVES: Given the need for easily managed treatment of osteoporosis in HIV-infected patients, we evaluated the efficacy and tolerability of two doses of zoledronate, by comparing three groups of patients: those with annual administration, those with biennial administration (one dose in 2 years) and a control group with no administration of zoledronate. METHODS: We randomized (2:1) 31 patients on antiretroviral therapy with low bone mineral density (BMD) to zoledronate (5 mg administered intravenously; 21 patients) plus diet counselling and to a control group (diet counselling; 10 patients). At week 48, patients treated with zoledronate were randomized again to receive a second dose (two-dose group; n = 12) or to continue with diet counselling only (single-dose group; n = 9). Changes in lumbar spine and hip BMD and bone turnover markers were compared. RESULTS: The median percentage change from baseline to week 96 in L1-L4 BMD was -1.74% [interquartile range (IQR) -2.56, 3.60%], 7.90% (IQR 4.20, 16.57%) and 5.22% (IQR 2.02, 7.28%) in the control, two-dose and single-dose groups, respectively (P < 0.01, control vs. two doses; P = 0.02, control vs. single dose; P = 0.18, two doses vs. single dose). Hip BMD changed by a median of 2.12% (IQR -0.12, 3.08%), 5.16% (IQR 3.06, 6.74%) and 4.47% (IQR 1, 5.58%), respectively (P = 0.04, control vs. two doses; P = 0.34, two doses vs. single dose). No differences between the two-dose and single-dose groups were detected in bone markers at week 96. CONCLUSIONS: The benefits for BMD of a single dose of zoledronate in 2 years may be comparable to those obtained with two doses of the drug after 96 weeks, although this study is insufficiently powered to exclude a real difference. Future studies should explore whether biennial administration of zoledronate is a useful alternative in the treatment of osteoporosis in HIV-infected patients.

A chain-of-states acceleration method for the efficient location of minimum energy paths.

We describe a robust and efficient chain-of-states method for computing Minimum Energy Paths (MEPs) associated to barrier-crossing events in poly-atomic systems, which we call the acceleration method. The path is parametrized in terms of a continuous variable t ∈ [0, 1] that plays the role of time. In contrast to previous chain-of-states algorithms such as the nudged elastic band or string methods, where the positions of the states in the chain are taken as variational parameters in the search for the MEP, our strategy is to formulate the problem in terms of the second derivatives of the coordinates with respect to t, i.e., the state accelerations. We show this to result in a very simple and efficient method for determining the MEP. We describe the application of the method to a series of test cases, including two low-dimensional problems and the Stone-Wales transformation in C60.

Flexible probe for in vivo quantification of corneal epithelium permeability through non-invasive tetrapolar impedance measurements.

Studies concerning the functional status of the corneal epithelium are of special interest due to its key role in preventing ocular surface disease and corneal infections. In particular, quantitative measurements of the epithelium permeability translayer electrical resistance (TER) have been proven as a sensitive in vitro test for evaluation of the corneal barrier function. In a recent work from the authors (Guimera et al. Biosens. Bioelectron. 31:55-61, 2012), a novel method to non-invasively assess the corneal epithelial permeability by using tetrapolar impedance measurements, based on the same TER theoretical principles, was presented and validated using a rigid sensing device. In this work, the usability of this method has been dramatically improved by using SU-8 photoresist as a substrate material. The flexibility of this novel sensing device makes no need to apply pressure on the cornea to ensure the electrical contact between the electrodes and the corneal surface. The feasibility of this flexible sensor has been evaluated in vivo by increasing the permeability of rabbit corneal epithelium. For that, different concentrations of benzalkonium chloride (BAC) solution were instilled on different rabbit corneas. The obtained results have been compared with measurements of the permeability to sodium fluorescein of different excised corneas, a well-known method used to evaluate the corneal barrier function, to demonstrate the feasibility of this novel flexible sensor for quantifying the corneal epithelium permeability in vivo in a non-invasive way.

The phase diagram of ice: a quasi-harmonic study based on a flexible water model.

The phase diagram of ice is studied by a quasi-harmonic approximation. The free energy of all experimentally known ice phases has been calculated with the flexible q-TIP4P/F model of water. The only exception is the high pressure ice X, in which the presence of symmetric O-H-O bonds prevents its modeling with this empirical interatomic potential. The simplicity of our approach allows us to study ice phases at state points of the T-P plane that have been omitted in previous simulations using free energy methods based on thermodynamic integration. The effect in the phase diagram of averaging the proton disorder that appears in several ice phases has been studied. It is found particularly relevant for ice III, at least for cell sizes typically used in phase coexistence simulations. New insight into the capability of the employed water model to describe the coexistence of ice phases is presented. We find that the H-ordered ices IX and XIV, as well as the H-disordered ice XII, are particularly stable for this water model. This fact disagrees with experimental data. The unexpected large stability of ice IX is a property related to the TIP4P-character of the water model. Only after omission of these three stable ice phases, the calculated phase diagram becomes in reasonable qualitative agreement to the experimental one in the T-P region corresponding to ices Ih, II, III, V, and VI. The calculation of the phase diagram in the quantum and classical limits shows that the most important quantum effect is the stabilization of ice II due to its lower zero-point energy when compared to that one of ices Ih, III, and V.

Increased serum hepcidin levels in patients with porphyria cutanea tarda.

BACKGROUND: Increased iron stores- are common in porphyria cutanea tarda (PCT) patients, but the pathophysiological pathways remain unknown. Down-regulation of hepcidin, a peptide which regulates systemic iron homeostasis, has been demonstrated in different conditions associated with PCT, such as haemochromatosis, chronic hepatitis C (CHC) and excessive alcohol intake. However, serum hepcidin levels have not yet been studied in PCT patients. OBJECTIVE: To measure the serum hepcidin levels in patients with PCT, CHC and control patients, and to assess the association of hepcidin with serum markers of inflammation, iron overload and oxidative stress. METHODS: Hepcidin levels were measured by a competitive enzyme-linked immunosorbent assay in serum samples of patients presenting PCT (n = 30), CHC (n = 31) and healthy volunteers (n = 52). RESULTS: The mean of serum hepcidin levels was significantly higher in the PCT group (129.6 ng/mL) in comparison with the mean values in the CHC (41.3 ng/mL) and control (70.8 ng/mL) groups. The serum concentration of ferritin and interleukin-6 (IL-6) was also significantly higher in the PCT group, and correlated strongly with the hepcidin levels. The PCT patients with hepatitis C virus (HCV) infection showed significantly higher hepcidin levels than the group of CHC patients without porphyria. CONCLUSION: Serum hepcidin levels are increased in patients with PCT suggesting that the mechanisms regulating iron homeostasis in PCT differ from those involved in other related disorders, such as haemochromatosis, HCV infection or alcohol abuse.

Postharvest Anthracnose of Persimmon Fruit Caused by Colletotrichum gloeosporioides First Reported in Spain.

Commercial production area and yield of sweet persimmon (Diospyros kaki L.) in Spain has doubled in the last 10 years to more than 5,000 ha and 50,000 tons, respectively, mainly because of the high quality and consumer demand for the Valencian autochthonous cultivar 'Rojo Brillante' in European markets. In a recent survey of decay on 'Rojo Brillante' persimmons stored in commercial packinghouses, fruit were found with disease symptoms of firm brown to dark brown round spots scattered on the fruit cheeks. Isolation of the potential causal agent (isolate IVIA QCV-2) was performed by disinfecting the surface of symptomatic fruit with alcohol, aseptically cutting pieces of infected peel tissue, and then plating them onto potato dextrose agar (PDA). The fungus grew fast, covering the entire plate surface (9 mm diameter) after 7 to 10 days of incubation at 25°C with cottony grayish mycelium that darkened with time. Masses of salmon-colored conidia were apparent in the center of some colonies. Conidia were one-celled, hyaline, aseptate, ovoid to oblong with rounded or obtuse ends, and 11.5 to 15.5 × 3.0 to 6.5 µm (n = 50). The identification of Colletotrichum gloeosporioides (Penz.) Penz. & Sacc. [synonym: Vermicularia gloeosporioides Penz.; teleomorph: Glomerella cingulata (Stoneman) Spauld. & H. Schrenk] was performed at the Instituto Valenciano de Microbiología (IVAMI, Bétera, Valencia, Spain) by macro and micro morphological observations and confirmed with the amplification and subsequent sequencing of the ribosomal DNA regions 5.8S-ITS2-28S, using the primers ITS3 and ITS4 (4). A representative nucleotide sequence was deposited in GenBank (Accession No. KC113600) and a BLAST search showed 99% identity with the strain C1254.3 of C. gloeosporioides (JX010153) (3). To fulfill Koch's postulates, selected healthy 'Rojo Brillante' persimmons were surface sterilized by dipping them for 2 min in a 0.5% sodium hypochlorite aqueous solution and thoroughly rinsing with fresh water. Mycelial plugs (5-mm diameter) from the edge of 7-day old colonies of isolate IVIA QCV-2 grown on PDA at 25°C were aseptically transferred to skin wounds (one plug per fruit). Wounded but not inoculated fruit were used as controls. Persimmons were placed in three humid chambers that each contained four fruit and incubated at 20°C for up to 21 days. The experiment was repeated twice. While inoculated persimmons developed anthracnose disease in all cases and C. gloeosporioides was consistently reisolated from these fruit, no decay was observed on control fruit. To our knowledge, this is the first report of C. gloeosporioides causing postharvest persimmon fruit rot in Spain. Persimmon anthracnose caused by this pathogen is well known in Asian countries such as China and Korea (1). This disease was also reported in Brazil (2). References: (1) J. H. Lee et al. Plant Pathol. J. 20:247, 2004. (2) M. A. S. Mendes et al. Fungos em Plants no Brasil. Embrapa-SPI/Embrapa-Cenargen, Brasilia, Brazil, 1998. (3) B. S. Weir et al. Stud. Mycol. 73:115, 2012. (4) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. Academic Press Inc., San Diego, CA, 1990.

First Report of Diplodia seriata Causing Loquat Fruit Rot in Spain.

Spain is the second largest loquat (Eriobotrya japonica Lindl.) producer in the world, with about 40,000 t per year. 'Algerie' is the main cultivar planted in Alicante province (SE of Spain; Lat. 38.40° N, Long. 0.08° W), where more than 80% of Spanish commercial loquat plantations are located. In a survey of fruit losses at harvest, irregular brownish superficial dry spots (5 to 15 mm) located mainly near the stem end were observed on fruits from different orchards. After incubation at 20°C for 14 days, the spots on fruit expanded rapidly and turned to dark brown or black, producing black, unilocular, ostiolate, and thick-walled pycnidia. Isolation was performed by disinfecting the surface of symptomatic fruits with alcohol and aseptically cutting pieces of infected peel tissue and plating them in potato dextrose agar (PDA) dishes. The potential causal agent (isolate IVIA GCA-5) was identified in the Spanish Type Culture Collection (CECT, University of Valencia, Valencia, Spain). The fungus grew rapidly on both PDA and malt extract agar (MEA) at 26°C, covering the entire plate surface with dark gray mycelium within 4 days. The plate reverse was dark gray to black. The conidia were brown and aseptate, with the apex broadly rounded and the base rounded or truncate, and 23 × 11 µm (n = 50). The identification of Diplodia seriata De Not. was molecularly confirmed with the amplification with the primers ITS1 and ITS4 and subsequent sequencing of the internal transcribed spacer ITS1-5.8S-ITS2 region of the rDNA extracted from the isolate IVIA GCA-5 (GenBank Accession No. JX987099). Furthermore, the region D1/D2 in the 5' end of the 28S rDNA gene was amplified with the primers NL1 and NL4 and sequenced (JX997743). A nucleotide BLAST analysis showed in both cases 100% identity with D. seriata [EF127892 (3) and AY928050, respectively]. To fulfill Koch's postulates, 5-mm diameter mycelial plugs from 7-day-old colonies of isolate IVIA GCA-5 grown on PDA at 25°C were aseptically transferred to skin wounds on superficially disinfected 'Algerie' loquats (one plug per fruit; n = 9). Wounded but not inoculated fruit were used as controls. The experiment was repeated three times. Inoculated fruit developed lesions of 18 to 100 mm after 7 to 21 days of incubation at 20°C. No lesion was observed on controls. The fungus was consistently reisolated from inoculated fruit. D. seriata is a broadly spread pathogen causing cankers, blight, dieback, and fruit rots in vines and many fruit trees. In Spain, it has been reported to cause fruit rot of olive (1) and branch dieback in olive (2) and grapevine (4). To our knowledge, this is the first report worldwide of D. seriata causing loquat fruit rot. References: (1) J. Moral et al. Plant Dis. 92:311, 2008. (2) J. Moral et al. Phytopathology 100:1340, 2010. (3) A. J. L. Phillips et al. Fungal Divers. 25:141, 2007. (4) J. R. Úrbez-Torres et al. Plant Dis. 90:835, 2006.

First Report of Alternaria alternata Causing Postharvest Black Spot of Fresh Date Palm Fruit in Spain.

Commercial production of date palm fruit (Phoenix dactylifera L.) for fresh consumption has increased in the grove of Elx (Alacant Province, southeast Spain) after the successful development of tissue culture technologies and induced ripening and cold storage protocols. In a survey of losses after harvest, disease symptoms consisting of superficial, small, and firm black spots irregularly distributed throughout the fruit skin were observed in commercially handled and cold-stored fruit. At room temperature, superficial lesions expanded and produced dark mycelium. The potential causal agent was transferred to potato dextrose agar (PDA), incubated at 25°C in darkness, and subcultured on PDA. The identification was performed at the Spanish Type Culture Collection (CECT, University of Valencia, Spain) using colony morphology on PDA and malt extract agar at 26 or 37°C. At 26°C, the fungus rapidly produced cottony white mycelium that turned olivaceous and dark brown to black. Conidiophores were simple, straight or bent, with plain walls. Conidia were brown, obpyriform to ellipsoid (average 22 to 39 × 8 to 15 µm; n = 50), with both transversal and longitudinal septa, often observed in branched chains with more than 5 conidia. Growth occurred at 37°C. The identification of Alternaria alternata (Fr.:Fr.) Keissler was confirmed by the amplification and subsequent sequencing with the primers NL1 and NL4 of the region D1/D2 in the 5' end of the 28S rRNA gene of the isolate IVIA DAA-4 (GenBank Accession No. JX987100). A BLAST search showed 100% identity with A. alternata strain DAOM 216376 (JN938894). Selected healthy 'Medjool' dates were surface disinfected by dipping them for 2 min in a 0.5% sodium hypochlorite solution and thoroughly rinsed with fresh water. To fulfill Koch's postulates, 20 µl of a spore suspension at 1 × 105 spores per ml prepared from 7-day-old colonies grown on PDA were placed in fresh skin wounds made in disinfected fruit using a sterile stainless steel rod with a probe tip 1 mm wide and 2 mm in length (one wound per fruit; three humid chambers with nine fruits each). Wounded but not inoculated fruit were used as controls (one humid chamber with nine fruit). While disease symptoms were observed on all fruit inoculated with A. alternata (average black spots of 3, 6, and 12 mm after 4, 7, and 10 days of incubation at 20°C), no decay was observed on any of the control fruit. Reisolation of the fungus was performed from 10 infected dates and it was positive in all cases. A. alternata has been reported to cause date palm fruit disease in Israel (1) and Egypt (2), whereas Alternaria spp. have been cited in California (3) and Iran (4). To our knowledge, this is the first report of A. alternata causing date palm fruit rot in Spain. References: (1) R. Barkai-Golan et al. Hassadeh 69:1446, 1989. (2) H. M. El-Deeb et al. Acta Hort. 736:421, 2007. (3) H. S. Fawcett and L. J. Klotz. University of California Bulletin 522, 1932. (4) F. Karampourland and H. Pejman. Acta Hort. 736:431, 2007.

First Report of Penicillium expansum Causing Postharvest Blue Mold of Fresh Date Palm Fruit (Phoenix dactylifera) in Spain.

A survey of postharvest losses of commercially handled and cold-stored fruit of fresh date palm (Phoenix dactylifera L.), cvs. Medjool and Hayani, was conducted in the 2009 and 2010 seasons in the grove of Elx (Alacant Province, Southeast Spain). Disease symptoms consisting of circular, light brown, soft spots located in any part of the fruit skin were observed in 2 to 5% of the fruit. At room temperature, the lesions expanded rapidly and blue mold symptoms were apparent. The potential causal agent (isolate IVIA NiAA-2) was transferred to PDA and incubated at 25°C. The identification was performed at the Spanish Type Culture Collection (CECT, University of Valencia, Spain) based on colony morphology of the isolate grown on Czapeck yeast extract agar (CYA) and malt extract agar (MEA) at 26°C. Colonies were circular (average diameter of 40 mm at 7 days), radially sulcate, with dense velvety white mycelium, and very abundant, bluish green conidia. The underside of the plates showed light brown and pale green colonies on CYA and MEA, respectively. On CYA, but not on MEA, a light yellow exudate was produced and a brownish pigment diffused into the medium. At 5 and 37°C on CYA, white microcolonies and no colonies were observed, respectively. Conidia were ellipsoidal to subglobose, smooth and thin walled, measuring 3.0 to 3.5 × 2.5 to 3.0 µm (n = 50) (4). Based on these morphological characteristics, the isolate IVIA NiAA-2 was tentatively identified as Penicillium expansum L. To confirm the identity, we amplified and sequenced the rDNA internal transcribed spacer (ITS) region with primers ITS1 and ITS4 (GenBank Accession No. KC169942). A BLAST search showed 99% identity and 100% query coverage with P. expansum strain NRRL 6069 (DQ339562) (2). Selected healthy dates cv. Medjool were surface disinfected by dipping in 0.5% sodium hypochlorite for 2 min followed by thorough rinsing in deionized water. Pathogenicity was tested by pipetting 20 µl of a spore suspension (1 × 106 spores per ml), prepared from 7-day PDA cultures, onto fresh skin wounds, which were made on disinfected fruit using a sterile, stainless steel rod with a probe tip 1 mm in width × 2 mm in length (one wound on each of nine dates, incubated in one humid chamber). Disinfected, wounded, and non-inoculated dates were used as controls. The procedure was repeated three times. Disease symptoms were observed on all inoculated fruit (average lesion size of 6, 15, and 22 mm after 4, 7, and 10 days of incubation at 20°C, respectively) and P. expansum was consistently reisolated, thereby fulfilling Koch's postulates. No decay was observed on any of the non-inoculated fruit. Unidentified species of Penicillium have been reported to cause date palm fruit rot (1,3). To our knowledge, this is the first report of P. expansum causing postharvest decay of date palm fruit in Spain. References: (1) M. Djerbi. Diseases of the Date Palm. FAO Regional Project, Rome, 1983. (2) M. A. Dombrink-Kurtzman. Antonie Van Leeuwenhoek 91:179, 2007. (3) S. Ibrahim and M. A. Rahma. Bayero J. Pure Appl. Sci. 2:127, 2009. (4) R. A. Samson et al. Introduction to Food-Borne Fungi. Centraalbureau voor Schimmelcultures, Baarn, the Netherlands, 1995.

New developments in erythropoietic porphyrias.

In recent years, important advances have been made in our understanding of the genetics of porphyrias, particularly with respect to erythropoietic protoporphyria (EPP) and congenital erythropoietic porphyria (CEP), 2 forms of erythropoietic porphyria no longer considered to be monogenic. The identification of mutations in genes not previously associated with these disorders as causative factors or modulators of severity has helped to explain the presence of genotypic and phenotypic differences between patients carrying the same mutations. These advances have also led to the identification of causative genetic defects in patients who, based on molecular studies, had no mutations in the uroporphyrinogen III synthase gene UROS (in CEP) or in the ferrochelatase gene FECH (in EPP). Better understanding and characterization of the genetics of porphyrias will allow us to determine genotypic and phenotypic correlations and improve the molecular classification of these diseases, which will have both practical and prognostic implications.

Hedgehog signaling and osteoblast gene expression are regulated by purmorphamine in human mesenchymal stem cells.

Several biological events are controlled by Hedgehog (Hh) signaling, including osteoblast phenotype development. This study aimed at evaluating the gene expression profile of human mesenchymal stem cells (hMSCs) treated with the Hh agonist, purmorphamine, focusing on Hh signaling and osteoblast differentiation. hMSCs from bone marrow were cultured in non-osteogenic medium with or without purmorphamine (2 µM) for periods of up to 14 days. Purmorphamine up-regulated gene expression of the mediators of Hh pathway, SMO, PTCH1, GLI1, and GLI2. The activation of Hh pathway by purmorphamine increased the expression of several genes (e.g., RUNX2 and BMPs) related to osteogenesis. Our results indicated that purmorphamine triggers Hh signaling pathway in hMSCs, inducing an increase in the expression of a set of genes involved in the osteoblast differentiation program. Thus, we conclude that Hh is a crucial pathway in the commitment of undifferentiated cells to the osteoblast lineage.

Anomalous nuclear quantum effects in ice.

One striking anomaly of water ice has been largely neglected and never explained. Replacing hydrogen (1H) by deuterium (2H) causes ice to expand, whereas the normal isotope effect is volume contraction with increased mass. Furthermore, the anomaly increases with temperature T, even though a normal isotope shift should decrease with T and vanish when T is high enough to use classical nuclear motions. In this study, we show that these effects are very well described by ab initio density-functional theory. Our theoretical modeling explains these anomalies, and allows us to predict and to experimentally confirm a counter effect, namely, that replacement of 16O by 18O causes a normal lattice contraction.

Does osteomyelitis in the feet of patients with diabetes really recur after surgical treatment? Natural history of a surgical series.

AIMS/HYPOTHESIS: The aim of this study was to determine the rate of recurrence, reulceration and new episodes of osteomyelitis and the duration of postoperative antibiotic treatment in a prospective cohort of patients with diabetes who underwent conservative surgery for osteomyelitis. METHODS: The prospective cohort included patients with diabetes and a definitive diagnosis of osteomyelitis who were admitted to the Diabetic Foot Unit (Surgery Department, La Paloma Hospital, Las Palmas de Gran Canaria, Spain) and underwent surgical treatment from 1 November 2007 to 30 May 2010. RESULTS: Eighty-one patients were operated on for osteomyelitis during the study period. Seven patients were lost to follow-up at different stages of the study. The median duration of follow-up was 101.8 weeks (quartile 1 = 56.6, quartile 3 = 126.7). Forty-eight patients (59.3%) underwent conservative surgery, 32 (39.5%) had minor amputations and there was one (1.2%) major amputation. Twenty patients (24.7%) required reoperation because of persistent infection. Postoperative antibiotic treatment over a median period of 36 days was provided. Wound healing was achieved by secondary intention for a median of 8 weeks. Sixty-five patients were available for follow-up after healing. The percentage of recurrence, reulceration, and new episodes of osteomyelitis was 4.6% (3/65), 43% (28/65) and 16.9% (11/65), respectively. Mortality during follow-up (excluding in-hospital deaths and patients lost to follow-up) was 13% (9/69). CONCLUSION: A low rate of recurrence of osteomyelitis after surgical treatment for osteomyelitis was achieved. Despite new episodes, our approach to managing this cohort of patients with diabetes and foot osteomyelitis achieved 98.8% limb salvage.

The phase diagram of ice Ih, II, and III: a quasi-harmonic study.

The phase diagram of ice Ih, II, and III is studied by a quasi-harmonic approximation. The results of this approach are compared to phase diagrams previously derived by thermodynamic integration using path integral and classical simulations, as well as to experimental data. The studied models are based on both flexible (q-TIP4P/F) and rigid (TIP4P/2005, TIP4PQ/2005) descriptions of the water molecule. Many aspects of the simulated phase diagrams are reasonably reproduced by the quasi-harmonic approximation. Advantages of this simple approach are that it is free from the statistical errors inherent to computer simulations, both classical and quantum limits are easily accessible, and the error of the approximation is expected to decrease in the zero temperature limit. We find that the calculated phase diagram of ice Ih, II, and III depends strongly on the hydrogen disorder of ice III, at least for cell sizes typically used in phase coexistence simulations. Either ice II (in the classical limit) or ice III (in the quantum one) may become unstable depending upon the proton disorder in ice III. The comparison of quantum and classical limits shows that the stabilization of ice II is the most important quantum effect in the phase diagram. The lower vibrational zero-point energy of ice II, compared to either ice Ih or III, is the microscopic origin of this stabilization. The necessity of performing an average of the lattice energy over the proton disorder of ice III is discussed.

Quasi-harmonic approximation of thermodynamic properties of ice Ih, II, and III.

Several thermodynamic properties of ice Ih, II, and III are studied by a quasi-harmonic approximation and compared to results of quantum path integral and classical simulations. This approximation allows to obtain thermodynamic information at a fraction of the computational cost of standard simulation methods, and at the same time permits studying quantum effects related to zero-point vibrations of the atoms. Specifically, we have studied the crystal volume, bulk modulus, kinetic energy, enthalpy, and heat capacity of the three ice phases as a function of temperature and pressure. The flexible q-TIP4P/F model of water was employed for this study, although the results concerning the capability of the quasi-harmonic approximation are expected to be valid independently of the employed water model. The quasi-harmonic approximation reproduces with reasonable accuracy the results of quantum and classical simulations showing an improved agreement at low temperatures (T< 100 K). This agreement does not deteriorate as a function of pressure as long as it is not too close to the limit of mechanical stability of the ice phases.