Potential models for the simulation of methane adsorption on graphene: development and CCSD(T) benchmarks.

Different force fields for the graphene-CH4 system are proposed including pseudo-atom and full atomistic models. Furthermore, different charge schemes are tested to evaluate the electrostatic interaction for the CH4 dimer. The interaction parameters are optimized by fitting to interaction energies at the DFT level, which were themselves benchmarked against CCSD(T) calculations. The potentials obtained with both the pseudo-atom and full atomistic approaches describe accurately enough the average interaction in the methane dimer as well as in the graphene-methane system. Moreover, the atom-atom potentials also correctly provide the energies associated with different orientations of the molecules. In the atomistic models, charge schemes including small charges allow for the adequate representation of the stability sequence of significant conformations of the methane dimer. Additionally, an intermediate charge of -0.63e on the carbon atom in methane leads to bond energies with errors of ca. 0.07 kcal mol-1 with respect to the CCSD(T) values for the methane dimer. For the graphene-methane interaction, the atom-atom potential model predicts an average interaction energy of 2.89 kcal mol-1, comparable to the experimental interaction energy of 3.00 kcal mol-1. Finally, the presented force fields were used to obtain self-diffusion coefficients that were checked against the experimental value found in the literature. The no-charge and Hirshfeld charge atom-atom models perform extremely well in this respect, while the cheapest potential considered, a pseudo-atom model without charges, still performs reasonably well.

Adsorption of Hydrogen Molecules on Carbon Nanotubes Using Quantum Chemistry and Molecular Dynamics.

Physisorption and storage of molecular hydrogen on single-walled carbon nanotube (SWCNT) of various diameters and chiralities are studied by means of classical molecular dynamics (MD) simulations and a force field validated using DFT-D2 and CCSD(T) calculations. A nonrigid carbon nanotube model is implemented with stretching (C-C) and valence angle potentials (C-C-C) formulated as Morse and Harmonic cosine potentials, respectively. Our results evidence that the standard Lennard-Jones potential fails to describe the H2-H2 binding energies. Therefore, our simulations make use of a potential that contains two-body term with parameters obtained from fitting CCSD(T)/CBS binding energies. From our MD simulations, we have analyzed the interaction energies, radial distribution functions, gravimetric densities (% wt), and the distances of the adsorbed H2 layers to the three zigzag type of nanotubes (5,0), (10,0), and (15,0) at 100 and 300 K.

Energy transfer upon collision of selectively excited CO2 molecules: State-to-state cross sections and probabilities for modeling of atmospheres and gaseous flows.

Carbon dioxide molecules can store and release tens of kcal/mol upon collisions, and such an energy transfer strongly influences the energy disposal and the chemical processes in gases under the extreme conditions typical of plasmas and hypersonic flows. Moreover, the energy transfer involving CO2 characterizes the global dynamics of the Earth-atmosphere system and the energy balance of other planetary atmospheres. Contemporary developments in kinetic modeling of gaseous mixtures are connected to progress in the description of the energy transfer, and, in particular, the attempts to include non-equilibrium effects require to consider state-specific energy exchanges. A systematic study of the state-to-state vibrational energy transfer in CO2 + CO2 collisions is the focus of the present work, aided by a theoretical and computational tool based on quasiclassical trajectory simulations and an accurate full-dimension model of the intermolecular interactions. In this model, the accuracy of the description of the intermolecular forces (that determine the probability of energy transfer in molecular collisions) is enhanced by explicit account of the specific effects of the distortion of the CO2 structure due to vibrations. Results show that these effects are important for the energy transfer probabilities. Moreover, the role of rotational and vibrational degrees of freedom is found to be dominant in the energy exchange, while the average contribution of translations, under the temperature and energy conditions considered, is negligible. Remarkable is the fact that the intramolecular energy transfer only involves stretching and bending, unless one of the colliding molecules has an initial symmetric stretching quantum number greater than a threshold value estimated to be equal to 7.

Functional imaging in neuroendocrine tumors: assessment of molecular heterogeneity using [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT.

OBJECTIVE: The aim of the study was evaluate the diagnostic performance of [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT in patients with histologically proven neuroendocrine tumors (NETs), as well as the correlation of the visualized findings with the tumor grade. MATERIAL AND METHODS: We included 50 patients with NETs who underwent both [68Ga]Ga-DOTA-TOC and [18F]FDG PET/TC. The pooled sensitivity of both scans was compared, as well as [68Ga]Ga-DOTA-TOC and [18F]FDG for each tumor grade (grade 1/G1, grade 2/G2 and grade 3/G3). Also, the sensitivity of [68Ga]Ga-DOTA-TOC and [18F]FDG as a function of the continuous variable Ki-67 was investigated. Finally, the number of lesions detected by both PET radiopharmaceuticals for each tumor grade was compared. RESULTS: The pooled sensitivity of both PET/CT (96%) was higher than [68Ga]Ga-DOTA-TOC (84%) and [18F]FDG (44%) separately, with statistically significant differences. The sensitivity of [68Ga]Ga-DOTA-TOC was higher than [18F]FDG in both G1 (p = 0.004) and G2 (p < 0.001). In G3 the performance of both scans detected disease in 100% of this subgroup. The sensitivity of [68Ga]Ga-DOTA-TOC and [18F]FDG PET/CT correlated significantly with the Ki-67 proliferative index. In G2 patients the number of lesions detected with [68Ga]Ga-DOTA-TOC was higher than [18F]FDG. CONCLUSIONS: The performance of both PET/CT, particularly in G2 and G3, demonstrates the molecular heterogeneity of metastatic NETs and contributes to the selection of a more appropriate treatment, particularly in those high-grade patients who may benefit from radionuclide therapy (PRRT).

Efficient gene expression from integration-deficient lentiviral vectors in the spinal cord.

Gene transfer to spinal cord cells may be crucial for therapy in spinal muscular atrophy, amyotrophic lateral sclerosis and spinal cord injury. Lentiviral vectors are efficient for transduction of a variety of cells, but like all integrating vectors they pose a risk of insertional mutagenesis. Integration-deficient lentiviral vectors (IDLVs) remain episomal but retain the transduction efficiency of standard integrating lentiviral vectors, particularly when the episomes are not diluted out through repeated cell division. We have now applied IDLVs for transduction of spinal cord in vitro, in explants and in vivo. Our results demonstrate similar efficiency of eGFP expression from integrating lentiviral vectors and IDLVs in most cell types analyzed, including motor neurons, interneurons, dorsal root ganglia (DRG) neurons and astroglia. IDLV-mediated expression of pro-glial-cell-derived neurotrophic factor (Gdnf) rescues motor neuron cultures from death caused by removal of exogenous trophic support. IDLVs also mediate efficient RNA interference in DRG neuron cultures. After intraparenchymal injection in the rat and mouse cervical and lumbar regions in vivo, transduction is mainly neuronal, with both motor neurons and interneurons being efficiently targeted. These results suggest that IDLVs could be efficient and safer tools for spinal cord transduction in future therapeutic strategies.

Effect of lithium in pyramidal neurons of Cornu Ammonis in an animal model.

Bipolar disorder has been associated with a decrease in hippocampal size, and lithium appears to reverse this neuroanatomical abnormality. The objective of this work was to evaluate, at a cellular level, the size of both cell body and nucleus of pyramidal neurons located throughout the Cornu Ammonis (CA1 to CA4 regions). To perform this duty, we used 16 rats that were randomized into two groups: control and dietary lithium-treated. After one month, they were sacrificed and their brains removed for histopathological analysis. Serial photos of the entire Cornu Ammonis were taken and, after dividing them into 4 regions of interest, we measured the cell body and nucleus on each pyramidal neuron belonging to the first 5 photos of each region of interest. As a result of this histological analysis, cell body area and nuclear area were significantly larger in the experimental group in a specific area of the Cornu Ammonis that could correspond to CA2 or the transition between CA1 and CA2. These results suggest that the effect of lithium is not homogeneous throughout the hippocampus and allows directing future studies to a specific area of this structure.

Role of systemic inflammatory factors in gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT): From biology to theragnosis.

AIM: Systemic inflammatory factors have been validated as indicators of ongoing systemic inflammation that could be predictive markers of poor prognosis for oncological outcomes. However, the prognostic impact of systemic inflammation markers is unknown in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) treated with peptide receptor radionuclide therapy (PRRT). METHODS: We conducted an observational, retrospective, multicentric study of 40 patients with GEP or unknown origin NETs treated with PRRT between 2016 and 2020. The systemic inflammatory markers were calculated as follows: neutrophil to lymphocyte ratio (NLR)=neutrophil count/lymphocyte count, monocyte to lymphocyte ratio (MLR)=monocyte count/lymphocyte count, platelet to lymphocyte ratio (PLR)=platelet count/lymphocyte count, albumin to lymphocyte ratio (ALR)=albumin levels/lymphocyte count and derived Neutrophil to Lymphocyte ratio (dNLR)=neutrophil count/(leucocytes count - neutrophils count). Baseline analysis and after the second dose were used for the calculation of different ratios. RESULTS: The median age was 63 years (range 41-85), 55% were male. The baseline cut-off values for NLR were 2.61, for MLR 0.31, for PLR 110.14, for ALR 2.39 and for dNLR 1.71. The cut-off values after the 2° dose were, for NLR 2.3, for MLR 0.3, for PLR 131.61, ALR 4.16, and dNLR 1.48. Median progression-free survival (PFS) was 21.7 months (95% CI 10.7-32.8 months) and overall survival (OS) was 32.1 months (95% CI 19.6-44.7 months), PFS was shorter in patients with elevated NLR (p=0.001), ALR (0.03), and dNLR (p=0.001) in baseline analysis. DCR was 81% and ORR 18%. CONCLUSIONS: In GEP or unknown origin NETs treated with PRRT, we have identified the predictive and prognostic impact of baseline systemic inflammatory factors.

Oligodeoxynucleotide IMT504: lack of effect on immune parameters during islet regeneration in single dose streptozotocin-induced diabetes.

BACKGROUND: We have shown that oligodeoxynucleotide IMT504 improved blood glucose and islet beta-cell content in streptozotocin (STZ)-induced diabetic rats, inducing early expression of progenitor markers. Here we determined the effect of IMT504 on islet infiltration and on immunomodulatory proteins indoleamine 2,3-dioxygenase (IDO) and TNF-α-stimulated gene/protein 6 (TSG-6) in islets of STZ-diabetic rats, at the time of progenitor markers expression. METHODS: Male rats were i.p. injected with STZ [60 mg/kg body weight (BW)] or citrate buffer (control) (day 1). Starting on day 4, STZ animals were daily treated with saline (STZ-saline) or IMT504 (20 mg/kg BW/day s.c., STZ-IMT504) and killed after two consecutive decreases in blood glucose. Islet area and insulin expression, CD3 (T lymphocytes), CD68 (macrophages), IDO and TSG-6 immunostainings were determined. Islet infiltration was also evaluated by haematoxylin staining. RESULTS: STZ-induced diabetes in rats, with an important decrease in islet area was reversed by IMT504. Diabetes development did not involve islet infiltration, determined by haematoxylin and by the absence of significant T lymphocyte and macrophage presence. IMT504 did not induce changes in these parameters. IDO was not expressed in controls; the percentages of IDO-positive islets were very low and similar in STZ-saline and STZ-IMT504. Scarce TSG-6 was expressed in all groups, without significant differences. CONCLUSIONS: IMT504 improved insulin content but did not alter IDO or TSG-6 staining in islets of STZ-diabetic rats, suggesting that they do not participate in the IMT504-induced repair process. IMT504 did not per se modify leukocyte presence in islets of diabetic rats.

Ion size influence on the Ar solvation shells of M(+)-C6F6 clusters (M = Na, K, Rb, Cs).

The size-specific influence of alkali metal ions in the gradual transition from cluster rearrangement to solvation dynamics is investigated by means of molecular dynamics simulations for alkali metal cation-hexafluorobenzene systems, M(+)-C(6)F(6) (M = Na, K, Rb and Cs), surrounded by Ar atoms. To analyze such transition, different small aggregates of the M(+)-C(6)F(6)-Ar(n) (n = 1, ..., 30) type and M(+)-C(6)F(6) clusters solvated by about 500 Ar atoms are considered. The Ar-C(6)F(6) interaction contribution has been described using two different formalisms, based on the interaction decomposition in atom-bond and in atom-effective atom terms, which have been applied to study the small aggregates and to investigate the Ar solvated M(+)-C(6)F(6) clusters, respectively. The selectivity of the promoted phenomena from the M(+) ion size and their dependence from the number of Ar atoms is characterized.

Impact of risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy of space-occupying lesions.

INTRODUCTION: Ultrasound-guided percutaneous liver biopsy is considered the technique of choice for the histological diagnosis of space-occupying lesions, given its high level of safety and diagnostic performance. However, since it is an invasive diagnostic procedure, complications can occur. Various clinical and radiological parameters have been analysed as factors related with the efficacy of the technique or with its complications; however, the results have been contradictory. Thus, we aimed to evaluate the impact of various risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy in the diagnosis of space-occupying lesions in ordinary clinical practice. MATERIAL AND METHODS: This retrospective observational study included all patients who underwent real-time ultrasound-guided percutaneous biopsies of space-occupying liver lesions with the free-hand technique between December 2012 and February 2018 in the diagnostic imaging department at the Hospital Clínico Universitario de Santiago de Compostela. We analysed the following risk factors: location of the lesion in upper liver segments (II, IVa, VII, or VIII); proximity to the liver capsule, distance from the skin >100mm, interposition of osseus or vascular structures, inability to go through healthy parenchyma, and lack of patient cooperation during the procedure. Efficacy was analysed in terms of the number of cylinders obtained and the percentage of adequate biopsies; safety was analysed in terms of the percentage of complications, which were classified as major or minor. RESULTS: We included 295 biopsies in 278 patients (median age, 69 years; 64.1% male; 44.7% had prior neoplasms). In 61.4%, the biopsy was indicated for the initial diagnosis; 82.4% of biopsies were done in hospitalised patients, and 65% of the lesions were located in the right liver lobe. The median number of cylinders obtained was 3 (range 1-6); 91.2% of the biopsies were adequate and 92.2% were considered clinically useful. These percentages did not differ significantly according to the presence of risk factors. Complications occurred in 10 (3.4%) patients. Complications were considered major in 3 (0.9%) patients (2 (0.6%) bleeding complications and 1 (0.3%) infectious complication) and minor in 7 (2.4%). The percentage of complications was significantly higher in patients who did not cooperate during the procedure (P=.04). CONCLUSIONS: Ultrasound-guided percutaneous liver biopsy is an efficacious and safe technique for the histological diagnosis of space-occupying liver lesions. Our results confirm the increased rate of complications when patients fail to cooperate during the procedure.

Sex and gender disparities in patients with advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry.

BACKGROUND: Recommendations for research articles include the use of the term sex when reporting biological factors and gender for identities or psychosocial or cultural factors. There is an increasing awareness of incorporating the effect of sex and gender on cancer outcomes. Thus, these types of analyses for advanced gastroesophageal adenocarcinoma are relevant. PATIENTS AND METHODS: Patients with advanced gastroesophageal adenocarcinoma from the Spanish AGAMENON-SEOM registry treated with first-line combination chemotherapy were selected. Epidemiology, characteristics of the disease, treatment selection, and results were examined according to sex. RESULTS: This analysis included 3274 advanced gastroesophageal adenocarcinoma patients treated with combination chemotherapy between 2008 and 2021: 2313 (70.7%) men and 961 (29.3%) women. Tumors in females were more frequently HER2-negative (67.8% versus 60.8%; P < 0.0001), grade 3 (45.4% versus 36.8%; P < 0.001), diffuse (43.3% versus 26.5%; P < 0.0001), and signet ring cell histology (40.5 versus 23.9%; P < 0.0001). Peritoneal spread was more common in women (58.6% versus 38.9%; P < 0.0001), while liver burden was lower (58.9% versus 71.1%; P < 0.0001). There were no significant differences in treatment recommendation. Treatment doses, density, and duration were comparable between sexes. Women experienced more diarrhea (46% versus 37%; P < 0.0001), neutropenia (51% versus 43%; P < 0.0001), and anemia (62% versus 57%; P < 0.0001). After a median 59.6-month follow-up [95% confidence interval (CI) 54.5-70.8], there were no statistically significant differences between the sexes in progression-free survival [6.21 months (95% CI 5.8-6.5 months) versus 6.08 months (95% CI 5.8-6.3 months); log-rank test, χ2 = 0.1, 1 df, P = 0.8] or in overall survival [10.6 months (95% CI 9.8-11.1 months) versus 10.9 months (95% CI 10.4-11.4 months); log-rank test: χ2 = 0.6, 1 df, P = 0.5]. CONCLUSION: This sex analysis of patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry receiving first-line polychemotherapy found no differences in survival. Although women had worse prognostic histopathology, metastatic disease pattern, and greater toxicity, treatment allocation and compliance were equivalent.

Mitochondrial dysfunction as a mediator of hippocampal apoptosis in a model of hepatic encephalopathy.

In this study, we describe the presence of apoptosis, associated with a mitochondrial dysfunction in the hippocampus of animals in an experimental model defined as minimal hepatic encephalopathy (MHE). This experimental model was studied after 10 days of induced portal vein calibrated stricture, leading to portal hypertension and to a moderate hyperammonemia, without the presence of other evident central nervous system changes. The molecular mechanisms here proposed indicate the presence of apoptotic intrinsic pathways that point to hippocampal mitochondria as an important mediator of apoptosis in this experimental model. In this model of MHE, the presence of DNA fragmentation is documented by 2.3-times increased number of TUNEL-positive cells. These findings together with a higher ratio of the Bcl-2 family members Bax/Bcl-xL in the outer mitochondrial membrane of the MHE animals together with 11% of cytochrome c release indicate the presence of apoptosis in this experimental model. A detailed analysis of the hippocampal mitochondrial physiology was performed after mitochondrial isolation. The determination of the respiratory rate in the presence of malate plus glutamate and ADP showed a 45% decrease in respiratory control in MHE animals as compared with the sham group. A marked decrease of cytochrome oxidase (complex IV of the electron transport chain) was also observed, showing 46% less activity in hippocampal mitochondria from MHE animals. In addition, mitochondria from these animals showed less ability to maintain membrane potential (ΔΨ (m)) which was 13% lower than the sham group. Light scattering experiments showed that mitochondria from MHE animals were more sensitive to swell in the presence of increased calcium concentrations as compared with the sham group. In addition, in vitro studies performed in mitochondria from sham animals showed that mitochondrial permeability transition (MPT) could be a mitochondrial mediator of the apoptotic signaling in the presence of NH(4) (+) and calcium.

A portable intermolecular potential for molecular dynamics studies of NMA-NMA and NMA-H2O aggregates.

A recently formulated intermolecular potential has been adapted to describe the interaction of the N-methylacetamide (NMA) dimer and of the NMA-H(2)O adduct. The pure electrostatic component of the intermolecular potential functional representation is as usual expressed in terms of a set of punctual charges distributed over the molecular frames, consistently with the permanent molecular dipole values. In contrast, the remainder of the intermolecular potential is expressed in terms of Improved Lennard Jones effective pair potential functions, referred to multiple interaction centers (or sites) placed on the N-methylacetamide molecule and to a single interaction center placed on the water molecule. The characteristic of this pair potential relies on a mix of transferable and non-transferable descriptions of the parameters. The first set of parameters has a structural connotation bearing a site-site interaction nature and exploiting the molecular polarizability decomposability. The second one, depending on the particles clustering and charge distribution and transfer, bears a delocalized and ambient bulk nature. This choice has been tested against ab initio calculations and molecular dynamics simulations. The results show that the model potential is appropriate for describing the energetic of the various stable configurations of NMA-NMA and NMA-H(2)O weakly interacting aggregates, including the formation of hydrogen bonds.

Ar solvation shells in K(+)-HFBz: from cluster rearrangement to solvation dynamics.

The effect of some leading intermolecular interaction components on specific features of weakly bound clusters involving an aromatic molecule, a closed shell ion, and Ar atoms is analyzed by performing molecular dynamics simulations on potential energy surfaces properly formulated in a consistent way. In particular, our investigation focuses on the three-dimensional Ar distributions around the K(+)-hexafluorobenzene (K(+)-HFBz) dimer, in K(+)-HFBz-Ar(n) aggregates (n ≤ 15), and on the gradual evolution from cluster rearrangement to solvation dynamics when ensembles of 50, 100, 200, and 500 Ar atoms are taken into account. Results indicate that the Ar atoms compete to be placed in such a way to favor an attractive interaction with both K(+) and HFBz, occupying positions above and below the aromatic plane but close to the cation. When these positions are already occupied, the Ar atoms tend to be placed behind the cation, at larger distances from the center of mass of HFBz. Accordingly, three different groups of Ar atoms are observed when increasing n, with two of them surrounding K(+), thus, disrupting the K(+)-HFBz equilibrium geometry and favoring the dissociation of the solvated cation when the temperature increases. The selective role of the leading intermolecular interaction components directly depending on the ion size repulsion is discussed in detail by analyzing similarities and differences on the behavior of the Ar-solvated K(+)-HFBz and Cl(-)-Bz aggregates.

Oligodeoxynucleotide IMT504 induces a marked recovery in a streptozotocin-induced model of diabetes in rats: correlation with an early increase in the expression of nestin and neurogenin 3 progenitor cell markers.

AIMS/HYPOTHESIS: IMT504 is an oligonucleotide that promotes tissue repair in bone injury and neuropathic pain models by stimulating progenitor cells. Here we evaluated the effect of IMT504 on the recovery of islet function in a streptozotocin (STZ)-induced model of diabetes in the rat. METHODS: Male Sprague-Dawley rats were injected with STZ (60 mg/kg, i.p., day 1) or citrate buffer (Control). Animals with glycaemia between 11 and 20 mmol/l on day 4 were injected with IMT504 (4 mg/animal in saline, s.c., STZ-IMT504) or with saline (STZ-Saline) for 10 days. Glycaemia and water and food intake were recorded for 33 days. Intraperitoneal glucose tolerance tests (IPGTTs) were performed on day 30. On day 35, overnight-fasted animals were killed and blood samples and pancreases collected for hormonal and histological studies. A second group of STZ-IMT504 rats was killed, together with Control and STZ-Saline rats, after two consecutive days of blood glucose decreases after the beginning of IMT504 treatment. Pancreases were collected and proliferating cell nuclear antigen (PCNA), nestin and neurogenin 3 (NGN3) detected by immunohistochemistry. RESULTS: IMT504 greatly improved blood glucose and food and water intakes in STZ-IMT504 rats by day 8, as well as IPGTTs on day 30. Significant increases in islet number and beta cell content were observed in STZ-IMT504 rats (day 33). Furthermore, after two to five IMT504 injections, blood glucose decreased, and an increase in pancreatic nestin (mainly in endothelial cells), PCNA and NGN3 production (in islets) was observed in STZ-IMT504 rats. CONCLUSIONS/INTERPRETATION: IMT504 induced a marked recovery of STZ-induced diabetes that correlated with early production of progenitor cell markers, such as nestin and NGN3.

Characterization of stx2 tubular response in a rat experimental model of hemolytic uremic syndrome.

BACKGROUND/AIMS: In Argentina, hemolytic uremic syndrome (HUS) constitutes the most frequent cause of acute renal failure in children. The aim of our study was to analyze the early tubular response under the effect of Shiga toxin type 2 (Stx2) in a rat experimental model of HUS. METHODS: Adult male Sprague-Dawley rats were injected intraperitoneally with culture supernatant from recombinant Escherichia coli expressing Stx2. Functional, histological, immunohistochemical and Western blot studies were performed at 48 h postinoculation. RESULTS: Renal tubules showed the loss of the epithelial markers E-cadherin and ß-catenin, and an increase in transforming growth factor-ß1 expression. We detected the expression of α-smooth muscle actin in the interstitium and fibrosis in the periglomerular areas. CONCLUSION: Our results indicate that the early tubular response to the effects of Stx2 is related to an immunophenotype change of tubular cells and the presence of mild fibrosis in the interstitium.

Efficacy of anthelminthic control programs against natural Muellerius capillaris infection in sheep in the north-west of Spain. Effect on blood gases and pH in venous blood samples.

The field efficacy of a single dose treatment against natural M. capillaris infection using different anthelmintic drugs, extensively employed in ovine parasite control programs in Galicia (N.W. Spain), and the effect of protostrongylid infection on ovine respiratory functions, were evaluated. Five groups (n = 5) of ewes were used in this study; animals were treated with injectable ivermectin 10.2 mg/kg), levamisole (7.5 mg/kg) and albendazole (5 mg/kg) and monitored at 0, 7, 21, 42 and 63 days posttreatment (d.p.t.) by enumeration of the lungworm larvae per gram of faeces (l.p.g.) and determination of gas tension and pH in venous blood using an i-Stat portable clinical analyzer. No statistical difference was found either in larval elimination between untreated and treated groups or in the reduction in larval counts in all of the treated groups. A significant increase in partial oxygen tension (pO2) and saturation (sO2) between day 0 and 7 p.t. was observed in all treated animals. These values decreased significantly at day 21 to previous levels. There were no statistical differences in blood gases between uninfected and treated groups. We can conclude that under Galician field conditions, parasitic control programs are not totally effective against M. capillaris infection.

Impact of risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy of space-occupying lesions. / Impacto de los factores de riesgo en la eficacia y complicaciones de la biopsia hepática percutánea ecoguiada de lesiones ocupantes de espacio.

INTRODUCTION: Ultrasound-guided percutaneous liver biopsy is considered the technique of choice for the histological diagnosis of space-occupying lesions, given its high level of safety and diagnostic performance. However, since it is an invasive diagnostic procedure, complications can occur. Various clinical and radiological parameters have been analyzed as factors related with the efficacy of the technique or with its complications; however, the results have been contradictory. Thus, we aimed to evaluate the impact of various risk factors on the efficacy and complications of ultrasound-guided percutaneous liver biopsy in the diagnosis of space-occupying lesions in ordinary clinical practice. MATERIAL AND METHODS: This retrospective observational study included all patients who underwent real-time ultrasound-guided percutaneous biopsies of space-occupying liver lesions with the free-hand technique between December 2012 and February 2018 in the diagnostic imaging department at the Hospital Clínico Universitario de Santiago de Compostela. We analyzed the following risk factors: location of the lesion in upper liver segments (II, IVa, VII, or VIII); proximity to the liver capsule, distance from the skin > 100mm, interposition of osseus or vascular structures, inability to go through healthy parenchyma, and lack of patient cooperation during the procedure. Efficacy was analyzed in terms of the number of cylinders obtained and the percentage of adequate biopsies; safety was analyzed in terms of the percentage of complications, which were classified as major or minor. RESULTS: We included 295 biopsies in 278 patients (median age, 69 years; 64.1% male; 44.7% had prior neoplasms). In 61.4%, the biopsy was indicated for the initial diagnosis; 82.4% of biopsies were done in hospitalized patients, and 65% of the lesions were located in the right liver lobe. The median number of cylinders obtained was 3 (range 1-6); 91.2% of the biopsies were adequate and 92.2% were considered clinically useful. These percentages did not differ significantly according to the presence of risk factors. Complications occurred in 10 (3.4%) patients. Complications were considered major in 3 (0.9%) patients (2 (0.6%) bleeding complications and 1 (0.3%) infectious complication) and minor in 7 (2.4%). The percentage of complications was significantly higher in patients who did not cooperate during the procedure (p=0.04). CONCLUSIONS: Ultrasound-guided percutaneous liver biopsy is an efficacious and safe technique for the histological diagnosis of space-occupying liver lesions. Our results confirm the increased rate of complications when patients fail to cooperate during the procedure.

Efficacy and safety of trifluridine/tipiracil in third-line and beyond for the treatment of patients with metastatic colorectal cancer in routine clinical practice: patterns of use and prognostic nomogram.

INTRODUCTION: Trifluridine/tipiracil combination has shown a benefit over placebo in the treatment of patients with chemorefractory metastatic colorectal cancer (mCRC). We evaluated the efficacy and safety of this combination in the real-life setting at eight Galician centers in Spain. PATIENTS AND METHODS: This is a retrospective study of a cohort of patients with mCRC in treatment with trifluridine/tipiracil within usual clinical practice who have been previously treated or are not considered candidates for treatment with available therapies. RESULTS: A total of 160 mCRC patients were included. Our data showed that 11.9% of patients achieved disease control. Median progression-free survival was 2.75 months; at 5.66 months follow-up, median overall survival was 7.94 months. Asthenia and neutropenia (48.1% both) were the most frequent adverse events. Overall survival was lower in patients with ECOG 2, multiple metastatic sites, platelets count 350,000/µl, alkaline phosphatase > 500 IU/l, and carcinoembryonic antigen > 10 ng/ml. CONCLUSION: The results of this study confirm the efficacy and safety of trifluridine/tipiracil in chemorefractory mCRC patients. However, patients in clinical practice differ from patients in clinical trials. Due to this, prognostic factors have special importance to offer the best therapeutic approach.

Tetrahedral ordering in water: Raman profiles and their temperature dependence.

The supramolecular organization of liquid water is discussed in connection with both the spectral profile of the OH stretching Raman signal measured in pure water and the distribution of tetrahedral order computed by molecular dynamics simulations. Both curves show common features and a similar temperature dependence never pointed out before. Energetic information extracted from the Raman profiles using a recently proposed integration method is also discussed. Overall results confirm that thermally induced structural variations of water in the interval of temperature ranging from 10 to 75 degrees C involve a change of the local tetrahedral order associated with a redistribution energy of 1.6-1.7 kcal/mol.