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Three geminal zwitterionic compounds are synthesized pursuing five parameters of green chemistry: atomic economy, environmental factor, mass intensity, mass reaction efficiency, and carbon efficiency; and evaluated as corrosion inhibitors for carbon steel (AISI–1018). The zwitterions are produced with variable length from amines (i.e., hydrocarbon chains), achieving mass reaction efficiencies higher than 80%, without the generation of wastes. The molecular structures are characterized using infrared spectroscopy and nuclear magnetic resonance. AISI–1018 steel coupons (blank corrosion) are used to test the corrosion inhibition of the geminal compounds at different concentrations (10, 25, 50, 75, and 100 ppm) in 1.0 M NaCl saturated with CO2 (pH = 3.5 and 70 °C). Electrochemical characterization is conducted using the open circuit potential (OCP) method, and polarization curves (±320 mV vs OCP) to determine the optimum concentrations in which the inhibitors decrease the corrosion rate of the steel. The corr...

OBJECTIVE Specific lipid molecular changes leading to type 2 diabetes (T2D) are largely unknown. We assessed lipidome factors associated with future occurrence of T2D in a population at high cardiovascular risk. RESEARCH DESIGN AND METHODS We conducted a case-cohort study nested within the PREDIMED trial, with 250 incident T2D cases diagnosed during 3.8 years of median follow-up, and a random sample of 692 participants (639 noncases and 53 overlapping cases) without T2D at baseline. We repeatedly measured 207 plasma known lipid metabolites at baseline and after 1 year of follow-up. We built combined factors of lipid species using principal component analysis and assessed the association between these lipid factors (or their 1-year changes) and T2D incidence. RESULTS Baseline lysophosphatidylcholines and lysophosphatidylethanolamines (lysophospholipids [LPs]), phosphatidylcholine-plasmalogens (PC-PLs), sphingomyelins (SMs), and cholesterol esters (CEs) were inversely associated with risk of T2D (multivariable-adjusted P for linear trend ≤0.001 for all). Baseline triacylglycerols (TAGs), diacylglycerols (DAGs), and phosphatidylethanolamines (PEs) were positively associated with T2D risk (multivariable-adjusted P for linear trend CONCLUSIONS Two plasma lipid profiles made up of different lipid classes were found to be associated with T2D in participants at high cardiovascular risk. A profile including LPs, PC-PLs, SMs, and CEs was associated with lower T2D risk. Another profile composed of TAGs, DAGs, and PEs was associated with higher T2D risk.

A completely regioselective and highly stereoselective palladium-catalyzed intramolecular hydroarylation of arenesulfonyl ynamines to benzothiazoles was developed. The presence of an electron-withdrawing group on the triple bond of the sulfonyl ynamine was crucial for the success of the reaction and our mechanistic studies suggest an alkyne-directed 5-exo-dig cyclization pathway. The products easily underwent photoinduced rearrangement to 3-amino-1-benzothiophene-1,1-diones (up to 35 % yields after two steps).

The epidemological analysis of data regarding the efficacy of artificial reproduction techniques reveáis certain problems in those most widely used. Aside from these empirical difficulties comes the affront on human dignity that some of them entail. It is necessary to deal with the problem of sterility in a manner that safeguards the excellence of the human being.

Family planning through natural means is the result of previous ethical and anthropological reflection. Deprived of this foundation, one easily falls prey to widespread errors regarding its inefficacy, its scarce demand and the difficulty of its learning and utilization. Neither would it be possible here to ignore the moral dimensión of this human act.

Resumen Introduccion La Escala de Ansiedad y Depresion Hospitalaria (HADS) es un instrumento autoadministrable para pacientes ambulatorios cuyo comportamiento difiere segun la poblacion clinica a la que se aplica. En Mexico no esta validada en pacientes con enfermedad inflamatoria intestinal (EII). Objetivos Validar la HADS en la poblacion mexicana con EII. Metodos Se incluyeron 112 pacientes del Instituto Nacional de Ciencias Medicas y Nutricion «Salvador Zubiran» con EII a los cuales se les aplico la HADS y se valoraron algunas caracteristicas demograficas y clinicas del padecimiento. Se realizo un analisis factorial exploratorio y obtencion de la congruencia factorial para determinar la validez de constructo de la HADS y la confiabilidad se evaluo mediante el alfa de Cronbach. Resultados El resultado de la rotacion varimax de los 14 items de la HADS explico el 50,1% de la varianza, teniendo 2 factores principales. Diez items mostraron altas cargas factoriales para las dimensiones originalmente propuestas. La consistencia interna de la HADS fue alta (alfa = 0,88) con altos valores en los coeficientes de congruencia. Conclusiones La HADS es un instrumento valido para detectar posibles casos de ansiedad y depresion en pacientes mexicanos con EII. La validacion de este instrumento permite su utilizacion rutinaria para la evaluacion integral del paciente y su referencia oportuna a salud mental.

Introduction The Hospital Anxiety and Depression Scale (HADS) is a self-administered instrument for outpatients, but its behaviour differs according to the clinical population to which it is applied. In Mexico it is not validated in patients with inflammatory bowel disease (IBD). Objectives To validate the HADS scale in the Mexican population with IBD. Methods 112 patients with IBD from the “Salvador Zubiran” National Institute of Medical Sciences and Nutrition were included, to whom the HADS was applied and some demographic and clinical characteristics of the disease were evaluated. An exploratory factor analysis was performed and factorial congruence was calculated to determine the construct validity of the HADS, while reliability was evaluated using Cronbach's alpha. Results The result of the varimax rotation of the 14 items of the HADS explained 50.1% of the variance, having two main factors. Ten items showed high factor loading for the dimensions originally proposed. The internal consistency of the HADS was high (alpha = 0.88) with high values for the congruence coefficients. Conclusions The HADS scale is a valid instrument to detect possible cases of Anxiety and Depression in Mexican patients with IBD. The validation of this instrument allows its routine use for the integral evaluation of the patient and their timely referral to mental health.

Globally, congenital toxoplasmosis remains a significant cause of morbidity and mortality, and outbreaks of infection with T. gondii represent a significant, emerging public health burden, especially in the developing world. This parasite is a threat to public health. Disease often is not recognized and is inadequately managed. Herein, we analyze the status of congenital toxoplasmosis in Morocco, Colombia, the United States, and France. We identify the unique challenges faced by each nation in the implementation of optimal approaches to congenital toxoplasmosis as a public health problem. We suggest that developed and developing countries use a multipronged approach, modeling their public health management protocols after those in France. We conclude that education, screening, appropriate treatment, and the development of novel modalities will be required to intervene successfully in caring for individuals with this infection. Gestational screening has been demonstrated to be cost-effective, morbidity-sparing, and life-saving. Recognition of the value and promise of public health interventions to prevent human suffering from this emerging infection will facilitate better patient and societal outcomes.

Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of histopathological changes ranging from non-inflammatory intracellular fat deposition to non-alcoholic steatohepatitis (NASH), which may progress into hepatic fibrosis, cirrhosis, or hepatocellular carcinoma. Recent data suggest that impaired hepatic cholesterol homeostasis and its accumulation are relevant to the pathogenesis of NAFLD/NASH. Despite a vital physiological function of cholesterol, mitochondrial dysfunction is an important consequence of dietary-induced hypercholesterolemia and was, subsequently, linked to many pathophysiological conditions. The aim in the current study was to evaluate the morphological and molecular changes of cholesterol overload in mouse liver and particularly, in mitochondria, induced by a high-cholesterol (HC) diet for one month. Histopathological studies revealed microvesicular hepatic steatosis and significantly elevated levels of liver cholesterol and triglycerides leading to impaired liver synthesis. Further, high levels of oxidative stress could be determined in liver tissue as well as primary hepatocyte culture. Transcriptomic changes induced by the HC diet involved disruption in key pathways related to cell death and oxidative stress as well as upregulation of genes related to glutathione homeostasis. Impaired liver function could be associated with a decrease in mitochondrial membrane potential and ATP content and significant alterations in mitochondrial dynamics. We demonstrate that cholesterol overload in the liver leads to mitochondrial changes which may render damaged hepatocytes proliferative and resistant to cell death whereby perpetuating liver damage.

Este artículo analiza cómo Santo Tomás de Villanueva, “Padre de los pobres” según su decreto de su beatificación, es digno de este título en virtud de la preocupación que mostró por estos en su vida y actuación. Se profundiza en la relevancia que los pobres y la pobreza adquieren en la predicación y doctrina del santo agustino. Comenzando por el análisis del trasfondo de su personalidad caritativa, esta investigación aborda la configuración de una posible teología de los pobres desde él en la que, como se verá, los indigentes y menesterosos adquieren una importancia singular. Por último, se expone cómo la comprensión de los pobres y la pobreza que mostró Santo Tomás de Villanueva, proyectan en su pensamiento un exigente deseo de reforma eclesial que repercuta en un cambio de modelo social.

Early detection of PCa faces severe limitations as PSA displays poor‐specificity/sensitivity. As we recently demonstrated that plasma ghrelin O‐acyltransferase (GOAT)‐enzyme is significantly elevated in PCa‐patients compared with healthy‐controls, using a limited patients‐cohort, we aimed to further explore the potential of GOAT to improve PCa diagnosis using an ample patients‐cohort (n = 312) and defining subgroups (i.e. significant PCa/metastatic patients, etc.) that could benefit from this biomarker. Plasma GOAT‐levels were evaluated by ELISA in patients with (n = 183) and without (n = 129) PCa. Gleason Score ≥ 7 was considered clinically significant PCa. GOAT‐levels were higher in PCa patients vs control patients, and in those with significant PCa vs non‐significant PCa. GOAT‐levels association with the diagnoses of significant PCa was independent from traditional clinical variables (i.e. PSA/age/DRE). Remarkably, GOAT outperformed PSA in patients with PSA‐levels ranging 3‐20 ng/mL for the significant PCa diagnosis [GOAT‐AUC = 0.612 (0.531‐0.693) vs PSA‐AUC = 0.494 (0.407‐0.580)]. A panel of key variables including GOAT/age/DRE/testosterone also outperformed the same panel but with PSA [AUC = 0.720 (0.710‐0.730) vs AUC = 0.705 (0.695‐0.716), respectively]. Notably, GOAT‐levels could also represent a novel predictive biomarker of aggressiveness, as its levels are positively associated with Gleason Score and the presence of metastasis at the time of diagnoses. Altogether, our data reveal that GOAT‐levels can be used as a non‐invasive biomarker for significant PCa diagnosis in patients at risk of PCa (with PSA: 3‐20 ng/mL).

Introduction and aim. Obesity is a worldwide epidemic problem, described as a risk factor for hepatic diseases, such as non-alcoholic fatty liver disease and other pathologies related to development of cholesterol crystals and cholesterol gallbladder stones. It has been reported that cholesterol overload may cause hepatic damage; however, little is known about the effects of an acute hypercholesterolemic diet on the gallbladder. The aim of this manuscript was to evaluate the impact of a cholesterol-rich diet on the gallbladder. Material and methods. The study included ten eight-week-old C57BL6 male mice, which were divided into two study groups and fed different diets for 48 h: a hypercholesterolemic diet and a balanced Chow diet. After 48 h, the mice were analyzed by US with a Siemens Acuson Antares equipment. Mice were subsequently sacrificed to carry out a cholesterol analysis with a Refloton System (Roche), a crystal analysis with a Carl Zeiss microscope with polarized light, and a histological analysis with Hematoxylin-eosin staining. Results. The hypercholesterolemic diet induced an increase in gallbladder size and total cholesterol content in the bile, along with important histological changes. Conclusion. Cholesterol overloads not only trigger hepatic damage, but also affect the gallbladder significantly.

Management of active surveillance (AS) in low-risk prostate cancer (PCa) patients could be improved with new biomarkers, such as the 4Kscore test. We analyze its ability to predict tumor reclassification by upgrading at the confirmatory biopsy at 6 months. Observational, prospective, blinded, and non-randomized study, within the Spanish National Registry on AS (AEU/PIEM/2014/0001; NCT02865330) with 181 patients included after initial Bx and inclusion criteria: PSA ≤10 ng/mL, cT1c-T2a, Grade group 1, ≤2 cores, and ≤5 mm/50% length core involved. Central pathological review of initial and confirmatory Bx was performed on all biopsy specimens. Plasma was collected 6 months after initial Bx and just before confirmatory Bx to determine 4Kscore result. In order to predict reclassification defined as Grade group ≥2, we analyzed 4Kscore, percent free to total (%f/t) PSA ratio, prostate volume, PSA density, family history, body mass index, initial Bx, total cores, initial Bx positive cores, initial Bx % of positive cores, initial Bx maximum cancer core length and initial Bx cancer % involvement. Wilcoxon rank-sum test, non-parametric trend test or Fisher’s exact test, as appropriate established differences between groups of reclassification. A total of 137 patients met inclusion criteria. Eighteen patients (13.1%) were reclassified at confirmatory Bx. The %f/t PSA ratio and 4Kscore showed differences between the groups of reclassification (Yes/No). Using 7.5% as cutoff for the 4Kscore, we found a sensitivity of 89% and a specificity of 29%, with no reclassifications to Grade group 3 for patients with 4Kscore below 7.5% and 2 (6%) missed Grade group 2 reclassified patients. Using this threshold value there is a biopsy reduction of 27%. Additionally, 4Kscore was also associated with changes in tumor volume. Our preliminary findings suggest that the 4Kscore may be a useful tool in the decision-making process to perform a confirmatory Bx in active surveillance management.

Invariants under rotation of the magnetotelluric impedance tensor relax the directional requirements when fitting data using two-dimensional (2D) models. This happens, for instance, when using the familiar impedance derived from the determinant of the tensor. In this work, we use two particular invariants that reduce in 2D to the traditional transverse electric (TE) and transverse magnetic (TM) impedances. They are obtained as the missing first link of an infinite chain of invariants that are computed iteratively without any reference to a strike direction. We challenge the current view that the TE and TM impedances are not invariant. We argue in favor of the invariance. We apply our approach to the well-known and difficult BC87 dataset. These data present (1) electro-galvanic distortions, (2) static shifts and (3) inconsistent strikes. To remove the electro-galvanic distortions, we use recent developments that combine the phase tensor with the quadratic equation. To handle statics, we use a mimic of the electromagnetic array profiling (EMAP) method; the property of the TE mode of acting as a natural filter for static effects, as reported recently in the literature. Finally, the multiple strikes are handled by the invariant character of the TE and TM impedances. The processed TE responses are interpreted as one-dimensional models to construct a 2D resistivity image of the subsurface, which is accompanied by the complementary image of the multiple strikes. Our model correlates very well with an independent EMAP survey over the Nelson Batholith and with seismic reflection and refraction lines.

Background The role of trimethylamine-N-oxide (TMAO) in type 2 diabetes (T2D) is currently partially understood and controversial. Objective The aim of this study was to investigate associations between TMAO and related metabolites with T2D risk in subjects at high risk of cardiovascular disease. Design This is a case-cohort design study within the Prevencion con Dieta Mediterranea (PREDIMED) study, with 251 incident T2D cases and a random sample of 694 participants (641 noncases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 y). We used liquid chromatography-tandem mass spectrometry to measure plasma TMAO, l-carnitine, betaine, lyso-phosphatidylcholine (LPC) and lyso-phosphatidylethanolamine (LPE) species, phosphocholine, α-glycerophosphocholine, and choline at baseline and after 1 y. We examined associations with the use of weighted Cox proportional hazard models, accounting for the weighted case-cohort design by the Barlow method. Results After adjustment for recognized T2D risk factors and multiple testing, individuals in the highest quartile of baseline TMAO and α-glycerophosphocholine had a lower risk of T2D [HR (95% CI): 0.52 (0.29, 0.89) and 0.46 (0.24, 0.89), respectively]. The HR (95% CI) comparing the extreme quartiles of betaine was 0.41 (0.23, 0.74). Similar trends were observed for C16:0 LPC, C18:1 LPC, C18:0 LPC, C20:4 LPC, C22:6 LPC, C18:1 LPC plasmalogen, and C16:0 LPE. After correcting for multiple comparisons, participants in the highest quartile of 1-y changes in oleic acid LPC plasmalogen concentrations had a lower T2D risk than the reference quartile. Conclusion Whether the associations between plasma TMAO and certain metabolite concentrations with T2D risk reflect its pathophysiology or represent an epiphenomenon needs to be elucidated. This trial is registered at http://www.controlled-trials.com as ISRCTN35739639.

Monodentate phosphine ligands are frequently employed in the Ni-catalyzed C–O functionalization of aryl esters. However, the extensive body of preparative work on such reactions contrasts with the lack of information concerning the structure and reactivity of the relevant nickel intermediates. In fact, experimental evidence for a seemingly trivial oxidative addition into the C–O bond of aryl esters with monodentate phosphines and low-valent nickel complexes still remains elusive. Herein, we report a combined experimental and theoretical study on the Ni(0)/PCy3-catalyzed silylation of aryl pivalates with CuF2/CsF additives that reveals the involvement of unorthodox dinickel oxidative addition complexes in C–O bond cleavage and their relevance in C–Si bond formation. We have obtained a mechanistic picture that clarifies the role of the additives and demonstrates that dinickel complexes act as reservoirs of the propagating monomeric nickel complexes by disproportionation. We believe this study will serve as a useful entry point to unravelling the mechanistic underpinnings of other related Ni-catalyzed C–O functionalization reactions employing monodentate phosphines.

BACKGROUND: The important role of knee menisci to maintain adequate knee function is frequently impaired since early stages of knee joint degeneration. A better understanding of meniscal impairment may help the orthopaedic surgeon to orient the treatment of the degenerative knee. This review focuses on changes in meniscal cells and matrix when degeneration is in progress. MAIN BODY: Differences in the meniscal structure and metabolism have been investigated in the degenerative knee, both in experimental animal models and in surgical specimens. Cell population reduction, extracellular matrix disorganization, disturbances in collagen and non-collagen protein synthesis and/or expression have been found in menisci along with knee degeneration. These changes are considered disease-specific, different from those due to aging. CONCLUSION: Significant cellular and matrix differences are found in menisci during knee degeneration. These investigations may help to further progress in the understanding of knee degeneration and in the search of more biological treatments. Sin financiación No data 2018 UEM

The aim of this study was to examine the association between the consumption of total and specific types of dairy products and the risk of incident cataracts in an elderly Mediterranean population at high cardiovascular risk. We prospectively analyzed 5860 subjects from the PREvencion con DIeta MEDiterranea (PREDIMED) Study. The time to cataract surgery was calculated as the time between recruitment and the date of the surgery, last visit of the follow-up, date of death, or until the end of the study. Dairy products intake was assessed using validated food frequency questionnaires. We used Cox proportional hazard regression to assess the risk of cataract surgery according to average dietary energy-adjusted total dairy products, milk, yogurt and cheese consumption. We documented a total of 768 new cataract events after a median of 5.6 years of follow-up. Subjects in the second [hazard ratio (HR) 0.62; 95% CI 0.52, 0.74] and third tertile (HR: 0.71; 95% CI 0.60, 0.85) of skimmed yogurt intake had a significantly lower risk of cataracts after adjusting for potential confounders. No significant associations were observed for total dairy products, whole and skimmed milk, whole yogurt and cheese consumption. The intake of skimmed yogurt was associated with a reduced risk of cataracts in an elderly Mediterranean population with high cardiovascular risk. No significant associations were observed for other type of dairy product. International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.

Background There is limited, and inconsistent, data on the prospective association between physical activity and surrogate markers of adiposity in older adults. We aim to determine the prospective association of leisure time physical activity (LTPA) with body mass index (BMI), waist circumference (WC) and the incidence of obesity. Methods This prospective analysis included 7144 individuals with a mean age of 67 ± 6.2 years, from the PREvencion con DIeta MEDiterranea (PREDIMED) study. BMI and WC were measured and LTPA was recorded using the Minnesota Leisure Time Physical Activity Questionnaire. Exposure and outcome variables were calculated as cumulative average of repeated measurements. Results Total LTPA was inversely associated (P < 0.001) with BMI and WC. The difference in BMI and WC between extreme quintiles of LTPA (Q1-Q5) was 2.1 kg/m2 (95% confidence interval (CI) 1.68; 2.49, P < 0.001) and 4.8 cm (CI 2.28; 7.25, P < 0.001), respectively. Low-intensity LTPA was inversely associated with BMI but not with WC, while moderate/vigorous LTPA showed an inverse relationship with BMI and WC. The hazard of general and abdominal obesity incidence decreased across quintiles of total and moderate/vigorous LTPA (P < 0.001 for both), whereas low-intensity LTPA was inversely associated with the incidence of general obesity (P < 0.001). Conclusion LTPA was inversely associated with BMI, WC and incidence of general and abdominal obesity. The finding that low-intensity LTPA was inversely related to BMI and the incidence of obesity is of particular importance because this level of physical activity could be a feasible option for many older adults.

The magnetotelluric (MT) method is a well-known geophysical technique in tectonic and reservoir exploration studies. In recent years, several works have proven that the MT method is a valuable tool for monitoring fluid injection for enhanced geothermal systems and CO 2 sequestration due to its sensitivity to resistivity changes. However, most of these works report variations only in apparent resistivity and phase data, without estimating changes in the underground structure. Few studies have tried to deal with this problem. Efforts were made for DC-resistivity time-lapse monitoring (Goldstein et al., 1985a) and for the MT case using theoretical examples (Sholpo, 2006, 2010). Promising results had been obtained, but with scarce application to real scenarios. We propose a methodology to estimate resistivity variations in the underground geo-electrical structure by applying a linearized iterative nonlinear least-square inversion scheme using the Marquardt-Levenberg method to stabilize the inversion. The method is tested first with synthetic MT data, then with data registered on a permanent MT station in the Mexicali Valley, Mexico; and finally, with data measured before and after a M w 7.2 earthquake, also in the Mexicali Valley. We propose a strategy to define and apply a reference model for situations where the available constraining information is not enough. Our method seems to produce stable and coherent results, as long as the ground resistivity change is able to produce response differences larger than the data uncertainty.

We thank all PREDIMED-Plus participants and investigators. CIBEROBN, CIBERESP, and CIBERDEM are initiatives of the Instituto de Salud Carlos III (ISCIII), Madrid, Spain. The Hojiblanca (Lucena, Spain) and Patrimonio Comunal Olivarero (Madrid, Spain) food companies donated extra-virgin olive oil. The Almond Board of California (Modesto, CA, USA), American Pistachio Growers (Fresno, CA, USA), and Paramount Farms (Wonderful Company, LLC, Los Angeles, CA, USA) donated nuts for the PREDIMED-Plus pilot study. A.T.-R. is a Serra-Hunter fellow. SCB thanks the Spanish Ministry of Science Innovation and Universities for the Formacion de Profesorado Universitario (FPU17/00785) contract., Previous studies suggested that dietary polyphenols could reduce the incidence and complications of type-2 diabetes (T2D); although the evidence is still limited and inconsistent. This work analyzes whether changing to a diet with a higher polyphenolic content is associated with an improved glucose profile. At baseline, and at 1 year of follow-up visits, 5921 participants (mean age 65.0 +/- 4.9, 48.2% women) who had overweight/obesity and metabolic syndrome filled out a validated 143-item semi-quantitative food frequency questionnaire (FFQ), from which polyphenol intakes were calculated. Energy-adjusted total polyphenols and subclasses were categorized in tertiles of changes. Linear mixed-effect models with random intercepts (the recruitment centers) were used to assess associations between changes in polyphenol subclasses intake and 1-year plasma glucose or glycosylated hemoglobin (HbA1c) levels. Increments in total polyphenol intake and some classes were inversely associated with better glucose levels and HbA1c after one year of follow-up. These associations were modified when the analyses were run considering diabetes status separately. To our knowledge, this is the first study to assess the relationship between changes in the intake of all polyphenolic groups and T2D-related parameters in a senior population with T2D or at high-risk of developing T2D., Spanish Government FPU17/00785

The mechanism of damage of the biliary epithelium remains partially unexplored. However, recently many works have offered new evidence regarding the cholangiocytes' damage process, which is the main target in a broad spectrum of pathologies ranging from acute cholestasis, cholangiopathies to cholangiocarcinoma. This is encouraging since some works addressed this epithelium's relevance in health and disease until a few years ago. The biliary tree in the liver, comprised of cholangiocytes, is a pipeline for bile flow and regulates key hepatic processes such as proliferation, regeneration, immune response, and signaling. This review aimed to compile the most recent advances on the mechanisms of cholangiocellular damage during cholestasis, which, although it is present in many cholangiopathies, is not necessarily a common or conserved process in all of them, having a relevant role cAMP and PKA during obstructive cholestasis, as well as Ca2+-dependent PKC in functional cholestasis. Cholangiocellular damage could vary according to the type of cholestasis, the aggressor, or the bile ducts' location where it develops and what kind of damage can favor cholangiocellular carcinoma development.

Transition metal (Ni, Pd, Pt) promoted carbocyclizations of alkenes and alkynes have been computationally investigated to rationalize the easiness or difficulty of such processes depending on the size of the forming ring. Special emphasis has been placed on measuring the activation barriers and the exo versus endo selectivities of the processes. The study leads us to propose some qualitative rules for metal controlled ring closures, noting some discrepancies with the classical Baldwin’s rules for nonmetallic cyclizations. Also, some unexpected results were found, like the extremely low activation barriers for 3-exo-dig and 3-exo-trig closures, contrasting with the scarcity of such experimental procedures, which can be computationally interpreted by the reversibility and endergonicity of cyclopropane/cyclopropene ring formation in the presence of these metals. The consistency of the present rules has been further checked by introduction of selected structural variations in the substrates.