Multiomics of the intestine-liver-adipose axis in multiple studies unveils a consistent link of the gut microbiota and the antiviral response with systemic glucose metabolism.

BACKGROUND: The microbiota is emerging as a key factor in the predisposition to insulin resistance and obesity. OBJECTIVE: To understand the interplay among gut microbiota and insulin sensitivity in multiple tissues. DESIGN: Integrative multiomics and multitissue approach across six studies, combining euglycaemic clamp measurements (used in four of the six studies) with other measurements of glucose metabolism and insulin resistance (glycated haemoglobin (HbA1c) and fasting glucose). RESULTS: Several genera and species from the Proteobacteria phylum were consistently negatively associated with insulin sensitivity in four studies (ADIPOINST, n=15; IRONMET, n=121, FLORINASH, n=67 and FLOROMIDIA, n=24). Transcriptomic analysis of the jejunum, ileum and colon revealed T cell-related signatures positively linked to insulin sensitivity. Proteobacteria in the ileum and colon were positively associated with HbA1c but negatively with the number of T cells. Jejunal deoxycholic acid was negatively associated with insulin sensitivity. Transcriptomics of subcutaneous adipose tissue (ADIPOMIT, n=740) and visceral adipose tissue (VAT) (ADIPOINST, n=29) revealed T cell-related signatures linked to HbA1c and insulin sensitivity, respectively. VAT Proteobacteria were negatively associated with insulin sensitivity. Multiomics and multitissue integration in the ADIPOINST and FLORINASH studies linked faecal Proteobacteria with jejunal and liver deoxycholic acid, as well as jejunal, VAT and liver transcriptomic signatures involved in the actin cytoskeleton, insulin and T cell signalling. Fasting glucose was consistently linked to interferon-induced genes and antiviral responses in the intestine and VAT. Studies in Drosophila melanogaster validated these human insulin sensitivity-associated changes. CONCLUSION: These data provide comprehensive insights into the microbiome-gut-adipose-liver axis and its impact on systemic insulin action, suggesting potential therapeutic targets.Cite Now.

How to Find Correct Transection Plane in Laparoscopic Right Hepatectomy Extended to S1 for Bismuth IIIa Perihilar Cholangiocarcinoma.

BACKGROUND: Perihilar cholangiocarcinoma (pCCA) is one of the most challenging tumours for hepatic surgeons. To reach radical resection, it is mandatory to extend the hepatectomy to segment 1 and biliary tract. With the advent of minimally invasive techniques, an increasing number of centres have begun to treat this tumour using robotic or laparoscopic approaches, demonstrating the ability to maintain oncological standards as well as morbidity and mortality criteria. PATIENTS AND METHODS: This video presents a case of a 79-year-old man with pCCA Bismuth type IIIa, undergoing right hepatectomy extended to segment 1 and biliary tract after preoperative optimization including biliary drainage and portal vein and right hepatic vein embolization. Unlike conventional right hepatectomy, extending transection to include segment 1 requires identifying the plane defined by the Arantius duct. RESULTS: To reach this plane, we suggest using three approaches, previously described in other hepatectomies, were employed: dorsal and caudal approaches to the middle hepatic vein (MHV) and an extraglissonian intrahepatic approach to the left portal pedicle. CONCLUSION: With this method, we achieved oncologically radical resection of pCCA using minimally invasive surgical techniques.

The COVID-19 pandemic as an opportunity to weaken environmental protection in Brazil.

This paper examines the effects of the COVID-19 pandemic on environmental protection and legislation in Brazil. We evaluate major legislative actions, environmental fines and deforestation since January 2019. We show that 57 legislative acts aimed at weakening environmental protection in Brazil during the current administration, almost half of which in the seven-month period of the pandemic in Brazil, with September 2020 as the month with the most legislative acts (n = 16). These acts either deregulated or weakened current environmental legislation, with a number of them aimed at dismantling the main federal institutions in charge of environmental protection. We also found a 72% reduction in environmental fines during the pandemic, despite an increase in Amazonian deforestation during this period. We conclude that the current administration is taking advantage of the COVID-19 pandemic to intensify a pattern of weakening environmental protection in Brazil. This has the potential to intensify ongoing loss of biodiversity, greenhouse gas emissions, and the likelihood of other zoonotic disease outbreaks, and inflict substantial harm to traditional and indigenous peoples. We highlight the key role of the scientific community, media and civil society, national and international levels, in order to reverse these harmful actions.

Co-occurrence of analogous enzymes determines evolution of a novel (ßα)8-isomerase sub-family after non-conserved mutations in flexible loop.

We investigate the evolution of co-occurring analogous enzymes involved in L-tryptophan and L-histidine biosynthesis in Actinobacteria Phylogenetic analysis of trpF homologues, a missing gene in certain clades of this lineage whose absence is complemented by a dual-substrate HisA homologue, termed PriA, found that they fall into three categories: (i) trpF-1, an L-tryptophan biosynthetic gene horizontally acquired by certain Corynebacterium species; (ii) trpF-2, a paralogue known to be involved in synthesizing a pyrrolopyrrole moiety and (iii) trpF-3, a variable non-conserved orthologue of trpF-1 We previously investigated the effect of trpF-1 upon the evolution of PriA substrate specificity, but nothing is known about the relationship between trpF-3 and priA After in vitro steady-state enzyme kinetics we found that trpF-3 encodes a phosphoribosyl anthranilate isomerase. However, mutation of this gene in Streptomyces sviceus did not lead to auxothrophy, as expected from the biosynthetic role of trpF-1 Biochemical characterization of a dozen co-occurring TrpF-2 or TrpF-3, with PriA homologues, explained the prototrophic phenotype, and unveiled an enzyme activity trade-off between TrpF and PriA. X-ray structural analysis suggests that the function of these PriA homologues is mediated by non-conserved mutations in the flexible L5 loop, which may be responsible for different substrate affinities. Thus, the PriA homologues that co-occur with TrpF-3 represent a novel enzyme family, termed PriB, which evolved in response to PRA isomerase activity. The characterization of co-occurring enzymes provides insights into the influence of functional redundancy on the evolution of enzyme function, which could be useful for enzyme functional annotation.

Evolution of laparoscopic surgery in a high volume hepatobiliary unit: 150 consecutive pure laparoscopic hepatectomies. / Evolución de la cirugía laparoscópica en una unidad hepatobiliar de alto volumen: 150 hepatectomías laparoscópicas consecutivas.

INTRODUCTION: Compared to other surgical areas, laparoscopic liver resection (LLR) has not been widely implemented and currently less than 20% of hepatectomies are performed laparoscopically worldwide. The aim of our study was to evaluate the feasibility, and the ratio of implementation of LLR in our department. METHODS: We analyzed a prospectively maintained database of 749 liver resections performed during the last 10-year period in a single centre. RESULTS: A total of 150 (20%) consecutive pure LLR were performed between 2005 and 2015. In 87% of patients the indication was the presence ofprimary or metastatic liver malignancy. We performed 30 major hepatectomies (20%) and (80%) were minor resections, performed in all liver segments. Twelve patients were operated twice and 2 patients underwent a third LLR. The proportion of LLR increased from 12% in 2011 to 62% in the last year. Conversion rate was 9%. Overall morbidity rate was 36% but only one third were classified as severe. The 90-day mortality rate was 1%. Median hospital stay was 4 days and the rate of readmissions was 6%. CONCLUSIONS: The implementation of LLR has been fast with morbidity and mortality comparable to other published series. In the last 2 years more than half of the hepatectomies are performed laparoscopically in our centre.

Insights into the evolution of enzyme substrate promiscuity after the discovery of (ßα)8 isomerase evolutionary intermediates from a diverse metagenome.

BACKGROUND: Current sequence-based approaches to identify enzyme functional shifts, such as enzyme promiscuity, have proven to be highly dependent on a priori functional knowledge, hampering our ability to reconstruct evolutionary history behind these mechanisms. Hidden Markov Model (HMM) profiles, broadly used to classify enzyme families, can be useful to distinguish between closely related enzyme families with different specificities. The (ßα)8-isomerase HisA/PriA enzyme family, involved in L-histidine (HisA, mono-substrate) biosynthesis in most bacteria and plants, but also in L-tryptophan (HisA/TrpF or PriA, dual-substrate) biosynthesis in most Actinobacteria, has been used as model system to explore evolutionary hypotheses and therefore has a considerable amount of evolutionary, functional and structural knowledge available. We searched for functional evolutionary intermediates between the HisA and PriA enzyme families in order to understand the functional divergence between these families. RESULTS: We constructed a HMM profile that correctly classifies sequences of unknown function into the HisA and PriA enzyme sub-families. Using this HMM profile, we mined a large metagenome to identify plausible evolutionary intermediate sequences between HisA and PriA. These sequences were used to perform phylogenetic reconstructions and to identify functionally conserved amino acids. Biochemical characterization of one selected enzyme (CAM1) with a mutation within the functionally essential N-terminus phosphate-binding site, namely, an alanine instead of a glycine in HisA or a serine in PriA, showed that this evolutionary intermediate has dual-substrate specificity. Moreover, site-directed mutagenesis of this alanine residue, either backwards into a glycine or forward into a serine, revealed the robustness of this enzyme. None of these mutations, presumably upon functionally essential amino acids, significantly abolished its enzyme activities. A truncated version of this enzyme (CAM2) predicted to adopt a (ßα)6-fold, and thus entirely lacking a C-terminus phosphate-binding site, was identified and shown to have HisA activity. CONCLUSION: As expected, reconstruction of the evolution of PriA from HisA with HMM profiles suggest that functional shifts involve mutations in evolutionarily intermediate enzymes of otherwise functionally essential residues or motifs. These results are in agreement with a link between promiscuous enzymes and intragenic epistasis. HMM provides a convenient approach for gaining insights into these evolutionary processes.

Pure laparoscopic liver resection reduces surgical site infections and hospital stay. Results of a case-matched control study in 50 patients.

BACKGROUND: Laparoscopic resection is an emerging tool in surgical oncology, but its role in liver tumors is far from being universally accepted. METHODS: We designed a case-matched control study, comparing laparoscopic (LAP) vs. open hepatectomies (OP) performed in the same center during the same period of time. Fifty LAP were performed (34 liver metastases, 7 hepatocellular carcinomas, 2 hydatid cysts, and 5 benign tumors). Cases were compared with 100 OP matched according to: diagnosis, number of lesions, type of resection, age, ASA score, and ECOG performance status. We evaluated intraoperative and postoperative parameters, focusing on morbidity and mortality. RESULTS: Preoperative data were comparable in both groups. Operative features were similar in terms of overall morbidity 18 (36 %) vs. 36 (36 %), p = 1; intraoperative bleeding, 401 (18-2192) vs. 475 (20-2000) mL, p = 0.89; pedicle clamping, 37 (74 %) vs. 88 (88 %), p = 0.55; margin, 0.6 (0-5) vs. 0.65 (0-5) cm, p = 0.94, and mortality p = 0.65 for the LAP and OP groups, respectively. There was a significant decrease in surgical site infections 1 (2 %) vs. 18 (18 %) p = 0.007 in the LAP group. Operative time was longer: 295 (120-600) vs. 200 (70-450) min (p = 0.0001), and hospital stay significantly shorter: 4 (1-60) vs. 7 (3-44) days, p = 0.0001 with less readmissions (0 vs. 7 %) in the LAP. DISCUSSION: In adequately selected patients, laparoscopic hepatectomy is feasible, safe, shortens hospital stay, and decreases surgical site infections.

[Liver resections as radical surgery for hepatic hydatidosis: results in 50 patients]. / Resultados de las resecciones hepáticas como tratamiento radical de la hidatidosis hepatica en 50 pacientes.

INTRODUCTION: Among several regions in the world hepatic hydatidosis can be considered endemic. Currently there are many available treatments for this disease, been surgery the most effective one. Surgical procedures can be divided in two main groups, radical and non-radical procedures. The goal of this work is to evaluate the morbidity, mortality and percentage of recurrence in patients treated with hepatectomies, comparing them with other publications. MATERIAL AND METHODS: This retrospective study was carried out in a series from Spain and Argentina. We analyzed the following data: sex, age, type of resection, associated surgical gestures, presence of liver disease, operative time, blood transfusion, morbidity, mortality, hospital stay, re-hospitalization, recurrence and follow up. Dindo--Clavien classification was used for complications, and International Hepato-Pancreato-Biliary Association (IHPBA) Brisbane classification for hepatectomies. Mortality was considered until 90 days after surgery. To evaluate the recurence we only included patients followed over 6 months. RESULTS: Indications for liver resections were performed in patients with cysts larger than 5 centimeters, multiple cysts, large cysts, with bile duct communicated or suspicion of this communication. Five patients required blood transfusions (10%) with a median for these 5 patients of 740 ml and 74 ml for the complete series. The median operative time was 186 minutes (range 45 to 1,050 minutes). Median hospital stay was 7.7 days. Monitoring more than 6 months was conducted in 38 patients. CONCLUSIONS: We believe that hepatic hydatid disease is a multifaceted disease and requires more than one therapeutic approach. Hepatectomy with complete resection of the parasite offers the possibility of doing so in a controlled and safe way by experienced hands, ensuring good results in the treatment of this disease.

Numerical Simulation of Stresses in Functionally Graded HCS-MgO Cylinder Using Iterative Technique and Finite Element Method.

In this study, a thick hollow axisymmetric functionally graded (FG) cylinder is investigated for steady-state elastic stresses using an iteration technique and the finite element method. Here, we have considered a functionally graded cylinder tailored with the material property, namely, Young's modulus, varying in an exponential form from the inner to outer radius of the cylinder. A mathematical formulation for stress analysis of functionally graded cylinder under internal and external pressure conditions is developed using constitutive relations for stress-strain, strain-displacement relations and the equation of equilibrium. The effect of the in-homogeneity parameter on radial displacement, radial and tangential stresses in a functionally graded cylinder made up of a High Carbon Steel (HCS) metal matrix, reinforced with Magnesium Oxide (MgO) ceramic is analyzed. The iterative method implemented is fast and converges to the solution which can be further improved by considering a higher number of iterations. This is depicted graphically by using radial displacement and stresses in a pressurized functionally graded cylinder obtained for the first two iterations. An iterative solution for non-FGM (or homogeneous material) is validated using the finite element method. The mechanical responses of the functionally graded cylinder obtained from the iterative method and the finite element method are then compared and found to be in good agreement. Results are presented in graphical and tabular form along with their interpretations.

Secondary Creep Analysis of FG Rotating Cylinder with Exponential, Linear and Quadratic Volume Reinforcement.

Creep is an irreversible time-dependent deformation in which a material under constant mechanical stress and elevated temperature for a considerably prolonged period of time, starts to undergo permanent deformation. Creep deformation occurs in three stages namely, primary, secondary and tertiary. Out of these three stages, secondary or steady state creep is particularly an area of engineering interest as it has almost a constant creep rate. Creep deformation plays a significant role in understanding effective service life of an engineering component working under high temperature conditions as such components such as super-heater and re-heater tubes and headers in a boiler, jet engines operating at temperature as high as 1200 ∘C, usually experience a failure or rupture due to creep phenomenon. Design engineers keep a close attention on working stress conditions and elevated temperature under which an engineering component is expected to work as these conditions determine the onset of creep behavior in an engineering component. By recognizing the parameters of material response to creep behavior, engineers can analyse the useful service life and hazardous working conditions for an engineering components. Recognizing the creep phenomenon as high temperature design limitation, ASME Boiler and Pressure Vessel Code have provided guidelines on maximum allowable stresses for materials to be used in creep range. One of the criteria for determination of allowable stresses is 1% creep deformation of material in 100,000 h of service. Thus, the study of creep behavior in engineering components pertaining to high stress and temperature working conditions is very important as it affects the reliability and performance of the engineering components. The aim of our study is to understand the behavior of secondary creep deformation so that an advanced reinforced functionally graded material with better creep resistance, can be designed. In this paper, a secondary creep analysis of functionally graded (FG) thick-walled rotating cylinder under internal and external pressure is conducted. The novelty of the model intends to specify secondary creep stresses and strains by employing exponential, linear and quadratic volume reinforcement for SiCp ceramic in Al metal matrix in radial direction. This will help us to understand the effect of volume reinforcement in FG cylinder under internal/external pressure and rotating centrifugal body force by obtaining secondary creep stresses and strains. The response of the FG cylinder with isotropic material is analyzed and the solution for stress-strain rates in radial and tangential directions are obtained in closed form. Comparison of steady state creep stresses and strains under exponential, linear and quadratic volume reinforcement profiles are discussed and presented graphically.

Characterization of Mesothelin Glycosylation in Pancreatic Cancer: Decreased Core Fucosylated Glycoforms in Pancreatic Cancer Patients' Sera.

Currently, there are no reliable biomarkers for the diagnosis of pancreatic cancer (PaC). Glycoproteomic approaches that analyze the glycan determinants on specific glycoproteins have proven useful to develop more specific cancer biomarkers than the corresponding protein levels. In PaC, mesothelin (MSLN) is a neo-expressed glycoprotein. MSLN glycosylation has not been described and could be altered in PaC. In this work, we aimed to characterize MSLN glycans from PaC cells and serum samples to assess their potential usefulness as PaC biomarkers. First, we analyzed MSLN glycans from PaC cell lines and then we developed an enzyme-linked lectin assay to measure core fucosylated-MSLN (Cf-MSLN) glycoforms. MSLN glycans from PaC cells were analyzed by glycan sequencing and through Western blotting with lectins. All of the cell lines secreted MSLN, with its three N-glycosylation sites occupied by complex-type N-glycans, which were mainly α2,3-sialylated, core fucosylated and highly branched. The Cf-MSLN glycoforms were quantified on PaC serum samples, and compared with MSLN protein levels. The Cf-MSLN was significantly decreased in PaC patients compared to control sera, while no differences were detected by using MSLN protein levels. In conclusion, Cf-MSLN glycoforms were differently expressed in PaC, which opens the way to further investigate their usefulness as PaC biomarkers.

Semantic Analysis and Topic Modelling of Web-Scrapped COVID-19 Tweet Corpora through Data Mining Methodologies.

The evolution of the coronavirus (COVID-19) disease took a toll on the social, healthcare, economic, and psychological prosperity of human beings. In the past couple of months, many organizations, individuals, and governments have adopted Twitter to convey their sentiments on COVID-19, the lockdown, the pandemic, and hashtags. This paper aims to analyze the psychological reactions and discourse of Twitter users related to COVID-19. In this experiment, Latent Dirichlet Allocation (LDA) has been used for topic modeling. In addition, a Bidirectional Long Short-Term Memory (BiLSTM) model and various classification techniques such as random forest, support vector machine, logistic regression, naive Bayes, decision tree, logistic regression with stochastic gradient descent optimizer, and majority voting classifier have been adapted for analyzing the polarity of sentiment. The effectiveness of the aforesaid approaches along with LDA modeling has been tested, validated, and compared with several benchmark datasets and on a newly generated dataset for analysis. To achieve better results, a dual dataset approach has been incorporated to determine the frequency of positive and negative tweets and word clouds, which helps to identify the most effective model for analyzing the corpora. The experimental result shows that the BiLSTM approach outperforms the other approaches with an accuracy of 96.7%.

[Celiac artery stenosis and cephalic duodenopancreatectomy: an undervalued risk?]. / La estenosis del tronco celiaco y duodenopancreatectomía cefálica: ¿un riesgo infravalorado?

INTRODUCTION: Significant celiac trunk or artery stenosis (CAS) is normally asymptomatic. However, when the arteries of the pancreatoduodenal arcade are occluded, it could trigger a visceral ischaemia. The objective of this study is to determine whether preoperative CAS is a risk factor for developing complications in patients subjected to duodenopancreatectomy (DPC). MATERIAL AND METHODS: We have retrospectively analysed 58 consecutive patients subjected to DPC. We have associated significant CAS with post-surgical outcome. In all cases a 16-channel multidetector computed tomography (MDCT) in three hepatic phases was performed. We have reviewed the pre-surgical MDCT focusing on the morphology of the celiac artery (CA), particularly in the presence or absence of significant stenosis (>50%). RESULTS: We found CAS >50% in 13 patients (22%). The overall mortality was 5% (3 patients). Serious complications developed in 16 (28%) patients, 8 (62%) of whom belonged to the group with significant CAS (P=.004). Ten patients (17%) had a pancreatic fistula, 5 (38%) vs. 5 (11%) (P=.036); Fourteen patients (24%) needed new surgery, 7 (54%) vs. 7 (16%) (P=.009); Seven patients (12%) had a haemoperitoneum, 4 (31%) vs. 3 (7%) (P=.038), in the group with and without CAS, respectively. CONCLUSIONS: Significant radiological CAS is a risk factor of serious complications after DPC. The study of the calibre of the superior mesenteric artery (SMA) with MDCT should be routine before a DPC. The correction of a significant CAS should be evaluated preoperatively.

Sustainability issues in a tropical mega trail.

Sustainability is a target that involves many socio-ecological questions, depends on opportunities and combines different initiatives. This can be especially difficult in regions with high biodiversity scores, mega cities, high level of human populations and an intense and long-standing land use. Here, we show how a mega trail, named Atlantic Forest Trail, within the Brazilian Atlantic Forest can join the protection of biodiversity and sustainable tourism through a 4270 km corridor connecting protected areas and crossing a variety of landscapes. Further, we show some initiatives of ongoing biodiversity monitoring, and an analysis of ecological restoration in private lands that can be applied in many regions to improve habitat connectivity for both biodiversity and human use.

Microfibril associated protein 4 (MFAP4) is a carrier of the tumor associated carbohydrate sialyl-Lewis x (sLex) in pancreatic adenocarcinoma.

Late diagnosis of pancreatic ductal adenocarcinoma (PDA) is one of the reasons of its low 5-year survival rate and it is due to its unspecific symptoms during the first stages of the disease and the lack of reliable serological markers. Since PDA shows an altered glycan expression, here we have focused on finding novel potential biomarkers, namely glycoproteins that express the tumor associated carbohydrate structure sialyl-Lewis x (sLex), which is described in PDA. Through a glycoproteomic approach, we have analyzed target proteins containing sLex from PDA tissues by 2DE and immunodetection techniques, and have identified by mass spectrometry the protein MFAP4 as a carrier of sLex in PDA. MFAP4 showed a higher expression in PDA tissues compared with pancreatic control tissues. In addition, the colocalization of sLex over MFAP4 was found only in PDA and not in control pancreatic tissues. The analysis of MFAP4 expression in PDA cell lines and their secretome, in combination with immunohistochemistry of pancreatic tissues, revealed that MFAP4 was not produced by PDA cells, but it was found in the pancreatic extracellular matrix. The specificity of MFAP4 glycoform containing sLex in PDA tissues shows its relevance as a potential PDA biomarker. SIGNIFICANCE: Despite advances in the field of cancer research, pancreatic ductal adenocarcinoma (PDA) lacks of a specific and sensitive biomarker for its early detection, when curative resection is still possible before metastases arise. Thus, efforts to discover new PDA biomarkers represent the first line in the fight against the increase of its incidence reported in recent years. Glycan alterations on glycoconjugates, such as glycoproteins have emerged as a rich source for the identification of novel cancer markers. In the present work, we aimed to shed light on novel biomarkers based on altered glycosylation in PDA, in particular those glycoproteins of PDA tissues carrying the tumor carbohydrate antigen sialyl-Lewis x (sLex). Through a glycoproteomic approach, we have shown that the glycoprotein MFAP4 carries sLex in PDA tissues and not in control pancreatic tissues. MFAP4 is found in the extracellular matrix in PDA and although its role in cancer progression is unclear, its sLex glycoform could be a potential biomarker in pancreatic ductal adenocarcinoma.

Ética médica y atención a pacientes en estadio terminal en el nivel primario de atención / Medical Ethics and End-stage Patient Care at the Primary Care Level

Introducción: El artículo reflexiona sobre la naturaleza multidimensional y compleja de la ética y su relación con las ciencias médicas. Objetivo: Reflexionar sobre la atención a pacientes en estadio terminal desde el punto de vista de la ética médica para una atención médica integral en el primer nivel de atención. Métodos: estudio cualitativo; se emplearon análisis documental, sistematización, análisis y síntesis de publicaciones sobre la temática estudiada como métodos teóricos, para ello se valoran los criterios de autores y resultados que se expresan en artículos publicados. Se realizaron búsquedas, tanto en bases de datos estudiadas como en las plataformas de productos del Nacional Council for Biotechnology Information de la Nacional Library of Medicine of United States of America; y de Elsevier, esta última productora de Embase y Scopus, a través del motor de búsqueda Google Académico, en español e inglés, y sin límite de tiempo. Se emplearon los términos: ética médica, deontología médica, relación médico-paciente, paciente terminal y cuidados paliativos. Se excluyeron aquellos artículos que no habían sido revisados por pares o no mostraban el texto completo. Se revisó la información suministrada por cada fuente y se sintetizó. Conclusiones: En Cuba, la bioética avanza en la medida que lo permite la estrategia de Atención Primaria de Salud, con un Programa del Médico y Enfermera de la Familia resiliente y de valores humanos demostrados nacional e internacionalmente. Como reto se plantea estimular el debate entre saberes para generar cambios a favor de los pacientes, las familias, las comunidades y la sociedad(AU)

Introduction: The article reflects on the multidimensional and complex nature of ethics and its relationship to the medical sciences. Objective: To reflect on the care of terminally ill patients from the point of view of medical ethics for comprehensive medical care at the primary level of care. Methods: A qualitative study was carried out using documentary analysis, systematization, analysis and synthesis of publications on the subject studied as theoretical methods. For this purpose, the criteria of authors and results expressed in published articles were evaluated. Searches were carried out in Spanish and English through Google Scholar, and without time limit, both in the databases studied and in the product platforms of the National Council for Biotechnology Information of the National Library of Medicine of the United States of America and Elsevier. The terms: medical ethics, medical deontolog, physician-patient relationship, terminal patient and palliative care were used. Articles that were not peer-reviewed and those that did not show the full text were excluded. The information provided by each source was reviewed and synthesized. Conclusions: In Cuba, bioethics advances to the extent allowed by the Primary Health Care strategy, with a resilient Family Physician and Nurse Practitioner Program and human values demonstrated nationally and internationally. The challenge is to stimulate the debate between knowledge to generate changes in favor of patients, families, communities and society(AU)

[Hepatic angiomyolipoma in two patients infected with hepatitis C virus]. / Angiomiolipoma hepático en dos pacientes con infección por el virus de la hepatitis C.

AIM: The aim of this study is to present our experience with two cases of hepatic angiomyolioma in hepatitis C virus (HCV) positive patients, and to up-date the clinical manage, diagnostic and treatment of this entity. CLINICAL OBSERVATIONS: Both cases were presented in women in their 4-5th decade of life. Clinical presentation was with symptoms in one but incidental in the other. Both were HCV positive. Values of alpha-fetoprotein were normal. Radiological imaging was not diagnostic. Histopathological examination and immunohistochemical findings gave the diagnosis of angiomyolipoma. At time of diagnosis the size of tumours was 4.8 and 8 cm of diameter. Both cases were treated with surgery in order to definetly rule out malignancy. After 6 and 3 years of follow-up, there is no evidence of recurrence. DISCUSSION AND CONCLUSION: The hepatic angiomyolipoma is a rare benign tumour, mimicking other liver tumours. Although no patognomonic features, there are some radiological findings that point out to the diagnosis of angiomy olipoma. Nevertheless, definitive diagnosis is done by his tological and immunohistochemical findings (HMB-45). The hepatic angiomyolipoma consists of varing proportion of three elements, mature fat cells, smooth muscle cells and blood vessels. Although it is a benign tumour, the difficulty in ruling out malignancy, prompted surgical management. It is not described its relation with HCV virus, thus we consider our cases as an coincident finding.

Evolution of substrate specificity in a retained enzyme driven by gene loss.

The connection between gene loss and the functional adaptation of retained proteins is still poorly understood. We apply phylogenomics and metabolic modeling to detect bacterial species that are evolving by gene loss, with the finding that Actinomycetaceae genomes from human cavities are undergoing sizable reductions, including loss of L-histidine and L-tryptophan biosynthesis. We observe that the dual-substrate phosphoribosyl isomerase A or priA gene, at which these pathways converge, appears to coevolve with the occurrence of trp and his genes. Characterization of a dozen PriA homologs shows that these enzymes adapt from bifunctionality in the largest genomes, to a monofunctional, yet not necessarily specialized, inefficient form in genomes undergoing reduction. These functional changes are accomplished via mutations, which result from relaxation of purifying selection, in residues structurally mapped after sequence and X-ray structural analyses. Our results show how gene loss can drive the evolution of substrate specificity from retained enzymes.

[Major hepatectomies are safe in patients with cholangiocarcinoma and jaundice]. / Las hepatectomías mayores en pacientes con colangiocarcinoma e ictericia son seguras.

BACKGROUND: Surgical resection is the only possibility of long term survival in patients with Klatskin tumours. However, surgical resection is a challenging problem and hepatic resection is often necessary. OBJECTIVE: The aim of our study was to assess the need for biliary drainage, resection rate and outcome of hilar cholangiocarcinoma in a single tertiary referral centre. PATIENTS AND METHODS: From 2005 to 2008, 26 patients with Klatskin tumours were identified and assessed prospectively with multidetector CT and MR cholangiography in special cases. Seven patients (27%) were deemed to be unresectable in pre-operative staging. A total of 19 surgical procedures were performed, 8 left hepatectomies, 5 right hepatectomies and 6 resections exclusively of the biliary tree. RESULTS: Resection rate was 73%, transfusion rate 53% and preoperative biliary drainage was performed only in 7 cases (37%). Major complications occurred in 11 (58%), including two post-operative deaths (10%). There were no differences in the epidemiological data, when we separately analysed the outcomes of the 9 patients with bilirubin<15 mg/dL and the 10 patients with bilirubin>15 mg/dL. Biliary drainage was required in 6 (67%) patients in the group with low bilirubin levels vs. 1(10%) in the other group (P=0.02). The mean bilirubin level in the jaundiced group was 22.1+/-3.9 vs. 4.7+/-4.3 (P<0.001) in the other group. There were no differences in the postoperative outcome between both groups. CONCLUSION: Resection and survival rates have increased recently but still carries the risk of significant morbidity and mortality. Major hepatectomies in selected patients without percutaneous biliary drainage are safe.

3,6-Dihydroxy-2-(11-phenylundecanoyl)cyclohex-2-en-1-one from Virola venosa bark.

The structure of the title compound, C23H32O4, an arylalkanone isolated from the petroleum ether fraction of the ethanol extract of the bark of Virola venosa, has been established by NMR spectroscopy and, for the first time, by X-ray structure analysis. Two independent molecules of the same enantiomer are present in the unit cell. Both molecules exhibit an intramolecular hydrogen bond, which can be correlated with a rare signal observed at 18.28 p.p.m. in the 1H NMR spectrum. The packing, in space group P1, is determined by a pseudo-center of symmetry leading to a short intermolecular contact, which is present in one molecule but does not occur in the other. As a consequence, the O-C-C-O torsion angles [-16.9 (3) and -12.7 (3) degrees ] through the ketone and its adjacent hydroxy group are significantly different in the two molecules.