The second Mexican consensus on hepatocellular carcinoma. Part II: Treatment.

Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this second part of the document, the topics related to the treatment of HCC are presented.

The second Mexican consensus on hepatocellular carcinoma. Part I: Epidemiology and diagnosis.

Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this first part of the document, the topics related to epidemiology and diagnosis are presented.

Inhibition of toll-like receptor 4 protects against inflammation-induced mechanobiological alterations to intervertebral disc cells.

Intervertebral disc (IVD) degeneration is associated with elevated levels of inflammatory cytokines implicated in disease aetiology and matrix degradation. Toll-like receptor-4 (TLR4) has been shown to participate in the inflammatory responses of the nucleus pulposus (NP) and its levels are upregulated in disc degeneration. Activation of TLR4 in NP cells leads to significant, persistent changes in cell biophysical properties, including hydraulic permeability and osmotically active water content, as well as alterations to the actin cytoskeleton. The study hypothesis was that inflammation-induced changes to cellular biomechanical properties and actin cytoskeleton of NP cells could be prevented by inhibiting TLR4 signalling. Isolated NP cells from bovine discs were treated with lipopolysaccharide (LPS), the best studied TLR4 agonist, with or without treatment with the TLR4 inhibitor TAK-242. Cellular volume regulation responses to step osmotic loading were measured and the transient volume-response was captured by time-lapse microscopy. Volume-responses were analysed using mixture theory framework to investigate hydraulic permeability and osmotically active intracellular water content. Hydraulic permeability and cell radius were significantly increased with LPS treatment and these changes were blocked in cells treated with TAK-242. LPS-induced remodelling of cortical actin and IL-6 upregulation were also mitigated by TAK-242 treatment. These findings indicated that TLR4 signalling participated in NP cell biophysical regulation and may be an important target for mitigating altered cell responses observed in IVD inflammation and degeneration.

Volatile organic compounds (VOCs) in solid waste landfill cover soil: Chemical and isotopic composition vs. degradation processes.

Landfills for solid waste disposal release to the atmosphere a large variety of volatile organic compounds (VOCs). Bacterial activity in landfill cover soils can play an important role in mitigating VOC emission. In order to evaluate the effects of degradation processes and characterize VOCs composition in landfill cover soil, gases from 60 sites and along 7 vertical profiles within the cover soil were collected for chemical and isotopic analysis at two undifferentiated urban solid waste disposal sites in Spain: (i) Pinto (Madrid) and (ii) Zurita (Fuerteventura, Canary Islands). The CO2/CH4 ratios and δ13C-CO2 and δ13C-CH4 values were controlled by either oxidation or reduction processes of landfill gas (LFG). VOCs were dominated by aromatics, alkanes and O-substituted compounds, with minor cyclics, terpenes, halogenated and S-substituted compounds. Degradation processes, depending on both (i) waste age and (ii) velocity of the uprising biogas through the soil cover, caused (i) an increase of degradation products (e.g., CO2, O-substituted compounds) and (ii) a decrease of degradable components (e.g., CH4, alkanes, alkylated aromatics, cyclic and S-substituted compounds). Terpenes, halogenated compounds, phenol and furans were unaffected by degradation processes and only depended on waste composition. These results highlight the fundamental role played by microbial activity in mitigating atmospheric emissions of VOCs from landfills. Nevertheless, the recalcitrant behaviour shown by compounds hazardous for health and environment remarks the importance of a correct landfill management that has to be carried out for years after the waste disposal activity is completed, since LFG emissions can persist for long time.

High concentrations of atorvastatin reduce in-vitro function of conventional T and regulatory T cells.

Regulatory T cells (Tregs ) modulate the magnitude of immune responses and possess therapeutic potential in an array of immune diseases. Statins reduce the activation and proliferation of conventional T cells (Tcons ), and they seem to up-regulate the frequency and function of Tregs . However, there is a lack of simultaneous evaluation of the in-vitro effect of statins on the functional profile of Tregs versus Tcons . Herein, magnetically purified Tcons and Tregs were stimulated with CD3/CD28/interleukin (IL)-2 in the presence of atorvastatin (ATV) at 1 or 10 µM. The suppressive function of Tregs , the expression of markers associated with Treg function, activation levels, cytokine production and calcium flux in both subpopulations were assessed by flow cytometry. ATV had no cytotoxic effect on T cells at the concentrations used. Interestingly, 10 µM ATV hampered the suppressive capacity of Tregs . Moreover, this higher concentration reduced the expression of forkhead box protein 3 (FoxP3), cytotoxic T lymphocyte antigen (CTLA-4) and programmed death 1 (PD-1). In Tcons , ATV at 10 µM decreased PD-1 and CD45RO expression. The expression of CD25, CD69, CD95, CD38, CD62L, CCR7 and perforin was not affected in both subpopulations or at any ATV concentrations. Remarkably, 10 µM ATV increased the percentage of tumour necrosis factor (TNF)-α-producing Tregs . Although there was a reduction of calcium flux in Tcons and Tregs , it was only significant in 10 µM ATV-treated Tcons . These results suggested that 10 µM ATV affects the cellular functions of both populations; however, this concentration particularly affected several aspects of Treg biology: its suppressive function, cytokine production and expression of Treg -specific markers.

In vitro study of a modified sagittal split osteotomy fixation technique of the mandible: a mechanical test.

This study was performed to evaluate the compressive mechanical strength of rigid internal fixation (RIF) using 1.5-mm L-shaped plates fixed with monocortical screws in sagittal split osteotomy (SSO). Thirty synthetic hemimandibles, which had all undergone a 5-mm advancement, were divided into three groups: three 12-mm bicortical titanium screws were placed in an inverted L pattern in group A; one straight 2.0-mm system spaced titanium plate fixed with four 5-mm monocortical screws was used in group B; two 1.5-mm system L-shaped titanium plates, each fixed with four 5-mm monocortical screws, were used in group C. The models were subjected to compressive and progressive mechanical tests with forces applied in the area between the second premolar and first molar to verify resistance in Newtons (N). A displacement speed of 1mm/min was applied, with a maximum 10mm displacement of the distal segment or until disruption of the fixation. The deformity and/or eventual rupture of the plates were evaluated, and consequently their technical stability was determined. The results showed that the modified fixation technique tested in this study on synthetic mandibles resulted in adequate stability and superior mechanical behaviour compared to simulated osteosynthesis with the use of a straight 2.0-mm titanium plate.

Sexual behavior and seminal characteristics of fertile mature New Zealand White male rabbits of different body weights.

Body weight in different mammalian species influences reproductive potential. The aim of the present study was to determine the relationship of body weight at the time of semen collection with libido, seminal characteristics and number of semen doses for artificial insemination (AI) in New Zealand White mature fertile male rabbits. Data came from 728 semen collections of 14 rabbits, 15-months of age that were sexually experienced with proven semen quality and fertility. Semen collection was performed twice a week with two ejaculates at each collection time and lasted 14 weeks. A second ejaculation was collected at 1-2h after the first. Data from each male from first and second ejaculates from 1 day of semen collection throughout the trial were averaged (n=324) and partial correlation coefficients and regression equations were estimated to describe the relationship of male body weight to ejaculation reaction time and 12 semen and sperm characteristics. As body weight increased there was a linear (P<0.05) increase in reaction time, abnormal sperm with an intact membrane and abnormal sperm with a damaged membrane and a linear (P<0.05) decrease in semen volume, sperm concentration per ejaculate, normal sperm with an intact membrane, number of normal motile sperm with an intact membrane and suitable semen doses for AI. Body weight of the mature male rabbit at semen collection had some influence on libido, semen and sperm characteristics, with a general trend toward a lesser reproduction potential as body weight increases.

Implementation of quality systems by Mexican exporters of processed meat.

Requirements of hazard analysis and critical control points (HACCP) are becoming essential for international trade in food commodities as a safety assurance component. This research reports the level of the adoption of ISO 9000 and the HACCP system by Federal Inspection Type (TIF) pork-exporting enterprises. Implementation and operating costs are reported as well as the benefits involved in this food industry process. In Mexico, there are 97 companies classified as TIF enterprises, and 22 are registered as exporters of processed pork with the National Services for Safety and Quality and Animal Health of the Secretariat of Agriculture, Livestock, Rural Development, Fisheries and Food. Surveys were administered to 22 companies, with a 95.2% response rate. Enterprise characteristics were evaluated, as well as their operating activities. Fieldwork consisted of administering structured questionnaires to TIF exporters. All the surveyed enterprises had implemented HACCP, whereas the ISO 9000 regulation was applied in only 30%. Of total production, 75% is exported to 13 countries, and 25% goes to the Mexican market niche. Results indicate that the main factors for adopting HACCP are related to accessibility to international markets, improving quality, and reducing product quality audits by customers. The results also indicated that staff training was the most important issue. Microbiological testing was the highest cost of the operation. The main benefits reported were related to better access to international markets and a considerable reduction in microbial counts. This study shows the willingness of Mexican pork processors to implement food safety protocols for producing safe and quality products to compete in the international food trade.

Accuracy assessment of prototypes produced using multi-slice and cone-beam computed tomography.

The objective of this study was to assess and quantify the dimensional error of prototypes produced using multi-slice and cone-beam computed tomography (MSCT and CBCT). Titanium screws were inserted into a dry skull at different points of the midface. The skull was scanned using MSCT (LightSpeed16) with pixel size 0.3 mm and CBCT (i-CAT Cone-Beam 3D) with voxel sizes 0.25 and 0.4 mm. Prototypes were printed (fabricated) using a ZPrinter 310 device. Both the dry skull (gold standard) and the prototypes were measured using a Mitutoyo 3D coordinate measuring system with three perpendicular axes (X, Y, and Z). The prototype produced from MSCT data presented a mean dimensional error of 0.62%; the two models produced with CBCT images yielded errors of 0.74% with voxel size 0.25 mm and 0.82% with voxel size 0.40 mm. No significant differences in dimensional errors were observed across the prototypes (p=0.767; Friedman's non-parametric test). Prototypes produced from CBCT data using voxel sizes of 0.25 and 0.4mm, and also the one produced from MSCT data using pixel size 0.3mm, showed acceptable dimensional errors and can therefore be used in the fabrication of prototypes in dentistry.

Rabbit sexual behavior, semen and sperm characteristics when supplemented with sprouted wheat.

The sprouted wheat (SW) contains the 6-methoxy-2-benzoxazolinone (6-MBOA), a phenol compound that stimulates reproduction in certain small wild herbivorous mammals. The objective of the present study was to evaluate the effect of short-term supplemental dietary SW on libido, semen and sperm characteristics of rabbit bucks. Five-month old New Zealand White pubertal rabbits (n=18) were randomly allocated to one of two treatments: supplementation or not (control) supplemented with SW. The experimental design was completely random with nine replications, experimental unit was one buck. Semen collection for each male was conducted once a week with two ejaculations during 20 weeks. The SW was given during four consecutive days prior to each semen collection. Analysis of variance was under a mixed model: treatment, ejaculate number and season were fixed and rabbit random effects. There was no effect of treatment (P>0.05) on reaction time, gel presence, volume, pH, sperm motility, sperm number per ml and sperm number per ejaculate. The percentage of normal alive spermatozoa was 13.5% greater in SW-supplemented bucks than in the control and the percentage of abnormal alive spermatozoa was 44.1% greater in the control than in the SW-supplemented bucks. The morphology of dead spermatozoa, integrity of acrosome, number of normal alive motile sperm and semen doses per ejaculate were not influenced (P>0.05) by SW supplementation. The proportion of presence of gel and semen volume in the first ejaculate was greater than the second ejaculate (+140% and +56.4%). However, the semen quality in the latter was greater (P=0.0001) than the former in terms of an increase in motility (+29.7%). Reproductive traits were more desirable (P<0.05) in winter than autumn. Dietary wilted SW as a source of biological 6-MBOA enhanced sperm characteristics in terms of a greater percentage of normal alive and lesser percentage of abnormal alive spermatozoa but did not affect the number of normal motile live sperm and suitable semen doses in rabbit bucks in autumn and winter.

Controlled doe exposure as biostimulation of buck rabbits.

Female exposure of males could be a low-cost biostimulation option that benefits AI in commercial rabbit operations by improving buck rabbits reproductive performance. The objective of the study was to evaluate exposure of buck rabbits to females as a biostimulation option to improve reproductive potential. Treatments were: exposure (biostimulated) or not (control) of bucks to does. Bucks were New Zealand White, 15-month-old, sexually experienced and fertile. Experimental design was completely random with nine replications, experimental unit was one buck. Doe exposure was permanent using replacement pubertal does housed in an adjacent wire-mesh cage and changed for new ones every other week. Semen collection lasted 14 weeks (late winter and early spring) twice a week with two ejaculates at each collection. Analyses of variance were under a mixed model: treatments, ejaculate number and season were fixed and rabbit random effects and buck weight at each collection as covariable. Biostimulated bucks showed greater (P<0.05) reproductive potential due to: 7% lesser reaction time (greater libido); and increased semen volume (40%), sperm motility (29%), sperm per ejaculate (31%), normal alive motile sperm (65%) and number of semen doses (64%). Semen characteristics differed by season in control bucks but not in doe exposed bucks (treatment × ejaculate number, P<0.05). Reproductive potential in spring was greater (P<0.05) than in winter in both treatments. Doe exposure is a biostimulation method that improves sexual drive and sperm production and quality of buck rabbits.

Unidades de Cuidados Especiales Intermedios, ¿qué utilidad tienen en un Servicio de Medicina Intensiva? / Special Intermediate Care Units, what utility does this have in an Intensive Medicine Department?

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Characterizing brain anatomical connections using diffusion weighted MRI and graph theory.

A new methodology based on Diffusion Weighted Magnetic Resonance Imaging (DW-MRI) and Graph Theory is presented for characterizing the anatomical connections between brain gray matter areas. In a first step, brain voxels are modeled as nodes of a non-directed graph in which the weight of an arc linking two neighbor nodes is assumed to be proportional to the probability of being connected by nervous fibers. This probability is estimated by means of probabilistic tissue segmentation and intravoxel white matter orientational distribution function, obtained from anatomical MRI and DW-MRI, respectively. A new tractography algorithm for finding white matter routes is also introduced. This algorithm solves the most probable path problem between any two nodes, leading to the assessment of probabilistic brain anatomical connection maps. In a second step, for assessing anatomical connectivity between K gray matter structures, the previous graph is redefined as a K+1 partite graph by partitioning the initial nodes set in K non-overlapped gray matter subsets and one subset clustering the remaining nodes. Three different measures are proposed for quantifying anatomical connections between any pair of gray matter subsets: Anatomical Connection Strength (ACS), Anatomical Connection Density (ACD) and Anatomical Connection Probability (ACP). This methodology was applied to both artificial and actual human data. Results show that nervous fiber pathways between some regions of interest were reconstructed correctly. Additionally, mean connectivity maps of ACS, ACD and ACP between 71 gray matter structures for five healthy subjects are presented.

Influence of supplemental dietary sprouted wheat on reproduction in artificially inseminated doe rabbits.

The sprouted wheat contains great amounts of 6-methoxybenzoxazolinone (6-MBOA) a phenol compound that stimulates reproduction in certain small wild herbivorous mammals. The objective of the present study was to evaluate the effect of dietary sprouted wheat as supplement on reproduction in artificially inseminated doe rabbits. Two-month-old New Zealand White doe rabbits (n = 48) were randomly allocated to one of two treatments: (1) pelleted diet plus sprouted wheat for 6 consecutive days prior to service, (2) pelleted diet only (control). First insemination occurred when does reach 3200g body weight and bred 6 days after parturition across 6 months period during summer and autumn. Records from 41 does completing the experiment accounted for 192 inseminations and 142 kindlings equivalent to 4.6 +/- 0.15 and 3.5 +/- 0.15 litters per doe, respectively. Mean daily intake of sprouted wheat on wet and dry matter bases were 196.1 +/- 7.5 and 75.4 +/- 2.9g, respectively. The number of young born produced per doe during the trail was significantly (P = 0.02) greater in does fed sprouted wheat (28.1 +/- 1.2 versus 23.6 +/ -1.3 control). Does fed sprouted wheat had 0.65 +/- 0.06 receptivity rate at AI over 28 per cent greater (P = 0.001) than does in the control treatment. Sexual receptivity was not influenced by physiological status of does and season (P > 0.05). Diet and season had no effect (P>0.05) on kindling rate. However, physiological status had an effect (P = 0.002) on this variable. Kindling rates for nulliparous, lactating and non-lactating does were 0.95 +/- 0.08, 0.63 +/- 0.04 and 0.78 +/ -0.11, respectively. Sexually receptive does had a greater (P = 0.0001) kindling rate (0.95 +/- 0.05) than non-receptive females (0.63 +/-0.05). Does fed sprouted wheat produced larger (P = 0.02) litters than those in the control group: 7.7 +/- 0.30 and 6.8 +/- 0.32, respectively. There was an effect of season (P = 0.04) on the size of the litter at birth. Largest litters were born during autumn (7.9 +/- 0.37) than during summer (6.6 +/- 0.41). Receptive does had more (P = 0.002) young in the litter (7.9 +/- 0.28) than non-receptive (6.6 +/- 0.35). Feeding sprouted wheat as a source of biological 6-MBOA enhanced sexual receptivity and prolificacy in artificially inseminated doe rabbits bred in summer and autumn.

3-Year clinical evaluation of posterior packable composite resin restorations.

This study evaluated the clinical performance of four packable resin composite restorative materials in posterior teeth (Class I and II) compared with one hybrid composite after 3 years. Eighty-four restorations were placed in 16 patients. The tested materials were: (i) Solitaire + Solid Bond; (ii) ALERT + Bond-1; (iii) Surefil + Prime & Bond NT; (iv) Filtek P60 + Single Bond and (v) TPH Spectrum + Prime & Bond 2.1. All restorations were made using rubber dam isolation, and the cavity design was restricted to the elimination of carious tissue. Deeper cavities were covered with calcium hydroxide and/or glass-ionomer cement. Each adhesive system and composite resin was placed according to the manufacturer's instructions. One week later, the restorations were finished/polished and evaluated according USPHS modified criteria. Fourteen patients attended the 3-year recall and 75 restorations were evaluated at that time based on the same evaluation criteria. Friedman repeated measures analysis of variance by rank and Wilcoxon sign-ranked test for pair-wise comparison was used for data analysis (alpha = 0.05). The analysis was performed only for the baseline and for the 3-year period. Solitaire showed some fractures at marginal ridges in 25% of the cases. Solitaire and ALERT showed some concerns related to colour match (43 and 77%, respectively) and surface texture (86 and 77%, respectively). TPH Spectrum showed a great percentage of colour mismatch after 3 years, around 50%. Surefil and Filtek P60 showed an excellent clinical performance after 3 years, similar to the hybrid resin tested, TPH Spectrum. Solitaire did not fulfil the ADA acceptance criteria for restorative materials and, therefore, is not recommended for use in posterior restorations.

Carbon dioxide degassing by advective flow from Usu volcano, Japan.

Magmatic carbon dioxide (CO2) degassing has been documented before the 31 March 2000 eruption of Usu volcano, Hokkaido, Japan. Six months before the eruption, an increase in CO2 flux was detected on the summit caldera, from 120 (September 1998) to 340 metric tons per day (September 1999), followed by a sudden decrease to 39 metric tons per day in June 2000, 3 months after the eruption. The change in CO2 flux and seismic observations suggests that before the eruption, advective processes controlled gas migration toward the surface. The decrease in flux after the eruption at the summit caldera could be due to a rapid release of CO2 during the eruption from ascending dacitic dikes spreading away from the magma chamber beneath the caldera.

Limited risk of kidney stone formation during long-term calcium citrate supplementation in nonstone forming subjects.

The physiological and physicochemical effects of long-term calcium citrate supplementation (25 mmol. calcium per day) were assessed in 7 normal premenopausal women. Calcium citrate increased urinary calcium from 3.27 +/- 0.42 mmol. per day (standard deviation) before treatment to 5.16 +/- 0.75 mmol. per day after 1-month of treatment (p < 0.0125). After 3 months of treatment urinary calcium decreased from the 1-month value to 4.54 +/- 0.67 mmol. per day (p < 0.0125) but remained higher than the pretreatment value (p < 0.0125). Fractional intestinal calcium absorption and serum 1,25-dihydroxyvitamin D levels decreased marginally at 1 month of calcium citrate therapy, from 0.457 +/- 0.092 to 0.374 +/- 0.035 (p < 0.05) and from 103 +/- 7 to 77 +/- 14 pmol./l. (p < 0.05), respectively. After 3 months of treatment fractional intestinal calcium absorption decreased further to 0.341 +/- 0.061 (p < 0.0125 compared to pretreatment), whereas serum 1,25-dihydroxyvitamin D remained unchanged at 82 +/- 14 pmol./l. Calcium citrate treatment decreased urinary phosphorus levels significantly from 18.9 +/- 3.3 to 15.0 +/- 2.5 mmol. per day (p < 0.0125) and 14.0 +/- 2.5 mmol. per day (p < 0.05) at 1 and 3 months, respectively. Mean urinary oxalate decreased by 15 to 20% and urinary citrate increased marginally during treatment. Urinary saturation of calcium oxalate and brushite did not change during calcium citrate therapy, except at 1 month when the saturation of calcium oxalate increased marginally. The inhibitory activity of urine against spontaneous nucleation of calcium oxalate and brushite (formation product) did not change during treatment. In conclusion, long-term calcium citrate supplementation in normal subjects does not increase the propensity for crystallization of calcium salts in the urine. This protective effect is probably due to the attenuated increase in urinary calcium excretion (from a decrease in fractional intestinal calcium absorption), a decrease in urinary phosphorus and an increase in urinary citrate.