Hepatocellular carcinoma: Review of disease and tumor biomarkers.

© The Author(s) 2016.Hepatocellular carcinoma (HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial. International guidelines advise regular surveillance of high-risk populations but the current tools lack sufficient sensitivity for early stage tumors on the background of a cirrhotic nodular liver. A number of novel biomarkers have now been suggested in the literature, which may reinforce the current surveillance methods. In addition, recent metabonomic and proteomic discoveries have established specific metabolite expressions in HCC, according to Warburgs phenomenon of altered energy metabolism. With clinical validation, a simple and non-invasive test from the serum or urine may be performed to diagnose HCC, particularly benefiting low resource regions where the burden of HCC is highest

Hypernatremia: Complication of Renal Homotransplantation

Hypernatremia was observed in five recipients of renal homografts during the first postoperative week. The peak serum levels of sodium varied between 152 and 158 mEq/liter. The postoperative diuresis was associated with sodium concentration in the urine, consistently lower than that in the extracellular water; moderate urinary hypertonicity, with urea being the main urinary solute; and urea excretion exceeding 60% of its filtered load in most instances. The inability of elaborate urine with sodium concentration equal or higher than that in the serum, possibly related to osmotic diuresis and/or altered renal hemodynamics, appears to be the primary cause responsible for the development of hypernatremia in these patients. © 1971, American Medical Association. All rights reserved

Acute renal response to large doses of intravenous prednisolone in kidney homograft recipients and in normal subjects

The immediate renal response to large intravenous doses of prednisolone was studied in 18 kidney homograft recipients and in 6 normal subjects. Clearance rates of inulin (CIN), creatinine (CCR), p-aminohippurate (CPAH), and electrolytes were measured over 3 one-hour periods following intravenous infusion of prednisolone (1 Gm.) and compared with corresponding clearance rates after a placebo infusion. CIN, CCR, and CPAH rates and ( CCR CIN) ratios exhibited a substantial decrease during all collection periods following the infusion of prednisolone, both in the normal subjects and in the patients. Fractional excretion of potassium ( CK CIN) increased in a progressive fashion reaching peak values after 3 hours. Biphasic variations were observed in the fractional excretion of sodium ( CNA CIN); an increase during the first hour was followed by a decrease during the third hour. The changes in the fractional excretions of ultrafiltrable calcium ( CCa CIN), ultrafiltrable magnesium ( CMg CIN), and phosphorus ( CP CIN) were minimal. Normal subjects exhibited significant decreases in ( CCa CIN) and ( CMg CIN) following the infusion of prednisolone; there was no significant change in the patients. ( CP CIN) increased significantly both in the normal subjects and in the patients. These results indicate that acute suppression of kidney function is a general renal response to large doses of glucocorticoids. The marked decrease in the creatinine clearance ratio ( CCR CIN) observed after the administration of prednisolone is consistent with a depressed tubular secretion of creatinine and emphasizes the inadequacy of cCR as an indication of glomerular filtration rate (GFR) under conditions in which large doses of glucocorticoids are employed. © 1971

On relating rheology and oral tribology to sensory properties in hydrogels

The aim of this study was to understand the relationship between rheological, tribological and sensory properties (n = 11 panellists) of hydrogels differing in hydrocolloid type, concentration and degree of inhomogeneity. Fracture properties of hydrogels containing different ratios of κ-carrageenan (κC) and/or locust bean gum (LBG), sodium alginate (NaA), 300/1000 μm calcium alginate beads (CaA) at 1–4 wt% concentration were determined. Viscosity and friction coefficients (μ) of the hydrogel-boli after simulated oral processing were characterized. Tribology measurements were conducted in a polydimethylsiloxane ball/disc set-up with pre-adsorbed artificial salivary film at 37 °C. ’Scaling’ with boli viscosity showed good agreement of observed data with the Stribeck master curve, however only in the mixed regime i.e. at intermediate values of the product of velocity and lubricant viscosity (Uη). Low μ values of gel boli in the boundary regime were largely driven by the formation of a viscous layer of bolus fragments between opposing surfaces. Fracture properties of hydrogels and boli viscosity were correlated with all chewing-related texture attributes i.e. ‘firm’, ‘elastic’, ‘chewy’ and ‘cohesive’ and inversely correlated with lubrication-related attributes ‘melting’ and ‘pasty’ (p<0.05). On the other hand, μ of the bolus filtrate at orally relevant speeds (50 mm/s) was inversely correlated with lubrication-related attributes ‘pasty’ and positively with ‘slippery’ (p<0.05). The lack of correlations with ‘smooth’ could be explained due to sample inhomogeneity and the absence of ‘ball-bearing’-ability of the gel beads. A combination of initial fracture properties, boli viscosity and tribology of bolus filtrates (mixed regime) impacted the lubrication-related attribute ‘salivating’ (p<0.05)

Treatment decision-making and the form of risk communication: results of a factorial survey

BACKGROUND: Prospective users of preventive therapies often must evaluate complex information about therapeutic risks and benefits. The purpose of this study was to evaluate the effect of relative and absolute risk information on patient decision-making in scenarios typical of health information for patients. METHODS: Factorial experiments within a telephone survey of the Michigan adult, non-institutionalized, English-speaking population. Average interview lasted 23 minutes. Subjects and sample design: 952 randomly selected adults within a random-digit dial sample of Michigan households. Completion rate was 54.3%. RESULTS: When presented hypothetical information regarding additional risks of breast cancer from a medication to prevent a bone disease, respondents reduced their willingness to recommend a female friend take the medication compared to the baseline rate (66.8% = yes). The decrease was significantly greater with relative risk information. Additional benefit information regarding preventing heart disease from the medication increased willingness to recommend the medication to a female friend relative to the baseline scenario, but did not differ between absolute and relative risk formats. When information about both increased risk of breast cancer and reduced risk of heart disease were provided, typical respondents appeared to make rational decisions consistent with Expected Utility Theory, but the information presentation format affected choices. Those 11% – 33% making decisions contrary to the medical indications were more likely to be Hispanic, older, more educated, smokers, and to have children in the home. CONCLUSIONS: In scenarios typical of health risk information, relative risk information led respondents to make non-normative decisions that were "corrected" when the frame used absolute risk information. This population sample made generally rational decisions when presented with absolute risk information, even in the context of a telephone interview requiring remembering rates given. The lack of effect of gender and race suggests that a standard strategy of presenting absolute risk information may improve patient decision-making

The role of the right temporoparietal junction in perceptual conflict: detection or resolution?

The right temporoparietal junction (rTPJ) is a polysensory cortical area that plays a key role in perception and awareness. Neuroimaging evidence shows activation of rTPJ in intersensory and sensorimotor conflict situations, but it remains unclear whether this activity reflects detection or resolution of such conflicts. To address this question, we manipulated the relationship between touch and vision using the so-called mirror-box illusion. Participants' hands lay on either side of a mirror, which occluded their left hand and reflected their right hand, but created the illusion that they were looking directly at their left hand. The experimenter simultaneously touched either the middle (D3) or the ring finger (D4) of each hand. Participants judged, which finger was touched on their occluded left hand. The visual stimulus corresponding to the touch on the right hand was therefore either congruent (same finger as touch) or incongruent (different finger from touch) with the task-relevant touch on the left hand. Single-pulse transcranial magnetic stimulation (TMS) was delivered to the rTPJ immediately after touch. Accuracy in localizing the left touch was worse for D4 than for D3, particularly when visual stimulation was incongruent. However, following TMS, accuracy improved selectively for D4 in incongruent trials, suggesting that the effects of the conflicting visual information were reduced. These findings suggest a role of rTPJ in detecting, rather than resolving, intersensory conflict

Universality of interpersonal psychotherapy (IPT) problem areas in Thai depressed patients

<p>Abstract</p> <p>Background</p> <p>Many studies have shown the efficacy of interpersonal psychotherapy (IPT) on depression; however, there are limited studies concerning the universality of the IPT problem areas in different countries. This study identifies whether the interpersonal problem areas defined in the IPT manual are endorsed by Thai depressed patients.</p> <p>Methods</p> <p>The Thai Hamilton Rating Scale for Depression (Thai HRSD) and Thai Interpersonal Questionnaire were used to assess 90 depressed and 90 non-depressed subjects in King Chulalongkorn Memorial Hospital, during July 2007 - January 2008. The association between interpersonal problem areas/sociodemographic variables and depressive disorder were analyzed by chi-square test. A multivariable analysis was performed by using logistic regression to identify the remaining factors associated with depressive disorder.</p> <p>Results</p> <p>Most of the subjects were young to middle-aged females living in Bangkok and the Central Provinces. All four interpersonal problem areas (grief, interpersonal role disputes, role transitions, and interpersonal deficits) were increased in the depressed subjects as compared to the non-depressed subjects, as were the sociodemographic variables (low education, unemployment, low income, and having a physical illness). Logistic regression showed that all interpersonal problem areas still remained problems associated with depression (grief: adjusted OR = 6.01, 95%CI = 1.93 - 18.69, p < 0.01; interpersonal role disputes: adjusted OR = 6.01, 95%CI = 2.18 - 16.52, p < 0.01; role transitions: adjusted OR = 26.30, 95%CI = 7.84 - 88.25, p < 0.01; and interpersonal deficits: adjusted OR = 2.92, 95%CI = 1.12 - 7.60, p < 0.05).</p> <p>Conclusion</p> <p>All four interpersonal problem areas were applicable to Thai depressed patients.</p

Microevolution of Helicobacter pylori during prolonged infection of single hosts and within families

Our understanding of basic evolutionary processes in bacteria is still very limited. For example, multiple recent dating estimates are based on a universal inter-species molecular clock rate, but that rate was calibrated using estimates of geological dates that are no longer accepted. We therefore estimated the short-term rates of mutation and recombination in Helicobacter pylori by sequencing an average of 39,300 bp in 78 gene fragments from 97 isolates. These isolates included 34 pairs of sequential samples, which were sampled at intervals of 0.25 to 10.2 years. They also included single isolates from 29 individuals (average age: 45 years) from 10 families. The accumulation of sequence diversity increased with time of separation in a clock-like manner in the sequential isolates. We used Approximate Bayesian Computation to estimate the rates of mutation, recombination, mean length of recombination tracts, and average diversity in those tracts. The estimates indicate that the short-term mutation rate is 1.4×10−6 (serial isolates) to 4.5×10−6 (family isolates) per nucleotide per year and that three times as many substitutions are introduced by recombination as by mutation. The long-term mutation rate over millennia is 5–17-fold lower, partly due to the removal of non-synonymous mutations due to purifying selection. Comparisons with the recent literature show that short-term mutation rates vary dramatically in different bacterial species and can span a range of several orders of magnitude

Genetic variation at mouse and human ribosomal DNA influences associated epigenetic states

Background Ribosomal DNA (rDNA) displays substantial inter-individual genetic variation in human and mouse. A systematic analysis of how this variation impacts epigenetic states and expression of the rDNA has thus far not been performed. Results Using a combination of long- and short-read sequencing, we establish that 45S rDNA units in the C57BL/6J mouse strain exist as distinct genetic haplotypes that influence the epigenetic state and transcriptional output of any given unit. DNA methylation dynamics at these haplotypes are dichotomous and life-stage specific: at one haplotype, the DNA methylation state is sensitive to the in utero environment, but refractory to post-weaning influences, whereas other haplotypes entropically gain DNA methylation during aging only. On the other hand, individual rDNA units in human show limited evidence of genetic haplotypes, and hence little discernible correlation between genetic and epigenetic states. However, in both species, adjacent units show similar epigenetic profiles, and the overall epigenetic state at rDNA is strongly positively correlated with the total rDNA copy number. Analysis of different mouse inbred strains reveals that in some strains, such as 129S1/SvImJ, the rDNA copy number is only approximately 150 copies per diploid genome and DNA methylation levels are < 5%. Conclusions Our work demonstrates that rDNA-associated genetic variation has a considerable influence on rDNA epigenetic state and consequently rRNA expression outcomes. In the future, it will be important to consider the impact of inter-individual rDNA (epi)genetic variation on mammalian phenotypes and diseases