Screening is associated with a lower risk of hepatocellular carcinoma-related mortality in patients with chronic hepatitis B

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IGF-1 alters the human parietal pleural electrochemical profile by inhibiting ion trans-cellular transportation after interaction with its receptor

ObjectiveThe effect of IGF-1 in the human pleural permeability and the underlying mechanisms involved were investigated.DesignSpecimens from thoracic surgical patients were mounted in Ussing chambers. Solutions containing IGF-1 (1 nM–100 nM) and IGF-1 Receptor Inhibitor (1 μΜ), amiloride 10 μM (Na⁺ channel blocker) and ouabain 1 mM (Na⁺–K⁺ pump inhibitor) were used in order to investigate receptor and ion transporter involvement respectively. Trans-mesothelial Resistance (R_TM) across the pleural membrane was determined as a permeability indicator. Immunohistochemistry for IGF-1 receptors was performed.ResultsIGF-1 increased R_TM when added on the interstitial surface for all concentrations (p = .008, 1 nM–100 nM) and decreased it on the mesothelial surface for higher concentrations (p = .046, 100 nM). Amiloride and ouabain inhibited this effect. The IGF-1 Receptor Inhibitor also totally inhibited this effect. Immonuhistochemistry demonstrated the presence of IGF-1 receptors in the pleura.ConclusionsIt is concluded that IGF-1 changes the electrophysiology of the human parietal pleura by hindering the normal ion transportation and therefore the pleural fluid recycling process. This event is achieved after IGF-1 interaction with its receptor which is present in the human pleura.     

Responsive robotic prey reveal how predators adapt to predictability in escape tactics

To increase their chances of survival, prey often behave unpredictably when escaping from predators. However, the response of predators to, and hence the effectiveness of, such tactics is unknown. We programmed interactive prey to flee from an approaching fish predator (the blue acara, Andinoacara pulcher) using real-time computer vision and two-wheeled robots that controlled the prey’s movements via magnets. This allowed us to manipulate the prey’s initial escape direction and how predictable it was between successive trials with the same individual predator. When repeatedly exposed to predictable prey, the predators adjusted their behavior before the prey even began to escape: prey programmed to escape directly away were approached more rapidly than prey escaping at an acute angle. These faster approach speeds compensated for a longer time needed to capture such prey during the subsequent pursuit phase. By contrast, when attacking unpredictable prey, the predators adopted intermediate approach speeds and were not sensitive to the prey’s escape angle but instead showed greater acceleration during the pursuit. Collectively, these behavioral responses resulted in the prey’s predictability having no net effect on the time taken to capture prey, suggesting that unpredictable escape behavior may be advantageous to prey in fewer circumstances than originally thought. Rather than minimizing capture times, the predators in our study appear to instead adjust their behavior to maintain an adequate level of performance during prey capture.

Rapid evasive responses are a vital tool prey use to minimize capture by predators (1, 2). Despite their ubiquity, it can be challenging to demonstrate the benefit of escape strategies, due to the difficulties involved in designing studies which integrate realistic predation with manipulation of prey behavior that experimentally controls for confounding effects. Studying the behavior of real predators is crucial when attempting to demonstrate the adaptive value of prey adaptations, especially when these are dependent on features of predator cognition (3–5). This applies particularly to unpredictable escape behavior by prey, which is thought to enhance prey survival by compromising the ability of predators to anticipate the movement of their target (6). Although unpredictable escape tactics are widespread taxonomically (7, 8), we know little about how real predators respond to unpredictability in prey escape strategies and whether this prevents predators from adjusting their behavior over multiple interactions with prey (9, 10).Controlled experiments in which human predators target continuously moving virtual prey have demonstrated that abrupt and unpredictable changes in direction reduce the accuracy of prey targeting (11, 12). However, it is unknown whether the survival advantage conferred by unpredictable motion also applies against nonhuman predators. Additionally, the escape responses of prey which are initially stationary are common in nature, as numerous prey taxa freeze once they have detected a potential threat or remain motionless to avoid detection by predators, before eventually fleeing only once a predator gets too close (1, 13–15). One way for stationary prey to be unpredictable is to vary the initial escape angle from one encounter to the next (16). This is a distinct tactic to the unpredictable movements made by prey which move continuously regardless of the presence of a predatory threat (6) or the abrupt turns made by some prey in anticipation of a predator’s attack (17). Although theoretical models predict that for a predator of a given speed, prey should select a single optimal escape trajectory which maximizes the distance from an approaching predator (18, 19), predators might anticipate the movements of prey which repeatedly escape at a fixed angle relative to their approach (20). Contrary to expectations based on a single optimal escape path, a wide range of prey species show a substantial degree of variability in their initial escape angles (16), including amphibians (21), crustaceans (22, 23), fish (24–27), insects (28, 29), mammals (30), and reptiles (31). Given that this variability is so widespread taxonomically, investigating whether it represents an antipredator strategy aimed at generating unpredictability could have major implications for our understanding of prey escape behavior (32, 33).Many predator-prey interactions are typified by feedback between the attacker and the target (34), making it difficult to disentangle the effects of prey defenses on predators from the impact of predator behavior on prey using a purely observational approach. One way to determine the importance of prey defensive tactics is to present real predators with standardized virtual prey, whose movements and behavior can be precisely controlled and experimentally manipulated (35–39). However, previous experiments with virtual prey have used unresponsive prey items which do not react to predators, and do not allow the predator to capture prey and be rewarded, making it extremely challenging to study repeated interactions between predators and prey. These limitations can be overcome by using interactive robotic prey (40).To study the effect of unpredictability in prey escape on predators, we developed an experimental system [Fig. 1A; see also Swain et al. (41)], in which artificial robot-controlled prey were programmed to flee from blue acara cichlid (Andinoacara pulcher) predatory fish. Blue acaras are opportunistic predators with a broad diet but actively pursue highly evasive prey such as Trinidadian guppies (Poecilia reticulata) (42, 43). Prey initiated their escape response once the predator had approached within a threshold distance (Fig. 1B), mimicking the tendency of many prey to flee from a distant predator at submaximal speeds (14, 44). After an initial period in which groups of blue acaras were trained to attack the prey (the training period, SI Appendix, SI Methods), individual predators were repeatedly presented with prey which escaped either in predictable or unpredictable directions over 20 successive experimental trials (the test period). For individuals assigned to the predictable treatment (which acted as the control), prey escaped at the same angle relative to the predator’s approach from one trial to the next, whereas in the unpredictable treatment, prey were programmed to flee in random directions over successive trials (Fig. 1C). To successfully capture prey, pursuit predators must respond to changes in prey direction, which occur at the start of a chase (45–47). Across trials with predictable prey, the predators had the opportunity to gain reliable information about the prey’s likely escape direction, in contrast to the unpredictable treatment where the prey’s escape angle in previous trials was not a reliable indicator of its escape direction in future encounters. If unpredictable escape behavior is adaptive, increased uncertainty about the prey’s likely escape direction in the unpredictable treatment should reduce the performance of the predator in these trials, with slower speeds of approach (i.e., before the prey respond), longer times taken to capture prey, and/or greater kinematic costs resulting from higher speeds, increased acceleration, and more turning during the pursuit.Open in a separate windowFig. 1.The robotic prey system. (A) Diagram (not to scale) showing a side view of the experimental system, with the Bluetooth-controlled robot situated on a platform underneath the experimental tank and the webcam used to monitor the predator’s movements suspended overhead. The prey’s movements are controlled by the robot via magnets, enabling the prey to escape from an attacking predator once the predator approaches within 27 cm of the prey’s starting position. See ref. 41 for a similar system designed for robotic predators attacking prey fish shoals. (B) Prey escape angles were defined relative to the predator’s approach direction. (C) In the predictable treatment, prey escaped at the same initial angle over successive trials (the escape angle varied between individual predators). In the unpredictable treatment, the prey’s initial escape angle varied randomly from trial to trial. While the experiment manipulated the prey’s initial escape angle, the prey’s subsequent escape trajectory was fixed as a straight-line path in both treatments.     

Analysis of delta-globin gene mutations in Greek cypriots

We recently described four delta-globin gene mutations in Greek Cypriots studied by polymerase chain reaction (PCR) amplification and automated fluorescence-based DNA sequence analysis (Blood 78:3298, 1991). Selective restriction enzyme digestion of PCR products facilitated direct mutation detection. Twenty-eight additional samples from unrelated Cypriots with Hb A2 levels ranging from 0.6% to 3.6% were studied by PCR and showed the following: twelve had the delta 27 (ala-->ser) mutation, one was heterozygous for the delta IVS-2 AG-->GG change, and none had either the delta 116 (arg-->cys) or delta 141 (leu- ->pro) mutations. The remaining samples were divided into two groups: 11 with borderline normal Hb A2 values that were not pursued; and four with abnormal Hb A2 values. The delta-globin genes from these four samples were sequenced and the same four changes identified in each: a C-->T at -199, a C-->T at codon 4 (thr-->ile), a silent C-->T at codon 97, and an AT deletion at position 722 in IVS-2. The codon 4 change abolishes a Ple I site whereas the codon 97 creates an Nla III site, thus facilitating rapid identification. All four changes are in cis position, suggesting that the -199 C-->T, the C-->T at codon 97, and the AT deletion in IVS-2 are neutral polymorphisms present on the codon 4 (thr-->ile) chromosome. DNA haplotype analysis suggests all five delta-globin gene mutant alleles arose independently on different chromosomal backgrounds.     

Juvenile dermatomyositis with Sjögren’s syndrome

Juvenile dermatomyositis (JDM) is a rare disease, and Sjögren’s syndrome (SS) is unusual in adolescents. We report the first case of biopsy-proven JDM and SS with pulmonary involvement. A 15-year-old adolescent boy presented with recurrent parotid gland hypertrophy, severe muscle weakness, pronounced skin rash and widespread lymphadenopathy. JDM was diagnosed by clinical examination, elevated muscle enzymes, electromyography and muscle biopsy; SS was diagnosed by xerostomia, anti-Ro (SS-A) positivity and histopathological analysis of salivary gland tissue. This case illustrates a systematic approach which we feel is especially important in the younger patient with a more plastic immune system.

     

Application of terbium sensitized fluorescence for the determination of fluoroquinolone antibiotics pefloxacin, ciprofloxacin and norfloxacin in serum

A simple, rapid and sensitive spectrofluorimetric method for the determination of fluoroquinolone antibiotics, norfloxacin (NOR), ciprofloxacin (CIP) and pefloxacin (PEF) is described. The method is based on the radiative energy transfer from fluoroquinolones to terbium ions (Tb³⁺) in the presence of tri-n-octylphosphine oxide (TOPO) in weakly acidic (pH 5.5) micellar solution of cetylpyridinium chloride (CPCI). Optimum conditions for the formation of the fluoroquinolone-Tb³⁺-TOPO ternary complexes have been investigated. Under optimized conditions the detection limits are 1.7, 1.2 and 4.4 nM for NOR, CIP and PEF, respectively, while the range of application for all three drugs is 0.05–10 μM. The method has been successfully applied to the determination of NOR, CIP and PEF in serum samples after deproteinization with acetonitrile (serum-acetonitrile; 1:2, v/v). The mean recoveries from serum samples spiked with NOR, CIP and PEF (5.0–50.0 μM) were (90.3 ± 4.9), (105.0 ± 3.6) and (95.3 ± 1.5)%, respectively. Within-run and day-to-day s_r values for 5.0, 25.0 and 50.0 μM of each fluoroquinolone varied from 1.7 to 5.4% and from 3.3 to 12.8%, respectively. The influence of several usually coadministered drugs on the determination of fluoroquinolones in serum has been investigated.     

Allyl isothiocyanate: comparative disposition in rats and mice

Allyl isothiocyanate (AITC), the major component of volatile oil of mustard, was recently reported to induce transitional-cell papillomas in the urinary bladder of male Fischer 344 rats, but not in the bladders of female rats or B6C3F1 mice. The present investigation of comparative disposition in both sexes of each species was designed to detect sex or species differences in disposition which might explain susceptibility to AITC toxicity. AITC was readily cleared from all rat and mouse tissues so that within 24 hr after administration less than 5% of the total dose was retained in tissues. The highest concentration of AITC-derived radioactivity was observed in male rat bladder. Clearance of AITC-derived radioactivity by each species was primarily in urine (70 to 80%) and in exhaled air (13 to 15%) with lesser amounts in feces (3 to 5%). Rats excreted one major and four minor metabolites in urine. The major metabolite from rat urine was identified by NMR spectroscopy to be the mercapturic acid N-acetyl-S-(N-allylthiocarbamoyl)-L-cysteine. Mice excreted in urine the same major metabolite identified in rat urine as well as three other major and two minor metabolites. Sex-related variations were observed in the relative amounts of these metabolites. Both species excreted a single metabolite in feces. Metabolism of AITC by male and female rats was similar, but female rats excreted over twice the urine volume of male rats. Results of the present study indicate that excretion of a more concentrated solution of AITC metabolite(s) in urine may account for the toxic effects of AITC on the bladder of male rats.     

An unusual case of weight loss in a patient with refractory rheumatoid arthritis

We describe a case of metastatic malignant melanoma with no primary cutaneous lesion presenting as weight loss in a man with refractory, seropositive rheumatoid arthritis (RA). The patient had undergone multiple investigations previously and the case highlights the importance of repeat assessment in elderly patients presenting with unexplained weight loss.     

Plasma citrulline levels in preterm neonates with necrotizing enterocolitis

Background and aim

Citrulline is a non-protein amino acid synthesized in the small intestine. In children with short-bowel syndrome, citrulline has served as a reliable marker of the residual bowel length and parenteral nutrition (PN) independence. In the present study we aim to assess the value of citrulline measurement in preterm neonates developing necrotizing enterocolitis (NEC).

Methods

Plasma citrulline levels were measured prospectively in 17 preterm neonates with NEC stage II during the entire course of the disease. Serial citrulline determinations in 24 healthy preterm neonates on 2, 7, 14, 21 and 28 days of life (DOL), served as reference values.

Results

In healthy preterm neonates plasma citrulline levels showed a progressive increase in relation to age. In neonates presenting with NEC, mean citrulline levels were significantly lower as compared to controls' citrulline levels of the most approximate day of life (DOL 7: 16.85 ± 4.2 vs 20.5 ± 4.5 μmol/L, p < 0.05; DOL 14: 18 ± 4.2 vs 23.5 ± 4.3 μmol/L, p < 0.01; DOL 21: 17 ± 2.5 vs 30 ± 5.7 μmol/L, p < 0.01). The optimal citrulline cut-off distinguishing NEC patient from controls was 17.75 μmol/L (sensitivity 76%, specificity 87%). Plasma citrulline at presentation correlated inversely with the duration of parenteral nutrition (r = − 0.49, p < 0.05). Consecutive citrulline determinations revealed that plasma citrulline increased during reintroduction and gradual increase of enteral nutrition.

Conclusions

Our findings provide preliminary evidence that citrulline levels that are reduced in preterm neonates with NEC in comparison to age-matched controls and serial citrulline determinations could help to monitor improvement of functional enterocyte mass during the course and resolution of NEC.     

Evaluation of a multi‐disease carrier screening programme in Ashkenazi Jewish high schools

Ioannou L, Massie J, Lewis S, Petrou V, Gason A, Metcalfe S, Aitken MA, Bankier A, Delatycki MB. Evaluation of a multi‐disease carrier screening programme in Ashkenazi Jewish high schools. A screening programme for Tay Sachs disease (TSD) carrier status was introduced in high schools in Victoria, Australia in 1997, and was expanded to screen for six other genetic conditions common in the Ashkenazi Jewish population in 2008. The aim of this study was to evaluate the current programme and compare it with an evaluation of the programme when screening was offered for TSD alone. All students from Jewish high schools in Melbourne who offered the programme in 2009 were invited to participate in the study. A purpose‐designed questionnaire explored the following domains: knowledge (disease and genetics), reasons for screening, anxiety, and predicted negative feelings if found to be a carrier. Two hundred and seventy‐three students were offered screening, and 272 (99.6%) completed the questionnaire. Only two students chose not to have screening. Two hundred and seventy‐one students were in the penultimate year of high school (99.6%) and 222 were of Ashkenazi Jewish descent (82.5%). The main reasons for choosing screening were the desire to know carrier status and convenience. Knowledge level decreased and negative feelings increased in the current cohort compared to that when screening was offered for TSD alone. We conclude that the current programme is efficient, although increasing the number of conditions resulted in a decrease in knowledge and increase in predicted negative feelings if found to be a carrier of one of the conditions. This has implications for multi‐disease screening programmes that will increase in frequency as more conditions can be screened for and costs diminish.