The aim of this study was to determine if baseline analysis of the NS3 viral region using ultra-deep pyrosequencing (UDPS) could help to predict SVR to triple therapy. Methods: Forty genotype 1 patients failing to achieve a SVR with Peg-IFNa + Ribavirin combination

(null responders: n=18; partial responders: n=14, relapsers: n=8 and retreated with triple therapy adding BOC or TPV were included. Their main characteristics were: mean age 55+/-8 years, 47.5% subtype 1a, 77.5% F3-F4. Baseline UDPS of the NS3-protease viral gene was performed on plasma and peripheral blood mononuclear cells (PBMC). Sequences obtained were analyzed in terms of resistance mutations with a threshold of 1% determined by using a control this website transcript. Heterogeneity of quasispecies was evaluated by the calculation of Shannon Entropy (SE). Results: Baseline mutations were found in 4 patients who achieved SVR with triple Selleckchem HKI 272 therapy and in 4 patients who did not. For these last patients, mutations were already major in three patients and persisted

until viral breakthrough. In the fourth patient, the mutated population accounted for only 1.4% of the total viral population at baseline but dramatically rose upon failure. In two patients, minor mutations were found in PBMC while not in plasma, and corresponded to mutations observed at the viral rebound. Compartmentalization between plasma and PBMC was confirmed with the analysis of the obtained sequences. More broadly, the NS3 quasipecies heterogeneity expressed

as SE was significantly lower at baseline in patients achieving SVR compared MCE公司 to nonSVR (SE= 26.98016.64 x 10-3 vs 44.93 ± 19.58 x 10-3, p=0, 0049). By multivariate analysis, independent predictors of SVR were F0F2 fibrosis stage (OR =13.3, CI95% 1.25141.096, p<0.03) and SE below median value (oR=5.4, CI95% 1.22-23.87, p<0.03). Conclusion: More than the presence of baseline minor mutations in plasma or in PBMC, NS3 viral heterogeneity determined by UDPS is an independent factor of SVR in previously treated patients receiving a triple therapy with an anti-protease drug. This parameter could be included in a score predicting response to therapy. Disclosures: Jean-Pierre H.

All 69 patients had no previous treatment with TACE or hepatic arterial infusion. No serious adverse events were observed in either group. The response rates, including complete response (CR) and partial response (PR), of the EPIR group and the MPT group were 85.7% and 81.5%, respectively, with a time to treatment failure of 5.1 and 7.5 months, respectively. Excluding whole liver TACE cases, time to Selleckchem 5-Fluoracil treatment failure was 5.4 months for the EPIR group and 10.1 months for the MPT group. In TACE naïve cases, there was no significant difference in local control between EPIR and MPT. “
“The stress-activated mitogen-activated protein kinases (MAPKs), c-Jun NH2-terminal kinase (JNK), and

p38 have been implicated in hepatocarcinogenesis. Although the many interrelated functions of JNK and p38 are precisely regulated by upstream signaling molecules, little is known about upstream regulators. We investigated the role of apoptosis signal-regulating kinase 1 (ASK1), a major player in the regulation of JNK and p38 activities, in hepatocarcinogenesis using a mouse hepatocellular carcinoma (HCC) model. ASK1-deficient (ASK1−/−) click here and wildtype (WT) mice were treated with diethylnitrosamine on postnatal day 14. Strikingly, after 7 months, approximately three times as many tumors developed in ASK1−/− mice as in WT mice. Although JNK and

p38 activation were attenuated in ASK1−/− HCCs relative to WT HCCs, cell proliferation was comparable in HCCs from both types MCE公司 of mice. On the other hand, both cancer cell apoptosis and hyperphosphorylation of BimEL, a proapoptotic Bcl-2 family member, were suppressed in the ASK1−/− HCCs. ASK1−/− mice showed remarkable resistance to Fas-induced hepatocyte apoptosis in vivo, probably because of attenuated JNK-mediated BimEL phosphorylation and

mitochondrial apoptotic pathway activation. The reintroduction of ASK1 to ASK1−/− mouse liver using an adenoviral vector restored Fas-induced hepatocyte death and phosphorylation of JNK and BimEL. Similar findings were obtained in tumor necrosis factor alpha-induced hepatocyte apoptosis. Furthermore, ASK1 was involved in DNA damage-induced p21 up-regulation through a p38 pathway. Conclusion: ASK1 is involved in death receptor-mediated apoptosis and DNA-damage response by way of stress-activated MAPK in the liver, and thus acts as a tumor suppressor in hepatocarcinogenesis. This study provides new insight into the regulation of stress- activated MAPK signaling in hepatocarcinogenesis. (HEPATOLOGY 2011;) Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality; thus, understanding the molecular carcinogenic mechanism is an important issue.1 Several molecular pathways have been reported to play important roles in hepatocarcinogenesis.

Large-scale, multicenter treatment trials should be evaluated using robust clinical outcomes, such as in-hospital and remote survival, liver-related and total deaths, completeness and speed of

recovery from HE, number of days in intensive care, total length of hospital stay, quality-of-life measures, and associated costs. Markers for HE, such as psychometric testing, can be employed if standardized and validated tools are available in all centers. Individual centers can utilize additional, accessible, learn more validated markers if they choose. Proof-of-concept trials will additionally be monitored using tools that best relate to the endpoints anticipated or expected; this may involve use of neural imaging or measurement of specific biomarkers. Trials in this population should be randomized and placebo controlled. Patients receiving treatment for OHE or those with previous episodes of OHE should be excluded. In single-center or proof-of-concept studies, investigators may use tests for assessing PLX4032 order the severity of HE with which they are familiar, provided that normative reference

data are available and the tests have been validated for use in this patient population. Further information is needed on the interchangeability and standardization of tests to assess the severity of HE for use in multicenter trials. As an interim, two or more of the current validated tests should be used and applied uniformly across centers. “
“This chapter contains sections titled: Definition of irritable bowel syndrome Prevalence and incidence of irritable bowel syndrome Irritable bowel syndrome and health services Pathogenesis of irritable bowel syndrome Making a diagnosis of irritable bowel syndrome Treatment of irritable bowel syndrome Prognosis of irritable bowel syndrome References “
“Endoscopic submucosal dissection

(ESD) is now accepted as a minimally invasive treatment for early gastric cancer (EGC). To our knowledge, however, the functional effects of ESD have not been determined in patients with EGC. We therefore investigated whether gastric motility was affected by ESD. Using the 13C-octanoic acid breath test, gastric emptying of solid test meals was examined in 26 EGC patients and 18 healthy controls, with EGC patients assayed before and about MCE公司 2 months after ESD. Based on 13CO2 breath-excretion curves, the lag-phase time (Tlag), half-emptying time (T1/2), and gastric emptying coefficient (GEC) were calculated as indices of gastric emptying. In healthy controls, the mean Tlag, T1/2, and GEC were 85.5 ± 4.9 min, 148.5 ± 8.0 min, and 3.01 ± 0.09 h, respectively. Before ESD, the mean Tlag, T1/2, and GEC in the EGC patients were 90.1 ± 5.5 min, 174.7 ± 10.4 min, 2.64 ± 0.08 h, respectively. GEC, but not Tlag or T1/2, differed significantly in the two groups, with gastric emptying slower in EGC patients than in controls.

Large-scale, multicenter treatment trials should be evaluated using robust clinical outcomes, such as in-hospital and remote survival, liver-related and total deaths, completeness and speed of

recovery from HE, number of days in intensive care, total length of hospital stay, quality-of-life measures, and associated costs. Markers for HE, such as psychometric testing, can be employed if standardized and validated tools are available in all centers. Individual centers can utilize additional, accessible, R428 molecular weight validated markers if they choose. Proof-of-concept trials will additionally be monitored using tools that best relate to the endpoints anticipated or expected; this may involve use of neural imaging or measurement of specific biomarkers. Trials in this population should be randomized and placebo controlled. Patients receiving treatment for OHE or those with previous episodes of OHE should be excluded. In single-center or proof-of-concept studies, investigators may use tests for assessing DAPT in vitro the severity of HE with which they are familiar, provided that normative reference

data are available and the tests have been validated for use in this patient population. Further information is needed on the interchangeability and standardization of tests to assess the severity of HE for use in multicenter trials. As an interim, two or more of the current validated tests should be used and applied uniformly across centers. “
“This chapter contains sections titled: Definition of irritable bowel syndrome Prevalence and incidence of irritable bowel syndrome Irritable bowel syndrome and health services Pathogenesis of irritable bowel syndrome Making a diagnosis of irritable bowel syndrome Treatment of irritable bowel syndrome Prognosis of irritable bowel syndrome References “
“Endoscopic submucosal dissection

(ESD) is now accepted as a minimally invasive treatment for early gastric cancer (EGC). To our knowledge, however, the functional effects of ESD have not been determined in patients with EGC. We therefore investigated whether gastric motility was affected by ESD. Using the 13C-octanoic acid breath test, gastric emptying of solid test meals was examined in 26 EGC patients and 18 healthy controls, with EGC patients assayed before and about 上海皓元 2 months after ESD. Based on 13CO2 breath-excretion curves, the lag-phase time (Tlag), half-emptying time (T1/2), and gastric emptying coefficient (GEC) were calculated as indices of gastric emptying. In healthy controls, the mean Tlag, T1/2, and GEC were 85.5 ± 4.9 min, 148.5 ± 8.0 min, and 3.01 ± 0.09 h, respectively. Before ESD, the mean Tlag, T1/2, and GEC in the EGC patients were 90.1 ± 5.5 min, 174.7 ± 10.4 min, 2.64 ± 0.08 h, respectively. GEC, but not Tlag or T1/2, differed significantly in the two groups, with gastric emptying slower in EGC patients than in controls.

g. model ψ(area + AS) p(.) for S. salamandra]. In addition to these models, we set up candidate models with combinations of predictor variables. The first model describing the terrestrial habitat included the predictors ‘area’, ‘forest’, ‘slope’ and ‘PCA climate’ [model ψ(habitat) p(.)]. The second model, which was only used for the S. salamandra data, included the predictors ‘slope’, ‘stream bank slope’, ‘pools’ and ‘hides’ to assess http://www.selleckchem.com/products/ink128.html the effect of stream parameters on the species’ occupancy probability [model ψ(stream) p(.)]. Two more candidate models were obtained by adding the presence of the other species to the two multi-variable models.

Based on the results of the a priori models for each species, we additionally combined the predictors of the QAIC best ranked models into

four new a posteriori candidate models with combination of two or three predictor variables (see Supporting Information Tables S1 and S2). Because there was a model selection uncertainty, we used model Proteasome inhibition assay averaging techniques for parameter estimation (Burnham & Anderson, 2002). For model averaging, models with ΔQAIC >7 were dropped from the set of candidate models for each species and Akaike weights were recalculated for the set of models with ΔQAIC ≤7. Based on the new Akaike weights, model averaging was performed for all predictor variables in models that were retained in order to assess their effect on the species’ occupancy probability. During field surveys (mean duration per visit ± standard deviation was 53.8 ± 14.5 min for Zug; 46.4 ± 14.0 min for Nidwalden), we detected Salamandra salamandra at 16/23 of

the sampling sites in the contact zone in Zug and 13/19 in Nidwalden. Salamandra atra was found at 5/23 of the sampling sites in Zug compared with 17/19 in Nidwalden. Co-occurrence of the salamanders was found at 3/23 sampling site in Zug and at 12/19 sites in Nidwalden. Table 2 shows the top-ranking models (based on QAIC) for both salamander species. For both species, top-ranking models always included ecological predictor variables and were better than the intercept-only 上海皓元 models (i.e. null models). The analysis revealed that the model including ‘slope’ and ‘pools’ as predictors for the fire salamander’s occupancy probability was best supported by the data. Model averaging showed that only the 95% confidence interval of ‘slope’ did not include zero (Table 3). The positive effect of the slope of the sampling sites on the occupancy probability is shown in Fig. 2. The confidence intervals of all other predictor variables included zero. In particular, while the estimated effect of alpine salamander on fire salamander occupancy was negative, the 95% confidence interval included zero (Table 3). The observed data for S. atra were best explained by the model with the predictor variable ‘area’. In this model, we estimated a four times lower occupancy rate for S. atra in Zug (0.22, se 0.

Gretch, MD, PhD, Minjun Chung Apodaca, BS, ASCP, Rohit Shankar, BC, ASCP, Natalia Antonov, M.Ed. New England Research Institutes, Watertown, MA: (Contract N01-DK-9-2328) Teresa M. Curto, MSW, MPH, Margaret C. Bell, Venetoclax MS, MPH. Inova Fairfax Hospital, Falls Church, VA: Zachary D. Goodman, MD, PhD, Fanny Monge, Michelle Parks. Data and Safety Monitoring Board Members: (Chair) Gary L. Davis, MD, Guadalupe Garcia-Tsao, MD, Michael Kutner, PhD, Stanley M. Lemon, MD, Robert P. Perrillo, MD. “
“Here, we identify (−)-epigallocatechin-3-gallate (EGCG) as a new inhibitor of hepatitis C virus (HCV) entry. EGCG is a flavonoid present in green tea extract belonging to the subclass of catechins, which has many properties.

Particularly, EGCG possesses antiviral activity and impairs cellular lipid metabolism. Because of close links between HCV life cycle and lipid metabolism, we postulated that EGCG may interfere with HCV infection. We demonstrate that a concentration of 50 μM of EGCG inhibits HCV infectivity by more than 90% at an early step of the viral life cycle, most likely the entry step. This inhibition was not observed with other members of the Flaviviridae family tested. The antiviral activity of EGCG on HCV entry was confirmed with pseudoparticles Selleckchem Dinaciclib expressing HCV envelope glycoproteins E1 and E2 from six different genotypes. In

addition, using binding assays at 4°C, we demonstrate that EGCG prevents attachment of the virus to the cell surface, probably by acting directly on the particle. We also show that EGCG has no effect on viral replication and virion secretion. By inhibiting cell-free virus transmission using agarose or neutralizing antibodies, we show that EGCG inhibits HCV cell-to-cell spread. Finally, by successive inoculation of

naïve cells with supernatant of HCV-infected cells in the presence of EGCG, we observed that EGCG leads to undetectable levels of infection after four passages. Conclusion: EGCG is a new, interesting anti-HCV molecule that could be used in combination with other direct-acting antivirals. Furthermore, it is a novel tool to further dissect the mechanisms of HCV entry into the hepatocyte. (HEPATOLOGY 2012;) Hepatitis C virus (HCV) is a major cause of chronic liver disease. It is estimated that 3% of the world population is currently infected and thus is at high risk of developing cirrhosis and hepatocellular 上海皓元医药股份有限公司 carcinoma. 1 No vaccine is available, and the current standard-of-care therapy with pegylated interferon-alpha (IFN-α) and ribavirin has a limited efficacy and significant side effects. 2 Very recently, an addition to the therapy of new direct-acting antivirals (DAAs) targeting HCV nonstructural protein (NS)3-4A protease, telaprevir, and boceprevir was shown to increase the sustained virological response in patients infected with HCV genotype 1 by up to 70%. 3 Efforts are currently being made to identify new DAAs with additive potency. The majority of these molecules target the replication step.

0%. Conclusion:  A combination of liver stiffness and serum markers identified SF with a high

degree of accuracy. Approximately half of all patients with CHB could avoid liver biopsy through the utilization of the HALF index. “
“Elevated serum PF-562271 chemical structure immunoglobulin G4 (sIgG4) is a feature of autoimmune pancreatitis (AIP) and IgG4-associated cholangitis (IAC); a >2-fold increase in sIgG4 is considered highly specific for these disorders. Many patients with IAC present with biliary strictures and obstructive jaundice, making cholangiocarcinoma (CCA) an important differential diagnosis. We determined the value of sIgG4 in distinguishing IAC from CCA. sIgG4 levels were measured in a test cohort of 126 CCA and 50 IAC patients. The results were confirmed in a validation cohort of 161 CCA and 47 IAC patients. Of the 126 CCA patients in the test cohort, 17 (13.5%) had elevated sIgG4 (>140 mg/dL) and four (3.2%) had a >2-fold (>280 mg/dL) increase. Primary sclerosing cholangitis (PSC) was present in 31/126 CCA patients, of whom seven (22.6%) had elevated sIgG4 and two (6.5%) 3-deazaneplanocin A nmr had a >2-fold elevation. Of the 50 IAC patients, 39 (78.0%) had elevated sIgG4 and 25 (50.0%) had a >2-fold increase. The results in the validation cohort were consistent with those of the test cohort.

Conclusion: Although elevated sIgG4 levels are characteristic of IAC, some patients with CCA, particularly

with PSC, have elevated sIgG4 levels, including a small percentage with a more than a 2-fold increase in sIgG4. Therefore, sIgG4 elevation alone does not exclude the diagnosis of CCA. Depending on the prevalence of the two diagnoses, the use of a 2-fold cutoff for sIgG4 may not reliably distinguish IAC from CCA. MCE公司 At a cutoff of 4 times the upper limit of normal, sIgG4 is 100% specific for IAC. (HEPATOLOGY 2011;) IgG4-related systemic disease (ISD) is a multisystem fibroinflammatory syndrome characterized by elevated levels of serum immunoglobulin G subclass 4 (sIgG4) and a multifocal IgG4-rich lymphoplasmacytic infiltration of affected organs. The condition is generally associated with intense sclerosis and responds favorably to glucocorticoids.1-3 The prototype of ISD is autoimmune pancreatitis (AIP), which by virtue of its clinical and radiologic characteristics (pancreatic mass, painless jaundice, weight loss, and diabetes) can mimic pancreatic adenocarcinoma.4, 5 Other organs that can be involved in this condition include the biliary tree, salivary glands, retroperitoneum, lymph nodes, kidneys, and aorta.2, 6, 7 Both the pancreatic and extrapancreatic variants of ISD respond well to steroid therapy.8 In 2001 it was reported that an elevated sIgG4 level is highly sensitive and specific for AIP.

This research improves our understanding of within-population foraging variations in bottlenose dolphins. “
“Counts of pinnipeds provide a minimal estimate of population Dasatinib size because some unknown proportion of individuals is in the water during surveys. We determined a correction factor (CF) for Pacific harbor seals (Phoca vitulina richardii) by estimating the proportion ashore of 180 seals tagged with flipper-mounted radio tags throughout California. The mean proportions of tagged individuals ashore during four complete surveys in 2004 were not different between central and northern California (F= 1.85, P= 0.18) or between sexes (F= 0.57, P= 0.45), but a lesser proportion of

weaners was ashore than subadults or adults (F= 7.97, P= 0.001), especially in northern California. The CF calculated for the statewide census of harbor seals was 1.65, using transmitters operating during the survey (n= 114). Using a mark-recapture estimator for tag survival (phi) and the four telemetry surveys

the mean CF for central and northern California was 1.54 ± 0.38 (95% CI). A CF for southern California of 2.86 was based on a single survey. Using the mean CF of 1.54 and a statewide count in 2009 we estimated 30,196 (95% CI = 22,745–37,647) harbor seals in California. “
“This study describes pulsed signals from bottlenose dolphins of the central Mediterranean Sea. Data were collected during 2011 and 2012 in 27 surveys in the Sicilian Channel, during which 163 animals were sighted. Based mainly on the pulse repetition rate, the signals were classified as Low-frequency click (LF; single clicks without a regular pulse rate), Train click (TC; with a interclick interval Doxorubicin ic50 of 80 ± 2 ms), Burst (with a interclick interval of 3.4 ± 0.2 ms), or Packed click (with a lower number of clicks per train and median interclick interval of 3.2 ± 0.0 ms). The measured parameters were peak sound pressure level (SPLpk); signal duration; the 1st, 2nd, and 3rd peak of frequency; number of peaks frequency; bandwidth; centroid frequency; and the 10th, 25th,

75th, and 90th percentiles of the power spectrum distribution. Most of the parameters medchemexpress were significantly different among the groups, reflecting the different functions of these signals. LF clicks showed a lower peak frequency and percentiles and a longer duration and could be used to explore a wide area without a specific target focalization and with less resolution. The TC showed a higher SPLpk, higher peak frequency, lower duration, and lower number of secondary peaks frequency, showing a better resolution to investigate a specific target. “
“The population of Irrawaddy dolphins that occupies the Mekong River in southern Lao People’s Democratic Republic and Cambodia is classified as Critically Endangered by the IUCN. Based on capture-recapture of photo-identified individuals, we estimated that the total population numbered 93 ±  SE 3.90 individuals (95% CI 86–101), as of April 2007.

Secondly, we examined variations of these four variables throughout the depth selleckchem range experienced during transits. This enabled us to investigate

how penguins may anticipate the nature of the dive they are going to undertake in terms of transit rates. The study was carried out on Possession Island, Crozet Archipelago (46.4°S, 51.8°E) from December 2003 to March 2004. Birds used in the study were king penguins breeding at La Baie du Marin, a colony of approximately 16 000 pairs (Delord, Barbraud & Weimerskirch, 2004). The procedures received the approval of the ethics committee of the French Polar Institute (IPEV) and of the French Ministry of the Environment. Detailed description of the general surgical and handling procedure are given in Froget et al. (2004). Six breeding male king penguins were captured while brooding an egg and immediately subjected AP24534 clinical trial to isoflurane-anaesthesia, during which they were fitted with data loggers. SMAD data loggers (DEPE-IPHC, Strasbourg, France; 80 × 25 × 10 mm, 54 g) were externally attached to the lower-back feathers of each animal to diminish hydrodynamic drag (Bannasch, Wilson & Culik, 1994) and recorded depth every 2 s. SMAD were also programmed to measure tail-to-head (surge) and ventral-to-dorsal (heave) accelerations during two 1-h high-frequency sessions per day when penguins performed deep dives, and stored these measurements 32 times

per second. Cross-sectional area (CSA) of the external logger (2.5 cm2) represented less than 1% of the smallest bird’s CSA. Modified Mk7 data loggers (Wildlife Computers, Redmond, WA, USA) were also implanted subcutaneously for a study

of peripheral temperatures; these results have been described previously in Schmidt (2006). Together, the mass of both loggers (87 g) represented less than 0.8% of the smallest bird’s mass. The penguins undertook a foraging trip at sea 15–18 days later, after being relieved by their partners. After their return to the colony, the birds were recaptured and anaesthetized using the same procedure, and the loggers MCE were removed. All the loggers were recovered, of which five had recorded usable data. Data from these loggers were extracted, prepared and analysed using purpose-written computer programs in Matlab 6.0 (The MathsWorks, Natick, MA, USA). Dives >50 m, hereafter called ‘deep dives’, were used for analysis as they represent the majority of the foraging dives of king penguins (Charrassin et al., 1998). For each dive analysed, the following parameters were calculated: maximum dive depth (m), dive duration (s), subsequent surface interval duration until the next dive of any depth (s), subsequent time interval until the next deep dive (s), rank of the dive in a bout (i.e. sequence of successive dives), number of wiggles during the bottom phase or the entire dive. Wiggles are a particular, undulation-like pattern in the dive profile over time.

Even when predation does occur, pseudothumbs may not be effective against predators because they face inward and the projected spines can only attack something within their arms. Also, most of the Otton frogs did not aggressively attack humans with their pseudothumbs when captured; aggression occurred only when their chest was irritated, which can be considered a reflex related to male–male combat or amplexus. Thus, the possibility of pseudothumb use for obtaining food or protection is slight. The pseudothumbs of the male Otton frogs were sometimes wounded. This seemed to be because the spine pierced its sheath during use. Otton frogs jab their pseudothumbs into

their opponents so strongly that the spines emerge by cutting through the sheath. When the author pulled down SB203580 mw Selleck BI 2536 the sheath, the spine emerged and became visible in more than half of the male Otton frogs. Presumably, those with a visible spine might have used them recently in combat, whereas those that were not visible had not been used recently (at least for more than the period during which the wound healed). Piercing of the skin while using spines or claws has been observed in other frog species (Blackburn, Hanken & Jenkins, 2008) and in salamanders (Brodie,

Nussbaum & DiGiovanni, 1984). Blackburn et al. (2008) showed that the claws of Astylosternus and Trichobatrachus pierce their way to functionality, and Brodie et al. (1984) showed that Echinotriton andersoni has sharp ribs that protrude through the body wall against predators. Blackburn et al. (2008, p. 356) stated MCE公司 that the bony ribs of E. andersoni are the only comparative structures to the claws of Astylosternus and Trichobatrachus, and that the claws were not analogous to the prepollical spines of five-fingered frog species as ‘the spines … appear to grow through the skin rather than traumatically pierce it’. However, the spines of Otton frogs do not grow through the skin, but rather pierce the sheath traumatically. Thus, the claws of Astylosternus and Trichobatrachus, the ribs of E. andersoni and the prepollical spines of Otton frogs might have some common developmental features. Although amphibians are known

to have remarkable regenerative capacity (Brockes & Kumar, 2005), a structure that damages the animal itself in its use does not seem adaptive. This topic needs to be examined further and will be an interesting case study for the development of self-damaging structures. Although females do not appear to use their pseudothumbs and spines, they are still present, and a few individuals had spines that projected slightly from the sheath or showed a weak jabbing response. This could be because formation of the pseudothumb is linked developmentally with other important traits. The fact that the development of pseudothumbs in Otton frogs occurs at a fairly early stage, even in larvae (Tokita & Iwai, 2010), supports this idea. Corresponding formation of spines in females was also observed in some adult females of H.