bluuebunny/crossref_metadata_2025 huggingface dataset:
Rare hemoglobin variants in Tunisian population
Authors: Zorai A. , Moumni I. , Mosbahi I. , Douzi K. , Chaouachi D. , Guemira F. , Abbes S.
Published: June 2014

During the last 30 years, many studies concerning hemoglobinopathies were realized among Tunisians. More than twenty different thalassemic alleles were detected on the β‐globin gene, and less are affecting the α‐globin genes. Unusual hemoglobin (Hb) variants other than Hb S, Hb C, and Hb O‐arab, which are the most frequent variants in Tunisia, were also detected. Eight Tunisian subjects were studied at phenotypic and molecular levels. Hematological indices and hemoglobin (Hb) pattern were performed by alkaline electrophoresis and isoelectric focusing (IEF),and the Hb fractions were quantitated by cation exchange HPLC. On genomic level, coding regions were amplified by polymerase chain reaction (PCR) followed by a sequencing of the purified PCR products using the dye terminator method. Seven uncommon Hb variants were detected and described for the first time among Tunisians. HbA2‐Tunis [δ46(CD5), Gly → Glu, GGG → GAG] is the newly described δ‐chain variant in our laboratory, and some other variants (Hb Constant Spring, G San Jose, and Hb J‐Bangkok) are very uncommon in the Mediterranean region. We present here an updated review of the Hb variants detected among Tunisians. Twenty‐one rare Hb variants were detected affecting the α1‐, α2‐, δ‐, γ‐, and β‐globin genes, leading in some cases to a severe phenotype especially when the stability is completely altered. The ethnical history of Tunisia could explain this important variability of the observed rare Hb variants.
Imbalance of regulatory T cells and T helper type 17 cells in patients with chronic hepatitis C
Authors: Hao Chunqiu , Zhou Yun , He Yu , Fan Chao , Sun Li , Wei Xin , Wang Linxu , Peng Meijuan , Wang Pingzhong , Lian Jianqi , Jia Zhansheng
Published: June 2014

Pegylated interferon and ribavirin combination therapy is known to be effective in suppressing viral replication in 50–60% of hepatitis C virus (HCV) ‐infected patients. However, HCV‐infected patients often exhibit varied responses to therapy. Therefore, the identification of immunological markers associated with the clinical outcomes of antiviral treatment is critical for improvement of therapeutic options. In this study, we aimed to investigate the ratio of CD4+ CD25+ FoxP3+ regulatory T (Treg) cells to interleukin‐17A (IL‐17A) ‐producing T helper type 17 (Th17) cells, and its association with clinical outcomes in response to anti‐HCV treatment. In all, 114 patients with HCV infection received pegylated interferon‐α2a and ribavirin therapy for 48 weeks, and the frequency of Treg cells and Th17 cells as well as the levels of secreted cytokines were longitudinally analysed by flow cytometry and ELISA. Treg cell proportions and IL‐10 production were significantly elevated in HCV‐infected patients, especially for HCV genotype 1b. However, the frequency of Th17 cells as well as the secretion of IL‐17, IL‐22 and IL‐23 did not reveal notable difference between HCV infections and healthy individuals. Inhibition of HCV replication was accompanied by a reduction in Treg cells, but little influence on Th17 cells, which led to a significant decrease in Treg : Th17 ratios. Skewed Treg : Th17 ratios existed in chronic hepatitis C. HCV RNA load is closely associated with Treg : Th17 ratios during pegylated interferon‐α2a and ribavirin treatment in HCV‐infected patients. The imbalance of Treg cells to Th17 cells might play an important role in persistent HCV infection.
Parthenogenesis in a whitetip reef shark Triaenodon obesus involves a reduction in ploidy
Authors: Portnoy D. S. , Hollenbeck C. M. , Johnston J. S. , Casman H. M. , Gold J. R.
Published: June 2014

Genetic analysis of a female whitetip reef shark Triaenodon obesus and her stillborn pup, assumed to be of parthenogenetic origin, revealed that the pup was homozygous at all 24 nuclear‐encoded microsatellites assayed, consistent with the idea that diploidy in the pup had been restored via terminal fusion. Flow cytometric analysis, however, indicated that the genome size of the pup was no more than half that of the mother, and microscopy revealed that nuclear volume was c. 1·73 times larger in the mother than in the pup. Together these data suggest that the pup was genetically haploid, developing directly from an unfertilized egg; as far as is known, this is the first observation of a spontaneously produced haploid vertebrate.
Textural and Sensory Characteristics of Rice Chiffon Cake Formulated with Sugar Alcohols instead of Sucrose
Authors: Kim Ji‐Na , Park Soojin , Shin Weon‐Sun
Published: June 2014

We measured the stability and the sensory and textural properties of rice chiffon cake batter and cake prepared with various sugar alcohols in place of sucrose. Mannitol substitution increased batter stability by 30% that of sugar cake and specific volume, allowing greater air retention than that achieved with other polyols, as well as formation of networks with equal cells. Nevertheless, the 100% sensory score of mannitol‐substituted cake was low because of dryness. In contrast, maltitol, sorbitol and xylitol had no effect on the textural properties of cake batter and baked products. The sweetness and overall acceptability of chiffon cakes prepared with maltitol, sorbitol and xylitol, but not mannitol, were similar to those of sugar‐added rice chiffon cake. In conclusion, maltitol, sorbitol and xylitol can be used to prepare low‐calorie, gluten‐free rice chiffon cake without affecting its quality.

Practical Applications

Previous studies have reported rice flour substitutions of 0–100% in products such as sponge cake, yellow layer cake, butter cake and chiffon cake. The use of sugar alcohols (polyols) as bulking agents for low‐calorie baked products has been tested previously. In this study, maltitol, sorbitol and xylitol could replace sucrose in rice chiffon cake with no significant changes in batter stability or baking and sensory properties. However, mannitol had an unfavorable impact on textural and sensory qualities, although it increased batter stability and loaf volume of the baked cake.
Insurance Fraud in the Workplace? Evidence From a Dependent Verification Program
Authors: Geruso Michael , Rosen Harvey S.
Published: June 2014

Many employers have implemented dependent verification (DV) programs, which aim to reduce employee benefits costs by ensuring that ineligible persons are not enrolled in their health insurance plans as dependents. We evaluate a DV program using a panel of health plan enrollment data from a large, single‐site employer. We find that dependents were 2.7 percentage points less likely to be reenrolled in the year that DV was introduced, indicating that this fraction of dependents was ineligibly enrolled prior to the program's introduction. There is some evidence consistent with the notion that these dependents were actually ineligible, rather than merely discouraged from reenrollment by compliance costs. We find no indication that the removal of these ineligible dependents spilled over to affect the enrollment of eligible dependents within the same family.
The Pension Option in Labor Insurance and Its Effect on Household Saving and Consumption: Evidence From Taiwan
Authors: Chen Hua , Hsu Wen‐Yen , Weiss Mary A.
Published: June 2014

Starting in 2009, the Labor Insurance (LI) program in Taiwan has allowed workers to choose between pension old‐age benefits and one‐time old‐age benefits. The introduction of the pension option not only mitigates longevity risk for workers but also provides a higher expected present value of old‐age benefits to workers than the one‐time benefit option (on average). Based on a lifecycle model with uncertain lifespan, we expect that workers will increase current consumption and reduce saving in response to this policy intervention. We use data from the Survey of Family Income and Expenditure in Taiwan to empirically test this prediction. In order to isolate other systematic structural changes or economic shocks from the true impact of the pension option on saving and consumption, we adopt a difference‐in‐differences approach in this study. Our results indicate that the implementation of pension benefits in LI lowers households' saving by 8.41 percent (NT$50,587) and raises consumption by 5.73 percent (NT$42,897) for LI workers. In addition, we find that, in general, households with less saving or consumption tend to be more responsive to this policy in terms of reducing saving or increasing consumption.
Intracavernous Delivery of Stromal Vascular Fraction Restores Erectile Function Through Production of Angiogenic Factors in a Mouse Model of Cavernous Nerve Injury
Authors: Song Kang-Moon , Jin Hai-Rong , Park Jin-Mi , Choi Min Ji , Kwon Mi-Hye , Kwon Ki-Dong , Batbold Dulguun , Yin Guo Nan , Kim Woo Jean , Koh Gou Young , Ryu Ji-Kan , Suh Jun-Kyu
Published: June 2014

Introduction

Erectile dysfunction (ED) is a major complication of radical prostatectomy. Men with radical prostatectomy-induced ED respond less positively to oral phosphodiesterase-5 inhibitors.

Aim

The study aims to examine whether and how stromal vascular fraction (SVF) restores erectile function in mice with cavernous nerve injury (CNI).

Methods

Twelve-week-old male C57BL/6J mice were used and the animals were distributed into five groups: sham operation group and CNI group receiving a single intracavernous injection of phosphate-buffered saline (PBS) or SVF (1 × 104, 1 × 105, or 3 × 105 cells/20 μL, respectively). SVF was isolated from epididymal adipose tissues of green fluorescence protein transgenic mice.

Main Outcome Measures

Two weeks after injection, erectile function was measured by cavernous nerve stimulation. The penis was stained with antibodies to platelet/endothelial cell adhesion molecule-1, phosphohistone H3, and phosphorylated endothelial nitric oxide synthase (phospho-eNOS). We also performed Western blot for angiopoietin-1 (Ang-1), vascular endothelial growth factor-A, hepatocyte growth factor, phospho-eNOS, and eNOS in the corpus cavernosum tissue.

Results

Local delivery of SVF restored erectile function in a dose-dependent manner in CNI mice. The highest erectile response was noted at a dose of 3 × 105 cells, for which the response was comparable with that in the sham operation group. Local delivery of SVF significantly increased the expression of angiogenic factor proteins and induced cavernous endothelial cell proliferation and eNOS phosphorylation compared with that in the PBS-treated CNI group. SVF-induced promotion of cavernous angiogenesis and erectile function was diminished in the presence of soluble antibody to Tie2, a receptor tyrosine kinase of Ang-1.

Conclusion

Secretion of angiogenic factors from SVF is an important mechanism by which SVF induces cavernous endothelial regeneration and restores erectile function. These findings suggest that cavernous endothelial regeneration by using SVF may represent a promising treatment strategy for radical prostatectomy-induced ED.
Right or Flawed: Relationship Obsessions and Sexual Satisfaction
Authors: Doron Guy , Mizrahi Moran , Szepsenwol Ohad , Derby Danny
Published: June 2014

Introduction

Relationship obsessive–compulsive disorder (ROCD) is marked by the presence of obsessions and compulsions focusing on romantic relationships. ROCD symptoms were previously linked with decreased relationship quality and might interfere with sexual functioning.

Aim

The study aims to examine the association between ROCD symptoms and sexual satisfaction.

Methods

Participants completed an online survey assessing ROCD symptoms and relationship and sexual satisfaction levels. Depression, general worry, obsessive–compulsive disorder (OCD) symptoms, and attachment orientation were also measured.

Main Outcome Measure

The main outcome measures were self reported relationship satisfaction and sexual satisfaction.

Results

ROCD symptoms were associated with decreased sexual satisfaction over and above symptoms of depression, general worry, OCD, and attachment orientation. The link between ROCD symptoms and sexual satisfaction was mediated by relationship satisfaction.

Conclusions

Identifying and addressing ROCD symptoms may be important for treatment of sexual functioning.
Emotional working memory during sustained wakefulness
Authors: Tempesta Daniela , De Gennaro Luigi , Presaghi Fabio , Ferrara Michele
Published: June 2014

In the present study we investigated whether one night of sleep deprivation can affect working memory (WM) performance with emotional stimuli. Twenty‐five subjects were tested after one night of sleep deprivation and after one night of undisturbed sleep at home. As a second aim of the study, to evaluate the cumulative effects of sleep loss and of time‐of‐day changes on emotional WM ability, the subjects were tested every 4 h, from 22:00 to 10:00 hours, in four testing sessions during the sleep deprivation period (deprivation sessions: D1, D2, D3 and D4). Subjects performed the following test battery: Psychomotor Vigilance Task, 0‐back task, 2‐back task and an ‘emotional 2‐back task’ with neutral, positive and negative emotional pictures selected from the International Affective Picture System. Results showed lower accuracy in the emotional WM task when the participants were sleep‐deprived relative to when they had slept, suggesting the crucial role of sleep for preserving WM ability. In addition, the accuracy for the negative pictures remains stable during the sessions performed from 22:00 to 06:00 hours (D1, D2 and D3), while it drops at the D4 session, when the participants had accumulated the longest sleep debt. It is suggested that, during sleep loss, attentional and WM mechanisms may be sustained by the higher arousing characteristics of the emotional (negative) stimuli.
Closantel plasma and milk disposition in dairy goats: assessment of drug residues in cheese and ricotta
Authors: Iezzi S. , Lifschitz A. , Sallovitz J. , Nejamkin P. , Lloberas M. , Manazza J. , Lanusse C. , Imperiale F.
Published: June 2014

Closantel (CLS) is currently used in programs for the strategic control of gastrointestinal nematodes. CLS is extralabel used in different dairy goat production systems. From available data in dairy cows, it can be concluded that residues of CLS persist in milk. The current work evaluated the concentration profiles of CLS in plasma and milk from lactating orally treated dairy goats to assess the residues pattern in dairy products such as cheese and ricotta. Six (6) female Saanen dairy goats were treated orally with CLS administered at 10 mg/kg. Blood and milk samples were collected between 0 and 36 days post‐treatment. The whole milk production was collected at 1, 4, 7, and 10 days post‐treatment to produce soft cheese and ricotta. CLS concentrations in plasma, milk, cheese, whey, and ricotta were determined by HPLC. The concentrations of CLS measured in plasma were higher than those measured in milk at all sampling times. However, the calculated withdrawal time for CLS in milk was between 39 and 43 days postadministration to dairy goats. CLS residual concentrations in cheese (between 0.93 and 1.8 μg/g) were higher than those measured in the milk used for its production. CLS concentrations in ricotta were sixfold higher than those in the milk and 20‐fold higher than those in the whey used for its production. The persistent and high residual concentrations of CLS in the milk and in the cheese and ricotta should be seriously considered before issuing any recommendation on the extralabel use of CLS in dairy goat farms.
Characterization and treatment of persistent hepatocellular secretory failure
Authors: van Dijk Remco , Kremer Andreas E. , Smit Wouter , van den Elzen Bram , van Gulik Thomas , Gouma Dirk , Lameris Johan S. , Bikker Hennie , Enemuo Valentine , Stokkers Pieter C. F. , Feist Mark , Bosma Piter , Jansen Peter L. M. , Beuers Ulrich
Published: June 2014

Background & Aims

Hepatocellular secretory failure induced by drugs, toxins or transient biliary obstruction may sometimes persist for months after removal of the initiating factor and may then be fatal without liver transplantation. We characterized patients with severe persistent hepatocellular secretory failure (PHSF) and treated them with the pregnane X receptor (PXR) agonist, rifampicin. We also studied the effect of rifampicin on PXR‐dependent expression of genes involved in biotransformation and secretion in vitro.

Methods

Thirteen patients (age 18–81 years, 6 male) with hepatocellular secretory failure that persisted after removal of the inducing factor (drugs/toxin: 9) or biliary obstruction (4) were identified over 6 years. Six of these patients were screened for ATP8B1 or ABCB11 mutations. All were treated with rifampicin (300 mg daily) for 1–10 weeks. Expression of genes involved in biotransformation and secretion was determined by rtPCR in human hepatocytes and intestinal cells incubated with rifampicin (10 μmol/L).

Results

Serum bilirubin of patients with PHSF ranged from 264 to 755 μmol/L. Normal γGT was found in 10/13 patients of whom 3/6 tested positive for ATP8B1/ABCB11 mutations. Serum bilirubin declined to <33 μmol/L after 1–10 weeks of rifampicin treatment. In vitro, rifampicin PXR‐dependently upregulated biotransformation phase 1 (CYP3A4), phase 2 (UGT1A1) and phase 3 (MRP2) enzymes/carriers as well as the basolateral bile salt exporter OSTβ.

Conclusion

Persistent hepatocellular secretory failure may develop in carriers of transporter gene mutations. In severe cases, rifampicin may represent an effective therapeutic option of PHSF. PXR‐dependent induction of CYP3A4, UGT1A1, MRP2 and OSTβ could contribute to the anticholestatic effect of rifampicin in PHSF.
Upregulation of matrilin‐2 expression in murine hepatic stellate cells during liver injury has no effect on fibrosis formation and resolution
Authors: Hintermann Edith , Bayer Monika , Pfeilschifter Josef M. , Deák Ferenc , Kiss Ibolya , Paulsson Mats , Christen Urs
Published: June 2014

Background & Aims

Matrilins are a family of four oligomeric adaptor proteins whose functions in extracellular matrix assembly during pathophysiological events still need to be explored in more detail. Matrilin‐2 is the largest family member and the only matrilin expressed in the naive liver. Several studies demonstrate that matrilin‐2 interacts with collagen I, fibronectin or laminin‐111‐nidogen‐1 complexes. All these matrix components get upregulated during hepatic scar tissue formation. Therefore, we tested whether matrilin‐2 has an influence on the formation and/or the resolution of fibrotic tissue in the mouse liver.

Methods

Fibrosis was induced by infection with an adenovirus encoding cytochrome P450 2D6 (autoimmune liver damage) or by exposure to the hepatotoxin carbon tetrachloride. Fibrosis severity and matrilin‐2 expression were assessed by immunohistochemistry. Hepatic stellate cells (HSCs) were isolated and analysed by immunocytochemistry and Transwell migration assays.

Results

Both autoimmune as well as chemically induced liver damage led to simultaneous upregulation of matrilin‐2 and collagen I expression. Discontinuation of carbon tetrachloride exposure resulted in concomitant dissolution of both proteins. Activated HSCs were the source of de novo matrilin‐2 expression. Comparing wild type and matrilin‐2‐deficient mice, no differences were detected in fibronectin and collagen I upregulation and resolution kinetics as well as amount or location of fibronectin and collagen I production and degradation.

Conclusions

Our findings suggest that the absence of matrilin‐2 has no effect on HSC activation and regression kinetics, synthetic activity, proliferative capacity, motility, or HSC apoptosis.
Efficacy of telbivudine compared with entecavir in hepatitis B virus‐related cirrhosis: 2 year follow‐up data
Authors: Kim Hae Rim , Yim Hyung Joon , Kang Seonghee , Suh Sang Jun , Kim Seung Young , Hyun Jong Jin , Koo Ja Seol , Kim Ji Hoon , Seo Yeon Seok , Yeon Jong Eun , Lee Sang Woo , Byun Kwan Soo , Um Soon Ho
Published: June 2014

Background & Aims

Entecavir (ETV) is effective in the treatment of chronic hepatitis B virus (HBV) infections, even in patients with underlying cirrhosis. However, there is little information on the effect of telbivudine (TBV) in chronic hepatitis B patients with cirrhosis.This study compared the antiviral efficacy of TBV and ETV in HBV‐related cirrhosis.

Methods

We consecutively enrolled 151 treatment‐naïve patients with HBV‐related cirrhosis who started antiviral therapy with TBV (n = 61) or ETV (n = 90).

Results

After 24 months of treatment, per‐protocol analysis showed similar virological response rates (HBV DNA <20 IU/ml) in the TBV group (80.6%, 25/31) and in the ETV group (90.2%, 74/82) (P = 0.167). However, intention‐to‐treat analysis showed lower virological response rates in the TBV group (41.7%, 25/60) than in the ETV group (83.1%, 74/89) (P = 0.001). Mean reduction in HBV DNA levels was greater in the ETV group (−3.72 ± 1.94 vs. −4.87 ± 1.57 respectively, P = 0.001). Serologic and biochemical response rates at month 24 did not differ significantly between the groups. Child‐Turcotte‐Pugh score was significantly improved after 24 months compared to the pretreatment state without difference between the groups. During 24 months of therapy, 15 patients (27.3%) showed antiviral resistance to TBV while no resistance (0%) was reported in the ETV group (P = 0.001).

Conclusions

Compared to ETV, TBV therapy shows lower efficacy in viral suppression and higher risk of antiviral resistance despite comparable effect on improvement of hepatic function for the treatment of HBV‐related cirrhosis.
Renin‐angiotensin system and fibrosis in non‐alcoholic fatty liver disease
Authors: Goh George B , Pagadala Mangesh R , Dasarathy Jaividhya , Unalp‐Arida Aynur , Sargent Ruth , Hawkins Carol , Sourianarayanane Achuthan , Khiyami Amer , Yerian Lisa , Pai Rish , McCullough Arthur J , Dasarathy Srinivasan
Published: June 2014

Background & Aims

Therapeutic options are limited for patients with non‐alcoholic fatty liver disease (NAFLD). One promising approach is the attenuation of necroinflammation and fibrosis by inhibition of the renin‐angiotensin system (RAS). We explored whether the risk of fibrosis was associated with the use of commonly used medications in NAFLD patients with hypertension. Specifically, we sought to determine the association between RAS blocking agents and severity of hepatic fibrosis in NAFLD patients with hypertension.

Methods

Cross‐sectional study where clinical information including demographics, anthropometry, medical history, concomitant medication use, biochemical and histological features were ascertained in 290 hypertensive patients with biopsy proven NAFLD followed at two hepatology outpatient clinics. Stage of hepatic fibrosis was compared in patients with and without RAS blocker use. Other risk factors for fibrosis were evaluated from the electronic medical records and patient follow‐up.

Results

Baseline characteristics of hypertensive patients treated with and without RAS blockers were similar except for less ballooning (1.02 vs. 1.31, P = 0.001) and lower fibrosis stage (1.63 vs. 2.16, P = 0.002) in patients on RAS blockers On multivariate analysis, advancing age (OR: 1.04; 95%CI: 1.01–1.06, P = 0.012) and presence of diabetes (OR: 2.55; 95%CI: 1.28–5.09, P = 0.008) had an independent positive association, while use of RAS blockers (OR: 0.37; 95%CI: 0.21–0.65, P = 0.001) and statins (OR: 0.52; 95%CI: 0.29–0.93, P = 0.029) had a negative association with advanced fibrosis.

Conclusion

Hypertensive patients with NAFLD on baseline RAS blockers had less advanced hepatic fibrosis suggesting a beneficial effect of RAS blockers in NAFLD.
Revisiting liver disease progression in HIV/HCV‐coinfected patients: the influence of vitamin D, insulin resistance, immune status, IL28B and PNPLA3
Authors: Mandorfer Mattias , Payer Berit A. , Schwabl Philipp , Steiner Sebastian , Ferlitsch Arnulf , Aichelburg Maximilian C. , Stättermayer Albert F. , Ferenci Peter , Obermayer‐Pietsch Barbara , Grabmeier‐Pfistershammer Katharina , Trauner Michael , Peck‐Radosavljevic Markus , Reiberger Thomas
Published: June 2014

Background & Aims

To perform a comprehensive study on independent modulators of liver fibrosis progression and determinants of portal pressure considering immune status, insulin resistance (IR), serum 25‐hydroxyvitamin D (25(OH)D) levels, genetic variants of patatin‐like phospholipase domain‐containing protein 3 (PNPLA3) and interleukin 28B (IL28B) in a thoroughly documented cohort of HIV/hepatitis C‐coinfected (HIV/HCV) patients.

Patients & Methods

25(OH)D deficiency (25(OH)DDEF), IR and low CD4+ T‐lymphocyte nadir (lowCD4NAD) were defined as 25(OH)D <20 ng × ml−1, HOMA‐IR >2 and CD4nadir <200 cells × μl−1 respectively. Liver fibrosis progression rate (FPR) was calculated as METAVIR F units divided by the number of years since HCV infection. Patients with a FPR > median FPR were assigned to the highFPR group.

Results

Among 86 HIV/HCV, the median FPR was 0.167 units × years−1. While the prevalence of prior alcohol abuse, lowCD4NAD and 25(OH)DDEF was higher among highFPR patients, the prevalence of IR was comparable. The association between 25(OH)DDEF and FPR was confirmed in a subgroup of patients with METAVIR stage F0/F1/F2 in which 25(OH)D levels are not affected by the severity of liver disease. The distribution of IL28B C/C and PNPLA3 non‐C/C was similar, while PNPLA3 G/G was exclusively observed in highFPR patients. LowCD4NAD (OR: 2.95; 95% CI: 1.05–8.24; P = 0.039) and 25(OH)DDEF (OR: 5.62; 95% CI: 2.05–15.38; P = 0.001) were independently associated with highFPR and showed an additive effect. Portal pressure correlated with prior alcohol abuse, HCV‐genotype 3, CD4+ nadir and 25(OH)D levels.

Conclusions

Two potentially modifiable factors, CD4+ nadir and 25(OH)D levels, were both independent modulators of liver fibrosis progression and determinants of portal pressure. Further studies are warranted to assess the relevance of PNPLA3 for FPR in HIV/HCV.
High post‐transplant virological response in hepatitis C virus infected patients treated with pretransplant protease inhibitor‐based triple therapy
Authors: Verna Elizabeth C. , Shetty Kirti , Lukose Thresiamma , Terry Nicole , Mentore Kimiknu , Olsen Sonja K. , Fox Alyson N. , Dove Lorna M. , Brown Robert S.
Published: June 2014

Background & Aims

Prevention of recurrent hepatitis C virus (HCV) following liver transplant (LT) with pre‐LT antiviral therapy is limited by poor tolerability and efficacy. We aimed to evaluate the safety and efficacy of NS3/4A protease inhibitor (PI)‐based triple therapy in patients awaiting LT.

Methods

Consecutive patients treated with triple therapy pre‐LT from two centers were prospectively enrolled in an observational cohort. Overall 12 week sustained virological response (SVR12) was the primary outcome. Pre‐ and post‐LT (pTVR) virological response rates and safety were secondary outcomes.

Results

Twenty‐nine patients (mean age 57.9, 79% male, 66% prior non‐responders) were treated with telaprevir (93%) or boceprevir‐based (7%) triple therapy for a median (range) of 27 (3–50) weeks, including a pegylated‐interferon and ribavirin lead‐in in 18%. Median (range) MELD at treatment was 8 (6–16), 39% had hepatocellular carcinoma and all patients were Child‐Turcotte‐Pugh class A (62%) or B (38%). Twelve patients underwent LT, 75% with undetectable viral load. The overall SVR12 rate was 52%, including pre‐LT SVR12 of 41% in patients who completed treatment and follow‐up on the wait list and pTVR12 of 67% among transplanted patients. The pTVR12 rate was 89% among those patients with undetectable viral load at LT. Serious adverse events occurred in nine (31%) patients including one (3%) on‐treatment death and eight (28%) hospitalizations.

Conclusions

Overall SVR12 and pTVR12 rates are high among patients treated with PI‐based triple therapy while awaiting LT, even in this difficult to treat population. However, caution is needed as early discontinuation and serious adverse events are common.
New invasive copepod Oithona davisae Ferrari and Orsi, 1984: seasonal dynamics in Sevastopol Bay and expansion along the Black Sea coasts
Authors: Altukhov Denis A. , Gubanova Alexandra D. , Mukhanov Vladimir S.
Published: June 2014

Seasonal and interannual dynamics of abundance of the recent invader Oithona davisae (Copepoda: Cyclopoida) were investigated in Sevastopol Bay from October 2005, when the species appeared in the plankton, to December 2009. The study was based on bi‐weekly plankton sampling at three stations located within and adjacent to Sevastopol Bay, Crimea, Northern Black Sea. The abundance of O. davisae increased steadily in Sevastopol Bay in 2006–2009. The species was more abundant at the centre of the bay than at its mouth. During the investigated period, an absolute maximum of the invader abundance at the centre of Sevastopol Bay was observed in early December 2008 (91,650 ind. m−3) and at the mouth of the bay in late October 2007 (46,200 ind. m−3). The maximum contribution of O. davisae to the total copepod abundance was about 99%. Expansion of the invasive copepod along the Black Sea coasts is reported. Changes in structure of the zooplankton community for the last 20 years that preconditioned the invasion of the new copepod species in the Black Sea as well as the changes in the community structure caused by O. davisae are discussed.
AtMYB93 is a novel negative regulator of lateral root development in Arabidopsis
Authors: Gibbs Daniel J. , Voß Ute , Harding Susan A. , Fannon Jessica , Moody Laura A. , Yamada Erika , Swarup Kamal , Nibau Candida , Bassel George W. , Choudhary Anushree , Lavenus Julien , Bradshaw Susan J. , Stekel Dov J. , Bennett Malcolm J. , Coates Juliet C.
Published: June 2014

Plant root system plasticity is critical for survival in changing environmental conditions. One important aspect of root architecture is lateral root development, a complex process regulated by hormone, environmental and protein signalling pathways.

Here we show, using molecular genetic approaches, that the MYB transcription factor AtMYB93 is a novel negative regulator of lateral root development in Arabidopsis.

We identify AtMYB93 as an interaction partner of the lateral‐root‐promoting ARABIDILLO proteins. Atmyb93 mutants have faster lateral root developmental progression and enhanced lateral root densities, while AtMYB93‐overexpressing lines display the opposite phenotype. AtMYB93 is expressed strongly, specifically and transiently in the endodermal cells overlying early lateral root primordia and is additionally induced by auxin in the basal meristem of the primary root. Furthermore, Atmyb93 mutant lateral root development is insensitive to auxin, indicating that AtMYB93 is required for normal auxin responses during lateral root development.

We propose that AtMYB93 is part of a novel auxin‐induced negative feedback loop stimulated in a select few endodermal cells early during lateral root development, ensuring that lateral roots only develop when absolutely required. Putative AtMYB93 homologues are detected throughout flowering plants and represent promising targets for manipulating root systems in diverse crop species.
Outcomes of esophageal surgery, especially of the lower esophageal sphincter
Authors: Bonavina Luigi , Siboni Stefano , Saino Greta I. , Cavadas Demetrio , Braghetto Italo , Csendes Attila , Korn Owen , Figueredo Edgar J. , Swanstrom Lee L. , Wassenaar Eelco
Published: June 2014

This paper includes commentaries on outcomes of esophageal surgery, including the mechanisms by which fundoduplication improves lower esophageal sphincter (LES) pressure; the efficacy of the Linx™ management system in improving LES function; the utility of radiologic characterization of antireflux valves following surgery; the correlation between endoscopic findings and reported symptoms following antireflux surgery; the links between laparoscopic sleeve gastrectomy and decreased LES pressure, endoscopic esophagitis, and gastroesophageal reflux disease (GERD); the less favorable outcomes following fundoduplication among obese patients; the application of bioprosthetic meshes to reinforce hiatal repair and decrease the incidence of paraesophageal hernia; the efficacy of endoluminal antireflux procedures, and the limited efficacy of revisional antireflux operations, underscoring the importance of good primary surgery and diligent work‐up to prevent the necessity of revisional procedures.
Stents for benign and malignant esophageal strictures
Authors: Hourneaux de Moura Eduardo Guimarães , Toma Kengo , Goh Khean‐Lee , Romero Ronald , Dua Kulwinder S. , Felix Valter Nilton , Levine Marc S. , Kochhar Rakesh , Appasani Sreekanth , Gusmon Carla Cristina
Published: June 2014

This paper presents commentaries on endotherapy for esophageal perforation/leaks; treatment of esophageal perforation; whether esophageal stents should be used for treating benign esophageal strictures; what determines the optimal stenting period in benign esophageal strictures/leaks; how to choose an esophageal stent; how a new fistula secondary to an esophageal stent should be treated; which strategy should be adopted when a fistula of a cervical anastomosis occurs; intralesional steroids for refractory esophageal strictures; balloon and bougie dilators for esophageal strictures and predictors of response to dilation; whether refractory strictures from different etiologies respond differently to endotherapy; surgical therapy of benign esophageal strictures; and whether stenoses following severe esophageal burns should be treated by esophageal resection or esophageal bypass.
Nonspecific motility disorders, irritable esophagus, and chest pain
Authors: Krarup Anne Lund , Liao Donghua , Gregersen Hans , Drewes Asbjørn Mohr , Hejazi Reza A. , McCallum Richard W. , Vega Kenneth J. , Frazzoni Marzio , Frazzoni Leonardo , Clarke John O. , Achem Sami R.
Published: June 2014

This paper presents commentaries on whether Starling's law applies to the esophagus; whether erythromycin affects esophageal motility; the relationship between hypertensive lower esophageal sphincter and vigorous achalasia; whether ethnic‐ and gender‐based norms affect diagnosis and treatment of esophageal motor disorders; health care and epidemiology of chest pain; whether normal pH excludes esophageal pain; the role of high‐resolution manometry in noncardiac chest pain; whether pH–impedance should be included in the evaluation of noncardiac chest pain; whether there are there alternative therapeutic options to PPI for treating noncardiac chest pain; and the usefulness of psychological treatment and alternative medicine in noncardiac chest pain.
Upper esophageal sphincter dysfunction: diverticula–globus pharyngeus
Authors: Schindler Antonio , Mozzanica Francesco , Alfonsi Enrico , Ginocchio Daniela , Rieder Erwin , Lenglinger Johannes , Schoppmann Sebastian F. , Scharitzer Martina , Pokieser Peter , Kuribayashi Shiko , Kawamura Osamu , Kusano Motoyasu , Zelenik Karol
Published: June 2014

The following discussion of upper esophageal sphincter dysfunction includes commentaries on the role of the cricopharyngeus muscle in reflux disease; the etiology and treatment of Zenker diverticulum; the use of videofluoroscopy in patients with dysphagia, suspicion of aspiration, or globus; the role of pH–impedance monitoring in globus evaluation; and treatment for reflux‐associated globus.
Distribution and morphological pattern of clefts in the craniofacial region seen in a sub‐Saharan tertiary hospital
Authors: Olusanya A.A. , Michael A.I. , Olawoye O.A. , Akinmoladun V.I. , Ademola S.A. , Iyun A.O. , Oluwatosin O.M.
Published: June 2014

Aim

Clefts in the craniofacial region are one of the commonest congenital anomalies recorded in literature. The incidence varies globally with racial differences observed. In Nigeria, the evaluation of the absolute incidence of oral clefts is a challenge as births and deaths are not adequately registered. Especially lacking is the relative prevalence of rare craniofacial clefts to the more common cleft lip and palate anomaly.

This study aims to document the pattern of distribution of craniofacial clefts, including cleft lip and palate anomaly, rare craniofacial clefts, unusual presentation of some of these anomalies, as well as other abnormalities noted in affected cleft patients seen at our centre.

Material and methods

Information on age, gender, weight at presentation, type of cleft anomaly, other abnormalities, as well as affected relatives were extracted from the clinic records of the Cleft Clinic of the University College Hospital, Ibadan, Oyo, Nigeria, from April 2010 to September 2012.

Results

One hundred and forty‐two cases were seen within the 30‐month period, consisting of 58 men and 84 women with a mean age of 43.54 months and a median of 2.0 months. Eighty‐eight per cent of the cases were cleft lip and palate anomalies, while 12.0% were craniofacial clefts. Thirteen per cent had other abnormalities, while 3.5% were considered to be unusual cleft anomalies.

Conclusion

The pattern of distribution of clefts in the craniofacial region in our centre has been documented. Cleft of the primary palate was the commonest while rare craniofacial clefts constituted about one‐eighth of all the craniofacial clefts.
Relationship between starch degradation and carbon demand for maintenance and growth in Arabidopsis thaliana in different irradiance and temperature regimes
Authors: PILKINGTON SARAH M. , ENCKE BEATRICE , KROHN NICOLE , HÖHNE MELANIE , STITT MARK , PYL EVA‐THERESA
Published: June 2014

Experiments were designed to compare the relationship between starch degradation and the use of carbon for maintenance and growth in Arabidopsis in source‐limited and sink‐limited conditions. It is known that starch degradation is regulated by the clock in source‐limited plants, which degrade their starch in a linear manner such that it is almost but not completely exhausted at dawn. We asked whether this response is maintained under an extreme carbon deficit. Arabidopsis was subjected to a sudden combination of a day of low irradiance, to decrease starch at dusk, and a warm night. Starch was degraded in a linear manner through the night, even though the plants became acutely carbon starved. We conclude that starch degradation is not increased to meet demand in carbon‐limited plants. This network property will allow stringent control of starch turnover in a fluctuating environment. In contrast, in sink‐limited plants, which do not completely mobilize their starch during the night, starch degradation was accelerated in warm nights to meet the increased demand for maintenance and growth. Across all conditions, the rate of growth at night depends on the rate of starch degradation, whereas the rate of maintenance respiration decreases only when starch degradation is very slow.
Carbon isotope compositions (δ13C) of leaf, wood and holocellulose differ among genotypes of poplar and between previous land uses in a short‐rotation biomass plantation
Authors: VERLINDEN M. S. , FICHOT R. , BROECKX L. S. , VANHOLME B. , BOERJAN W. , CEULEMANS R.
Published: June 2014

The efficiency of water use to produce biomass is a key trait in designing sustainable bioenergy‐devoted systems. We characterized variations in the carbon isotope composition (δ13C) of leaves, current year wood and holocellulose (as proxies for water use efficiency, WUE) among six poplar genotypes in a short‐rotation plantation. Values of δ13Cwood and δ13Cholocellulose were tightly and positively correlated, but the offset varied significantly among genotypes (0.79–1.01‰). Leaf phenology was strongly correlated with δ13C, and genotypes with a longer growing season showed a higher WUE. In contrast, traits related to growth and carbon uptake were poorly linked to δ13C. Trees growing on former pasture with higher N‐availability displayed higher δ13C as compared with trees growing on former cropland. The positive relationships between δ13Cleaf and leaf N suggested that spatial variations in WUE over the plantation were mainly driven by an N‐related effect on photosynthetic capacities. The very coherent genotype ranking obtained with δ13C in the different tree compartments has some practical outreach. Because WUE remains largely uncoupled from growth in poplar plantations, there is potential to identify genotypes with satisfactory growth and higher WUE.
Broader autism phenotype in mothers predicts social responsiveness in young children with autism spectrum disorders
Authors: Hasegawa Chiaki , Kikuchi Mitsuru , Yoshimura Yuko , Hiraishi Hirotoshi , Munesue Toshio , Nakatani Hideo , Higashida Haruhiro , Asada Minoru , Oi Manabu , Minabe Yoshio
Published: June 2014

Aims

The aim of this study was to identify phenotypes in mothers and fathers that are specifically associated with disturbances in reciprocal social interactions and communication in their young children with autism spectrum disorder (ASD) in a Japanese sample.

Methods

Autistic traits in parents were evaluated using the Autism‐spectrum Quotient (AQ), the Empathy Quotient (EQ) and the Systemizing Quotient (SQ) in 88 parents (44 mothers and corresponding fathers) of children with ASD and in 60 parents (30 mothers and corresponding fathers) of typically developing (TD) children. For the measurement of autistic traits in children, we employed the Social Responsiveness Scale (SRS).

Results

In two of the five AQ subscales (social skills and communication), the parents of ASD children scored significantly higher than did the parents of TD children, regardless of whether the parent was a mother or a father. In addition, in mothers of ASD children, there were significant positive correlations between two of the five AQ subscales (attention‐switching and communication) and the SRS T‐score in their children.

Conclusions

This is the first study to demonstrate that the social skills and communication subscales in the AQ are more sensitive as autism traits in a Japanese sample and to demonstrate that some autistic traits in mothers are specifically associated with disturbances in the social ability of their young children with ASD, as measured by the SRS score. Further study is necessary to determine whether these results were caused by genetic or environmental factors.
Human filarial Wolbachia lipopeptide directly activates human neutrophils in vitro
Authors: Tamarozzi F. , Wright H. L. , Johnston K. L. , Edwards S. W. , Turner J. D. , Taylor M. J.
Published: June 2014

The host inflammatory response to the Onchocerca volvulus endosymbiont, Wolbachia, is a major contributing factor in the development of chronic pathology in humans (onchocerciasis/river blindness). Recently, the toll‐like pattern recognition receptor motif of the major inflammatory ligands of filarial Wolbachia, membrane‐associated diacylated lipoproteins, was functionally defined in murine models of pathology, including mediation of neutrophil recruitment to the cornea. However, the extent to which human neutrophils can be activated in response to this Wolbachia pattern recognition motif is not known. Therefore, the responses of purified peripheral blood human neutrophils to a synthetic N‐terminal diacylated lipopeptide (WoLP) of filarial Wolbachia peptidoglycan‐associated lipoprotein (PAL) were characterized. WoLP exposure led to a dose‐dependent activation of healthy, human neutrophils that included gross morphological alterations and modulation of surface expressed integrins involved in tethering, rolling and extravasation. WoLP exposure induced chemotaxis but not chemokinesis of neutrophils, and secretion of the major neutrophil chemokine, interleukin 8. WoLP also induced and primed the respiratory burst, and enhanced neutrophil survival by delay of apoptosis. These results indicate that the major inflammatory motif of filarial Wolbachia lipoproteins directly activates human neutrophils in vitro and promotes a molecular pathway by which human neutrophils are recruited to sites of Onchocerca parasitism.
KIR3DS1*0130108 isolated using full length sequence‐based typing
Authors: Yindom L.‐M. , Wang L. , Zhang Y. , Rowland‐Jones S.L. , Dong T.
Published: June 2014

KIR3DS1*0130108 possesses three SNPs at: 12548C>G, 13804C>G and 13819G>A (introns 6 and 7, respectively) compared to KIR3DS1*0130101.
Towards a Polycentric Region? The Socio‐economic Trajectory of Rome, an ‘Eternally Mediterranean’ City
Authors: Salvati Luca
Published: June 2014

The present study explores the long‐term changes (1971–2001) in the socio‐economic structure of a monocentric Mediterranean urban region (Rome's province, central Italy) undergoing moderately polycentric development. Descriptive and correlation statistics and a multiway factor analysis (MFA) have been used to analyse the spatio‐temporal evolution of 24 socio‐economic indicators made available at the urban district/municipal scale. The socio‐economic disparities observed along the urban‐rural gradient in 1971 decreased only moderately in 2001. The MFA clearly separates urban districts from suburban municipalities in both 1971 and 2001. Results indicate that exurban development has impacted only partly Rome's urban form which remained mainly compact and dense with persisting socio‐economic gaps between urban and suburban areas. The paper discusses the partial failure of Rome's master plan to promote a really polycentric development and a new, more sustainable, urban form.
Comparative Approaches to Gentrification: A Research Framework
Authors: Lagendijk Arnoud , van Melik Rianne , de Haan Freek , Ernste Huib , Ploegmakers Huub , Kayasu Serap
Published: June 2014

Comparative research on gentrification is on the rise, especially since gentrification is no longer confined to historical, central neighbourhoods in First World countries, but also appeared in rural, new‐built areas and Second World countries. In this paper we present our comparative approach to investigate gentrification processes in four European cities (Arnhem, Istanbul, Vienna, Zurich), which differs from previous studies in its use of assemblage theory as research framework. The multi‐layered framework discerns three levels: ‘metrics’, ‘interpretations’, and ‘practices’. We argue that many comparative studies mainly focus on metrics, while researching interpretations and practices instead – and how these three levels influence each other through processes of actualisation and counteractualisation – would enhance our knowledge on gentrification. In doing so, we aim to provide a precise account of the nested relations of different layers of empirical reality and thus respond to various calls in the debate to intensively examine ‘geographies of gentrification’.
Long‐chain base phosphates modulate pollen tube growth via channel‐mediated influx of calcium
Authors: Wu Juyou , Qin Xiaoya , Tao Shutian , Jiang Xueting , Liang Yun‐Kuan , Zhang Shaoling
Published: June 2014

Long‐chain base phosphates (LCBPs) have been correlated with amounts of crucial biological processes ranging from cell proliferation to apoptosis in animals. However, their functions in plants remain largely unknown. Here, we report that LCBPs, sphingosine‐1‐phosphate (S1P) and phytosphingosine‐1‐phosphate (Phyto‐S1P), modulate pollen tube growth in a concentration‐dependent bi‐phasic manner. The pollen tube growth in the stylar transmitting tissue was promoted by SPHK1 overexpression (SPHK1‐OE) but dampened by SPHK1 knockdown (SPHK1‐KD) compared with wild‐type of Arabidopsis; however, there was no detectable effect on in vitro pollen tube growth caused by misexpression of SPHK1. Interestingly, exogenous S1P or Phyto‐S1P applications could increase the pollen tube growth rate in SPHK1‐OE, SPHK1‐KD and wild‐type of Arabidopsis. Calcium ion (Ca2+)‐imaging analysis showed that S1P triggered a remarkable increase in cytosolic Ca2+ concentration in pollen. Extracellular S1P induced hyperpolarization‐activated Ca2+ currents in the pollen plasma membrane, and the Ca2+ current activation was mediated by heterotrimeric G proteins. Moreover, the S1P‐induced increase of cytosolic free Ca2+ inhibited the influx of potassium ions in pollen tubes. Our findings suggest that LCBPs functions in a signaling cascade that facilitates Ca2+ influx and modulates pollen tube growth.