bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of adenoviral keratoconjunctivitis with a combination of povidone‐iodine 1.0% and dexamethasone 0.1% drops: a clinical prospective controlled randomized study
Authors: Kovalyuk Natalya , Kaiserman Igor , Mimouni Michael , Cohen Ornit , Levartovsky Shmuel , Sherbany Hilda , Mandelboim Michal
Published: March 2017

Purpose

To determine the efficacy of combination povidone‐iodine (PVP‐I) 1.0% eyedrops and dexamethasone 0.1% eyedrops in the treatment of adenoviral keratoconjunctivitis.

Materials and methods

In a prospective, randomized, controlled, double‐blinded clinical trial patients with recent adenoviral keratoconjunctivitis (diagnosed clinically and confirmed by PCR), we randomly divided into three treatment groups: study group – received PVP‐I 1.0% and dexamethasone 0.1%, control 1 group – received dexamethasone 0.1% and control 2 group – received lubricating eyedrops (hypromellose 0.3%). The treatment was administered four times a day in each group. All patients were examined and filled a questionnaire before treatment and on the 3rd, 5th and 7th days of treatment.

Results

We included in the study 78 eyes (26 in each group). Adenovirus type 8 was the most common pathogen (83% of cases). The fastest improvement in patients red eyes, discharge, superficial punctate keratitis and pseudomembranes was observed in the study group (p < 0.001). Those patients reached a near complete recovery in 5–7 days, which was also confirmed by reduction in Adenovirus titres by PCR. The slowest improvement was in the control 2 group. Subepithelial infiltrates (SEI) were observed in 44% of the control 1 group, 20% of the control 2 group and in 0% of the study group. The rate of reduction in Adenovirus titres was the slowest in the control 1 group.

Conclusion

The combination of PVP‐I 1.0% and dexamethasone 0.1% four times a day can reduce symptoms and expedite recovery in epidemic keratoconjunctivitis patients.
Comparative analysis of pulmonary hypertension in patients treated with imatinib, nilotinib and dasatinib
Authors: Minami Mariko , Arita Takeshi , Iwasaki Hiromi , Muta Tsuyoshi , Aoki Takatoshi , Aoki Kenichi , Yamasaki Satoshi , Matsushima Takamitsu , Kato Koji , Takenaka Katsuto , Tanimoto Kazuki , Kamimura Tomohiko , Ogawa Ryosuke , Akashi Koichi , Miyamoto Toshihiro
Published: March 2017

Pulmonary hypertension (PH) is a rare, but life‐threatening, adverse event in patients treated with tyrosine kinase inhibitors (TKIs), such as dasatinib, but has not been fully evaluated in patients treated with imatinib or nilotinib. We used echocardiography to noninvasively assess the incidence of PH in 105 patients with chronic myeloid leukaemia (CML) treated with imatinib (n = 37), nilotinib (n = 30) or dasatinib (n = 38). The mean triscupid regurgitation peak gradient (TRPG), which reflects pulmonary arterial pressure, was 22·7 mmHg in the imatinib group, 23·1 mmHg in the nilotinib group and 23·4 mmHg for dasatinib group. These values were not significantly different, but higher than those (19·0 mmHg) in newly diagnosed CML patients. A TRPG > 31 mmHg, marking possible PH onset, was detected in 9 of 105 patients: one (2·7%) treated with imatinib, three (10·0%) with nilotinib and five (13·2%) with dasatinib. Only three patients complained of dyspnoea, whereas the other six were asymptomatic. In addition, there was a tendency toward correlation of TRPG value and age or TKI treatment duration. These results suggested that treatment with not only dasatinib, but also imatinib and nilotinib, can be associated with subclinical PH. Noninvasive echocardiography is useful for screening, especially in older patients with long‐term TKI treatment.
Telomere length is a critical determinant for survival in multiple myeloma
Authors: Hyatt Sam , Jones Rhiannon E. , Heppel Nicole H. , Grimstead Julia W. , Fegan Chris , Jackson Graham H. , Hills Robert , Allan James M. , Pratt Guy , Pepper Chris , Baird Duncan M.
Published: March 2017

The variable clinical outcomes of Multiple Myeloma (MM) patients are incompletely defined by current prognostication tools. We examined the clinical utility of high‐resolution telomere length analysis as a prognostic marker in MM. Cohort stratification, using a previously determined length threshold for telomere dysfunction, revealed that patients with short telomeres had a significantly shorter overall survival (P < 0·0001; HR = 3·4). Multivariate modelling using forward selection identified International Staging System (ISS) stage as the most important prognostic factor, followed by age and telomere length. Importantly, each ISS prognostic subset could be further risk‐stratified according to telomere length, supporting the inclusion of this parameter as a refinement of the ISS.
The Emergence of Episodic Foresight and Its Consequences
Authors: Suddendorf Thomas
Published: March 2017

Imagining future events and adjusting current behavior accordingly is a hallmark of human cognition. The development of such episodic foresight is attracting increasing research attention. In this article, I review a selection of recent work on the emergence of episodic foresight and its role in different domains, including learning, deliberate practice, affective forecasting, intertemporal choices, and anxiety. Studies suggest that during the preschool years, children begin to consider future scenarios, enabling them to plan, prepare, and shape their future, but many other consequences, such as the role of developing foresight in anticipating hazards, remain unexamined. The potential predictive effects of early individual differences in episodic foresight on later cognitive capacities and developmental outcomes deserve closer scrutiny.
Expression of oxysterol pathway genes in oestrogen‐positive breast carcinomas
Authors: Kloudova Alzbeta , Brynychova Veronika , Vaclavikova Radka , Vrana David , Gatek Jiri , Mrhalova Marcela , Kodet Roman , Soucek Pavel
Published: March 2017

Objective

This study investigated whether gene expression levels of key modulators of the oxysterol signalling pathway modify the prognosis of patients with oestrogen receptor‐positive (ER+) breast carcinomas via interaction with endocrine therapy.

Context

The prognosis of patients with ER+ breast carcinoma depends on several factors. Previous studies have suggested that some oxygenated forms of cholesterol (oxysterols) bind to oestrogen receptor and anti‐oestrogen binding site which may deregulate cholesterol homoeostasis and influence effect of therapy.

Design

The expression levels of 70 oxysterol pathway genes were evaluated in a test set of breast carcinomas differing in ER expression. The genes differentially expressed in ER+ tumours were assessed in a comprehensive set of ER+ tumours to evaluate their clinical significance.

Patients

A total of 193 primary patients with breast carcinoma were included.

Measurements

The transcript levels were determined by quantitative real‐time polymerase chain reaction.

Results

The expression levels of 23 genes were found to be specifically dysregulated in ER+ tumours compared to ER− tumours of the test set. The expression levels of ABCG2, CYP7B1, CYP24A1, CYP39A1 and CH25H genes were found to be strongly associated with disease stage; however, none of the gene expression levels were associated with disease‐free survival in patients treated with endocrine therapy.

Conclusions

The expression of a number of oxysterol pathway genes is significantly modulated by ER expression and associated with the clinical stage of patients. However, the expression of oxysterol pathway genes was not found to modify the prognosis of ER+ patients with breast carcinoma treated with endocrine therapy.
The lipid‐lowering effect of levothyroxine in patients with subclinical hypothyroidism: A systematic review and meta‐analysis of randomized controlled trials
Authors: Li Xiang , Wang Yupeng , Guan Qingbo , Zhao Jiajun , Gao Ling
Published: March 2017

Objectives

Dyslipidaemia is common in patients with subclinical hypothyroidism (SCH). To date, there is no universal agreement regarding the lipid‐lowering effect of substitution treatment with L‐T4 in patients with SCH. We aimed to clarify the effect by conducting this systematic review and meta‐analysis of randomized controlled trials (RCTs).

Design

We systematically searched PubMed, the Cochrane Library, ClinicalTrials.gov and EMBASE for RCTs comparing substitution treatment to placebo treatment or observation. We focused on the primary outcomes of changes from baseline of total, low‐density lipoprotein and high‐density lipoprotein cholesterol (TC, LDL‐C and HLD‐C) and triglycerides. Subgroup analyses were performed, assessing the effect of treatment duration, disease severity and ethnicity on the occurrence of discrepancy.

Results

Twelve trials, with 940 participants, were eligible for analysis. Compared with the control group, levothyroxine substitution yielded a mean reduction in TC (−0.29 mmol/L, [−0.42 to −0.16]) and LDL‐C (−0.22 mmol/L, [−0.36 to −0.09]), with no significant effects on HDL‐C (−0.04 mmol/L, [−0.08 to 0.01]) or triglycerides (−0.04 mmol/L, [−0.08 to 0.00]). Trials in which only patients with mild SCH (thyrotropin <10 mIU/L) were enrolled showed equivalent effects. The lowering effects were weaker, but still significant, in long‐term treatment (>6 months) compared with short‐term treatment (≤6 months) for TC (−0.19 mmol/L [−0.35, −0.03] vs −0.50 mmol/L [−0.68, −0.31], P=.047) and LDL‐C (−0.09 mmol/L [−0.16, −0.02] vs −0.46 mmol/L [−0.68, −0.25], P=.006).

Conclusions

Levothyroxine treatment has clear benefits on TC and LDL‐C in SCH patients, including those with mild SCH.
Prenatal course of metaphyseal anadysplasia associated with homozygous mutation in MMP9 identified by exome sequencing
Authors: Sharony R. , Borochowitz Z. , Cohen L. , Shtorch‐Asor A. , Rosenfeld R. , Modai S. , Reinstein E.
Published: March 2017

Metaphyseal anadysplasia (MANDP) is a rare autosomal recessive form of skeletal dysplasia characterized by normal length at birth and transitory bowing of the legs. Although several families with MANDP have been reported, homozygous mutations in the matrix metalloproteinase type 9 (MMP9) gene have been described in only one consanguineous family, and thus the pre and postnatal phenotypic spectrum is still obscure. A clinically similar but more severe type is caused by autosomal‐dominant inheritance and is caused by mutations in matrix metalloproteinase type 13 gene (MMP13). Here, we report the prenatal and early postnatal course of two affected sib fetuses with early sonographic evidence of long bone shortening and postnatally no metaphyseal changes. Whole‐exome sequencing revealed homozygous mutation in MMP9 in both fetuses suggesting a diagnosis of MANDP. We propose that MANDP should be considered in pregnancies with early prenatal shortening of the long bones without associated finding of lethal skeletal dysplasias. In addition, the finding of homozygous mutation in non‐consanguineous parents of Jewish‐Caucasus ancestry may suggest unawareness of such relation or the occurrence of a founder mutation in this gene.
A randomised controlled trial of sodium citrate spray for non‐conductive olfactory disorders
Authors: Philpott C.M. , Erskine S.E. , Clark A. , Leeper A. , Salam M. , Sharma R. , Murty G.E. , Hummel T.
Published: March 2017

Objectives

Previous research has suggested that sodium citrate improves hyposmia by decreasing mucus calcium levels in the nose. This study aimed to confirm or refute this effect in a single application and assess potential side‐effects.

Design

Study design was a randomised double‐blind controlled trial of sodium citrate nasal spray (intervention) vs sterile water (control). Fifty‐five patients with non‐conductive olfactory loss were randomised to receive the intervention or placebo.

Setting

Tertiary care clinic.

Main outcome measures

The primary outcome measure was improvement in measured olfactory thresholds for phenyl ethyl alcohol (PEA) over 2 hours. Other outcome measures assessed were improvement in olfactory thresholds in 1‐butanol, eucalyptol and acetic acid; number of responders with a clinically relevant response in each arm; and adverse effects.

Results

A significant effect was seen in the intervention arm for PEA and for 1‐butanol and eucalyptol when compared to the control arm (P<.05); 32% of the intervention arm responded in terms of improved sensitivity towards some of the odours. Minor adverse effects noted included sore throat, nasal paraesthesia, slight rhinorrhoea and itching. The duration of effect of the citrate is transient, peaking at 30‐60 minutes after application.

Conclusions

Sodium citrate yields some potential as a treatment for non‐conductive olfactory loss; however, these findings require corroboration in further clinical trials looking at longer term regular use of the spray as a viable therapeutic option for patients where it would be applied at frequent intervals such as before mealtimes.
Connecting today's climates to future climate analogs to facilitate movement of species under climate change
Authors: Littlefield Caitlin E. , McRae Brad H. , Michalak Julia L. , Lawler Joshua J. , Carroll Carlos
Published: March 2017

Increasing connectivity is an important strategy for facilitating species range shifts and maintaining biodiversity in the face of climate change. To date, however, few researchers have included future climate projections in efforts to prioritize areas for increasing connectivity. We identified key areas likely to facilitate climate‐induced species’ movement across western North America. Using historical climate data sets and future climate projections, we mapped potential species’ movement routes that link current climate conditions to analogous climate conditions in the future (i.e., future climate analogs) with a novel moving‐window analysis based on electrical circuit theory. In addition to tracing shifting climates, the approach accounted for landscape permeability and empirically derived species’ dispersal capabilities. We compared connectivity maps generated with our climate‐change‐informed approach with maps of connectivity based solely on the degree of human modification of the landscape. Including future climate projections in connectivity models substantially shifted and constrained priority areas for movement to a smaller proportion of the landscape than when climate projections were not considered. Potential movement, measured as current flow, decreased in all ecoregions when climate projections were included, particularly when dispersal was limited, which made climate analogs inaccessible. Many areas emerged as important for connectivity only when climate change was modeled in 2 time steps rather than in a single time step. Our results illustrate that movement routes needed to track changing climatic conditions may differ from those that connect present‐day landscapes. Incorporating future climate projections into connectivity modeling is an important step toward facilitating successful species movement and population persistence in a changing climate.
Straight‐to‐test colonoscopy for 2‐week‐wait referrals improves time to diagnosis of colorectal cancer and is feasible in a high‐volume unit
Authors: Banerjea A. , Voll J. , Chowdhury A. , Siddika A. , Thomson S. , Briggs R. , Humes D. J. ,   Nottingham Colorectal Service
Published: March 2017

Aim

We have introduced ‘straight‐to‐test’ (STT) colonoscopy as part of our 2‐week‐wait (2WW) pathway to address increasing numbers of urgent referrals for colorectal cancer (CRC) within the National Health Service. In this study we evaluated the ability of this initiative to shorten the time to diagnosis of CRC.

Method

We amended our 2WW referral form to include performance status and comorbidities. General practitioners were asked to provide data on estimated glomerular filtration rate and full blood count/ferritin. Our 2WW referrals were screened by a colorectal consultant and a nurse specialist. Those deemed unsuitable for STT were offered outpatient assessment (OPA).

Results

Of 553 2WW referrals screened, 352 were considered suitable, 65 of whom failed a telephone assessment or were uncontactable, and accordingly 287 were offered the STT pathway. The STT group was significantly younger than the OPA group (median 65.9 years vs 78.7 years; P < 0.0001). STT colonoscopy significantly reduced the time to first test (13 days vs 22 days; P < 0.0001) and tissue diagnosis from the referral date (17 days vs 24.5 days; P < 0.0001). Thirty‐seven (6.8%) CRCs were detected. Proportionately fewer patients in the STT pathway were managed with ‘best supportive care only’ compared with patients attending OPA (one of 15 vs six of 22, respectively). STT colonoscopy obviated the need for clinic attendance before testing in 287 patients, representing a potential net cost benefit of at least £48 500 in 4 months.

Conclusion

STT colonoscopy was safe and effective for selecting out a group of symptomatic patients who could proceed straight to endoscopic examination and receive a diagnosis more rapidly.
Farmer Perceptions and Behaviors Related to Wildlife and On‐Farm Conservation Actions
Authors: Kross Sara M. , Ingram Katherine P. , Long Rachael F. , Niles Meredith T.
Published: March 2017

Policy makers are increasingly encouraging farmers to protect or enhance habitat on their farms for wildlife conservation. However, a lack of knowledge of farmers’ opinions toward wildlife can lead to poor integration of conservation measures. We surveyed farmers to assess their perceptions of ecosystem services and disservices from perching birds, raptors, and bats—three taxa commonly targeted by conservation measures. The majority of farmers thought that perching birds and bats were beneficial for insect pest control and that raptors were beneficial for vertebrate pest control; however, fruit farmers viewed perching birds more negatively than did farmers growing other crops. Farmers using organic methods viewed all three wildlife groups more positively than conventional farmers. Farmer perception toward each wildlife group predicted their action to either attract or deter those taxa, suggesting the need to focus research and outreach on the effects of wildlife on farms for conservation programs to positively influence farmer perceptions.
Pharmacokinetic and pharmacogenetic analysis of immunosuppressive agents after laparoscopic sleeve gastrectomy
Authors: Diwan Tayyab S. , Lichvar Alicia B. , Leino Abbie D. , Vinks Alexander A. , Christians Uwe , Shields Adele R. , Cardi Michael A. , Fukuda Tsuyoshi , Mizuno Tomoyuki , Kaiser Tiffany , Woodle E. Steve , Alloway Rita R.
Published: March 2017

Background

Severe obesity has been shown to limit access to renal transplantation in patients with end‐stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (LSG) has been performed in the ESRD population to assist in achieving waitlist and transplant eligibility. Little is known about how LSG impacts the bioequivalence of tacrolimus products and immunosuppression pharmacokinetics.

Methods

This was a prospective, open‐label, single‐dose, crossover, two‐period pharmacokinetic (PK) study. The purpose of this study was to assess single‐dose PK of immediate‐release tacrolimus (IR‐TAC), extended‐release tacrolimus (ER‐TAC), and mycophenolic acid (MPA) in adult ESRD patients post‐LSG.

Results

Twenty‐three subjects were included in the 24‐hour PK assessments. The ratio of geometric means between ER‐TAC and IR‐TAC was 103.5% (90% CI; 89.6%‐119.6%) for AUC0‐24 and 92.5% (90% CI; 80.4%‐106.4%) for Cmax. PK parameters were similar between ER‐TAC and IR‐TAC, except for Cmin (P=.004) and Cmax (P=.04). MPA AUC0‐24 was similar when given with either ER‐TAC or IR‐TAC (P=.32). Patients expressing CYP3A5*1 genotypes had lower tacrolimus AUC0‐24 values vs those with CYP3A5*3/*3 (IR‐TACP<.001; ER‐TACP=.008). Genotype did not impact MPA PK.

Conclusion

Dose modification of immunosuppressants post‐LSG may not be necessary aside from standard therapeutic drug monitoring.
Characteristics of compatible pair participants in kidney paired donation at a single center
Authors: Weng Francis L. , Grogan Tracy , Patel Anup M. , Mulgaonkar Shamkant , Morgievich Marie M.
Published: March 2017

Compatible pairs of living kidney donors and their intended recipients can enter into kidney paired donation (KPD) and facilitate additional living donor kidney transplants (LDKTs). We examined 11 compatible pairs (the intended recipients and their intended, compatible donors) who participated in KPD, along with the recipients’ 11 matched, exchange donors. The 11 pairs participated in 10 separate exchanges (three were multicenter exchanges) that included 33 total LDKTs (22 additional LDKTs). All the intended donors were blood group O and female, with a mean living kidney donor profile index (LKDPI) of 27.6 (SD 16.8). The matched donors had a mean LKDPI of 9.4 (SD 31.7). Compatible pairs entered KPD for altruistic reasons (N=2) or due to mismatch of age (N=7) or body/kidney size (N=2) between the recipient and intended donor. In four cases, retrospective calculation of the LKDPI revealed that the matched donor had a higher LKDPI than the intended donor. Of the 22 recipients of LDKTs enabled by the compatible pairs, three were highly sensitized, with PRA >80%. In conclusion, most compatible pairs entered into KPD so that the recipient could receive a LDKT transplant from a donor whose age or body/kidney size were more favorable to post‐transplant outcomes.
Primary cutaneous anaplastic large cell lymphoma
Authors: Brown Ryanne A. , Fernandez‐Pol Sebastian , Kim Jinah
Published: March 2017

Primary cutaneous anaplastic large cell lymphoma (PC‐ALCL) is a CD30+ lymphoproliferative disorder (LPD) of the skin with a relatively good prognosis in the absence of high‐stage disease. CD30+ LPDs comprise approximately 25%‐30% of primary cutaneous lymphomas and as a group represent the second most common clonal T‐cell neoplasm of the skin behind mycosis fungoides. Diagnosis of PC‐ALCL relies strongly on clinicopathologic correlation given the potential morphologic, clinical and molecular overlap with the other cutaneous CD30+ LPD, lymphomatoid papulosis, and more aggressive hematolymphoid neoplasms.
SOX10 immunohistochemistry in sweat ductal/glandular neoplasms
Authors: Cassarino David S. , Su Albert , Robbins Bruce A. , Altree‐Tacha David , Ra Seong
Published: March 2017

Background

SOX10 is a newer Schwannian and melanocytic marker that has generated great interest for its relative sensitivity and specificity in the diagnosis of neural crest‐derived tumors. Previous studies with SOX10 have shown positive immunohistochemical expression in cutaneous eccrine glands and negative expression in eccrine ducts, apocrine glands and hair follicles. Thus, we hypothesized that some sweat gland tumors of presumed eccrine origin would be positive for SOX10, whereas apocrine‐derived sweat gland tumors would not.

Methods

A mouse monoclonal anti‐SOX10 (clone BC34: Biocare Medical; Concord, California) immunohistochemical antibody was performed on various sweat gland tumors and basal cell carcinoma.

Results

SOX10 showed positivity in spiradenomas (13/13), cylindromas (9/10), hidradenoma papilliferum (10/10), syringocystadenoma papilliferum (8/10), apocrine adenomas (8/10), and negativity in poromas (0/12), syringomas (0/10), and basal cell carcinomas (0/13). There was mixed staining of hidradenomas (6/15).

Conclusions

SOX10 immunohistochemistry may be of utility in distinguishing some of the varying adnexal tumors from each other, and from basal cell carcinoma (BCC), but given the staining of both apocrine and eccrine tumors, does not seem to provide information as to their origins as either eccrine or apocrine tumors.
Equine gastric ulcer syndrome in adult donkeys: Investigation on prevalence, anatomical distribution, and severity
Authors: Sgorbini M. , Bonelli F. , Papini R. , Busechian S. , Briganti A. , Laus F. , Faillace V. , Zappulla F. , Rizk A. , Rueca F.
Published: March 2017

The study was performed on 39 live donkeys that underwent gastroscopic examination. The lesions were recorded in accordance with the European College of Equine Internal Medicine Consensus Statement guidelines. The presence of Gasterophilus sp. larvae was also recorded. Larvae were collected and identified to species level. Fisher's exact test was used to compare different prevalence values for sex, age, and anatomical distribution of lesions. Gastric lesions were present in 20/39 (51.3% [35.6–67%]) donkeys; 19/39 (48.7% [95% confidence interval = 33–64.4%]) were affected only by equine squamous gastric disease (ESGD), while 1/39 (2.6% [0–7.5%]) showed both ESGD and equine glandular gastric disease (EGGD), thus 95% of positive donkeys showed lesions located in the nonglandular mucosa. The ESGD grade was 0/4 (48.7% [33–64.4%]) in 19/39, 1/4 (12.8% [2.3–23.3%]) in 5/39, 2/4 (25.6% [11.9–39.5%]) in 10/39, 3/4 in 4/39 (10.3% [0.7–19.8%]) and 4/4 in 1/39 (2.6% [0–7.5%]) donkeys, respectively. The EGGD lesion was a mild depression in the ventral glandular fundus. ESGD was primary in all the donkeys included and lesions were located around the cardia and along the lesser curvature. Gasterophilus sp. larvae were present in all animals and were identified as third‐stage larvae of Gasterophilus intestinalis. No animals showed clinical signs of equine gastric ulcer syndrome (EGUS). No significant differences relating to sex, age or breed were found in the prevalence of EGUS in this study, while the proportion of donkeys affected by ESGD was statistically higher than those affected by EGGD. To the best of our knowledge, this is the first report on the gastroscopic evaluation of EGUS in live donkeys. Our results show a higher prevalence of EGUS in live donkeys than values previously reported by other authors in donkeys that were dead or had been subjected to euthanasia. The detection of third‐stage G. intestinalis larvae was not unexpected since these can be found in the stomach of equids throughout the year, and G. intestinalis has been reported as the most common Gasterophilus sp. in Italy.
Verapamil treatment induces cytoprotective autophagy by modulating cellular metabolism
Authors: Kania Elżbieta , Pająk Beata , O'Prey Jim , Sierra Gonzalez Pablo , Litwiniuk Anna , Urbańska Kaja , Ryan Kevin M. , Orzechowski Arkadiusz
Published: March 2017

Verapamil, an L‐type calcium channel blocker, has been used successfully to treat cardiovascular diseases. Interestingly, we have recently shown that treatment of cancer cells with verapamil causes an effect on autophagy. As autophagy is known to modulate chemotherapy responses, this prompted us to explore the impact of verapamil on autophagy and cell viability in greater detail. We report here that verapamil causes an induction of autophagic flux in a number or tumor cells and immortalized normal cells. Moreover, we found that inhibition of autophagy in COLO 205 cells, via treatment with the chloroquine (CQ) or by CRISPR/Cas9‐mediated disruption of the autophagy genes Atg7 and Atg5, causes an upregulation of apoptotic markers in response to verapamil. In search of a mechanism for this effect and because autophagy can often mitigate metabolic stress, we examined the impact of verapamil on cellular metabolism. This revealed that in normal prostate cells, verapamil diminishes glucose and glycolytic intermediate levels leading to adenosine 5′‐triphosphate (ATP) depletion. In contrast, in COLO 205 cells it enhances aerobic glycolysis and maintains ATP. Importantly, we found that the autophagic response in these cells is related to the activity of l‐lactate dehydrogenase A (LDHA, EC 1.1.1.27), as inhibition of LDHA reduces both basal and verapamil‐induced autophagy and consequently decreases cell viability. In summary, these findings not only identify a novel mechanism of cytoprotective autophagy induction but they also highlight the potential of using verapamil together with inhibitors of autophagy for the treatment of malignant disease.

Enzymes

l‐lactate dehydrogenase (LDHA, EC 1.1.1.27).
Ribosomal protein L7/L12 is required for GTPase translation factors EF‐G, RF3, and IF2 to bind in their GTP state to 70S ribosomes
Authors: Carlson Markus A. , Haddad Bassam G. , Weis Amanda J. , Blackwood Colby S. , Shelton Catherine D. , Wuerth Michelle E. , Walter Justin D. , Spiegel Paul Clint
Published: March 2017

Ribosomal protein L7/L12 is associated with translation initiation, elongation, and termination by the 70S ribosome. The guanosine 5′ triphosphate hydrolase (GTPase) activity of elongation factor G (EF‐G) requires the presence of L7/L12, which is critical for ribosomal translocation. Here, we have developed new methods for the complete depletion of L7/L12 from Escherichia coli 70S ribosomes to analyze the effect of L7/L12 on the activities of the GTPase factors EF‐G, RF3, IF2, and LepA. Upon removal of L7/L12 from ribosomes, the GTPase activities of EF‐G, RF3, and IF2 decreased to basal levels, while the activity of LepA decreased marginally. Upon reconstitution of ribosomes with recombinant L12, the GTPase activities of all GTPases returned to full activity. Moreover, ribosome binding assays indicated that EF‐G, RF3, and IF2 require L7/L12 for stable binding in the GTP state, and LepA retained > 50% binding. Lastly, an EF‐G∆G′ truncation mutant possessed ribosome‐dependent GTPase activity, which was insensitive to L7/L12. Our results indicate that L7/L12 is required for stable binding of ribosome‐dependent GTPases that harbor direct interactions to the L7/L12 C‐terminal domains, either through a G′ domain (EF‐G, RF3) or a unique N‐terminal domain (IF2). Furthermore, we hypothesize this interaction is concomitant with counterclockwise ribosomal intersubunit rotation, which is required for translocation, initiation, and post‐termination.
Intraflagellar transport: mechanisms of motor action, cooperation, and cargo delivery
Authors: Prevo Bram , Scholey Jonathan M. , Peterman Erwin J. G.
Published: March 2017

Intraflagellar transport (IFT) is a form of motor‐dependent cargo transport that is essential for the assembly, maintenance, and length control of cilia, which play critical roles in motility, sensory reception, and signal transduction in virtually all eukaryotic cells. During IFT, anterograde kinesin‐2 and retrograde IFT dynein motors drive the bidirectional transport of IFT trains that deliver cargo, for example, axoneme precursors such as tubulins as well as molecules of the signal transduction machinery, to their site of assembly within the cilium. Following its discovery in Chlamydomonas, IFT has emerged as a powerful model system for studying general principles of motor‐dependent cargo transport and we now appreciate the diversity that exists in the mechanism of IFT within cilia of different cell types. The absence of heterotrimeric kinesin‐2 function, for example, causes a complete loss of both IFT and cilia in Chlamydomonas, but following its loss in Caenorhabditis elegans, where its primary function is loading the IFT machinery into cilia, homodimeric kinesin‐2‐driven IFT persists and assembles a full‐length cilium. Generally, heterotrimeric kinesin‐2 and IFT dynein motors are thought to play widespread roles as core IFT motors, whereas homodimeric kinesin‐2 motors are accessory motors that mediate different functions in a broad range of cilia, in some cases contributing to axoneme assembly or the delivery of signaling molecules but in many other cases their ciliary functions, if any, remain unknown. In this review, we focus on mechanisms of motor action, motor cooperation, and motor‐dependent cargo delivery during IFT.
TGFβ‐TAZ/SRF signalling regulates vascular smooth muscle cell differentiation
Authors: Pagiatakis Christina , Sun Dandan , Tobin Stephanie W. , Miyake Tetsuaki , McDermott John C.
Published: March 2017

Vascular smooth muscle cells (VSMCs) do not terminally differentiate; they modulate their phenotype between proliferative and differentiated states, which is a major factor contributing to vascular diseases. TGFβ signalling has been implicated in inducing VSMC differentiation, although the exact mechanism remains largely unknown. Our goal was to assess the network of transcription factors involved in the induction of VSMC differentiation, and to determine the role of TAZ in promoting the quiescent VSMC phenotype. TGFβ robustly induces VSMC marker genes in 10T1/2 mouse embryonic fibroblast cells and the potent transcriptional regulator TAZ has been shown to retain Smad complexes on DNA. Thus, the role of TAZ in regulation of VSMC differentiation was studied. Using primary aortic VSMCs coupled with siRNA‐mediated gene silencing, our studies reveal that TAZ is required for TGFβ induction of smooth muscle genes and is also required for the differentiated VSMC phenotype; synergy between TAZ and SRF, and TAZ and Myocardin (MyoC856), in regulating smooth muscle gene activation was observed. These data provide evidence of components of a novel signalling pathway that links TGFβ signalling to induction of smooth muscle genes through a mechanism involving regulation of TAZ and SRF proteins. In addition, we report a physical interaction of TAZ and MyoC856. These observations elucidate a novel level of control of VSMC induction which may have implications for vascular diseases and congenital vascular malformations.
Characterization of 60 types of Chinese biomass waste and resultant biochars in terms of their candidacy for soil application
Authors: Sun Xiaoyin , Shan Ruifeng , Li Xuhui , Pan Jihua , Liu Xing , Deng Ruonan , Song Junyao
Published: March 2017

The composition and pyrolysis characteristics of 60 types of biomass waste from the following six source categories were compared: agricultural residues, woody pruning waste from gardens and lawns, aquatic plant material from eutrophic water bodies, nutshells and fruit peels, livestock manure and residual sludge from municipal wastewater treatment. The yield and physicochemical characteristics of the biochar produced from these feedstocks at 350 °C, 500 °C and 650 °C were also examined. Results of correlation and canonical correspondence analysis between feedstock composition and biochar properties showed that feedstock type played an important role in controlling yield and properties of biochars. The yields of biochar dry ash‐free (daf.) basis were positively correlated with cellulose, lignin and lignin/cellulose content of feedstock; and ash content hampered the biochar production. Furthermore, the intensity of correlation between biochar yield and its feedstock composition was improved with pyrolysis temperature and degree of feedstock decomposition. The fixed carbon content in biochar was also negatively influenced by ash content of feedstock, and it increased with increasing pyrolysis temperature when the ash content was below 34.57% in feedstock and decreased when the ash content exceeded. The fixed carbon production in biochar per unit ash‐free mass (af.) was positively related to cellulose, lignin and lignin/cellulose content in feedstock, which were same with the yield of biochar (daf.). But on the contrary, the volatiles content in biochar (af.) had negative correlation with these organic constituents. For most feedstocks, the differences in the biochar characteristics among the biomass categories were greater than within any individual category. C/N, H/C and O/C atomic ratio and bulk density of biochar from different types of biomass were also compared. The results will provide guidance for the reutilization of biomass wastes and production of biochar with specified properties for soil amendment applications.
p53 immunohistochemistry in high‐grade urothelial carcinoma of the bladder is prognostically significant
Authors: Hodgson Anjelica , Xu Bin , Downes Michelle R
Published: March 2017

Aims

TP53 mutations are characteristic of the high‐grade pathway in the dual pathway of urothelial carcinogenesis. These mutations have been correlated with aberrant accumulation of p53 protein; however the definition and significance of this vary in the literature. The aim of this study was to assess p53 immunostaining in a cohort of high‐grade urothelial carcinomas by using standard published cut‐offs and a novel binarized method that included assessment of the null phenotype. Each scoring method was correlated with oncological outcome.

Methods and results

A triplicate core tissue microarray was constructed from 207 cases of high‐grade urothelial carcinoma treated by cystectomy, and was stained with p53. The percentage nuclear staining was recorded for each core and averaged for every case (206 cases were evaluable). Cases were categorized as positive/negative according to published cut‐offs (10%, 40%) or by binarizing them as abnormal (null phenotype or >50% positivity) and wild type (1–49% positivity). Correlation with disease‐specific survival was not significant according to standard definitions of p53 positivity. When a 40% cut‐off was used, a correlation with relapse‐free survival was significant on univariate analysis (P = 0.038) but not on multivariate analysis (P = 0.079). Abnormal p53 expression showed a near‐significant trend for association with disease‐specific survival (P = 0.052) and was a significant predictor for relapse‐free survival on both univariate analysis (P = 0.047) and multivariate analysis (P = 0.035).

Conclusions

Prior to this study, the p53 null phenotype was not well described in urothelial carcinoma of the bladder. Abnormal p53 immunoexpression (null staining pattern or staining in >50% of cells) is prognostic in terms of oncological outcome.
Does party identification associate with consumer preferences? Analyzing Finnish consumers in 2009 and 2014
Authors: Koivula Aki , Räsänen Pekka , Saarinen Arttu
Published: March 2017

This article examines the association between Finn's political orientation and preferences regarding hedonistic and mundane consumer activities. Data derived from national‐level surveys collected in Finland in 2009 (n=1,202) and 2014 (n=1,351) suggests that political party identification is an important predictor of perceived consumption, even after controlling for the effects of key socio‐demographic factors. In general, supporters of the right‐wing National Coalition Party consider themselves as high‐level consumers more often than the supporters of other political parties do. The results also show that there have been very few temporal changes in the association between party identification and consumption preferences. The effect of party identification is stronger for hedonistic activities than for mundane activities. It is argued that political party identification has similar impact on individual's consumer preferences as other lifestyle and social network factors have. The findings offer us new possibilities for further research addressing consumer activities, and other behavioural correlates of political orientation.
Household characteristics and the change of financial risk tolerance during the financial crisis in the United States
Authors: Chiang Tsun‐Feng , Xiao Jing Jian
Published: March 2017

This study examines how household financial risk tolerance is affected during the period of 2007 and 2009, which covered the eve and trough of the financial crisis in the United States and what types of households are associated with the change of risk tolerance. Risk tolerance is measured by two objective indicators, narrowly and broadly defined stock ownership, and a subjective indicator, risk taking attitude. Using panel data from 2007 to 2009 Survey of Consumer Finances, results show that during the financial crisis, the households in general are more risk averse, indicated by withdrawing from stock markets and holding a less risk taking attitude. In addition, Black and Hispanic households are more likely and households with higher education are less likely to withdraw from stock markets. Older households are less likely to change in risk tolerance during the financial crisis, as are richer households. The findings show panel data could generate novel results and contribute to the literature of financial risk tolerance.
The digital divide experienced by older consumers in smart environments
Authors: Hwang Hyesun , Nam Su‐Jung
Published: March 2017

The continuing transition of the Internet from wired to mobile has facilitated changes in Internet use. By focusing on older consumers as a potentially disadvantaged group, this study examines whether smart environments have the potential to bridge the digital divide. Data were derived from an analysis of the 2013 South Korean Information Divide data set (n = 2386 for those 60 years and older; n = 5841 for those under 60 years). The existence of a digital divide in the smart environment was verified by comparing younger and older South Koreans; this showed that continuing consumer education is needed to enhance older people's experience and skills regarding information and in its use of communication technology. The digital divide was measured based on three aspects: accessibility, competence, and usage. In smart environments, gaps in accessibility and competence between the age groups increased whereas the gap in information usage decreased. Compared with the personal computer‐based environment, members of both groups in the smart environment exhibited increased usage levels with regard to social relationship services, while the gap between the groups with regard to use of convenience services was reduced.
Food co‐operatives sustainably managing common pool resources as hyper‐communities as outlined by Consumer Culture Theory
Authors: Berge Simon
Published: March 2017

This paper presents the interview results from nine managers operating in the co‐operative food sector in Ontario, Canada. The interview results are framed within the context of Consumer Culture Theory to show how co‐operatives can be considered hyper‐communities that are built around an opposition to the current economic system's management of food as a common pool resource. The co‐operative managers interviewed present a view that co‐operatives act as drivers of sustainable innovation by allowing individuals to act as a group with a common interest in sustainable practices. The co‐operative model provides these hyper‐communities with guidance to interact with the economic system through the co‐operative principles. The co‐operative principles assist co‐operative managers in establishing member control over the common pool resource. This paper supports the growing literature on the co‐operative economy and self‐governance of common pool resources for a sustainable future.
Preparation and photoluminescence properties with the site‐selected excitations of Bi3+‐activated Ba3Sc4O9 phosphors
Authors: Wang Yichao , Ding Jianyan , Wang Yuhua
Published: March 2017

A series of novel Bi3+‐doped Ba3Sc4O9 phosphors were synthesized through the solid‐state reaction. Their photoluminescence, decay curves, and thermal quenching properties were investigated in detail. The Ba3Sc4O9:Bi3+ phosphors could be efficiently excited in the ultraviolet and near‐ultraviolet region (300‐400 nm), and the photoluminescence properties possess an obvious site‐selected excitations phenomenon. When excited at the ultraviolet light (320‐360 nm), the phosphors present a green or a bluish green emission, and when excited at the near‐ultraviolet light (370‐390 nm), the phosphors always show a yellow emission. The emission spectra excited at the different wavelength can be decomposed into four components, which accord with the four cationic sites in the structure of Ba3Sc4O9. The influence of the Bi3+ concentration on the photoluminescence properties is also investigated. Upon excitation at 330 and 377 nm, the Ba3Sc4O9:Bi3+ both have good thermal quenching properties; their emission intensity of the peak at 150°C both exceed 60% of the initial value. The above results indicate that the Ba3Sc4O9:Bi3+ phosphor is a promising candidate to provide green or yellow components for UV or near‐UV LEDs.
Microstructural evolution in infiltration‐growth processed MgB2 bulk superconductors
Authors: Bhagurkar Ashutosh G. , Yamamoto Akiyasu , Dennis Anthony R. , Durrell John H. , Aljohani Talal A. , Nadendla Hari B. , Cardwell David A.
Published: March 2017

The study reports phase and microstructural evolution in MgB2 bulk superconductors fabricated by an infiltration and growth (IG) process. Three distinct stages, (1) intermediate boride formation, (2) bulk liquid Mg infiltration, and (3) MgB2 layer formation, were identified in IG process after detailed examination of series of samples prepared with varied heating conditions. The intermediate phase Mg2B25, isomorphous to β‐boron, was detected prior to MgB2 phase formation in stage (1). Due to volume expansion involved in stage 1, cracks formed in the β‐boron particles and propagated radially inwards during stage 3. The growing MgB2 particles sintered simultaneously with formation of grain boundaries during the process, as evidenced by the measured hardness and critical current density in these samples. From our observations, we estimate the total time needed for complete transformation to MgB2.
Interactions of Ta2O5 with water vapor at elevated temperatures
Authors: Myers Dwight L. , Kulis Michael J. , Horwath Joseph P. , Jacobson Nathan S. , Fox Dennis S.
Published: March 2017

Tantalum pentoxide (Ta2O5) and its solid solution phases are candidate coatings for components to be used in combustion environments. Thus, it is important to understand the response of Ta2O5 to high‐temperature water vapor, a product of combustion. Thermogravimetric methods are used to examine the oxide in reactant streams of controlled water vapor contents at 1250°C‐1450°C. The observed weight loss indicates a reaction of the general form ½ Ta2O5(s) + x H2O(g)=TaOy(OH)x(g). Methodical variation in the water vapor pressure suggests the products are a mix of TaO(OH)3(g) and Ta(OH)5(g). Evidence of TaO(OH)3(g) was observed with a sampling mass spectrometer. The measured hydroxide and oxyhyroxide vapor fluxes from Ta2O5 are compared with calculated vapor fluxes from SiO2 and Al2O3. Ta2O5 exhibits fluxes similar to those from SiO2 due to gaseous metal hydroxide formation.
At first sight or second glance: clinical presentation of mosaic manifestations of autosomal dominant skin disorders – a case series
Authors: Toberer F. , Happle R. , Schneiderbauer R. , Hausser I. , Kröhl V. , Epple A. , Moog U. , Enk A.H. , Lonsdorf A.S.
Published: March 2017

Background

Several autosomal dominant disorders may manifest in mosaic patterns with cutaneous involvement. Genomic mosaicism results from postzygotic autosomal mutations, giving rise to clonal proliferation of two genetically distinct cell groups, which clinically present as lesions following the lines of Blaschko.

Objective

To increase the awareness of the clinical variability of mosaic manifestations in autosomal dominant skin disorders in order to avoid delayed diagnosis.

Methods

Clinicopathologic correlation in a case series including three patients with mosaic manifestations of different autosomal dominant skin diseases.

Results

Here, we describe a patient with type 1 segmental mosaicism of epidermolytic ichthyosis (case 1) and two patients with either type 1 (case 2) or type 2 (case 3) segmental neurofibromatosis 1 (NF1).

Conclusion

Dermatologists should be familiar with mosaic manifestations of autosomal dominant skin diseases to ensure appropriate guidance of the affected patient. Genetic counselling is mandatory as even limited forms of mosaicism may involve the patient's germline with a moderately increased risk to transmit the mutation to their offspring, resulting in a more severe, generalized form of the respective disease.