bluuebunny/crossref_metadata_2025 huggingface dataset:
Photo‐patch and patch tests in patients with dermatitis over the photo‐exposed areas: A study of 101 cases from a tertiary care centre in India
Authors: Sharma Vinod Kumar , Bhari Neetu , Wadhwani Ashok Roopchand , Bhatia Riti
Published: June 2016

Background

Many patients with dermatitis over photo‐exposed body areas are positive to many contact allergens and have a pre‐existing allergic contact dermatitis.

Methods

This study included patients who presented to a tertiary centre in India with dermatitis on photo‐exposed body areas suspected of chronic actinic dermatitis. Their detailed histories were recorded and cutaneous and systemic examinations were performed. Patch testing was done in all the patients and photo‐patch testing was carried out in 86 patients.

Results

Altogether 101 patients were included (69 males, 32 females). The most common presentation was lichenified hyperpigmented plaques on the photo‐exposed sites. Photosensitivity was recorded in 64 (63%) patients and summer exacerbation in 52 (52%). Exposure to the Parthenium hysterophorus weed was recorded in 70 (69%) patients, 27 (26.7%) had a history of hair dye application and 20 (20%) had a history of atopy. Photo‐patch test was positive in 11 (12.8%) patients and patch testing was positive in 71 (70%). Parthenium hysterophorus was the most common allergen implicated and was positive in three (4%) photo‐patch and 52 (52%) patch tests. Other positive photo‐patch test allergens were perfume mix, balsam of Peru, thiuram mix, Compositae mix and promethazine hydrochloride. Other common patch test allergens were parthenolide, colophony, fragrance mix and p‐phenylenediamine (PPD) base.

Conclusion

In the Indian population parthenium and perfume mix are the most common photoallergens in patients with dermatitis over photo‐exposed areas, while parthenium, colophony, fragrance mix and PPD are the common positive allergens.
Linear atrophoderma of Moulin: a disease related to immunity or a kind of connective tissue disease?
Authors: Yan Wei , Wang Sheng , Liu Hong‐Jie , Wang Lin , Li Wei , Ran Yu‐Ping , Zhang Min
Published: June 2016

We describe a 28‐year‐old man with linear atrophoderma of Moulin (LAM), whose serum immunological markers were abnormal (including antinuclear antibody, ribonucleoprotein, immunoglobulin M and anti‐SM antibody). In addition, however, a histological analysis identified unexpected connective tissue disease changes in this patient. We speculate that the pathogenesis of LAM is associated with immunity or that LAM itself is a kind of connective tissue disease.
Outcomes following management of squamous cell carcinoma of the scalp: A retrospective series of 235 patients treated at the Peter MacCallum Cancer Centre
Authors: Estall Vanessa , Allen Angela , Webb Angela , Bressel Mathias , McCormack Chris , Spillane John
Published: June 2016

Background

Squamous cell carcinoma of the scalp is a common clinical problem in an aging population. Despite its high incidence, little has been documented regarding treatment or outcomes.

Methods

We retrospectively analysed 235 cases treated with curative intent at Peter MaCallum Cancer Centre between 1998 and 2010. The cohort was analysed for its characteristics, management, survival and prognostic factors.

Results

The patients were primarily male (88%) with a median age of 79 years (range 53–98 years). There was a high proportion of immunosuppressed patients (29%) and stage T2 (48%) tumours. Management included surgery (45%), radiotherapy (28%) and surgery and adjuvant radiotherapy (26%). Median follow up from treatment was 4.5 years. Estimated 5‐year overall survival (OS), disease‐specific survival and progression‐free survival (PFS) were 59, 94 and 51%, respectively. The 5‐year cumulative incidence of local and regional relapse was 11 and 7%, respectively. There were four patients who developed distant metastases and died of their disease. Statistically significant prognostic factors identified for poor outcomes for OS and PFS were T2 stage (hazard ratio [1.7 and 2.1) and immunosuppression (HR 3.3 and 3.4).

Conclusions

We conclude the presence of immunosuppression and T2 stage is prognostic for survival. Further research to establish treatment principles is warranted.
Private sector surgical training: feasibility through the lens of appendicectomy
Authors: Yap Raymond , Cullinan Mark
Published: June 2016

Background

Training in medicine and surgery has been a public hospital responsibility in Australia. Increasing specialist training needs has led to pressure on speciality societies to find additional training posts, with one utilized solution being the establishment of private hospital training. This growing use has been despite no previously published evaluations of private hospital training in Australia. This article seeks to evaluate the feasibility of surgical training in private hospitals in appendicectomy.

Methods

Data were prospectively collected on registrar involvement in appendicectomy cases at a single private tertiary institution over 1 year. These data were divided into groups according to registrar involvement and analysed, looking at training caseload, operating theatre time and complications.

Results

A total of 122 cases were analysed over the study period. Registrars were more likely to have increased primary operator responsibility if they were an accredited versus unaccredited registrar (P = 0.04) and if the case was open versus laparoscopic (P < 0.001). There was an increase of 15% in total procedure time when the registrar was involved (P = 0.04). There was no significant difference in complications whether the registrar was involved or not.

Conclusion

Training in the private sector in Australia appears feasible, with a small loss of efficiency and no increase in complications. This article hopes to further encourage implementation and evaluation of private sector training programs to expand current training positions. Further studies, in different specialty and procedural domains, are needed to assess and evaluate the ongoing feasibility of private sector training.
Cerebral Microembolization During Aortic Valve Replacement Using Minimally Invasive or Conventional Extracorporeal Circulation: A Randomized Trial
Authors: Basciani Reto , Kröninger Felix , Gygax Erich , Jenni Hansjörg , Reineke David , Stucki Monika , Hagenbuch Niels , Carrel Thierry , Eberle Balthasar , Erdoes Gabor
Published: June 2016

To compare intraoperative cerebral microembolic load between minimally invasive extracorporeal circulation (MiECC) and conventional extracorporeal circulation (CECC) during isolated surgical aortic valve replacement (SAVR), we conducted a randomized trial in patients undergoing primary elective SAVR at a tertiary referral hospital. The primary outcome was the procedural phase‐related rate of high‐intensity transient signals (HITS) on transcranial Doppler ultrasound. HITS rate was used as a surrogate of cerebral microembolism in pre‐defined procedural phases in SAVR using MiECC or CECC with (+F) or without (−F) an oxygenator with integrated arterial filter. Forty‐eight patients were randomized in a 1:1 ratio to MiECC or CECC. Due to intraprocedural Doppler signal loss (n = 3), 45 patients were included in final analysis. MiECC perfusion regimen showed a significantly increased HITS rate compared to CECC (by a factor of 1.75; 95% confidence interval, 1.19–2.56). This was due to different HITS rates in procedural phases from aortic cross‐clamping until declamping [phase 4] (P = 0.01), and from aortic declamping until stop of extracorporeal perfusion [phase 5] (P = 0.05). Post hoc analysis revealed that MiECC−F generated a higher HITS rate than CECC+F (P = 0.005), CECC−F (P = 0.05) in phase 4, and CECC−F (P = 0.03) in phase 5, respectively. In open‐heart surgery, MiECC is not superior to CECC with regard to gaseous cerebral microembolism. When using MiECC for SAVR, the use of oxygenators with integrated arterial line filter appears highly advisable. Only with this precaution, MiECC confers a cerebral microembolic load comparable to CECC during this type of open heart surgery.
Variety of Black and White Limestone Tesserae Used in Ancient Mosaics in Slovenia
Authors: Šmuc A. , Dolenec M. , Lesar‐Kikelj M. , Lux J. , Pflaum M. , Šeme B. , Županek B. , Gale L. , Kramar S.
Published: June 2016

This study concerns the microfacies characterization of white and black limestone tesserae from selected Roman floor mosaics in Slovenia, with the aim of defining their provenance. We investigated 42 tesserae from 15 different mosaics from the archaeological sites of Ljubljana, Izola, Mošnje, Ptuj, Črnomelj and Šentpavel, dated from the first century bc to the fifth century ad. Among the studied tesserae, 13 different microfacies were identified: eight black and five white. The most common were mudstones with ostracods (65% of black tesserae) and wacke‐packstones with miliolids (85% of white tesserae). The majority of the identified facies can be found in the Cretaceous successions of the Dinaric Carbonate Platform in south‐western Slovenia, north‐eastern Italy and south‐eastern Croatia, suggesting a regional or imported origin of the tesserae.
Human Hepatic HepaRG Cells Maintain an Organotypic Phenotype with High Intrinsic CYP450 Activity/Metabolism and Significantly Outperform Standard HepG2/C3A Cells for Pharmaceutical and Therapeutic Applications
Authors: Nelson Leonard J. , Morgan Katie , Treskes Philipp , Samuel Kay , Henderson Catherine J. , LeBled Claire , Homer Natalie , Grant M. Helen , Hayes Peter C. , Plevris John N.
Published: June 2016

Conventional in vitro human hepatic models for drug testing are based on the use of standard cell lines derived from hepatomas or primary human hepatocytes (PHHs). Limited availability, interdonor functional variability and early phenotypic alterations in PHHs restrict their use, whilst standard cell lines such as HepG2 lack a substantial and variable set of liver‐specific functions such as CYP450 activity. Alternatives include the HepG2‐derivative C3A cells selected as a more differentiated and metabolically active hepatic phenotype. Human HepaRG cells are an alternative organotypic co‐culture model of hepatocytes and cholangiocytes reported to maintain in vivo‐like liver‐specific functions, including intact Phase I–III drug metabolism. In this study, we compared C3A and human HepaRG cells using phenotypic profiling, CYP450 activity and drug metabolism parameters to assess their value as hepatic models for pre‐clinical drug testing or therapeutics. Compared with C3As, HepaRG co‐cultures exhibit a more organotypic phenotype, including evidence of hepatic polarity with the strong expression of CYP3A4, the major isoform involved in the metabolism of over 60% of marketed drugs. Significantly greater CYP450 activity and expression of CYP1A2, CYP2E1 and CYP3A4 genes in HepaRG cells (comparable with that of human liver tissue) was demonstrated. Moreover, HepaRG cells also preferentially expressed the hepatic integrin α5β1 – an important modulator of cell behaviour including growth and survival, differentiation and polarity. Drug metabolite profiling of phenacetin (CYP1A2) and testosterone (CYP3A4) using LC‐MS/MS and HPLC, respectively, revealed that HepaRGs had more intact (Phase I–II) metabolism profile. Thus, HepaRG cells significantly outperform C3A cells for the potential pharmaceutical and therapeutic applications.
Structure–activity relationship studies of benzyl‐, phenethyl‐, and pyridyl‐substituted tetrahydroacridin‐9‐amines as multitargeting agents to treat Alzheimer's disease
Authors: Osman Wesseem , Mohamed Tarek , Sit Victor Munsing , Vasefi Maryam S. , Beazely Michael A. , Rao Praveen P. N.
Published: June 2016

A library of substituted tetrahydroacridin‐9‐amine derivatives were designed, synthesized, and evaluated as dual cholinesterase and amyloid aggregation inhibitors. Compound 8e (N‐(3,4‐dimethoxybenzyl)‐1,2,3,4‐tetrahydroacridin‐9‐amine) was identified as a potent inhibitor of butyrylcholinesterase (BuChE IC50 = 20 nm; AChE IC50 = 2.2 μm) and was able to inhibit amyloid aggregation (40% inhibition at 25 μm). Compounds 9e (6‐chloro‐N‐(3,4‐dimethoxybenzyl)‐1,2,3,4‐tetrahydroacridin‐9‐amine, AChE IC50 = 0.8 μm; BuChE IC50 = 1.4 μm; Aβ‐aggregation inhibition = 75.7% inhibition at 25 μm) and 11b (6‐chloro‐N‐(3,4‐dimethoxyphenethyl)‐1,2,3,4‐tetrahydroacridin‐9‐amine, AChE IC50 = 0.6 μm; BuChE IC50 = 1.9 μm; Aβ‐aggregation inhibition = 85.9% inhibition at 25 μm) were identified as the best compounds with dual cholinesterase and amyloid aggregation inhibition. The picolylamine‐substituted compound 12c (6‐chloro‐N‐(pyridin‐2‐ylmethyl)‐1,2,3,4‐tetrahydroacridin‐9‐amine) was the most potent AChE inhibitor (IC50 = 90 nm). These investigations demonstrate the utility of 3,4‐dimethoxyphenyl substituent as a novel pharmacophore possessing dual cholinesterase inhibition and anti‐Aβ‐aggregation properties that can be used in the design and development of small molecules with multitargeting ability to treat Alzheimer's disease.
Why, when and how should immunosuppressive therapy considered in patients with immunoglobulin A nephropathy?
Authors: Rasche F M , Keller F , Rasche W G , Schiekofer S , Boldt A , Sack U , Fahnert J
Published: June 2016

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Lifelong mesangial deposition of IgA1 complexes subsist inflammation and nephron loss, but the complex pathogenesis in detail remains unclear. In regard to the heterogeneous course, classical immunosuppressive and specific therapeutic regimens adapted to the loss of renal function will here be discussed in addition to the essential common renal supportive therapy. Renal supportive therapy alleviates secondary, surrogate effects or sequelae on renal function and proteinuria of high intraglomerular pressure and subsequent nephrosclerosis by inhibition of the renin angiotensin system (RAASB). In patients with physiological (ΔGFR < 1·5 ml/min/year) or mild (ΔGFR 1·5–5 ml/min/year) decrease of renal function and proteinuric forms (> 1 g/day after RAASB), corticosteroids have shown a reduction of proteinuria and might protect further loss of renal function. In patients with progressive loss of renal function (ΔGFR > 3 ml/min within 3 months) or a rapidly progressive course with or without crescents in renal biopsy, cyclophosphamide with high-dose corticosteroids as induction therapy and azathioprine maintenance has proved effective in one randomized controlled study of a homogeneous cohort in loss of renal function (ΔGFR). Mycophenolic acid provided further maintenance in non-randomized trials. Differentiated, precise, larger, randomized, placebo-controlled studies focused on the loss of renal function in the heterogeneous forms of IgAN are still lacking. Prospectively, fewer toxic agents will be necessary in the treatment of IgAN.
Expanding non‐invasive prenatal testing beyond chromosomes 21, 18, 13, X and Y
Authors: Benn P.
Published: June 2016

Non‐invasive prenatal testing (NIPT) based on cell‐free DNA in maternal plasma is being expanded to include additional chromosome abnormalities beyond those involving chromosomes 21, 18, 13, X and Y. Review of population cytogenetic data provides insight into the likely number of additional abnormalities detectable. Additional clinically significant and cytogenetically recognizable abnormalities are present in less than 0.1% of newborns but clinically significant, or potentially significant, sub‐microscopic imbalances are expected to be present in 1.7%. Cytogenetic studies on chorionic villus samples suggests that after excluding abnormalities involving chromosomes 21, 18, 13, X and Y, approximately 0.6% of NIPT results may be positive for an unbalanced abnormality attributable to mosaicism but most of these will not be confirmed at amniocentesis or in newborns. NIPT has also been developed for specific microdeletion syndromes and initial experience is now available. Laboratory procedures such as deeper sequencing and additional data analytics are rapidly evolving but even with existing protocols, it is already clear that NIPT does not necessarily need to be limited to trisomies 21, 18, 13 and the sex‐chromosome abnormalities. Patient educational materials and genetic counseling services need to be available for women offered expanded NIPT.
Implant surface roughness alterations induced by different prophylactic procedures: an in vitro study
Authors: Cafiero Carlo , Aglietta Marco , Iorio‐Siciliano Vincenzo , Salvi Giovanni E. , Blasi Andrea , Matarasso Sergio
Published: June 2016

Aim

To evaluate surface roughness alterations at the smooth neck of dental implants after the use of eight different prophylactic procedures.

Materials and methods

50 tissue level implants (Institut Straumann AG, Basel, Switzerland) were used for the present investigation. The smooth collar of each implant was divided into two segments, each treated with one of eight cleaning procedures: use of a rubber cup (RCZ) or a brush (BZ) combined with an abrasive paste containing zirconium or a paste derived from perlite (RCP, BP); use of 2 composite resin burs reinforced by zirconium glass fibers (F1, F2); and use of an air‐polishing system with glycine powder and two power settings (AP1, AP2). The qualitative alterations were recorded by means of a laser profilometer and the mean roughness (Ra) and mean roughness profile depth (Rz) were reported. Twenty untreated surfaces were used as controls.

Results

The implant collars treated with RCZ (Ra = 0.33 μm, Rz = 2.43 μm) or BZ (Ra = 0.30 μm, Rz = 3.70 μm) yielded the highest roughness values, followed by the surfaces treated with RCP (Ra = 0.28 μm, Rz = 2.02 μm), with BP (Ra = 0.25 μm, Rz = 2.16 μm) and by the use of F1 (Ra = 0.27 μm, Rz = 2.22 μm) and F2 (Ra = 0.27 μm, Rz = 2.04 μm). The lowest roughness values were observed in the AP1 (Ra = 0.23 μm, Rz = 1.60 μm) and AP2 (Ra = 0.16 μm, Rz = 1.06 μm) group, respectively. Implant collars treated with AP2 yielded statistically significantly lower (P = 0.01) Rz values compared with untreated surfaces.

Conclusion

All tested procedures did not increase implant surface roughness significantly. Treatment with an air‐powder abrasive system at high‐pressure setting resulted in a smoothening of the implant collar surface.
Th17‐related cytokines in mucositis: is there any difference between peri‐implantitis and periodontitis patients?
Authors: Teixeira Mayla Kezy Silva , Lira‐Junior Ronaldo , Telles Daniel Moraes , Lourenço Eduardo José Veras , Figueredo Carlos Marcelo
Published: June 2016

Objective

This study aimed to compare Th17‐related cytokines named IL‐1β, IL‐4, IL‐6, IL‐10, IL‐17A, IL‐17F, IL‐21, IL‐22, IL‐23, IL‐25, IL‐31, IL‐33, IFN‐γ, sCD40L and TNF‐α in peri‐implant fluid (PIF) from mucositis sites in patients having either peri‐implantitis, periodontitis or without interproximal alveolar bone loss.

Material and methods

Thirty‐three patients diagnosed with peri‐implant mucositis were divided into three groups: individuals with peri‐implant mucositis but without any signs of interproximal alveolar bone loss (group 1, n = 10), individuals with peri‐implantitis (group 2, n = 14) and individuals with periodontitis (group 3, n = 9). Probing depth (PD), clinical attachment level (CAL), visible plaque index and bleeding on probing were measured. PIF was collected from mucositis sites in patients from the three groups and from peri‐implantitis (group 2) and periodontitis sites (group 3). Cytokines were measured by a bead‐based multiplex assay.

Results

Probing depth was significantly lower in group 1 when compared to both groups 2 and 3 (P < 0.001 and P = 0.01, respectively). There was no significant difference in cytokine levels in mucositis sites among the three groups. In group 2, IL‐21 level was significantly higher in mucositis compared to peri‐implantitis sites (P = 0.04).

Conclusion

The expression of Th17‐related cytokines in PIF from mucositis sites seems to be similar regardless the presence or not of alveolar bone loss around implants or teeth.
Positive effect of strontium‐oxide layer on the osseointegration of moderately rough titanium surface in non‐osteoporotic rabbits
Authors: Fan Yan‐pin , Chen Xiao‐yi , Chen Yun , Yang Guo‐li , Wang Hui‐ming , He Fu‐ming
Published: June 2016

Objectives

To evaluate the effect of strontium‐oxide layer on new bone formation and osseointegration of sandblasted large‐grit double‐acid‐etched (SLA) implant.

Material and methods

Strontium‐oxide layer on the SLA surface was produced by hydrothermal treatment using a Sr‐containing solution. The surface topographies, roughness, hardness values, chemical elements and ionic release of SLA and the strontium‐containing SLA (Sr‐SLA) surface were measured by special instruments separately. Sixty‐four SLA and Sr‐SLA implants were inserted into the proximal tibiae and femoral condyles of sixteen non‐osteoporotic New Zealand white rabbits. The biological effects were evaluated by removal torque (RTQ) testing and histomorphometric analysis after 3 and 6 weeks of implantation.

Results

The surface characteristics showed Sr‐SLA surfaces with dotted nanostructures can release appropriate amount of strontium ions into surrounding tissue till 14 days. In vivo, the Sr‐SLA implants presented significantly higher RTQ than SLA implants at 3 and 6 weeks (P < 0.05). The Sr‐SLA implants presented higher bone‐to‐implant contact (BIC) than SLA implants in cortical bone at 3 and 6 weeks (P < 0.05). The bone area was slightly higher for the Sr‐SLA implants at 3 and 6 weeks (P > 0.05).

Conclusions

The strontium‐oxide layer on the SLA surface has the potential to improve implant osseointegration in non‐osteoporotic rabbits.
Synergistic effect of environmental media and stress on the fatigue fracture behaviour of aluminium alloys
Authors: Yang H‐H , Wang Y‐L , Wang X‐S , Pan P , Jia D‐W
Published: June 2016

The present study aims at explaining the synergistic effect of environmental media and stress/strain on fatigue lives of aluminium alloys. Rotating bending fatigue tests were carried out using four different aluminium alloys LY12‐CZ, 2024‐T4, 7475‐T7351 and 7075‐T651, at air state, 3.5% and 5.0% NaCl aqueous solutions. These results indicated that synergistic actions of the environmental media and cyclic loading accelerated the fatigue crack propagation of aluminium alloys. Furthermore, various influence factors (such as solution concentration, cyclic numbers, high (low) strength aluminium alloys etc.) of the fatigue life at synergistic actions of the environmental media and stress were quantificationally discussed in this paper.
Niche width impacts vertebrate diversification
Authors: Rolland Jonathan , Salamin Nicolas
Published: June 2016

AimThe size of the climatic niche of a species is a major factor determining its distribution and evolution. In particular, it has been proposed that niche width should be associated with the rate of species diversification. Here, we test whether species niche width affects the speciation and extinction rates of three main clades of vertebrates: amphibians, mammals and birds.

LocationGlobal.

MethodsWe obtained the time‐calibrated phylogenies, IUCN conservation status, species distribution maps and climatic data for 2340 species of amphibians, 4563 species of mammals and 9823 species of birds. We computed the niche width for each species as the mean annual temperature across the species range. We estimated speciation, extinction and transition rates associated with lineages with either narrow (specialist) or wide (generalist) niches using phylogeny‐based birth–death models. We also tested if current conservation status was correlated with the niche width of species.

ResultsWe found higher net diversification rates in specialist species than in generalist species. This result was explained by both higher speciation rates (for the three taxonomic groups) and lower extinction rates (for mammals and birds only) in specialist than in generalist species. In contrast, current specialist species tended to be more threatened than generalist species.

Main conclusionsOur diversification analysis shows that the width of the climatic niche is strongly associated with diversification rates and may thus be a crucial factor for understanding the emergence of diversity patterns in vertebrates. The striking difference between our diversification results and current conservation status suggests that the current extinction process may be different from extinction rates estimated from the whole history of the group.
STARK, NECESSARY AND NOT PERMANENT: HUTS IN THE WORK OF PAUL CELAN AND J. H. PRYNNE
Authors: Thomas Nicola
Published: June 2016

This article examines the motif of the hut in the work of Paul Celan and J. H. Prynne as a metaphor for poetry which also mediates the relationship between poetry, language and place. Both Prynne's and Celan's use of the hut motif intersects with the role played by huts in work by Martin Heidegger, but this article demonstrates, through close reading of poems by Prynne and Celan, that each develops Heidegger's understanding of the hut further, with reference to the ethical imperatives which underpin linguistic (and especially poetic) production.

Dieser Beitrag untersucht das Motiv der Hütte in der poetischen Arbeit Paul Celans und J. H. Prynnes als Metapher des poetischen Denkens und als Vermittler zwischen Dichtung, Sprache und Ort. Es bestehen deutliche Überschneidungen zwischen dem Gebrauch des Hüttenmotivs bei Prynne und bei Celan und der Rolle, die Hütten im Werk Martin Heideggers spielen. Mithilfe von Gedichtanalysen wird dieser Beitrag jedoch zeigen, dass Prynne und Celan Heideggers Hüttenmotiv mit Bezug auf die für die sprachliche (und insbesondere für die poetische) Produktion grundlegenden ethischen Imperative weiterentwickeln.
Functional remnant liver assessment predicts liver‐related morbidity after hepatic resection in patients with hepatocellular carcinoma
Authors: Itoh Shinji , Yoshizumi Tomoharu , Shirabe Ken , Kimura Koichi , Okabe Hirohisa , Harimoto Norifumi , Ikegami Toru , Uchiyama Hideaki , Nishie Akihiro , Maehara Yoshihiko
Published: June 2016

Aim

We aimed to evaluate whether functional assessment of the future remnant liver is a predictor of postoperative morbidity after hepatic resection in patients with hepatocellular carcinoma (HCC).

Methods

One hundred forty‐six patients who underwent hepatic resection for HCC were enrolled in this study. Gadolinium‐ethoxybenzyl‐diethylenetriamine pentaacetic acid enhanced MRI (EOB‐MRI) analysis for functional liver assessment was carried out before hepatic resection. The signal intensity in the remnant liver was measured and divided by the signal intensity of the major psoas muscle (the liver to major psoas muscle ratio, LMR) for standardization. The remnant liver function was calculated using the formula (LMR on the hepatobiliary phase/LMR on the precontrast image). Computed tomography liver volumetry was also carried out. The remnant functional liver was calculated as the remnant liver volume or volumetric rate × remnant liver function by EOB‐MRI.

Results

Morbidities developed in 19 (13.0%) patients. Morbidities associated with the liver occurred in 7 patients (4.7%). There was no mortality during surgery. Median remnant liver function scores using EOB‐MRI and remnant functional liver using volumetric rate or volumetry were 1.82 (range, 1.25–2.96), 155.9 (range, 64.7–285.3), and 1027 (range, 369–2148), respectively. Logistic regression analysis identified the remnant functional liver volume as the only independent predictor for liver‐related morbidity.

Conclusion

Remnant functional liver volume using computed tomography liver volumetry and EOB‐MRI was a significantly useful predictor for liver‐related morbidity after hepatic resection in patients with HCC.
Ranolazine and Vernakalant Prevent Ventricular Arrhythmias in an Experimental Whole‐Heart Model of Short QT Syndrome
Authors: FROMMEYER GERRIT , ELLERMANN CHRISTIAN , DECHERING DIRK G. , KOCHHÄUSER SIMON , BÖGEHOLZ NILS , GÜNER FATIH , LEITZ PATRICK , POTT CHRISTIAN , ECKARDT LARS
Published: June 2016

Ranolazine and Vernakalant in Short QT Syndrome

Background

Ranolazine has been reported to have an antiarrhythmic potential. The aim of this study was to assess the electrophysiologic effects of ranolazine and to compare its effects to vernakalant in an experimental whole‐heart model of short‐QT syndrome.

Methods

Rabbit hearts were isolated and Langendorff‐perfused. After obtaining baseline data, pinacidil, an IKATP channel opener, was administered (1 μM).

Results

Endo‐ and epicardial monophasic action potentials and a 12‐lead ECG showed a significant abbreviation of QT interval (− 34 milliseconds, P < 0.05) and action potential duration (APD90; − 31 milliseconds, P < 0.05). This was accompanied by a reduction of effective refractory period (ERP; − 32 milliseconds, P < 0.05). Subsequently, hearts were additionally perfused with ranolazine (10 μM, n = 12) or vernakalant (10 μM, n = 14). Ranolazine led to an increase of QT‐interval (+ 29 milliseconds, P < 0.05), APD90 (+ 18 milliseconds, P < 0.05) and ERP (+ 28 milliseconds, P < 0.05) as compared with sole pinacidil treatment. Similar results were observed under the influence of vernakalant (APD90: + 25 milliseconds, QT‐interval: + 34 milliseconds, ERP: + 31 milliseconds).

Under the influence of pinacidil, ventricular fibrillation (VF) was inducible by a standardized pacing protocol including programmed stimulation and aggressive burst stimulation in 8 of 12 hearts (ranolazine group, 34 episodes) and 7 of 14 hearts (vernakalant group, 24 episodes). Additional infusion of ranolazine (1 of 12 hearts, 1 episode) or vernakalant (1 of 14 hearts, 3 episodes) led to a significant suppression of VF.

Conclusion

In the present pharmacologic model of short QT syndrome treatment with pinacidil led to an increased inducibility of VF in association with a reduction in ERP. Additional treatment with ranolazine or vernakalant reversed this effect and demonstrated potent antiarrhythmic properties based on an increase of ERP.
Questions and answers in chronic urticaria: where do we stand and where do we go?
Authors: Maurer M. , Church M. K. , Marsland A. M. , Sussman G. , Siebenhaar F. , Vestergaard C. , Broom B.
Published: June 2016

This supplement reports proceedings of the second international Global Urticaria Forum, which was held in Berlin, Germany in November 2015. In 2011, a report of the GA2LEN task force on urticaria outlined important and unanswered questions in chronic urticaria (CU). These included, but were not limited to, questions on the epidemiology and course of chronic spontaneous urticaria (CSU) [also called chronic idiopathic urticaria (CIU)], the resources allocated for the diagnosis and treatment of CSU, whether patients with angioedema as an isolated symptom can be regarded as a subgroup of CSU, and the efficacy and long‐term safety of therapies. Many of these questions have been addressed by recent studies. Some of the answers obtained raise new questions. Here, we summarize some of the key insights on CU obtained over recent years, and we discuss old and new unmet needs and how to address them with future studies. We need to analyze the influence of recent advances in understanding of the burden of CU on patients and society, disease management and the CU patient journey. Our increased understanding of urticarial pathophysiology and consideration of the patient as a whole will need to be translated to better treatment algorithms and protocols. Actions to address these challenges include the 5th International Consensus Meeting on Urticaria, which will take place later this year. The formation of a global network of Urticaria Centers of Reference and Excellence over the next few years has also been proposed, with the aim of providing consistent excellence in urticaria management and a clear referral route, furthering knowledge of urticaria through additional research and educating/promoting awareness of urticaria.
Effect of Chitosan Edible Coating Enriched with Eucalyptus Essential Oil and α‐Tocopherol on Silver Carp Fillets Quality During Refrigerated Storage
Authors: Valipour Kootenaie Faranak , Ariaii Peiman , Khademi Shurmasti Dariush , Nemati Mahrokh
Published: June 2016

The effects of chitosan coating incorporated with eucalyptus essential oil and α‐tocopherol on the quality of silver carp fillet during chilled storage (4 + 1°C) were examined over a period of 16 days. The control samples (without any coating), chitosan coating (CH), chitosan coating incorporated with eucalyptus essential oil (CH+EEO) and chitosan coating incorporated with eucalyptus essential oil and α‐tocopherol (CH+EEO+α) were analyzed by chemical, microbiological and sensory characteristics. Results showed that, total viable counts, total psychrotrophic counts and total volatile basic nitrogen of CH+EEO and CH+EEO+α were significantly lower than control and CH (P ≤ 0.05). Addition of α‐tocopherol to EEO retarded lipid oxidation. According to the sensory analysis results, CH+EEO+α was acceptable even at the end of the 16‐day storage. The results indicated that chitosan coating was improved extending of meat shelf life. Using eucalyptus essential oil and α‐tocopherol increased its efficiency significantly.

Practical Apllications

Fresh fish are usually more perishable than most other muscle foods. Many attempts have been made to prevent the spoilage of fresh fish. To avoid the use of synthetic food additives, numerous studies are currently focused on using natural products to improve the quality of sea food products. The results of the present study report the efficacy of chitosan edible coating enriched with eucalyptus essential oil and α‐tocopherol as a new natural preservative for developing the shelf life of silver carp fillets.
Avoid falling for a jerk(ette): Effectiveness of the Premarital Interpersonal Choices and Knowledge Program among Emerging Adults
Authors: Bradford Kay , Stewart J. Wade , Pfister Roxane , Higginbotham Brian J.
Published: June 2016

Premarital education may help emerging adults form healthy relationships, but evaluation research is needed, particularly with community samples. We studied emerging adults in the Premarital Interpersonal Choices and Knowledge (PICK) program, using a pre‐ to post‐ and a posttest‐then‐retrospective‐pretest design to examine change in perceived relationship skills, partner selection, relational patterns, and relationship behaviors and attitudes. Mixed models analyses showed that scores for the treatment group (n = 682) increased from pre to post on all four outcomes. Changes in scores for the nonequivalent comparison group (n = 462) were nonsignificant. In addition, significant differences between pre‐ and retrospective prescores demonstrated evidence for response shift bias. The results suggest that the PICK program helps participants increase their knowledge regarding the components of healthy relationship formation.
Women's Experiences Being Diagnosed With Peripartum Cardiomyopathy: A Qualitative Study
Authors: Dekker Rebecca L. , Morton Christine H. , Singleton Paula , Lyndon Audrey
Published: June 2016

Introduction

Cardiovascular disease has been identified as the leading cause of maternal mortality in the United States, with cardiomyopathy, including peripartum cardiomyopathy (PPCM), accounting for 12% to 16% of all pregnancy‐related deaths. The purpose of this study was to describe women's experiences being diagnosed with PPCM.

Methods

This investigation was conducted using a qualitative design. We collected publicly available narratives posted by 92 women with PPCM (mean [SD] age 29 [6] years, mean [SD] ejection fraction 25.5 [10.8]%) in 3 online support groups. Data were coded and thematically organized so as to produce a richly detailed account of this experience.

Results

The experience of diagnosis was marked by the women's distinct memories of their initial symptoms and whether they were dismissed or taken seriously. The most commonly reported symptoms were extreme shortness of breath, orthopnea, tachycardia, palpitations, chest pain, cough, and edema. Nearly 40% of women experienced symptom dismissal by health care providers. One‐fourth of women were initially given inaccurate diagnoses ranging from “new mom anxiety” to asthma. Women described their initial reaction to diagnosis as feeling terrified, devastated, and feeling a sense of doom. Women had difficulty caring for their newborns during the postpartum period, and they struggled with the medical advice they received to not get pregnant again.

Discussion

Despite experiencing severe subjective and objective symptoms, nearly 40% of women with PPCM experienced symptom dismissal by health care providers, in part due to the overlap between normal symptoms of pregnancy or the postpartum period and symptoms of heart failure.
Roles of Response Inhibition and Gene–Environment Interplay in Pathways to Adolescents' Externalizing Problems
Authors: Wang Frances L. , Chassin Laurie , Lee Matthew , Haller Moira , King Kevin
Published: June 2016

This study used two waves of data to investigate pathways through which adolescents' response inhibition related to later externalizing problems. A polygenic risk score indexed genetic risk for poor response inhibition. Adolescents' performance on a response inhibition task mediated the relation between adolescents' polygenic risk scores and mother's inconsistent parenting (i.e., evocative rGE), even after controlling for mothers' genetic risk (i.e., passive rGE). Mothers' inconsistent parenting subsequently prospectively predicted adolescents' externalizing problems. Adolescents' response inhibition also prospectively predicted later externalizing behaviors. These findings were subgroup‐specific, with greater risk for non‐Hispanic Caucasian boys with substance‐disordered parents. Results suggest that poor response inhibition may increase risk for adolescents' externalizing problems both directly and by evoking certain environmental conditions.
The pharmacological potential of Phyllanthus niruri
Authors: Lee Nathanael Y S , Khoo William K S , Adnan Mohammad Akmal , Mahalingam Tanes Prasat , Fernandez Anne R , Jeevaratnam Kamalan
Published: June 2016

Introduction

Phyllanthus niruri is a traditional shrub of the genus Phyllanthaceae with long-standing Ayurvedic, Chinese and Malay ethnomedical records. Preliminary studies from cell and animal model have provided valuable scientific evidence for its use.

Aim

This review aims to summarize selected scientific evidence on the pharmacological properties of P. niruri over the past 35 years while identifying potential areas of further development of this herb as an economical adjunct.

Methods

The review covers literature pertaining to the evidence base therapeutic potential of P. niruri spanning from 1980 to 2015 available on PubMed.

Results

Evidence suggests that the extracts of P. niruri possess hepatoprotective, antiviral, antibacterial, hypolipidaemic, hypoglycaemic, analgesic, anti-inflammatory, cardioprotective, anti-urolithiatic and antihyperuricaemic properties due its novel bioactive compounds.

Conclusion

Scientific evidence suggests that there is strong pharmacological potential in developing P. niruri as a drug to be used in liver disorders and in antiviral therapy. Despites this, large-scale heterogeneity in study protocol and unstandardized reporting standards limit the ability for valuable comparison and may mask the ability to replicate these studies. Thus interpretation of findings should be performed with caution and further studies should be performed in line with best practices. More cheminformatics, toxicological and mechanistic studies would aid the progress to clinical trial studies.
LC-MS analysis of Hep-2 and Hek-293 cell lines treated with Brazilian red propolis reveals differences in protein expression
Authors: da Silva Frozza Caroline O , da Silva Brum Emyle , Alving Anjali , Moura Sidnei , Henriques João A P , Roesch-Ely Mariana
Published: June 2016

Objective

Red propolis, an exclusive variety of propolis found in the northeast of Brazil has shown to present antitumour activity, among several other biological properties. This article aimed to help to evaluate the underlying molecular mechanisms of the potential anticancer effects of red propolis on tumour, Hep-2, and non-tumour cells, Hek-293.

Methods

Differentially expressed proteins in human cell lines were identified through label-free quantitative MS-based proteomic platform, and cells were stained with Giemsa to show morphological changes.

Key findings

A total of 1336 and 773 proteins were identified for Hep-2 and Hek-293, respectively. Among the proteins here identified, 16 were regulated in the Hep-2 cell line and 04 proteins in the Hek-293 line. Over a total of 2000 proteins were identified under MS analysis, and approximately 1% presented differential expression patterns. The GO annotation using Protein Analysis THrough Evolutionary Relationships classification system revealed predominant molecular function of catalytic activity, and among the biological processes, the most prominent was associated to cell metabolism.

Conclusion

The proteomic profile here presented should help to elucidate further molecular mechanisms involved in inhibition of cancer cell proliferation by red propolis, which remain unclear to date.
Hot melt extrusion as an approach to improve solubility, permeability and oral absorption of a psychoactive natural product, piperine
Authors: Ashour Eman A , Majumdar Soumyajit , Alsheteli Abdulla , Alshehri Sultan , Alsulays Bader , Feng Xin , Gryczke Andreas , Kolter Karl , Langley Nigel , Repka Michael A
Published: June 2016

Objective

The aims of the current research project were to investigate the efficiency of various polymers to enhance the solubility and increase the systemic absorption of piperine using hot melt extrusion technology.

Methods

Piperine 10–40% w/w and Eudragit® EPO/Kollidon® VA 64 or Soluplus® were mixed, and the resulting blends were extruded using a twin-screw extruder (Process 11, Thermo Fisher Scientific). Drug release profiles and piperine solubility studies of the extrudates were evaluated. A non-everted intestinal sac was employed for the most promising formulation, 10% w/w piperine/Soluplus®, and pure piperine to study the permeability characteristics.

Key Findings

Dissolution studies demonstrated enhancement in piperine per cent release of 10% and 20% w/w piperine/Soluplus® extrudates up to 95% and 74%, respectively. The solubility of 10% and 20% piperine/Soluplus® increased more than 160- and 45-fold in water, respectively. Furthermore, permeability studies demonstrated the enhancement in piperine absorption of 10% w/w piperine/Soluplus® extrudates up to 158.9 μg/5 ml compared with pure piperine at 1.3 μg/5 ml within 20 min.

Conclusion

These results demonstrated that increasing the bioavailability of piperine may be achieved as demonstrated by findings in this study.
Dexamethasone – PAMAM dendrimer conjugates for retinal delivery: preparation, characterization and in vivo evaluation
Authors: Yavuz Burçin , Bozdağ Pehlivan Sibel , Sümer Bolu Burcu , Nomak Sanyal Rana , Vural İmran , Ünlü Nurşen
Published: June 2016

Objective

Ocular diseases affecting retina, such as diabetic retinopathy (DR), age-related macular degeneration (AMD) and glaucoma are the major causes of blindness, and their treatment is still a challenge due to the special structure of the eye. The purpose of this study was to prepare a sustained release DEX conjugate formulation with enhanced ocular permeation using poly(amidoamine) (PAMAM) dendrimers and to evaluate the effects of conjugation on DEX release and ocular residence time.

Methods

PAMAM G3.5 and PAMAM G4.5 dendrimers were used to prepare DEX conjugates, and conjugation was confirmed using 1H-NMR. Formulations were evaluated in terms of drug release in the presence of ocular enzymes and cytotoxicity on ARPE19 cell lines. Fluorotron analysis was performed and ocular pharmacokinetic properties of DEX–PAMAM conjugates were studied in Sprague Dawley rats following intravitreal and subconjunctival applications.

Key Findings

The results indicated that DEX–PAMAM conjugates were able to enhance ocular permeability and ocular tissue levels of DEX following subconjunctival injection, and results were encouraging when compared to the literature that has reported DEX getting cleared from vitreous in 3 h.

Conclusion

Current studies are focused on formulation improvement to enhance hydrolysis and clearance time.
Population genomics of sexual and asexual lineages in fissiparous ribbon worms (Lineus, Nemertea): hybridization, polyploidy and the Meselson effect
Authors: Ament‐Velásquez S. L. , Figuet E. , Ballenghien M. , Zattara E. E. , Norenburg J. L. , Fernández‐Álvarez F. A. , Bierne J. , Bierne N. , Galtier N.
Published: June 2016

Comparative population genetics in asexual vs. sexual species offers the opportunity to investigate the impact of asexuality on genome evolution. Here, we analyse coding sequence polymorphism and divergence patterns in the fascinating Lineus ribbon worms, a group of marine, carnivorous nemerteans with unusual regeneration abilities, and in which asexual reproduction by fissiparity is documented. The population genomics of the fissiparous L. pseudolacteus is characterized by an extremely high level of heterozygosity and unexpectedly elevated πN/πS ratio, in apparent agreement with theoretical expectations under clonal evolution. Analysis of among‐species allele sharing and read‐count distribution, however, reveals that L. pseudolacteus is a triploid hybrid between Atlantic populations of L. sanguineus and L. lacteus. We model and quantify the relative impact of hybridity, polyploidy and asexuality on molecular variation patterns in L. pseudolacteus and conclude that (i) the peculiarities of L. pseudolacteus population genomics result in the first place from hybridization and (ii) the accumulation of new mutations through the Meselson effect is more than compensated by processes of heterozygosity erosion, such as gene conversion or gene copy loss. This study illustrates the complexity of the evolutionary processes associated with asexuality and identifies L. pseudolacteus as a promising model to study the first steps of polyploid genome evolution in an asexual context.