bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultra-low reflectance, high absorption microcrystalline silicon nanostalagmite
Authors: Thiyagu Subramani , Devi Balasubramaniam Parvathy , Pei Zingway , Chen Yu-Hung , Liu Jun-Chin
Published: March 2012

In this work, microcrystalline silicon nanostalagmite [μc-SiNS] arrays have been successfully fabricated on glass by catalytic etching process through a template. The template, polystyrene [PS] nanospheres, with diameter and density of 30 to approximately 50 nm and 1010/cm2, respectively, was obtained by a modified nanophase separation of PS-containing block copolymer. The length of μc-SiNS could be controlled by the duration of etching time. The μc-SiNS exhibits ultra-low reflection approximately 0.3% and absorption around 99% over 300 to 800 nm in wavelength. Reflection is also suppressed for a wide range of angles of incidence in wide range of wavelength. This indicates the extensive light-trapping effect by the μc-SiNS and could possibly harvest a large amount of solar energy at infrared regime.
Prospective blind comparative clinical study of two point fixation of zygomatic complex fracture using wire and mini plates
Authors: Gandi Lakshmi N , Kattimani Vivekanand S , Gupta Amit V , Chakravarthi V Srinivas , Meka Sridhar S
Published: March 2012

Background

The zygomatic maxillary complex (ZMC) fractures are one of the most frequent injuries of the facial skeleton due to its position and facial contour. Assaults, road traffic accidents and falls are the principal etiologic factors that may cause fractures of zygomatic bone. The different fixation methods are applied to treat the zygomatic bone fractures, with many more classifications which have been described in the literature for the ease of management. The type of the fracture, its severity and associated facial fractures usually interferes the treatment modality.

Purpose of study

The aim of this paper is to show the results of 18yrs prospective blind comparative study using wire and plate osteosynthesis which needed open reduction and internal fixation involving Type II to Type IV Spissel and Schroll ZMC fractures.

Materials and methods

Total 80 cases included in the study out of 1780 ZMC cases which were treated using wire and plate osteosynthesis over a period of 18 yrs, involving only Type II to Type IV Spissel and Schroll ZMC fractures. Other types excluded from study to prevent observer bias. All the fixations carried out through Standard Dingman's incision using stainless steel 26 gauze wire and titanium 1.5 mm mini plate system under general anesthesia by single maxillofacial surgeon and evaluated by another maxillofacial surgeon who is blinded for surgical procedure after 2 and 4 wks of follow-up for facial symmetry, wound healing, functional assessment (mouth opening, diplopia), and sensory disturbance. All the data tabulated in Excel software (Microsoft) for statistical analysis. P-value calculated to know the Significance of treatment modality in all aspects.

Results

Result shows no significant p-values indicating both the operating techniques are equally efficient in the surgical management of ZMC fracture.

Conclusion

Osteosynthesis by mini plates is simple, logical and effective treatment compared to wire osteosynthesis in regard to stability of fracture fragments. Wire osteosynthesis will be helpful in emergency surgeries or where the mini plates are not available. Even though the wire osteosynthesis is economical compared to mini plate fixation; but the time and skill is required for fixation of wires.
Taking alcohol by deception: an analysis of ethanol concentration of "paraga" an alcoholic herbal mixture in Nigeria
Authors: Kehinde Oluwadiya S , Adegoke Akinola E
Published: March 2012

Background

Alcohol related road traffic injuries are on the rise in Nigeria. A sizable proportion of the alcohol intake is disguised as herbal medicines which are commonly available at motor parks in most urban centres. This study aims to determine the ethanol concentration of the herbal preparations and the vendors' knowledge about their preparation and use. Twenty-eight samples of the paraga mixtures were obtained for analysis from 22 paraga vendors. The vendors were interviewed in the motor parks using a semi-structured questionnaire.

Results

All the paraga outlets were located in or near motor parks. Commercial motor drivers and motorcyclists accounted for most customers. There were no formal recipes, production involved no calibrations or weighing and thus the components and concentration of different batches varied. The alcohol by volume (ABV) of the samples ranged between 1.20% and 20.84%. Nine samples were weaker than beers (Alcohol By Volume (ABV) of 1-3.1%). Ten were equivalent to beer (ABV:3-8%) and the rest were equivalent to wine (ABV:8-12%) or stronger (ABV: 18-20%).

Conclusions

Paraga should be classified as alcoholic beverages, and its sale restricted as such. The production should come under scrutiny, because the haphazard ways they are prepared may pose other health risks apart from those due to their alcoholic contents.
Subtropical grass pollen allergens are important for allergic respiratory diseases in subtropical regions
Authors: Davies Janet Mary , Li Hongzhuo , Green Melissa , Towers Michelle , Upham John Warrick
Published: March 2012

Background

Grass pollen allergens are a major cause of allergic respiratory disease but traditionally prescribing practice for grass pollen allergen‐specific immunotherapy has favoured pollen extracts of temperate grasses. Here we aim to compare allergy to subtropical and temperate grass pollens in patients with allergic rhinitis from a subtropical region of Australia.

Methods

Sensitization to pollen extracts of the subtropical Bahia grass (Paspalum notatum), Johnson grass (Sorghum halepense) and Bermuda grass (Cynodon dactylon) as well as the temperate Ryegrass (Lolium perenne) were measured by skin prick in 233 subjects from Brisbane. Grass pollen‐specific IgE reactivity was tested by ELISA and cross‐inhibition ELISA.

Results

Patients with grass pollen allergy from a subtropical region showed higher skin prick diameters with subtropical Bahia grass and Bermuda grass pollens than with Johnson grass and Ryegrass pollens. IgE reactivity was higher with pollen of Bahia grass than Bermuda grass, Johnson grass and Ryegrass. Patients showed asymmetric cross‐inhibition of IgE reactivity with subtropical grass pollens that was not blocked by temperate grass pollen allergens indicating the presence of species‐specific IgE binding sites of subtropical grass pollen allergens that are not represented in temperate grass pollens.

Conclusions

Subtropical grass pollens are more important allergen sources than temperate grass pollens for patients from a subtropical region. Targeting allergen‐specific immunotherapy to subtropical grass pollen allergens in patients with allergic rhinitis in subtropical regions could improve treatment efficacy thereby reducing the burden of allergic rhinitis and asthma.
Differential regulation of osteoclastogenesis by Notch2/Delta-like 1 and Notch1/Jagged1 axes
Authors: Sekine Chiyoko , Koyanagi Akemi , Koyama Noriko , Hozumi Katsuto , Chiba Shigeru , Yagita Hideo
Published: March 2012

Introduction

Osteoclastogenesis plays an important role in the bone erosion of rheumatoid arthritis (RA). Recently, Notch receptors have been implicated in the development of osteoclasts. However, the responsible Notch ligands have not been identified yet. This study was undertaken to determine the role of individual Notch receptors and ligands in osteoclastogenesis.

Methods

Mouse bone marrow-derived macrophages or human peripheral blood monocytes were used as osteoclast precursors and cultured with receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage-colony stimulating factor (M-CSF) to induce osteoclasts. Osteoclasts were detected by tartrate-resistant acid phosphatase (TRAP) staining. K/BxN serum-induced arthritic mice and ovariectomized mice were treated with anti-mouse Delta-like 1 (Dll1) blocking monoclonal antibody (mAb).

Results

Blockade of a Notch ligand Dll1 with mAb inhibited osteoclastogenesis and, conversely, immobilized Dll1-Fc fusion protein enhanced it in both mice and humans. In contrast, blockade of a Notch ligand Jagged1 enhanced osteoclastogenesis and immobilized Jagged1-Fc suppressed it. Enhancement of osteoclastogenesis by agonistic anti-Notch2 mAb suggested that Dll1 promoted osteoclastogenesis via Notch2, while suppression by agonistic anti-Notch1 mAb suggested that Jagged1 suppressed osteoclastogenesis via Notch1. Inhibition of Notch signaling by a gamma-secretase inhibitor suppressed osteoclastogenesis, implying that Notch2/Dll1-mediated enhancement was dominant. Actually, blockade of Dll1 ameliorated arthritis induced by K/BxN serum transfer, reduced the number of osteoclasts in the affected joints and suppressed ovariectomy-induced bone loss.

Conclusions

The differential regulation of osteoclastogenesis by Notch2/Dll1 and Notch1/Jagged1 axes may be a novel target for amelioration of bone erosion in RA patients.
Risk factors for cardiovascular mortality in patients with systemic lupus erythematosus, a prospective cohort study
Authors: Gustafsson Johanna T , Simard Julia F , Gunnarsson Iva , Elvin Kerstin , Lundberg Ingrid E , Hansson Lars-Olof , Larsson Anders , Svenungsson Elisabet
Published: March 2012

Introduction

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease. Cardiovascular disease (CVD) is common and a major cause of mortality. Studies on cardiovascular morbidity are abundant, whereas mortality studies focusing on cardiovascular outcomes are scarce. The aim of this study was to investigate causes of death and baseline predictors of overall (OM), non-vascular (N-VM), and specifically cardiovascular (CVM) mortality in SLE, and to evaluate systematic coronary risk evaluation (SCORE).

Methods

208 SLE patients were included 1995-1999 and followed up after 12 years. Clinical evaluation, CVD risk factors, and biomarkers were recorded at inclusion. Death certificates and autopsy protocols were collected. Causes of death were divided into CVM (ischemic vascular and general atherosclerotic diseases), N-VM and death due to pulmonary hypertension. Predictors of mortality were investigated using multivariable Cox regression. SCORE and standardized mortality ratio (SMR) were calculated.

Results

During follow-up 42 patients died at mean age of 62 years. SMR 2.4 (CI 1.7-3.0). 48% of deaths were caused by CVM. SCORE underestimated CVM but not to a significant level. Age, high cystatin C levels and established arterial disease were the strongest predictors for all- cause mortality. After adjusting for these in multivariable analyses, only smoking among traditional risk factors, and high soluble vascular cell adhesion molecule-1 (sVCAM-1), high sensitivity C-reactive protein (hsCRP), anti-beta2 glycoprotein-1 (abeta2GP1) and any antiphospholipid antibody (aPL) among biomarkers, remained predictive of CVM.

Conclusion

With the exception of smoking, traditional risk factors do not capture the main underlying risk factors for CVM in SLE. Rather, cystatin C levels, inflammatory and endothelial markers, and antiphospholipid antibodies (aPL) differentiate patients with favorable versus severe cardiovascular prognosis. Our results suggest that these new biomarkers are useful in evaluating the future risk of cardiovascular mortality in SLE patients.
Dutch translation and cross-cultural adaptation of the PROMIS® physical function item bank and cognitive pre-test in Dutch arthritis patients
Authors: Oude Voshaar Martijn AH , ten Klooster Peter M , Taal Erik , Krishnan Eswar , van de Laar Mart AFJ
Published: March 2012

Introduction

Patient-reported physical function is an established outcome domain in clinical studies in rheumatology. To overcome the limitations of the current generation of questionnaires, the Patient-Reported Outcomes Measurement Information System (PROMIS®) project in the USA has developed calibrated item banks for measuring several domains of health status in people with a wide range of chronic diseases. The aim of this study was to translate and cross-culturally adapt the PROMIS physical function item bank to the Dutch language and to pretest it in a sample of patients with arthritis.

Methods

The items of the PROMIS physical function item bank were translated using rigorous forward-backward protocols and the translated version was subsequently cognitively pretested in a sample of Dutch patients with rheumatoid arthritis.

Results

Few issues were encountered in the forward-backward translation. Only 5 of the 124 items to be translated had to be rewritten because of culturally inappropriate content. Subsequent pretesting showed that overall, questions of the Dutch version were understood as they were intended, while only one item required rewriting.

Conclusions

Results suggest that the translated version of the PROMIS physical function item bank is semantically and conceptually equivalent to the original. Future work will be directed at creating a Dutch-Flemish final version of the item bank to be used in research with Dutch speaking populations.
Altered responsiveness to TGF-β results in reduced Papss2 expression and alterations in the biomechanical properties of mouse articular cartilage
Authors: Ramaswamy Girish , Sohn Philip , Eberhardt Alan , Serra Rosa
Published: March 2012

Introduction

Previous studies have indicated that transforming growth factor β (TGF-β) signaling has a critical role in cartilage homeostasis and repair, yet the mechanisms of TGF-β's chondroprotective effects are not known. Our objective in this study was to identify downstream targets of TGF-β that could act to maintain biochemical and biomechanical properties of cartilage.

Methods

Tibial joints from 20-week-old mice that express a dominant-negative mutation of the TGF-β type II receptor (DNIIR) were graded histologically for osteoarthritic changes and tested by indentation to evaluate their mechanical properties. To identify gene targets of TGF-β, microarray analysis was performed using bovine articular chondrocytes grown in micromass culture that were either treated with TGF-β or left untreated. Phosphoadenosine phosphosynthetase 2 (PAPSS2) was identified as a TGF-β-responsive gene. Papss2 expression is crucial for proper sulfation of cartilage matrix, and its deficiency causes skeletal defects in mice and humans that overlap with those seen in mice with mutations in TGF-β-signaling genes. Regulation of Papss2 was verified by real time RT-PCR and Western blot analyses. Alterations in sulfation of glycosaminoglycans were analyzed by critical electrolyte concentration and Alcian blue staining and immunofluorescence for chondroitin-4-sulfate, unsulfated chondroitin and the aggrecan core protein.

Results

DNIIR mutants showed reduced mechanical properties and osteoarthritis-like changes when compared to wild-type control mice. Microarray analysis identified a group of genes encoding matrix-modifying enzymes that were regulated by TGF-β. Papss2 was upregulated in bovine articular chondrocytes after treatment with TGF-β and downregulated in cartilage from DNIIR mice. Articular cartilage in DNIIR mice demonstrated reduced Alcian blue staining at critical electrolyte concentrations and reduced chondroitin-4-sulfate staining. Staining for unsulfated chondroitin sulfate was increased, whereas staining for the aggrecan core protein was comparable in DNIIR and wild-type mice.

Conclusion

TGF-β maintains biomechanical properties and regulates expression of Papss2 and sulfation of glycosaminoglycans in mouse articular cartilage.
Protein tyrosine phosphatase Meg2 dephosphorylates signal transducer and activator of transcription 3 and suppresses tumor growth in breast cancer
Authors: Su Fuqin , Ren Fangli , Rong Yu , Wang Yangmeng , Geng Yongtao , Wang Yinyin , Feng Mengyao , Ju Yanfang , Li Yi , Zhao Zhizhuang J , Meng Kun , Chang Zhijie
Published: March 2012

Introduction

Signal transducer and activator of transcription 3 (STAT3) is over-activated or phosphorylated in breast cancers. The hyper-phosphorylation of STAT3 was attributed to either up-regulated phosphorylation by several tyrosine-kinases or down-regulated activity of phosphatases. Although several factors have been identified to phosphorylate STAT3, it remains unclear how STAT3 is dephosphorylated by PTPMeg2. The aim of this study was to determine the role of PTPMeg2 as a phosphatase in regulation of the activity of STAT3 in breast cancers.

Methods

Immunoprecipitation assays were used to study the interaction of STAT3 with PTPMeg2. A series of biochemistry experiments were performed to evaluate the role of PTPMeg2 in the dephosphorylation of STAT3. Two breast cancer cell lines MCF7 (PTPMeg2 was depleted as it was endogenously high) and MDA-MB-231 (PTPMeg2 was overexpressed as it was endogenously low) were used to compare the level of phosphorylated STAT3 and the tumor growth ability in vitro and in vivo. Samples from breast carcinoma (n = 73) were subjected to a pair-wise Pearson correlation analysis for the correlation of levels of PTPMeg2 and phosphorylated STAT3.

Results

PTPMeg2 directly interacts with STAT3 and mediates its dephosphorylation in the cytoplasm. Over-expression of PTPMeg2 decreased tyrosine phosphorylation of STAT3 while depletion of PTPMeg2 increased its phosphorylation. The decreased tyrosine phosphorylation of STAT3 is coupled with suppression of STAT3 transcriptional activity and reduced tumor growth in vitro and in vivo. Levels of PTPMeg2 and phosphorylated STAT3 were inversely correlated in breast cancer tissues (P = 0.004).

Conclusions

PTPMeg2 is an important phosphatase for the dephosphorylation of STAT3 and plays a critical role in breast cancer development.
Ultrasound-guided percutaneous tracheostomy in critically ill obese patients
Authors: Guinot Pierre-Grégoire , Zogheib Elie , Petiot Sandra , Marienne Jean-Pierre , Guerin Anne-Marie , Monet Pauline , Zaatar Rody , Dupont Hervé
Published: March 2012

Introduction

The purpose of this study was to evaluate the feasibility of ultrasound (US)-guided percutaneous tracheostomy (PCT) and the incidence of complications in critically ill, obese patients.

Methods

Fifty consecutive patients were included in a prospective study in two surgical and critical care medicine departments. Obesity was defined as a body mass index (BMI) of at least 30 kg/m2. The feasibility of PCT and the incidence of complications were compared in obese patients (n = 26) and non-obese patients (n = 24). Results are expressed as the median (25th-75th percentile) or number (percentage).

Results

The median BMIs were 34 kg/m2 (32-38) in the obese patient group and 25 kg/m2 (24-28) in the non-obese group (p < 0.001). The median times for tracheostomy were 10 min (8-14) in non-obese patients and 9 min (5-10) in obese-patients (p = 0.1). The overall complication rate was similar in obese and non-obese patient groups (35% vs. 33%, p = 0.92). Most complications were minor (hypotension, desaturation, tracheal cuff puncture and minor bleeding), with no differences between obese and non-obese groups. Bronchoscopic inspection revealed two cases of granuloma (8%) in obese patients. One non-obese patient developed a peristomal skin infection, which was treated with intravenous antibiotics. Ultrasound-guided PCT was possible in all enrolled patients and there were no surgical conversions or deaths.

Conclusions

This study demonstrated that US-guided PCT is feasible in obese patients with a low complication rate. Obesity may not constitute a contra-indication for US-guided PCT. A US examination provides information on cervical anatomy and hence modifies and guides choice of the PCT puncture site.

Trial registration

ClinicalTrials.gov: NCT01502657.
Cardiovascular Status of Childhood Cancer Survivors Exposed and Unexposed to Cardiotoxic Therapy
Authors: Lipshultz Steven E. , Landy David C. , Lopez-Mitnik Gabriela , Lipsitz Stuart R. , Hinkle Andrea S. , Constine Louis S. , French Carol A. , Rovitelli Amy M. , Proukou Cindy , Adams M. Jacob , Miller Tracie L.
Published: March 2012

Purpose

To determine whether cardiovascular abnormalities in childhood cancer survivors are restricted to patients exposed to cardiotoxic anthracyclines and cardiac irradiation and how risk factors for atherosclerotic disease and systemic inflammation contribute to global cardiovascular status.

Methods

We assessed echocardiographic characteristics and atherosclerotic disease risk in 201 survivors of childhood cancer with and without exposure to cardiotoxic treatments at a median of 11 years after diagnosis (range, 3 to 32 years) and in 76 sibling controls.

Results

The 156 exposed survivors had below normal left ventricular (LV) mass, wall thickness, contractility, and fractional shortening and above normal LV afterload. The 45 unexposed survivors also had below normal LV mass overall, and females had below normal LV wall thickness. Exposed and unexposed survivors, compared with siblings, had higher levels of N-terminal pro-brain natriuretic peptide (81.7 and 69.0 pg/mL, respectively, v 39.4 pg/mL), higher mean fasting serum levels of non–high-density lipoprotein cholesterol (126.5 and 121.1 mg/dL, respectively, v 109.8 mg/dL), higher insulin levels (10.4 and 10.5 μU/mL, respectively, v 8.2 μU/mL), and higher levels of high-sensitivity C-reactive protein (2.7 and 3.1 mg/L, respectively, v 0.9 mg/L; P < .001 for all comparisons). Age-adjusted, predicted-to-ideal 30-year risk of myocardial infarction, stroke, or coronary death was also higher for exposed and unexposed survivors compared with siblings (2.16 and 2.12, respectively, v 1.70; P < .01 for both comparisons).

Conclusion

Childhood cancer survivors not receiving cardiotoxic treatments nevertheless have cardiovascular abnormalities, systemic inflammation, and an increased risk of atherosclerotic disease. Survivorship guidelines should address cardiovascular concerns, including the risk of atherosclerotic disease and systemic inflammation, in exposed and unexposed survivors.
Phase II Study of Weekly Vinblastine in Recurrent or Refractory Pediatric Low-Grade Glioma
Authors: Bouffet Eric , Jakacki Regina , Goldman Stewart , Hargrave Darren , Hawkins Cynthia , Shroff Manohar , Hukin Juliette , Bartels Ute , Foreman Nicholas , Kellie Stewart , Hilden Joanne , Etzl Michael , Wilson Beverly , Stephens Derek , Tabori Uri , Baruchel Sylvain
Published: March 2012

Purpose

To evaluate the efficacy of single-agent vinblastine in pediatric patients with recurrent or refractory low-grade glioma.

Patients and Methods

Patients were eligible if they had experienced previous treatment failure (chemotherapy and/or radiation) for incompletely resected or unresectable low-grade glioma (LGG). Vinblastine (6 mg/m2) was administered weekly for 1 year unless unacceptable toxicity or progression (confirmed on two consecutive imaging studies) occurred.

Results

Fifty-one patients (age range, 1.4 to 18.2 years; median age, 7.2 years) were prospectively enrolled onto this phase II study. Fifty patients had previously received at least one prior regimen of chemotherapy, and 10 patients had previously received radiation treatment. Fifty patients were evaluable for response; 18 patients (36%) had a complete, partial, or minor response, and 31 patients completed 1 year of treatment. At a median follow-up of 67 months, 23 patients had not experienced progression; three patients have died. Five-year overall survival was 93.2% ± 3.8%, and 5-year progression-free survival was 42.3% ± 7.2%. Toxicity was manageable and mostly hematologic, although a few patients needed transfusions.

Conclusion

Weekly vinblastine seems to be a reasonable alternative to radiation for pediatric patients with LGG who have experienced treatment failure with first-line chemotherapy. The 5-year progression-free survival observed in this phase II trial is comparable to results observed with first-line chemotherapy in chemotherapy-naive patients. The role of single-agent vinblastine and other vinca alkaloid in the management of pediatric LGGs deserves further investigation.
Cohort Study of Somatostatin-Based Radiopeptide Therapy With [90Y-DOTA]-TOC Versus [90Y-DOTA]-TOC Plus [177Lu-DOTA]-TOC in Neuroendocrine Cancers
Authors: Villard Linda , Romer Anna , Marincek Nicolas , Brunner Philippe , Koller Michael T. , Schindler Christian , Ng Quinn K.T. , Mäcke Helmut R. , Müller-Brand Jan , Rochlitz Christoph , Briel Matthias , Walter Martin A.
Published: March 2012

Purpose

Radiopeptide therapy is commonly performed with a single radioisotope. We aimed to compare the effectiveness of somatostatin-based radiopeptide therapy with a single versus a combination of radioisotopes.

Patients and Methods

In a cohort study, patients with metastasized neuroendocrine cancer were treated with repeated cycles of 90yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([90Y-DOTA]-TOC) or with cycles alternating between [90Y-DOTA]-TOC and 177lutetium-labeled DOTA-TOC ([177Lu-DOTA]-TOC) until tumor progression or permanent toxicity. Multivariable Cox regression and competing risk regression were used to study predictors of survival and renal toxicity in patients completing three or more treatment cycles.

Results

A total of 486 patients completed three or more treatment cycles; 237 patients received [90Y-DOTA]-TOC and 249 patients received [90Y-DOTA]-TOC + [177Lu-DOTA]-TOC. Patients receiving [90Y-DOTA]-TOC + [177Lu-DOTA]-TOC had a significantly longer survival than patients receiving [90Y-DOTA]-TOC alone (5.51 v 3.96 years; hazard ratio, 0.64; 95% CI, 0.47 to 0.88; P = .006). The rates of severe hematologic toxicities (6.3% v 4.4%; P = .25) and severe renal toxicity (8.9% v 11.2%; P = .47) were comparable in both groups.

Conclusion

[90Y-DOTA]-TOC + [177Lu-DOTA]-TOC was associated with improved overall survival compared with [90Y-DOTA]-TOC alone in patients completing three or more cycles of treatment. Contrary to the current practice in radiopeptide therapy, our results suggest an advantage of using a combination of radioisotopes.
The Novel Histologic International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification System of Lung Adenocarcinoma Is a Stage-Independent Predictor of Survival
Authors: Warth Arne , Muley Thomas , Meister Michael , Stenzinger Albrecht , Thomas Michael , Schirmacher Peter , Schnabel Philipp A. , Budczies Jan , Hoffmann Hans , Weichert Wilko
Published: March 2012

Purpose

Our aim was to analyze and validate the prognostic impact of the novel International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society (ATS)/European Respiratory Society (ERS) proposal for an architectural classification of invasive pulmonary adenocarcinomas (ADCs) across all tumor stages.

Patients and Methods

The architectural pattern of a large cohort of 500 patients with resected ADCs (stages I to IV) was retrospectively analyzed in 5% increments and classified according to their predominant architecture (lepidic, acinar, solid, papillary, or micropapillary), as proposed by the IASLC/ATS/ERS. Subsequently, histomorphologic data were correlated with clinical data, adjuvant therapy, and patient outcome.

Results

Overall survival differed significantly between lepidic (78.5 months), acinar (67.3 months), solid (58.1 months), papillary (48.9 months), and micropapillary (44.9 months) predominant ADCs (P = .007). When patterns were lumped into groups, this resulted in even more pronounced differences in survival (pattern group 1, 78.5 months; group 2, 67.3 months; group 3, 57.2 months; P = .001). Comparable differences were observed for overall, disease-specific, and disease-free survival. Pattern and pattern groups were stage- and therapy-independent prognosticators for all three survival parameters. Survival differences according to patterns were influenced by adjuvant chemoradiotherapy; in particular, solid-predominant tumors had an improved prognosis with adjuvant radiotherapy. The predominant pattern was tightly linked to the risk of developing nodal metastases (P < .001).

Conclusion

Besides all recent molecular progress, architectural grading of pulmonary ADCs according to the novel IASLC/ATS/ERS scheme is a rapid, straightforward, and efficient discriminator for patient prognosis and may support patient stratification for adjuvant chemoradiotherapy. It should be part of an integrated clinical, morphologic, and molecular subtyping to further improve ADC treatment.
Pertuzumab Monotherapy After Trastuzumab-Based Treatment and Subsequent Reintroduction of Trastuzumab: Activity and Tolerability in Patients With Advanced Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer
Authors: Cortés Javier , Fumoleau Pierre , Bianchi Giulia Valeria , Petrella Teresa M. , Gelmon Karen , Pivot Xavier , Verma Shailendra , Albanell Joan , Conte Pierfranco , Lluch Ana , Salvagni Stefania , Servent Veronique , Gianni Luca , Scaltriti Maurizio , Ross Graham A. , Dixon Joanna , Szado Tania , Baselga José
Published: March 2012

Purpose

The combination of pertuzumab and trastuzumab resulted in a clinical benefit rate (CBR) of 50% in patients with human epidermal growth factor receptor 2 (HER2) –positive breast cancer whose disease progressed during prior trastuzumab-based therapy. To define whether this previously observed encouraging activity was a result of the combination of pertuzumab and trastuzumab or of pertuzumab alone, we recruited a third cohort of patients who received pertuzumab without trastuzumab. We then investigated the impact of reintroducing trastuzumab to patients whose disease progressed on pertuzumab monotherapy.

Patients and Methods

Twenty-nine patients with HER2-positive breast cancer whose disease progressed during prior trastuzumab-based therapy received pertuzumab (840 mg loading dose, then 420 mg every 3 weeks) until progressive disease or unacceptable toxicity. Seventeen patients with disease progression continued to receive pertuzumab (at the same dose), with the addition of trastuzumab (4 mg/kg loading dose and then 2 mg/kg weekly or 8 mg/kg loading dose and then 6 mg/kg every 3 weeks).

Results

All 29 patients enrolled for pertuzumab monotherapy experienced disease progression. The objective response rate (ORR) and CBR were 3.4% and 10.3%, respectively, during pertuzumab monotherapy. With the addition of trastuzumab, the ORR and CBR were 17.6% and 41.2%, respectively. Progression-free survival was longer with combination therapy than pertuzumab monotherapy (17.4 v 7.1 weeks, respectively). Treatment was well tolerated with minimal cardiac dysfunction.

Conclusion

Although pertuzumab has some activity in patients with HER2-positive breast cancer that progressed during therapy with trastuzumab, the combination of pertuzumab and trastuzumab seems to be more active than monotherapy.
Identification of a Poor-PrognosisBRAF-Mutant–Like Population of Patients With Colon Cancer
Authors: Popovici Vlad , Budinska Eva , Tejpar Sabine , Weinrich Scott , Estrella Heather , Hodgson Graeme , Van Cutsem Eric , Xie Tao , Bosman Fred T. , Roth Arnaud D. , Delorenzi Mauro
Published: March 2012

Purpose

Our purpose was development and assessment of a BRAF-mutant gene expression signature for colon cancer (CC) and the study of its prognostic implications.

Materials and Methods

A set of 668 stage II and III CC samples from the PETACC-3 (Pan-European Trails in Alimentary Tract Cancers) clinical trial were used to assess differential gene expression between c.1799T>A (p.V600E) BRAF mutant and non-BRAF, non-KRAS mutant cancers (double wild type) and to construct a gene expression–based classifier for detecting BRAF mutant samples with high sensitivity. The classifier was validated in independent data sets, and survival rates were compared between classifier positive and negative tumors.

Results

A 64 gene-based classifier was developed with 96% sensitivity and 86% specificity for detecting BRAF mutant tumors in PETACC-3 and independent samples. A subpopulation of BRAF wild-type patients (30% of KRAS mutants, 13% of double wild type) showed a gene expression pattern and had poor overall survival and survival after relapse, similar to those observed in BRAF-mutant patients. Thus they form a distinct prognostic subgroup within their mutation class.

Conclusion

A characteristic pattern of gene expression is associated with and accurately predicts BRAF mutation status and, in addition, identifies a population of BRAF mutated-like KRAS mutants and double wild-type patients with similarly poor prognosis. This suggests a common biology between these tumors and provides a novel classification tool for cancers, adding prognostic and biologic information that is not captured by the mutation status alone. These results may guide therapeutic strategies for this patient segment and may help in population stratification for clinical trials.
Regulation of cranial morphogenesis and cell fate at the neural crest-mesoderm boundary by engrailed 1
Authors: Deckelbaum Ron A. , Holmes Greg , Zhao Zhicheng , Tong Chunxiang , Basilico Claudio , Loomis Cynthia A.
Published: March 2012

The characterization of mesenchymal progenitors is central to understanding development, postnatal pathology and evolutionary adaptability. The precise identity of the mesenchymal precursors that generate the coronal suture, an important structural boundary in mammalian skull development, remains unclear. We show in mouse that coronal suture progenitors originate from hedgehog-responsive cephalic paraxial mesoderm (Mes) cells, which migrate rapidly to a supraorbital domain and establish a unidirectional lineage boundary with neural crest (NeuC) mesenchyme. Lineage tracing reveals clonal and stereotypical expansion of supraorbital mesenchymal cells to form the coronal suture between E11.0 and E13.5. We identify engrailed 1 (En1) as a necessary regulator of cell movement and NeuC/Mes lineage boundary positioning during coronal suture formation. In addition, we provide genetic evidence that En1 functions upstream of fibroblast growth factor receptor 2 (Fgfr2) in regulating early calvarial osteogenic differentiation, and postulate that it plays an additional role in precluding premature osteogenic conversion of the sutural mesenchyme.
Microprocessor dynamics and interactions at endogenous imprinted C19MC microRNA genes
Authors: Clément Bellemer , Marie-Line Bortolin-Cavaillé , Ute Schmidt , Rask Jensen Stig Mølgaard , Jørgen Kjems , Edouard Bertrand , Cavaillé Jérôme
Published: March 2012

Nuclear primary microRNA (pri-miRNA) processing catalyzed by the DGCR8-Drosha (Microprocessor) complex is highly regulated. Little is known, however, about how microRNA biogenesis is spatially organized within the mammalian nucleus. Here, we image for the first time, in living cells and at the level of a single microRNA cluster, the intra-nuclear distribution of untagged, endogenously-expressed pri-miRNAs generated at the human imprinted Chromosome 19 MicroRNA Cluster (C19MC), from the environment of transcription sites to single molecules of fully released DGCR8-bound pri-miRNAs dispersed throughout the nucleoplasm. We report that a large fraction of Microprocessor concentrates onto unspliced C19MC pri-miRNA deposited in close proximity to their genes. Our live-cell imaging studies provide direct visual evidence that DGCR8 and Drosha are targeted post-transcriptionally to C19MC pri-miRNAs as a preformed complex but dissociate separately. These dynamics support the view that, upon pri-miRNA loading and most likely concomitantly with Drosha-mediated cleavages, Microprocessor undergoes conformational changes that trigger the release of Drosha while DGCR8 remains stably bound to pri-miRNA.
CD82 expression alters with human endometrial cycles and affects the uterine endometrial receptivity in vitro
Authors: Wei Xiaowei , Liu Shuai , Wang Xiaoqi , Yan Qiu
Published: March 2012

Embryo implantation is a process that requires both temporal and spatial synchronization of the uterine endometrium and the embryo, and the endometrium becomes receptive to the embryo during the window of implantation. Although the expression patterns of many implantation-related molecules change dynamically during this process, the impact of CD82 on endometrial receptivity has not been elucidated. By immunohistochemical staining, we found that CD82 levels rose from the proliferative phase to the secretory phase in human endometrium. Specifically, the highest level appeared in mid- and late-secretory phases. Consistently, RL95-2 cells, representative of high-receptive endometrial epithelium, expressed higher levels of CD82 than did HEC-1A cells, which are representative of low-receptive endometrial epithelium, as detected by reverse transcription-polymerase chain reaction, Western blot and immunofluorescence. Furthermore, progesterone up-regulated the expression of CD82 in both epithelial cell lines. Down-regulation of CD82 in RL95-2 cells by either CD82 siRNA transfection or treatment with a CD82 antibody significantly decreased the adhesion of human embryonic JAR cells to RL95-2 cell monolayers ( P < 0.01) and inhibited the phosphorylation of focal adhesion kinase (FAK). In contrast, up-regulation of CD82 in HEC-1A cells by CD82 cDNA transfection promoted embryonic JAR cell adhesion to HEC-1A monolayers ( P < 0.05) and activated the phosphorylation of FAK. In conclusion, the expression of CD82 increases in endometrial tissues during the window of embryo implantation, CD82 expression affects endometrial receptivity of the uterine epithelial cells in vitro, and the FAK signaling pathway may be involved in this phenomenon. The correlation between CD82 and endometrial receptivity suggests that CD82 may serve as a potential marker of endometrial function.
Postmenopausal vaginal bleeding in women using hormone replacement therapy
Authors: Burbos Nikolaos , Musonda Patrick , Duncan Timothy J , Crocker Simon G , Nieto Joaquin J , Morris Edward P
Published: March 2012

Objective

To estimate the risk of endometrial cancer in postmenopausal women presenting with vaginal bleeding using estrogen–progestogen hormone replacement therapy (HRT) regimens and to assess if the duration of HRT use has an effect on the risk of diagnosing endometrial cancer.

Study design

Cross-sectional study of consecutive women presenting with postmenopausal vaginal bleeding at a gynaecological oncology centre in the UK.

Main outcome measures

Endometrial cancer diagnosis.

Results

Over a 62-month period, 4847 women were investigated for postmenopausal vaginal bleeding. The majority of women (4097, 84.5%) did not use any HRT preparation at the time of initial referral and 750 (15.5%) women were using combined HRT preparations. A total of 298 (6.1%) women were diagnosed with endometrial carcinoma. Women using HRT preparations were significantly less likely to be diagnosed with endometrial cancer compared with women not using HRT (adjusted odds ratio = 0.229, 95% CI 0.116–0.452; P < 0.0001). The longer duration of HRT use did increase the risk of diagnosing endometrial cancer in women presenting with postmenopausal vaginal bleeding, but this was not statistically significant.

Conclusions

Postmenopausal women presenting with vaginal bleeding and using combined HRT preparations have significantly lower risk of being diagnosed with endometrial cancer when compared with women not using HRT.
Menopause and schizophrenia
Authors: Gupta Rina , Assalman Iyas , Bottlender Ronald
Published: March 2012

We have come a long way from our understanding of the menopause as it was described in the 11th century by Trotula of Salerno, a female gynaecologist who said ‘there are older women who give forth blood matter especially as menopause approaches them’. Yet very little is known about the impact menopause has on the mental health of women especially severe and enduring illnesses like schizophrenia. A lot of research has shown that estrogen acts as a protective factor due to its antidopaminergic properties, thus providing an explanation for the increase in risk of a new psychotic disorder during the menopause. This has further led to the hypothesis of hormone replacement therapy providing benefits in the management of these disorders in menopausal women. This review article highlights the importance of a clear understanding of this phase of life in patients suffering from or who present with a risk of developing schizophrenia.
The subgenomic promoter of brome mosaic virus folds into a stem–loop structure capped by a pseudo-triloop that is structurally similar to the triloop of the genomic promoter
Authors: Skov Joan , Gaudin Mathieu , Podbevšek Peter , Olsthoorn René C.L. , Petersen Michael
Published: March 2012

In brome mosaic virus, both the replication of the genomic (+)-RNA strands and the transcription of the subgenomic RNA are carried out by the viral replicase. The production of (−)-RNA strands is dependent on the formation of an AUA triloop in the stem–loop C (SLC) hairpin in the 3′-untranslated region of the (+)-RNA strands. Two alternate hypotheses have been put forward for the mechanism of subgenomic RNA transcription. One posits that transcription commences by recognition of at least four key nucleotides in the subgenomic promoter by the replicase. The other posits that subgenomic transcription starts by binding of the replicase to a hairpin formed by the subgenomic promoter that resembles the minus strand promoter hairpin SLC. In this study, we have determined the three-dimensional structure of the subgenomic promoter hairpin using NMR spectroscopy. The data show that the hairpin is stable at 30°C and that it forms a pseudo-triloop structure with a transloop base pair and a nucleotide completely excluded from the helix. The transloop base pair is capped by an AUA triloop that possesses an extremely well packed structure very similar to that of the AUA triloop of SLC, including the formation of a so-called clamped-adenine motif. The similarities of the NMR structures of the hairpins required for genomic RNA and subgenomic RNA synthesis show that the replicase recognizes structure rather than sequence-specific motifs in both promoters.
Percutaneous cholecystostomy as an alternative to cholecystectomy in high risk patients with biliary sepsis: a district general hospital experience
Authors: Al–Jundi W , Cannon T , Antakia R , Anoop U , Balamurugan R , Everitt N , Ravi K
Published: March 2012

INTRODUCTION

Cholecystectomy is the standard treatment for patients with acute cholecystitis. However, percutaneous cholecystostomy (PC) is an alternative for patients at high risk for surgery. We present our five-year clinical experience with the aim of evaluating the efficacy of PC in high risk patients.

METHODS

A retrospective review was performed on 30 consecutive patients who underwent PC at our institution. The indications for cholecystostomy, route of insertion, technical success, clinical improvement, length of hospitalisation, in-hospital or 30-day mortality, complications, subsequent admissions and performance of interval cholecystectomy were recorded. The median follow-up period was 25 months (range: 1–52 months).

RESULTS

Thirty-two PCs were performed in thirty patients (mean age: 76.1 years; range: 52–90 years). The indications for PC were acute calculous cholecystitis (29/32), acalculous cholecystitis (1/32) and emphysematous cholecystitis (2/32). The route of insertion was transperitoneal for 22/32 PCs (68.8%) and transhepatic for 10/32 (31.2%). The procedure was technically successful in all patients although 2/22 transperitoneal drains (9.1%) were dislodged subsequently. Twenty-seven PCs (84.4%) resulted in clinical improvement within five days. The in-hospital or 30–day mortality rate was 16.7% (5/30). Eleven patients (36.7%) had a subsequent cholecystectomy: 6 were laparoscopic and 5 converted to open procedures at a median interval of 58 days (range: 1–124 days).

CONCLUSIONS

PCs are straightforward with few complications. Most patients improve clinically and the procedure can therefore be used as a definitive treatment in unfit patients or as a bridge to surgery in those who might subsequently prove fit for a definitive operation.
Phytobezoar: a rare cause of late upper gastrointestinal perforation following gastric bypass surgery
Authors: Sammut SJ , Majid S , Shoab S
Published: March 2012

Marginal ulcers are a well described complication following Roux-en-Y gastric bypass. These may be a cause for perforation. We describe a case of upper gastrointestinal perforation 18 months following a laparoscopic Roux-en-Y gastric bypass that appeared to be caused by a food bezoar. The perforation occurred at the site of the jejunojejunal anastomosis and was repaired after an exploratory laparotomy. After extracting the food debris (phytobezoar) through the perforation, direct closure resulted in an uneventful post-operative recovery. To our knowledge, this is the first description of a food bezoar causing an intestinal perforation in such a manor after bariatric surgery. Patients should be educated carefully on what and how to eat after having undergone surgery for superobesity.
Inverted cyclops lesion after anterior cruciate ligament reconstruction
Authors: Kambhampati S , Ware H
Published: March 2012

We report the case of an inverted cyclops lesion limiting extension of the knee joint after a four-strand hamstring anterior cruciate ligament (ACL) reconstruction. One case has been reported previously following a bone-tendon-bone reconstruction of the ACL but a similar case has not been reported.
The Evolution of Modern Breast Surgery
Authors: Skillman J
Published: March 2012

Breast surgery is changing from a purely resectional specialty to one in which aesthetic outcomes are becoming increasingly important. Breast conservation surgery has moved beyond ablation to techniques that maintain or improve breast shape. Knowledge and surgical skills, traditionally the remit of plastic surgeons, are crucial to the success of these new techniques and are being adopted and adapted by a new breed of oncoplastic surgeons. Professional boundaries are becoming blurred as new breast surgeons are trained both oncologically and in plastic surgery. Breast surgeons have welcomed the opportunity for interface training but plastic surgery trainees are underrepresented in applications and successful appointment to oncoplastic fellowships. This article aims to summarise the development of breast surgery as a separate specialty and how improved training, financial pressures and the attitudes of surgeons may influence the future of oncoplastic surgery.
Lessons to be learnt from the PIP saga
Authors: Williams Norman
Published: March 2012

In the course of my surgical career I have witnessed many groundbreaking developments that have dramatically improved and saved patients' lives and been truly transformational. Such breakthroughs have invariably occurred from a combination of science, surgical ingenuity and skill underpinned by the enthusiasm and drive of a variety of surgical innovators and medical device manufacturers. We should all be proud of the progress that has been made and the lives that have been saved and improved. However, from time to time I have also witnessed scandals involving surgical implants that have marred the reputation of not only the manufacturers but also, on occasion, the surgeons involved. These scandals have a significant impact on the specialty and can often inhibit progress, cause suffering to patients and destroy professional lives.
Minor oral surgery in the primary care setting
Authors: McHenry Paula
Published: March 2012

Research suggests that the level of dental undergraduate experience of core clinical skills in oral surgery could be enhanced. Surgical extraction of teeth has been identified as one of the areas that vocational dental practitioners and their trainers feel least prepared for by their undergraduate training. Furthermore, many dental graduates do not feel that they have sufficient practical experience in minor surgical procedures to complete them in practice. The resultant effect is that minor oral surgery cases are often referred to secondary care facilities despite the possibility that some cases could have been treated in the primary care sector.