bluuebunny/crossref_metadata_2025 huggingface dataset:
Early unclamping technique during robot‐assisted laparoscopic partial nephrectomy can minimise warm ischaemia without increasing morbidity
Authors: Peyronnet Benoit , Baumert Hervé , Mathieu Romain , Masson‐Lecomte Alexandra , Grassano Yohann , Roumiguié Mathieu , Massoud Walid , Abd El Fattah Vincent , Bruyère Franck , Droupy Stéphane , de la Taille Alexandre , Doumerc Nicolas , Bernhard Jean‐Christophe , Vaessen Christophe , Rouprêt Morgan , Bensalah Karim
Published: April 2014

Objective

To compare perioperative outcomes of early unclamping (EUC) vs standard unclamping (SUC) during robot‐assisted partial nephrectomy (RAPN), as early unclamping of the renal pedicle has been reported to decrease warm ischaemia time (WIT) during laparoscopic PN.

Patients and Methods

A retrospective multi‐institutional study was conducted at eight French academic centres between 2009 and 2013. Patients who underwent RAPN for a renal mass were included in the study. Patients without vascular clamping or for whom the decision to perform a radical nephrectomy was taken before unclamping were excluded. Perioperative outcomes were compared using the chi‐squared and Fisher's exact tests for discrete variables and the Mann–Whitney test for continuous variables. Predictors of WIT and estimated blood loss (EBL) were assessed using multiple linear regression analysis.

Results

In all, there were 430 patients: 222 in the EUC group and 208 in the SUC group. Tumours were larger (35.8 vs 32.3 mm, P = 0.02) and more complex (R.E.N.A.L. nephrometry score 6.9 vs 6.1, P < 0.001) in the EUC group but surgeons were more experienced (>50 procedures 12.2% vs 1.4%, P < 0.001). The mean WIT was shorter (16.7 vs 22.3 min, P < 0.001) and EBL was higher (369.5 vs 240 mL, P = 0.001) in the EUC group with no significant difference in complications or transfusion rates. The results remained the same when analysing subgroups of complex renal tumours (R.E.N.A.L. nephrometry score ≥7) or RAPN performed by less experienced surgeons (<20 procedures). In multivariable analysis, EUC was predictive of decreased WIT (β –0.34; P < 0.001) but was not associated with EBL (β –0.09, P = 0.16).

Conclusions

EUC can reduce WIT during RAPN without increasing morbidity even for complex renal tumours or when being performed by less experienced surgeons.
Combining depot antipsychotic with an assertive monitoring programme for treating first‐episode schizophrenia in a resource‐constrained setting
Authors: Chiliza Bonginkosi , Ojagbemi Akin , Esan Oluyomi , Asmal Laila , Oosthuizen Piet , Kidd Martin , Gureje Oye , Emsley Robin
Published: April 2014

Aim

To assess the feasibility and effectiveness of depot antipsychotic (flupenthixol decanoate) combined with an assertive monitoring programme (AMP) in first‐episode schizophrenia.

Methods

This was a prospective, non‐comparative, longitudinal study conducted over 12 months assessing patient acceptance, adherence, outcome in domains of psychopathology, functionality and quality of life, and tolerability.

Results

Of 207 participants, 149 (72%) completed 12 months of treatment. Acceptance of and adherence to depot was good. Treatment response was achieved by 170 (82%) participants and remission by 124 (60%). Thirty‐three (19%) responders relapsed and 10 (5%) participants met a priori criteria for treatment resistance. Treatment was generally well tolerated.

Conclusions

Combination of depot antipsychotic with an AMP may be an effective and safe intervention in early phases of schizophrenia, and may be particularly suitable for resource‐constrained settings.
Stroke in first‐degree relatives of patients with cervical artery dissection
Authors: Kloss M. , Grond‐Ginsbach C. , Pezzini A. , Metso T. M. , Metso A. J. , Debette S. , Leys D. , Dallongeville J. , Caso V. , Thijs V. , Bersano A. , Touzé E. , Bonati L. H. , Tatlisumak T. , Arnold M.‐L. , Lyrer P. A. , Engelter S. T. ,   for the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) Study Group
Published: April 2014

Background and purpose

Patients with ischaemic stroke (IS) caused by a spontaneous cervical artery dissection (CeAD) worry about an increased risk for stroke in their families. The occurrence of stroke in relatives of patients with CeAD and in those with ischaemic stroke attributable to other (non‐CeAD) causes were compared.

Methods

The frequency of stroke in first‐degree relatives (family history of stroke, FHS) was studied in IS patients (CeAD patients and age‐ and sex‐matched non‐CeAD patients) from the Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) database. FHS ≤ 50 and FHS > 50 were defined as having relatives who suffered stroke at the age of ≤50 or >50 years. FHS ≤ 50 and FHS > 50 were studied in CeAD and non‐CeAD IS patients and related to age, sex, number of siblings, hypertension, hypercholesterolemia, smoking and body mass index (BMI).

Results

In all, 1225 patients were analyzed. FHS ≤ 50 was less frequent in CeAD patients (15/598 = 2.5%) than in non‐CeAD IS patients (38/627 = 6.1%) (P = 0.003; odds ratio 0.40, 95% confidence interval 0.22–0.73), also after adjustment for age, sex and number of siblings (P = 0.005; odds ratio 0.42, 95% confidence interval 0.23–0.77). The frequency of FHS > 50 was similar in both study groups. Vascular risk factors did not differ between patients with positive or negative FHS ≤ 50. However, patients with FHS > 50 were more likely to have hypertension and higher BMI.

Conclusion

Relatives of CeAD patients had fewer strokes at a young age than relatives of non‐CeAD IS stroke patients.
Ion Channels and Migraine
Authors: Yan Jin , Dussor Gregory
Published: April 2014

Migraine is one of the most common neurological disorders. Despite its prevalence, the basic physiology of the molecules and mechanisms that contribute to migraine headache is still poorly understood, making the discovery of more effective treatments extremely difficult. The consistent presence of head‐specific pain during migraine suggests an important role for activation of the peripheral nociceptors localized to the head. Accordingly, this review will cover the current understanding of the biological mechanisms leading to episodic activation and sensitization of the trigeminovascular pain pathway, focusing on recent advances regarding activation and modulation of ion channels.
Career decisions: factors that influence the Māori doctor
Authors: Lucas C. , Edmonds L. , Leroy J. , Reith D.
Published: April 2014

Background

Māori have known health disparities that may be addressed through increasing the cultural competency of New Zealand's medical workforce. There is a paucity of Māori health professionals choosing paediatrics or adult medicine as a career and the factors influencing their career decision are yet to be explored.

Aims

First, to differentiate factors influencing the medical career choice of non‐Māori paediatricians and physicians, Māori paediatricians and physicians and other Māori doctors. Second, to identify ways in which Māori doctors may be encouraged to choose paediatricians or adult medicine.

Methods

A questionnaire was distributed by email to New Zealand physicians and paediatricians and to Māori doctors. Questions included demographic information, a matrix rating table and open‐ended questions.

Results

Altogether 199 people accessed the questionnaire. Response rates were 9% (n = 118) for non‐Māori paediatricians and physicians, 70% (n = 19) for Māori paediatricians and physicians, and 31% (n = 62) for other Māori doctors. Māori paediatricians and physicians highlighted mentoring as having significant impact on career choice. Non‐Māori paediatricians and physicians regarded interest as having the most influence on career choice (P < 0.01). Lifestyle factors influenced other Māori doctors (P < 0.001). All three groups regarded poor lifestyle as having the largest negative influence. No group regarded potential income as important.

Conclusion

Mentoring provides an opportunity to attract Māori into paediatric and adult physician training. The use of existing mentoring programmes could facilitate in expanding Māori RACP workforce development. This extended Māori workforce would have benefits for the health of New Zealand as a whole.
Renal sodium glucose cotransporter 2 inhibitors as a novel therapeutic approach to treatment of type 2 diabetes: Clinical data and mechanism of action
Authors: Fujita Yoshihito , Inagaki Nobuya
Published: April 2014

Type 2 diabetes is characterized by impaired insulin secretion from pancreatic β‐cells and/or reduced response of target tissues to insulin. Good glycemic control delays the development and slows the progression of micro‐ and macrovascular complications. Although there are numerous glucose‐lowering agents in clinical use, only approximately half of type 2 diabetic patients achieve glycemic control, and undesirable side‐effects often hamper treatment in those treated with the medications. There is a need for novel treatment options that can help overcome these difficulties. Sodium glucose cotransporter 2 (SGLT2) inhibitors have recently been developed as a novel potential therapeutic option for the treatment of type 2 diabetes. These drugs lower the plasma glucose concentration through inhibition of glucose reuptake in the kidney, independent of insulin secretion and insulin action, with a consequent lower risk of hypoglycemia. The data of clinical trials with monotherapy as well as combination therapy show that SGLT2 inhibitors have a blood glucose‐lowering effect and also reduce bodyweight. A follow‐up study shows long‐term efficacy and the durability of these effects. SGLT2 inhibitors have the potential to reverse glucose toxicity, and to improve insulin resistance, blood pressure and lipid profile. The available data suggest a good tolerability profile. However, clinicians should carefully prescribe these drugs in light of already reported and/or unexpected side‐effects. Further studies in larger numbers and longer‐term clinical use data are required to place these agents in standard treatment of type 2 diabetes.
Change in Inflammatory Markers and Cognitive Status in the Oldest‐Old Women from the Study of Osteoporotic Fractures
Authors: Metti Andrea L. , Yaffe Kristine , Boudreau Robert M. , Ganguli Mary , Lopez Oscar L. , Stone Katie L. , Cauley Jane A.
Published: April 2014

Objectives

To determine the association between interleukin‐6 (IL‐6), IL‐6 soluble receptor (sR), and soluble tumor necrosis factor receptor‐1 (sTNF‐R1) and cognitive status in the oldest‐old women.

Design

Twenty‐year longitudinal cohort study.

Setting

Four clinical sites in the United States.

Participants

Women from the Study of Osteoporotic Fractures (N = 905; mean age 88.3 ± 2.8 at cognitive status adjudication).

Measurements

At Year 20, cognitive status was adjudicated as normal, mild cognitive impairment (MCI), or dementia. Inflammatory markers were measured from blood serum at Years 10 and 16 in a random sample of women.

Results

Over 10 years, 199 (22.0%) women developed MCI and 145 (16.0%) dementia. There were no significant associations between IL‐6 or sTNF‐R1 and cognitive status. High IL‐6‐sR (≥37,401.36 pg/mL, highest tertile) at Year 16 was significantly associated with lower risk of dementia (odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.30–0.97) than in women with lower levels (<37,401.36 pg/mL, lower two tertiles). Women with high IL‐6‐sR at both time points (OR = 0.39, 95% CI = 0.17–0.89) or who transitioned to a high level (OR = 0.35, 95% CI = 0.14–0.88) had a lower risk of dementia.

Conclusion

In this cohort of white, high‐functioning oldest‐old women, a consistently high or an increasing level of IL‐6‐sR was associated with lower risk of dementia. Compared with other studies of younger‐old adults, this suggests that the effect of inflammation on dementia may differ in younger‐old and the oldest‐old individuals. Understanding these differences will be crucial in interpreting results from ongoing clinical trials and in targeting therapeutic strategies to the oldest‐old individuals.
NICE to HELP: Operationalizing National Institute for Health and Clinical Excellence Guidelines to Improve Clinical Practice
Authors: Yue Jirong , Tabloski Patricia , Dowal Sarah L. , Puelle Margaret R. , Nandan Rakesh , Inouye Sharon K.
Published: April 2014

The National Institute for Health and Clinical Excellence (NICE) in the United Kingdom developed guidelines for the diagnosis, prevention, and management of delirium in July 2010 that included 10 recommendations for delirium prevention. The Hospital Elder Life Program (HELP) is a targeted multicomponent strategy that has proven effective and cost‐effective at preventing functional and cognitive decline in hospitalized older persons. HELP provided much of the basis for seven of the NICE recommendations. Given interest by new HELP sites to meet NICE guidelines, three new protocols addressing hypoxia, infection, and pain that were not previously included in the HELP program were developed. In addition, the NICE dehydration guideline included constipation, which was not specifically addressed in the HELP protocols. This project describes the systematic development of three new protocols (hypoxia, infection, pain) and the expansion of an existing HELP protocol (constipation and dehydration) to achieve alignment between the HELP protocols and NICE guidelines. Following the Institute of Medicine recommendations for developing trustworthy guidelines, an interdisciplinary group of experts conducted a systematic review of current literature, rated the quality of the evidence, developed intervention protocols based on the highest‐quality evidence, and submitted the protocols first to internal review and then to external review by an interdisciplinary panel of experts. The protocols were revised based on the review process and incorporated into the HELP materials. Inclusion of these protocols enhances the scope of the HELP program and allows fulfillment of NICE guideline recommendations for delirium prevention. The rigorous process applied may provide a useful example for updating existing guidelines or protocols that may be applicable to a broad range of clinical applications.
Identifying Common Characteristics of Frailty Across Seven Scales
Authors: Theou Olga , Brothers Thomas D. , Peña Fernando G. , Mitnitski Arnold , Rockwood Kenneth
Published: April 2014

Objectives

To determine whether commonly used frailty scales exhibit shared characteristics when applied to a representative sample of middle‐aged and older Europeans.

Design

Secondary analysis of the Survey of Health, Ageing, and Retirement in Europe (SHARE).

Setting

Eleven European countries.

Participants

Community‐dwelling adults (N = 27,527; mean age 65.3 ± 10.5, 55% female).

Measurements

Frailty was assessed using SHARE‐operationalized versions of seven frailty scales: Edmonton Frail Scale, FRAIL scale, Groningen Frailty Indicator, frailty phenotype, Tilburg Frailty Indicator, a 70‐item frailty index (FI), and a 44‐item frailty index based on Comprehensive Geriatric Assessment.

Results

All frailty scales demonstrated right‐skewed density distributions. On all scales, frailty scores increased nonlinearly with age, between 1% (FRAIL) and 3.6% (FI) per year on a log scale. Frailty scores on all scales exhibited dose‐response relationships with 5‐year mortality. On all scales, women had higher frailty scores than men of the same age but demonstrated better survival than did men with the same frailty score. On all scales except the frailty phenotype, 99% of participants had scores below the scale's theoretical maximum.

Conclusion

On each frailty scale, frailty score increased nonlinearly with age, mortality risk increased with frailty score, and women had higher scores than men but demonstrated better survival. Each scale except the frailty phenotype demonstrated an upper limit to frailty below the scale's theoretical maximum. Across commonly used frailty scales, these characteristics are common in nature but differ in magnitude.
Successfully Reducing Antibiotic Prescribing in Nursing Homes
Authors: Zimmerman Sheryl , Sloane Philip D. , Bertrand Rosanna , Olsho Lauren E. W. , Beeber Anna , Kistler Christine , Hadden Louise , Edwards Alrick , Weber David J. , Mitchell C. Madeline
Published: April 2014

Objectives

To determine whether antibiotic prescribing can be reduced in nursing homes using a quality improvement (QI) program that involves providers, staff, residents, and families.

Design

A 9‐month quasi‐experimental trial of a QI program in 12 nursing homes (6 comparison, 6 intervention) conducted from March to November 2011.

Setting

Nursing homes in two regions of North Carolina, roughly half of whose residents received care from a single practice of long‐term care providers.

Participants

All residents, including 1,497 who were prescribed antibiotics.

Intervention

In the intervention sites, providers in the single practice and nursing home nurses received training related to prescribing guidelines, including situations for which antibiotics are generally not indicated, and nursing home residents and their families were sensitized to matters related to antibiotic prescribing. Feedback on prescribing was shared with providers and nursing home staff monthly.

Measurements

Rates of antibiotic prescribing for presumed urinary tract, skin and soft tissue, and respiratory infections.

Results

The QI program reduced the number of prescriptions ordered between baseline and follow‐up more in intervention than in comparison nursing homes (adjusted incidence rate ratio = 0.86, 95% confidence interval = 0.79–0.95). Based on baseline prescribing rates of 12.95 prescriptions per 1,000 resident‐days, this estimated adjusted incidence rate ratio implies 1.8 prescriptions avoided per 1,000 resident‐days.

Conclusion

This magnitude of effect is unusual in efforts to reduce antibiotic use in nursing homes. Outcomes could be attributed to the commitment of the providers; outreach to providers and staff; and a focus on common clinical situations in which antibiotics are generally not indicated; and suggest that similar results can be achieved on a wider scale if similar commitment is obtained and education provided.
Up‐regulation of the chemo‐attractive receptor ChemR23 and occurrence of apoptosis in human chondrocytes isolated from fractured calcaneal osteochondral fragments
Authors: Sena Paola , Manfredini Giuseppe , Benincasa Marta , Mariani Francesco , Smargiassi Alberto , Catani Fabio , Palumbo Carla
Published: April 2014

To study the expression level of a panel of pro/anti‐apoptotic factors and inflammation‐related receptors in chondral fragments from patients undergoing surgical treatment for intra‐articular calcaneal fractures, cartilage fragments were retrieved from calcaneal fractures of 20 patients subjected to surgical treatment. Primary cultures were performed using chondral fragments from fractured and control patients. Chondrocyte cultures from each patient of the fractured and control groups were subjected to immunofluorescence staining and quantitatively analyzed under confocal microscopy. Proteins extracted from the cultured chondrocytes taken from the fractured and control groups were processed for Western blot experiments and densitometric analysis. The percentage of apoptotic cells was determined using the cleaved PARP‐1 antibody. The proportion of labelled cells was 35% for fractured specimens, compared with 7% for control samples. Quantification of caspase‐3 active and Bcl‐2 proteins in chondrocyte cultures showed a significant increase of the apoptotic process in fractured specimens compared with control ones. Fractured chondrocytes were positively stained for ChemR23 with statistically significant differences with respect to control samples. Densitometric evaluation of the immunoreactive bands confirmed these observations. Human articular chondrocytes obtained from patients with intra‐articular calcaneal fractures express higher levels of pivotal pro‐apoptotic factors, and of the chemo‐attractive receptor ChemR23, compared with control cultures. On the basis of these observations, the authors hypothesize that consistent prolonged chondrocyte death, associated with the persistence of high levels of pro‐inflammatory factors, could enhance the deterioration of cartilage tissue with consequent development of post‐traumatic arthritis following intra‐articular bone fracture.
Mutational analysis of FOXL2 p.C134W and expression of bone morphogenetic protein 2 in Japanese patients with granulosa cell tumor of ovary
Authors: Oseto Kumiko , Suzumori Nobuhiro , Nishikawa Ryutaro , Nishikawa Hiroshi , Arakawa Atsushi , Ozaki Yasuhiko , Asai Hidekazu , Kawai Michiyasu , Mizuno Kimio , Takahashi Satoru , Shirai Tomoyuki , Yamada‐Namikawa Chisato , Nakanishi Makoto , Kajiyama Hiroaki , Kikkawa Fumitaka , Sugiura‐Ogasawara Mayumi
Published: April 2014

Aim

To assess whether FOXL2 p.C134W mutation may play a role in the development of human ovarian tumors in the Japanese, we investigated the FOXL2 codon 134 mutation and protein expression of inhibin‐α, bone morphogenetic protein 2 (BMP2) and follistatin (FST) in Japanese patients with granulosa cell tumor (GCT) of the ovary and other ovarian tumors.

Methods

We analyzed 114 tumor tissues from ovarian tumors, including 44 adult‐type and two juvenile‐type GCT of the ovary and 68 ovarian tumors by DNA sequencing. Immunohistochemistry was also performed in the adult and juvenile GCT tissues by immunostaining inhibin‐α, BMP2 and FST.

Results

We found the FOXL2 p.C134W mutation in 27 out of 44 (61.4%) adult‐type GCT of the ovary, but none in other ovarian tumors. Histologically, all of the adult‐type GCT sections were positive for inhibin‐α, and the expression of BMP2 and FST was detected in 14 of 44 (31.8%) and zero of 47 (0%), respectively. No significant differences regarding the diagnosed age, preoperative serum carbohydrate antigen 125 levels, or BMP2 immunopositivity between the FOXL2 p.C134W mutation‐positive and mutation‐negative were found in the adult‐type GCT patients.

Conclusion

Our findings suggest that FOXL2 p.C134W mutation‐positive adult‐type GCT of the ovary may not be common in the Japanese as compared to the previous data.
Heat shock protein 70 is involved in malignant behaviors and chemosensitivities to cisplatin in cervical squamous cell carcinoma cells
Authors: Yoshidomi Keiko , Murakami Akihiro , Yakabe Kazuyuki , Sueoka Kotaro , Nawata Shugo , Sugino Norihiro
Published: April 2014

Aim

Heat shock protein 70 (HSP70) was previously found to be highly expressed in cervical squamous cell carcinoma (SCC) tissues compared with normal tissues by proteomic analyses. The present study investigated the roles of HSP70 in malignant behaviors and chemosensitivity to cisplatin in cervical SCC cells in vitro.

Methods

Effects of HSP70 knockdown on activities of cell migration, cell invasion and cell proliferation, cell cycle status, and apoptosis were examined using siRNA in two human cervical cancer cells (SiHa and SKG II). Furthermore, the effect of HSP70 knockdown on the apoptotic effect by cisplatin was examined.

Results

HSP70 knockdown significantly suppressed activities of cell migration, cell invasion and cell proliferation. The cell cycle was arrested at the S‐ and G2/M‐phases with the increase in apoptosis by HSP70 knockdown. Although cisplatin had no apoptotic effect in the control cell, it showed a dose‐dependent apoptotic effect in the HSP70 knockdown cells in SiHa. In SKG II, 5 μg/mL of cisplatin induced apoptosis, and the apoptotic effect by cisplatin was enhanced by HSP70 knockdown.

Conclusion

It was suggested that HSP70 played functional roles in the progression of uterine cervical SCC, and HSP70 knockdown enhanced chemosensitivities to cisplatin in cervical SCC cells.
Association of functional polymorphisms in FAS and FASLigand genes promoter with pre‐eclampsia
Authors: Salimi Saeedeh , Moudi Bita , Farajian Mashhadi Farzaneh , Tavilani Heidar , Hashemi Mohammad , Zand Hamid , Yaghmaei Minoo
Published: April 2014

Aim

Pre‐eclampsia (PE) is a complex disorder of pregnancy with unknown etiology. FAS‐mediated apoptosis is assumed to prevent the development of PE; therefore FAS and FAS Ligand may be represented as candidate genes involved in PE pathogenesis. In the present study, we evaluated the relation between FAS Ligand A‐670G (rs1800682) and FAS Ligand C‐844T (rs763110) gene polymorphisms with PE in southeast Iran.

Methods

One hundred and twenty‐seven unrelated women with PE and 139 healthy control subjects were genotyped for the FAS A‐670G and FAS Ligand C‐844T polymorphisms by polymerase chain reaction restriction fragment length polymorphism method.

Results

The AA, AG and GG genotype frequency of the FAS A‐670G polymorphism were 21.3%, 53.5% and 25.2% in pre‐eclamptic women and 46.0%, 41.5% and 11.5% in controls and were statistically different (P = 0.0001). The risk of PE was 2.7‐ and 4.7‐fold higher in pregnant women with AG and GG genotypes respectively. Although the frequency TT genotype and T allele of FAS Ligand C‐844T gene polymorphism was higher in the PE group, the differences were not significant.

Conclusion

FAS A‐670G polymorphism is associated with a higher risk for PE. There was no association between FAS Ligand C‐844T polymorphism and PE.
Safety of less aggressive surgery for stage IA1 squamous cell carcinoma of the cervix
Authors: Lee Jung‐Yun , Kim Hee Seung , Kim Kidong , Chung Hyun Hoon , Kim Jae Weon , Park Noh Hyun , Song Yong‐Sang
Published: April 2014

Aim

To determine the risk of extracervical disease in patients with stage IA1 squamous cell carcinoma of the cervix.

Methods

A retrospective analysis was performed of 169 patients who had stage IA1 cervical cancer after conization at Seoul National University Hospital between 1997 and 2007.

Results

During the study period, 18 patients had conization as a definite treatment and 151 underwent subsequent surgery ranging from simple hysterectomy to radical hysterectomy with lymphadenectomy. Of the 151 patients who underwent subsequent surgery following conization, 35 (23.3%) patients underwent a simple hysterectomy, 20 (13.1%) a simple hysterectomy with pelvic lymphadenectomy and 96 (63.6%) radical surgery with lymphadenectomy. No parametrial involvement or lymph node metastasis was noted in any of the patients who underwent parametrial resection and/or lymphadenectomy. Of the 62 patients who had negative resection margins in conization specimens, only one presented with residual tumor in subsequent surgery. One recurrence of the disease was identified in the total sample (169 patients) with a median follow‐up time of 99 months.

Conclusion

The risk of extracervical disease following conization is negligible, even for patients with positive resection margins in conization specimens. A more conservative and less aggressive approach may be possible for this patient subset.
Factors contributing to mortality and morbidity in pregnancy‐associated intracerebral hemorrhage in Japan
Authors: Yoshimatsu Jun , Ikeda Tomoaki , Katsuragi Shinji , Minematsu Kazuo , Toyoda Kazunori , Nagatsuka Kazuyuki , Naritomi Hiroaki , Miyamoto Susumu , Iihara Koji , Yamamoto Haruko , Ohno Yasumasa
Published: April 2014

Aim

The aim of this study was to analyze the causes and outcomes for intracerebral hemorrhage (ICH) occurring during pregnancy and postnatally.

Material and Methods

A nationwide study of pregnancy‐related ICH in Japan was performed. We contacted 1582 facilities to identify women with ICH in pregnancy or postnatally between 1 January 2006 and 31 December 2006. A total of 1012 facilities (70%) responded with completed questionnaires. Risk factors for ICH, neurological features, onset to diagnosis time (O–D time), and obstetric data were recorded.

Results

Thirty‐eight cases of pregnancy‐associated ICH were identified, corresponding to 3.5 per 100 000 deliveries. There were seven maternal deaths, giving a case mortality rate of 18.4%. Pre‐eclampsia was identified in 10 cases (26.3%) and hemolysis elevated liver enzymes and low platelet count (HELLP) syndrome was present in five. There were four cases (10.5%) with Moyamoya disease and seven (18.4%) with arteriovenous malformation. HELLP syndrome and moderately or severely disturbed consciousness at disease onset were significantly associated with a poor outcome (modified Rankin Scale ≥3). Pre‐eclampsia, HELLP syndrome and O–D time >3 h were significantly associated with maternal mortality.

Conclusion

Early diagnosis may prevent maternal death, even in severe cases of pregnancy‐related ICH. However, maternal–fetal care centers do not always have full‐time neurosurgeons or diagnostic imaging tools suitable for diagnosis of ICH. Thus, a network should be established between maternity centers and neurosurgery departments with computed tomography or magnetic resonance imaging available at all times. We recommend transferal of pregnant women with neurological symptoms to a regional facility that is equipped to treat such patients.
Age‐specific cost and public funding of a live birth following assisted reproductive treatment in Japan
Authors: Maeda Eri , Ishihara Osamu , Saito Hidekazu , Kuwahara Akira , Toyokawa Satoshi , Kobayashi Yasuki
Published: April 2014

Aim

The aim of this study was to calculate and assess the cost of assisted reproductive technology (ART) treatment cycles and live‐birth events in Japan in 2010.

Material and Methods

We performed a retrospective analysis of 238 185 ART cycles, registered with the national registry of assisted reproductive treatment during 2010. Costs were calculated, using a decision analysis model.

Results

The average cost per live birth was ¥1 974 000. This varied from ¥1 155 000 in women aged < 30 years to ¥50 189 000 in women aged ≥ 45, which was 29.6 times higher than that of women aged 35–39 years. This rose sharply in the early 40s and upwards. Public funding per live birth was ¥442 000. This was ¥6 118 000 in women aged ≥ 45, 15.4 times higher than that of the 35–39‐year‐old age group.

Conclusions

The costs and public funding of a live birth after ART treatment rises with age due to the lower success rates in older women. It may provide economic background to improve the current subsidy system for ART and to provide practical knowledge about fertility for the general population.
Absence of nonprimate hepacivirus‐related genomes in blood donors seroreactive for hepatitis C virus displaying indeterminate blot patterns
Authors: Levi J. E. , Cabral S. P. N. , Nishiya A. , Ferreira S. , Romano C. M. , Polite M. B. C. , Pereira R. A. A. , Mota M. A. , Kutner J. M.
Published: April 2014

Despite intensive search, no primate homologue to the Hepatitis C Virus (HCV) has ever been found. The search for a zoonotic origin for HCV has been renewed recently when a virus, now known as non‐primate hepacivirus (NPHV), with a high homology to HCV was found in dogs. A variable proportion of anti‐HCV reactive blood donors submitted to the immunoblot (IB) to confirm their HCV status, present indeterminate results. The degree of homology between HCV and NPHV suggests that humans may be infected by NPHV or NPHV‐like viruses. Maximum similarity between NHPV and HCV is observed in the nonstructural regions 3 and 5. Peptides representing both domains are present in IB assays, so it is reasonable to suppose that blood donors harboring such viruses may display cross‐reactivity to the HCV antigenic fractions. Fifty‐nine plasma samples from blood donors found reactive for anti‐HCV and presenting IB indeterminate results were submitted to five distinct PCR reactions under low‐stringency conditions, employing primers targeting GBV‐C 5'UTR and NS3, Flavivirus‐genus NS5 and NPHV 5'UTR and NS3. No amplification was obtained with all primer pairs tested except for five samples that amplified both 5'UTR and NS3 fragments from GBV‐C. Unbiased next‐generation sequencing may prove or rule out the existence of HCV‐related viruses in IB indeterminate samples.
Immediate Effect of Passive Smoking on Microcirculatory Flow
Authors: Henriksson Peter , Lu Qing , Diczfalusy Ulf , Freyschuss Anna
Published: April 2014

Objective

Exposure to SHS, as by passive smoking, seems to increase the incidence of cardiovascular events. It has been shown that active smoking of a single cigarette causes an immediate and significant decrease in microcirculatory blood flow velocity, whereas the acute effects of exposure to SHS on microcirculatory flow have as yet not been demonstrated.

Methods

Healthy nonsmoking volunteers of both genders were studied during acute exposure to SHS of two cigarettes burning up to 10 minutes. Microvessels were examined by in vivo vital capillaroscopy (Capiflow®), allowing continuous assessment of CBV.

Results

CBV decreased from 514 mm/sec (CI 383–646) at baseline to 306 mm/sec (CI 191–420) at end of SHS exposure with a further decrease to a nadir of 240 mm/sec (CI 155–325) four minutes after the end of this exposure (p < 0.0001; ANOVA).

Conclusions

The result of this study shows that passive inhalation of secondhand cigarette smoke induces an immediate and prolonged marked reduction in CBV in nonsmoking healthy volunteers.
InnateandLearned: Carey, Mad Dog Nativism, and the Poverty of Stimuli and Analogies (Yet Again)
Authors: REY GEORGES
Published: April 2014

In her recent (2009) book,The Origins of Concepts, Susan Carey argues that what she calls ‘Quinean Bootstrapping’ and processes of analogy in children show that the expressive power of a mind can be increased in ways that refute Jerry Fodor's (1975, 2008) ‘Mad Dog’ view that all concepts are innate. I argue that it is doubtful any evidence about themanifestationof concepts in children will bear upon thelogico‐semanticissues ofexpressive power. Analogy and bootstrapping may be ways to bring about the former, but only by presupposing the very expressive powers Carey is claiming they explain. Analogies must beunderstood, and bootstrapping involves confirmation of hypotheses alreadyexpressible; otherwise they can't select among an infinitude of hypotheses compatible with the finite data the child has encountered, a fact rendered vivid by Goodman's ‘grue’ paradox and Chomsky's poverty of stimulus argument. The problems have special application to minds, since there is no reason to expect a child's concepts to be ‘projectible’ or to correspond to mind‐independent natural kinds. I conclude with an ecumenical view that concepts are reasonably regarded asbothinnate and often learned, and that what is learned can in fact increase what really concerns Carey, thefunctioning psychological expressive powerof the child, even if it leaves untouched what concerns Fodor,the semantic expressive power. Less ecumenically: maybe Fodor (2008) miscast the debate, and the real issue that bothers people concerns not nativism, but an issue on which Carey and Fodor surprisingly agree, his conceptualAtomism, or the view that all mono‐morphemic concepts are primitive and unanalyzable. The issue deserves further discussion independently of Mad‐doggery.
Making rivers governable: Ecological monitoring, power and scale
Authors: Tadaki Marc , Brierley Gary , Fuller Ian C.
Published: April 2014

The recently proposed centralisation of freshwater monitoring networks reveals how rivers themselves are being disciplined by the nature of the national monitoring apparatus. Freshwater monitoring is being reimagined and re‐practiced through new rationalities relating to international economic branding and particular national methodological capabilities built around reductionist monitoring frameworks. While a reductionist scaling may serve certain important (and powerful) disciplinary and discursive interests, we argue that the biophysical basis for reductionist scaling is flawed and that a national monitoring framework should work to enable place‐based understandings of river systems, which might be related to the national scale in more biophysically meaningful, institutionally innovative and democratic ways.
Who's in and who's out? Inclusion and exclusion in Canterbury's freshwater governance
Authors: Nissen Sylvia
Published: April 2014

The question of who is included, or who is excluded, from environmental governance arrangements is at the heart of debates of institutional legitimacy. The recent redefinition of representation as a claim to ‘speak for’ another provides an opportunity to re‐examine the inclusiveness of environmental governance arrangements. This article builds on these developments by empirically evaluating the inclusiveness of three representative claims embedded in freshwater governance in Canterbury since 2002. The contribution argues that accounts of environmental governance must consider implicit forms of representation that can exclude or marginalise and raises some caveats relating to expansion of network governance.
Impact of sevoflurane anesthesia on brain oxygenation in children younger than 2 years
Authors: Rhondali Ossam , Juhel Simon , Mathews Sylvain , Cellier Quentin , Desgranges François‐Pierrick , Mahr Aurélie , De Queiroz Mathilde , Pouyau Agnès , Rhzioual‐Berrada Khalid , Chassard Dominique
Published: April 2014

Objective/Aim

To assess the impact of sevoflurane and anesthesia‐induced hypotension on brain oxygenation in children younger than 2 years.

Background

Inhalational induction with sevoflurane is the most commonly used technique in young children. However, the effect of sevoflurane on cerebral perfusion has been only studied in adults and children older than 1 year. The purpose of this study was to assess the impact of sevoflurane anesthesia on brain oxygenation in neonates and infants, using near‐infrared spectroscopy.

Methods

Children younger than 2 years, ASA I or II, scheduled for abdominal or orthopedic surgery were included. Induction of anesthesia was started by sevoflurane 6% and maintained with an expired fraction of sevoflurane 3%. Mechanical ventilation was adjusted to maintain an endtidal CO2 around 39 mmHg. Brain oxygenation was assessed measuring regional cerebral saturation of oxygen (rSO2c), measured by NIRS while awake and 15 min after induction, under anesthesia. Mean arterial pressure (MAP) variation was recorded.

Results

Hundred and ninety‐five children were included. Anesthesia induced a significant decrease in MAP (−27%). rSO2c increased significantly after induction (+18%). Using children age for subgroup analysis, we found that despite MAP reduction, rSO2c increase was significant but smaller in children ≤6 months than in children >6 months (≤6 months: rSO2c = +13%, >6 months: rSO2c = +22%; P < 0.0001). Interindividual comparison showed that, during anesthesia at steady‐state with comparable CMRO2, rSO2c values were significantly higher when MAP was above 36 mmHg. And the higher the absolute MAP value during anesthesia was, the higher the rSO2c was. We observed a rSO2c variation ≤0 in 21 patients among the 195 studied, and the majority of these patients were younger than 6 months (n = 19). No increase or decrease of rSO2c during anesthesia despite reduction of CMRO2 can be explained by a reduction of oxygen supply. Using the ROC curves, we determined that the threshold value of MAP under anesthesia, associated with rSO2c variation ≤0%, was 39 mmHg in all the studied population (AUC: 0.90 ± 0.02; P < 0.001). In children younger than 6 months, this value of MAP was 33 mmHg, and 43 mmHg in children older than 6 months.

Conclusion

Despite a significant decrease of MAP, 1 MAC of sevoflurane induced a significant increase in regional brain oxygenation. But subgroup analysis showed that MAP decrease had a greater impact on brain oxygenation, in children younger than 6 months. According to our results, MAP value during anesthesia should not go under 33 mmHg in children ≤6 months and 43 mmHg in children >6 months, as further changes in MAP, PaCO2 or hemoglobin during anesthesia may be poorly tolerated by the brain.
Mesophyll cells of C4 plants have fewer chloroplasts than those of closely related C3 plants
Authors: STATA MATT , SAGE TAMMY L. , RENNIE TROY D. , KHOSHRAVESH ROXANA , SULTMANIS STEFANIE , KHAIKIN YANNAY , LUDWIG MARTHA , SAGE ROWAN F.
Published: April 2014

The evolution of C4 photosynthesis from C3 ancestors eliminates ribulose bisphosphate carboxylation in the mesophyll (M) cell chloroplast while activating phosphoenolpyruvate (PEP) carboxylation in the cytosol. These changes may lead to fewer chloroplasts and different chloroplast positioning within M cells. To evaluate these possibilities, we compared chloroplast number, size and position in M cells of closely related C3, C3–C4 intermediate and C4 species from 12 lineages of C4 evolution. All C3 species had more chloroplasts per M cell area than their C4 relatives in high‐light growth conditions. C3 species also had higher chloroplast coverage of the M cell periphery than C4 species, particularly opposite intercellular air spaces. In M cells from 10 of the 12 C4 lineages, a greater fraction of the chloroplast envelope was pulled away from the plasmalemma in the C4 species than their C3 relatives. C3–C4 intermediate species generally exhibited similar patterns as their C3 relatives. We interpret these results to reflect adaptive shifts that facilitate efficient C4 function by enhancing diffusive access to the site of primary carbon fixation in the cytosol. Fewer chloroplasts in C4 M cells would also reduce shading of the bundle sheath chloroplasts, which also generate energy required by C4 photosynthesis.
Alien interference: disruption of infochemical networks by invasive insect herbivores
Authors: DESURMONT GAYLORD A. , HARVEY JEFF , VAN DAM NICOLE M. , CRISTESCU SIMONA M. , SCHIESTL FLORIAN P. , COZZOLINO SALVATORE , ANDERSON PETER , LARSSON MATTIAS C. , KINDLMANN PAVEL , DANNER HOLGER , TURLINGS TED C.J.
Published: April 2014

Insect herbivores trigger various biochemical changes in plants, and as a consequence, affect other organisms that are associated with these plants. Such plant‐mediated indirect effects often involve herbivore‐induced plant volatiles (HIPVs) that can be used as cues for foraging herbivores and their natural enemies, and are also known to affect pollinator attraction. In tightly co‐evolved systems, the different trophic levels are expected to display adaptive response to changes in HIPVs caused by native herbivores. But what if a new herbivore invades such a system? Current literature suggests that exotic herbivores have the potential to affect HIPV production, and that plant responses to novel herbivores are likely to depend on phylogenetic relatedness between the invader and the native species. Here we review the different ways exotic herbivores can disrupt chemically mediated interactions between plants and the key users of HIPVs: herbivores, pollinators, and members of the third (i.e. predators and parasitoids) and fourth (i.e. hyperparasitoids) trophic levels. Current theory on insect invasions needs to consider that disruptive effects of invaders on infochemical networks can have a short‐term impact on the population dynamics of native insects and plants, as well as exerting potentially negative consequences for the functioning of native ecosystems.
Non‐specific phospholipase C5 and diacylglycerol promote lateral root development under mild salt stress in Arabidopsis
Authors: PETERS CARLOTTA , KIM SANG‐CHUL , DEVAIAH SHIVAKUMAR , LI MAOYIN , WANG XUEMIN
Published: April 2014

Developing a robust root system is crucial to plant survival and competition for soil resources. Here we report that the non‐specific phospholipase C5 (NPC5) and its derived lipid mediator diacylglycerol (DAG) mediate lateral root (LR) development during salt stress in Arabidopsis thaliana. T‐DNA knockout mutant npc5‐1 produced few to no LR under mild NaCl stress, whereas overexpression of NPC5 increased LR number. Roots of npc5‐1 contained a lower level of DAG than wild type, whereas NPC5 overexpressor exhibited an increase in DAG level. Application of DAG, but not phosphatidic acid, fully restored LR growth of npc5‐1 to that of wild type under NaCl stress. NPC5 expression was significantly induced in Arabidopsis seedlings treated with NaCl. Npc5‐1 was less responsive to auxin‐mediated root growth than the wild type. These results indicate that NPC5 mediates LR development in response to salt stress and suggest that DAG functions as a lipid mediator in the stress signalling.
Effects of elevated [CO2] on maize defence against mycotoxigenic Fusarium verticillioides
Authors: VAUGHAN MARTHA M. , HUFFAKER ALISA , SCHMELZ ERIC A. , DAFOE NICOLE J. , CHRISTENSEN SHAWN , SIMS JAMES , MARTINS VITOR F. , SWERBILOW JAY , ROMERO MARITZA , ALBORN HANS T. , ALLEN LEON HARTWELL , TEAL PETER E. A.
Published: April 2014

Maize is by quantity the most important C4 cereal crop; however, future climate changes are expected to increase maize susceptibility to mycotoxigenic fungal pathogens and reduce productivity. While rising atmospheric [CO2] is a driving force behind the warmer temperatures and drought, which aggravate fungal disease and mycotoxin accumulation, our understanding of how elevated [CO2] will effect maize defences against such pathogens is limited. Here we report that elevated [CO2] increases maize susceptibility to Fusarium verticillioides proliferation, while mycotoxin levels are unaltered. Fumonisin production is not proportional to the increase in F. verticillioides biomass, and the amount of fumonisin produced per unit pathogen is reduced at elevated [CO2]. Following F. verticillioides stalk inoculation, the accumulation of sugars, free fatty acids, lipoxygenase (LOX) transcripts, phytohormones and downstream phytoalexins is dampened in maize grown at elevated [CO2]. The attenuation of maize 13‐LOXs and jasmonic acid production correlates with reduced terpenoid phytoalexins and increased susceptibility. Furthermore, the attenuated induction of 9‐LOXs, which have been suggested to stimulate mycotoxin biosynthesis, is consistent with reduced fumonisin per unit fungal biomass at elevated [CO2]. Our findings suggest that elevated [CO2] will compromise maize LOX‐dependent signalling, which will influence the interactions between maize and mycotoxigenic fungi.
Are solar UV‐B‐ and UV‐A‐dependent gene expression and metabolite accumulation in Arabidopsis mediated by the stress response regulator RADICAL‐INDUCED CELL DEATH1?
Authors: MORALES LUIS O. , BROSCHÉ MIKAEL , VAINONEN JULIA P. , SIPARI NINA , LINDFORS ANDERS V. , STRID ÅKE , APHALO PEDRO J.
Published: April 2014

Wavelengths in the ultraviolet (UV) region of the solar spectrum, UV‐B (280–315 nm) and UV‐A (315–400 nm), are key environmental signals modifying several aspects of plant physiology. Despite significant advances in the understanding of plant responses to UV‐B and the identification of signalling components involved, there is limited information on the molecular mechanisms that control UV‐B signalling in plants under natural sunlight. Here, we aimed to corroborate the previous suggested role for RADICAL‐INDUCED CELL DEATH1 (RCD1) in UV‐B signalling under full spectrum sunlight. Wild‐type Arabidopsis thaliana and the rcd1‐1 mutant were used in an experimental design outdoors where UV‐B and UV‐A irradiances were manipulated using plastic films, and gene expression, PYRIDOXINE BIOSYNTHESIS1 (PDX1) accumulation and metabolite profiles were analysed in the leaves. At the level of transcription, RCD1 was not directly involved in the solar UV‐B regulation of genes with functions in UV acclimation, hormone signalling and stress‐related markers. Furthermore, RCD1 had no role on PDX1 accumulation but modulated the UV‐B induction of flavonoid accumulation in leaves of Arabidopsis exposed to solar UV. We conclude that RCD1 does not play an active role in UV‐B signalling but rather modulates UV‐B responses under full spectrum sunlight.