bluuebunny/crossref_metadata_2025 huggingface dataset:
C5andC7intramolecular hydrogen bonds stabilize the structure ofN-pyrazinoyl-gabapentin (Pyr-Gpn-OH)
Authors: Wani Naiem Ahmad , Gupta Vivek Kumar , Kant Rajni , Aravinda Subrayashastry , Rai Rajkishor
Published: September 2013

2-{1-[(Pyrazin-2-ylformamido)methyl]cyclohexyl}acetic acid (Pyr-Gpn-OH), C14H19N3O3, is an N-protected derivative of gabapentin (Gpn). The compound crystallizes in the triclinic space groupP\overline{1} and the molecular conformation is stabilized by intramolecular five- (C5) and seven-membered (C7) hydrogen-bonded rings. The packing of the molecules reveals intermolecular O—H...O and C—H...N hydrogen bonds, together with π–π interactions.
Solvent-mediated pseudo-quadruple hydrogen-bond motifs in three lamotrigine–carboxylic acid complexes
Authors: Sridhar Balasubramanian , Nanubolu Jagadeesh Babu , Ravikumar Krishnan
Published: September 2013

Lamotrigine, an antiepileptic drug, has been complexed with three aromatic carboxylic acids. All three compounds crystallize with the inclusion ofN,N-dimethylformamide (DMF) solvent,viz.lamotriginium [3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazin-2-ium] 4-iodobenzoateN,N-dimethylformamide monosolvate, C9H8Cl2N5+·C7H4IO2−·C3H7NO, (I), lamotriginium 4-methylbenzoateN,N-dimethylformamide monosolvate, C9H7Cl2N5+·C8H8O2−·C3H7NO, (II), and lamotriginium 3,5-dinitro-2-hydroxybenzoateN,N-dimethylformamide monosolvate, C9H8Cl2N5+·C7H3N2O7−·C3H7NO, (III). In all three structures, proton transfer takes place from the acid to the lamotrigine molecule. However, in (I) and (II), the acidic H atom is disordered over two sites and there is only partial transfer of the H atom from O to N. In (III), the corresponding H atom is ordered and complete proton transfer has occurred. Lamotrigine–lamotrigine, lamotrigine–acid and lamotrigine–solvent interactions are observed in all three structures and they thereby exhibit isostructurality. The DMF solvent extends the lamotrigine–lamotrigine dimers into a pseudo-quadruple hydrogen-bonding motif.
The role of social environment on parental care: offspring benefit more from the presence of female than male helpers
Authors: Brouwer Lyanne , van de Pol Martijn , Cockburn Andrew
Published: September 2013

Investment in offspring depends on the costs and benefits to the carer, which can vary with sex and social status. Investment also depends on the effort of others by allowing for compensation (load‐lightening), with biparental care studies showing that this depends on the state and type of the other carer. By contrast, studies on cooperative breeders have solely focussed on the effects of group size rather than its composition (i.e. social environment).

Here we propose and provide the first test of the ‘Social Environment’ hypothesis, that is, how the characteristics (here the sex) of other helpers present in the group affect parental care and how this in turn affects offspring fitness in cooperatively breeding red‐winged fairy‐wrens (Malurus elegans).

Breeders provisioned nestlings at a higher rate than helpers, but there was no sex difference in provisioning rate. Compensation to increasing group size varied little with sex and status, but strongly depended on social environment. All group members reduced their provisioning rates in response to an increasing number of male (load‐lightening), but not female helpers (additive care).

As a result, nestlings received more food and grew faster in the presence of female helpers. The increased nestling growth did convey a fitness advantage due to a higher post‐fledging survival to adulthood.

Our study provides the first evidence that parental care can depend on social environment. This could be an important overlooked aspect to explain variation in parental care in cooperative breeders in general and in particular the enormous variation between the sexes, which we reveal in a literature overview.
Expression analysis and immunohistochemical localization of putative tumor suppressor QM homologue from the cabbage butterfly, Pieris rapae
Authors: Park Bo Mi , Patnaik Bharat Bhusan , Oh Seunghan , Kim Dong Hyun , Jo Yong Hun , Jeong Heon Cheon , Lee Yong Seok , Ko Kisung , Kim Iksoo , Han Yeon Soo
Published: September 2013

The tumor suppressor, QM has been cloned and characterized from eukaryotic organisms including humans, vertebrates, invertebrates, plants and yeast. However, no study on Pieris rapae QM (PrQM) has been reported to date. In this study, cDNA encoding a putative QM protein (PrQM) was obtained from expressed sequence tags (ESTs) of the Pieris rapae cDNA library. Phylogenetic analysis of PrQM showed high similarity of amino acid sequence with other putative homologues identified from Heliothis virescens (95%), Bombyx mori (92%), Plutella xylostella (92%), Drosophila melanogaster (89%) and Polyrhachis vicina (85%), indicating that QM is highly conserved among insects. Semi‐quantitative PCR datasets revealed that PrQM transcripts are highly expressed in head, silk gland, integument and fat body, with pronounced expression observed during the egg stage. The coding region of the PrQM gene was cloned into the pET28 (+) expression vector and the recombinant protein purified by His‐tag affinity chromatography was used for antibody production. Western blotting with the anti‐PrQM antibody detected a single band corresponding to the expected molecular weight of both endogenous (26 kDa) and recombinant (29 kDa) PrQM. Furthermore, immunohistochemical and confocal microscopic analysis with the anti‐PrQM antibody showed that the QM gene is highly expressed in the cytoplasm of fat body, gut and Malpighian tubules in virus‐uninfected control larvae, but down‐regulated at 4 days post Pieris rapae granulovirus (PiraGV) infection. These data show that PrQM is negatively regulated upon virus infection and suggests a putative immunomodulatory function.
Evolutionary engineering of a glycerol‐3‐phosphate dehydrogenase‐negative, acetate‐reducing Saccharomyces cerevisiae strain enables anaerobic growth at high glucose concentrations
Authors: Guadalupe‐Medina Víctor , Metz Benjamin , Oud Bart , van Der Graaf Charlotte M. , Mans Robert , Pronk Jack T. , van Maris Antonius J. A.
Published: September 2013

Glycerol production by Saccharomyces cerevisiae, which is required for redox‐cofactor balancing in anaerobic cultures, causes yield reduction in industrial bioethanol production. Recently, glycerol formation in anaerobic S. cerevisiae cultures was eliminated by expressing Escherichia coli (acetylating) acetaldehyde dehydrogenase (encoded by mhpF) and simultaneously deleting the GPD1 and GPD2 genes encoding glycerol‐3‐phosphate dehydrogenase, thus coupling NADH reoxidation to reduction of acetate to ethanol. Gpd– strains are, however, sensitive to high sugar concentrations, which complicates industrial implementation of this metabolic engineering concept. In this study, laboratory evolution was used to improve osmotolerance of a Gpd– mhpF‐expressing S. cerevisiae strain. Serial batch cultivation at increasing osmotic pressure enabled isolation of an evolved strain that grew anaerobically at 1 M glucose, at a specific growth rate of 0.12 h−1. The evolved strain produced glycerol at low concentrations (0.64 ± 0.33 g l−1). However, these glycerol concentrations were below 10% of those observed with a Gpd+ reference strain. Consequently, the ethanol yield on sugar increased from 79% of the theoretical maximum in the reference strain to 92% for the evolved strains. Genetic analysis indicated that osmotolerance under aerobic conditions required a single dominant chromosomal mutation, and one further mutation in the plasmid‐borne mhpF gene for anaerobic growth.
In vivo analysis of dermal and systemic absorption of silver nanoparticles through healthy human skin
Authors: George Robert , Merten Steve , Wang Tim T , Kennedy Peter , Maitz Peter
Published: September 2013

Background

Research into nanoparticles has increased markedly during the last decade, especially in light of their potential diagnostic and therapeutic use. While silver has been used since ancient times, a detailed understanding of the kinetics of its dermal absorption requires further study. Thus far, only in vitro and animal models have been used to analyse the absorption characteristics of nanocrystalline silver particles and no in vivo study using intact human skin has demonstrated silver absorption.

Method

A nanocrystalline silver dressing was applied to a sample of 16 healthy patients with normal intact skin approximately 5 days prior to surgery. The treated skin samples, removed as surgical waste, were then analysed with a tissue mass spectrometry, light microscopy, scanning electron microscopy (SEM) and an X‐ray diffusion spectrography (XRD). Silver serum levels were also analysed before and after application of the dressing.

Results

A limited amount of silver penetration could be noted even with light microscopy. However, definitive analysis required SEM and XRD confirmation. With SEM, metallic particles could be seen within the dermis. XRD confirmed that these were silver species, possible in oxide form. Furthermore, silver clusters as large as 750 nm could be discerned. In addition, there was no demonstrable rise in serum silver levels post‐treatment with the silver dressing.

Conclusion

Our results suggest that silver nanoparticles are able to penetrate intact human skin in vivo beyond the stratum corneum and can be found as deep as the reticular dermis. The absorbed silver might be in silver oxide form and the silver species appear to form sizeable clusters once absorbed across the epidermis. However, despite silver deposition into the dermis, the silver nanoparticles did not reach systemic circulation and should thus have no end organ consequences.
Prospective randomized double‐blind multicentre phase II study comparing gemcitabine and cisplatin plus sorafenib chemotherapy with gemcitabine and cisplatin plus placebo in locally advanced and/or metastasized urothelial cancer: SUSE (AUO‐AB 31/05)
Authors: Krege Susanne , Rexer Heidrun , vom Dorp Frank , de Geeter Patrick , Klotz Theodor , Retz Margitte , Heidenreich Axel , Kühn Michael , Kamradt Joern , Feyerabend Susan , Wülfing Christian , Zastrow Stefan , Albers Peter , Hakenberg Oliver , Roigas Jan , Fenner Martin , Heinzer Hans , Schrader Mark
Published: September 2013

Objective

To evaluate the efficacy and safety of gemcitabine and cisplatin in combination with sorafenib, a tyrosine‐kinase inhibitor, compared with chemotherapy alone as first‐line treatment in advanced urothelial cancer.

Patients and Methods

The study was a randomized phase II trial. Its primary aim was to show an improvement in progression‐free survival (PFS) of 4.5 months by adding sorafenib to conventional chemotherapy. Secondary objectives were objective response rate (ORR), overall survival (OS) and toxicity.

The patients included in the trial had histologically confirmed locally advanced and/or metastatic urothelial cancer of the bladder or upper urinary tract.

Chemotherapy with gemcitabine (1250 mg/qm on days 1 and 8) and cisplatin (70 mg/qm on day 1) repeated every 21 days, was administered to all patients in a double‐blind randomization of additional sorafenib (400 mg twice daily) vs placebo (two tablets twice daily) on days 3–21.

Treatment continued until progression or unacceptable toxicity, the maximum number of cycles was limited to eight. The response assessment was repeated after every two cycles.

Results

Between October 2006 and October 2010, 98 of 132 planned patients were recruited. Nine patients were ineligible. The final analysis included 40 patients in the sorafenib and 49 patients in the placebo arm.

There were no significant differences between the two arms concerning ORR (sorafenib: complete response [CR] 12.5%, partial response [PR] 40%; placebo: CR 12%, PR 35%), median PFS (sorafenib: 6.3 months, placebo: 6.1 months) or OS (sorafenib: 11.3 months, placebo: 10.6 months).

Toxicity was moderately higher in the sorafenib arm. Diarrrhoea occurred significantly more often in the sorafenib arm and hand‐foot syndrome occurred only in the sorafenib arm.

The study was closed prematurely because of slow recruitment.

Conclusion

Although the addition of sorafenib to standard chemotherapy showed acceptable toxicity, the trial failed to show a 4.5 months improvement in PFS.
Bladder outlet obstruction (BOO) in men with castration‐resistant prostate cancer
Authors: Rom Maximilian , Waldert Matthias , Schatzl Georg , Swietek Natalia , Shariat Shahrokh F. , Klatte Tobias
Published: September 2013

Objective

To evaluate the frequency of bladder outlet obstruction (BOO) and detrusor overactivity (DO) in patients with castration‐resistant prostate cancer (CRPC) and lower urinary tract symptoms (LUTS).

Patients and Methods

Our prospective urodynamics database was queried.

Inclusion criteria were CRPC and an International Prostate Symptom Score (IPSS) ≥ 20.

Exclusion criteria were previous local therapy to the prostate gland, known urethral stricture disease, and a neurological component of LUTS.

Twenty‐one patients were identified.

Urodynamic findings were analysed and compared with those of a matched cohort of 42 patients with benign prostatic enlargement (BPE).

Results

The median age of patients in the CRPC group was 74 years, and the median prostate‐specific antigen (PSA) level at the time of the urodynamic study was 90 ng/mL.

According to the BOO index, three patients (14%) were obstructed, three were equivocally obstructed (14%) and 15 were unobstructed.

DO was seen in 12 patients (57%).

Compared with the BPE group, patients with CRPC had lower cystometric bladder capacities (P = 0.003), were less likely to have BOO (14 vs 43%, P = 0.009) and more likely to have DO (57 vs 29%, P = 0.028).

Conclusions

This study generates the hypothesis that only a minority of CRPC patients with LUTS have BOO, and that more than half of patients have DO.

LUTS in CRPC may therefore be seldom attributable to BOO, but are, at least in part, related to DO and reduced cystometric capacity.

A urodynamic investigation may be necessary before palliative transurethral resection of the prostate to select appropriate candidates.

Larger prospective studies are needed to confirm our findings.
Impact of peri‐operative blood transfusion on the outcomes of patients undergoing radical cystectomy for urothelial carcinoma of the bladder
Authors: Kluth Luis A. , Xylinas Evanguelos , Rieken Malte , El Ghouayel Maya , Sun Maxine , Karakiewicz Pierre I. , Lotan Yair , Chun Felix K.‐H. , Boorjian Stephen A. , Lee Richard K. , Briganti Alberto , Rouprêt Morgan , Fisch Margit , Scherr Douglas S. , Shariat Shahrokh F.
Published: September 2013

Objective

To determine the association between peri‐operative blood transfusion (PBT) and oncological outcomes in a large multi‐institutional cohort of patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB).

Patients and Methods

We conducted a retrospective analysis of 2895 patients treated with RC for UCB.

Univariable and multivariable Cox regression models were used to analyse the effect of PBT administration on disease recurrence, cancer‐specific mortality, and any‐cause mortality.

Results

Patients' median (interquartile range [IQR]) age was 67 (60, 73) years and the median (IQR) follow‐up was 36.1 (15, 84) months.

Patients who received PBT were more likely to have advanced disease (P < 0.001), high grade tumours (P = 0.047) and nodal metastasis (P = 0.004).

PBT was associated with a higher risk of disease recurrence (P = 0.003), cancer‐specific mortality (P = 0.017), and any‐cause mortality (P = 0.010) in univariable, but not multivariable, analyses (P > 0.05).

In multivariable analyses, pathological tumour stage, pathological nodal stage, soft tissue surgical margin, lymphovascular invasion and administration of adjuvant chemotherapy were independent predictors of disease recurrence, cancer‐specific mortality and any‐cause mortality (all P values <0.002).

Conclusions

Patients with UCB who underwent RC and received PBT had a greater risk of disease recurrence, cancer‐specific mortality and any‐cause mortality in univariable, but not multivariable, analysis.

Although the greater need for PBT with more advanced disease is probably caused by a number of factors, including surgical and cancer‐related factors, the present analysis showed that the disease characteristics rather than need for PBT led to worse outcomes.
Validation of pretreatment neutrophil–lymphocyte ratio as a prognostic factor in a European cohort of patients with upper tract urothelial carcinoma
Authors: Dalpiaz Orietta , Ehrlich Georg C. , Mannweiler Sebastian , Hernández Jessica M.Martín , Gerger Armin , Stojakovic Tatjana , Pummer Karl , Zigeuner Richard , Pichler Martin , Hutterer Georg C.
Published: September 2013

Objective

To investigate the potential prognostic significance of the neutrophil–lymphocyte ratio (NLR) in a large European cohort of patients with upper urinary tract urothelial cell carcinoma (UUT‐UCC).

Patients and Methods

We retrospectively evaluated data from 202 consecutive patients with non‐metastatic upper urinary tract urothelial cell carcinoma (UUT‐UCC), who underwent surgery between 1990 and 2012 at a single tertiary academic centre.

Patients' cancer‐specific survival (CSS) and overall survival (OS) were assessed using the Kaplan–Meier method.

To evaluate the independent prognostic significance of the NLR, multivariate proportional Cox regression models were applied for both endpoints.

Results

A higher NLR was significantly associated with shorter CSS (P = 0.002, log‐rank test), as well as with shorter OS (P < 0.001, log‐rank test).

Multivariate analysis identified a high NLR as an independent prognostic factor for patients' CSS (hazard ratio 2.72, 95% CI 1.25–5.93, P = 0.012), and OS (hazard ratio 2.48, 95% CI 1.31–4.70, P = 0.005).

Conclusions

In the present cohort, patients with a high preoperative NLR had higher cancer‐specific and overall mortality after radical surgery for UUT‐UCC, compared with those with a low preoperative NLR.

This easily identifiable laboratory measure should be considered as an additional prognostic factor in UUT‐UCC in future.
Cytoreductive nephrectomy in patients with metastatic non‐clear‐cell renal cell carcinoma (RCC)
Authors: Aizer Ayal A. , Urun Yuksel , McKay Rana R. , Kibel Adam S. , Nguyen Paul L. , Choueiri Toni K.
Published: September 2013

Objective

To determine whether patients with metastatic non‐clear‐cell renal cell carcinoma (RCC) benefit from cytoreductive nephrectomy (CN).

Patients and Methods

We used the Surveillance, Epidemiology, and End Results (SEER) programme to identify a population‐based sample of 4914 patients diagnosed with metastatic RCC between 2000 and 2009.

Of the 4914 patients, 591 had non‐clear‐cell histology.

The median follow‐up was 20 months.

The primary outcome measure was RCC‐specific mortality.

Results

Approximately 64% of patients underwent CN.

Patients with non‐clear‐cell histology who underwent CN had lower RCC‐specific and all‐cause mortality than those who did not (P < 0.001 in both cases).

After adjustment for age, gender, race, marital status, year of diagnosis, geographical location and histology, the associations between CN and lower RCC‐specific mortality (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.48–0.80, P < 0.001) and between CN and all‐cause mortality (HR 0.45, 95% CI 0.37–0.55, P < 0.001) remained highly significant.

Among patients diagnosed between 2006 and 2009 (targeted therapy era), the results remained unchanged (HR 0.50, 95% CI 0.34–0.72, P < 0.001 and HR 0.43, 95% CI 0.31–0.59, P < 0.001, respectively).

An interaction model found lower all‐cause mortality for all histologies after CN.

Conclusions

Patients from the SEER programme with metastatic non‐clear‐cell RCC, including those treated in the targeted therapy era, appear to derive a survival benefit from CN, an association which remained significant regardless of histological subtype.

This observation suggests that CN should remain standard in patients with advanced RCC who are deemed to be surgical candidates.
Recombinant human soluble thrombomodulin prevents peripheral HMGB1‐dependent hyperalgesia in rats
Authors: Tanaka Junichi , Seki Yukari , Ishikura Hiroyasu , Tsubota Maho , Sekiguchi Fumiko , Yamaguchi Kaoru , Murai Akira , Umemura Takehiro , Kawabata Atsufumi
Published: September 2013

Background and Purpose

High‐mobility group box 1 (HMGB1), a nuclear protein, is actively or passively released during inflammation. Recombinant human soluble thrombomodulin (rhsTM), a medicine for treatment of disseminated intravascular coagulation (DIC), sequesters HMGB1 and promotes its degradation. Given evidence for involvement of HMGB1 in pain signalling, we determined if peripheral HMGB1 causes hyperalgesia, and then asked if rhsTM modulates the HMGB1‐dependent hyperalgesia.

Experimental Approach

Mechanical nociceptive threshold and swelling in rat hindpaw were determined by the paw pressure test and by measuring paw thickness, respectively, and HMGB1 levels in rat hindpaw plantar tissue, dorsal root ganglion (DRG) and serum were determined by Western blotting or elisa.

Key Results

Intraplantar (i.pl.) administration of HMGB1 rapidly evoked paw swelling and gradually caused hyperalgesia in rats. Systemic administration of rhsTM abolished HMGB1‐induced hyperalgesia, and partially blocked paw swelling. LPS, administered i.pl., rapidly produced mild paw swelling, and gradually caused hyperalgesia. The anti‐HMGB1 neutralizing antibody abolished LPS‐induced hyperalgesia, but partially inhibited paw swelling. rhsTM at a high dose, 10 mg kg−1, prevented both hyperalgesia and paw swelling caused by LPS. In contrast, rhsTM at low doses, 0.001–1 mg kg−1, abolished the LPS‐induced hyperalgesia, but not paw swelling. HMGB1 levels greatly decreased in the hindpaw, but not DRG. Serum HMGB1 tended to increase after i.pl. LPS in rats pretreated with vehicle, but not rhsTM.

Conclusion and Implications

These data suggest that peripheral HMGB1 causes hyperalgesia, and that rhsTM abolishes HMGB1‐dependent hyperalgesia, providing novel evidence for therapeutic usefulness of rhsTM as an analgesic.
Involvement of homologous recombination in the synergism between cisplatin and poly (ADP‐ribose) polymerase inhibition
Authors: Sakogawa Kenji , Aoki Yoshiro , Misumi Keizo , Hamai Yoichi , Emi Manabu , Hihara Jun , Shi Lin , Kono Kazuteru , Horikoshi Yasunori , Sun Jiying , Ikura Tsuyoshi , Okada Morihito , Tashiro Satoshi
Published: September 2013

Poly (ADP‐ribose) polymerase (PARP) plays a critical role in responding to DNA damage, by activating DNA repair pathways responsible for cellular survival. Inhibition of PARP is used to treat certain solid cancers, such as breast and ovarian cancers. However, its effectiveness with other solid cancers, such as esophageal squamous cell carcinoma (ESCC), has not been clarified. We evaluated the effects of PARP inhibition on the survival of human esophageal cancer cells, with a special focus on the induction and repair of DNA double‐strand breaks. The effects were monitored by colony formation assays and DNA damage responses, with immunofluorescence staining of γH2AX and RAD51. We found that PARP inhibition synergized with cisplatin, and the cells were highly sensitive, in a similar manner to the combination of cisplatin and 5‐fluorouracil (5‐FU). Comparable increases in RAD51 foci formation were observed after each combined treatment with cisplatin and either 3‐aminobenzamide (3‐AB) or 5‐FU in three human esophageal cancer cell lines, TE11, TE14, and TE15. In addition, decreasing the amount of RAD51 by RNA interference rendered the TE11 cells even more hypersensitive to these treatments. Our findings suggested that the homologous recombinational repair pathway may be involved in the synergism between cisplatin and either 3‐AB or 5‐FU, and that 3‐AB and 5‐FU may similarly modify the cisplatin‐induced DNA damage to types requiring the recruitment of RAD51 proteins for their repair. Understanding these mechanisms could be useful for improving the clinical outcome of ESCC patients who suffer from aggressive disease that presently lacks effective treatment options.
Enhanced heat shock protein 25 immunoreactivity in cranial nerve motoneurons and their related fiber tracts in rats prenatally‐exposed to X‐irradiation
Authors: Sawada Kazuhiko , Saito Shigeyoshi , Horiuchi‐Hirose Miwa , Murase Kenya
Published: September 2013

Alterations in histoarchitecture of the brainstem were examined immunohistochemically in 4‐week‐old rats with a single whole body X‐irradiation at a dose of 0.5, 1.0, or 1.5 Gy on embryonic day (ED) 15 using anti‐heat shock protein 25 (HSP25). HSP25 immunostaining was seen in the neuronal perikarya of cranial nerve motoneurons, that is, the motor and mesencephalic nuclei of the trigeminal nerve, facial nucleus, abducens nucleus and accessory facial nucleus in the pons, and the ambiguous nucleus, dorsal nucleus of vagus nerve and hypoglossus nucleus in the medulla oblongata of intact controls. In 0.5 to 1.5 Gy‐irradiated rats, HSP25 immunostaining in those neurons was more intense than in controls, while the most intense immunostaining was marked in 1.5 Gy‐irradiated rats. HSP25 immunostaining was also apparent in the spinal tract of the trigeminal nerve and facial nerve tracts in 0.5 to 1.5 Gy‐irradiated rats, but was faint in controls. Interestingly, HSP25 immunostaining was aberrantly enhanced in dendritic arbors in the magnocellular region of medial vestibular nucleus of 0.5–1.5 Gy‐irradiated rats. Those arbors were identified as excitatory secondary vestibulo‐ocular neurons by double immunofluorescence for HSP25 and SMI‐32. The results suggest an increase of HSP25 expression in cranial nerve motoneurons and their related fiber tracts from prenatal exposure to ionizing irradiation. This may be an adaptive response to chronic hypoxia due to malformed brain arteries caused by prenatal ionizing irradiation.
Growth patterns of patients with 1p36 deletion syndrome
Authors: Sangu Noriko , Shimojima Keiko , Shimada Shino , Ando Tomohiro , Yamamoto Toshiyuki
Published: September 2013

1p36 deletion syndrome is one of the most common subtelomeric deletion syndromes. Obesity is frequently observed in patients with this syndrome. Thus, it is important to evaluate the growth status of an individual patient. For this purpose, we accumulated recorded growth data from 44 patients with this syndrome and investigated the growth patterns of patients. Most of the patients showed weight parameters within normal limits, whereas a few of these patients showed intrauterine growth delay and microcephaly. The length of the patients after birth was under the 50th centile in most patients. Many patients showed poor weight gain after birth, and only two female patients were overweight. These findings indicate two different phenotypes of the 1p36 deletion syndrome. The overweight patients with 1p36 deletion started excessive weight gain after two years of life. This characteristic of the patients with 1p36 deletion syndrome is similar to Prader‐Willi syndrome.
Preliminary Report on the Outcome of Tilted Implants with Longer Lengths (20–25 mm) in Low‐Density Bone: One‐Year Follow‐Up of a Prospective Cohort Study
Authors: Maló Paulo , de Araújo Nobre Miguel , Lopes Armando , Rodrigues Rolando
Published: September 2013

Purpose

The aim of this preliminary study was to report on the short‐term outcome of tilted implants with 20 to 25 mm of length in immediate function with bicortical anchorage for prosthetic rehabilitation of complete edentulous jaws with low‐density bone.

Material and Methods

Sixteen patients (with 25 study implants and 43 nonstudy implants) presenting low‐density bone were included in a prospective single cohort study to evaluate the short‐term outcome of partial and complete edentulous rehabilitations using implants with 20 to 25 mm of length (NobelSpeedy Groovy, Nobel Biocare AB, Gothenburg, Sweden) in immediate function with bicortical anchorage (maxilla: alveolar ridge and nasal corticals; mandible: mandibular corticals). The patients were followed between 6 and 26 months (average of 14 months). Outcome measures were implant survival, marginal bone remodeling, biological and mechanical complications assessed at 10 days, 2, 4, and 6 months, 1‐year posttreatment, and thereafter every 6 months.

Results

Two patients with four implants were lost to follow‐up after 6 and 11 months. There were no implant failures, rendering a cumulative implant survival rate of 100%. The average marginal bone remodeling was 0.50 mm (SD = 0.34 mm) and 0.86 mm (SD = 0.46 mm), after 6 months and 1 year, respectively. There was one mechanical complication in one patient (abutment loosening) 1 month post‐surgery.

Conclusion

Within the limitations of this study, the short‐term outcome of prosthetic rehabilitations of patients with low‐density bone using implants of 20 to 25 mm in length in immediate function with bicortical anchorage is viable judging by the high implant survival rate, low marginal bone remodeling, and low incidence of complications. Long‐term evaluation of these implants through studies using a prospective design is mandatory.
Extramaxillary Surgical Technique: Clinical Outcome of 352 Patients Rehabilitated with 747 Zygomatic Implants with a Follow‐Up between 6 Months and 7 Years
Authors: Maló Paulo , de Araújo Nobre Miguel , Lopes Armando , Ferro Ana , Moss Steven
Published: September 2013

Background

The use of zygomatic implants inserted in immediate function through the extramaxillary technique needs validation.

Purpose

To report the outcome of rehabilitating 352 patients with complete edentulous atrophied maxillae using 747 zygomatic implants in immediate function inserted through the extramaxillary technique.

Materials and Methods

Three hundred‐fifty‐two consecutive edentulous patients with atrophic maxillae were rehabilitated between 2006 and 2012 with 747 zygomatic implants and 795 conventional implants. Implant and prosthetic cumulative survival and success rates were estimated through Kaplan–Meier product limit estimator. Biological and prosthetic complications were recorded after 10 days; 2, 4, and 6 months; and thereafter every 6 months.

Results

Forty‐three patients (12.2%) dropped‐out, one patient lost the prosthesis (cumulative survival rate = 99.7%), and four patients lost 7 zygomatic implants, rendering an estimated cumulative survival rate of 98.2% (Kaplan–Meier). Ten patients lost 17 conventional implants (patient‐specific and implant‐specific cumulative survival rates of 96.7% and 97.9%, respectively). Biological complications were observed in 80 patients (22.7%) and resolved in the majority of situations, rendering an estimated cumulative success rate of 94.4% at 7 years for zygomatic implants (Kaplan–Meier). Mechanical complications occurred in 156 patients (44%), with one‐third of these complications occurring in patients diagnosed with bruxism before the rehabilitation.

Conclusions

The rehabilitation of atrophic maxillae with zygomatic implants inserted through the extramaxillary technique in immediate function, alone or in combination with standard implants, is a viable procedure. Until the biomechanical aspects are more predictable and also because of the complexity of the surgical technique, this rehabilitation approach is not ready for every implant clinician to begin using in practice, and prior special training is recommended.
From outcome prediction to action selection: developmental change in the role of action–effect bindings
Authors: Verschoor Stephan A. , Spapé Michiel , Biro Szilvia , Hommel Bernhard
Published: September 2013

Ideomotor theory considers bidirectional action–effect associations to be the fundamental building blocks for intentional action. The present study employed a novel pupillometric and oculomotor paradigm to study developmental changes in the role of action‐effects in the acquisition of voluntary action. Our findings suggest that both 7‐ and 12‐month‐olds (and adults) can use acquired action–effect bindings to predict action outcomes but only 12‐month‐olds (and adults) showed evidence for employing action‐effects to select actions. This dissociation supports the idea that infants acquire action–effect knowledge before they have developed the cognitive machinery necessary to make use of that knowledge to perform intentional actions.
Resting gamma power is linked to reading ability in adolescents
Authors: Tierney Adam , Strait Dana L. , Kraus Nina
Published: September 2013

Infants who have more power within the gamma frequency range at rest develop better language and cognitive abilities over their first 3 years of life (Benasich et al., 2008). This positive trend may reflect the gradual increase in resting gamma power that peaks at about 4 years (Takano & Ogawa, 1998): infants further along the maturational curve may exhibit both increased resting gamma power and more advanced language and cognitive function. Similar to other neural characteristics such as synaptic density, resting gamma power subsequently decreases with further development into adulthood (Tierney, Strait, O'Connell & Kraus, 2013). If previously reported relationships between resting gamma power and behavioral performance reflect variance in maturation, at least in part, negative correlations between resting gamma and behavior may predominate in later developmental stages, during which resting gamma activity is decreasing. We tested this prediction by examining resting gamma activity and language‐dependent behavioral performance, reflected by a variety of reading‐related tests, in adolescents between the ages of 14 and 15 years. Consistent with our predictions, resting gamma power inversely related to every aspect of reading assessed (i.e. reading fluency, rapid naming, and basic reading proficiency). Our results suggest that resting gamma power acts as an index of maturational progress in adolescents.
The A‐Dip of Aortic Regurgitation
Authors: Fadel Bahaa M. , Ahmed Dalia , Almahdi Bader , Di Salvo Giovanni
Published: September 2013

Careful analysis of the aortic regurgitation (AR) Doppler signal often provides important information regarding left heart hemodynamics. Here we illustrate a pattern on the AR signal, known as the A‐dip that suggests the presence of elevated LVEDP.
Stress intensity factors calculation for surface crack in cylinders under longitudinal gradient pressure using general point load weight function
Authors: Saeidi Googarchin H. , Ghajar R.
Published: September 2013

General point load weight function (GPLWF) for a longitudinal semi‐elliptical crack in a thick‐walled cylinder with outer radius to inner radius ratio of 1.25 is derived. GPLWF is used to calculate stress intensity factors (SIFs) for any point along the crack front with the crack faces subjected to uniform and longitudinal gradient internal pressure. The comparison between the results obtained from the GPLWF and those available in the literature is presented, indicating an acceptable accuracy. The proposed GPLWF can be easily used in order to calculate SIFs for surface crack in cylinders subjected to any longitudinal gradient mechanical and thermal load to determine the pattern of crack growth and estimate the fatigue life.
Defining functional gene‐circuit interfaces in the mouse nervous system
Authors: Soden M. E. , Gore B. B. , Zweifel L. S.
Published: September 2013

Complexity in the nervous system is established by developmental genetic programs, maintained by differential genetic profiles and sculpted by experiential and environmental influence over gene expression. Determining how specific genes define neuronal phenotypes, shape circuit connectivity and regulate circuit function is essential for understanding how the brain processes information, directs behavior and adapts to changing environments. Mouse genetics has contributed greatly to current percepts of gene‐circuit interfaces in behavior, but considerable work remains. Large‐scale initiatives to map gene expression and connectivity in the brain, together with advanced techniques in molecular genetics, now allow detailed exploration of the genetic basis of nervous system function at the level of specific circuit connections. In this review, we highlight several key advances for defining the function of specific genes within a neural network.
Dry mouth and denture plaque microflora in complete denture and palatal obturator prosthesis wearers
Authors: Murakami Mamoru , Nishi Yasuhiro , Seto Katsura , Kamashita Yuji , Nagaoka Eiichi
Published: September 2013

Objective and background

The purpose of this study was to investigate the association of dry mouth with denture plaque microflora in patients with palatal obturator prostheses from the viewpoint of infection control.

Methods

Thirty palatal obturator prosthesis wearers were compared with 30 healthy maxillary complete denture wearers. Dry mouth was examined using a moisture‐checking device and was diagnosed by the measured moisture levels. Denture plaque was collected by rubbing the mucosal surface of the denture with a swab; collected microorganisms were cultured and identified using culture‐dependent methods. The number of colonising microorganisms and prevalence of microorganisms were examined according to the type of prostheses and presence of dry mouth using nonparametric tests and frequency analysis (α = 0.05).

Results

The prevalence of Candida spp. and Staphylococcus spp. in palatal obturator prostheses was significantly higher than that in complete dentures. In palatal obturator prostheses, the total number of colonising microorganisms showed no significant differences between the groups with and without dry mouth on each side of the prostheses. However, the prevalence of Candida spp. and Staphylococcus spp. in the group with dry mouth was significantly higher than that in the group without dry mouth. The number of microorganisms and moisture levels of palatal obturator prosthesis wearers showed a significantly negative correlation with Candida spp. and Staphylococcus spp., but a positive correlation with Neisseria spp.

Conclusion

It was concluded that palatal obturator prosthesis wearers with a dry mouth have greater colonisation by Candida spp. and Staphylococcus spp. than do complete denture wearers.
Characteristics of Groundwater Recharge on the North China Plain
Authors: Tan Xiu‐Cui , Wu Jing‐Wei , Cai Shu‐Ying , Yang Jin‐Zhong
Published: September 2013

Groundwater recharge is an important component of the groundwater system. On the North China Plain (NCP), groundwater is the main water supply. Because of large‐scale overexploitation, the water table has declined, which has produced severe adverse effects on the environment and ecosystem. In this article, tracer experiment and watershed model were used to calculate and analyze NCP groundwater recharge. In the tracer experiment, average recharge was 108 mm/year and recharge coefficient 0.16. With its improved irrigation, vegetation coverage and evapotranspiration modules, the INFIL3.0 model was used for calculation of groundwater recharge. Regional modeling results showed an average recharge of 102 mm/year and recharge coefficient 0.14, for 2001–2009. These values are very similar to those from the field tracer experiment. Influences in the two methods were analyzed. The results can provide an important reference for NCP groundwater recharge.
The Religious Meaning of Culture: Paul Tillich and Beyond
Authors: Re Manning Russell
Published: September 2013

Throughout his theological career Paul Tillich (1886–1965) was fundamentally concerned with the question of the religious meaning of culture. The answers that he gave – initially in the revolutionary ferment of 1920s–1930s Germany and then again in the brave new world of post‐World War II America – were profound and far‐reaching in their importance for twentieth‐century theology. This article will explore the development of Tillich's interpretations of the religious meaning of culture and apply his analyses to our contemporary religious and cultural situation by suggesting a trinitarian enlargement of Tillich's concept of theonomous metaphysics towards a multidimensional theology of culture.
Exertional heat stroke, rhabdomyolysis and susceptibility to malignant hyperthermia
Authors: Thomas J. , Crowhurst T.
Published: September 2013

Unexpectedly severe exertional heat stroke and rhabdomyolysis should prompt a clinician to look for susceptibility to malignant hyperthermia. We report a case of exertional heat stroke and rhabdomyolysis in a man later determined to have the malignant hyperthermia phenotype. We review the existing literature regarding this association and suggest future research that could address areas of remaining clinical uncertainty.
Muscle disorders: the latest investigations
Authors: Ghaoui R. , Clarke N. , Hollingworth P. , Needham M.
Published: September 2013

Patients with muscle disorders can present a diagnostic challenge to physicians because of the different ways they can present and the large number of different underlying causes. Recognition of the ‘myopathic phenotype’ coupled with investigations usually including electrodiagnostic and histological investigations have been essential for diagnosing the underlying cause of a myopathy. Despite these standard investigations, some patients can remain undiagnosed. New tests including more specific antibody tests for immune‐mediated myopathies and the introduction of next‐generation sequencing promise to revolutionise diagnostic approaches for immune and inherited myopathies, but clinical expertise remains essential to choose the most appropriate tests and interpret the results. The aim of this review is to provide an overview of the different presentations to the neuromuscular clinic and the latest investigations that can be helpful in the diagnosis of muscle disorders.
Causes of hospitalisation before and after the 2009 L'Aquila earthquake
Authors: Petrazzi L. , Striuli R. , Polidoro L. , Petrarca M. , Scipioni R. , Struglia M. , Giorgini P. , Necozione S. , Festuccia V. , Ferri C.
Published: September 2013

On 6 April 2009, an earthquake struck L'Aquila. The San Salvatore Hospital was evacuated, and a field hospital was built. The study aimed to assess the epidemiologic impact of the earthquake through the analysis of patient population admitted to the field hospital during a 2‐month period following the disaster. We retrospectively evaluated causes of hospitalisation and demographic data of patients admitted to (i) the Division of Internal Medicine and (ii) the Division of Emergency Medicine of the field hospital from 6 April, 2009 to 29 May, 2009. All data were compared with the admissions made at the same divisions of the San Salvatore Hospital during the same period of previous year. (i) Patient group (n = 102) and comparison group (n = 108). Mean patient age was higher, patients living in L'Aquila were more numerous, while mean length of stay was lower after than before the earthquake. Infectious diseases increased, while ‘other’ diseases decreased after the disaster both in admission and in discharge diagnoses. Gastroenterological diseases decreased with the earthquake but only in admission diagnoses. (ii) Patient group (n = 5255) and comparison group (n = 6564). Triage codes changed with the earthquake. Cardiovascular, psychiatric, gynaecological, infectious and chronic diseases increased, while pneumologic, gastroenterological, traumatic and ‘other’ diseases decreased after the quake. The number of hospitalised patients decreased with the tremor, while those discharged transferred to other hospitals and those who rejected hospitalisation increased. A natural disaster completely changes causes of hospitalisation in the Divisions of Internal and Emergency Medicine. These findings can be useful for the design of specific intervention programmes and for softening the detrimental effects of quakes.
Estimating the Optimal Dynamic Antipsychotic Treatment Regime: Evidence from the Sequential Multiple-Assignment Randomized Clinical Antipsychotic Trials of Intervention and Effectiveness Schizophrenia Study
Authors: Shortreed Susan M. , Moodie Erica E. M.
Published: September 2013

Treatment of schizophrenia is notoriously difficult and typically requires personalized adaption of treatment because of lack of efficacy of treatment, poor adherence or intolerable side effects. The Clinical Antipsychotic Trials in Intervention Effectiveness schizophrenia study is a sequential multiple-assignment randomized trial comparing the typical antipsychotic medication perphenazine with several newer atypical antipsychotics. The paper describes the marginal structural modelling method for estimating optimal dynamic treatment regimes and applies the approach to this schizophrenia study. Missing data and valid estimation of confidence intervals are also addressed.
Fast Linked Analyses for Scenario-Based Hierarchies
Authors: Williamson Daniel , Goldstein Michael , Blaker Adam
Published: September 2013

When using computer models to provide policy support it is normal to encounter ensembles that test only a handful of feasible or idealized decision scenarios. We present a new methodology for performing multilevel emulation of a complex model as a function of any decision within a predefined class that makes specific use of a scenario ensemble of opportunity on a fast or early version of a simulator and a small, well-chosen, design on our current simulator of interest. The method exploits a geometrical approach to Bayesian inference and is designed to be fast, to facilitate detailed diagnostic checking of our emulators by allowing us to carry out many analyses very quickly. Our motivating application involved constructing an emulator for the UK Met Office Hadley Centre coupled climate model HadCM3 as a function of carbon dioxide forcing, which was part of a ‘RAPID’ programme deliverable to the UK Met Office funded by the Natural Environment Research Council. Our application involved severe time pressure as well as limited access to runs of HadCM3 and a scenario ensemble of opportunity on a lower resolution version of the model.
The Effect of Late Onset, Short-Term Caloric Restriction on the Core Temperature and Physical Activity in Mice
Authors: Golightly Andrew , Boys Richard J. , Cameron Kerry M. , Zglinicki Thomas von
Published: September 2013

Caloric restriction (CR) has been shown to delay the onset of cancer and other diseases that are associated with aging. Currently there are very few studies examining the whole-animal physiological response to late onset CR. We study the ways by which mice physiologically compensate for reduced availability of food given exposure to late onset CR and compare these with mice fed ad libitum. The data arise from a 70-day experiment that was undertaken by the authors. A joint model is developed to describe core body temperature and levels of activity and the model parameters assessed for temporal dependence by using dynamic linear models. A Bayesian approach is used throughout. The dynamic parameters are shown to be plausibly constant over time and the constant parameter model is then embedded within a random-effects structure to explore differences between the responses of CR and ad libitum mice. This model is shown to provide a good description of the data.
Dynamic Bradley–Terry Modelling of Sports Tournaments
Authors: Cattelan Manuela , Varin Cristiano , Firth David
Published: September 2013

In the course of national sports tournaments, usually lasting several months, it is expected that the abilities of teams taking part in the tournament will change over time. A dynamic extension of the Bradley–Terry model for paired comparison data is introduced to model the outcomes of sporting contests, allowing for time varying abilities. It is assumed that teams’ home and away abilities depend on past results through exponentially weighted moving average processes. The model proposed is applied to sports data with and without tied contests, namely the 2009–2010 regular season of the National Basketball Association tournament and the 2008–2009 Italian Serie A football season.