bluuebunny/crossref_metadata_2025 huggingface dataset:
Aβ40 modulates GABAA receptor α6 subunit expression and rat cerebellar granule neuron maturation through the ERK/mTOR pathway
Authors: Zhan Xiao‐Qin , Yao Jin‐Jing , Liu Dong‐Dong , Ma Qianqian , Mei Yan‐Ai
Published: October 2013

In addition to their neurotoxic role in Alzheimer's disease (AD), β‐amyloid peptides (Aβs) are also known to play physiological roles. Here, we show that recombinant Aβ40 significantly increased the outward current of the GABAA receptor containing (GABAAα6) in rat cerebellar granule neurons (CGNs). The Aβ40‐mediated increase in GABAAα6 current was mediated by an increase in GABAAα6 protein expression at the translational rather than the transcriptional level. The exposure of CGNs to Aβ40 markedly induced the phosphorylation of ERK (pERK) and mammalian target of rapamycin (pmTOR). The increase in GABAAα6 current and expression was attenuated by specific inhibitors of ERK or mTOR, suggesting that the ERK and mTOR signaling pathways are required for the effect of Aβ40 on GABAAα6 current and expression in CGNs. A pharmacological blockade of the p75 neurotrophin receptor (p75NTR), but not the insulin or α7‐nAChR receptors, abrogated the effect of Aβ40 on GABAAα6 protein expression and current. Furthermore, the expression of GABAAα6 was lower in CGNs from APP−/− mice than in CGNs from wild‐type mice. Moreover, the internal granule layer (IGL) in APP−/− mice was thinner than the IGL in wild‐type mice. The injection of Aβ40 into the cerebellum reversed this effect, and the application of p75NTR blocking antibody abolished the effects of Aβ40 on cerebellum morphology in APP−/− mice. Our results suggest that low concentrations of Aβ40 play a role in regulating CGN maturation through p75NTR.

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In addition to its neurotoxic role in Alzheimer's disease, Aβ is known to play important physiological roles. Whether Aβ improves neuronal development and maturation remains elusive. Our results demonstrate that low concentrations of Aβ40 significantly increase the GABAA receptor α6 subunit expression and associated current in cerebellar granule neurons (CGNs) via the p75NTR and MEK/ERK pathway. Aβ also increases the thickness of the internal granule layer in APP−/− mice cerebellum. Our data provide new evidence for the role of Aβ40 in regulating the maturation of CGNs.
Inflammation induces multinucleation of Microglia via PKC inhibition of cytokinesis, generating highly phagocytic multinucleated giant cells
Authors: Hornik Tamara C. , Neniskyte Urte , Brown Guy C.
Published: October 2013

Microglia are brain macrophages, which can undergo multinucleation to give rise to multinucleated giant cells that accumulate with ageing and some brain pathologies. However, the origin, regulation and function of multinucleate microglia remain unclear. We found that inflammatory stimuli, including lipopolysaccharide, amyloid β, α‐synuclein, tumour necrosis factor‐α and interferon γ, but not interleukin‐4, induced multinucleation of cultured microglia: primary rat cortical microglia and the murine microglial cell line BV‐2. Inflammation‐induced multinucleation was prevented by a protein kinase C (PKC) inhibitor Gö6976 (100 nM) and replicated by a PKC activator phorbol myristate acetate (160 nM). Multinucleation was reversible and not because of cell fusion or phagocytosis, but rather failure of cytokinesis. Time‐lapse imaging revealed that some dividing cells failed to abscise, even after formation of long cytoplasmic bridges, followed by retraction of bridge and reversal of cleavage furrow to form multinucleate cells. Multinucleate microglia were larger and 2–4 fold more likely to phagocytose large beads and both dead and live PC12 cells. We conclude that multinucleate microglia are reversibly generated by inflammation via PKC inhibition of cytokinesis, and may have specialized functions/dysfunctions including the phagocytosis of other cells.

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Inflammation resulted in the accumulation of multiple nuclei per cell in cultured microglia. This multinucleation was reversible and due to a PKC‐dependent block of the last step of cell division. Multinucleate microglia were larger and had a greater capacity to phagocytose other cells, suggesting they might remove neurons in the brain.
Neurobiological consequences of acute footshock stress: effects on tyrosine hydroxylase phosphorylation and activation in the rat brain and adrenal medulla
Authors: Ong Lin Kooi , Guan Liying , Damanhuri Hanafi , Goodchild Ann K. , Bobrovskaya Larisa , Dickson Phillip W. , Dunkley Peter R.
Published: October 2013

Stress activates selected neuronal systems in the brain and this leads to activation of a range of effector systems. Our aim was to investigate some of the relationships between these systems under basal conditions and over a 40‐min period in response to footshock stress. Specifically, we investigated catecholaminergic neurons in the locus coeruleus (LC), ventral tegmental area and medial prefrontal cortex (mPFC) in the brain, by measuring tyrosine hydroxylase (TH) protein, TH phosphorylation and TH activation. We also measured the effector responses by measuring plasma adrenocorticotrophic hormone, corticosterone, glucose and body temperature as well as activation of adrenal medulla protein kinases, TH protein, TH phosphorylation and TH activation. The LC, ventral tegmental area and adrenal medulla all had higher basal levels of Ser19 phosphorylation and lower basal levels of Ser31 phosphorylation than the mPFC, presumably because of their cell body versus nerve terminal location, while the adrenal medulla had the highest basal levels of Ser40 phosphorylation. Ser31 phosphorylation was increased in the LC at 20 and 40 min and in the mPFC at 40 min; TH activity was increased at 40 min in both tissues. There were significant increases in body temperature between 10 and 40 min, as well as increases in plasma adrenocorticotropic hormone at 20 min and corticosterone and glucose at 20 and 40 min. The adrenal medulla extracellular signal‐regulated kinase 2 was increased between 10 and 40 min and Ser31 phosphorylation was increased at 20 min and 40 min. Protein kinase A and Ser40 phosphorylation were increased only at 40 min. TH activity was increased between 20 and 40 min. TH protein and Ser19 phosphorylation levels were not altered in any of the brain regions or adrenal medulla over the first 40 min. These findings indicate that acute footshock stress leads to activation of TH in the LC, pre‐synaptic terminals in the mPFC and adrenal medullary chromaffin cells, as well as changes in activity of the hypothalamic‐pituitary‐adrenal axis.

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We measured the basal levels of tyrosine hydroxylase phosphorylation and determined the effects of footshock stress over a 40 minute period. Footshock leads to changes in the activity of neurons in the locus coeruleus (LC) and presynaptic terminals in the medial prefrontal cortex (mPFC), as well as changes in activity of the hypothalamic‐pituitary‐adrenal (HPA) axis and adrenal medullary (AM) chromaffin cells.
Phosphoproteomic evaluation of pharmacological inhibition of leucine‐rich repeat kinase 2 reveals significant off‐target effects of LRRK‐2‐IN‐1
Authors: Luerman Gregory C. , Nguyen Chuong , Samaroo Harry , Loos Paula , Xi Hualin , Hurtado‐Lorenzo Andres , Needle Elie , Stephen Noell G. , Galatsis Paul , Dunlop John , Geoghegan Kieran F. , Hirst Warren D.
Published: October 2013

Genetic mutations in leucine‐rich repeat kinase 2 (LRRK2) have been linked to autosomal dominant Parkinson's disease. The most prevalent mutation, G2019S, results in enhanced LRRK2 kinase activity that potentially contributes to the etiology of Parkinson's disease. Consequently, disease progression is potentially mediated by poorly characterized phosphorylation‐dependent LRRK2 substrate pathways. To address this gap in knowledge, we transduced SH‐SY5Y neuroblastoma cells with LRRK2 G2019S via adenovirus, then determined quantitative changes in the phosphoproteome upon LRRK2 kinase inhibition (LRRK2‐IN‐1 treatment) using stable isotope labeling of amino acids in culture combined with phosphopeptide enrichment and LC‐MS/MS analysis. We identified 776 phosphorylation sites that were increased or decreased at least 50% in response to LRRK2‐IN‐1 treatment, including sites on proteins previously known to associate with LRRK2. Bioinformatic analysis of those phosphoproteins suggested a potential role for LRRK2 kinase activity in regulating pro‐inflammatory responses and neurite morphology, among other pathways. In follow‐up experiments, LRRK2‐IN‐1 inhibited lipopolysaccharide‐induced tumor necrosis factor alpha (TNFα) and C‐X‐C motif chemokine 10 (CXCL10) levels in astrocytes and also enhanced multiple neurite characteristics in primary neuronal cultures. However, LRRK2‐IN‐1 had almost identical effects in primary glial and neuronal cultures from LRRK2 knockout mice. These data suggest LRRK2‐IN‐1 may inhibit pathways of perceived LRRK2 pathophysiological function independently of LRRK2 highlighting the need to use multiple pharmacological tools and genetic approaches in studies determining LRRK2 function.

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Genetic mutations in leucine‐rich repeat kinase 2 (LRRK2) have been linked to Parkinson's disease, potentially contributing to the pathogenesis through increased kinase activity acting via phosphorylation‐dependent LRRK2 substrate pathways. To determine the potential pathways, we performed SILAC combined with phosphopeptide enrichment and LC‐MS/MS analysis +/‐ LRRK2 inhibitor. Bioinformatic analysis of those phosphoproteins suggested a potential role for LRRK2 kinase activity in regulating pro‐inflammatory responses and neurite morphology, among other pathways.
The dermal arteries of the human thumb pad
Authors: Geyer S. H. , Nöhammer M. M. , Tinhofer I. E. , Weninger W. J.
Published: October 2013

The arteries of the skin have been postulated to form a profound plexus at the dermal/hypodermal junction and a superficial plexus in the papillary dermis. Our article aims to rebut this concept and to provide an alternative description of the arrangement of the dermal arteries. Employing a novel technique, we produced digital volume data (volume size: 2739 × 2054 × 3000 μm3; voxel size: 1.07 × 1.07 × 2 μm3) from biopsies of the skin of the thumb pads of 15 body donors. Utilizing these data, we analysed the arrangement of the dermal arteries with the aid of virtual re‐sectioning tools, and, in three specimens, with high‐quality three‐dimensional (3D) surface models. In all specimens we observed a tree‐like ramification of discrete dermal arteries. The terminal branches of the arterial trees gave rise to the ascending segments of the capillary loops of the dermal papillae. None of the specimens showed a superficial arterial plexus. This suggests that the skin of the human thumb pad can be split in discrete ‘arterial units’. Each unit represents the zone of the papillary dermis and epidermal/dermal junction, to which blood is supplied exclusively by the branches of a single dermal artery. The concept of dermal arterial units is in contrast to all existing descriptions of the architecture of the dermal arteries. However, whether it can be transferred to the skin of other body parts, remains to be tested. Likewise, the consequences of arterial units for understanding the mechanisms of wound healing and the appearance and genesis of skin diseases remain to be examined.
A New System of Labour Management in African Large‐Scale Agriculture?
Authors: Gibbon Peter , Riisgaard Lone
Published: October 2013

This paper applies a convention theory (CT) approach to the analysis of labour management systems in African large‐scale farming. The reconstruction of previous analyses of high‐value crop production on large‐scale farms in Africa in terms of CT suggests that, since 1980–95, labour management has moved from a ‘domestic’ to a ‘market’ system. However, data collected by the authors from a sample of 11 large‐scale rose farms in Kenya in 2011 (covering around 20% of national output) points to the adoption of systems that, in CT terms, combine ‘industrial’ and ‘civic’ elements. The paper concludes by suggesting a series of hypotheses that might explain this trend.
Effects of glycolic acid chemical peeling on facial pigment deposition: Evaluation using novel computer analysis of digital‐camera‐captured images
Authors: Kakudo Natsuko , Kushida Satoshi , Suzuki Kenji , Kusumoto Kenji
Published: October 2013

Background

Chemical peeling is becoming increasingly popular for skin rejuvenation in dermatological cosmetic medicine. However, the improvements seen with chemical peeling are often very minor, and it is difficult to conduct a quantitative assessment of pre‐ and post‐treatment appearance.

Aims

We report the pre‐ and postpeeling effects for facial pigment deposition using a novel computer analysis method for digital‐camera‐captured images.

Patients/Methods

Glycolic acid chemical peeling was performed a total of 5 times at 2‐week intervals in 23 healthy women. We conducted a computer image analysis by utilizing Robo Skin Analyzer CS 50 and Clinical Suite 2.1 and then reviewed each parameter for the area of facial pigment deposition pre‐ and post‐treatment. Parameters were pigmentation size and four pigmentation categories: little pigmentation and three levels of marked pigmentation (Lv1, 2, and 3) based on detection threshold. Each parameter was measured, and the total area of facial pigmentation was calculated.

Results

The total area of little pigmentation and marked pigmentation (Lv1) was significantly reduced. On the other hand, a significant difference was not observed for the total area of marked pigmentation Lv2 and Lv3.

Conclusion

This suggests that glycolic acid chemical peeling has an effect on small facial pigment disposition or has an effect on light pigment deposition. As the Robo Skin Analyzer is useful for objectively quantifying and analyzing minor changes in facial skin, it is considered to be an effective tool for accumulating treatment evidence in the cosmetic and esthetic skin field.
Registered nurses' reflections on discussing sexuality with patients: responsibilities, doubts and fears
Authors: Saunamäki Nina , Engström Maria
Published: October 2013

Aims and objectives

To describe registered nurses' reflections on discussing sexuality with patients.

Background

It is known that many diseases and treatments have a negative impact on sexual health. Despite these facts, registered nurses typically do not address sexual issues with patients.

Design

A descriptive design and a qualitative approach were used.

Methods

Interviews were conducted in 2010 with 10 registered nurses. The data were analysed using qualitative content analysis.

Results

The themes ‘Doing the right thing and doing good’, ‘Could've, would've, should've: a nurse's conflicting feelings’ and ‘I just don't talk about it: sexuality as a nontopic’ confirmed the notion that discussing sexuality in nursing care is still challenging and difficult for nurses, but also revealed that nurses who do talk to patients about sexual issues do so based on their strong sense of wanting to help. They felt a responsibility because of their knowledge in the area, but the topic also brought out conflicting feelings such as fear and embarrassment. Lack of time, support and places to talk to patients in private as well as prejudice were contributing factors to their not addressing sexuality. Some nurses also felt that sexuality was someone else's responsibility and a taboo subject.

Conclusions

Patients' sexuality is still surrounded by silence. But factors exist that can facilitate discussion of sexuality. Nurses have a key role in detecting ill‐health. This study suggests that when nurses use their knowledge and go beyond their comfort zone and address sexuality, they can identify patients' sexual problems.

Relevance to clinical practice

Nurses need to understand how their knowledge can help patients who are experiencing sexual problems; they also need support from the workplace and to have access to routines that reinforce the notion that sexuality is a topic worth discussing.
Administration of oral and vaginal prebiotic lactoferrin for a woman with a refractory vaginitis recurring preterm delivery: Appearance of lactobacillus in vaginal flora followed by term delivery
Authors: Otsuki Katsufumi , Tokunaka Mayumi , Oba Tomohiro , Nakamura Masamitsu , Shirato Nahoko , Okai Takashi
Published: October 2013

Lactoferrin (LF) is one of the prebiotics present in the human body. A 38‐year‐old multiparous woman with poor obstetrical histories, three consecutive preterm premature rupture of membrane at the 19th, 23rd and 25th week of pregnancy, was referred to our hospital. She was diagnosed as having refractory vaginitis. Although estriol vaginal tablets were used for 4 months, the vaginitis was not cured. We administrated vaginal tablets and oral agents of prebiotic LF, resulting in a Lactobacillus predominant vaginal flora. When she was pregnant, she continued to use the LF, and the Lactobacillus in the vaginal flora was continuously observed during pregnancy. An elective cesarean section was performed at the 38th week of pregnancy. When the administration of LF was discontinued after the delivery, Lactobacillus in the vaginal flora was disappeared.
Uterine artery pseudoaneurysm hidden behind septic abortion: Pseudoaneurysm without preceding procedure
Authors: Matsubara Shigeki , Nakata Manabu , Baba Yosuke , Suzuki Haruna , Nakamura Hiroyasu , Suzuki Mitsuaki
Published: October 2013

Uterine artery pseudoaneurysm (UAP) can occur after cesarean section or traumatic delivery, usually manifesting as postpartum hemorrhage. Here we report a patient with UAP possibly caused by septic abortion. She had high fever and bleeding with positive urine pregnancy test. We diagnosed this condition as septic abortion. Ultrasound revealed an intrauterine echogenic mass and color Doppler revealed swirling blood flow within the mass. Contrast‐enhanced computed tomography showed a heterogeneously enhanced intrauterine mass. Selective internal iliac artery angiography revealed contrast medium within the mass immediately after medium injection. Bilateral uterine artery embolization was performed, after which medium no longer accumulated in the uterus, and hemostasis was achieved, confirming the diagnosis as UAP. Antibiotic treatment ameliorated the infection and the uterine content was expelled and absorbed. UAP can occur even without preceding procedures and may manifest abortive, and not postpartum, hemorrhage. UAP may be hidden behind septic abortion.
Use of periurethral injections of polyacrylamide hydrogel for treating post‐vesicovaginal fistula closure urinary stress incontinence
Authors: Krause Hannah G. , Lussy Justin P. , Goh Judith T. W.
Published: October 2013

Aims

Following successful closure of obstetric genitourinary fistula, stress urinary incontinence (SUI) is a common and challenging problem. Despite many decades of various treatment options, the effective management of post‐fistula SUI remains unresolved. This study aims to assess the feasibility of periurethral injections of polyacrylamide hydrogel, commonly used for urinary stress incontinence in non‐fistula women, in women with post‐fistula closure SUI.

Material and Methods

Women with urinary incontinence following successful fistula closure were assessed to exclude detrusor overactivity and urinary residual volumes of more than 100 mL. The urethrovesical junction was identified and polyacrylamide hydrogel was injected through the periurethral skin and vaginal epithelium at three sites.

Results

Four women with post‐fistula SUI were treated with polyacrylamide hydrogel injections. Three of the four women were dry post‐operatively and remained continent at discharge.

Conclusion

In the short‐term, periurethral injections of polyacrylamide hydrogel appears to be a promising method to treat post‐obstetric fistula urinary stress incontinence.
Melatonin and female reproduction
Authors: Tamura Hiroshi , Takasaki Akihisa , Taketani Toshiaki , Tanabe Manabu , Lee Lifa , Tamura Isao , Maekawa Ryo , Aasada Hiromi , Yamagata Yoshiaki , Sugino Norihiro
Published: October 2013

Melatonin (N‐acetyl‐5‐methoxytryptamine) is secreted during the dark hours at night by the pineal gland. After entering the circulation, melatonin acts as an endocrine factor and a chemical messenger of light and darkness. It regulates a variety of important central and peripheral actions related to circadian rhythms and reproduction. It also affects the brain, immune, gastrointestinal, cardiovascular, renal, bone and endocrine functions and acts as an oncostatic and anti‐aging molecule. Many of melatonin's actions are mediated through interactions with specific membrane‐bound receptors expressed not only in the central nervous system, but also in peripheral tissues. Melatonin also acts through non‐receptor‐mediated mechanisms, for example serving as a scavenger for reactive oxygen species and reactive nitrogen species. At both physiological and pharmacological concentrations, melatonin attenuates and counteracts oxidative stress and regulates cellular metabolism. Growing scientific evidence of reproductive physiology supports the role of melatonin in human reproduction. This review was conducted to investigate the effects of melatonin on female reproduction and to summarize our findings in this field.
Anorectal abscess during pregnancy
Authors: Koyama Shinsuke , Hirota Masaki , Kobayashi Masaki , Tanaka Yusuke , Kubota Satoshi , Nakamura Ryo , Isobe Masanori , Shiki Yasuhiko
Published: October 2013

Anorectal symptoms and complaints caused by hemorrhoids or anal fissures are common during pregnancy. It is known that one‐third of pregnant women complain of anal pain in the third trimester. Anal pain may be caused by a wide spectrum of conditions, but if it begins gradually and becomes excruciating within a few days it may indicate anorectal abscess. We experienced a case of anorectal abscess during pregnancy which was diagnosed by magnetic resonance imaging and treated by incision and seton drainage at 36 weeks of gestation, followed by a normal spontaneous delivery at 38 weeks of gestation. To our knowledge, this is the first case report of anorectal abscess during pregnancy in the English‐language published work. The clinical course of our case and clinical considerations of anorectal abscesses are discussed.
Combined Paclitaxel‐Eluting Balloon and Genous Cobalt–Chromium Alloy Stent Utilization in De Novo Coronary Stenoses (PEGASUS)
Authors: JIM MAN‐HONG , FUNG RAYMOND CHI‐YAN , YIU KAI‐HANG , NG ANDREW KEI‐YAN , SIU CHUNG‐WAH , FAN KATHERINE YU‐YAN
Published: October 2013

Objectives

The aim of this study was to examine the angiographic result and its outcome predictors using the combination of paclitaxel‐eluting balloon (PEB) and Genous stent.

Background

This approach to treat coronary stenoses is a logical strategy to strike a balance between minimizing restenosis and stent thrombosis.

Methods

From November 2010 to June 2012, 40 symptomatic patients with 44 de novo coronary lesions of diameter stenosis ≥50% were treated with the combination of PEB and Genous stents. Angiographic and clinical follow‐up were intended at 6 and 9 months, respectively.

Results

The mean age of patients was 61 ± 11 years, with male predominance (83%). Diabetes mellitus and end‐stage renal failure on peritoneal dialysis were found in 15 (38%) and 10 (25%) patients, respectively. Patients received dual antiplatelet therapy for 5.1 ± 1.5 months post procedure. The size and length of PEB used was larger than the stents (3.13 ± 0.46 mm and 28 ± 9 mm vs. 2.98 ± 0.36 mm and 23 ± 7 mm). Restudy angiography was performed on 41 (95%) lesions in 37 (93%) patients at 5.9 ± 1.7 months. Angiographic restenosis was seen in 5 (12%) lesions, and significantly associated with diabetes mellitus and dialysis dependency; the late lumen loss was 0.38 ± 0.37 mm. At 9‐month follow‐up, no stent thrombosis was observed.

Conclusions

The use of PEB combined with Genous stent is associated with a reasonably low restenosis and late lumen loss, whereas diabetes mellitus and renal failure with dialysis are poor predictors of angiographic restenosis.
Muricholic bile acids are potent regulators of bile acid synthesis via a positive feedback mechanism
Authors: Hu X. , Bonde Y. , Eggertsen G. , Rudling M.
Published: October 2013

Objective

Bile acid (BA) synthesis is regulated by negative feedback end‐product inhibition, initiated by farnesoid X receptors (FXRs) in liver and gut. Studies on cholic acid (CA)‐free Cyp8b1−/− mice have concluded that CA is a potent suppressor of BA synthesis. Cyp8b1−/− mice have increased BA synthesis and an enlarged BA pool, a phenotype shared with bile‐duct‐ligated, antibiotics‐administered and with germ‐free mice. Studies on such mice have concluded BA synthesis is induced due to reduced hormonal signalling by fibroblast growth factor (FGF)15 from intestine to liver. A mutual finding in these models is that potent FXR‐agonistic BAs are reduced. We hypothesized that the absence of the potent FXR agonist deoxycholic acid (DCA) may be important for the induction of BA synthesis in these situations.

Design

Two of these models were investigated, antibiotic treatment and Cyp8b1−/− mice and their combination. Secondary BA formation was inhibited by ampicillin (AMP) given to wild‐type and Cyp8b1−/− mice. We then administered CA, chenodeoxycholic acid (CDCA) or DCA to AMP‐treated Cyp8b1−/− mice.

Results

Our data show that the phenotype of AMP‐treated wild‐type mice resembles that of Cyp8b1−/− mice with fourfold induced Cyp7a1 expression, increased intestinal apical sodium‐dependent BA transporter expression and increased hepatic BA levels. We also show that reductions in the FXR‐agonistic BAs CDCA, CA, DCA or lithocholic acid cannot explain this phenotype; instead, it is likely due to increases in levels of α‐ and β‐muricholic BAs and ursodeoxycholic acid, three FXR‐antagonistic BAs.

Conclusions

Our findings reveal a potent positive feedback mechanism for regulation of BA synthesis in mice that appears to be sufficient without endocrine effects of FGF15 on Cyp7a1. This mechanism will be fundamental in understanding BA metabolism in both mice and humans.
Laminin‐5 gamma 2 chain expression is associated with intensity of tumor budding and density of stromal myofibroblasts in oral squamous cell carcinoma
Authors: Marangon Junior Helvécio , Rocha Valéria Nazaré , Leite Camila Ferreira , de Aguiar Maria Cássia Ferreira , Souza Paulo Eduardo Alencar , Horta Martinho Campolina Rebello
Published: October 2013

Background

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide. Laminin‐5 gamma 2 chain (laminin‐5 γ2) is a protein associated to a migratory phenotype in epithelial neoplastic cells. Stromal myofibroblasts also play a significant role in tumor invasion, due to its ability to modify the extracellular matrix. Tumor budding is a morphologic marker of tumor invasion. The aim of this study was to evaluate the expression of laminin‐5 γ2 inOSCCand its association with intensity of tumor budding and density of stromal myofibroblasts.

Methods

Paraffin‐embedded archival samples of 57OSCCpatients were evaluated. Immunohistochemistry was employed to detect laminin‐5 γ2, alpha smooth muscle actin (marker of stromal myofibroblasts), and multicytokeratin (to identifyOSCCcells in tumor budding evaluation). Laminin‐5 γ2 expression and its association with intensity of tumor budding and density of stromal myofibroblasts were analyzed. Association among intensity of tumor budding and density of stromal myofibroblasts was also evaluated.

Results

Higher laminin‐5 γ2 expression was associated with high‐intensity tumor budding (P < 0.05) and with higher density of stromal myofibroblasts (P < 0.05). Moreover, high‐intensity tumor budding was associated with higher density of stromal myofibroblasts (P < 0.05).

Conclusions

InOSCC, higher laminin‐5 γ2 expression is associated with high‐intensity tumor budding and with higher density of stromal myofibroblasts, suggesting that this expression is related to the establishment of an invasive phenotype of neoplastic cells and a permissive environment for tumor invasion in this neoplasia.
Inhibition of autophagy augments chemotherapy in human salivary adenoid cystic carcinoma
Authors: Jiang Licheng , Huang Shengyun , Zhang Dongsheng , Zhang Bin , Li Keyi , Li Wengang , Zhang Shizhou , Zhang Weidong , Zheng Peihui
Published: October 2013

Although cisplatin (DDP)‐based adjuvant chemotherapy is widely used in the treatment of salivary adenoid cystic carcinoma (SACC), SACCs have developed resistance to cisplatin, resulting in chemotherapy failure. Autophagy serves as a critical adaptive response, which was increased in tumor cells in chemotherapy. However, the function of autophagy is not clear in SACC. In this study, apoptosis induced by DDP in SACC high metastatic cell line (ACC‐M) was revealed using MTT assay, flow cytometry, and caspase‐3 immunoblotting. The autophagy activation induced by DDP treatment was measured by transmission electron microscopy, green fluorescent protein–light chain 3 plasmid transfection LC3 immunoblotting and p62 immunoblotting. 3‐methyladenine (3‐MA) or small interference RNA targeting beclin 1 (beclin 1 siRNA) inhibited autophagy and significantly enhanced DDP‐induced apoptosis. ACC‐M xenografts in nude mice further verified the synergistic effect of DDP and 3‐MA. In conclusion, autophagy activation was caused to protect cancer cells from DDP‐induced apoptosis and autophagy inhibition could be a promising strategy for adjuvant chemotherapy in SACC.
Full‐Mouth Rehabilitation of Severely Worn Dentition Due to Soda Swishing: A Clinical Report
Authors: Alqahtani Fawaz
Published: October 2013

Diagnosis and treatment planning of severely worn dentition are complex and complicated. Erosion is one of the common causes of lost tooth surface. Defining the etiology of the erosion is essential before proceeding with treatment to be able to provide the most predictable treatment outcome. Multiple specialists including psychologists, family medicine practioners, and social workers should be involved in the diagnosis and the prevention of a continuing erosion process. The treatment plan should be based on the severity of the tooth surface lost. It can range from simple direct restorations to a full‐mouth rehabilitation. This clinical report is a detailed description of a complex prosthodontic diagnostic index class IV patient based on current evidence‐based dentistry.
Coping With LGBT and Racial–Ethnic‐Related Stressors: A Mixed‐Methods Study of LGBT Youth of Color
Authors: Kuper Laura E. , Coleman Brett R. , Mustanski Brian S.
Published: October 2013

This study examines how racial–ethnic minority lesbian, gay, bisexual, and transgender (LGBT) youth cope with both racial–ethnic and LGBT‐related stress. Within a sample of 213 LGBT youth of color, the present study presents (1) quantitative and qualitative results from an approach and avoidance–based measure of parental racial coping socialization across six conversation domains, and (2) qualitative responses regarding LGBT stressors and associated coping strategies. The emphasis on approach versus avoidance varied across the racial–ethnic conversation domains. However, both racial–ethnic‐ and LGBT‐related coping strategies emphasized a combination of cognitive and behavioral strategies. Similarities and differences also existed in the types of stressors encountered across racial–ethnic and LGBT statuses. We discuss the potential for coping skill transfer across these minority statuses.
The sociolinguistics of exogamy: Dialect acquisition in a Zhuang village
Authors: Stanford James N. , Pan Yanhong
Published: October 2013

Adult dialect acquisition is typically studied in relatively idiosyncratic situations where adults happen to move to another community. But how does dialect acquisition play out in indigenous minority societies that have systemic adult migration due to exogamy? Do the in‐married spouses acquire the local variety? Why or why not? How much do they acquire? We investigated an indigenous Zhuang community in southern China. Sociophonetic analyses of in‐married women and local villagers show that the in‐married women acquired the local variety in most respects but not in aspirated consonants. To the limits of their phonological ability as adult learners, the wives followed the local sociolinguistic norm: they acquired the husbands’ variety. By contrast, in societies experiencing greater external cross‐cultural contact, exogamous women sometimes use their liminal status to challenge such gendered sociolinguistic expectations. Comparing the present study with outcomes in different societies, we lay the foundation for a typology of the sociolinguistics of exogamy. In this way, we help expand the study of language and gender toward new horizons and under‐represented social settings.
Relative Consumption Concerns and the Optimal Tax Mix
Authors: ECKERSTORFER PAUL
Published: October 2013

This paper studies the optimal tax mix (taxes on income and commodities) under asymmetric information in a two‐type model, when individuals make relative consumption comparisons. The model includes both positional and nonpositional goods, taking into account the fact that relative concerns matter for some but not for all commodities. We find that in general the whole tax system is affected by the externalities caused by the consumption of positional goods, notably also the taxes on income and on a nonpositional good. The tax rates on positional goods are higher than in the absence of status effects, reflecting their Pigouvian role. The sign of the Pigouvian part in the income tax schedule is ambiguous and depends crucially on whether status goods are complements or substitutes to leisure.
Early childhood caries and associated determinants: a cross‐sectional study on Italian preschool children
Authors: Congiu Giovanna , Campus Guglielmo , Sale Silvana , Spano Giovanni , Cagetti Maria Grazia , Lugliè Pietrina Francesca
Published: October 2013

Objectives

This study evaluates the influence of several determinants on the presence of early childhood caries (ECC) in preschool children living in northern Sardinia, Italy. These determinants include the educational level and occupational status of the parents as a proxy for the socioeconomical level (SES) and behavioral factors (dietary and oral hygiene).

Methods

An observational cross‐sectional study was designed with a dental examination and a standardized questionnaire. Five hundred forty‐four subjects (260 girls and 284 boys) were enrolled and categorized into two age groups: 359 children were aged 18‐47 months and 185 children were aged 48‐60 months.

Results

The total caries prevalence was 15.99%. Caries risk increased with lower parents' educational level (P = 0.01), increased number of siblings (P < 0.01), the use of bottle feeding (P = 0.02), and the use of a sweetened baby's pacifier at night (P = 0.01). In robust multivariate analysis, a high parental educational level played a protective role on the presence of caries lesion [odds ratio (OR) = 0.51, 95% confidence interval (CI) 0.34‐0.78]; the mother's being employed had a positive statistically significant association with the child having decayed, missing, filled tooth surfaces = 0 (OR = 0.64, 95% CI 0.23‐0.97). The presence of more than one sibling in the family was associated with caries (OR = 1.70, 95% CI 1.20‐2.40).

Conclusion

ECC prevalence evaluated was similar to other western countries, and SES and behavioral habits influence the development of ECC.
Dissolution and pharmacokinetics of baicalin–polyvinylpyrrolidone coprecipitate
Authors: Li Bibo , He Mei , Li Wei , Luo Zhibin , Guo Ying , Li Yajun , Zang Chunbao , Wang Bo , Li Fang , Li Shaolin , Ji Ping
Published: October 2013

Objectives

Baicalin–polyvinylpyrrolidone coprecipitate was prepared with the aim of improving the dissolution and bioavailability of the baicalin.

Methods

The dissolution of the coprecipitate in capsule form was tested and compared with baicalin active pharmaceutical ingredient (API) capsules. A sensitive high-performance liquid chromatography-ultraviolet detection method was established to determine the concentration of baicalin in plasma. The liquid–liquid extraction and solid phase extraction methods were used to pretreat the baicalin plasma sample. The pharmacokinetics of the coprecipitate capsules were tested and compared with the API capsules in six beagle dogs after crossover oral administration.

Key findings

The results of the dissolution demonstrated that the dissolution of the coprecipitate capsules was 21.02, 2.02 and 3.29 times that of the API capsules in 0.1 mol/l HCl solution, pH 4.5 solution and water, respectively, but it was slightly lower than that of the API capsules in a pH 6.8 solution. The calibration curve showed a good linearity at concentrations between 3.648 ng/mL and 364.8 ng/mL (r = 0.998). The baicalin plasma sample was successfully pretreated, with endogenous impurities almost completely removed. The pharmacokinetics of the coprecipitate capsules and the API capsules indicated that the mean values of Cmax were 127.04 ± 10.6 and 27.49 ± 36 μg/l, and those of AUC(0-24h) were 1080.23 ± 336.43 and 337.84 ± 127.64 μg/l × h, respectively. Compared with the baicalin API capsules, the relative bioavailability of the coprecipitate capsules was 338.2% ± 93.2%.

Conclusions

From these observations of improved dissolution and pharmacokinetic behaviours, a good relationship was found in vitro and in vivo, indicating that the coprecipitate could be a promising formulation strategy for insoluble baicalin.
Effect of meal and antisecretory agents on the pharmacokinetics of danoprevir/ritonavir in healthy volunteers
Authors: Morcos Peter N , Moreira Sebastian A , Navarro Mercidita T , Bech Núria , Quatkemeyer Amanda , Smith Patrick F , Brennan Barbara J
Published: October 2013

Objectives

To evaluate the effect of a low- and high-fat meal and co-administration of ranitidine or omeprazole on the pharmacokinetics of ritonavir-boosted danoprevir (DNVr).

Methods

In this randomised, open-label, cross-over study, healthy subjects received a single dose of DNVr. In group 1, DNVr was administered while fasting or with a low-fat or high-fat meal. In group 2, DNVr was administered alone or with ranitidine 150 mg (single dose) or omeprazole 40 mg (multiple doses).

Key findings

Group 1 (n = 16): relative to fasting conditions, food slightly prolonged absorption but did not alter the extent of absorption. DNV area under the plasma concentration–time curve extrapolated to infinity (AUC0–∞), maximum plasma concentration (Cmax), and plasma concentration 12 h after administration (C12h) geometric mean ratios (GMR%) (90% confidence interval (CI)) with a low-fat meal were 92.3 (80.2–106), 61.8 (51.0–74.9) and 95.2 (80.9–112), versus fasting conditions, and with a high-fat meal 99.5 (86.4–115), 58.9 (48.5–71.6) and 101 (86.0–119). Group 2 (n = 13): ranitidine or omeprazole had no clinically significant effect on DNV pharmacokinetics. DNV AUC0–∞, Cmax and C12h GMR% (90% CI) with ranitidine: 81.9 (68.3–98.1), 104 (86.9–123) and 87.5 (69.3–111), and with omeprazole: 83.0 (67.4–102), 92.7 (70.6–122) and 93.3 (65.6–133).

Conclusions

The absence of clinically relevant effects of food, ranitidine or omeprazole on DNVr pharmacokinetics suggests that DNVr can be administered without regard to meals and in combination with H2 antagonists or proton pump inhibitors.
The role of 5-hydroxytryptamine receptor subtypes in the regulation of brain-derived neurotrophic factor gene expression
Authors: Zetterström Tyra S C , Coppell Alexander A , Khundakar Ahmad A
Published: October 2013

Objectives

The study aims to investigate the role of 5-hydroxytryptamine receptor subtypes in mediating the inhibitory effect of the selective serotonin reuptake inhibitor (fluoxetine on brain-derived neurotrophic factor gene (bdnf) expression in rat hippocampus.

Methods

In situ hybridization was used for regional determination of bdnf expression levels in hippocampal brain slices from normal, lesioned (5-hydroxytryptamine or noradrenaline) or adrenalectomized rats; treated with fluoxetine and/or 5-hydroxytryptamine selective ligands.

Key findings

Our study shows that the transient fluoxetine-induced down-regulation of bdnf gene expression depends on an intact 5-hydroxytryptamine but not noradrenaline system or circulating glucocorticoids. Pretreatment with the 5-hydroxytryptamine4 antagonist SB-204070 blocked the overall fluoxetine-induced inhibition of bdnf levels in hippocampus, while pretreatment with the 5-hydroxytryptamine2 antagonists ketanserin had an effect in the CA3 but not in the dentate gyrus sub-region of hippocampus. The 5-hydroxytryptamine1A antagonist WAY-100635 and the 5-hydroxytryptamine3 antagonist granisetron were both ineffective.

Conclusions

Our study found strong support for a primary effect of 5-hydroxytryptamine but not noradrenaline or circulating glucocorticoids in the mediation of fluoxetine-induced down-regulation of bdnf expression. More specifically, we also show that 5-hydroxytryptamine4 receptor-stimulation seems to play a pivotal role in this effect.
Melatonin enhances chondrogenic differentiation of human mesenchymal stem cells
Authors: Gao Wenjie , Lin Mianlong , Liang Anjing , Zhang Liangming , Chen Changhua , Liang Guoyan , Xu Caixia , Peng Yan , Chen Chong , Huang Dongsheng , Su Peiqiang
Published: October 2013

Intramembranous ossification and endochondral ossification are two ways through which bone formation and fracture healing occur. Accumulating amounts of evidence suggests that melatonin affects osteoblast differentiation, but little is known about the effects of melatonin on the process of chondrogenic differentiation. In this study, the effects of melatonin on human mesenchymal stem cells (MSCs) undergoing chondrogenic differentiation were investigated. Cells were induced along chondrogenic differentiation via high‐density micromass culture in chondrogenic medium containing vehicle or 50 nm melatonin. Histological study and quantitative analysis of glycosaminoglycan (GAG) showed induced cartilage tissues to be larger and richer in GAG, collagen type II and collagen type X in the melatonin group than in the untreated controls. Real‐time RT‐PCR analysis demonstrated that melatonin treatment significantly up‐regulated the expression of the genes involved in chondrogenic differentiation, including aggrecan (ACAN), collagen type II (COL2A1), collagen type X (COL10A1), SRY (sex‐determining region Y)‐box 9 (SOX9), runt‐related transcription factor 2 (RUNX2) and the potent inducer of chondrogenic differentiation, bone morphogenetic protein 2 (BMP2). And the expression of melatonin membrane receptors (MT) MT1 and MT2 were detected in the chondrogenic‐induced‐MSCs by immunofluorescence staining. Luzindole, a melatonin receptor antagonist, was found to partially block the ability of melatonin to increase the size and GAG synthesis of the induced cartilage tissues, as well as to completely reverse the effect of melatonin on the gene expression of ACAN, COL2A1, COL10A1, SOX9 and BMP2 after 7 days of differentiation. These findings demonstrate that melatonin enhances chondrogenic differentiation of human MSCs at least partially through melatonin receptors.
Peyronie's Disease Plaque Calcification—Prevalence, Time to Identification, and Development of a New Grading Classification
Authors: Levine Laurence , Rybak James , Corder Christopher , Farrel Michael Ryan
Published: October 2013

Introduction

Peyronie's disease (PD) is a connective tissue disorder of the penis in which a fibrous scar in the tunica albuginea can result in multiple penile deformities.

Aim

The study aims to investigate the prevalence and time to identification of plaque calcification (PC) in our PD patient population and whether stratification of calcification based on severity seen on ultrasound would serve as a predictor of treatment progression to surgery.

Methods

A retrospective review of 1,041 men presenting with PD from 1993 to 2009 was performed. Eight hundred thirty-four underwent penile duplex ultrasound.

Main Outcome Measures

PC was graded as: grade 1 (<0.3 cm), grade 2 (>0.3 cm, <1.5 cm), grade 3 (>1.5 cm; or ≥2 plaques >1.0 cm). A matched control group with noncalcified plaques (n = 236) was selected for comparison.

Results

Two hundred eighty-four men (34%) were found to have PC noted on ultrasound, and 98 had fully documented dimensions of the PC. Forty-one percent were found to have grade 1, 28% grade 2, and 32% grade 3. When analyzed by grade and progression to surgery, 23% of grade 1, 32% of grade 2, and 55% of grade 3 patients had surgery. Those with grade 3 PC were more likely to undergo surgical intervention for PD (OR 2.28 95% CI 1.07–4.86) and more likely to undergo a grafting procedure than control patients (P < 0.0001).

Conclusions

Men with PC are not more likely to undergo surgery than those without PC (OR 0.95, 95% CI 0.58–1.57). PC is not uncommon, as it was found in 34% of our cohort. PC does not appear to be an indication of mature or stable disease, as it was identified by ultrasound in 37% of patients less than 12 months after onset of symptoms. Men with grade 3 PC have an increased likelihood of progression to surgical intervention and a higher likelihood of undergoing a grafting procedure.
Time in bed, sleep quality and associations with cardiometabolic markers in children: the Prevention and Incidence of Asthma and Mite Allergy birth cohort study
Authors: Berentzen Nina E. , Smit Henriëtte A. , Bekkers Marga B. M. , Brunekreef Bert , Koppelman Gerard H. , De Jongste Johan C. , Kerkhof Marjan , Van Rossem Lenie , Wijga Alet H.
Published: October 2013

We investigated associations of time in bed and multiple sleep quality characteristics with cardiometabolic markers in children. Data from the prevention and incidence of asthma and mite allergy study, a population‐based prospective birth‐cohort study started in 1996–1997 in the Netherlands, were analysed. In total 1481 children aged 11–12 years completed a questionnaire (including questions on sleep) and underwent a medical examination. We measured body mass index, waist circumference, total‐ and high‐density lipoprotein cholesterol, blood pressure and glycated haemoglobin. Results showed that in girls, some sleep characteristics were related to anthropometrics (body mass index, waist circumference) and cholesterol. Girls who had a long time in bed (11–12.5 h) had 0.16 lower body mass index z‐score (95% confidence interval −0.31; −0.01) and 0.99 cm smaller waist circumference (95% confidence interval −2.01; −0.13) compared with girls who spent 10–10.5 h in bed. Girls who went to bed late and rose early had 0.16 mm higher total cholesterol (95% confidence interval 0.01; 0.31) and 0.08 mm higher high‐density lipoprotein cholesterol (95% confidence interval 0.01; 0.14) than ‘early to bed/early rise’ girls. Girls with night‐time awakenings had 0.14 mm higher total cholesterol (95% confidence interval 0.03; 0.25) than girls without night‐time awakenings. Girls who felt sleepy/tired ≥1 day per week had 0.10 mm lower high‐density lipoprotein cholesterol (95% confidence interval −0.16; −0.04) and 0.17 mm higher total cholesterol/high‐density lipoprotein cholesterol ratio (95% confidence interval 0.02; 0.32) than girls who did not feel sleepy. No associations were found for boys. Sleep characteristics were not related to blood pressure and glycated haemoglobin, and effect sizes of the associations in girls were small. Therefore, we consider it premature to propose that improved sleep could reduce cardiovascular risk during childhood.