Eosinophilic Esophagitis in Children

Abstract

Purpose of Review

EoE is a significant cause of gastrointestinal morbidity affecting 1:2000. Patients with EoE typically have multiple atopic comorbidities, and additionally, many patients with EoE can be controlled well with elimination diets. The purpose of this review is to summarize the care of pediatric eosinophilic esophagitis patients.

Recent Findings

EoE represents a distinct clinical syndrome which is characterized by esophageal dysfunction and eosinophil-predominant inflammation of the esophageal mucosa. Patients with EoE can present with varying symptoms depending on their age; in this review, we review the presenting features of eosinophilic esophagitis in children as well as a diagnostic algorithm for EoE. The mucosal inflammation in EoE is driven by exposure to food antigens in many patients with EoE. Therefore, for the majority of patients, the mainstays of treatment remain food elimination diets or swallowed steroids.

Summary

This review summarizes the diagnostic approach to eosinophilic esophagitis (EoE) in pediatric patients, focusing on the importance of accurate diagnosis and selection of appropriate therapy.

http://ift.tt/2rS9NLg

Eosinophilic Esophagitis in Children

Abstract

Purpose of Review

EoE is a significant cause of gastrointestinal morbidity affecting 1:2000. Patients with EoE typically have multiple atopic comorbidities, and additionally, many patients with EoE can be controlled well with elimination diets. The purpose of this review is to summarize the care of pediatric eosinophilic esophagitis patients.

Recent Findings

EoE represents a distinct clinical syndrome which is characterized by esophageal dysfunction and eosinophil-predominant inflammation of the esophageal mucosa. Patients with EoE can present with varying symptoms depending on their age; in this review, we review the presenting features of eosinophilic esophagitis in children as well as a diagnostic algorithm for EoE. The mucosal inflammation in EoE is driven by exposure to food antigens in many patients with EoE. Therefore, for the majority of patients, the mainstays of treatment remain food elimination diets or swallowed steroids.

Summary

This review summarizes the diagnostic approach to eosinophilic esophagitis (EoE) in pediatric patients, focusing on the importance of accurate diagnosis and selection of appropriate therapy.

http://ift.tt/2rS9NLg

Professional Ethics: Making the Right Decision

Professionals today are faced with many ethical dilemmas and it has become crucial for clinicians to understand how ethical decisions are made, what are the necessary considerations and how to apply each to the many ethical dilemmas they may face. This course will give an overview of the why's and how's to making an ethical decision and will provide the practitioner with a framework for exploring ethical dilemmas.

http://ift.tt/2tbtmlL

Vanderbilt Audiology Journal Club - Research Examining Benefit of Hearing Aid Features

Dr. Todd Ricketts from Vanderbilt University discusses recent key journal articles regarding evidence for the benefits of select hearing aid features, and their implications for audiology clinical practice.

http://ift.tt/2tb00Ul

A gastric MANEC with an adenocarcinoma of fundic-gland type as exocrine component

http://ift.tt/2tL2A12

Chondrolipoma of the breast as a rare variant of myofibroblastoma: an immunohistochemical study of two cases

Abstract

Chondrolipoma of the breast is a very rare tumor whose histogenesis remains obscure. We report two cases (56-year-old and 43-year-old women) and present the results of an immunohistochemical study which strongly suggests that this tumor is a variant of myofibroblastoma. The tumors predominantly consisted of lipoma-like, mature adipose tissue, and many islands of hyaline cartilage. A proliferation of spindle cells associated with the deposition of collagen fibers was also seen. On immunohistochemical examination, spindle cells showed cytoplasmic reactivity for vimentin, desmin, bcl-2, and α-smooth muscle actin, as well as nuclear reactivity for estrogen receptor (ER) and progesterone receptor (PgR). Chondrocytes were immunoreactive for ER, PgR, S-100 protein, and Sox9. The nuclei of adipocytes, chondrocytes, and spindle cells were not immunoreactive for Rb (retinoblastoma) protein. The immunoreactivity of spindle cells for muscle markers indicates myofibroblastic differentiation, and the lack of the nuclear expression of Rb protein suggests the close relationship of this tumor with myofibroblastoma and spindle cell lipoma. The immunoreactivity of chondrocytes for ER and PgR suggests that they are derived from metaplasia of hormone-sensitive spindle cells. These findings support the concept that chondrolipoma of the breast could be a lipomatous variant of myofibroblastoma associated with cartilaginous metaplasia and that it should be added to members of the "13q/Rb family of tumors."

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Cancer epigenetics: Therapy-induced transcription is cryptically widespread

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Disease genetics: Repeat expansion disorders — going through a phase

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Synthetic lethality and cancer

The authors review the concept of synthetic lethality — when the perturbation of one of two genes alone is viable, but the perturbation of both genes simultaneously results in the loss of viability — from model organisms to human cancers, and discuss how genetic interactions can be exploited for the identification of new drug targets in cancer.

http://ift.tt/2sRtnbM

Granuloma faciale associated with IgG4-related disease

http://ift.tt/2t7Rrtm

Therapeutic efficacy and safety of oral tranexamic acid and that of tranexamic acid local infiltration with microinjections in patients with melasma: a comparative study

Summary

Background

Tranexamic acid (TXA) has been used orally, intravenously, topically and intradermally (microinjection, microneedling) for treating melasma. However, the comparative efficacy of these different routes of administration remains underevaluated.

Aim

To ascertain the comparative efficacy of different routes of administration of TXA.

Methods

In total, 100 consecutive patients with melasma (8 men, 92 women, age range 18–55 years) were randomly assigned to one of two groups comprising 50 patients each. Group A (3 men, 47 women) received oral TXA 250 mg twice daily, while group B (5 men, 45 women) received intradermal microinjections of TXA 4 mg/mL every 4 weeks. The treatment continued for 12 weeks in both groups. Percentage reduction in baseline Melasma Area and Severity Index (MASI) was assessed at 4-week intervals, and response was scored as very good (> 75% reduction), good (50% to < 75% reduction), moderate (25% to < 50% reduction), mild (< 25% reduction) or no response.

Results

The study was completed by 39 patients in group A and 41 patients in group B. Very good response was seen in 25 and 32 patients in groups A and B, respectively, while good response was seen in 14 and 9 patients, respectively. Both treatment methods were equally effective, with an average reduction of MASI at 12 weeks of 77.96 ± 9.39 in group A and 79.00 ± 9.64 in group B. The main adverse effects were mild epigastric discomfort, hypomenorrhea, headache and injection site pain, which did not warrant discontinuation of treatment. Two patients in group A had relapses at 24 weeks.

Conclusion

TXA appears to be an effective and safe treatment for melasma, irrespective of its route of administration.

http://ift.tt/2u5aPEw

Long-term management of chronic spontaneous urticaria with omalizumab

Summary

Background

Clinical trials have shown the efficacy of omalizumabs efficacy in refractory chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), but real-life management strategies are lacking.

Aim

To assess the long-term efficacy and safety of omalizumab, and to identify predictive factors and optimum dosage regimens.

Methods

This was a prospective study of 13 patients (11 women, 2 men) with severe CSU [weekly urticaria activity score (UAS7) > 28] resistant to anti-H1 antihistamines. Patients were started on omalizumab 150 mg subcutaneously every 4 weeks. Dose and interval between administrations were adjusted according to clinical response (189 administrations; treatment duration range 2–38 months).

Results

Mean UAS7 was 36.3 ± 5.4. Of the 13 patients, all had experienced angio-oedema, while in addition, 7 had delayed pressure urticaria (DPU) and 1 had solar urticaria (SU). After omalizumab treatment, 4 (30.8%) of the 13 patients had complete response (CR), and the remaining 8 (61.5%) had partial response. CR was achieved with a dose of 150 mg every 4 (n = 2 patients) or 5 (n = 2) weeks. One of these patients remained disease-free after stopping treatment. Partial responses were achieved with 150 mg every 4 weeks (n = 4) and with 300 mg (n = 4) at intervals of 5 weeks (n = 1), 4 weeks (n = 2) or 3 weeks (n = 1). Only one patient (7.7%) did not show significant improvement, despite a dose of 300 mg every 4 weeks. There were no significant differences in epidemiological, clinical and laboratory data between the different response groups. Only two adverse events were observed: one was mild headache and the other was severe angio-oedema and aggravation of urticaria within 6 h of omalizumab administration.

Conclusion

Omalizumab dose and interval between administrations could be individualized for long-term management of CSU.

http://ift.tt/2t7znPQ

Adjuvant therapy with low-dose interferon-beta for stage II and III melanoma: results of a retrospective analysis

Summary

Interferon (IFN)-alfa as an adjuvant therapy has been found to improve relapse-free survival in patients with malignant melanoma (MM). However, the efficacy of IFN-beta has not been studied in detail. This study evaluated the contribution of adjuvant IFN-beta therapy to improvements in the prognosis of patients with MM. We reviewed 63 patients with resected stage II/III primary MM at our institution. Of these, 36 had been treated with IFN-beta adjuvant therapy (subcutaneous injection, 3 × 10⁶ IU/day, 10 days), while 27 patients had undergone observation alone. In comparisons of all patients (stage II/III), overall survival and relapse-free survival were significantly better in the IFN-beta group than in the observation group (P < 0.001 for both). The 75-month overall survival rate was 41.2% in the observation group and 68.7% in the IFN-beta group. Adjuvant therapy with IFN-beta may become a new treatment option for patients with stage II/III MM.

http://ift.tt/2u5CncW

Granuloma faciale associated with IgG4-related disease

http://ift.tt/2t7Rrtm

Therapeutic efficacy and safety of oral tranexamic acid and that of tranexamic acid local infiltration with microinjections in patients with melasma: a comparative study

Summary

Background

Tranexamic acid (TXA) has been used orally, intravenously, topically and intradermally (microinjection, microneedling) for treating melasma. However, the comparative efficacy of these different routes of administration remains underevaluated.

Aim

To ascertain the comparative efficacy of different routes of administration of TXA.

Methods

In total, 100 consecutive patients with melasma (8 men, 92 women, age range 18–55 years) were randomly assigned to one of two groups comprising 50 patients each. Group A (3 men, 47 women) received oral TXA 250 mg twice daily, while group B (5 men, 45 women) received intradermal microinjections of TXA 4 mg/mL every 4 weeks. The treatment continued for 12 weeks in both groups. Percentage reduction in baseline Melasma Area and Severity Index (MASI) was assessed at 4-week intervals, and response was scored as very good (> 75% reduction), good (50% to < 75% reduction), moderate (25% to < 50% reduction), mild (< 25% reduction) or no response.

Results

The study was completed by 39 patients in group A and 41 patients in group B. Very good response was seen in 25 and 32 patients in groups A and B, respectively, while good response was seen in 14 and 9 patients, respectively. Both treatment methods were equally effective, with an average reduction of MASI at 12 weeks of 77.96 ± 9.39 in group A and 79.00 ± 9.64 in group B. The main adverse effects were mild epigastric discomfort, hypomenorrhea, headache and injection site pain, which did not warrant discontinuation of treatment. Two patients in group A had relapses at 24 weeks.

Conclusion

TXA appears to be an effective and safe treatment for melasma, irrespective of its route of administration.

http://ift.tt/2u5aPEw

Long-term management of chronic spontaneous urticaria with omalizumab

Summary

Background

Clinical trials have shown the efficacy of omalizumabs efficacy in refractory chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), but real-life management strategies are lacking.

Aim

To assess the long-term efficacy and safety of omalizumab, and to identify predictive factors and optimum dosage regimens.

Methods

This was a prospective study of 13 patients (11 women, 2 men) with severe CSU [weekly urticaria activity score (UAS7) > 28] resistant to anti-H1 antihistamines. Patients were started on omalizumab 150 mg subcutaneously every 4 weeks. Dose and interval between administrations were adjusted according to clinical response (189 administrations; treatment duration range 2–38 months).

Results

Mean UAS7 was 36.3 ± 5.4. Of the 13 patients, all had experienced angio-oedema, while in addition, 7 had delayed pressure urticaria (DPU) and 1 had solar urticaria (SU). After omalizumab treatment, 4 (30.8%) of the 13 patients had complete response (CR), and the remaining 8 (61.5%) had partial response. CR was achieved with a dose of 150 mg every 4 (n = 2 patients) or 5 (n = 2) weeks. One of these patients remained disease-free after stopping treatment. Partial responses were achieved with 150 mg every 4 weeks (n = 4) and with 300 mg (n = 4) at intervals of 5 weeks (n = 1), 4 weeks (n = 2) or 3 weeks (n = 1). Only one patient (7.7%) did not show significant improvement, despite a dose of 300 mg every 4 weeks. There were no significant differences in epidemiological, clinical and laboratory data between the different response groups. Only two adverse events were observed: one was mild headache and the other was severe angio-oedema and aggravation of urticaria within 6 h of omalizumab administration.

Conclusion

Omalizumab dose and interval between administrations could be individualized for long-term management of CSU.

http://ift.tt/2t7znPQ

Adjuvant therapy with low-dose interferon-beta for stage II and III melanoma: results of a retrospective analysis

Summary

Interferon (IFN)-alfa as an adjuvant therapy has been found to improve relapse-free survival in patients with malignant melanoma (MM). However, the efficacy of IFN-beta has not been studied in detail. This study evaluated the contribution of adjuvant IFN-beta therapy to improvements in the prognosis of patients with MM. We reviewed 63 patients with resected stage II/III primary MM at our institution. Of these, 36 had been treated with IFN-beta adjuvant therapy (subcutaneous injection, 3 × 10⁶ IU/day, 10 days), while 27 patients had undergone observation alone. In comparisons of all patients (stage II/III), overall survival and relapse-free survival were significantly better in the IFN-beta group than in the observation group (P < 0.001 for both). The 75-month overall survival rate was 41.2% in the observation group and 68.7% in the IFN-beta group. Adjuvant therapy with IFN-beta may become a new treatment option for patients with stage II/III MM.

http://ift.tt/2u5CncW

Rationale for two influenza B lineages in seasonal vaccines: A meta-regression study on immunogenicity and controlled field trials

Publication date: Available online 24 June 2017
Source:Vaccine
Author(s): W.E.P. Beyer, A.M. Palache, M. Boulfich, A.D.M.E. Osterhaus
B lineage mismatch prompted introduction of quadri-valent influenza vaccines (QIV) with two influenza B viruses representing distinct antigenic lineages. To explore the impact on antibody induction and vaccine effectiveness predicted from antibody (VEab), we performed a systematic literature search on immunogenicity studies conducted to assess antibody superiority of QIV over trivalent influenza vaccine (TIV). Thirteen relevant articles described 31 trials from 2007 and 2013. Log-transformed GMT trial estimates and their variances were converted to clinical protection rates predicted from antibody (PRab). VEab estimates were calculated from pre- and post-vaccination PRab. Without specific pre-vaccination immunity, average VEab was 69% for match, and −4% for lineage mismatch. With increasing pre-vaccination seropositivity, mismatch impact declined to 2%. We also performed an umbrella literature search for randomised controlled trials and test-negative case-control trials with TIV, and estimated vaccine effectiveness against laboratory-confirmed influenza B (VEf). Sixty-eight eligible clinical articles described 110 season-trials from 1965 to 2012, covering seasons with B lineage match (n=52), lineage drift (n=15) and lineage mismatch (n=43). With no pre-vaccination antibody levels determined, we used chance of previous exposure to influenza B (Ppe) as pre-seasonal immunity measure. When Ppe was 0%, average VEf for matched seasons was 67%, and for mismatched seasons 35%, indicating a moderate, yet significant mismatch impact on VEf. With increasing Ppe, mismatch impact declined to 3%. Thus serological and field trials indicate that B lineage mismatch impact is negatively related to pre-seasonal immunity and that the gain of QIV over TIV most benefits infants and children not yet exposed to influenza B.



http://ift.tt/2u4fgPT

Protein kinase STK25 aggravates the severity of non-alcoholic fatty pancreas disease in mice

Characterising the molecular networks that negatively regulate pancreatic β-cell function is essential for understanding the underlying pathogenesis and developing new treatment strategies for type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a critical regulator of ectopic fat storage, meta-inflammation, and fibrosis in liver and skeletal muscle. Here, we assessed the role of STK25 in control of progression of non-alcoholic fatty pancreas disease in the context of chronic exposure to dietary lipids in mice. We found that overexpression of STK25 in high-fat-fed transgenic mice aggravated diet-induced lipid storage in the pancreas compared with that of wild-type controls, which was accompanied by exacerbated pancreatic inflammatory cell infiltration, stellate cell activation, fibrosis and apoptosis. Pancreas of Stk25 transgenic mice also displayed a marked decrease in islet β/α-cell ratio and alteration in the islet architecture with an increased presence of α-cells within the islet core, whereas islet size remained similar between genotypes. After a continued challenge with a high-fat diet, lower levels of fasting plasma insulin and C-peptide, and higher levels of plasma leptin, were detected in Stk25 transgenic vs wild-type mice. Furthermore, the glucose-stimulated insulin secretion was impaired in high-fat-fed Stk25 transgenic mice during glucose tolerance test, in spite of higher net change in blood glucose concentrations compared with wild-type controls, suggesting islet β-cell dysfunction. In summary, this study unravels a role for STK25 in determining the susceptibility to diet-induced non-alcoholic fatty pancreas disease in mice in connection to obesity. Our findings highlight STK25 as a potential drug target for metabolic disease.

http://ift.tt/2sb41Uz

Skeletal energy homeostasis: a paradigm of endocrine discovery

Throughout the last decade, significant developments in cellular, molecular and mouse models have revealed major endocrine functions of the skeleton. More recent studies have evolved the interplay between bone-specific hormones, the skeleton, marrow adipose tissue, muscle and the brain. This review focuses on literature from the last decade, addressing the endocrine regulation of global energy metabolism via the skeleton. In addition, we will highlight several recent studies that further our knowledge of new endocrine functions of some organs; explore remaining unanswered questions; and, finally, we will discuss future directions for this more complex era of bone biology research.

http://ift.tt/2sFYjNV

Hypothalamic effects of neonatal diet: reversible and only partially leptin dependent

Early life diet influences metabolic programming, increasing the risk for long-lasting metabolic ill health. Neonatally overfed rats have an early increase in leptin that is maintained long term and is associated with a corresponding elevation in body weight. However, the immediate and long-term effects of neonatal overfeeding on hypothalamic anorexigenic pro-opiomelanocortin (POMC) and orexigenic agouti-related peptide (AgRP)/neuropeptide Y (NPY) circuitry, and if these are directly mediated by leptin, have not yet been examined. Here, we examined the effects of neonatal overfeeding on leptin-mediated development of hypothalamic POMC and AgRP/NPY neurons and whether these effects can be normalised by neonatal leptin antagonism in male Wistar rats. Neonatal overfeeding led to an acute (neonatal) resistance of hypothalamic neurons to exogenous leptin, but this leptin resistance was resolved by adulthood. While there were no effects of neonatal overfeeding on POMC immunoreactivity in neonates or adults, the neonatal overfeeding-induced early increase in arcuate nucleus (ARC) AgRP/NPY fibres was reversed by adulthood so that neonatally overfed adults had reduced NPY immunoreactivity in the ARC compared with controls, with no further differences in AgRP immunoreactivity. Short-term neonatal leptin antagonism did not reverse the excess body weight or hyperleptinaemia in the neonatally overfed, suggesting factors other than leptin may also contribute to the phenotype. Our findings show that changes in the availability of leptin during early life period influence the development of hypothalamic connectivity short term, but this is partly resolved by adulthood indicating an adaptation to the metabolic mal-programming effects of neonatal overfeeding.

http://ift.tt/2sbbjaz

MiRNA-143 mediates the proliferative signaling pathway of FSH and regulates estradiol production

MicroRNAs (MiRNAs) play important regulatory roles in many cellular processes. MiR-143 is highly enriched in the mouse ovary, but its roles and underlying mechanisms are not well understood. In the current study, we show that miR-143 is located in granulosa cells of primary, secondary and antral follicles. To explore the specific functions of miR-143, we transfected miR-143 inhibitor into primary cultured granulosa cells to study the loss of function of miR-143 and the results showed that miR-143 silencing significantly increased estradiol production and steroidogenesis-related gene expression. Moreover, our in vivo and in vitro studies showed that follicular stimulating hormone (FSH) significantly decreased miR-143 expression. This function of miR-143 is accomplished by its binding to the 3'-UTR of KRAS mRNA. Furthermore, our results demonstrated that miR-143 acts as a negative regulating molecule mediating the signaling pathway of FSH and affecting estradiol production by targeting KRAS. MiR-143 also negatively acts in regulating granulosa cells proliferation and cell cycle-related genes expression. These findings indicate that miR-143 plays vital roles in FSH-induced estradiol production and granulosa cell proliferation, providing a novel mechanism that involves miRNA in regulating granulosa cell functions.

http://ift.tt/2sG7az6

The metabolic syndrome in mice overexpressing neuropeptide Y in noradrenergic neurons

A gain-of-function polymorphism in human neuropeptide Y (NPY) gene (rs16139) associates with metabolic disorders and earlier onset of type 2 diabetes (T2D). Similarly, mice overexpressing NPY in noradrenergic neurons (OE-NPY^DBH) display obesity and impaired glucose metabolism. In this study, the metabolic syndrome-like phenotype was characterized and mechanisms of impaired hepatic fatty acid, cholesterol and glucose metabolism in pre-obese (2-month-old) and obese (4–7-month-old) OE-NPY^DBH mice were elucidated. Susceptibility to T2D was assessed by subjecting mice to high caloric diet combined with low-dose streptozotocin. Contribution of hepatic Y1-receptor to the phenotype was studied using chronic treatment with an Y1-receptor antagonist, BIBO3304. Obese OE-NPY^DBH mice displayed hepatosteatosis and hypercholesterolemia preceded by decreased fatty acid oxidation and accelerated cholesterol synthesis. Hyperinsulinemia in early obese state inhibited pyruvate- and glucose-induced hyperglycemia, and deterioration of glucose metabolism of OE-NPY^DBH mice developed with aging. Furthermore, streptozotocin induced T2D only in OE-NPY^DBH mice. Hepatic inflammation was not morphologically visible, but upregulated hepatic anti-inflammatory pathways and increased 8-isoprostane combined with increased serum resistin and decreased interleukin 10 pointed to increased NPY-induced oxidative stress that may predispose OE-NPY^DBH mice to insulin resistance. Chronic treatment with BIBO3304 did not improve the metabolic status of OE-NPY^DBH mice. Instead, downregulation of beta-1-adrenoceptors suggests indirect actions of NPY via inhibition of sympathetic nervous system. In conclusion, changes in hepatic fatty acid, cholesterol and glucose metabolism favoring energy storage contribute to the development of NPY-induced metabolic syndrome, and the effect is likely mediated by changes in sympathetic nervous system activity.

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Effect of mitotane on mouse ovarian follicle development and fertility

Mitotane (MTT) is an adrenolytic drug used in advanced and adjuvant treatment of adrenocortical carcinoma, in Cushing's disease and in ectopic syndrome. However, knowledge about its effects on the ovary is still scarce. The purpose of this study is to investigate the effect of MTT on the ovary using in vivo and in vitro models. The study was performed in CD1 mice and in the COV-434 human ovarian granulosa cell line. We examined ovarian morphology, follicle development, steroidogenesis and procreative function in mice and the effect of MTT on cell growth in vitro. Our results revealed that treatment of CD1 mice with MTT induces a decrease in early antral follicles with a subsequent increase in the secondary follicles, measured by the increased levels of anti-Mullerian Hormone (P < 0.05) and decreased levels of FSH receptor (P < 0.05). Moreover, we observed a significant decrease in Cyp11a1 (P < 0.01) and Cyp17a1 (P < 0.001) mRNA level in MTT-treated animals. Ovulation, induced by PMSG/hCG stimulation, was also significantly impaired, with a reduction in the number of ovulated oocytes (P < 0.01) and fewer corpora lutea in treated animals. Likewise, the mating experiment demonstrated a delay in the time of conception as well as fewer pups per litter in MTT-treated mice (P < 0.05). Experiments performed on the COV-434 cell line showed a significant inhibition of growth followed by apoptosis (P < 0.01). In conclusion, our study highlights the key points of ovarian folliculogenesis affected by MTT and demonstrates impairment of the ovulation process with a negative impact on conception, which is nevertheless preserved.

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Attention, processing speed, and executive functioning in pediatric brain tumor survivors treated with proton beam radiation therapy

Publication date: Available online 24 June 2017
Source:Radiotherapy and Oncology
Author(s): Tanya N. Antonini, M. Douglas Ris, David R. Grosshans, Anita Mahajan, M. Fatih Okcu, Murali Chintagumpala, Arnold Paulino, Amanda E. Child, Jessica Orobio, Heather H. Stancel, Lisa S. Kahalley
Background and purposeThis study examines attention, processing speed, and executive functioning in pediatric brain tumor survivors treated with proton beam radiation therapy (PBRT).Material and methodsWe examined 39 survivors (age 6–19years) who were 3.61years post-PBRT on average. Craniospinal (CSI; n=21) and focal (n=18) subgroups were analyzed. Attention, processing speed, and executive functioning scores were compared to population norms, and clinical/demographic risk factors were examined.ResultsAs a group, survivors treated with focal PBRT exhibited attention, processing speed, and executive functioning that did not differ from population norms (all p>0.05). Performance in the CSI group across attention scales was normative (all p>0.05), but areas of relative weakness were identified on one executive functioning subtest and several processing speed subtests (all p<0.01).ConclusionsSurvivors treated with PBRT may exhibit relative resilience in cognitive domains traditionally associated with radiation late effects. Attention, processing speed, and executive functioning remained intact and within normal limits for survivors treated with focal PBRT. Among survivors treated with CSI, a score pattern emerged that was suggestive of difficulties in underlying component skills (i.e., processing speed) rather than true executive dysfunction. No evidence of profound cognitive impairment was found in either group.



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Mind Games: Game Engines as an Architecture for Intuitive Physics

Publication date: Available online 24 June 2017
Source:Trends in Cognitive Sciences
Author(s): Tomer D. Ullman, Elizabeth Spelke, Peter Battaglia, Joshua B. Tenenbaum
We explore the hypothesis that many intuitive physical inferences are based on a mental physics engine that is analogous in many ways to the machine physics engines used in building interactive video games. We describe the key features of game physics engines and their parallels in human mental representation, focusing especially on the intuitive physics of young infants where the hypothesis helps to unify many classic and otherwise puzzling phenomena, and may provide the basis for a computational account of how the physical knowledge of infants develops. This hypothesis also explains several 'physics illusions', and helps to inform the development of artificial intelligence (AI) systems with more human-like common sense.



http://ift.tt/2tJnsFK

Controlling the pro-inflammatory function of 6-sulfo LacNAc (slan) dendritic cells with dimethylfumarate

Publication date: Available online 24 June 2017
Source:Journal of Dermatological Science
Author(s): Stephanie Oehrl, Florina Olaru, Anja Kunze, Michael Maas, Silvia Pezer, Marc Schmitz, Knut Schäkel
BackroundThe fumaric acid ester (FAE) dimethylfumarate (DMF) is a small molecule immunomodulator successfully used for the treatment of psoriasis and multiple sclerosis (MS). DMF is thought to inhibit pathogenic immune responses with Th17/Th1T cells, and IL-23/IL-12 producing dendritic cells (DCs). 6-sulfo LacNAc expressing dendritic cells (slanDCs) are a human pro-inflammatory cell type found frequently among the infiltrating leukocytes in skin lesions of psoriasis and brain lesions of MS.ObjectiveTo explore the influence of DMF on functional properties and cell signaling pathways of slanDCs.MethodsIn the context of slanDCs we studied the role of DMF in modulating cell migration, phenotypic maturation, cytokine production, cell signaling and T cell stimulation.ResultsInitially, we observed the reduction of slanDCs numbers in psoriasis skin lesions of FAE treated patients. Studying whether DMF controls the migratory capacity of slanDCs to chemotactic factors expressed in psoriasis we observed an inhibition of the CX3CL1 and C5a depedent cell migration. DMF also attenuated the rapid spontaneous phenotypic maturation of slanDCs, as judged by a reduced CD80, CD86, CD83 and HLA-DR expression. In addition, we observed a DMF-dependent decrease of IL-23, IL-12, TNF-α and IL-10 secretion, and noticed a reduced capacity to stimulate Th17/Th1 responses. DMF targeted in slanDCs different intracellular cell signaling pathways including NFκB, STAT1 and HO-1.ConclusionsWith this study we identify a frequent pro-inflammatory cell type found in psoriasis and MS as a relevant target for the therapeutic immunomodulatory effects of DMF.



http://ift.tt/2rQwsHU

Wolf–Hirschhorn Syndrome Candidate 1 (whsc1) Functions as a Tumor Suppressor by Governing Cell Differentiation

Publication date: August 2017
Source:Neoplasia, Volume 19, Issue 8
Author(s): Chuan Yu, Xiaomin Yao, Linjie Zhao, Ping Wang, Qian Zhang, Chengjian Zhao, Shaohua Yao, Yuquan Wei
Wolf–Hirschhorn syndrome candidate 1 (WHSC1) is a histone 3 lysine 36 (H3K36) specific methyltransferase that is frequently deleted in Wolf–Hirschhorn syndrome (WHS). Whsc1 is also found mutated in a subgroup of B-cell derived malignant diseases by genomic translocation or point mutation, both of which resulted in hyperactivity of WHSC1 mediated H3K36 methylation and uncontrolled cell proliferation, suggesting that whsc1 functions as an oncogene. However, here we provided evidences to show that whsc1 also has tumor suppressor functions. We used zebrafish as an in vivo model and generated homozygous whsc1 mutant lines via clustered regularly interspaced short palindromic repeats-associated protein Cas9 (CRISPR/Cas9) technology. Then western-blot (WB) and immunofluorescence (IF) were performed to analysis the expression level of H3K36Me2 and H3K36Me3, and we identified the diseased tissue via hematoxylin–eosin (HE) staining, IF staining or immunohistochemistry (IHC). Whsc1 lose-of-function led to significant decrease in di- and tri-methylation of H3K36. A series of WHS related phenotypes were found in whsc1^−/− zebrafish, including growth retardation, neural development defects and heart failure. In addition, loss of function of whsc1 led to defects in the development of swim bladder, possibly through the dis-regulation of key genes in swim bladder organogenesis and inhibition of progenitor cell differentiation, which was correlated with its expression in this organ during embryonic development. At later stage, these whsc1^−/− zebrafishes are inclined to grow tumors in the swim bladder. Our work suggested that whsc1 may function as a tumor suppressor by governing progenitor cell differentiation.



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The Mitochondrial dynamics in cancer and immune-surveillance

Publication date: Available online 24 June 2017
Source:Seminars in Cancer Biology
Author(s): Luca Simula, Francesca Nazio, Silvia Campello
Mitochondria-shaping proteins control the dynamic equilibrium between fusion and fission of the mitochondrial network. Their balance is strictly required to regulate various processes, including the quality of mitochondria, cell metabolism, cell death, proliferation and cell migration. Alterations in these processes are frequently encountered in cancer, during both its onset and later progression, as evidence emerge connecting alterations in mitochondrial dynamics with cancer development. In recent years, novel therapeutic approaches to fight against different human tumors aim at exploiting the immune system's ability to specifically recognize tumor antigens, thus killing malignant cells in a process named immune-surveillance. Interestingly, data are accumulating on the role that mitochondrial dynamics play also for the correct function of both the innate and the adaptive immune system. By this review, we overview how mitochondrial dynamics can affect various processes during cancer development, acting directly on tumor cells or indirectly on cells responsible for tumor aggression and defence.



http://ift.tt/2t5RllL

Visceral sensitivity, anxiety, and smoking among treatment-seeking smokers

Publication date: December 2017
Source:Addictive Behaviors, Volume 75
Author(s): Michael J. Zvolensky, Jafar Bakhshaie, Peter J. Norton, Jasper A.J. Smits, Julia D. Buckner, Lorra Garey, Kara Manning
It is widely recognized that smoking is related to abdominal pain and discomfort, as well as gastrointestinal disorders. Research has shown that visceral sensitivity, experiencing anxiety around gastrointestinal sensations, is associated with poorer gastrointestinal health and related health outcomes. Visceral sensitivity also increases anxiety symptoms and mediates the relation with other risk factors, including gastrointestinal distress. No work to date, however, has evaluated visceral sensitivity in the context of smoking despite the strong association between smoking and poor physical and mental health. The current study sought to examine visceral sensitivity as a unique predictor of cigarette dependence, threat-related smoking abstinence expectancies (somatic symptoms and harmful consequences), and perceived barriers for cessation via anxiety symptoms. Eighty-four treatment seeking adult daily smokers (Mage=45.1years [SD=10.4]; 71.6% male) participated in this study. There was a statistically significant indirect effect of visceral sensitivity via general anxiety symptoms on cigarette dependence (b=0.02, SE=0.01, Bootstrapped 95% CI [0.006, 0.05]), smoking abstinence somatic expectancies (b=0.10, SE=0.03, Bootstrapped 95% CI [0.03, 0.19]), smoking abstinence harmful experiences (b=0.13, SE=0.05, Bootstrapped 95% CI [0.03, 0.25]), and barriers to cessation (b=0.05, SE=0.06, Bootstrapped 95% CI [0.01, 0.13]). Overall, the present study serves as an initial investigation into the nature of the associations between visceral sensitivity, anxiety symptoms, and clinically significant smoking processes among treatment-seeking smokers. Future work is needed to explore the extent to which anxiety accounts for relations between visceral sensitivity and other smoking processes (e.g., withdrawal, cessation outcome).



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New nano-hydroxyapatite in bone defect regeneration: a histological study in rats

Publication date: Available online 24 June 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Paweł Kubasiewicz-Ross, Jakub Hadzik, Julia Seeliger, Karol Kozak, Kamil Jurczyszyn, Hanna Gerber, Marzena Dominiak, Christiane Kunert-Keil
Many types of bone substitute materials are available on the market. Researchers are refining new bone substitutes to make them comparable to autologous grafting materials in treatment of bone defects. The purpose of the study was to evaluate the osseoconductive potential and bone defect regeneration in rat calvaria bone defects treated with new synthetic nano-hydroxyapatite. The study was performed on 30 rats divided into 5 equal groups. New preproduction of experimental nano-hydroxyapatite material by NanoSynHap (Poznań, Poland) was tested and compared with commercially available materials. Five mm critical size defects were created and filled with the following bone grafting materials: 1) Geistlich Bio-Oss^®; 2) nano-hydroxyapatite + β-TCP; 3) nano-hydroxyapatite; 4) nano-hydroxyapatite+collagen membrane. The last group served as controls without any augmentation. Bone samples from calvaria were harvested for histological and micro-ct evaluation after 8 weeks. New bone formation was observed in all groups. Histomorphometric analysis revealed an amount of regenerated bone between 34.2 and 44.4% in treated bone defects, whereas only 13.0% regenerated bone was found in controls. Interestingly, in group 3, no significant particles of the nano-HA material were found. In contrast, residual bone substitute material could be detected in all other test groups. Micro-CT study confirmed the results of the histological examinations. The new nano-hydroxyapatite provides comparable results to other grafts in the field of bone regeneration.



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Radical approach gets polymerization just right

Publication date: Available online 24 June 2017
Source:Materials Today
Author(s): Cordelia Sealy




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Air conditioning without the AC

Publication date: Available online 24 June 2017
Source:Materials Today
Author(s): David Bradley




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Osteonecrosis of the jaws: a review and update in etiology and treatment

Publication date: Available online 24 June 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Guilherme H. Ribeiro, Emanuely S. Chrun, Kamile L. Dutra, Filipe I. Daniel, Liliane J. Grando
IntroductionOsteonecrosis of the jaws (ONJ) can result either from radiation, used in radiotherapy (RT) for treatment of malignant tumors, or medications used for bone remodeling and anti-angiogenesis such as bisphosphonates (BPs). These conditions can be associated with triggering factors such as infection, trauma and decreased vascularity. The management of patients with ONJ requires caution since there is no specific treatment that acts isolated and decidedly. However, different treatment modalities can be employed in an associated manner to control and stabilize lesions.ObjectiveTo review the current knowledge on etiology and management of ONJ, both radio-induced and medication-related, aiming to improve knowledge of professionals seeking to improve the quality of life of their patients.MethodsLiterature review in PubMed as well as manual search for relevant publications in reference list of selected articles. Articles in English ranging from 1983 to 2017, which assessed ONJ as main objective, were selected and analyzed.ResultsInfections, traumas and decreased vascularity have a triggering role for ONJ. Prophylactic and/or stabilizing measures can be employed in association with therapeutic modalities to properly manage ONJ patients.ConclusionSelecting an appropriate therapy for ONJ management based on current literature is a rational decision that can help lead to a proper treatment plan.



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Toward a molecular design of porous carbon materials

Publication date: Available online 24 June 2017
Source:Materials Today
Author(s): Lars Borchardt, Qi-Long Zhu, Mirian E. Casco, Reinhard Berger, Xiaodong Zhuang, Stefan Kaskel, Xinliang Feng, Qiang Xu
The molecular design of porous solids from predefined building blocks, in particular metal-organic and covalent frameworks, has been a tremendous success in the past two decades approaching record porosities and more importantly was an enabler for integrating predefined molecular functionality (enantioselectivity, optical and catalytic properties) into pore walls. Recent efforts indicate that this concept could also be applicable to rationally design porous and nanostructured carbonaceous materials, a class of materials hitherto and especially in the past often considered as "black magic" in terms of pore-wall structure definition and surface functionality. Carbon precursors with structural and compositional information in their molecular backbone, pre-formed covalent bonds, or integrated functional groups enable the design of carbon materials that can be tailored for certain applications. We review this exciting field of synthetic approaches based on molecular building blocks such as ionic liquids, bio molecules, or organic precursor monomers enabling the design of advanced carbonaceous architectures such as porous carbons, porous carbon-rich polymers or graphene nanoribbons. Moreover, our review includes approaches using the reactive and thermal transformation of periodic crystalline structures such as metal-organic frameworks, or carbides into equally defined carbon material. Such molecularly designed carbons are not only ideal model materials for fundamental science but also emerge in applications with until now unattained functionality.

Graphical abstract

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Could dye-sensitised solar cells work in the dark?

Publication date: Available online 24 June 2017
Source:Materials Today
Author(s): Laurie Winkless




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Chemistry behind bars

Publication date: Available online 24 June 2017
Source:Materials Today
Author(s): David Bradley




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Iron's cool orange glow

Publication date: Available online 24 June 2017
Source:Materials Today
Author(s): David Bradley




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Tuned graphene nanoribbons

Publication date: Available online 24 June 2017
Source:Materials Today
Author(s): David Bradley




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Inspired by fish: designing a high-performance, flexible armour

Publication date: Available online 24 June 2017
Source:Materials Today
Author(s): Laurie Winkless




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Psychiatric Consultation in the Collaborative Care Model: the “bipolar sieve” effect

Publication date: Available online 24 June 2017
Source:Medical Hypotheses
Author(s): James R. Phelps, James James
Around the world, psychiatrists are in exceptionally short supply. The majority of mental health treatment is delivered in primary care. In the United States, the Collaborative Care Model (CCM) addresses the shortfall of psychiatrists by providing indirect consultation in primary care. A Cochrane meta-analysis affirms the efficacy this model for depression and anxiety. However, our experience with the CCM suggests that most patients referred for consultation have problems far more complex than simple depression and anxiety. Based on preliminary data, we offer five linked hypotheses: (1) in an efficient collaborative care process, the majority of mental illnesses can be handled by providers who are less expensive and more plentiful than psychiatrists. (2) A majority of the remaining cases will be bipolar disorder variations. Differentiating these from PTSD, the most common alternative or comorbid diagnosis, is challenging and often requires a psychiatrist's input. (3) Psychiatric consultants can teach their primary care colleagues that bipolar diagnoses are estimations based on rigorously assessed probabilities, and that cases fall on a spectrum from unipolar to bipolar. (4) All providers must recognize that when bipolarity is missed, antidepressant prescription often follows. Antidepressants can induce bipolar mixed states, with extreme anxiety and potentially dangerous impulsivity and suicidality. (5) Psychiatrists can help develop clinical approaches in primary care that identify bipolarity and differentiate it from (or establish comorbidity with) PTSD; and psychiatrists can facilitate appropriate treatment, including bipolar-specific psychotherapies as well as use of mood stabilizers.



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Chronic fatigue syndrome and idiopathic intracranial hypertension: different manifestations of the same disorder of intracranial pressure?

Publication date: Available online 24 June 2017
Source:Medical Hypotheses
Author(s): J Nicholas P Higgins, John D Pickard, Andrew M L Lever
Though not discussed in the medical literature or considered in clinical practice, there are similarities between chronic fatigue syndrome and idiopathic intracranial hypertension (IIH) which ought to encourage exploration of a link between them. The cardinal symptoms of each – fatigue and headache - are common in the other and their multiple other symptoms are frequently seen in both. The single discriminating factor is raised intracranial pressure, evidenced in IIH usually by the sign of papilloedema, regarded as responsible for the visual symptoms which can lead to blindness. Some patients with IIH, however, do not have papilloedema and these patients may be clinically indistinguishable from patients with chronic fatigue syndrome. Yet IIH is rare, IIH without papilloedema (IIHWOP) seems rarer still, while chronic fatigue syndrome is common. So are the clinical parallels spurious or is there a way to reconcile these conflicting observations?We suggest that it is a quirk of clinical measurement that has created this discrepancy. Specifically, that the criteria put in place to define IIH have led to a failure to appreciate the existence, clinical significance or numerical importance of patients with lower level disturbances of intracranial pressure. We argue that this has led to a grossly implausible distortion of the epidemiology of IIH such that the milder form of the illness (IIHWOP) is seen as less common than the more severe and that this would be resolved by recognising a connection with chronic fatigue syndrome.We hypothesise, therefore, that IIH, IIHWOP, lesser forms of IIH and an undetermined proportion of chronic fatigue cases are all manifestations of the same disorder of intracranial pressure across a spectrum of disease severity, in which this subset of chronic fatigue syndrome would represent the most common and least severe and IIH the least common and most extreme.



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Prognostic Utility of Neuroinjury Biomarkers in post out-of-hospital cardiac arrest (OHCA) patient management

Publication date: Available online 24 June 2017
Source:Medical Hypotheses
Author(s): S.S. Gul, K.W. Huesgen, K.K. Wang, K. Mark, J.A. Tyndall
Despite aggressive intervention, patients who survive an out-of-hospital cardiac arrest (OHCA) generally have very poor prognoses, with nationwide survival rates of approximately 10-20%. Approximately 90% of survivors will have moderate to severe neurological injury ranging from moderate cognitive impairment to brain death. Currently, few early prognostic indicators are considered reliable enough to support patients' families and clinicians' in their decisions regarding medical futility. Blood biomarkers of neurological injury after OHCA may be of prognostic value in these cases. When most bodily tissues are oxygen-deprived, cellular metabolism switches from aerobic to anaerobic respiration. Neurons are a notable exception, however, being dependent solely upon aerobic respiration. Thus, after several minutes without circulating oxygen, neurons sustain irreversible damage, and certain measurable biomarkers are released into the circulation. Prior studies have demonstrated value in blood biomarkers in prediction of survival and neurologic impairment after OHCA. We hypothesize that understanding peptide biomarker kinetics in the early return of spontaneous circulation (ROSC) period, especially in the setting of refractory cardiac arrest, may assist clinicians in determining prognosis earlier in acute resuscitation. Specifically, during and after immediate resuscitation and return of ROSC, clinicians and families face a series of important questions regarding patient prognosis, futility of care and allocation of scarce resources such as the early initiation of extracorporeal cardiopulmonary resuscitation (ECPR). The ability to provide early prognostic information in this setting is highly valuable. Currently available, as well as potential biomarkers that could be good candidates in prognostication of neurological outcomes after OHCA or in the setting of refractory cardiac arrest will be reviewed and discussed.



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The effect of artesunate on short-term memory in Lyme borreliosis

Publication date: Available online 24 June 2017
Source:Medical Hypotheses
Author(s): B.K. Puri, J.S. Hakkarainen-Smith, J.A. Monro
Lyme borreliosis is associated with memory deficits. While this may be related to cerebral infection by Borrelia bacteria, it may also be caused by concomitant co-infection by Babesia protozoa. The anti-malarial artemisinin-derivative artesunate has been shown to be effective against a number of Babesia species and to have efficacy against human cerebral malaria. We hypothesised that concomitant administration of artesunate in Lyme borreliosis patients would help alleviate the severity of self-reported short-term memory impairment. This hypothesis was tested in a small pilot study in which patients were treated with both an intravenous antibiotic and oral artesunate (20 mg four times per day); treatment was associated with a reduction in the severity of short-term memory difficulties (P ≃ 0.08). In light of these findings, we recommend that a formal randomised, placebo-controlled study be carried out.



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Title: CpG methylation and the methyl CpG binding protein 2 (MeCP2) are required for restraining corticotropin releasing hormone (CRH) gene expression

Publication date: Available online 24 June 2017
Source:Molecular and Cellular Endocrinology
Author(s): Shreyas A. Bhave, Rosalie M. Uht
The hypothalamic-pituitary-adrenal (HPA) axis plays a critical role in mounting a stress response and maintaining homeostasis. A dysregulated HPA axis and elevated levels of CRH are associated with a number of disorders. Although extensive research has been devoted to understanding molecular events associated with stimulated CRH gene, less is known about the mechanisms that restrain CRH expression. Using a cell culture system, we report here two molecular aspects of CRH gene regulation that are required for maintenance of basal level of CRH gene expression. These are a specific CpG methylation at a single CpG, and adequate levels of the methyl CpG binding protein 2 (MeCP2). The single site methylation allows the recruitment of MeCP2 to the CRH gene promoter region, and MeCP2 knockdown leads to increased expression of CRH gene. Taken together, the results indicate that site-specific methylation and MeCP2 are required for maintenance of basal levels of CRH gene expression.



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Different hypersensitivities against homologous proteins of MGL_1304 in patients with atopic dermatitis

Publication date: Available online 24 June 2017
Source:Allergology International
Author(s): Takuma Kohsaka, Takaaki Hiragun, Kaori Ishii, Makiko Hiragun, Akiko Kamegashira, Michihiro Hide
BackgroundAtopic dermatitis (AD) is exacerbated by sweating, and the skin of most patients with AD are resided by Malassezia (M.) fungi. Recently, MGL_1304 produced by Malasseziaglobosa was identified as the major histamine releasing antigen in human sweat.MethodsThe full length cDNA of the counterpart of MGL_1304 in Malasseziarestricta (Mala r 8), was cloned by degenerate PCR and rapid identification of cDNA ends (RACE). Recombinant MGL_1304, and its counterparts, Mala s 8 (produced by Malasseziasympodialis) and Mala r 8 were prepared, and compared in their allergenicities by dot blot analysis and histamine release tests with sera and basophils of patients with AD.ResultsThe identities between MGL_1304 and Mala s 8, MGL_1304 and Mala r 8, and Mala s 8 and Mala r 8 were 68%, 78%, and 76%, respectively, in protein sequences. Dot blot analysis revealed that the level of IgE binding to Mala s 8 was higher than that of MGL_1304. However, histamine release tests revealed that MGL_1304 and Mala r 8 possessed higher activity than Mala s 8. In addition, the crude lysate of M. globosa showed higher histamine release ability than that of M. sympodialis.ConclusionsPatients with AD showed hypersensitivities against MGL_1304 and its homologs. However, the allergenicities of the homologs are variable and the histamine release activities may be different from the solid-phase binding activities for IgE. Sweat allergy should be carefully evaluated with biological activities of MGL_1304 and its homologs of other Malassezia fungi residing on the skin.



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In Silico Shear and Intramural Stresses are Linked to Aortic Valve Morphology in Dilated Ascending Aorta

Publication date: Available online 24 June 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): S. Pasta, G. Gentile, G.M. Raffa, D. Bellavia, G. Chiarello, R. Liotta, A. Luca, C. Scardulla, M. Pilato
Objective/BackgroundThe development of ascending aortic dilatation in patients with bicuspid aortic valve (BAV) is highly variable, and this makes surgical decision strategies particularly challenging. The purpose of this study was to identify new predictors, other than the well established aortic size, that may help to stratify the risk of aortic dilatation in BAV patients.MethodsUsing fluid–structure interaction analysis, both haemodynamic and structural parameters exerted on the ascending aortic wall of patients with either BAV (n = 21) or tricuspid aortic valve (TAV; n = 13) with comparable age and aortic diameter (42.7 ± 5.3 mm for BAV and 45.4 ± 10.0 mm for TAV) were compared. BAV phenotypes were stratified according to the leaflet fusion pattern and aortic shape.ResultsSystolic wall shear stress (WSS) of BAV patients was higher than TAV patients at the sinotubular junction (6.8 ± 3.3 N/m² for BAV and 3.9 ± 1.3 N/m² for TAV; p = .006) and mid-ascending aorta (9.8 ± 3.3 N/m² for BAV and 7.1 ± 2.3 N/m² for TAV; p = .040). A statistically significant difference in BAV versus TAV was also observed for the intramural stress along the ascending aorta (e.g., 2.54 × 10⁵ ± 0.32 × 10⁵ N/m² for BAV and 2.04 × 10⁵ ± 0.34 × 10⁵ N/m² for TAV; p < .001) and pressure index (0.329 ± 0.107 for BAV and 0.223 ± 0.139 for TAV; p = .030). Differences in the BAV phenotypes (i.e., BAV type 1 vs. BAV type 2) and aortopathy (i.e., isolated tubular vs. aortic root dilatations) were associated with asymmetric WSS distributions in the right anterior aortic wall and right posterior aortic wall, respectively.ConclusionThese findings suggest that valve mediated haemodynamic and structural parameters may be used to identify which regions of aortic wall are at greater stress and enable the development of a personalised approach for the diagnosis and management of aortic dilatation beyond traditional guidelines.



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Generation and characterization of a human oral squamous carcinoma cell line SCC-9 with CRISPR/Cas9-mediated deletion of the p75 neurotrophin receptor

Publication date: October 2017
Source:Archives of Oral Biology, Volume 82
Author(s): Ping Huang, Dongdong Tong, Jing Sun, Qing Li, Fenghe Zhang
ObjectiveTo investigate the importance of the p75 neurotrophin receptor (p75^NTR) in human tongue squamous carcinoma cells, we exploited the CRISPR/Cas9 technology to establish a p75^NTR-knockout SCC-9 cell line and to explore the effect on biological functions.Materials and methodsThe clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated endonuclease (Cas9) system was used to generate genomic deletion mutants of p75^NTR in the tongue squamous carcinoma cell lines SCC-9. Single-guide RNA (sgRNA) sequences were designed to target the p75^NTR genomic sequence and were cloned into plasmid pGK1.1. The linearized vector was electroporated into SCC-9 cells and p75^NTR deletion was confirmed using Cruiser™ enzyme digestion and PCR amplification. SCC-9 clones with successful deletion of p75^NTR were identified and verified by sequencing and selected for functional testing in cell proliferation, invasion, migration, and colony-forming assays.ResultsCompared with control cells, p75^NTR-knockout SCC-9 cells showed significantly diminished abilities to proliferate, invade, migrate, and form colonies, indicating a reduction in pro-tumorigenic behavior.ConclusionThese data demonstrate, first, that the CRISPR/Cas9 system is a simplified method for generating p75^NTR knockouts with relatively high efficiency, and second, that deletion of p75^NTR suppresses several tumor-promoting properties of SCC-9 cells, suggesting that p75^NTR is a potential target for the development of novel therapies for tongue cancer.



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Fibulins and matrilins are novel structural components of the periodontium in the mouse

Publication date: October 2017
Source:Archives of Oral Biology, Volume 82
Author(s): Andrea Schubert, Boris Schminke, Nicolai Miosge
Periodontitis refers to inflammatory disease of the periodontal structures (the gingiva, dental cementum, periodontal ligament (PDL) and alveolar bone) that ultimately leads to their destruction. Whereas collagens are well-examined main components of the periodontium, little is known about the other structural proteins that make up this tissue. The aim of this study was to identify new extracellular matrix (ECM) components, including fibulins and matrilins, in the periodontium of mice.After sacrificing 14 mice (Sv/129 strain), jaws were prepared. Each tissue sample contained a molar and its surrounding alveolar bone. Immunohistochemistry was carried out on paraffin-embedded sections.Our results show that mice exhibit fibulin-3, -4 and -5 and matrilin-1, -2, -3 and -4 in PDL and in blood vessels of alveolar bone and PDL as well as in the pericellular matrix of osteocytes and cementocytes. In dental cementum, only fibulin-4 is expressed.For the first time, we show that fibulin-3, -4 and -5 and matrilin-1, -2, -3 and -4 are essential components of the periodontal tissues. Our findings indicate an association of these proteins with collagens and oxytalan fibers that might be of future interest in regenerative periodontitis therapy.



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The impact of argon/oxygen low-pressure plasma on shear bond strength between a veneering composite and different PEEK materials

Publication date: Available online 24 June 2017
Source:Dental Materials
Author(s): Andreas Dominik Schwitalla, Friederike Bötel, Tycho Zimmermann, Mona Sütel, Wolf-Dieter Müller
ObjectiveThe aim of the study was to evaluate the impact of low-pressure argon/oxygen plasma with and without previous sandblasting on the shear bond strength (SBS) between dental PEEK compounds and a veneering composite.MethodsOf one type of unfilled PEEK and two pigment powder filled PEEK compounds, forty rectangular plates each were prepared and polished up to 4000 grit. The samples were randomly assigned to four surface pre-treatment groups, each consisting of ten specimens (1. Untreated; 2. Plasma treatment; 3. Sandblasting; 4. Sandblasting+plasma treatment). Plasma treatment was performed for 35min using a low-pressure plasma system with a 1:1 mixture of the process gases argon and oxygen. Surface roughness and water contact angles were recorded. An adhesive (Visio.link, Bredent GmbH & Co KG, Senden, Germany) was applied onto the specimen surfaces and light cured. A mold was used to shape the veneering composite (Vita VM LC, Vita Zahnfabrik, Bad Säckingen, Germany) into a cylindrical form on the sample surface before light curing. SBS was measured after 24h incubation at 37°C in distilled water using a universal testing machine.ResultsThe samples pre-treated according to group 4 (sandblasting and plasma treatment) showed the highest SBS overall, whereas the unfilled PEEK showed the highest SBS (19.8±2.46MPa) compared to the other PEEK materials (15.86±4.39MPa and 9.06±3.1MPa).SignificanceSandblasting and surface activation with low-pressure argon/oxygen plasma in combination with an adhesive causes a favorable increase in shear bond strength, especially on unfilled PEEK material.



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Predictive value of body mass index to metabolic syndrome risk factors in Syrian adolescents

Obesity has become a serious epidemic health problem in both developing and developed countries. There is much evidence that obesity among adolescents contributed significantly to the development of type 2 dia...

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Enhanced Skin Reaction with Palliative Thoracic Radiotherapy and Sorafenib

Publication date: Available online 24 June 2017
Source:Practical Radiation Oncology
Author(s): Diane C Ling, Danielle Bell, Michael Wollman, Seong-Kyun Cheong, Melvin Deutsch, John A Vargo




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Exposure to particulate matter 2.5 (PM2.5) induced macrophage-dependent inflammation, characterized by increased Th1/Th17 cytokine secretion and cytotoxicity

Publication date: September 2017
Source:International Immunopharmacology, Volume 50
Author(s): Qin-Yun Ma, Da-Yu Huang, Hui-Jun Zhang, Shaohua Wang, Xiao-Feng Chen
Particulate matter PM2.5 is a class of airborne particles and droplets with sustained high levels in many developing countries. Epidemiological studies have shown the association between sustained high level of PM2.5 and the risk of many diseases in the respiratory system, including lung cancer. However, the precise mechanisms through which PM2.5 induces respiratory diseases are still unclear. In this study, we demonstrated that CD4⁺ and CD8⁺ T cells following PM2.5 treatment demonstrated significantly elevated mRNA and protein levels of interferon (IFN)-γ, interleukin (IL)-10, IL-17, and IL-21 production. This increase in cytokines required the presence of macrophages, such that CD4⁺ and CD8⁺ T cells treated with PM2.5 in the absence of macrophages did not present higher IFN-γ, IL-10, or IL-21 expression. In contrast, PM2.5-treated macrophages could significantly upregulate T cell cytokine secretion, even when excess PM2.5 was removed from cell culture. We also observed a macrophage-dependent upregulation of granzyme A and granzyme B expression by CD4⁺ and CD8⁺ T cells following PM2.5 treatment. These PM2.5-stimulated CD4⁺ and CD8⁺ T cells potently induced the death of human bronchial epithelial (HBE) cells. Interestingly, the CD4⁺ and CD8⁺ T cells presented synergistic effects at inducing HBE cytotoxicity, such that CD4⁺ T cells and CD8⁺ T cells combined resulted in higher HBE cell death than the sum of the separate effects of CD4⁺ T cells and CD8⁺ T cells. While blocking cytotoxic molecule release significantly compromised the T cell-mediated cytotoxicity against HBE cells, blocking IFN-γ, but not IL-10, could also slightly but significantly reduce T cell-mediated cytotoxicity. Together, these data demonstrated that PM2.5 could promote the inflammation of cytotoxicity of T cells in a macrophage-dependent manner. In addition, PM2.5-treated macrophages presented long-lasting proinflammatory effects on T cells.



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Micro injection molding processing of UHMWPE using ultrasonic vibration energy

Publication date: 15 October 2017
Source:Materials & Design, Volume 132
Author(s): Xavier Sánchez-Sánchez, Marcelo Hernández-Avila, L.E. Elizalde, Oscar Martínez, Inés Ferrer, Alex Elías-Zuñiga
Ultrasonic micro injection molding was confirmed to be an efficient processing technique for the fabrication of a well-filled miniaturized dog-bone shaped specimen of ultra-high molecular weight polyethylene (UHMWPE). The influence of four process parameters on the filling phase of the reduced-size cavity was then analysed. It was established that it is possible to fabricate well-defined specimens when the highest ultrasonic amplitude is applied intermittently at specific intervals during the ultrasonic process to small compacted irregularly shaped UHMWPE samples and the mold temperature is set to 100°C. GPC results showed a decrease in the molecular weight, which was the greatest when 100% of the ultrasonic amplitude was applied. The degree of crystallinity of the processed sample was increased because the reduction of the molecular weight. TGA showed that the thermal stability of UHMWPE fabricated by ultrasonic processing was not significantly influenced by the decrease in the molecular weight. FTIR spectra indicated oxidative degradation in three different regions of the processed UHMWPE specimen. Additionally, the band identified at the wavenumber 910cm⁻¹ indicated a chain scission phenomenon the polymer experienced during the ultrasonic processing.

Graphical abstract

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Anatomical Regional Targeted (ART) BOTOX Injection Technique: A Novel Paradigm for Migraines and Chronic Headaches: Erratum

No abstract available

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