Meditation is associated with increased brain network integration

Publication date: September 2017
Source:NeuroImage, Volume 158
Author(s): Remko van Lutterveld, Edwin van Dellen, Prasanta Pal, Hua Yang, Cornelis Jan Stam, Judson Brewer
IntroductionThis study aims to identify novel quantitative EEG measures associated with mindfulness meditation. As there is some evidence that meditation is associated with higher integration of brain networks, we focused on EEG measures of network integration.MethodsSixteen novice meditators and sixteen experienced meditators participated in the study. Novice meditators performed a basic meditation practice that supported effortless awareness, which is an important quality of experience related to mindfulness practices, while their EEG was recorded. Experienced meditators performed a self-selected meditation practice that supported effortless awareness. Network integration was analyzed with maximum betweenness centrality and leaf fraction (which both correlate positively with network integration) as well as with diameter and average eccentricity (which both correlate negatively with network integration), based on a phase-lag index (PLI) and minimum spanning tree (MST) approach. Differences between groups were assessed using repeated-measures ANOVA for the theta (4–8 Hz), alpha (8–13 Hz) and lower beta (13–20 Hz) frequency bands.ResultsMaximum betweenness centrality was significantly higher in experienced meditators than in novices (P = 0.012) in the alpha band. In the same frequency band, leaf fraction showed a trend toward being significantly higher in experienced meditators than in novices (P = 0.056), while diameter and average eccentricity were significantly lower in experienced meditators than in novices (P = 0.016 and P = 0.028 respectively). No significant differences between groups were observed for the theta and beta frequency bands.ConclusionThese results show that alpha band functional network topology is better integrated in experienced meditators than in novice meditators during meditation. This novel finding provides the rationale to investigate the temporal relation between measures of functional connectivity network integration and meditation quality, for example using neurophenomenology experiments.



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Correction of metal-induced susceptibility artifacts for functional MRI during deep brain stimulation

Publication date: September 2017
Source:NeuroImage, Volume 158
Author(s): Myung-Ho In, Shinho Cho, Yunhong Shu, Hoon-Ki Min, Matt A. Bernstein, Oliver Speck, Kendall H. Lee, Hang Joon Jo
Functional magnetic resonance imaging (fMRI) is an emerging tool for investigating brain activation associated with, or modulated by, deep brain stimulation (DBS). However, DBS-fMRI generally suffers from severe susceptibility to artifacts in regions near the metallic stimulation electrodes, as well as near tissue/air boundaries of the brain. These result in strong intensity and geometric distortions along the phase-encoding (PE) (i.e., blipped) direction in gradient-echo echo-planar imaging (GE-EPI). Distortion presents a major challenge to conducting reliable data analysis and in interpreting the findings. A recent study showed that the point spread function (PSF) mapping-based reverse gradient approach has a potential to correct for distortions not only in spin-echo EPI, but also in GE-EPI acquired in both the forward and reverse PE directions. In this study, we adapted that approach in order to minimize severe metal-induced susceptibility artifacts for DBS-fMRI, and to evaluate the performance of the approach in a phantom study and a large animal DBS-fMRI study. The method combines the distortion-corrected GE-EPI pair with geometrically different intensity distortions due to the opposing encoding directions. The results demonstrate that the approach can minimize susceptibility artifacts that appear around the metallic electrodes, as well as in the regions near the tissue/air boundaries in the brain. We also demonstrated that an accurate geometric correction is important in improving BOLD contrast in the group dataset, especially in regions where strong susceptibility artifacts appear.



http://ift.tt/2t4U3b1

Epinephrine use for anaphylaxis: Too seldom, too late

During the past 20 years, food allergy has dramatically increased, with a concomitant increased risk for anaphylaxis.1 Anaphylaxis is "a serious allergic reaction that is rapid in onset and may cause death."2 Foods are one of the common causes of anaphylaxis3 over medications and insect stings, and food allergy has become a worldwide concern. Anaphylaxis is inadequately treated most of the time4 because of inconsistent signs and symptoms; anaphylaxis can manifest differently in the same person, even when triggered by the same allergen.

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Effects of allergen sensitization on response to therapy in children with eosinophilic esophagitis

In children with eosinophilic esophagitis (EoE) foods are the most common disease triggers, but environmental allergens are also suspected culprits.

http://ift.tt/2txIbza

Epinephrine use for anaphylaxis: Too seldom, too late

During the past 20 years, food allergy has dramatically increased, with a concomitant increased risk for anaphylaxis.1 Anaphylaxis is "a serious allergic reaction that is rapid in onset and may cause death."2 Foods are one of the common causes of anaphylaxis3 over medications and insect stings, and food allergy has become a worldwide concern. Anaphylaxis is inadequately treated most of the time4 because of inconsistent signs and symptoms; anaphylaxis can manifest differently in the same person, even when triggered by the same allergen.

http://ift.tt/2seYGMu

Effects of allergen sensitization on response to therapy in children with eosinophilic esophagitis

In children with eosinophilic esophagitis (EoE) foods are the most common disease triggers, but environmental allergens are also suspected culprits.

http://ift.tt/2txIbza

Chinese versus English: Insights on Cognition during Reading

Publication date: Available online 1 July 2017
Source:Trends in Cognitive Sciences
Author(s): Lili Yu, Erik D. Reichle
Chinese reading experiments have introduced important caveats to theories of reading that have been largely informed by studies of English reading – especially in relation to our understanding of lexical processing and eye-movement control. This article provides a brief primer on Chinese reading and examples of questions that arise from its study.



http://ift.tt/2sAxEPf

On the role of classical and novel forms of vitamin D in melanoma progression and management

Publication date: Available online 1 July 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Andrzej T. Slominski, Anna A Brozyna, Cezary Skobowiat, Michal A. Zmijewski, Tae-Kang Kim, Zorica Janjetovic, Allen S. Oak, Wojciech Jozwicki, Anton M. Jetten, Rebecca S. Mason, Craig Elmets, We Li, Robert M. Hoffman, Robert C. Tuckey
Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Calcitriol (1,25(OH)2D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-melanoma activities and protective properties against damage induced by UVB. The former activities include inhibitory effects on proliferation, plating efficiency and anchorage-independent growth of cultured human and rodent melanomas in vitro, as well as the in vivo inhibition of tumor growth by 20(OH)D3 after injection of human melanoma cells into immunodeficient mice. The literature indicates that low levels of 25(OH)D3 are associated with more advanced melanomas and reduced patient survivals, while single nucleotide polymorphisms of the vitamin D receptor or the D3 binding protein gene affect development or progression of melanoma, or disease outcome. An inverse correlation of VDR and CYP27B1 expression with melanoma progression has been found, with low or undetectable levels of these proteins being associated with poor disease outcomes. Unexpectedly, increased expression of CYP24A1 was associated with better melanoma prognosis. In addition, decreased expression of retinoic acid orphan receptors α and γ, which can also bind vitamin D3 hydroxyderivatives, showed positive association with melanoma progression and shorter disease-free and overall survival. Thus, inadequate levels of biologically active forms of D3 and disturbances in expression of the target receptors or D3 activating or inactivating enzymes, can affect melanomagenesis and disease progression. We therefore propose that inclusion of vitamin D into melanoma management should be beneficial for patients, at least as an adjuvant approach. The presence of multiple hydroxyderivatives of D3 in skin that show anti-melanoma activity in experimental models and which may act on alternative receptors, will be a future consideration when planning which forms of vitamin D to use for melanoma therapy.



http://ift.tt/2tDb911

Vitamin D-deficiency and sex-specific dysregulation of placental inflammation

Publication date: Available online 1 July 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Nancy Q. Liu, Dean P. Larner, Qingqiang Yao, Rene F. Chun, Yuxin Ouyang, Rui Zhou, Jennifer A. Tamblyn, Carol L. Wagner, Martin Hewison
To investigate an immunomodulatory role for vitamin D in pregnancy we used mice raised on vitamin D-sufficient (SUFF), or −deficient (DEF) diets. At embryonic day 14, pregnant mice received intraperitoneal injection of lipopolysaccharide (LPS) or vehicle for 24hrs, with age-matched non-pregnant mice as controls. In non-pregnant mice, 6 serum analytes (IL-1β, IL-18, MDC/CCL22, MIP-1α/CCL3, EGF, IgA) were lower in DEF mice. In pregnant DEF mice only GH was higher. In non-pregnant mice LPS induced 28 analytes, with 5 (IL-18, IP-10/CXCL10, MCP-1/CCL2, MIP-1β/CCL4, MIP-3β/CCL19) being highest in DEF mice. In pregnant SUFF mice 16 serum analytes increased with LPS, and 6 of these (IP-10/CXCL10, MCP-1/CCL2, SAP, TIMP-1, VCAM-1, vWF) were higher and 1 (GCP-2/CXCL6) lower in DEF mice. Parallel analysis of placental mRNAs showed elevated mRNA for Il-6, Ccl2 and Cxcl10 in placentae from male and female fetuses in LPS-DEF mice. However, LPS-induced expression of Ifnγ, Tnfα, and Cxcl6 was only observed in female placentae from DEF mice. LPS-DEF mice also showed smaller litter sizes relative to control SUFF mice. Numbers of female fetuses per dam were significantly lower for DEF mice with or without LPS challenge. LPS had no effect on numbers of male fetuses from DEF mothers, but significantly decreased male fetuses from SUFF mothers. These data indicate that vitamin D is an important component of anti-inflammatory immune responses during pregnancy, with the placenta and fetal sex playing pivotal roles in this process.



http://ift.tt/2ud1BGX

Small molecules to the rescue: Inhibition of cytokine signaling in immune-mediated diseases

Publication date: Available online 1 July 2017
Source:Journal of Autoimmunity
Author(s): Massimo Gadina, Nathalia Gazaniga, Laura Vian, Yasuko Furumoto
Cytokines are small, secreted proteins associated with the maintenance of immune homeostasis but also implicated with the pathogenesis of several autoimmune and inflammatory diseases. Biologic agents blocking cytokines or their receptors have revolutionized the treatment of such pathologies. Nonetheless, some patients fail to respond to these drugs or do not achieve complete remission. The signal transduction originating from membrane-bound cytokine receptors is an intricate network of events that lead to gene expression and ultimately regulate cellular functionality. Our understanding of the intracellular actions that molecules such as interleukins, interferons (IFNs) and tumor necrosis factor (TNF) set into motion has greatly increased in the past few years, making it possible to interfere with cytokines' signaling cascades. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT), the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), the mitogen activated protein kinase (MAPK) and the Phosphatidylinositol-3′-kinases (PI3K) pathways have all been intensively studied and key steps as well as molecules have been identified. These research efforts have led to the development of a new generation of small molecule inhibitors. Drugs capable of blocking JAK enzymatic activity or interfering with the proteasome-mediated degradation of intermediates in the NF-kB pathway have already entered the clinical arena confirming the validity of this approach. In this review, we have recapitulated the biochemical events downstream of cytokine receptors and discussed some of the drugs which have already been successfully utilized in the clinic. Moreover, we have highlighted some of the new molecules that are currently being developed for the treatment of immune-mediated pathologies and malignancies.



http://ift.tt/2tzciGd

Serum cytokine profile in pediatric Sweet’s syndrome: a case report

Sweet's syndrome is characterized by fever, leukocytosis, and tender erythematous papules or nodules. It is a rare condition, particularly in the pediatric population, and has recently been proposed to be an a...

http://ift.tt/2stOFj0

Copyright

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4





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Contributors

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4





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Contents

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4





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Forthcoming Issues

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4





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Kinase Inhibitors in the Treatment of Myeloid Malignancies

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4
Author(s): Ann Mullally




http://ift.tt/2tDhw4u

The Treatment of Myeloid Malignancies with Kinase Inhibitors

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4
Author(s): Ann Mullally




http://ift.tt/2ucoj1X

Tyrosine Kinase Inhibitor Treatment for Newly Diagnosed Chronic Myeloid Leukemia

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4
Author(s): Jerald P. Radich, Michael J. Mauro

Teaser

Chronic myeloid leukemia (CML) is a myeloproliferative disorder that accounts for approximately 10% of new cases of leukemia. The introduction of tyrosine kinase inhibitors has led to a reduction in mortalities. Thus, the estimated prevalence of CML is increasing. The National Comprehensive Cancer Network and the European Leukemia Net guidelines incorporate frequent molecular monitoring of the fusion BCR-ABL transcript to ensure that patients reach and keep treatment milestones. Most patients with CML are diagnosed in the chronic phase, and approximately 10% to 30% of these patients will at some time in their course meet definition criteria of resistance to imatinib.


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Mechanisms of Resistance to ABL Kinase Inhibition in Chronic Myeloid Leukemia and the Development of Next Generation ABL Kinase Inhibitors

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4
Author(s): Ami B. Patel, Thomas O'Hare, Michael W. Deininger

Teaser

Chronic myeloid leukemia is increasingly viewed as a chronic illness; most patients have a life expectancy close to that of the general population. Despite progress made using BCR-ABL1 tyrosine kinase inhibitors (TKIs), drug resistance via BCR-ABL1–dependent and BCR-ABL1–independent mechanisms continues to be an issue. BCR-ABL1–dependent resistance is primarily mediated through oncoprotein kinase domain mutations and usually results in overt resistance to TKIs. However, BCR-ABL1–independent resistance in the setting of effective BCR-ABL1 inhibition is recognized as a major contributor to minimal residual disease. Efforts to eradicate persistent leukemic stem cells have focused on combination therapy.


http://ift.tt/2uc9sVb

Tyrosine Kinase Inhibitors in the Treatment of Eosinophilic Neoplasms and Systemic Mastocytosis

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4
Author(s): Jason Gotlib

Teaser

The World Health Organization's semimolecular classification of eosinophilias emphasizes neoplasms driven by fusion tyrosine kinases. More than 80% of patients with systemic mastocytosis carry the KIT D816V mutation, the primary driver of disease pathogenesis. Genetic annotation of these diseases is critical and affords opportunities for targeted therapy. This article discusses our understanding of the mutated tyrosine kinome of eosinophilic neoplasms and systemic mast cell disease, and the successes and limitations of available therapies. Use of tyrosine kinase inhibitors as a bridge to hematopoietic stem cell transplantation, and development of more selective and potent tyrosine kinase inhibitors is also highlighted.


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Muscle synergies reveal impaired trunk muscle coordination strategies in individuals with thoracic spinal cord injury

Publication date: Available online 1 July 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Matija Milosevic, Hikaru Yokoyama, Murielle Grangeon, Kei Masani, Milos R. Popovic, Kimitaka Nakazawa, Dany H. Gagnon
Spinal cord injury (SCI) can result in paralysis of trunk muscles, which can affect sitting balance. The objective of this study was to analyze trunk muscle coordination of individuals with thoracic SCI and compare it to able-body individuals. A total of 27 individuals were recruited and subdivided into: (a) high thoracic SCI; (b) low thoracic SCI; and (c) able-body groups. Participants were seated and asked to lean their trunk in eight directions while trunk muscle activity was recorded. Muscle coordination was assessed using the non-negative matrix factorization (NMF) method to extract muscle modules, which are the synergistic trunk muscle activations, and their directional activation patterns. Our results showed that individuals with SCI used less muscle modules, more co-contractions, and less directional tuning, compared to able-bodied people. These results suggest impaired and simplified muscle coordination due to the loss of supraspinal input after SCI. Observed variability in muscle coordination within SCI groups also suggests that other mechanisms such as spasticity and muscle stretch reflexes or individual factors such as experience and training contributed to the postural muscle synergies. Overall, muscle coordination deficits revealed impaired neuromuscular strategies which provide implications for rehabilitation of trunk muscles during sitting balance after SCI.



http://ift.tt/2ucrw1u

Serum cytokine profile in pediatric Sweet’s syndrome: a case report

Sweet's syndrome is characterized by fever, leukocytosis, and tender erythematous papules or nodules. It is a rare condition, particularly in the pediatric population, and has recently been proposed to be an a...

http://ift.tt/2stOFj0

Table of Contents

Publication date: July–August 2017
Source:American Journal of Otolaryngology, Volume 38, Issue 4





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Guidelines for Contributing Authors

Publication date: July–August 2017
Source:American Journal of Otolaryngology, Volume 38, Issue 4





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Editorial Board

Publication date: July–August 2017
Source:American Journal of Otolaryngology, Volume 38, Issue 4





http://ift.tt/2tz6ZGq

Trends in prescribing behavior of systemic agents used in the treatment of acne among dermatologists and nondermatologists: A retrospective analysis, 2004-2013

Despite recommendations to limit the use of oral antibiotics and increasing support for hormonal agents in the treatment of acne, it is unclear whether there have been any significant changes in practice patterns.

http://ift.tt/2tz4Ydn

Anatomic mapping and clinicopathologic analysis of benign acral melanocytic neoplasms: A comparison between adults and children

The clinicopathologic features of benign acral melanocytic neoplasms (BAMNs) remain poorly understood.

http://ift.tt/2uwKz64

CD8+ mycosis fungoides: A low-grade lymphoproliferative disorder

The prognosis of the CD8+ subtype of mycosis fungoides (MF) is controversial. Although most authors believe that determining the presence of this cell surface antigen has no prognostic value, others have observed a more indolent course for CD8+ MF compared with CD4+ MF.

http://ift.tt/2tyM0Uu

Discrepancy between the clinical and histopathologic diagnosis of soft tissue vascular malformations

Soft tissue vascular malformations are generally diagnosed clinically, according to the International Society for the Study of Vascular Anomalies (ISSVA) classification. Diagnostic histopathologic examination is rarely performed.

http://ift.tt/2ux8an7

Multiple and repeated sampling increases the sensitivity of direct immunofluorescence testing for the diagnosis of mucous membrane pemphigoid

Mucous membrane pemphigoid (MMP) is an autoimmune disease characterized by the predominant blistering of mucosal surfaces and the linear deposition of complement, IgG, or IgA along the basement membrane detected by direct immunofluorescence (DIF) test.

http://ift.tt/2tyF89y

Evaluation of laser fluorescence in monitoring non-cavitated caries lesion progression on smooth surfaces in vitro

Abstract

The aim of this study was to evaluate the performance of a pen-type laser fluorescence (LF) device (LFpen: DIAGNOdent pen) to detect and monitor the progression of caries-like lesions on smooth surfaces. Fifty-two bovine enamel blocks were submitted to three different demineralisation cycles for caries-like lesion induction using Streptococcus mutans, Lactobacillus casei and Actinomyces naeslundii. At baseline and after each cycle, the enamel blocks were analysed under Knoop surface micro-hardness (SMH) and an LFpen. One enamel block after each cycle was randomly chosen for Raman spectroscopy analysis. Cross-sectional micro-hardness (CSMH) was performed at different depths (20, 40, 60, 80 and 100 μm) in 26 enamel blocks after the second cycle and 26 enamel blocks after the third cycle. Average values of SMH (± standard deviation (SD)) were 319.3 (± 21.5), 80.5 (± 31.9), 39.8 (± 12.7), and 29.77 (± 10.34) at baseline and after the first, second and third cycles, respectively. Statistical significant difference was found among all periods (p < 0.01). The LFpen values were 4.3 (± 1.5), 7.5 (± 9.4), 7.1 (± 7.1) and 5.10 (± 3.58) at baseline and after the first, second, and third cycles, respectively, among all periods (p < 0.05). The CSMH values after the second and third cycles at 20, 40, 60, 80 and 100 μm were 182.8 (± 69.8), 226.1 (± 79.6), 247.20 (± 69.36), 262.35 (± 66.36) and 268.45 (± 65.49), and for the third cycle were 193.7 (± 73.4), 239.5 (± 81.5), 262.64 (± 82.46), 287.10 (± 78.44) and 284.79 (± 72.63) (n = 24 and 23), respectively. No correlation was observed between the LFpen and SMH values (p > 0.05). One sample of each cycle was characterised through Raman spectroscopy analysis. It can be concluded that LF was effective in detecting the first demineralisation on enamel; however, the method did not show any effect in monitoring lesion progression after three cycles of in vitro demineralisation.

http://ift.tt/2tCY4os

Urolithiasis secondary to primary obstructive megaureter in an adult: a case report

Primary obstructive megaureter is relatively uncommon in adults. This condition usually regresses spontaneously or is treated during infancy. It can remain asymptomatic for decades until adulthood when symptom...

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Speech–language pathology in paediatric palliative care: A scoping review of role and practice

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Fluency adaptation in speakers with Parkinson disease: a motor learning perspective

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Urolithiasis secondary to primary obstructive megaureter in an adult: a case report

Primary obstructive megaureter is relatively uncommon in adults. This condition usually regresses spontaneously or is treated during infancy. It can remain asymptomatic for decades until adulthood when symptom...

http://ift.tt/2twT18I

Suppressive effects of thermal-treated oyster shells on cadmium and copper translocation in maize plants

Abstract

The effect of varied concentrations of thermal-treated oyster shells (TOS) on the suppression of cadmium (Cd) and copper (Cu) uptake and translocation into the shoots of maize plants was examined. Maize plants were grown in Cd- and Cu-contaminated Andosol for 70 days. The concentration of mobile Cd (extracted with 1 M NH₄NO₃) decreased with increasing TOS applications, whereas an increase in the concentration of mobile Cu in soil resulted from cumulative TOS additions. The addition of 2% TOS had no prohibitive effects on Cd uptake in maize shoots, but the 4 and 8% TOS treatments decreased Cd accumulation in shoots by 41 and 59%, respectively. The possible mechanisms underlying Cd suppression in maize shoots were the enhanced Cd adsorption caused by pH-induced increases in the negative charge of the soil and the antagonistic effects of Ca resulting from competition for exchange sites at the root surface. Cu accumulation in maize shoots increased by 34, 51, and 53% with the addition of 2, 4, and 8% TOS, respectively, but this increase was not observed for Cd accumulation. These results suggested that, in multi-metal-contaminated soils, attention should be paid to the potential mobility of target metals and the pH of the contaminated soil. From a plant physiological perspective, contaminated soils slightly reduced photosynthetic performance. However, the addition of TOS to the soil at levels higher than 4% substantially decreased photosynthetic performance, indicating that CaO-based suppressants at critical loads might damage the net photosynthetic rates of sensitive maize plants.

http://ift.tt/2t4tYZt

Insomnia disorder in adolescence: diagnosis, impact, and treatment

Insomnia disorder is very common in adolescents; it is particularly manifest in older adolescents and girls, with a prevalence comparable to that of other major psychiatric disorders (e.g., depressive disorders). However, insomnia disorder in adolescence is poorly characterized, under-recognized, under-diagnosed, and under-treated, and the reason for the female preponderance for insomnia that emerges after puberty is largely unknown. Insomnia disorder goes beyond an individual complaint of poor sleep or a sleep state misperception, and there is emerging evidence supporting the association of insomnia symptoms in adolescents with alterations in several bio-systems including functional cortical alterations and systemic inflammation.

http://ift.tt/2td9wUC

Simultaneous effect of dissolved organic carbon, surfactant, and organic acid on the desorption of pesticides investigated by response surface methodology

Abstract

Desorption of pesticides (fenobucarb, endosulfan, and dichlorodiphenyltrichloroethane (DDT)) from soil to aqueous solution with the simultaneous presence of dissolved organic carbon (DOC), sodium dodecyl sulfate (SDS), and sodium oxalate (Oxa) was investigated in batch test by applying a full factorial design and the Box–Behnken response surface methodology (RSM). Five concentration levels of DOC (8 to 92 mg L⁻¹), SDS (0 to 6.4 critical micelle concentration (CMC)), and Oxa (0 to 0.15 M) were used for the experiments with a rice field topsoil. The results of RSM analysis and analysis of variance (ANOVA) have shown that the experimental data could be well described by quadratic regression equations with determination coefficients (R ²) of 0.990, 0.976, and 0.984 for desorption of fenobucarb, endosulfan, and DDT, respectively. The individual effects and interaction of DOC, SDS, and Oxa were evaluated through quadratic regression equations. When the aqueous solution includes 50 mg L⁻¹ DOC, 3.75 CMC SDS, and 0.1 M Oxa, the maximum desorption concentrations of fenobucarb, endosulfan, and DDT were 96, 80, and 75 μg L⁻¹, respectively. The lowest concentration of SDS, DOC, and Oxa caused the minimum desorption. This point at conditions of concern for flooding water is high content of organic compounds causing potentially high contamination by desorption, and the remarkably lower desorption at organic matter-free conditions. The suspended organic matter is one of the common characteristics of flooding and irrigation water in rice fields, and surfactants from pollution increase the problem with desorption of legacy pesticides in the rice fields.

http://ift.tt/2tyP5nn

Hearing loss in children with growth hormone deficiency

Although insulin-like growth factor 1 (IGF-1) has been shown to be important for inner-ear development in animal models, little is known about the otologic and audiologic findings of children with growth hormone deficiency (GHD). The goal of this study is to evaluate the prevalence, type, and severity of hearing impairment in children with GHD.

http://ift.tt/2stXjhd

Intracranial complications of CSOM in pediatric patients: A persisting problem in developing countries

Intracranial complications (ICC) of chronic suppurative otitis media (CSOM) occur even in the antibiotic area. These complications are commonly seen in pediatric patients due to poor hygiene and low immunity. They are more prevalent in developing countries due to illiteracy, low socioeconomic status and lack of access to health care facilities.

http://ift.tt/2tcSlCx

Effects of residual hearing on cochlear implant outcomes in children: A systematic-review

to investigate if preoperative residual hearing in prelingually deafened children can interfere on cochlear implant indication and outcomes. Methods: a systematic-review was conducted in five international databases up to November-2016, to locate articles that evaluated cochlear implantation in children with some degree of preoperative residual hearing. Outcomes were auditory, language and cognition performances after cochlear implant. The quality of the studies was assessed and classified according to the Oxford Levels of Evidence table - 2011.

http://ift.tt/2stHKWI

Resolution of bilateral sensorineural hearing loss following ventriculoperitoneal shunt and literature review

The purpose of this study is to highlight the relationship between obstructive hydrocephalus, changes in intracranial pressure, and sensorineural hearing loss.

http://ift.tt/2tcUeiD

Exploring reasons for late identification of children with early-onset hearing loss

Several studies have shown that early identification of childhood hearing loss leads to better language outcomes. However, delays in the confirmation of hearing loss persist even in the presence of well-established universal newborn hearing screening programs (UNHS). The objective of this population-based study was to document the proportion of children who experienced delayed confirmation of congenital and early onset hearing loss in a UNHS program in one region of Canada. The study also sought to determine the reasons for delayed confirmation of hearing loss in children.

http://ift.tt/2stIgnT

Modeling Learning in Surgical Practice

Publication date: Available online 30 June 2017
Source:Journal of Surgical Education
Author(s): Epaminondas Markos Valsamis, Rajna Golubic, Thomas E. Glover, Henry Husband, Adnan Hussain, Amir-Reza Jenabzadeh
ObjectiveMethods that model surgical learning curves are frequently descriptive and lack the mathematical rigor required to extract robust, meaningful, and quantitative information. We aimed to formulate a method to model learning that is tailored to dealing with the high variability seen in surgical data and can readily extract important quantitative information such as learning rate, length of learning, and learnt level of performance.MethodsWe developed a method where progressively more complex models are fitted to learning data. These include novel models that split the learning data into 2 linear phases and fit adjoining lines using least squares regression. The models were compared and the least complex model was selected unless a more complex one was significantly better. Significance was tested by Fischer tests. We applied this method to total hip and knee replacements using imageless navigation, analyzing the operative time for a surgeon׳s first 50 and 60 operations, respectively. This method was then tested against 4 sets of simulated learning data.ResultsThe proposed method of progressive model complexity successfully modeled the learning curve among real operative data. It was also effective in reducing the underlying trends in simulated scenarios, created to represent atypical situations that can practically arise in any learning process.ConclusionsThe novel modeling method can be used to extract meaningful and quantitative information from learning data displaying high variability seen in surgical practice. By using simple and intuitive models, the method is accessible to researchers and educators without the need for specialist statistical knowledge.



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Residents and Program Director Perspectives Often Differ on Optimal Preparation Strategies and the Value of the Orthopedic In-Training Examination

Publication date: Available online 30 June 2017
Source:Journal of Surgical Education
Author(s): Christopher L. Camp, Ryan M. Degen, Arlen D. Hanssen, Joshua S. Dines, Matthew D. Karam, Norman S. Turner
ObjectivesThe purpose of this work was to compare resident and program director (PD) perspectives on the value of the Orthopaedic In-Training Examination (OITE), resident study habits, and best resources for optimal performance.DesignA national survey of orthopedic surgery residents and PDs.SettingMayo Clinic, Rochester, MNParticipantsThe survey was completed by 445 (41.5%) eligible orthopedic surgery residents and 37 (77.1%) PDs.ResultsAlthough residents and PDs agreed on when (p = 0.896) and how much (p = 0.171) residents currently study, residents felt that the OITE was not as valuable of an assessment of their knowledge, and also felt their individual scores were less likely to remain confidential compared to PDs (p < 0.001). The mean OITE score below which residents were concerned about their ability to pass American Board of Orthopaedic Surgeons Part 1 was 9.7 percentile points higher than PDs threshold (42.3% vs. 32.6%, respectively, p = 0.003). Both groups agreed that it is important to dedicate focused study time to the OITE (p = 0.680) and to perform well (p = 0.099). Regarding the best resources and preparation strategies, both residents and PDs tended to agree on the value of most (6 of 10) study methods. Residents ranked practice question websites (mean ranking of 2.6 vs. 3.8 of 10, respectively; p < 0.001) and formal rotations in a subspecialty (6.0 vs. 7.7 respectively, p < 0.001) higher than PDs. In contrast, PDs tended to value their program's formal OITE prep program (4.1. vs. 5.3, respectively, p = 0.012) and reading primary literature (5.6 vs. 6.6, respectively, p = 0.012) more than residents.ConclusionResidents and PDs agreed on many critical components of this process; however, a number of key differences in perspectives exist.



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A New Synthetic Model for Microvascular Anastomosis Training? A Randomized Comparative Study Between Silicone and Polyvinyl Alcohol Gelatin Tubes

Publication date: Available online 1 July 2017
Source:Journal of Surgical Education
Author(s): Michael Atlan, Alexandre G. Lellouch, Josette Legagneux, Marc Chaouat, Alain-Charles Masquelet, Didier Letourneur
IntroductionAssessment of a resident's microsurgical competency with the rodent model remains the current gold standard. However, cost and ethical issues related to animal welfare may limit training opportunities. Therefore, synthetic alternatives such as silicone tubes have been developed to provide easy access to training, shorten the learning curve, and have been incorporated into microsurgical courses as a low-fidelity model for basic skills acquisition. This study compares the use of polyvinyl alcohol (PVA) gelatin tubes with silicone for resident microsurgical training.Material and MethodsResidents were randomized into silicone (S) or PVA (P) groups and underwent the same training. Following basic instruction, microsurgical anastomoses were performed with the rat's aorta or carotid artery or both. Performance was assessed using the Objective Structured Assessment of Technical Skills (OSATS) score and 5 different items to assess the quality of the anastomosis. Posttest questionnaires were also conducted for qualitative assessment of both students' and trainers' experience with silicone and PVA in comparison with rat vessels.ResultsOSATS score in Group P was higher than Group S (18.2 ± 2.6 vs 16.6 ± 2.5, p = 0.015). Results of anastomoses were similarly better in Group P based on OSATS score (19.3 ± 1.2 vs 17.7 ± 0.7, p = 0.027). Subjectively, both students and trainers found that PVA tubes resembled the rat aorta more closely than silicone. The number of rats used was also significantly lower in Group P than Group S (65 vs 75 total, p = 0.023).ConclusionPVA gelatin tubes may be a viable alternative to silicone for microsurgical training because this synthetic model mirrors better rat vessels and can improve training performance based on objective assessment while using less animals overall.



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Identification of cytidine-5-triphosphate synthase1-selective inhibitory peptide from random peptide library displayed on T7 phage

Publication date: Available online 1 July 2017
Source:Peptides
Author(s): Kotaro Sakamoto, Yoshihiro Ishibashi, Ryutaro Adachi, Shin-ichi Matsumoto, Hideyuki Oki, Yusuke Kamada, Satoshi Sogabe, Yumi Zama, Jun-ichi Sakamoto, Akiyoshi Tani
Cytidine triphosphate synthase 1 (CTPS1) is an enzyme expressed in activated lymphocytes that catalyzes the conversion of uridine triphosphate (UTP) to cytidine triphosphate (CTP) with ATP-dependent amination, using either L-glutamine or ammonia as the nitrogen source. Since CTP plays an important role in DNA/RNA synthesis, phospholipid synthesis, and protein sialyation, CTPS1-inhibition is expected to control lymphocyte proliferation and size expansion in inflammatory diseases. In contrast, CTPS2, an isozyme of CTPS1 possessing 74% amino acid sequence homology, is expressed in normal lymphocytes. Thus, CTPS1-selective inhibition is important to avoid undesirable side effects. Here, we report the discovery of CTpep-3: Ac-FRLGLLKAFRRLF-OH from random peptide libraries displayed on T7 phage, which exhibited CTPS1-selective binding with a KD value of 210nM in SPR analysis and CTPS1-selective inhibition with an IC50 value of 110nM in the enzyme assay. Furthermore, two fundamentally different approaches, enzyme inhibition assay and HDX-MS, provided the same conclusion that CTpep-3 acts by binding to the amidoligase (ALase) domain on CTPS1. To our knowledge, CTpep-3 is the first CTPS1-selective inhibitor.



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Down-regulated microRNA-375 expression as a predictive biomarker in non-small cell lung cancer brain metastasis and its prognostic significance

Publication date: Available online 1 July 2017
Source:Pathology - Research and Practice
Author(s): Li-juan Chen, Xing-ya Li, Yan-qiu Zhao, Wen-jing Liu, Hui-juan Wu, Jie Liu, Xiao-qian Mu, Hong-bo Wu
Brain metastases (BM) are common among patients with non-small cell lung cancer (NSCLC) and have been associated with significant morbidity and limited survival. Early and sensitive detection of BM is essential for improving prognosis. Recently,microRNA-375(miR-375) which is specifically expressed in the brain has been found significantly dysregulated in many human cancers. However, there is still no data whether miR-375 is associated with higher risk of BM development in NSCLC. In this study, we detected the miR-375 expression using quantitative real-time PCR (qRT-PCR) and assessed its predictive and prognostic significance. Our result showed that miR-375 expression was significantly down-regulated in NSCLC patients with BM(BM+, N=30) compared with NSCLC without BM(BM-, N=30) (P<0.001). Statistical analysis indicated that low miR-375 expression was linked to advanced disease stage (P<0.001) and brain metastasis (P<0.001) in NSCLC patient. Survival analysis suggested that low-expression group had significantly shorter overall survival than high-expression group in NSCLC patients with BM(log-rank test: P<0.05) as well as the total cases(log-rank test: P<0.01). Multivariate Cox proportional hazards model analysis indicated that low miR-375 expression was independently linked to poor survival of patients with NSCLC (HR=5.48, 95% CI: 1.93-15.56, P=0.001). In addition, we found that VEGF and MMP-9 were over-expressed in down-regulated miR-375 expression cases. Collectively, this study demonstrated that miR-375 may play an important role as a predictive biomarker in brain metastasis and an independent prognostic factor in NSCLC. Over-expression of VEGF and MMP-9 may be the reason for poor prognosis of NSCLC patients with low miR-375 expression.



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Frameshift mutation and loss of expression of PLK2, a serine/threonine kinase-encoding gene, in colorectal cancers

Publication date: Available online 1 July 2017
Source:Pathology - Research and Practice
Author(s): Ju Hwa Lee, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee




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Prevalence of Protein C Receptor (PROCR) is Associated with Inferior Clinical Outcome in Breast Invasive Ductal Carcinoma

Publication date: Available online 1 July 2017
Source:Pathology - Research and Practice
Author(s): Qiu Yan, Zhong Xiaorong, Zhang Zhang, Wei Bing, Ye Feng, Bu Hong
Recently, PROCR is reported to play an important role in cell growth, apoptosis, proliferation and tumor relapse. Some researchers thought that PROCR⁺ cells had cancer stem cell ability, which might contribute to progressive behavior in breast cancer. Our study was to assess the expression of PROCR in invasive ductal carcinoma tissues with their prognostic implications. We enrolled formalin fixed paraffin-embedded tumor tissues of 271 patients diagnosed as invasive ductal breast cancer with clinical stage II or III into our study. Immunohistochemistry staining was performed on all the tissue microarray slides, and result were interpreted by two pathologists with blinded method. We analyzed PROCR expression levels with the clinical characteristics as well as their prognostic values. PROCR expression detected in the cell was interpreted. Chi-square test showed us its positive expression had a close association with distant metastases (p=0.035). Univariate survival analysis indicated that prevalence of PROCR expression in the invasive ductal breast cancer was significantly related with decreased disease-free survival (pDFS=0.010) and overall survival (pOS=0.008). In multivariate survival by Cox proportional hazard model, positive expression group for PROCR was found to have shorter DFS [pDFS=0.028, hazard ratio (95% CI): 1.183(1.069-3.140)].Our findings suggested that breast cancer patients with expression of PROCR is more prone to suffer from distant metastasis and bad clinical outcomes.



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Morphology based scoring of Chromosomal instability and its correlation with cell viability

Publication date: Available online 1 July 2017
Source:Pathology - Research and Practice
Author(s): Shubhlata Yadav, Alka Bhatia
ObjectiveThe aim of this study was to devise the quantitative scoring system for Chromosomal instability (CIN) based on morphological indicators like MPM, NB, NPB, CS, La and MN in cancer cell line and to correlate it with cell viability and death.MethodsHuman hepatocellular carcinoma (HepG2) cells were treated with drugs like Diethylstilbestrol 0- 100μM, Griseofulvin 0–40μg/ml, Vincristine sulphate 0–25μg/ml, Mitomycin C 0–600ng/ml, Bleomycin 0–10μg/ml, Doxorubicin 0–30μg/ml for 24hours. Following this, the CIN was assessed by counting the morphological indicators like Micronuclei (MN), Nuclear Buds (NB), Nucleoplasmic bridges, Laggards, Multipolar mitosis and chromatin strings/1000 cells in Giemsa stained smears by light microscopy and by determining the percentage of aneuploid cells by flow cytometry. The cell viability was assessed by MTT assay and percentage of apoptotic cells was determined by flow cytometry.ResultsThe MN and NB were most frequently seen indicators and main determinants of morphological CIN. However, the morphological CIN score did not show any correlation with cell viability and apoptosis. Aneuploidy however was found to correlate positively with cell viability and NB score in our study (P-value <0.05).ConclusionsThe study for the 1st time attempted to develop a scoring system for CIN based on morphological parameters. However, a no correlation was observed between the later and cell viability or apoptosis. More robust techniques to quantify CIN may perhaps be more helpful in exploring the true link between CIN and cell viability in future.



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The role of ARMC5 in human cell cultures from nodules of primary macronodular adrenocortical hyperplasia (PMAH)

Publication date: Available online 1 July 2017
Source:Molecular and Cellular Endocrinology
Author(s): Isadora P. Cavalcante, Miriam Nishi, Maria Claudia N. Zerbini, Madson Q. Almeida, Vania B. Brondani, Maria Lucia Botelho, Fabio Y. Tanno, Victor Srougi, José Luis Chambo, Berenice B. Mendonça, Jerôme Bertherat, Claudimara Ferini Pacicco Lotfi, Maria Candida B.V. Fragoso
The participation of aberrant receptors and intra-adrenal ACTH in hyperplastic tissue are considered mechanisms that regulate hypercortisolism in PMAH. Additionally, germline ARMC5 mutations have been described as the most frequent genetic abnormality found in patients diagnosed with PMAH. Previous functional studies analyzed ARMC5 role using H295R cells. Therefore, we investigated the role of ARMC5 in cell cultures obtained from PMAH nodules containing steroidogenic cells, aberrant receptors and intra-adrenal ACTH. ARMC5 silencing in non-mutated PMAH cell cultures decreased steroidogenesis-related genes and increased CCNE1 mRNA expression and proliferative capacity without affecting cell viability. Additionally, ARMC5 overexpression induced cell death in PMAH mutated cell cultures, thereby decreasing cell viability. We confirmed the role of ARMC5 as an important pro-apoptotic protein involved in PMAH-related steroidogenesis. We also report for the first time the involvement of ARMC5 in controlling proliferation and regulating cell cycle in PMAH cell cultures; these effects need to be explored further.



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Ecotoxicity of 1,3-dichloropropene, metam sodium, and dazomet on the earthworm Eisenia fetida with modified artificial soil test and natural soil test

Abstract

1,3-Dichloropropene (1,3-D), metam sodium (MS), and dazomet (DZ) are widely used as preplant soil fumigants to solve soilborne problems. To provide a more scientific and accurate evaluation of 1,3-D, MS, and DZ toxicity to the earthworm Eisenia fetida, modified artificial soil test and natural soil test were studied. The suitable soil moisture to maintain over 90% survival of the earthworms after 4 weeks of treatment in an enclosed system for modified artificial soil test and natural soil test were 26.9 to 86.4% of water-holding capacity (WHC) and 66.2 to 84.3% of WHC, respectively. The optimal soil moisture levels for modified artificial soil test and natural soil test (75 and 55% of WHC, respectively) were finally used to evaluate the toxicity of 1,3-D, MS, and DZ on earthworms. Each desiccator with 10 earthworms and natural or artificial soil was stored at 20 ± 1 °C under constant light of 400 to 800 lx for 2 weeks. The modified artificial soil test showed LC₅₀ values for 1,3-D, MS, and DZ of 3.60, 1.69, and 5.41 mg a.i. kg⁻¹ soil, respectively. The modified natural soil test of the fumigants showed similar LC₅₀ values of 2.77 and 0.65 mg a.i. kg⁻¹ soil, except for DZ at 0.98 mg a.i. kg⁻¹ soil. The present study confirms that both modified artificial soil test and modified natural soil test offer standard methods for acute toxicity test of 1,3-D, MS, and DZ on the earthworms and scientific evidences for assessing the effects of soil fumigants on non-target organisms in the soils.

Graphical Abstract

Two novel acute toxicity test methods for soil fumigants on the earthworm Eisenia fetida

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Improved SNR for combined TMS-fMRI: A support device for commercially available body array coil

Publication date: Available online 30 June 2017
Source:Journal of Neuroscience Methods
Author(s): Wen-Tung Wang, Benjamin Xu, John A. Butman
BackgroundTranscranial magnetic stimulation (TMS) is a noninvasive brain stimulation tool extensively used in clinical and cognitive neuroscience research. TMS has been applied during functional magnetic resonance imaging (i.e., concurrent/interleaved TMS-fMRI) to understand neural mechanisms underlying cognitive functions. However, no advanced commercial multi-channel whole-brain array MR coils can fit the large TMS coil. We developed a low-cost and easy-to-configure setup that takes advantage of the superior signal-to-noise ratio (SNR) performance of commercially available flexible body array coils that can accommodate the TMS coil.New methodTwo flexible MRI body array coils (i.e., the Combo coil) were fitted on a simple coil support with a TMS-coil holder. Phantom and in vivo images acquired using the Combo coil with and without a TMS coil were compared with those from a product 12-channel (12CH) form-fit head array coil.ResultsRelative to the 12CH head coil, images acquired using the Combo coil were of similar quality, but with increased noise levels, leading to moderately reduced temporal SNR values.Comparison with existing methodA previous study reported that the temporal SNR of a product 12CH head coil was twice that of a transmit/receive volume birdcage coil commonly used in combined TMS-fMRI. Together with the results of the present work, they indicate that the Combo-coil setup improves SNR performance for combined TMS-fMRI acquisition.ConclusionThe inexpensive and easy-to-configure Combo-coil setup offers an effective and likely superior alternative to transmit/receive birdcage coil for combined TMS-fMRI.



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Improving gentamicin B and gentamicin C1a production by engineering the glycosyltransferases that transfer primary metabolites into secondary metabolites biosynthesis

Publication date: Available online 1 July 2017
Source:Microbiological Research
Author(s): Zheng Wu, Wenli Gao, Shaotong Zhou, Zhaolin Wen, Xianpu Ni, Huanzhang Xia
Gentamicin B and gentamicin C1a are the direct precursor for Isepamicin and Etimicin synthesis, respectively. Although producing strains have been improved for many years, both gentamicin B titer and gentamicin C1a titer in the fermentation are still low. Because all gentamicin components are biosynthesized using UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) and UDP-xylose as precursors, we tried to explore strategies for development of strains capable of directing greater fluxes of these precursors into production of gentamicins. The glycosyltransferases KanM1 and GenM2, which are responsible for UDP-GlcNAc and UDP-xylose transfer, respectively, were overexpressed in gentamicin B producing strain Micromonospora echinospora JK4. It was found that gentamicin B could be improved by up to 54% with improvement of KanM1 and GenM2 expression during appropriately glucose feeding. To prove this strategy is widely usable, the KanM1 and GenM2 were also overexpressed in gentamicin C1a producing strain, titers of gentamicin C1a improved by 45% when compared with titers of the starting strain. These results demonstrated overexpression the glycosyltransferases that transfer primary metabolites into secondary metabolites is workable for improvement of gentamicins production.



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Influence of environmental factors on absorption characteristics of suspended particulate matter and CDOM in Liaohe River watershed, northeast China

Abstract

Absorption characteristics of optically active substances, including non-algal particles, phytoplankton, and chromophoric dissolved organic matter (CDOM), were measured in conjunction with environmental factors in five rivers within the Liaohe River watershed. Spectral absorption of non-algal particles [a _NAP(λ)] was similar to that of total particles for most samples, suggesting that the absorption of the total particles [a _p(λ)] was dominated by a _NAP(λ). The CDOM absorption spectra [a _CDOM(λ)] of West Liaohe and Taizihe rivers were easily distinguished from those of Hunhe, Liaohe, and East Liaohe rivers. Redundancy analysis indicated that absorption by optically active substances and anthropogenic nutrient disturbances probably resulted in the diversity of water quality parameters. The environmental variables including dissolved organic carbon, total alkalinity (TAlk), and total nitrogen (TN) had a significant correlation with CDOM absorption at 440 nm [a _CDOM(440)]. There was almost no correlation between a _p(λ) and chlorophyll a, TN, total phosphorus, and TAlk. Moreover, total copper ion concentration and mercury ion concentration had a strong correlation with a _p(440), a _p(675), a _NAP(440), and a _NAP(675). The concentration of total aluminum ions exhibited a positive correlation with a _p(675) and a _NAP(675) (p < 0.05), and a significant correlation was observed between total arsenic concentration and a _CDOM(440). Furthermore, the interaction between metal ions and optically active substances provided an insight into particulates and CDOM properties linked to water quality characteristics for rivers in semiarid areas.

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Spinal muscular atrophy carriers with two SMN1 copies

Publication date: Available online 1 July 2017
Source:Brain and Development
Author(s): Mawaddah Ar Rochmah, Hiroyuki Awano, Tomonari Awaya, Nur Imma Fatimah Harahap, Naoya Morisada, Yoshihiro Bouike, Toshio Saito, Yuji Kubo, Kayoko Saito, Poh San Lai, Ichiro Morioka, Kazumoto Iijima, Hisahide Nishio, Masakazu Shinohara
BackgroundSpinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder. Over 95% of SMA patients have homozygous deletions of the SMA-causative gene, SMN1. Thus, SMA carriers are usually diagnosed based on SMN1 copy number, with one copy indicating SMA carrier status. However, two SMN1 copies do not always exclude carrier status. In this study, we identified SMA carriers with two SMN1 copies.Subjects and methodsFrom 33 families, 65 parents of genetically confirmed SMA patients were tested to determine SMA carrier status. Molecular genetic analyses, including multiplex ligation-dependent probe amplification (MLPA) assay, were performed using blood samples from family members.ResultsOf the 65 parents, three parents from three families had two SMN1 copies. Accordingly, the frequency of carriers with two SMN1 copies was 4.6%. Two of these families were further studied. Patient 1 was homozygous for SMN1 deletion. Patient 1's mother had two SMN1 copies on one chromosome, with deletion of SMN1 on the other chromosome ([2+0] genotype). Patient 1 inherited SMN1-deleted chromosomes from both parents. Patient 2 was compound heterozygous for two SMN1 mutations: whole-gene deletion and intragenic missense mutation, c.826T>C (p.Tyr276His). Patient 2's father had two SMN1 copies with the same intragenic mutation in one copy ([1+1^d] genotype, ^d intragenic mutation). Patient 2 inherited the chromosome with an SMN1 mutation from the father and SMN1-deleted chromosome from the mother.ConclusionSMA carriers with two SMN1 copies may be rare, but its possibility should be taken into consideration in carrier testing and counseling for SMA families or population-based carrier screening.



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β-elemene regulates endoplasmic reticulum stress to induce the apoptosis of NSCLC cells through PERK/IRE1α/ATF6 pathway

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Ying Liu, Zi-yu Jiang, Yuan-li Zhou, Hui-hui Qiu, Gang Wang, Yi Luo, Jing-bing Liu, Xiong-wei Liu, Wei-quan Bu, Jie Song, Li Cui, Xiao-bin Jia, Liang Feng
Endoplasmic reticulum stress (ERs) has been regarded as an important cause for the pathogenesis of non-small-cell lung cancer (NSCLC). β-elemene is an active component in the essential oil extracted from a medicinal herb, Curcuma wenyujin, and has been reported to be effective against non-small-cell lung cancer (NSCLC). However, the potential effect and underlying mechanisms of β-elemene on regulating ERs to inhibit NSCLC are still unclear. In the present study, A549 cells and Lewis tumor-bearing C57BL/6J mice were established to evaluate this effect. Visualsonics Vevo 2100 Small Animal Dedicated High-frequency Color Ultrasound was performed to observe tumor volume in vivo. 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) was used to evaluate cell vitality of A549 cells. Furthermore, western blotting (WB), immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (q-PCR) were applied to detect the ERs-related proteins. Flow cytometry was also applied to detect cell apoptosis and assay kit for reactive oxygen species (ROS) generation. Our results showed that β-elemene inhibited lung cancer tumor growth and cell vitality in a dose- and time-dependent manner. Not only that, β-elemene could up-regulate ERs-related proteins like PERK, IRE1α, ATF6, ATF4, CHOP and down-regulate the Bcl-2 expression. More importantly, ERs inhibitor 4-PBA, IRE1α inhibitor STF-083010, ATF6 inhibitor Anti-ATF6 and PERK inhibitor GSK2656157 can all reduce the amplitude of protein expression changes and apoptosis rates, then weaken the anti-tumor effect of β-elemene. Therefore, the present in vivo and in vitro study revealed that the anti-NSCLC effect of β-elemene is closely related to the activation of ERs through PERK/IRE1α/ATF6 pathway, and this might be beneficial for clinical therapy of NSCLC.



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Pooled Analysis of Clinical Outcome of Patients with Chemorefractory Metastatic Colorectal Cancer Treated within Phase I/II Clinical Studies Based on Individual Biomarkers of Susceptibility: A Single-Institution Experience

Abstract

Background

Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value.

Objective

We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s).

Patients and Methods

From June 2011 to May 2016, 2044 patients with mCRC underwent molecular screening. Eighty patients (3.9%) were enrolled in ad hoc studies; the median age was 60 years (range 36–86) and the median number of previous treatment lines was five (range 2–8). Molecular characteristics exploited within these studies were MGMT promoter hypermethylation (48.7%), HER2 amplification (28.8%), BRAF ^V600E mutation (20%), and novel gene fusions involving ALK or NTRK (2.5%).

Results

One patient (1%) had RECIST (Response Evaluation Criteria In Solid Tumors) complete response (CR), 13 patients (16.5%) experienced a partial response (PR), and 28 (35%) stable disease (SD). Median progression-free survival (PFS) was 2.8 months (range 2.63–3.83), with 24% of patients displaying PFS >5 months. Median growth modulation index (GMI) was 0.85 (range 0–15.61) and 32.5% of patients had GMI >1.33. KRAS exon 2 mutations were found in 38.5% of patients, and among the 78 patients with known KRAS status, those with wild-type tumors had longer PFS than those with mutated tumors (3.80 [95% CI 2.80–5.03] vs. 2.13 months [95% CI 1.77–2.87], respectively, p = 0.001). Median overall survival (OS) was 7.83 months (range 7.17–9.33) for all patients, and patients with KRAS wild-type tumors had longer OS than those with mutated tumors (7.83 [95% CI 7.33–10.80] vs. 7.18 months [95% CI 5.63–9.33], respectively, p = 0.06).

Conclusions

This single-institution retrospective study indicates that in a heavily pretreated population approximately 4% of mCRC tumors display a potential actionable molecular context suitable for therapeutic intervention. Application of molecular selection is challenging but improves clinical outcome even in later lines of treatment.

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Sjogren's syndrome: New paradigms and areas for future research

Publication date: Available online 30 June 2017
Source:Clinical Immunology
Author(s): Julian L. Ambrus




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Sjogren's syndrome: New paradigms and areas for future research

Publication date: Available online 30 June 2017
Source:Clinical Immunology
Author(s): Julian L. Ambrus




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Translocator protein (18 kDa): an update on its function in steroidogenesis

Abstract

Translocator protein (18 kDa), TSPO, is a ubiquitous mitochondrial protein. Studies of its responses to drug and endogenous ligands have shown TSPO to be involved either directly or indirectly in numerous biological functions, including mitochondrial cholesterol transport and steroid hormone biosynthesis, porphyrin transport and heme synthesis, apoptosis, cell proliferation, and anion transport. Localized to the outer mitochondrial membrane of steroidogenic cells, TSPO has been shown to associate with cytosolic and mitochondrial proteins as part of a large multiprotein complex involved in mitochondrial cholesterol transport, the rate-limiting step in steroidogenesis. There is general agreement as to the structure and pharmacology of TSPO. Stimulation of TSPO has been shown to have therapeutic use as anxiolytics by inducing allopregnanolone production in the brain, and also potentially for reestablishing androgen levels in hypogonadal aging animals. Until recently, there has been general agreement as to the role of TSPO in steroidogenesis. However, recent studies involving genetic depletion of TSPO in mice have created controversy about the role of this protein in steroid and heme synthesis. We review herein the data on TSPO's structure and function, and recent results using various genetic animal models. Taken together, these studies suggest that TSPO is a unique mitochondrial pharmacological target for diseases that involve increased mitochondrial activity, including steroidogenesis. Although there is no known mammalian species that lacks TSPO, it is likely that due to the importance of this ancient protein in evolution and mitochondrial function, redundant mechanisms may exist to replace it under circumstances when it is removed.

This article is protected by copyright. All rights reserved.

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Diffusion-weighted MRI in image-guided adaptive brachytherapy: Tumor delineation feasibility study and comparison with GEC-ESTRO guidelines

Publication date: Available online 30 June 2017
Source:Brachytherapy
Author(s): Antoine Schernberg, Corinne Balleyguier, Isabelle Dumas, Sébastien Gouy, Alexandre Escande, Enrica Bentivegna, Philippe Morice, Eric Deutsch, Christine Haie-Meder, Cyrus Chargari
PurposeTo examine the feasibility of using diffusion-weighted images (DWIs) coregistered with T2-weighted (T2w) sequence in treatment planning system to improve target delineation for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer patients.Methods and MaterialsWe retrospectively examined the records of consecutive patients who were referred to our institution for pulse-dose-rate IGABT between May and December 2015 after concurrent chemoradiation. An MRI with T2w and DWI sequences with a maximum diffusion factor of 1000 s/mm² on a 1.5 or 3.0-T MR scanner was performed after placement of the vaginal mold applicator. T2w defined gross tumor volume (GTVT2) and diffusion volume on DWI sequences (CTVDWI) were retrospectively delineated, if achievable, by radiologist and radiation oncologist. Concordances between CTVDWI and GTVT2, high-risk and intermediate-risk clinical target volumes (CTVHR and CTVIR) were evaluated.ResultsForty-four patients were identified: 23 patients (52%) had a GTVT2 delineated, CTVDWI was delineated in 42 patients (95%). Intraobserver and interobserver conformity indexes were <0.75 in 11 patients (26%) and 23 patients (54%), respectively. There was a positive correlation between GTVT2 and CTVDWI volumes (p = 0.038, r = 0.58). Median CTVHR and CTVDWID90 were 37.3 Gy (17.1–48.9 Gy) and 33 Gy (22–97 Gy), respectively (p = 0.659). CTVDWI could have pointed CTVHR delineation modifications in a total of 32 of 44 (73%) patients with CTVDWI/CTVHR conformity < 1. CTVDWI volume was totally encompassed by CTVIR in all patients.ConclusionsThese results suggest that DWI images as anatomical sequence without apparent diffusion coefficient mapping might have led to CTVHR modifications. Still, interobserver and intraobserver variations in delineation are substantial, and artifacts make it difficult to implement.



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American Brachytherapy Society consensus report for accelerated partial breast irradiation using interstitial multicatheter brachytherapy

Publication date: Available online 1 July 2017
Source:Brachytherapy
Author(s): Jaroslaw T. Hepel, Douglas Arthur, Simona Shaitelman, Csaba Polgár, Dorin Todor, Imran Zoberi, Mitchell Kamrava, Tibor Major, Catheryn Yashar, David E. Wazer
PurposeTo develop a consensus report for the quality practice of accelerated partial breast irradiation (APBI) using interstitial multicatheter brachytherapy (IMB).Methods and MaterialsThe American Brachytherapy Society Board appointed an expert panel with clinical and research experience with breast brachytherapy to provide guidance for the current practice of IMB. This report is based on a comprehensive literature review with emphasis on randomized data and expertise of the panel.ResultsRandomized trials have demonstrated equivalent efficacy of APBI using IMB compared with whole breast irradiation for select patients with early-stage breast cancer. Several techniques for placement of interstitial catheters are described, and importance of three-dimensional planning with appropriate optimization is reviewed. Optimal target definition is outlined. Commonly used dosing schemas include 50 Gy delivered in pulses of 0.6–0.8 Gy/h using pulsed-dose-rate technique and 34 Gy in 10 fractions, 32 Gy in eight fractions, or 30 Gy in seven fractions using high-dose-rate technique. Potential toxicities and strategies for toxicity avoidance are described in detail. Dosimetric constraints include limiting whole breast volume that receives ≥50% of prescription dose to <60%, skin dose to ≤100% of prescription dose (≤60–70% preferred), chest wall dose to ≤125% of prescription dose, Dose Homogeneity Index to >0.75 (>0.85 preferred), V150 < 45 cc, and V200 < 14 cc. Using an optimal implant technique coupled with optimal planning and appropriate dose constraints, a low rate of toxicity and a good-to-excellent cosmetic outcome of ≥90% is expected.ConclusionsIMB is an effective technique to deliver APBI for appropriately selected women with early-stage breast cancer. This consensus report has been created to assist clinicians in the appropriate practice of APBI using IMB.



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Patient preferences for the attributes of a non-invasive treatment for superficial Basal cell carcinoma: a discrete choice experiment

Abstract

To examine which attributes of a non-invasive treatment for superficial BCC (sBCC) are valued by patients, a discrete choice experiment (DCE) was performed alongside a clinical trial in which methylaminolevulinate photodynamic therapy (MAL-PDT), 5-fluorouracil and imiquimod were compared.¹

Treatment options were described by the following attributes: effectiveness, cosmetic result, treatment process and side-effects. Effectiveness was defined as the probability that complete tumour clearance is achieved 12 months after treatment with levels of 75%,80%,85% and 90%.^2-4

This article is protected by copyright. All rights reserved.

http://ift.tt/2uvc0Nx

Functional melanoma-risk variant IRF4 rs12203592 associated with Breslow thickness: a pooled international study of primary melanomas

Abstract

Breslow thickness is considered to be the most important prognostic tumor feature in melanoma patients and is associated with age, sex, and phenotypic risk factors for melanoma such as number of nevi. However, its association with inherited genetic variants in recently identified melanoma risk loci is largely unknown.

In a Western Australian Melanoma Health Study (WAMHS) study, published in the British Journal of Dermatology, IRF4 rs12203592, OCA2 rs1800401 and TP53 rs1042522 were significantly associated (P < 0.05) with Breslow thickness; however, these associations did not pass false discovery.

This article is protected by copyright. All rights reserved.

http://ift.tt/2txjFxO

Lack of Response to Intravenous Sodium Thiosulfate in Three Cases of Extensive Connective Tissue Disease-Associated Calcinosis Cutis

Abstract

Dystrophic calcinosis cutis is a debilitating condition of calcium salt deposition in the skin often occurring in association with connective tissue disease (CTD). Available treatments for calcinosis cutis are unsatisfactory, but given the recent use of topical and intralesional sodium thiosulfate (STS) to treat calcifying disorders, we sought to describe the use of intravenous (IV) STS for CTD-associated dystrophic calcinosis cutis. We report three patients with longstanding and extensive CTD-associated calcinosis cutis treated with IV STS after having failed multiple prior therapies. All three patients experienced fatigue and nausea with STS infusions, and none of the patients had notable clinical or symptomatic improvement of calcinosis. It remains to be seen whether the administration of IV STS earlier in the onset of calcinosis might be of benefit given that these patients all had longstanding and refractory CTD-associated calcinosis. Given the small number of patients in this series, further investigation into the use of IV STS in calcinosis cutis is warranted.

This article is protected by copyright. All rights reserved.

http://ift.tt/2uvc2oD

Invasive dermatophyte infection with trichophyton interdigitale is associated with prurigo induced pseudoperforation and a STAT3 mutation

Abstract

Invasive dermatophyte infection, with extention beyond the dermis, in immunocompetent hosts is exceptionally rare. Dermatophytes are keratinophilic and are usually confined to the stratum corneum, hair and nails. Susceptibility to dermatophyte infections is incompletely understood but inherited mutations in key signaling pathways of the innate immune system have been identified.¹ We report the first case of an invasive dermatophyte infection associated with abrupt onset of a prurigo induced pseudoperforation and a loss of function mutation in Signal transducer and activator of transcription 3 (STAT 3).

This article is protected by copyright. All rights reserved.

http://ift.tt/2txgKoK

Experiences of rosacea and its treatment: An interpretative phenomenological analysis

Abstract

Background

Whilst rosacea is a chronic skin condition, the condition can often have a large psychosocial impact on the individual. There is therefore a need to understand the experience of living with rosacea from the patient perspective.

Objectives

To examine the experience of living with rosacea and the experience of seeking and receiving treatment.

Methods

Nine participants took part in semi-structured interviews, which were analysed using interpretative phenomenological analysis.

Results

Three superordinate themes were identified within the data; self-consciousness, which focused on the fear of others' assigning blame to participants for having caused symptoms; avoidance, concealment, and hiding emotions, referring to the coping strategies participants employed in response to rosacea; and inconsistencies in GP treatment and guidance, which focused on the need for medical professionals to assess the psychosocial well-being of patients with rosacea.

Conclusions

Rosacea can have a negative impact on the daily life of people with the condition, contributing to lowered self-esteem, embarrassment, and feelings of shame. Engaging in emotion-focused and behavioural/avoidant-focused coping strategies increased participant's confidence and reduced their avoidance of social situations. However, such strategies might still serve to maintain underlying unhelpful cognitive processes. Consequently, it is important for medical professionals to assess for the presence of cognitive factors that might contribute to maintaining distress in patients with rosacea, and where unhelpful thoughts or beliefs are reported, patients may need to be referred for psychological support.

This article is protected by copyright. All rights reserved.

http://ift.tt/2uvuYnc

Hidradenitis Suppurativa and electrocardiographic changes – a cross-sectional population study

Abstract

Background

Hidradenitis Suppurativa (HS) is a chronic, inflammatory skin disease, recently associated with metabolic syndrome, subclinical atherosclerosis and increased risk of cardiovascular disease.

Objectives

The aim of the study was to investigate the hitherto unknown electrocardiographic changes associated with HS, which recently have been associated with significant cardiovascular burden.

Methods

Data were derived from the cross-sectional population study, The Danish General Population Study (GESUS). HS diagnosis was based on a validated self-reported questionnaire and 404 individuals met the HS diagnosis criteria and 19,001 controls without HS were identified in the population. Severity of HS was staged according to a modified Hurley score. The electrocardiographic parameters, Heart Rate (HR), PR-interval, QRS-duration, JTc-interval and QTc-interval, were obtained from 12-lead resting electrocardiograms. We investigated the difference in means by unpaired t-test or the analysis of variance (ANOVA) test.

Results

Heart rate was significantly higher (mean difference: 2.3 bpm [1.2:3.4] p<0.01) when adjusting for age and gender but when multivariate adjusting, there was no significant difference (0.3 bpm [-0.7:1.4] p=0.52). Severe HS was significantly associated with increased heart rate across all models (2.9 bpm [0.7:5.1] p=0.01). Mean QRS-duration was significantly shorter in the mild HS group, but not in the moderate- and severe HS groups

Conclusion

Mean resting heart rate in severe HS was significantly higher compared to controls. Given that resting heart rate is associated with increased risk of all-cause and cardiovascular mortality, and that HS patients have increased risk of cardiovascular events, this finding is potentially important, easily testable and intervenable.

This article is protected by copyright. All rights reserved.

http://ift.tt/2syaxVl

A hyaluronic acid-based microneedle patch to treat psoriatic plaques: A pilot open trial

Abstract

Psoriasis, a common, chronic, relapsing, inflammatory skin disease characterised by multiple erythematous papules and plaques with silvery scales, affects 0.5–3% of the world's population. Recently, great advances have been made in the treatment of psoriasis, including the introduction of targeted biological agents.¹ However, topical treatment remains important; most patients have mild disease affecting less than 2% of the body surface area.²

This article is protected by copyright. All rights reserved.

http://ift.tt/2t2IyR3

AGREE II assessments of recent acne treatment guidelines: how well do they reveal trustworthiness as defined by the Institute of Medicine (IOM) criteria?

Abstract

Background

Up-to-date, trustworthy guidelines are a widely relied-upon means of promoting excellent patient care.

Objectives

To determine the quality of recently published acne treatment guidelines by utilizing the Appraisal of Guidelines for Research and Evaluation (AGREE) II Reporting Checklist, the US Institute of Medicine's (IOM) criteria of trustworthiness, Lenzer et al's red flags and CheckUp.

Methods

Systematic searches were conducted in bibliographic databases, guideline depositories and using Google^™ to identify acne treatment guidelines published since 2013. Six assessors independently scored each guideline using the AGREE II Reporting Checklist. Guidelines were concomitantly assessed for trustworthiness using the IOM criteria and for Lenzer et al's red flags indicative of potential bias. Updates were screened using CheckUp.

Results

Eight guidelines were identified, two of which were updates. Lowest scoring AGREE II domains across all guidelines were rigour (6/8 poor, one fair, one average) and applicability (4/8 poor, one fair, three average). Two out of the three highest scoring guidelines were developed using AGREE II. No guideline fully met each IOM criterion and all raised at least one red flag indicative of potential bias. One updated guideline did not address seven of 16 items on CheckUp and the other did not address four. Patient involvement in guideline development was minimal.

Conclusions

Use of the AGREE II Instrument during guideline development did not have as great an effect on guideline quality as might be expected. There is considerable room for improvement in acne treatment guidelines in order to satisfy the IOM trustworthiness criteria and avoid bias.

This article is protected by copyright. All rights reserved.

http://ift.tt/2syjtdt

European Heart SCORE may underestimates cardiovascular risk after assessing cardiovascular disease with carotid ultrasound in Hidradenitis Suppurativa

Abstract

Hidradenitis suppurativa (HS) is chronic recurrent inflammatory disease affecting intertriginous areas, especially the axilla and the groin¹. It is characterized by painful, deep-seated, inflamed lesions, including nodules, abscesses, and sinus tracts². A recent meta-analysis found an association between HS and traditional cardiovascular (CV) risk factors and metabolic syndrome³.

This article is protected by copyright. All rights reserved.

http://ift.tt/2t2LxZX

Patient preferences for the attributes of a non-invasive treatment for superficial Basal cell carcinoma: a discrete choice experiment

Abstract

To examine which attributes of a non-invasive treatment for superficial BCC (sBCC) are valued by patients, a discrete choice experiment (DCE) was performed alongside a clinical trial in which methylaminolevulinate photodynamic therapy (MAL-PDT), 5-fluorouracil and imiquimod were compared.¹

Treatment options were described by the following attributes: effectiveness, cosmetic result, treatment process and side-effects. Effectiveness was defined as the probability that complete tumour clearance is achieved 12 months after treatment with levels of 75%,80%,85% and 90%.^2-4

This article is protected by copyright. All rights reserved.

http://ift.tt/2uvc0Nx

Functional melanoma-risk variant IRF4 rs12203592 associated with Breslow thickness: a pooled international study of primary melanomas

Abstract

Breslow thickness is considered to be the most important prognostic tumor feature in melanoma patients and is associated with age, sex, and phenotypic risk factors for melanoma such as number of nevi. However, its association with inherited genetic variants in recently identified melanoma risk loci is largely unknown.

In a Western Australian Melanoma Health Study (WAMHS) study, published in the British Journal of Dermatology, IRF4 rs12203592, OCA2 rs1800401 and TP53 rs1042522 were significantly associated (P < 0.05) with Breslow thickness; however, these associations did not pass false discovery.

This article is protected by copyright. All rights reserved.

http://ift.tt/2txjFxO

Lack of Response to Intravenous Sodium Thiosulfate in Three Cases of Extensive Connective Tissue Disease-Associated Calcinosis Cutis

Abstract

Dystrophic calcinosis cutis is a debilitating condition of calcium salt deposition in the skin often occurring in association with connective tissue disease (CTD). Available treatments for calcinosis cutis are unsatisfactory, but given the recent use of topical and intralesional sodium thiosulfate (STS) to treat calcifying disorders, we sought to describe the use of intravenous (IV) STS for CTD-associated dystrophic calcinosis cutis. We report three patients with longstanding and extensive CTD-associated calcinosis cutis treated with IV STS after having failed multiple prior therapies. All three patients experienced fatigue and nausea with STS infusions, and none of the patients had notable clinical or symptomatic improvement of calcinosis. It remains to be seen whether the administration of IV STS earlier in the onset of calcinosis might be of benefit given that these patients all had longstanding and refractory CTD-associated calcinosis. Given the small number of patients in this series, further investigation into the use of IV STS in calcinosis cutis is warranted.

This article is protected by copyright. All rights reserved.

http://ift.tt/2uvc2oD

Invasive dermatophyte infection with trichophyton interdigitale is associated with prurigo induced pseudoperforation and a STAT3 mutation

Abstract

Invasive dermatophyte infection, with extention beyond the dermis, in immunocompetent hosts is exceptionally rare. Dermatophytes are keratinophilic and are usually confined to the stratum corneum, hair and nails. Susceptibility to dermatophyte infections is incompletely understood but inherited mutations in key signaling pathways of the innate immune system have been identified.¹ We report the first case of an invasive dermatophyte infection associated with abrupt onset of a prurigo induced pseudoperforation and a loss of function mutation in Signal transducer and activator of transcription 3 (STAT 3).

This article is protected by copyright. All rights reserved.

http://ift.tt/2txgKoK

Experiences of rosacea and its treatment: An interpretative phenomenological analysis

Abstract

Background

Whilst rosacea is a chronic skin condition, the condition can often have a large psychosocial impact on the individual. There is therefore a need to understand the experience of living with rosacea from the patient perspective.

Objectives

To examine the experience of living with rosacea and the experience of seeking and receiving treatment.

Methods

Nine participants took part in semi-structured interviews, which were analysed using interpretative phenomenological analysis.

Results

Three superordinate themes were identified within the data; self-consciousness, which focused on the fear of others' assigning blame to participants for having caused symptoms; avoidance, concealment, and hiding emotions, referring to the coping strategies participants employed in response to rosacea; and inconsistencies in GP treatment and guidance, which focused on the need for medical professionals to assess the psychosocial well-being of patients with rosacea.

Conclusions

Rosacea can have a negative impact on the daily life of people with the condition, contributing to lowered self-esteem, embarrassment, and feelings of shame. Engaging in emotion-focused and behavioural/avoidant-focused coping strategies increased participant's confidence and reduced their avoidance of social situations. However, such strategies might still serve to maintain underlying unhelpful cognitive processes. Consequently, it is important for medical professionals to assess for the presence of cognitive factors that might contribute to maintaining distress in patients with rosacea, and where unhelpful thoughts or beliefs are reported, patients may need to be referred for psychological support.

This article is protected by copyright. All rights reserved.

http://ift.tt/2uvuYnc

Hidradenitis Suppurativa and electrocardiographic changes – a cross-sectional population study

Abstract

Background

Hidradenitis Suppurativa (HS) is a chronic, inflammatory skin disease, recently associated with metabolic syndrome, subclinical atherosclerosis and increased risk of cardiovascular disease.

Objectives

The aim of the study was to investigate the hitherto unknown electrocardiographic changes associated with HS, which recently have been associated with significant cardiovascular burden.

Methods

Data were derived from the cross-sectional population study, The Danish General Population Study (GESUS). HS diagnosis was based on a validated self-reported questionnaire and 404 individuals met the HS diagnosis criteria and 19,001 controls without HS were identified in the population. Severity of HS was staged according to a modified Hurley score. The electrocardiographic parameters, Heart Rate (HR), PR-interval, QRS-duration, JTc-interval and QTc-interval, were obtained from 12-lead resting electrocardiograms. We investigated the difference in means by unpaired t-test or the analysis of variance (ANOVA) test.

Results

Heart rate was significantly higher (mean difference: 2.3 bpm [1.2:3.4] p<0.01) when adjusting for age and gender but when multivariate adjusting, there was no significant difference (0.3 bpm [-0.7:1.4] p=0.52). Severe HS was significantly associated with increased heart rate across all models (2.9 bpm [0.7:5.1] p=0.01). Mean QRS-duration was significantly shorter in the mild HS group, but not in the moderate- and severe HS groups

Conclusion

Mean resting heart rate in severe HS was significantly higher compared to controls. Given that resting heart rate is associated with increased risk of all-cause and cardiovascular mortality, and that HS patients have increased risk of cardiovascular events, this finding is potentially important, easily testable and intervenable.

This article is protected by copyright. All rights reserved.

http://ift.tt/2syaxVl

A hyaluronic acid-based microneedle patch to treat psoriatic plaques: A pilot open trial

Abstract

Psoriasis, a common, chronic, relapsing, inflammatory skin disease characterised by multiple erythematous papules and plaques with silvery scales, affects 0.5–3% of the world's population. Recently, great advances have been made in the treatment of psoriasis, including the introduction of targeted biological agents.¹ However, topical treatment remains important; most patients have mild disease affecting less than 2% of the body surface area.²

This article is protected by copyright. All rights reserved.

http://ift.tt/2t2IyR3

AGREE II assessments of recent acne treatment guidelines: how well do they reveal trustworthiness as defined by the Institute of Medicine (IOM) criteria?

Abstract

Background

Up-to-date, trustworthy guidelines are a widely relied-upon means of promoting excellent patient care.

Objectives

To determine the quality of recently published acne treatment guidelines by utilizing the Appraisal of Guidelines for Research and Evaluation (AGREE) II Reporting Checklist, the US Institute of Medicine's (IOM) criteria of trustworthiness, Lenzer et al's red flags and CheckUp.

Methods

Systematic searches were conducted in bibliographic databases, guideline depositories and using Google^™ to identify acne treatment guidelines published since 2013. Six assessors independently scored each guideline using the AGREE II Reporting Checklist. Guidelines were concomitantly assessed for trustworthiness using the IOM criteria and for Lenzer et al's red flags indicative of potential bias. Updates were screened using CheckUp.

Results

Eight guidelines were identified, two of which were updates. Lowest scoring AGREE II domains across all guidelines were rigour (6/8 poor, one fair, one average) and applicability (4/8 poor, one fair, three average). Two out of the three highest scoring guidelines were developed using AGREE II. No guideline fully met each IOM criterion and all raised at least one red flag indicative of potential bias. One updated guideline did not address seven of 16 items on CheckUp and the other did not address four. Patient involvement in guideline development was minimal.

Conclusions

Use of the AGREE II Instrument during guideline development did not have as great an effect on guideline quality as might be expected. There is considerable room for improvement in acne treatment guidelines in order to satisfy the IOM trustworthiness criteria and avoid bias.

This article is protected by copyright. All rights reserved.

http://ift.tt/2syjtdt

European Heart SCORE may underestimates cardiovascular risk after assessing cardiovascular disease with carotid ultrasound in Hidradenitis Suppurativa

Abstract

Hidradenitis suppurativa (HS) is chronic recurrent inflammatory disease affecting intertriginous areas, especially the axilla and the groin¹. It is characterized by painful, deep-seated, inflamed lesions, including nodules, abscesses, and sinus tracts². A recent meta-analysis found an association between HS and traditional cardiovascular (CV) risk factors and metabolic syndrome³.

This article is protected by copyright. All rights reserved.

http://ift.tt/2t2LxZX

Peak inspiratory flow as predictor for tracheotomy

Publication date: Available online 30 June 2017
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): M. Lesnik, J. J. Sanchez-Guerrero, O. De Crouy Chanel, C. Hervé, J. Guerlain, S. Périé
ObjectivesQuantitative evaluation of upper airway obstruction cannot be commonly performed under acute dyspnea, especially in head and neck cancer (HNC); the decision whether or not to perform airway control surgery may be difficult to reach. Peak inspiratory flow (PIF) has been previously demonstrated to be a useful tool to decide on decannulation after HNC surgery. The aim of the present study was to assess the role of PIF as a standardized non-invasive tool in quantifying severe inspiratory dyspnea requiring emergency tracheostomy.Materials and methodsA single-center prospective observational pilot study analyzed PIF measurements in 22 patients exhibiting acute dyspnea due to upper airway obstruction.Main outcome measuresThe decision whether or not to perform tracheotomy was taken prior to PIF measurement. PIF was measured with a hand-held PIF meter (In-Check method), and laryngeal fiberoscopy was then performed. Obstruction severity was defined by PIF values.ResultsPIF could be measured prior to tracheotomy (imminent in 21 cases, postponed in 1) in all cases. PIF values below 53.1 L/min (i.e., 18.3% of theoretic value) correlated with necessity for emergency tracheotomy. This threshold is concordant with that previously found for the feasibility of decannulation (60L/min).ConclusionsPIF is a non-invasive quantitative parameter assessing severity of upper airway obstruction, that may be helpful in decision-making for tracheostomy. Testing is simple, quick and reproducible.



http://ift.tt/2scNNLp

A pigmented lesion of the nasopharynx

Publication date: Available online 30 June 2017
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): J.-W. Kim, S.-D. Kim, K.-S. Cho




http://ift.tt/2tvTSpZ

Oral shedding of human herpesviruses in renal transplant recipients

Abstract

Objective

To describe the shedding profile of human herpesviruses in the saliva of renal transplant recipients.

Methods

This is a prospective case-control study of 50 renal transplant recipients and control group of 50 individuals (non-transplanted and immunocompetent). Mouthwash samples were collected via oral rinse and then submitted to screening for the presence of eight types of herpesviruses by using multiplex PCR. Fisher's exact, chi-square, and Student t tests were used for statistical analysis, and the significance level was set at 5%.

Results

The mean age of the study group was 49.42 ± 12.94 years, 28/50 (56%) were female, and the time elapsed after transplantation was 68.20 ± 67.19 months. Herpes simplex virus 1 (HSV-1) (P = 0.025) and Epstein-Barr virus (EBV) (P = 0.024) were, statistically, more excreted in the saliva of renal transplant recipients compared to control group. Gender (P = 1.00) and age (P = 0.563) did not influence the salivary shedding of herpesviruses in renal transplant recipients. Individuals who excreted varicella-zoster virus in saliva had a shorter mean time of transplantation (22:00 + 2.82 months) (P < 0.001).

Conclusion

Renal transplant recipients excreted herpesviruses more often than controls, especially HSV-1 and EBV, with salivary shedding of herpesviruses being more frequent in patients with recent kidney transplantation.

Clinical relevance

The present findings support other longitudinal studies evaluating the relationship between oral shedding of human herpesviruses and clinical presence of active infection and renal transplant failure.

http://ift.tt/2tvLhn8

Effect of root canal preparation techniques on chlorhexidine substantivity on human dentin: a chemical analysis

Abstract

Objectives

Chlorhexidine binds to dentine to provide sustained action. The aim of the present study was to evaluate and compare the substantivity of chlorhexidine using manual, rotary, and reciprocating systems for root canal preparation.

Methods

Forty-five extracted human single-rooted teeth were used for this study. The samples were divided into three groups (n = 15) according to the instrumentation technique used: manual instrumentation (K-File), rotary instrumentation (ProTaper), and reciprocating instrumentation (Reciproc R25). Chlorhexidine gel (2%) was used as auxiliary chemical substance during root canal preparation. Longitudinal grooves were carved on the free surfaces of the roots, providing two halves of each root and resulting in 30 samples per group. Each group was randomly divided into three subgroups (n = 10), and substantivity was evaluated after 48 h, 7 days, and 30 days of incubation. The amount of CHX (in mg/mL) was measured through reverse-phase high-performance liquid chromatography. Statistical analysis was performed by analysis of variance and the Tukey test for post hoc comparisons (α = 0.05).

Results

The manual did not show a statistical significant difference with rotary instrumentation (P > 0.05), but higher CHX substantivity was recorded in all periods of observation when compared to reciprocating instrumentation (P < 0.05).

Conclusions

The CHX substantivity on human dentine is lowest when using reciprocating compared to manual and rotary instrumentation.

Clinical significance

Using chemical analysis, this study showed that a manual and rotary multi-instrument system results in greater chlorhexidine substantivity on human dentin than a reciprocating single-instrument system.

http://ift.tt/2scTxEI

Editors / Publication Information

Publication date: 1 September 2017
Source:Appetite, Volume 116





http://ift.tt/2tBIsBo

Cultural Competency Training in Emergency Medicine

Publication date: Available online 1 July 2017
Source:The Journal of Emergency Medicine
Author(s): Oren J. Mechanic, Nicole M. Dubosh, Carlo L. Rosen, Alden M. Landry
BackgroundThe Emergency Department is widely regarded as the epicenter of medical care for diverse and largely disparate types of patients. Physicians must be aware of the cultural diversity of their patient population to appropriately address their medical needs. A better understanding of residency preparedness in cultural competency can lead to better training opportunities and patient care.ObjectiveThe objective of this study was to assess residency and faculty exposure to formal cultural competency programs and assess future needs for diversity education.MethodsA short survey was sent to all 168 Accreditation Council for Graduate Medical Education program directors through the Council of Emergency Medicine Residency Directors listserv. The survey included drop-down options in addition to open-ended input. Descriptive and bivariate analyses were used to analyze data.ResultsThe response rate was 43.5% (73/168). Of the 68.5% (50/73) of residency programs that include cultural competency education, 90% (45/50) utilized structured didactics. Of these programs, 86.0% (43/50) included race and ethnicity education, whereas only 40.0% (20/50) included education on patients with limited English proficiency. Resident comfort with cultural competency was unmeasured by most programs (83.6%: 61/73). Of all respondents, 93.2% (68/73) were interested in a universal open-source cultural competency curriculum.ConclusionsThe majority of the programs in our sample have formal resident didactics on cultural competency. Some faculty members also receive cultural competency training. There are gaps, however, in types of cultural competency training, and many programs have expressed interest in a universal open-source tool to improve cultural competency for Emergency Medicine residents.



http://ift.tt/2txEJEp

Verb Naming Fluency in Hypokinetic and Hyperkinetic Movement Disorders

Publication date: Available online 1 July 2017
Source:Cortex
Author(s): Ece Bayram, Muhittin Cenk Akbostanci
Cortical motor regions are also considered to play a role in action related language. These regions are affected differently in different types of movement disorders. Parkinson's disease, a hypokinetic movement disorder, has been shown to cause action language disruptions alongside movement deficits. Action language, however has not been investigated in primary cervical dystonia, a hyperkinetic movement disorder. The aim of this study is to investigate whether action language is affected differently in hypokinetic and hyperkinetic movement disorders which have different effects on movements. Thirty patients with Parkinson's disease, thirty with primary cervical dystonia patients and thirty healthy controls were included in the study. Participants performed phonemic, semantic and action fluency tasks. Verbs produced during action fluency were grouped as action and non-action verbs and group differences were investigated. Our results showed that all participants performed similarly in all of the fluency tasks. Mean action content of the verbs produced in action fluency did not differ in between groups. During action fluency, however, whereas healthy controls produced more action verbs than non-action verbs, both patient groups did not have this difference between verb groups. Primary cervical dystonia patients produced less action verbs compared to healthy controls. The lack of action language deficits in Parkinson's disease and only an action verb deficit in primary cervical dystonia without any other action language deficits rejects strong embodiment.



http://ift.tt/2sym0V2

Room Service Improves Nutritional Intake and Increases Patient Satisfaction While Decreasing Food Waste and Cost

Publication date: Available online 1 July 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Sally McCray, Kirsty Maunder, Renee Krikowa, Kristen MacKenzie-Shalders
BackgroundRoom service is a foodservice model that has been increasingly implemented across health care facilities in an effort to improve patient satisfaction and reduce food waste. In 2013, Mater Private Hospital Brisbane, Australia, was the first hospital in Australia to implement room service, with the aim of improving patient nutrition care and reducing costs.ObjectiveThe aim of this study was to comprehensively evaluate the nutritional intake, plate waste, patient satisfaction, and patient meal costs of room service compared to a traditional foodservice model.DesignA retrospective analysis of quality-assurance data audits was undertaken to assess patient nutritional intake between a facility utilizing a traditional foodservice model and a facility utilizing room service and in a pre−post study design to assess plate waste, patient satisfaction, and patient meal costs before and after the room service implementation.ParticipantsAudit data were collected for eligible adult inpatients in Mater Private Hospital Brisbane and Mater Hospital Brisbane, Australia, between July 2012 and May 2015.Main outcome measuresThe primary outcome measures were nutritional intake, plate waste, patient satisfaction, and patient meal costs.Statistical analyses performedIndependent samples t-tests and χ² analyses were conducted between pre and post data for continuous data and categorical data, respectively. Pearson χ² analysis of count data for sex and reasons for plate waste for data with counts more than five was used to determine asymptotic (two-sided) significance and n-1 χ² used for the plate waste analysis. Significance was assessed at P<0.05.ResultsThis study reported an increased nutritional intake, improved patient satisfaction, and reduced plate waste and patient meal costs with room service compared to a traditional foodservice model. Comparison of nutritional intake between a traditional foodservice model (n=85) and room service (n=63) showed statistically significant increases with room service in both energy (1,306 kcal/day vs 1,588 kcal/day; P=0.005) and protein (52 g/day vs 66 g/day, P=0.003) intake, as well as energy and protein intake as a percentage of requirements (63% vs 75%; P=0.024 and 65% vs 85%; P=0.011, respectively). Total mean plate waste decreased from 29% (traditional foodservice model) to 12% (room service) (P<0.001). Patient satisfaction ratings indicated improvement with room service across all Press Ganey meal scores: 68th to 86th percentile overall; 64th to 95th percentile for "quality of food"; and 60th to 99th percentile for "flavor of food." Evaluated during comparable times of the year, patient meal costs decreased by 15% with room service.ConclusionsA patient-centered foodservice model, such as room service, can improve patient nutritional intake and enhance patient satisfaction in a budget constrained health care environment.



http://ift.tt/2sxRWcb