Hypoxia-Inducible Factor-1α and Autoimmune Lupus, Arthritis

Abstract

Hypoxia elicits an orchestrated response in cells, tissues, and entire organisms to survive a hypoxic challenge. On a molecular level, this response can be controlled by oxygen-dependent stabilization of the transcription factor hypoxia-inducible factor (HIF)-1α. Recently, studies have shown that HIF-1α plays an important role in the development and function of T helper (Th) cells, regulatory T (Treg) cells, and dendritic cells (DCs). Because these cells are critical in the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis, the roles of HIF-1α in these autoimmune disorders cannot be neglected. In this review, we discuss recent findings on the important roles of HIF-1α in immune cells and the possible pathologic roles of HIF-1α in autoimmune diseases. The obtained information may lead to deeper insights into the roles of HIF-1α in these disorders.

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Evaluation of phenotypic tests for detection of Amp C beta-lactamases in clinical isolates from a tertiary care hospital of Rawalpindi, Pakistan

2016-05-27T09-20-32Z
Source: Journal of the Pakistan Medical Association
Nadia Saad, Tehmina Munir, Maliha Ansari, Mehreen Gilani, Mahwish Latif, Amira Haroon.
Objective: To evaluate sensitivity and specificity of disc approximation test compared to three-dimensional extract test as a phenotypic gold standard test for detection of AmpC beta-lactamase producing Escherichia coli and Klebsiella pneumoniae. Method: The cross-sectional validation study was conducted from November 2014 to April 2015 at Army Medical College, Rawalpindi, Pakistan. Extended spectrum beta lactamases (ESBLs) were isolated from various clinical specimens. Screening for AmpC beta-lactamases was done by using cefoxitin disc (30µg) showing inhibition zone diameter of


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Protective effect of procyanidins extracted from the lotus seedpod on immune function injury induced by extremely low frequency electromagnetic field

Publication date: August 2016
Source:Biomedicine & Pharmacotherapy, Volume 82
Author(s): Haihui Zhang, Yanxiang Cheng, Xiaoping Luo, Yuqing Duan
This study aimed to evaluate the protective effect of Lotus seedpod procyanidins (LSPCs) from extremely low frequency electromagnetic field (ELF-EMF) exposure (50Hz, 8mT, 28 days) and their protective mechanism against radiation damage. The results showed that LSPCs increased the organ index of mice and made the damaged blood-producing function and cytokine(INF-γ, TNF-α, IL-2, IL-6 and IL-10 in spleen) levels by ELF-EMF-irradiation recovered to normal appearance. And experimental results proved that dosing LSPCs inhibit more stagnation of splenocytes in G0/G1 phase caused by ELF-EMF, thus the spleen cells from G0/G1 phase to S phase shift, restore normal cell metabolism, promote the splenocytes proliferation, reduced the apoptosis of spleen cells, effective protect the damage induced by the ELF-EMF radiation. In addition, LSPCs prevented the decline of DNA content caused by ELF-EMF. Western blot determinated the levels of apoptosis genes including Bcl-2, Bax, Bcl-cl, Caspase-3 and Caspase-9. The results revealed that a significant suppression in Bcl-2 expression and increase in Bax, Caspase-3 and Caspase-9 expression in splenic cells in ELF-EMF group. However, LSPCs restored these changes. Taking these results together, it may be summarized that LSPCs could protect hematopoietic tissues and the immune system from ELF-EMF. And it may be hypothesized that ELF-EMF-induced apoptosis in splenocytes might occur via triggers the trans-activation of Bax and activates caspases-3 and −9, which then cleaves the death substrates, leading to apoptosis in splenocytes of mice treated with ELF-EMF.



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GM3 synthase deficiency due to ST3GAL5 variants in two Korean female siblings: Masquerading as Rett syndrome-like phenotype

There have been a few reports of GM3 synthase deficiency since the disease of the ganglioside biosynthetic pathway was first reported in 2004. It is characterized by infantile-onset epilepsy with severe intellectual disability, blindness, cutaneous dyspigmentation, and choreoathetosis. Here we report the cases of two Korean female siblings with ST3GAL5 variants, who presented with a Rett-like phenotype. They had delayed speech, hand stereotypies with a loss of purposeful hand movements, and choreoathetosis, but no clinical seizures. One of them had microcephaly, while the other had small head circumference less than 10th centile. There were no abnormal laboratory findings with the exception of a high lactate level. MECP2/CDKL5/FOXG1 genetic tests with an array comparative genomic hybridization revealed no molecular defects. Through whole-exome sequencing of the proband, we found compound heterozygous ST3GAL5 variants (p.Gly201Arg and p.Cys195Ser), both of which were novel. The siblings were the same compound heterozygotes and their unaffected parents were heterozygous carriers of each variant. Liquid chromatography–mass spectrometry analysis confirmed a low level of GM3 and its downstream metabolites, indicating GM3 synthase deficiency. These cases expanded the clinical and genetic spectrum of the ultra-rare disease, GM3 synthase deficiency with ST3GAL5 variants. © 2016 Wiley Periodicals, Inc.

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Microcephalic primordial dwarfism in an Emirati patient with PNKP mutation

Microcephaly is a rare neurological condition, both in isolation and when it occurs as part of a syndrome. One of the syndromic forms of microcephaly is microcephaly, seizures and developmental delay (MCSZ) (OMIM #613402), a rare autosomal recessive neurodevelopmental disorder with a range of phenotypic severity, and known to be caused by mutations in the polynucleotide kinase 3′ phosphatase (PNKP) gene. The PNK protein is a key enzyme involved in the repair of single and double stranded DNA breaks, a process which is particularly important in the nervous system. We describe an Emirati patient who presented with microcephaly, short stature, uncontrollable tonic-clonic seizures, facial dysmorphism, and developmental delay, while at the same time showing evidence of brain atrophy and agenesis of the corpus callosum. We used whole exome sequencing to identify homozygosity for a missense c.1385G > C (p.Arg462Pro) mutation in PNKP in the patient and heterozygosity for this mutation in her consanguineous parents. The Arg 462 residue forms a part of the lid subdomain helix of the P-loop Kinase domain. Although our patient's phenotype resembled that of MCSZ, the short stature and evidence of brain atrophy distinguished it from other classic cases of the condition. The report raises the question of whether to consider this case as an atypical variant of MCSZ or as a novel form of microcephalic primordial dwarfism. © 2016 Wiley Periodicals, Inc.

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Temporomandibular joint ankylosis as part of the clinical spectrum of Carey–Fineman–Ziter syndrome?

The Carey–Finema–Ziter syndrome (CFZS, MIM 254940) is an apparently autosomal recessively inherited disorder consisting of the combination of non-progressive congenital myopathy with Moebius and Pierre Robin sequence, facial anomalies and growth delay. Mental development has been described as normal or delayed. Temporomandibular joint (TMJ) ankylosis is the immobility of the joint caused by ankylotic fusion of the mandible to the cranial base or zygoma. It is a serious and disabling condition that may cause problems in mastication, digestion, speech, appearance, and oral hygiene. Most often is a true ankylosis of the TMJ but other pathological mechanisms are described (i.e., the fusion of the coronoid process to temporal bone or with the zygoma, or a variety of soft tissues disorders like Fibrodysplasia Ossificans Progressiva). Here we report a 2-year-old girl fitting with a clinical diagnosis of CFZS associated with a limited mouth opening in which temporomandibular joint ankylosis was suspected. Because it has been postulated that many clinical features in CFZS may only be secondary effects of brainstem anomalies and muscle weakness during development, the limited opening of the mouth observed in our patient could represent a rare clinical feature of CFZS itself. © 2016 Wiley Periodicals, Inc.

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Gastroschisis and maternal intake of phytoestrogens

The prevalence of gastroschisis has increased significantly in the past few decades. The strongest risks have been observed for women <25 years old or of low body mass index, and maternal diet also been proposed to be associated with risk. The objective of this study was to evaluate whether the risk of gastroschisis is associated with maternal dietary intake of phytoestrogens. The analysis includes data on mothers of 409 gastroschisis cases and 3,007 controls who delivered their infants from 2005 to 2010 and participated in the National Birth Defects Prevention Study, a multistate, population-based, case-control study. Detailed information was obtained from maternal telephone interviews that included a validated food frequency questionnaire. We conducted logistic regression analyses that included each phytoestrogen in its continuous form (to test for linearity) and quadratic form (to test for non-linearity), adjusted for maternal energy intake, age, BMI, race-ethnicity, and smoking in 1st trimester. Logistic regression analysis indicated that biochanin A, formonoetin, and coumestrol had a significant non-linear association with gastroschisis (P-value <0.05 for quadratic term). Lower intakes were associated with increased risk, with somewhat stronger but relatively modest associations at the lower end of the distribution; for example, the ORs for the 10th versus 50th percentiles ranged from 1.1 to 1.2. Associations were not significant for the other phytoestrogens. This study provides some evidence for association with certain phytoestrogens, after adjusting for covariates. The implications of our findings for clinical practice are uncertain pending other studies examining this association. © 2016 Wiley Periodicals, Inc.

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BAG-1/SODD, HSP70, and HSP90 are potential prognostic markers of poor survival in node-negative breast carcinoma

Publication date: August 2016
Source:Human Pathology, Volume 54
Author(s): Ben Davidson, Kristin Valborg Reinertsen, Don Trinh, Wenche Reed, Per Johannes Bøhler
The objective of this study was to analyze the expression and clinical role of 13 signaling molecules in a large cohort of breast carcinoma patients with long follow-up period. Breast carcinomas (n=410) were analyzed for protein expression of phosphorylated mitogen-activated protein kinases (p-ERK, p-JNK, p-p38) and phosphoinositide 3-kinase signaling pathway proteins (p-AKT, p-mTOR, p-p70S6K); the BAG family proteins BAG-1 and BAG-4/SODD; the antiapoptotic protein Bcl-2; the inhibitor of apoptosis family member Survivin; and the heat shock protein family members HSP27, HSP70, and HSP90. Protein expression was studied for association with clinicopathological parameters and survival. Significantly higher expression of p-AKT (P<.001), p-mTOR (P<.001), p-p70S6K (P<.001), Bcl-2 (P<.001), BAG-4/SODD (P<.001), HSP27 (P<.001), HSP70 (P=.012), HSP90 (P<.001), and Survivin (P=.004) was found in infiltrating ductal and lobular carcinomas compared to mucinous carcinomas. Bcl-2 expression was significantly higher in grades 1 and 2 compared to grade 3 carcinomas (P<.001). p-AKT expression was higher in tumors more than 2cm (P=.027), whereas p-mTOR expression was lowest in tumors more than 5cm (P=.019). Higher BAG-4/SODD, HSP70, and HSP90 expression was associated with poor overall survival (P=.016, P=.039, and P=.023, respectively) in univariate analysis, whereas the only independent prognosticator in Cox multivariate survival analysis was tumor diameter (P=.003). In conclusion, BAG-4/SODD, HSP70, and HSP90 are potential prognostic markers in node-negative breast carcinoma that merit further research.



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Evaluation of Sexual Dysfunction in Men With Spinal Cord Injury Using the Male Sexual Quotient

Publication date: June 2016
Source:Archives of Physical Medicine and Rehabilitation, Volume 97, Issue 6
Author(s): Eduardo P. Miranda, Cristiano Mendes Gomes, José de Bessa, Carmita Helena Najjar Abdo, Carlos Henrique Suzuki Bellucci, Jose Everton de Castro Filho, Fabrício Leite de Carvalho, Daniel Rubio de Souza, Linamara Rizzo Battistella, Márcia Scazufca, Homero Bruschini, Tarcisio Barros Filho, Miguel Srougi
ObjectiveTo assess different aspects of sexual function in men with spinal cord injury (SCI) using the Male Sexual Quotient (MSQ), a newly developed tool to assess sexual function and satisfaction.DesignCross-sectional study.SettingTertiary rehabilitation center.ParticipantsPatients (N=295) older than 18 years (mean age ± SD, 40.7±14.5y) with SCI for more than 1 year (median time since SCI, 3.6y; range, 1.6–7.0y) were assessed from February to August 2012. Patients completed the MSQ questionnaire and the Sexual Health Inventory for Men (SHIM).InterventionsNot applicable.Main Outcome MeasuresPerformance in various domains of sexual function was evaluated using the MSQ and SHIM questionnaires.ResultsErectile function, ejaculation, and orgasm were the most severely affected domains. The median MSQ score was 40 (range, 8–66), and the median SHIM score was 5 (range, 0–16). The diagnostic properties of the 2 instruments were similar in the discrimination of sexually active subjects. The area under the receiver operating characteristic curve was .950 (95% confidence interval [CI], .923–.979) for the MSQ and .942 (95% CI, .915–.968) for the SHIM. There was a strong correlation between the 2 instruments (r=.826; 95% CI, .802–.878).ConclusionsDifferent domains of sexual function are severely impaired in men with SCI, although their sexual interest remains high. The MSQ and SHIM scores strongly correlate, but the MSQ provides a more comprehensive assessment of sexual dysfunction in male patients with SCI.



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Study of the pattern of mortality caused by Traffic Accidents (TAs) in The South of Iran

2016-05-27T08-50-44Z
Source: Journal of the Pakistan Medical Association
Tayebeh Rakhshani, Fatemeh Rakhshani, Zahra Sadat Asadi, Mohammad Hadiabasi, Kazem Khorramdel, Mohammad Zarenezhad.
Objective: To investigate the pattern of mortality caused by road traffic accidents and its associated factors. Methods: The retrospective cross-sectional study was conducted in the Fars province of Iran and comprised data of all people having died in road traffic accidents from March 21, 2011, to March 19, 2012. Using census method, all files related to deaths in road accidents were reviewed at the Legal Medicine Centre. Data was analysed using SPSS20. Results: Of the 1668 people dead, 1291(77.4%) were male and 377(22.6 %) were female. The highest rate related to the age group 21-30 with 454(27%) killed. As for education level, the highest rate of mortality was 410(24.5%) for illiterate people and the least was 9(0.5%) for those having Masters degree or higher. In terms of time of year, the highest rate of mortality was 167(10%) between August 23and September 22, while the least was 82(5%) between July 23and August22. Head trauma was reported as the most important cause of death in 1191(71.4%) cases. Conclusion: Despite some minor differences, all provinces in Iran have the same patterns of death related to road traffic accidents.


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Functional reversal of (-)-Stepholidine analogues by replacement of benzazepine substructure using the ring-expansion strategy

Abstract

(-)-Stepholidine (l-SPD) is an active ingredient of the Chinese herb Stephania and naturally occurring tetrahydroprotoberberine (THPB) alkaloid with mixed dopamine receptor D₁ (D1R) agonistic and dopamine receptor D₂ (D2R) antagonistic activities. In this work, a series of novel hexahydrobenzo[4,5]azepino [2,1-a]isoquinolines were designed and synthesized as ring-expanded analogues of l-SPD. Initial pharmacological assays demonstrated that a benzazepine replacement was associated with significant increase of selectivity and functional reversal at D1R. Compound-(-)-15e (K_i = 5.32±0.01 nM) is more potent than l-SPD (Ki = 13 nM) and was identified as a selective D1R antagonist (IC₅₀ = 0.14 μM). Moreover, molecular modeling suggested that (-)-15e might exert its D1R antagonistic activities through interacting with the transmembrane helix 7 (TM7) of D1R.

This article is protected by copyright. All rights reserved.

A series of novel ring-expanded analogues of (−)-Stepholidine (l-SPD) were designed, synthesized and bioassayed as potent ligands at D1R. Compound-(-)-15e (Ki = 5.32±0.01 nM) is more potent than l-SPD (Ki = 13 nM) and was identified as a selective D1R antagonist (IC₅₀ = 0.14 μM). This structural modification was associated significant increase of selectivity and functional reversal at D1R in comparison to (-)-l-SPD with dual D1R agonistic and D2R antagnositic activities.

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Translating Perceptual Learning from the Laboratory to Applications

Publication date: Available online 27 May 2016
Source:Trends in Cognitive Sciences
Author(s): Zhong-Lin Lu, Zhicheng Lin, Barbara Anne Dosher
Human training studies in the laboratory have demonstrated plasticity in brain systems and, in some cases, large improvements in perceptual performance, inspiring a quest to develop training apps and systems. We consider the next steps in the translation from the laboratory to the clinic and commerce.



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Implementing evidenced based patient safety practices

2016-05-27T08-20-40Z
Source: Journal of the Pakistan Medical Association
Ali Yawar Alam.



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New perspectives in the management of diabetic retinopathy

2016-05-27T08-20-40Z
Source: Journal of the Pakistan Medical Association
M. A. Rehman Siddiqui, M. Amer Raza Awan.



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Structural considerations on the selectivity of an immunoassay for sulfamethoxazole

Publication date: 1 September 2016
Source:Talanta, Volume 158
Author(s): Holger Hoffmann, Stefanie Baldofski, Kristin Hoffmann, Sabine Flemig, Carla Patrícia Silva, Valdemar I. Esteves, Franziska Emmerling, Ulrich Panne, Rudolf J. Schneider
Sulfamethoxazole (SMX), a sulfonamide, is a widely used bacteriostatic antibiotic and therefore a promising marker for the entry of anthropogenic pollution in the environment. SMX is frequently found in wastewater and surface water. This study presents the production of high affinity and selective polyclonal antibodies for SMX and the development and evaluation of a direct competitive enzyme-linked immunosorbent assay (ELISA) for the quantification of SMX in environmental water samples. The crystal structures of the cross-reacting compounds sulfamethizole, N⁴-acetyl-SMX and succinimidyl-SMX were determined by x-ray diffraction aiming to explain their high cross-reactivity. These crystal structures are described for the first time. The quantification range of the ELISA is 0.82–63µg/L. To verify our results, the SMX concentration in 20 environmental samples, including wastewater and surface water, was determined by ELISA and tandem mass spectrometry (MS/MS). A good agreement of the measured SMX concentrations was found with average recoveries of 97–113% for the results of ELISA compared to LC-MS/MS.

Graphical abstract

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Determination of halogens and sulfur in high-purity polyimide by IC after digestion by MIC

Publication date: 1 September 2016
Source:Talanta, Volume 158
Author(s): Sindy R. Krzyzaniak, Rafael F. Santos, Flavia M. Dalla Nora, Sandra M. Cruz, Erico M.M. Flores, Paola A. Mello
In this work, a method for sample preparation of high-purity polyimide was proposed for halogens and sulfur determination by ion chromatography (IC) with conductivity detection and, alternatively, by inductively coupled plasma mass spectrometry (ICP-MS). A relatively high polyimide mass (600mg) was completely digested by microwave-induced combustion (MIC) using 20bar of O2 and 50mmolL⁻¹ NH4OH as absorbing solution. These conditions allowed final solutions with low carbon content (<10mgL⁻¹) and suitable pH for analysis by both IC and ICP-MS. The accuracy was evaluated using a certified reference material of polymer for Cl, Br and S and spike recovery experiments for all analytes. No statistical difference (t-test, 95% of confidence level) was observed between the results obtained for Cl, Br and S by IC after MIC and the certified values. In addition, spike recoveries obtained for F, Cl, Br, I and S ranged from 94% to 101%. The proposed method was suitable for polyimide decomposition for further determination of halogens and sulfur by IC and by ICP-MS (Br and I only). Taking into account the lack of methods and the difficulty of bringing this material into solution, MIC can be considered as a suitable alternative for the decomposition of polyimide for routine quality control of halogens and sulfur using IC or ICP-MS.

Graphical abstract

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WITHDRAWN: Wet effluent diffusion denuder: The tool for determination of monoterpenes in forest

Publication date: 1 September 2016
Source:Talanta, Volume 158
Author(s): Kamil Křůmal, Pavel Mikuška, Kristýna Večeřová, Otmar Urban, Emanuele Pallozzi, Zbyněk Večeřa
The Publisher regrets that this article is an accidental duplication of an article that has already been published, 10.1016/j.talanta.2016.03.032. The duplicate article has therefore been withdrawn.The full Elsevier Policy on Article Withdrawal can be found at http://ift.tt/1poHqya.



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Value of transcranial direct-current stimulation of the motor cortex for the management of refractory cancer pain in the palliative care setting: a case report

Publication date: Available online 27 May 2016
Source:Clinical Neurophysiology
Author(s): Jean-Paul Nguyen, Julien Esnault, Alcira Suarez, Véronique Dixneuf, Aurélie Lepeintre, Amélie Levesque, Michel Meignier, Jean-Pascal Lefaucheur, Julien Nizard




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Review on TAS-102 development and its use for metastatic colorectal cancer

Publication date: Available online 26 May 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): J.M. Mota, L.G. Fonseca, M.I. Braghiroli, P.M. Hoff
TAS-102 is the combination of trifluridine (TFT) with tipiracil (TPI) in a 1:0.5 molar ratio. TFT is a fluoropyrimidine that retains cytotoxic activity in 5-fluorouracil resistant cell lines. Due to TFT short half-life, early clinical development was discouraging. Thereafter, TFT was shown to be promptly degraded by thymidine phosphorylase, also known as platelet-derived endothelial cell growth factor, a pro-angiogenic protein and a poor prognosis marker in colorectal cancer. TPI is a specific antagonist of thymidine phosphorylase and led to an increase in TFT serum levels when both agents are combined. Moreover, TPI is a potential anti-angiogenic molecule and could exert antitumor actions per se. TAS-102 was tested in several Phase I studies published in the early 21st century. The best regimen was settled as 70mg/m²/day, q12h, orally given at days 1-5 and days 8-13, each 28 days. Recently, the first Phase III trial evaluating TAS-102 in refractory colorectal cancer patients was published. The RECOURSE trial demonstrated a survival advantage of the agent over supportive care, and definitely established TAS-102 as a novel strategy in the current armamentarium against colorectal cancer. Here we review the preclinical data regarding TFT and TPI that led to the development of TAS-102, and the set of clinical data that ultimately proved that TAS-102 improved outcomes in colorectal cancer patients.



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The Patient-Oriented Eczema Measure in young children: responsiveness and minimal clinically important difference

Abstract

Background

The Patient-Oriented Eczema Measure (POEM) has been recommended as the core patient-reported outcome measure for trials of eczema treatments. Using data from the Choice of Moisturiser for Eczema Treatment randomised feasibility study we assess the responsiveness to change and determine the minimal clinically important difference (MCID) of the POEM in young children with eczema.

Methods

Responsiveness to change by repeated administrations of the POEM was investigated in relation to change recalled using the Parent Global Assessment (PGA) measure. Five methods of determining the MCID of the POEM were employed; three anchor-based methods using PGA as the anchor: the within-patient score change, between-patient score change and sensitivity and specificity method, and two distribution-based methods: effect size estimate and the one half standard deviation of the baseline distribution of POEM scores.

Results

Successive POEM scores were found to be responsive to change in eczema severity. The MCID of the POEM change score, in relation to a slight improvement in eczema severity as recalled by parents on the PGA, estimated by the within-patient score change (4.27), the between-patient score change (2.89) and the sensitivity and specificity method (3.00) was similar to the one half standard deviation of the POEM baseline scores (2.94) and the effect size estimate (2.50).

Conclusions

The Patient-Oriented Eczema Measure as applied to young children is responsive to change and the MCID is around 3. This study will encourage the use of POEM and aid in determining sample size for future RCTs of treatments for eczema in young children.

This article is protected by copyright. All rights reserved.

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Respiratory Hypersensitivity Reactions to NSAIDs in Europe: The Global Allergy and Asthma Network (GA2LEN) Survey

Abstract

Background

Non-steroidal Anti-Inflammatory Drugs (NSAIDs) are among the most prevalent drugs inducing hypersensitivity reactions. The aim of this analysis was to estimate the prevalence of NSAIDs-induced respiratory symptoms in population across Europe and to assess its association with upper and lower respiratory tract disorders.

Methods

The GA²LEN survey was conducted in 22 centers in 15 European countries. Each of 19 centers selected random samples of 5000 adults aged 15-74 from their general population, and in three centers (Athens, Munich, Oslo) a younger population was sampled. Questionnaires including questions about age, gender, presence of symptoms of asthma, allergic rhinitis, chronic rhinosinusitis, smoking status and history of NSAIDs-induced hypersensitivity reactions were sent to participants by mail. Total 62, 737 participants completed the questionnaires.

Results

The mean prevalence of NSAIDs-induced dyspnea was 1.9% and was highest in the three Polish centers [Katowice (4.9%), Krakow (4.8%) and Lodz (4.4%)] and lowest in Skopje, (0.9%), Amsterdam (1.1%) and Umea (1.2%). In multivariate analysis, the prevalence of respiratory reactions to NSAIDs was higher in participants with chronic rhinosinusitis symptoms (Odds Ratio 2.12; 95%CI 1.78-2.74), asthma symptoms in last 12 months (2.7; 2.18-3.35), hospitalization due to asthma (1.53; 1.22-1.99), and adults vs children (1.53; 1.24-1.89), but was not associated with allergic rhinitis.

Conclusion

Our study documented significant variation between European countries in the prevalence of NSAIDs-induced respiratory hypersensitivity reactions, and association with chronic airway diseases, but also with environmental factors.

This article is protected by copyright. All rights reserved.

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Infrazygomatico-coronoid fixation in a segmental mandibular reconstruction with a free vascularized flap: A simple and correct repositioning method without interfering with reconstructive and microsurgical procedures

Abstract

Background

In a segmental mandibular reconstruction with a free vascularized flap, reproducing the optimal relationship between the condyle and glenoid fossa, and maintaining correct occlusion are important. We examined the practicality of a repositioning technique that combined bone plate fixation of the infrazygomatic crest and the coronoid process (infrazygomatico-coronoid fixation [IZCF]) with maxillo-mandibular fixation (MMF).

Methods

Eight patients were treated with this method. To investigate masticatory function, the status of the dental and temporomandibular joints were examined, and a food scale questionnaire was administered.

Results

IZCF and MMF resulted in correct repositioning of the segmented mandibles and enabled accurate reconstructions. Most patients recovered to be able to ingest the same preoperative food in scale with stable occlusion.

Conclusion

This method is a simple and correct repositioning method without interfering with reconstructive and microsurgical procedures. We propose this technique as a reliable method for obtaining a functional outcome in mandibular reconstruction. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

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Prospective study of the pattern of lymphatic metastasis in relation to the submandibular gland in patients with carcinoma of the oral cavity

Abstract

Background

The submandibular gland is responsible for 70% to 90% of unstimulated saliva production. Its excision causes a decrease in basal salivary flow resulting in increased symptoms of subjective xerostomia and decreased quality of life. In this study, we have tried to assess the pattern of nodal metastasis in relation to the submandibular gland. With this study, we have tried to find out whether submandibular gland preservation is a viable option in patients with carcinoma of the oral cavity.

Methods

This was a prospective study conducted in a tertiary care cancer center. The fibrofatty tissue surrounding the submandibular gland was divided into 6 parts depending upon its location with the submandibular gland. All these 6 parts along with the submandibular gland were separately sent for histopathological analysis. Metastasis pattern in level Ib region was noted.

Result

The study included 137 patients with carcinoma of the oral cavity who underwent neck dissections. Eighty-five patients had clinic-radiologically N0 neck, 52 patients had cN+ (clinically node positive) neck. Level Ib was involved in 8.2% of the cases with cN0 (clinically node negative neck). In patients with cN+ neck, level Ib metastasis was seen in 40% of the cases. Metastasis in N0 necks in the area deep to the submandibular gland was seen in only 1 case (9% of all pathologically node-positive patients) with cN0 neck. This was the only case in which submandibular gland mobilization would have been required to take out the metastatic node. Even in cases with N+ neck, deep metastasis was seen in 4 cases only (14.8%). None of them had a primary tumor in the tongue. Therefore, there is a possibility of preserving the submandibular gland in cases of carcinoma of the tongue.

Conclusion

Involvement of level Ib in early tongue cancers is not very common and direct metastases to the submandibular glands are rare. Even when metastasis is present in level Ib, it can be excised without affecting the submandibular gland. In early tongue lesions, submandibular gland mobilization for dissection at level Ib is not required as no metastases deep to the submandibular glands were seen in these patients. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

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Phase II trial of everolimus in patients with previously treated recurrent or metastatic head and neck squamous cell carcinoma

Abstract

Background

Patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) demonstrate aberrant activation of the phosphotidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway. We examined the efficacy of everolimus, an mTOR inhibitor, in patients with recurrent or metastatic HNSCC.

Methods

This single-arm phase II study enrolled biomarker-unselected patients with recurrent or metastatic HNSCC who failed at least 1 prior therapy. Everolimus was administered until progressive disease or unacceptable toxicity. Primary endpoint was clinical benefit rate (CBR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and evaluation of tissue and serum biomarkers related to the PIK3CA pathway.

Results

Seven of 9 patients treated in the first stage were evaluable. No objective responses were seen; CBR was 28%. Three patients discontinued everolimus because of toxicity. Median PFS and OS were 1.5 and 4.5 months, respectively. No activating PI3K mutations were identified in available tumor tissue.

Conclusion

Everolimus was not active as monotherapy in unselected patients with recurrent/metastatic HNSCC. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

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Histoire de la chirurgie plastique pédiatrique

Publication date: Available online 26 May 2016
Source:Annales de Chirurgie Plastique Esthétique
Author(s): J. Glicenstein
L'histoire de la chirurgie plastique pédiatrique est liée à celle de la pédiatrie. Avant le XIX^e siècle, il n'y avait pas d'hôpitaux d'enfants. Seules, quelques interventions (la fermeture simple des fentes labiales, l'ablation d'un doigt surnuméraire) étaient pratiquées avant que l'anesthésie, l'asepsie et l'antisepsie les rendent moins dangereuses. Dès le XIX^e siècle, des interventions furent proposées pour le traitement des fentes labiales, des divisions palatines, des hypospadias, des syndactylies. La première intervention de chirurgie esthétique pédiatrique fût une otoplastie en 1881. La chirurgie plastique pédiatrique se diversifia beaucoup dans la 2^e moitié du XX^e siècle. Les fentes labiomaxillofaciales, les brûlures, la chirurgie craniofaciale, la chirurgie de la main sont devenues des parties autonomes de la discipline.The history of pediatric plastic surgery is linked to that of paediatrics. Until the early 19th century, there was no children's hospital. Only some operations were performed before the discovery of anesthesia, aseptic and antisepsis: cleft lip repair, amputation for polydactyly. Many operations were described in the 19th century for cleft lip and palate repair, hypospadias, syndactylies. The first operation for protruding ears was performed in 1881. Pediatric plastic surgery is diversified in the 2nd half of the 20th century: cleft lip and palate, burns, craniofacial surgery, hand surgery become separate parts of the speciality.



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Intravoxel incoherent motion diffusion weighted MRI of cervical cancer — Correlated with tumor differentiation and perfusion

Publication date: October 2016
Source:Magnetic Resonance Imaging, Volume 34, Issue 8
Author(s): Yan Zhou, Jianyu Liu, Congrong Liu, Jing Jia, Nan Li, Lizhi Xie, Zhenyu Zhou, Ziheng Zhang, Dandan Zheng, Wei He, Yang Shen, Weidan Lu, Huici Zhu
ObjectivesTo investigate the value of parameters derived from IVIM model in grading of uterine cervical cancer and the relationship between perfusion parameters derived from IVIM and that from DCE-MRI.MethodsParameters of DWI (ADC, D, f, D*) and semi-quantitative parameters of DCE-MRI (Slop, Maxslop, CER, Washout, AUC90) were assessed in 24 female with cervical cancers. Except for ROIs encompassed all of the area of tumors in axial plane (A_all), ROIs on tumor edge (A_peri) and tumor center (A_central) were drawn. All of the parameters were compared among three pathology grades. Perfusion parameters derived from IVIM were correlated with that from DCE-MRI.ResultsFor G1, G2 and G3 tumors, on tumor edge ADC=(1.03±0.11), (1.05±0.10), (0.90±0.05)×10⁻³mm²/s, D=(0.80±0.11), (0.78±0.07), (0.69±0.06)×10⁻³mm²/s, and f=(0.19±0.03), (0.22±0.02), (0.24±0.03). The differences among groups were significant (P<0.05). On tumor center, ADC=(0.90±0.10), (0.85±0.03), (0.80±0.07)×10⁻³mm²/s with significant differences (P=0.027). The other parameter, D and f of tumor center, as well as D* of all tumor areas, were of no statistic significance. Most of the DCE-MRI parameters negatively correlated with tumor volume. Although the correlation between f and slop was statistic significant, R=0.277 meant a negligible correlation. f had week correlation with Maxslop, CER and AUC90 (R=0.361, 0.400 and 0.405; P<0.001). D* showed no statistic significant correlation with all of the DCE parameters.ConclusionIVIM model could possibly be used to evaluate tumor differentiation and perfusion, providing an alternative for DCE-MRI.



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Use of quantitative brain water imaging as concentration reference for J-edited MR spectroscopy of GABA

Publication date: October 2016
Source:Magnetic Resonance Imaging, Volume 34, Issue 8
Author(s): Georg Oeltzschner, Alfons Schnitzler, Frithjof Wickrath, Helge Jörn Zöllner, Hans-Jörg Wittsack
PurposeTo compare two different methods of obtaining the water reference for determination of quantitative water-scaled in vivo concentration estimates of γ-aminobutyric acid (GABA).MethodsWater-scaled GABA estimates from localized J-difference edited MR spectroscopy experiments can be computed using standard values for tissue-specific water content and relaxation times. Water content and relaxation may, however, be altered in pathology. This work re-analyzed data from a recent study in healthy controls and patients with minimal (mHE) or grade I (HE 1) hepatic encephalopathy, a disease associated with slight elevation of brain water content. J-difference edited MR spectroscopy data were combined with quantitative brain water measures, which provided individual water density references and T1 relaxation times. Resulting GABA estimates were compared to concentration values obtained using standard tissue-specific water content and relaxation values.ResultsOccipital GABA concentration values obtained from individual water and T1 maps were 1.64±0.35mM in controls, and significantly higher (P<0.01) than in mHE (1.15±0.28mM) and HE 1 patients (1.18±0.09mM). Results from the tissue-dependent approach (1.58±0.30mM (controls), 1.10±0.27mM (mHE) and 1.12±0.12mM (HE 1)) were slightly lower (P<0.05 in each group).ConclusionWater-scaled in vivo GABA estimates can be obtained with individual water density and T1 relaxation mapping. This approach may be useful for studying GABA levels in pathologies with substantial brain water content or relaxation changes.



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Editorial Board

Publication date: July 2016
Source:Magnetic Resonance Imaging, Volume 34, Issue 6





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Comprehensive cortical thickness and surface area comparison between young Uyghur and Han Chinese cohorts

Publication date: October 2016
Source:Magnetic Resonance Imaging, Volume 34, Issue 8
Author(s): Jun Lu, Chunhui Jiang, Jian Wang, Wenxiao Jia
We hypothesized that the brain structural differences as discovered previously between Westerners and East Asians could also be revealed between Han Chinese and Uyghur, which were genetically related ethnic groups with distinct languages. We conducted a brain MRI structural comparison in terms of cortical thickness and surface area between 15 healthy young Uyghurs and 15 age-matched Han Chinese. Widespread regions with significantly greater cortical thickness were found in the Uyghurs, and their distribution showed strong resemblance to previous "Westerners vs. Asians" findings. While surface area analysis displayed less widespread brain differences. Notably, our detected regions with structural differences contained a large part of language-specific or at least closely language-related brain areas, which may partly be attributable to the brain plasticity respectively driven by Uyghur and Mandarin. Our findings will help to better understand the neurobiological basis of interethnic differences along with the language processing mechanisms of Han Chinese and Uyghur.



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Table of Contents

Publication date: July 2016
Source:Magnetic Resonance Imaging, Volume 34, Issue 6





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Hospitalization and other risk factors for depressive and anxious symptoms in oncological and non-oncological patients

Abstract

Objective

Depression and anxiety are common in hospitalized patients. In particular, oncological patients might be vulnerable to depression and anxiety. The aim of this study is to assess and compare different variables and the prevalence of anxiety and depression symptoms between oncological and medically ill inpatients and to identify variables that can influence depressive and anxious symptoms during hospitalization of patients.

Methods

A total of 360 consecutive hospitalized patients completed the following questionnaires: Hospital Anxiety and Depression Scale (HADS), Patients Health Questionnaire-9, General Health Questionnaire (GHQ-12), 12-Item Short-Form Survey: physical component summary (PCS), and mental component summary (MCS). Patients were divided into oncological patients and non-oncological patients: groups 1 and 2.

Results

Only two significant differences were evident between the groups: the PCS of 12-item Short-form Survey was higher in non-oncological patient (p < 0.000), and the GHQ total score was higher in oncological patients. Variables significantly associated with HADS-D ≥ 8 were lower MCS, higher GHQ-12 score, lower PCS, more numerous previous hospitalizations, longer duration of hospitalization, and positive psychiatric family history. Variables significantly associated with HADS-A ≥ 8 were lower MCS, higher GHQ-12 score, positive psychiatric family history, longer duration of hospitalization, and younger age.

Conclusions

Anxiety and depression symptoms in concurrent general medical conditions were associated with a specific sociodemographic profile, and this association has implications for clinical care. Copyright © 2016 John Wiley & Sons, Ltd.

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Interferon-β produced by osteocytes may negatively regulate osteoclastogenesis

Publication date: Available online 26 May 2016
Source:Journal of Oral Biosciences
Author(s): Chiyomi Hayashida-Abe
BackgroundAlthough old and disordered bones are continuously remodeled with new tissue to maintain their integrity, most bone surfaces are in a non-resorbing state. We hypothesized that osteocytes negatively regulate osteoclast differentiation and function to maintain a non-resorbing state. In the present study, we examined the role of osteocytes in regulating osteoclastogenesis.HighlightWhen osteoclast precursors were formed from bone marrow cells (BMs) using an macrophage-colony stimulating factor treatment with conditioned medium (CM) from osteocytic MLO-Y4 cells (MLO-Y4-CM), the generated cells exhibited a diminished capacity for osteoclastogenesis. This decreased capability was consistent with increased protein kinase R mRNA expression and decreased c-Fos translation. Furthermore, CM induced phosphorylation of STAT-1 in the osteoclast precursors. To confirm the effect of the MLO-Y4-CM, we prepared non-osteocytic cell-free osteocyte-enriched bone fragments (OEBFs). OEBFs, as well as MLO-Y4-CM, reduced the commitment of BMs into osteoclast precursors. These effects were partially abrogated by an anti-interferon (IFN)-β neutralizing antibody. Indeed, the MLO-Y4 cells and primary osteocytes embedded in the OEBFs expressed more IFN-β than osteoclast lineage cells.ConclusionWe found that osteocytes secrete IFN-β as an inhibitory factor of osteoclastogenesis. Our findings provide a new insight into the mechanisms underlying the osteocytic regulation of bone remodeling.



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A case of acquired port wine stain: an association with repeated sunburn?

Abstract

Background

Unlike congenital port wine stain (PWS), an acquired PWS is a rare vascular lesion that develops later in life. Although solar damage is associated with acquired PWS, there is no reported case of acquired PWS after sunburn in the literature.

Methods

We report a case of a 54-year-old man diagnosed with acquired PWS possibly caused by repeated sunburn.

Results

We recommended laser treatment to our patient; however, the patient did not chose to receive any treatment.

Conclusions

Our case demonstrates a possible rare occurrence of an acquired PWS after sunburn with larger lesions and more diffuse distribution. For this reason, our case differs from other acquired PWS cases.

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Lichen sclerosis: clinicopathological study of 60 cases from Lebanon

Abstract

Background

Lichen sclerosus (LS) is an uncommon idiopathic chronic inflammatory debilitating disease with predilection for the genital region. Our recent encounter with an LS case exhibiting perineural inflammation microscopically prompted us to assess the features of all patients diagnosed with LS at our institution.

Materials and methods

All cases of LS diagnosed between 1990 and 2014 were retrospectively reviewed. Diagnosis was confirmed with demonstration of microscopic features typical of LS.

Results

Sixty patients (42 women and 18 men) with 65 biopsy specimens of LS were identified, of which 41 were extragenital, 16 genital, and three had both. Histopathologically, significantly higher proportions of follicular plugging, atrophy, and vacuolar interface changes were observed in extragenital LS cases, while angiokeratoma-like, mycosis fungoides-like, and pseudoepitheliomatous changes were only seen in genital LS. Perineural inflammation was observed as a novel finding in 22 cases (33.8%) of LS.

Conclusion

Features of patients with LS in this study are generally comparable to those published in the literature, with some differences. In contrast to the literature, extragenital LS was more frequently encountered. Histopathologically, perineural inflammation was not an uncommon feature of LS and thus may serve as a clue in the differentiation of LS from its mimickers.

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Classical Kaposi sarcoma: case reports with unusual presentation on the penis and scrotum

Abstract

Background

Kaposi sarcoma (KS) is the most common vascular neoplasm. Any skin area could be involved, including the genitalia. Traditionally, classic KS lesions have a general distribution, often involving skin of the feet and legs, and to a lesser extent, that of the hands, arms, and trunk. KS limited to the external genitalia is extremely rare in HIV seronegative individuals.

Methods

We report six patients of classic KS with generalized dermal KS lesions.

Results

Two of them presenting with unusual KS lesions on the penis and scrotum beside the other dermal lesions. Patients were HIV negative and human herpes virus eight positive. Histological examination showed classical KS.

Conclusions

Primary KS of the penis and scrotum is rare but could occur in HIV-negative patients.

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Extra-medial thickness of carotid artery in patients with Behçet's disease: evaluation of atherosclerotic vessel wall changes with a novel carotid artery ultrasound index

Abstract

Objectives

Chronic inflammation and endothelial dysfunction are the characteristic features of Behçet's disease (BD). We researched carotid extra-medial thickness (cEMT), a novel ultrasound parameter for atherosclerotic vessel wall changes, and carotid intima media thickness (cIMT), a widely accepted marker of subclinical atherosclerosis, in patients with BD, and we evaluated the relationship between these two parameters.

Materials and methods

In total, 31 patients with BD were matched to 26 control subjects based on age, gender, and major cardiovascular risk factors. Laboratory parameters, including lipid profile, were measured for both patients and controls. B-mode ultrasonography was used to assess the cEMT and cIMT.

Results

There was no significant difference in the cEMT values between the patients with BD and the control group (P = 0.90). cIMT in the BD group was significantly higher compared with the control group (P = 0.021). There was a significant positive correlation between cIMT and cEMT (r = 0.585, P = 0.001). Both cEMT and cIMT were positively correlated with age and the presence of arthritis. There was linear correlation with sedimentation, C-reactive protein, and cEMT.

Conclusions

To the best of our knowledge, this is the first study to evaluate both cEMT and cIMT in BD. This study presents morphological evidence of subclinical atherosclerosis in terms of cIMT. Although there was no significant increment in cEMT, it has the potential to assess endothelial dysfunction in BD. Further studies are required to confirm this finding.

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Rat Osteosarcoma Cells as a Therapeutic Target Model for Osteoregeneration via Sclerostin Knockdown

There are various conceptually different strategies to improve bone regeneration and to treat osteoporosis, each with distinct inherent advantages and disadvantages. The use of RNA interference strategies to suppress the biological action of catabolic factors or antagonists of osteogenic proteins is promising, and such strategies can be applied locally. They are comparably inexpensive and do not suffer from stability problems as protein-based approaches. In this study, we focus on sclerostin, encoded by the SOST gene, a key regulator of bone formation and remodeling. Sclerostin is expressed by mature osteocytes but also by late osteogenically differentiated cells. Thus, it is difficult and requires long-term cultures to investigate the effects of SOST silencing on the expression of osteogenic markers using primary cells. We, therefore, selected a rat osteosarcoma cell line, UMR-106, that has been shown to express SOST and secrete sclerostin in a comparable fashion as late osteoblasts and osteocytes. We investigated the effects of differentiating supplements on SOST expression and sclerostin secretion in UMR-106 cells and found that addition of 100 ng/ml of bone morphogenetic protein (BMP)-2 strongly induced sclerostin secretion, whereas dexamethasone inhibited secretion. Effects of silencing SOST in UMR-106 cells cultured in various differentiation media including BMP-2 and/or dexamethasone were determined next with the aim to find promising test conditions for a readout system for the evaluation of future small interfering RNA release formulations for local induction of bone formation. We found a direct correlation between attenuated SOST expression and an increase in the osteogenic potential of UMR-106 cells. The combination of SOST silencing and BMP-2 could synergistically improve osteogenic factors. A lowered proliferation rate in silenced groups may indicate a faster switch to differentiation.
Cells Tissues Organs 2015-16:201:366-379

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The relationship between the Nasality Severity Index 2.0 and perceptual judgments of hypernasality

Publication date: Available online 26 May 2016
Source:Journal of Communication Disorders
Author(s): Kim Bettens, Marc De Bodt, Youri Maryn, Anke Luyten, Floris L. Wuyts, Kristiane M. Van Lierde
PurposeThe Nasality Severity Index 2.0 (NSI 2.0) forms a new, multiparametric approach in the identification of hypernasality. The present study aimed to investigate the correlation between the NSI 2.0 scores and the perceptual assessment of hypernasality.MethodSpeech samples of 35 patients, representing a range of nasality from normal to severely hypernasal, were rated by four expert speech-language pathologists using visual analogue scaling (VAS) judging the degree of hypernasality, audible nasal airflow (ANA) and speech intelligibility. Inter- and intra-listener reliability was verified using intraclass correlation coefficients. Correlations between NSI 2.0 scores and its parameters (i.e. nasalance score of an oral text and vowel/u/, voice low tone to high tone ratio of the vowel/i/) and the degree of hypernasality were determined using Pearson correlation coefficients. Multiple linear regression analysis was used to investigate the possible influence of ANA and speech intelligibility on the NSI 2.0 scores.ResultsOverall good to excellent inter- and intra-listener reliability was found for the perceptual ratings. A moderate, but significant negative correlation between NSI 2.0 scores and perceived hypernasality (r=−0.64) was found, in which a more negative NSI 2.0 score indicates the presence of more severe hypernasality. No significant influence of ANA or intelligibility on the NSI 2.0 was observed based on the regression analysis.ConclusionBecause the NSI 2.0 correlates significantly with perceived hypernasality, it provides an easy-to-interpret severity score of hypernasality which will facilitate the evaluation of therapy outcomes, communication to the patient and other clinicians, and decisions for treatment planning, based on a multiparametric approach. However, research is still necessary to further explore the instrumental correlates of perceived hypernasality.Learning outcomesThe reader will be able to (1) describe and discuss current issues and influencing variables regarding perceptual ratings of hypernasality; (2) describe and discuss the relationship between the Nasality Severity Index 2.0, a new multiparametric approach to hypernasality, and perceptual judgments of hypernasality based on visual analogue scale ratings; (3) compare these results with the correlations based on a single parameter approach and (4) describe and discuss the possible influence of audible nasal airflow and speech intelligibility on the NSI 2.0 scores.



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Issue Information

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Frontal Fibrosing Alopecia Severity Index (FFASI): a validated scoring system for assessing frontal fibrosing alopecia

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Seudotumor inflamatorio orbitario IgG4 asociado a aplasia etmoido-maxilar unilateral

Publication date: Available online 26 May 2016
Source:Acta Otorrinolaringológica Española
Author(s): María Costales, Fernando López, Andrés Coca, José Luis Llorente




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Computer Assisted Optical Screening of Human Ovarian Cancer using Raman Spectroscopy

Publication date: Available online 26 May 2016
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Irfan Ullah, Iftikhar Ahmad, Hasan Nisar, Saranjam Khan, Rahat Ullah, Rashad Rashid, Hassan Mahmood
Conventional screening tools for ovarian cancer such as cancer antigen (CA-125) and trans-pelvic ultrasound have poor sensitivity and specificity, indicating the need for better and more reliable screening methodologies. Here, we investigate the capability of Raman spectroscopy as a screening technique for ovarian cancer. Raman spectra from the blood serum of healthy control and ovarian cancer subjects were measured. Highly significant Raman shifts (p<0.0001) and intensity variations were observed in the cancer group as compared to the healthy group. These spectral differences were exploited by support vector machine classifier towards computer assisted classification. Calculated evaluation metrics such as sensitivity (=90), specificity (=100), positive predictive value (=100) and negative predictive value (=87.5) for such classification indicated that these results are promising, with potential future application of Raman spectroscopy for ovarian cancer screening.



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Short-course radiotherapy with delayed surgery in unfit locally advanced rectal cancer patients

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Endoluminal diverticular abscess with endoscopic drainage: a new presentation and management of acute diverticulitis

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Ulcerate colitis and protein C system: is there a link of causality

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Functional diversity of stromal cell-derived factor 1 splice variants in colorectal cancer and melanoma

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The thrifty phenotype hypothesis: is sirtuin 6 the solution to the enigma?

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Prophylactic stoma mesh did not prevent parastomal hernias

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Severe acute kidney injury as a complication of collagenous colitis

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Non-neutropenic acute typhlitis associated to gram-positive bacillus: clinicopathological series

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