Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

Αρχειοθήκη ιστολογίου

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Η λίστα ιστολογίων μου

Δευτέρα 14 Δεκεμβρίου 2015

Ryan White HIV/AIDS Program Assistance and HIV Treatment Outcomes

Background. The Ryan White HIV/AIDS Program (RWHAP) provides persons infected with human immunodeficiency virus (HIV) with services not covered by other healthcare payer types. Limited data exist to inform policy decisions about the most appropriate role for RWHAP under the Patient Protection and Affordable Care Act (ACA).

Methods. We assessed associations between RWHAP assistance and antiretroviral therapy (ART) prescription and viral suppression. We used data from the Medical Monitoring Project, a surveillance system assessing characteristics of HIV-infected adults receiving medical care in the United States. Interview and medical record data were collected in 2009–2013 from 18 095 patients.

Results. Nearly 41% of patients had RWHAP assistance; 15% relied solely on RWHAP assistance for HIV care. Overall, 91% were prescribed ART, and 75% were virally suppressed. Uninsured patients receiving RWHAP assistance were significantly more likely to be prescribed ART (52% vs 94%; P < .01) and virally suppressed (39% vs 77%; P < .01) than uninsured patients without RWHAP assistance. Patients with private insurance and Medicaid were 6% and 7% less likely, respectively, to be prescribed ART than those with RWHAP only (P < .01). Those with private insurance and Medicaid were 5% and 12% less likely, respectively, to be virally suppressed (P ≤ .02) than those with RWHAP only. Patients whose private or Medicaid coverage was supplemented by RWHAP were more likely to be prescribed ART and virally suppressed than those without RWHAP supplementation (P ≤ .01).

Conclusions. Uninsured and underinsured HIV-infected persons receiving RWHAP assistance were more likely to be prescribed ART and virally suppressed than those with other types of healthcare coverage.



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First bite syndrome after bimaxillary osteotomy: case report

We read the recently published paper by Scholey and Suida,1 in which they described a case of first bite syndrome that developed after a bimaxillary osteotomy. They described symptoms consistent with first bite syndrome and diagnosed the condition with no evidence of intraoral or extraoral disease. The syndrome has a specific symptom of facial pain that occurs only with the first bite of a meal. We reproduced this by introducing lemon glycerine swabs into the mouth to stimulate the secretion of saliva, which seems to be a reliable technique for diagnosis.

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Le Fort I advancement osteotomies of 1 cm or more. How safe or stable?

We studied the results and stability of Le Fort I maxillary osteotomies with advancement of at least 1cm. We analysed prospective data from 32 consecutive patients who were operated on by a single surgeon between 1985 and 2007, and who had mean advancement of the maxilla of 14mm (range 10–22mm).Mean relapse for all cases antero-posteriorly was 1mm, 10% (range 0–4mm). Relapse was marginally greater in the 24 patients with a repaired cleft palate (11%) compared with those without a cleft (8%). The results were essentially stable at least one year after surgery and without significant complications.

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Non-invasive single-trial detection of variable population spike responses in human somatosensory evoked potentials

Non-invasive electroencephalography during peripheral nerve stimulation provides functional information about central stimulus processing. In particular, the clinically established low-frequency EEG (<100Hz) mainly reflects cortical postsynaptic potentials, i.e., the input of neuronal computation (Okada et al., 1997). In contrast, somatosensory evoked potentials (SEPs) contain an additional oscillatory high-frequency EEG burst (≈600Hz), denoted here as 'σ-burst', which is concomitant with the first cortical low-frequency component (the post-synaptically generated 'N20' for median nerve stimulation) and can be isolated by high-pass filtering above 400 Hz (Cracco and Cracco, 1976; Eisen et al., 1984).

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New technique for closure of an oroantral fistula using platelet-rich fibrin

An oroantral fistula forms when the blood clot comes out of an extraction socket after there has been a breach of the floor and the epithelial membrane of the maxillary sinus. The blood clot would have otherwise served as a "scaffold" for the epithelial cells to grow from the margins towards the centre of the wound to heal it.

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Evidence of small fiber neuropathy in a patient with Ehlers–Danlos syndrome, hypermobility-type

Joint hypermobility syndrome (JHS) and Ehlers-Danlos syndrome hypermobility type (EDS-HT) are two clinically overlapping heritable connective tissue diseases. Their clinical identity has been recently suggested and many researchers are now considering EDS-HT and JHS as one and the same (i.e. JHS/EDS-HT) (Castori et al., 2013). As the molecular basis of JHS/EDS-HT is largely unknown, the diagnosis remains based exclusively on clinical criteria. Generalized joint hypermobility, joint complications and skin hyperextensibility are the major features of JHS/EDS-HT and chronic pain, fatigue, headache and dysautonomia represent the major causes of patient disability (Castori et al., 2013; De Wandele et al., 2014).

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SHMT1 C1420T polymorphism contributes to the risk of non-Hodgkin lymphoma: evidence from 7309 patients

Abstract

Background

Serine hydroxymethyltransferase 1 (SHMT1) is a key enzyme in the folate metabolic pathway that plays an important role in biosynthesis by providing one carbon unit. SHMT1 C1420T may lead to the abnormal biosynthesis involved in DNA synthesis and methylation, and it may eventually increase cancer susceptibility. Many epidemiologic studies have explored the association between C1420T polymorphism and the risk of non-Hodgkin lymphoma (NHL), but the results have been contradictory. Therefore, we performed this meta-analysis to evaluate the relationship.

Methods

The meta-analyses were conducted to evaluate the effect of SHMT1 C1420T polymorphism on NHL risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association.

Results

Eight studies encompassing 3232 cases and 4077 controls were included. A statistically significant association was found between SHMT1 C1420T polymorphism and NHL risk under the allelic comparison (T vs. C: OR = 1.09, 95% CI 1.01–1.17); a borderline association was found between SHMT1 C1420T polymorphism and NHL risk under the homozygote model (TT vs. CC: OR = 1.18, 95% CI 1.00–1.39) and the dominant model (CT+TT vs. CC: OR = 1.10, 95% CI 1.00–1.21).

Conclusion

SHMT1 C1420T polymorphism may be associated with NHL risk, which needs to be validated in large, prospective studies.

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Virtual occlusal definition for orthognathic surgery

Computer-assisted surgical simulation is being used increasingly in orthognathic surgery. However, occlusal definition is still undertaken using model surgery with subsequent digitization via surface scanning or cone beam computed tomography. A software tool has been developed and a workflow set up in order to achieve a virtual occlusal definition. The results of a validation study carried out on 60 models of normal occlusion are presented. Inter- and intra-user correlation tests were used to investigate the reproducibility of the manual setting point procedure.

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Sociodemographic impact on survival in unresectable hepatocellular carcinoma: a survival epidemiology and end results study

Future Oncology Ahead of Print.

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Maternal obesity and malnourishment exacerbate perinatal oxidative stress resulting in diabetogenic programming in F1 offspring

Abstract

The effect of in-utero environment on fetal health and survival is long-lasting, and this is known as the fetal origin hypothesis. The oxidative stress state during gestation could play a pivotal role in fetal programming and development of diseases such as diabetes. In this study, we investigated the effect of intra-uterine obesity and malnutrition on oxidative stress markers in pancreatic and peripheral tissues of F1 offspring both prenatally and postnatally. Furthermore, the effect of postnatal diet on oxidative stress profile was evaluated. The results indicated that intra-uterine obesity and malnourishment significantly increased oxidative stress in F1 offspring. Moreover, the programming effect of obesity was more pronounced and protracted than malnutrition. The obesity-induced programming of offspring tissues was independent of high-caloric environment that the offspring endured; however, high-caloric diet potentiated its effect. In addition, pancreas and liver were the most affected tissues by fetal reprogramming both prenatally and postnatally. In conclusion, maternal obesity and malnutrition-induced oxidative stress could predispose offspring to insulin resistance and diabetes.

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Validity and reliability of the Korean version of the Speech Handicap Index in patients with oral cavity cancer

The aims of this study were to evaluate the cross-cultural adaptation of the Speech Handicap Index (SHI) for Korean subjects and to determine its reliability and utility in patients with oral cavity cancer. The Korean version of the SHI was administered to 50 healthy subjects and 56 patients with speech problems resulting from treatment for oral cavity cancers. The content and construct validity, internal consistency, and test–retest reliability were examined. Healthy subject and patient group scores were compared, and the Mann–Whitney U-test was used to determine discriminatory ability.

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‘Stylo-mandibular complex’ fracture from a maxillofacial surgeon’s perspective – review of the literature and proposal of a management algorithm

The incidence of fractures of styloid process, either in isolation or association with mandibular fractures, is rare, and frequently overlooked. When present, they pose clinical dilemma in diagnosis and management. Proper management of styloid fractures is essential, not just to alleviate the patients' symptoms, but also to prevent potential complications like post-traumatic styloid syndrome and injury to adjacent vital structures. This article features a review of literature on 'styloid fracture concomitant with mandibular fracture' along with a case report.

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Pluripotent stem cells for disease modeling and drug screening: new perspectives for treatment of cystic fibrosis?

Abstract

Despite continuous improvements in treating clinical symptoms and the identification of single compounds that effectively rescue some rare mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), associated lung and liver pathologies remain largely untreatable and no real breakthrough is visible for the majority of patients suffering from cystic fibrosis (CF).

Novel compounds have to be identified and tailored in combination to specific CFTR mutations, to different tissues, or even to the individual patient. Immortalized cell lines overexpressing mutant CFTR are typically used to screen candidate molecules but have proven to be poor predictors of clinical efficacy. The complexity of CFTR maturation and turnover requires the use of cellular models that closely recapitulate the specific properties of the clinically most affected organs. Importantly, current screening efforts based on primary airway cells or intestinal organoids cannot specifically target single rare CFTR mutations or mimic multiple cell types.

In the near future, genetically engineered induced pluripotent stem cells will provide an excellent basis for personalized organotypic models of CF disease and biological screens for identification of CFTR potentiators and correctors.

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Analytical Study of Vocal Vibrato and Mordent of Indian Popular Singers

Two very important ornamentations that singers introduce while singing are vibrato and mordent. Exploring vibrato characteristics of different styles of singing is currently a major interest in musical research. This work presents an analysis of vocal vibrato of Indian pop singers. This paper also reviews a direct relationship between tempo and vibrato, which has been established on Indian pop singers. Another ornament called mordent is also widely used by the Indian singers spontaneously. This study performs an analysis of mordent and tries to define its characteristics with the help of three proposed parameters: mid-extent, mordent duration and landing note deviation.

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Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Womens Health Initiative Randomized Trial

Background:

While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use.

Methods:

The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided.

Results:

After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22).

Conclusion:

In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence.

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Frontal white matter hyperintensities, clasmatodendrosis and gliovascular abnormalities in ageing and post-stroke dementia

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White matter hyperintensities as seen on brain T2-weighted magnetic resonance imaging are associated with varying degrees of cognitive dysfunction in stroke, cerebral small vessel disease and dementia. The pathophysiological mechanisms within the white matter accounting for cognitive dysfunction remain unclear. With the hypothesis that gliovascular interactions are impaired in subjects with high burdens of white matter hyperintensities, we performed clinicopathological studies in post-stroke survivors, who had exhibited greater frontal white matter hyperintensities volumes that predicted shorter time to dementia onset. Histopathological methods were used to identify substrates in the white matter that would distinguish post-stroke demented from post-stroke non-demented subjects. We focused on the reactive cell marker glial fibrillary acidic protein (GFAP) to study the incidence and location of clasmatodendrosis, a morphological attribute of irreversibly injured astrocytes. In contrast to normal appearing GFAP+ astrocytes, clasmatodendrocytes were swollen and had vacuolated cell bodies. Other markers such as aldehyde dehydrogenase 1 family, member L1 (ALDH1L1) showed cytoplasmic disintegration of the astrocytes. Total GFAP+ cells in both the frontal and temporal white matter were not greater in post-stroke demented versus post-stroke non-demented subjects. However, the percentage of clasmatodendrocytes was increased by >2-fold in subjects with post-stroke demented compared to post-stroke non-demented subjects (P = 0.026) and by 11-fold in older controls versus young controls (P < 0.023) in the frontal white matter. High ratios of clasmotodendrocytes to total astrocytes in the frontal white matter were consistent with lower Mini-Mental State Examination and the revised Cambridge Cognition Examination scores in post-stroke demented subjects. Double immunofluorescent staining showed aberrant co-localization of aquaporin 4 (AQP4) in retracted GFAP+ astrocytes with disrupted end-feet juxtaposed to microvessels. To explore whether this was associated with the disrupted gliovascular interactions or blood–brain barrier damage, we assessed the co-localization of GFAP and AQP4 immunoreactivities in post-mortem brains from adult baboons with cerebral hypoperfusive injury, induced by occlusion of three major vessels supplying blood to the brain. Analysis of the frontal white matter in perfused brains from the animals surviving 1–28 days after occlusion revealed that the highest intensity of fibrinogen immunoreactivity was at 14 days. At this survival time point, we also noted strikingly similar redistribution of AQP4 and GFAP+ astrocytes transformed into clasmatodendrocytes. Our findings suggest novel associations between irreversible astrocyte injury and disruption of gliovascular interactions at the blood–brain barrier in the frontal white matter and cognitive impairment in elderly post-stroke survivors. We propose that clasmatodendrosis is another pathological substrate, linked to white matter hyperintensities and frontal white matter changes, which may contribute to post-stroke or small vessel disease dementia.

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Continuous Joint Use of Estrogen and Progestin Decreases Risk of EC in Postmenopausal Women

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SHMT1 C1420T polymorphism contributes to the risk of non-Hodgkin lymphoma: evidence from 7309 patients

Serine hydroxymethyltransferase 1 (SHMT1) is a key enzyme in the folate metabolic pathway that plays an important role in biosynthesis by providing one carbon unit. SHMT1 C1420T may lead to the abnormal biosynthe…

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Axial myopathy: an overlooked feature of muscle diseases

Classically, myopathies are categorized according to limb or cranial nerve muscle affection, but with the growing use of magnetic resonance imaging it has become evident that many well-known myopathies have significant involvement of the axial musculature. New disease entities with selective axial muscle involvement have also been described recently, but overall the axial myopathy is unexplored. We performed a PubMed search using the search terms 'myopathy', 'paraspinal', 'axial' and 'erector'. Axial myopathy was defined as involvement of paraspinal musculature. We found evidence of axial musculature involvement in the majority of myopathies in which paraspinal musculature was examined. Even in diseases named after a certain pattern of non-axial muscle affection, such as facioscapulohumeral and limb girdle muscular dystrophies, affection of the axial musculature was often severe and early, compared to other muscle groups. Very sparse literature evaluating the validity of clinical assessment methods, electromyography, muscle biopsy and magnetic resonance imaging was identified and reference material is generally missing. This article provides an overview of the present knowledge on axial myopathy with the aim to increase awareness and spur interest among clinicians and researchers in the field.

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Accurate and sensitive real-time PCR assays using intergenic spacer 1 region to differentiate Cryptococcus gattii sensu lato and Cryptococcus neoformans sensu lato

In this work, two accurate and sensitive real-time polymerase chain reaction (PCR) assays to differentiate pathogenic Cryptococcus gattii sensu lato (s.l.) and C. neoformans sensu lato (s.l.) targeting the intergenic spacer 1 (IGS1) region from rDNA locus were developed. Specific primers were designed based on their IGS1 sequence analyses and the optimal real-time PCR assays showed that the dissociation curves generated two different melting peaks, at 82.8 and 84.2ºC for C. gattii s.l. and C. neoformans s.l., respectively. No amplifications were observed in the negative template control. The minimum limit of detection of both primers was 100 plasmid copies per reaction, and they were highly specific when tested with a range of fungal DNAs. Overall, the results showed that the designed primers completely differentiated C. gattii s.l. and C. neoformans s.l. from clinical and environmental sources with great accuracy when compared to phenotypic identification, with no cross-reactivity to other fungal DNA.

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Letter to the Editor Regarding “Is magnetic resonance imaging in addition to a computed tomographic scan necessary to identify clinically significant cervical spine injuries in obtunded blunt trauma patients?”

We would like to thank the authors Fisher et al. for raising an important issue regarding the utility of magnetic resonance imaging (MRI) in obtunded cervical spine (CS) blunt trauma patients in their study titled "Is magnetic resonance imaging in addition to a computed tomographic scan necessary to identify clinically significant cervical spine injuries in obtunded blunt trauma patients 1." This is a timely effort to address this longstanding controversy.

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Coronary artery bypass grafting in Takayasu’s disease – importance of the proximal anastomosis: a case report

IntroductionTreatment of coronary artery involvement in Takayasu's arteritis is challenging. Coronary artery bypass grafting may be required. The use of saphenous vein grafts is recommended because of possible inflammatory involvement of the internal thoracic arteries. However, inserting the proximal anastomosis on inflamed aortic tissue may give rise to stenosis. Only a few cases of inserting a proximal anastomosis in patients with Takayasu's arteritis have been reported in the literature. To date, no consensus has been reached on the best way to perform this procedure in patients with Takayasu's arteritis.Case presentationWe report a case of a 25-year-old white woman with Takayasu's arteritis who had recurrent angina after two previous treatments had failed, due to left main stem stenosis. She was successfully treated by coronary artery bypass grafting using a Dacron patch to insert the proximal anastomosis. Conclusions: We are the first to report an uncomplicated case in which a Dacron (Vascutek®, Renfrewshire) prosthetic patch was used to insert the proximal anastomosis on an inflamed aorta in a patient with Takayasu's arteritis. The patch prevents contact between inflamed tissue and the graft, which we believe reduces the risk of graft failure. This case might inspire other thoracic surgeons in the challenging task of performing revascularization techniques in patients with an inflamed and fragile aorta.

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Management of Acute Appendicitis in a Rural Population

Our system uses a Hub and Spoke Approach (HSA) to provide surgical care for our rural population. Patients access care anywhere in the system, but are transferred centrally for surgical care. We sought to determine if surgical outcome differed depending on where initial care occurred. We chose Acute Appendicitis (AA) to investigate our care model.

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Fatal coma in a young adult due to late-onset urea cycle deficiency presenting with a prolonged seizure: a case report

IntroductionUnexplained hyperammonemic coma in adults can be a medical dilemma in the absence of triggering factors and known comorbidities. Ornithine transcarbamylase deficiency presents most commonly with hyperammonemic coma. Although a rare disorder, ornithine transcarbamylase deficiency is the most common of the urea cycle disorders, which can occur both in children, and less commonly, in adults. The urea cycle disorder is usually acquired as an X-linked trait, and very rarely, similar to our reported case, may be acquired as a "new" mutation. Mutations that lead to later-onset presentations may lead to life-threatening disease and may be unrecognized, particularly when the first clinical symptoms occur in adulthood.Case presentationWe report the case of a previously healthy 17-year-old white man who developed a prolonged seizure and a rapid decline in mental status leading to coma over a 3-day period. Analysis of the OTC gene showed a 119G variant, which was identified in exon 2 of the OTC gene by sequencing. Conclusions: A diagnosis of ornithine transcarbamylase deficiency should be considered in adult patients who present with unexplained hyperammonemic coma and for all adult patients presenting with cryptogenic new-onset seizure and laboratory finding of elevated blood ammonia levels. This reported case highlights the importance of early recognition of this potentially reversible cause of life-threatening encephalopathy, as timely recognition and appropriate treatment can be lifesaving.

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Clinical Impact of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging on Hepatoma Management: A Prospective Study

Abstract

Background

For patients with hepatocellular carcinoma (HCC), gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) improved the diagnosis, migrated Barcelona Clinic Liver Cancer (BCLC) stage, and changed therapeutic decision in retrospective analysis.

Aim

This prospective study was to evaluate the clinical impact of EOB-MRI on HCC management.

Methods

From September 2012 to February 2014, consecutive patients with suspicion of HCC in BCLC early stage by multidetector computed tomography or dynamic MRI with non-specific gadolinium, well liver function reserve, and admitted for resection evaluation were enrolled prospectively. Additional EOB-MRI was performed. The HCC diagnosis, BCLC staging, and treatment decision were obtained in a liver cancer conference. EOB-MRI impact on HCC management was analyzed.

Results

One hundred and three patients including 68 with typical and 35 with atypical HCC nodules in dynamic imaging studies were enrolled. EOB-MRI characterized 3 (4.4 %) benign and 33 (94.3 %) HCC for patients with typical and atypical HCC nodules, respectively. For 90 HCC patients, additional EOB-MRI changed BCLC stage in 25 (27.8 %) and treatment decision in 17 (18.9 %) patients. There were 66 patients with 78 resected nodules including 65 HCCs, 4 intrahepatic cholangiocarcinomas, and 9 benign nodules. Dynamic study and EOB-MRI detected and characterized 69 and 77 nodules, respectively. The sensitivity and accuracy in HCC diagnosis were 98.5 and 85.7 % for EOB-MRI, which were better than those of dynamic study (p < 0.001).

Conclusions

Additional EOB-MRI improved HCC diagnosis in sensitivity, accuracy but not specificity. It changed BCLC staging and treatment decision in 27.8 and 18.9 % of early-stage HCC patients.

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Hyperbilirubinemia and Leukocytosis in Gangrenous Cholecystitis

After reading the article "Risk factors for acute gangrenous cholecystitis in emergency general surgery patients" by Bourikian et al,1 I found it surprising that leukocytosis was not a predictor of gangrenous cholecystitis. Hyperbilirubinemia and leukocytosis continue to be important predictors of gangrenous cholecystitis.

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A Century Later and Not Much Has Changed in Use of Anatomic Nomenclature: Should Surgeons and Anatomists Be Speaking the Same Language?

Recently, the Journal of the American Medical Association published in the "JAMA Revisited" section a centennial paper entitled "Anatomic Nomenclature"1 by anatomist Dr Albert Eycleshymer (1867-1925). Dr Eycleshymer's advocacy for uniformity in the use of anatomic terminology where its impact is most strongly felt echo's the sentiments of anatomists today who are vested in the education of future physicians. While the use of anatomical terminology is today governed by the international standard on human anatomic terminology the challenge of maintaining coherency between anatomical and clinical referencing persists.

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Epidural Analgesia Utilization Rate for Hepatic and Pancreatic Surgery, That Low?

I read with interest the article "a nationwide analysis of the use and outcomes of perioperative epidural analgesia in patients undergoing hepatic and pancreatic surgery" .1 I congratulate the authors for this important analysis and their publication in your esteemed journal; however, I have few concerns about this study I would like the authors to address. The first concern is the low post-operative epidural analgesia (EA) utilization rate (7.4%) reported in this study for the selected surgical procedures.

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A Conversation with Allan Balmain

Editor's Note: Allan Balmain is the Distinguished Professor of Cancer Genetics at the University of California, San Francisco and a Fellow of the Royal Society. He has been publishing important papers on RAS biology for almost 30 years. RAS Central editors recently interviewed Dr. Balmain about his personal history and scientific career.

Can we ask you how you came to be at the UCSF? What was your path? Are you a Scot originally, is that correct?

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A note of thanks

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Coronary artery bypass grafting in Takayasu’s disease – importance of the proximal anastomosis: a case report

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IntroductionTreatment of coronary artery involvement in Takayasu's arteritis is challenging. Coronary artery bypass grafting may be required. The use of saphenous vein grafts is recommended because of possible inflammatory involvement of the internal thoracic arteries. However, inserting the proximal anastomosis on inflamed aortic tissue may give rise to stenosis. Only a few cases of inserting a proximal anastomosis in patients with Takayasu's arteritis have been reported in the literature. To date, no consensus has been reached on the best way to perform this procedure in patients with Takayasu's arteritis.Case presentationWe report a case of a 25-year-old white woman with Takayasu's arteritis who had recurrent angina after two previous treatments had failed, due to left main stem stenosis. She was successfully treated by coronary artery bypass grafting using a Dacron patch to insert the proximal anastomosis. Conclusions: We are the first to report an uncomplicated case in which a Dacron (Vascutek®, Renfrewshire) prosthetic patch was used to insert the proximal anastomosis on an inflamed aorta in a patient with Takayasu's arteritis. The patch prevents contact between inflamed tissue and the graft, which we believe reduces the risk of graft failure. This case might inspire other thoracic surgeons in the challenging task of performing revascularization techniques in patients with an inflamed and fragile aorta.

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Chimeric transcripts resulting from complex duplications in chromosome Xq28

Abstract

Gene fusions have been observed in somatic alterations in cancer and in schizophrenia. However, the underlying mechanism(s) for their formation are poorly understood. We experimentally demonstrated the expression of splicing variants of in silico predicted chimeric genes F8/CSAG1 and BCAP31/TEX28 in two individuals with de novo complex genomic rearrangements of Xq28; F8/CSAG1 includes exonization of an ERVL-MaLR intronic repetitive element. We provide evidence that replicative repair may contribute to exon shuffling processes and diversify the repertoire of expressed transcripts.



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Coronary artery bypass grafting in Takayasu’s disease – importance of the proximal anastomosis: a case report

IntroductionTreatment of coronary artery involvement in Takayasu's arteritis is challenging. Coronary artery bypass grafting may be required. The use of saphenous vein grafts is recommended because of possible inflammatory involvement of the internal thoracic arteries. However, inserting the proximal anastomosis on inflamed aortic tissue may give rise to stenosis. Only a few cases of inserting a proximal anastomosis in patients with Takayasu's arteritis have been reported in the literature. To date, no consensus has been reached on the best way to perform this procedure in patients with Takayasu's arteritis.Case presentationWe report a case of a 25-year-old white woman with Takayasu's arteritis who had recurrent angina after two previous treatments had failed, due to left main stem stenosis. She was successfully treated by coronary artery bypass grafting using a Dacron patch to insert the proximal anastomosis. Conclusions: We are the first to report an uncomplicated case in which a Dacron (Vascutek®, Renfrewshire) prosthetic patch was used to insert the proximal anastomosis on an inflamed aorta in a patient with Takayasu's arteritis. The patch prevents contact between inflamed tissue and the graft, which we believe reduces the risk of graft failure. This case might inspire other thoracic surgeons in the challenging task of performing revascularization techniques in patients with an inflamed and fragile aorta.

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Fatal coma in a young adult due to late-onset urea cycle deficiency presenting with a prolonged seizure: a case report

IntroductionUnexplained hyperammonemic coma in adults can be a medical dilemma in the absence of triggering factors and known comorbidities. Ornithine transcarbamylase deficiency presents most commonly with hyperammonemic coma. Although a rare disorder, ornithine transcarbamylase deficiency is the most common of the urea cycle disorders, which can occur both in children, and less commonly, in adults. The urea cycle disorder is usually acquired as an X-linked trait, and very rarely, similar to our reported case, may be acquired as a "new" mutation. Mutations that lead to later-onset presentations may lead to life-threatening disease and may be unrecognized, particularly when the first clinical symptoms occur in adulthood.Case presentationWe report the case of a previously healthy 17-year-old white man who developed a prolonged seizure and a rapid decline in mental status leading to coma over a 3-day period. Analysis of the OTC gene showed a 119G variant, which was identified in exon 2 of the OTC gene by sequencing. Conclusions: A diagnosis of ornithine transcarbamylase deficiency should be considered in adult patients who present with unexplained hyperammonemic coma and for all adult patients presenting with cryptogenic new-onset seizure and laboratory finding of elevated blood ammonia levels. This reported case highlights the importance of early recognition of this potentially reversible cause of life-threatening encephalopathy, as timely recognition and appropriate treatment can be lifesaving.

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Clinical Impact of Gadoxetic Acid-Enhanced Magnetic Resonance Imaging on Hepatoma Management: A Prospective Study

Abstract

Background

For patients with hepatocellular carcinoma (HCC), gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) improved the diagnosis, migrated Barcelona Clinic Liver Cancer (BCLC) stage, and changed therapeutic decision in retrospective analysis.

Aim

This prospective study was to evaluate the clinical impact of EOB-MRI on HCC management.

Methods

From September 2012 to February 2014, consecutive patients with suspicion of HCC in BCLC early stage by multidetector computed tomography or dynamic MRI with non-specific gadolinium, well liver function reserve, and admitted for resection evaluation were enrolled prospectively. Additional EOB-MRI was performed. The HCC diagnosis, BCLC staging, and treatment decision were obtained in a liver cancer conference. EOB-MRI impact on HCC management was analyzed.

Results

One hundred and three patients including 68 with typical and 35 with atypical HCC nodules in dynamic imaging studies were enrolled. EOB-MRI characterized 3 (4.4 %) benign and 33 (94.3 %) HCC for patients with typical and atypical HCC nodules, respectively. For 90 HCC patients, additional EOB-MRI changed BCLC stage in 25 (27.8 %) and treatment decision in 17 (18.9 %) patients. There were 66 patients with 78 resected nodules including 65 HCCs, 4 intrahepatic cholangiocarcinomas, and 9 benign nodules. Dynamic study and EOB-MRI detected and characterized 69 and 77 nodules, respectively. The sensitivity and accuracy in HCC diagnosis were 98.5 and 85.7 % for EOB-MRI, which were better than those of dynamic study (p < 0.001).

Conclusions

Additional EOB-MRI improved HCC diagnosis in sensitivity, accuracy but not specificity. It changed BCLC staging and treatment decision in 27.8 and 18.9 % of early-stage HCC patients.

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A Conversation with Allan Balmain

Editor's Note: Allan Balmain is the Distinguished Professor of Cancer Genetics at the University of California, San Francisco and a Fellow of the Royal Society. He has been publishing important papers on RAS biology for almost 30 years. RAS Central editors recently interviewed Dr. Balmain about his personal history and scientific career.

Can we ask you how you came to be at the UCSF? What was your path? Are you a Scot originally, is that correct?

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A note of thanks

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Developmental Stage-Specific Embryonic Induction of HepG2 Cell Differentiation

Abstract

Background

Although hepatocellular carcinoma cells can sometimes undergo differentiation in an embryonic microenvironment, the mechanism is poorly understood.

Aim

The developmental stage-specific embryonic induction of tumor cell differentiation was investigated.

Methods

Both chick and mouse liver extracts and hepatoblast-enriched cells at different developmental stages were used to treat human hepatoma HepG2 cells, and the effects on the induction of differentiation were evaluated. The nuclear factors controlling differentiation, hepatocyte nuclear factor (HNF)-4α, HNF-1α, HNF-6 and upstream stimulatory factor-1 (USF-1), and the oncogene Myc and alpha-fetoprotein (AFP) were measured. HNF-4α RNA interference was used to verify the role of HNF-4α. Embryonic induction effects were further tested in vivo by injecting HepG2 tumor cells into immunodeficient nude mice.

Results

The 9–11-days chick liver extracts and 13.5–14.5-days mouse hepatoblast-enriched cells could inhibit proliferation and induce differentiation of HepG2 cells, leading to either death or maturation to hepatocytes. The maturation of surviving HepG2 cells was confirmed by increases in the expressions of HNF-4α, HNF-1α, HNF-6, and USF-1, and decreases in Myc and AFP. The embryonic induction of HepG2 cell maturation could be attenuated by HNF-4α RNA interference. Furthermore, the 13.5-days mouse hepatoblast culture completely eliminated HepG2 tumors with inhibited Myc and induced HNF-4α, confirming this embryonic induction effect in vivo.

Conclusions

This study demonstrated that developmental stage-specific embryonic induction of HepG2 cell differentiation might help in understanding embryonic differentiation and oncogenesis.

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Population mixing and childhood leukaemia

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Carbon monoxide exposure may underlie the increased leukaemia risk in children living next to motor highways

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Body mass index, gestational weight gain and fatty acid concentrations during pregnancy: the Generation R Study

Abstract

Obesity during pregnancy may be correlated with an adverse nutritional status affecting pregnancy and offspring outcomes. We examined the associations of prepregnancy body mass index and gestational weight gain with plasma fatty acid concentrations in mid-pregnancy. This study was embedded in a population-based prospective cohort study among 5636 women. We obtained prepregnancy body mass index and maximum weight gain during pregnancy by questionnaires. We measured concentrations of saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), n-3 polyunsaturated fatty acid (n-3 PUFA) and n-6 polyunsaturated fatty acid (n-6 PUFA) at a median gestational age of 20.5 (95 % range 17.1–24.9) weeks. We used multivariate linear regression models. As compared to normal weight women, obese women had higher total SFA concentrations [difference: 0.10 standard deviation (SD) (95 % Confidence Interval (CI) 0, 0.19)] and lower total n-3 PUFA concentrations [difference: − 0.11 SD (95 % CI − 0.20, − 0.02)]. As compared to women with sufficient gestational weight gain, those with excessive gestational weight gain had higher SFA concentrations [difference: 0.16 SD (95 % CI 0.08, 0.25)], MUFA concentrations [difference: 0.16 SD (95 % CI 0.08, 0.24)] and n-6 PUFA concentrations [difference: 0.12 SD (95 % CI 0.04, 0.21)]. These results were not materially affected by adjustment for maternal characteristics. Our results suggest that obesity and excessive weight gain during pregnancy are associated with an adverse fatty acids profile. Further studies are needed to assess causality and direction of the observed associations.

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The authors’ reply: Population mixing and childhood leukaemia

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Non-invasive single-trial detection of variable population spike responses in human somatosensory evoked potentials

Publication date: Available online 15 December 2015
Source:Clinical Neurophysiology
Author(s): Gunnar Waterstraat, Manuel Scheuermann, Gabriel Curio
ObjectiveSomatosensory evoked potentials (SEPs) around 600Hz ('σ-bursts') are correlates of cortical population spikes. Recently, single-trial σ-bursts were detected in human scalp EEG using 29-channel low-noise recordings in an electromagnetically shielded room. To achieve clinical applicability, this study aimed to establish a protocol using only 8 EEG channels in an unshielded environment and to quantify the variability of σ-bursts.MethodsMedian nerve SEPs were recorded in 10 healthy subjects using a custom-built low-noise EEG amplifier. A detection algorithm for single-trial σ-bursts was trained as combination of spatio-temporal filters and a non-linear classifier. The single-trial responses were probed for the presence of significant increases of amplitude and variability.ResultsSingle-trial σ-burst detection succeeded with Detection Rates and Positive Predictive Values above 80% in subjects with high SNR. A significant inter-trial variability in the amplitudes of early low-frequency SEPs and σ-bursts could be demonstrated.ConclusionsSingle-trial σ-bursts can be detected on scalp-EEG using only 8 EEG channels in an electromagnetically disturbed environment. The combination of dedicated hardware and detection algorithms allows quantifying and describing their variability.SignificanceThe variability of population spikes in the human somatosensory cortex can be traced non-invasively in a clinical setting.

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Evidence of small fiber neuropathy in a patient with Ehlers–Danlos syndrome, hypermobility-type

Publication date: Available online 14 December 2015
Source:Clinical Neurophysiology
Author(s): Angelo Pascarella, Vincenzo Provitera, Francesco Lullo, Annamaria Stancanelli, Anna Maria Saltalamacchia, Giuseppe Caporaso, Maria Nolano

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CCR5 limits cortical viral loads during West Nile virus infection of the central nervous system

Background: Cell-mediated immunity is critical for clearance of central nervous system (CNS) infection with the encephalitic flavivirus, West Nile virus (WNV). Prior studies from our laboratory have shown that WNV-infected neurons express chemoattractants that mediate recruitment of antiviral leukocytes into the CNS. Although the chemokine receptor, CCR5, has been shown to play an important role in CNS host defense during WNV infection, regional effects of its activity within the infected brain have not been defined. Methods: We used CCR5-deficient mice and an established murine model of WNV encephalitis to determine whether CCR5 activity impacts on WNV levels within the CNS in a region-specific fashion. Statistical comparisons between groups were made with one- or two-way analysis of variance; Bonferroni's post hoc test was subsequently used to compare individual means. Survival was analyzed by the log-rank test. Analyses were conducted using Prism software (GraphPad Prism). All data were expressed as means ± SEM. Differences were considered significant if P ≤ 0.05. Results: As previously shown, lack of CCR5 activity led to increased symptomatic disease and mortality in mice after subcutaneous infection with WNV. Evaluation of viral burden in the footpad, draining lymph nodes, spleen, olfactory bulb, and cerebellum derived from WNV-infected wild-type, and CCR5 −/− mice showed no differences between the genotypes. In contrast, WNV-infected, CCR5 −/− mice exhibited significantly increased viral burden in cortical tissues, including the hippocampus, at day 8 post-infection. CNS regional studies of chemokine expression via luminex analysis revealed significantly increased expression of CCR5 ligands, CCL4 and CCL5, within the cortices of WNV-infected, CCR5 −/− mice compared with those of similarly infected WT animals. Cortical elevations in viral loads and CCR5 ligands in WNV-infected, CCR5 −/− mice, however, were associated with decreased numbers of infiltrating mononuclear cells and increased permeability of the blood-brain barrier. Conclusions: These data indicate that regional differences in chemokine expression occur in response to WNV infection of the CNS, and that cortical neurons require CCR5 activity to limit viral burden in this brain region.

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Evaluation of the mutagenic and genotoxic effects of the ALC67 thiazolidine compound in Salmonella strains and human lymphocytes in vitro

ALC67 is an N-acylated thiazolidine compound with promising anticancer activity that led to the recent discovery of a series of 3-propionyl thiazolidine-4-carboxylic acid ethyl esters as a family of novel antiproliferative agents. Since the mutagenic and genotoxic properties of marketed anticancer molecules constitute a main issue to be addressed, this study focused on the analysis of the mutagenicity, antimutagenecity, and genotoxicity of this molecule. The mutagenicity and antimutagenicity of ALC67 were evaluated by Ames test performed on Salmonella TA98 and TA100 strains. The genotoxicity of this molecule was investigated in the chromosomal aberration assay on human lymphocytes. All results revealed that the analyzed structure is not mutagenic in the two Salmonella strains tested and was not genotoxic in human lymphocytes in vitro. On the other hand, it showed a weak antimutagenic effect in these two bacterial strains. The above results indicate that after performing some more mutagenicity assays using the other recommended strains, this compound can be safely used for the development of new structures exhibiting anticancer activities.

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Intracellular chloride concentration of the mouse vomeronasal neuron

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Background: The vomeronasal organ (VNO) is specialized in detecting pheromone and heterospecific cues in the environment. Recent studies demonstrate the involvement of multiple ion channels in VNO signal transduction, including the calcium-activated chloride channels (CACCs). Opening of CACCs appears to result in activation of VNO neuron through outflow of Cl − ions. However, the intracellular Cl − concentration remains undetermined. Results: We used the chloride ion quenching dye, MQAE, to measure the intracellular Cl − concentration of VNO neuron in live VNO slices. The resting Cl − concentration in the VNO neurons is measured at 84.73 mM. Urine activation of the VNO neurons causes a drop in Cl − concentration, consistent with the notion of an efflux of Cl − to depolarize the cells. Similar observation is made for VNO neurons from mice with deletion of the transient receptor potential canonical channel 2 (TRPC2), which have a resting Cl − concentrations at 81 mM. Conclusions: The VNO neurons rest at high intracellular Cl − concentration, which can lead to depolarization of the cell when chloride channels open. These results also provide additional support of TRPC2-independent pathway of VNO activation.

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Editorial Board

Publication date: September–December 2015
Source:Arab Journal of Gastroenterology, Volume 16, Issues 3–4

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1UrIOyc 223iakt

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A note from the Editor’s desk: Arab Journal of Gastroenterology in Thomson Reuters

Publication date: September–December 2015
Source:Arab Journal of Gastroenterology, Volume 16, Issues 3–4

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223ibot 1UrIO1m

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Editorial Board

Publication date: September–December 2015
Source:Arab Journal of Gastroenterology, Volume 16, Issues 3–4

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