bluuebunny/crossref_metadata_2025 huggingface dataset:
Carmi Syndrome in a Preterm Neonate: A Multidisciplinary Approach and Ethical Challenge
Authors: Hicks Timothy D. , Singh Himanshu , Mikhael Michel , Shah Anita R.
Published: December 2018

Epidermolysis bullosa (EB) is characterized by blistering of the skin and mucosal erosions caused by hemidesmosomal abnormalities. EB is divided into 3 major subgroups depending on the particular location of tissue separation: EB simplex, dystrophic EB, and junctional EB. Junctional EB (JEB) can further be broken down into Herlitz, non-Herlitz, and JEB with pyloric atresia (Carmi syndrome) depending on genetic and histologic testing. When extensive, management of a patient with EB can be challenging due to not only cutaneous but also extracutaneous manifestations as well. Families and health care teams are often faced with difficult decisions in their infant’s best interest. We report a case of a preterm neonate with Carmi syndrome and unique findings on immunofluorescence studies. The patient’s course was complicated by multisystem involvement and ultimately death. A multidisciplinary approach was crucial in the light of diagnostic, therapeutic, and ethical challenges.
Bioinspired Ultra-Low Adhesive Energy Interface for Continuous 3D Printing: Reducing Curing Induced Adhesion
Authors: Wu L. , Dong Z. , Du H. , Li C. , Fang N. X. , Song Y.
Published: December 2018

Additive manufacturing based on liquid resin curing is one of the most promising methods to construct delicate structures. However, precision and speed are limited by the vertical adhesion of in situ cured resin at the curing interface. To overcome the unavoidable adhesion and to develop a general curing interface, we propose a slippery surface taking inspiration of the peristome surface of the pitcher plant. Such surface shows ultra-low adhesive energy at the curing interface due to the inhibition of the direct contact between the cured resin and the solid surface, which also increases the refilling speed of liquid resin. This ultra-low adhesive energy interface is effective for continuous 3D printing and provides insights into the physical mechanisms in reducing vertical solid-solid interfacial adhesion.
Peritonitis due to Moraxella Osloensis: An Emerging Pathogen
Authors: Adapa Sreedhar , Gumaste Purva , Konala Venu Madhav , Agrawal Nikhil , Garcha Amarinder Singh , Dhingra Hemant
Published: December 2018

Peritonitis is a very serious complication encountered in patients undergoing peritoneal dialysis and healthcare providers involved in the management should be very vigilant. Gram-positive organisms are the frequent cause of peritonitis compared to gram-negative organisms. There has been recognition of peritonitis caused by uncommon organisms because of improved microbiological detection techniques. We report a case of peritonitis caused by Moraxella osloensis (M. osloensis), which is an unusual cause of infections in humans. A 68-year-old male, who has been on peritoneal dialysis for 2 years, presented with abdominal pain and cloudy effluent. Peritoneal fluid analysis was consistent with peritonitis and peritoneal fluid culture grew gram-negative bacteria. M. osloensis was identified by 16 S PCR phenotypic and sequencing techniques. Patient responded well to the treatment, with intraperitoneal cephalosporin, and repeat peritoneal fluid culture yielded no growth. M. osloensis rarely causes infection in humans and responds well to treatment, as reported in literature.
Role of miRNA in the Regulatory Mechanisms of Estrogens in Cardiovascular Ageing
Authors: Pérez-Cremades Daniel , Mompeón Ana , Vidal-Gómez Xavier , Hermenegildo Carlos , Novella Susana
Published: December 2018

Cardiovascular diseases are a worldwide health problem and are the leading cause of mortality in developed countries. Together with experimental data, the lower incidence of cardiovascular diseases in women than in men of reproductive age points to the influence of sex hormones at the cardiovascular level and suggests that estrogens play a protective role against cardiovascular disease and that this role is also modified by ageing. Estrogens affect cardiovascular function via their specific estrogen receptors to trigger gene expression changes at the transcriptional level. In addition, emerging studies have proposed a role for microRNAs in the vascular effects mediated by estrogens. miRNAs regulate gene expression by repressing translational processes and have been estimated to be involved in the regulation of approximately 30% of all protein‐coding genes in mammals. In this review, we highlight the current knowledge of the role of estrogen‐sensitive miRNAs, and their influence in regulating vascular ageing.
Alcohol Consumption and Risky Drinking Patterns among College Students from Selected Countries of the Carpathian Euroregion
Authors: Zadarko-Domaradzka Maria , Barabasz Zbigniew , Sobolewski Marek , Nizioł-Babiarz Edyta , Penar-Zadarko Beata , Szybisty Agnieszka , Zadarko Emilian
Published: December 2018

Reduction of excessive alcohol consumption still remains a significant challenge to the actions in the scope of public health of European citizens. The aim of this study is to present the prevalence of alcohol consumption and to estimate the occurrence of risky drinking among college students from the Polish, Slovak, Romanian, and Ukrainian parts of the Carpathian Euroregion, taking social contexts into account. The consumption of alcohol was estimated on the basis of the respondents’ statements regarding the quantity and frequency of their consumption of beer, wine, and vodka. The study included people from the first year of undergraduate studies. The analysis used the Chi-square independence test and odds ratios (ORs). There were significant differences in the frequency of alcohol consumption, as well as the individual types consumed, among the respondents from the analyzed countries. Of the examined college students, 70% admit to occasional drinking. The pattern of dangerous alcohol consumption occurs in the case of approximately every seventh person. Risky drinking occurs with much greater frequency among male students rather than their female counterparts. In Romania, a very small percentage of female students engage in risky drinking. The analysis did not show statistically significant differences in the frequency of risky drinking between countries. The coexistence of other adverse health behaviors, such as smoking and alcohol abuse, was confirmed.
Rotate-on-Retract Procedural Automation for Robotic-Assisted Percutaneous Coronary Intervention: First Clinical Experience
Authors: Al Nooryani Arif , Aboushokka Wael
Published: December 2018

The advent of percutaneous coronary intervention (PCI) has dramatically changed the outlook for patients with cardiovascular disease. However, room for improvement and advancement remains in the safety, speed, and efficiency of manually guided PCI. In recent years, the CorPath robotic platform (Corindus Inc., Waltham, MA) has been approved to aid the interventionalist during PCI and other endovascular interventions. Favorable results in several clinical studies suggest that robotic-assisted PCI may further improve patient outcomes while also benefiting the interventionalist through reduced orthopedic strain and less exposure to ionizing radiation. In this report, we communicate our experience with the first-in-human use of a new, optional automation feature that has been added to the platform’s guidance software. This “Rotate-on-Retract” feature is designed to facilitate faster and more precise maneuvering of the guidewire through tortuous vessels by automatically rotating the guidewire whenever it is retracted by the operator. This movement changes the tip’s orientation in preparation for the next advancement. We evaluated this feature in a patient undergoing PCI to treat a severe (90% stenotic), long, diffuse, and calcified lesion of the proximal to mid LAD segments.
Chemical Composition and Antioxidant Activity of Aloe vera from the Pica Oasis (Tarapacá, Chile) by UHPLC-Q/Orbitrap/MS/MS
Authors: Quispe Cristina , Villalobos Michael , Bórquez Jorge , Simirgiotis Mario
Published: December 2018

The chemical composition of Aloe vera growing in the small town of San Andrés de Pica, an oasis of warm waters and typical fruits, located in Tamarugal province in the Northern Chilean region of Tarapacá is reported. The chemical characterization was performed using liquid chromatography (UHPLC) coupled to PDA and high-resolution mass spectrometry (HESI-Q-Orbitrap®-MS) in four different plant parts of Aloe (peel, flowers, gel, and roots). Twenty-five phenolic compounds were identified, including cinnamic acids and other derivatives (e.g., caffeic and chlorogenic acids), chromones (e.g., aloesin and isoaloeresin D), anthracene compounds and derivatives (e.g., aloin A/B and emodin), and several C-flavonoids (e.g., orientin and isovitexin), among others. Total antioxidant activity of the ethanolic extracts of the peels, flowers, gel, and roots was measured as the capturing of the DPPH• and ABTS•+ radicals, while the iron-reducing antioxidant power (FRAP) was measured by spectroscopic methods. The peel had the highest antioxidant activity with values of 2.43 mM ET/g MF (DPPH•), 34.32 mM ET/g MF (ABTS•+), and 3.82 mM ET/g MF (FRAP). According to our results, the peel is the best part of the plant for the production of nutraceuticals or cosmetics products for its greatest number of bioactive compounds. This is a new and innovative finding since the only part used in traditional medicine is the gel of Aloe, and the peel is generally considered waste and discarded.
RNF213 Variant Diversity Predisposes Distinct Populations to Dissimilar Cerebrovascular Diseases
Authors: Lin Jing , Sheng Wenli
Published: December 2018

In recent years, the ring finger protein 213 gene (RNF213) has gradually attracted attention, mainly because it has been found that RNF213 c.14429 G>A is associated with moyamoya disease (MMD) in East Asian populations. Recent studies have revealed that RFN213 is not only associated with MMD but is also connected with intracranial major artery stenosis/occlusion (ICASO) and intracranial aneurysm (IA). However, only the relationship between RNF213 c.14429 G>A and ICASO has been confirmed, and whether RNF213 has other mutations related to ICASO remains unclear. RNF213 and IA are currently only confirmed to be correlated in French-Canadian Population and no correlation has been found in the Japanese population. This review summarizes the advances in the associations between RNF213 and different cerebrovascular diseases and highlights that variant diversity of RNF213 may predispose distinct populations to dissimilar cerebrovascular diseases.
Quantitative Analysis of Phenolic Acids and Flavonoids in Cuscuta chinensis Lam. by Synchronous Ultrasonic-Assisted Extraction with Response Surface Methodology
Authors: Du Kun-ze , Li Jin , Guo Xinrong , Li Yuhong , Chang Yan-xu
Published: December 2018

An effective ultrasonic-assisted extraction method for the separation of phenolic acids and flavonoids in Cuscuta chinensis Lam. was conducted by combining uniform design (UD) coupled with response surface methodology (RSM) and orthogonal design (OD) experiment. A sensitive and selective high-performance liquid chromatography-electrospray ionization tandem triple quadrupole mass spectrometry (HPLC-ESI-MS/MS) method was applied to quantify the sixteen active ingredients (chlorogenic acid, cryptochlorogenic acid, neochlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, isochlorogenic acid C, caffeic acid, hyperin, isoquercitrin, quercetin, campherol, p-coumaric acid, isorhamnetin, rutin, astragalin, and apigenin). The extraction method was optimized with respect to concentration of extraction solvent, extraction time, and ratio of liquid to solid as a consequence of getting a high sensitive and feasible method for simultaneous determination of contents of multiple components and evaluation of quality control of Cuscuta chinensis Lam. from different origins. It was also considered useful and valuable in the further study for quality control of Cuscuta chinensis Lam.
Rehabilitation of an Extremely Resorbed Edentulous Mandible by Short and Narrow Dental Implants
Authors: Kovacic Ines , Persic Sanja , Kranjcic Josip , Lesic Nikolina , Celebic Asja
Published: December 2018

Serious consequences of long-term complete denture wearing may be extreme residual ridge atrophy and a reduced area of keratinized oral mucosa of a denture-bearing area. This paper presents five clinical cases of extreme mandibular ridge atrophy, rehabilitated by means of mandibular overdentures retained by short mini dental implants. The patients had a reduced mandibular bone volume in the interforaminal region, bone height less than 10 mm, and buccolingual bone width less than 4 mm. In order to avoid bone augmentation, patients received four short mini dental implants (MDIs) (6 or 8 mm long; 2.0 or 2.5 mm wide) for the support of mandibular overdentures, which is a new rehabilitation option. After insertion, the MDIs were early loaded with new mandibular overdentures reinforced with the CoCr framework. The patients have been wearing their overdentures for 2 years. One MDI broke during insertion and a new one was added. One patient lost one MDI but successfully continued to wear the overdenture retained by the remaining three MDIs. Mean marginal bone loss (MBL) was 0.20 ± 0.19 mm. Patients significantly improved their OHRQoL and chewing function by reducing the summary scores of the OHIP-14 and the chewing function questionnaires. The improvements remained unchanged throughout the observation period.
Near Infrared Spectroscopy Based on Supervised Pattern Recognition Methods for Rapid Identification of Adulterated Edible Gelatin
Authors: Zhang Hao , Sun Haifeng , Wang Ling , Wang Shun , Zhang Wei , Hu Jiandong
Published: December 2018

The aim of this work is to identify the adulteration of edible gelatin using near-infrared (NIR) spectroscopy combined with supervised pattern recognition methods. The spectral data obtained from a total of 144 samples consisting of six kinds of adulterated gelatin gels with different mixture ratios were processed with multiplicative scatter correction (MSC), Savitzky–Golay (SG) smoothing, and min-max normalization. Principal component analysis (PCA) was first carried out for spectral analysis, while the six gelatin categories could not be clearly distinguished. Further, linear discriminant analysis (LDA), soft independent modelling of class analogy (SIMCA), backpropagation neural network (BPNN), and support vector machine (SVM) were introduced to establish discrimination models for identifying the adulterated gelatin gels, which gave a total correct recognition rate of 97.44%, 100%, 97.44%, and 100%, respectively. For the SIMCA model with significant level α = 0.05, sample overlapping clustering appeared; thus, the SVM model presents the best recognition ability among these four discrimination models for the classification of edible gelatin adulteration. The results demonstrate that NIR spectroscopy combined with unsupervised pattern recognition methods can quickly and accurately identify edible gelatin with different adulteration levels, providing a new possibility for the detection of industrial gelatin illegally added into food products.
Delayed Guillain-Barré Syndrome after Bariatric Surgery: A Report of Three Cases
Authors: Sunbol Alana H. , Almaghrabi Sarah , Al Aslany Shahd J. , Aldairi Mashael M. , Makhdum Sara A. , Trabulsi Nora , Almekhlafi Mohammed A. , Nassif Mohammed
Published: December 2018

Surgeries carry a risk of complications. Polyneuropathies, including Guillain-Barré syndrome (GBS), are potential complications of bariatric surgery. The incidence of these conditions is expected to increase as these surgeries become increasingly popular. We present a case report of three patients who developed a polyneuropathy after bariatric surgery. GBS was diagnosed in each patient, with nutritional deficiencies being suspected as a contributing factor. All patients began a 5-day intravenous immunoglobulin course in addition to receiving rehabilitative support, multivitamins, intravenous thiamine, vitamin D (therapeutic dose), and selenium. The patients’ symptoms improved but did not completely resolve. GBS can be a complication of bariatric surgery. Although a clear cause-effect relationship cannot be established for the present cases, the cumulative literature on the subject suggests that it is important to include it as a potential risk when counseling patients for such surgeries.
Evaluation of Dietary Intakes and Nutritional Knowledge in Thai Patients with Type 2 Diabetes Mellitus
Authors: Thewjitcharoen Yotsapon , Chotwanvirat Phawinpon , Jantawan Annapann , Siwasaranond Nantaporn , Saetung Sunee , Nimitphong Hataikarn , Himathongkam Thep , Reutrakul Sirimon
Published: December 2018

Introduction. Most nutritional guidelines for diabetes management emphasize the importance of having individualized goals, away from a one-size-fits-all approach. However, there is a dearth of information on the dietary intakes and nutritional knowledge of Thai patients with type 2 diabetes mellitus (T2DM). This study is aimed at clarifying dietary intakes in relationship to glycemic control and at examining nutritional knowledge among Thai patients with T2DM.Materials and Methods. A cross-sectional study of outpatients with T2DM at Theptarin Hospital and Ramathibodi Hospital (Bangkok, Thailand) was performed to assess dietary intakes by food records. Diabetes nutritional knowledge and dietary self-care behavior was also evaluated.Results. A total of 304 Thai patients with T2DM (female 52.6%, mean age 57.4 ± 10.9 years, body mass index (BMI) 27.3 ± 4.8 kg/m2, and baseline A1C 7.2 ± 1.3%) participated in the study. The mean daily calorie intake was 1427 ± 425 kcal, and mean intake for each macronutrient was acceptable (carbohydrate 52%, protein 17%, and fat 31%). However, the intake of free sugar was much higher (12.1 ± 5.8% of total daily energy intake) and dietary fiber intake (9 grams per day) was much lower than recommended. There were no correlations between dietary intake and glycemic control. A subset of patients (N=213) completed the diabetes nutritional knowledge survey. There was no association between diabetes nutritional knowledge and the actual dietary self-care behavior.Conclusion. These results indicate that compliance of Thai patients with T2DM to dietary recommendations is not completely satisfactory, especially for free sugar and dietary fiber intakes. Addressing the reality of how patients with T2DM eat in their daily lives and their knowledge gaps would enable them to adhere to medical nutrition therapy.
The Effect of Detoxification on Sleep: How Does Sleep Quality Change during Qualified Detoxification Treatment?
Authors: Neu Peter , Sofin Yvonne , Danker-Hopfe Heidi
Published: December 2018

Aims. Sleep disturbances are common in addiction and withdrawal. This study examined the course of sleep quality in a population of alcohol dependent patients during qualified detoxification treatment in a psychiatric hospital. Methods. The Pittsburgh Sleep Quality Index (PSQI) was administered to 77 electively admitted alcohol dependent patients hospitalized for qualified detoxification treatment. Sleep quality was measured at admission and at discharge. Results. The prevalence of bad sleep as measured by a PSQI-score > 5 was 70.1% at admission. During detoxification, male and female patients were equally affected by sleep disturbances and improvement of sleep was not significantly different between males and females. The PSQI score at admission predicted the change of the PSQI score during qualified detoxification treatment. After inpatient detoxification, sleep disturbances persisted in 59.7% of the patients. Conclusions. Contrary to our expectations, the average patient’s sleep quality improved in our study after two weeks of detoxification treatment. Sleep disturbances nevertheless persisted in almost two-thirds of the patients. In the view of that finding, patients may require individual evaluation of sleep quality and insomnia-specific treatment in the course of detoxification therapy.
Hypermethylation of SHISA3 Promotes Nasopharyngeal Carcinoma Metastasis by Reducing SGSM1 Stability
Authors: Zhang Jian , Li Ying-Qin , Guo Rui , Wang Ya-Qin , Zhang Pan-Pan , Tang Xin-Ran , Wen Xin , Hong Xiao-Hong , Lei Yuan , He Qing-Mei , Yang Xiao-Jing , Sun Ying , Ma Jun , Liu Na
Published: December 2018

Altered DNA methylation is a key feature of cancer, and aberrant methylation is important in nasopharyngeal carcinoma (NPC) development. However, the methylation mechanisms underlying metastasis of NPC remain unclear. Analyzing data from public databases and conducting our own experiments, we report here that promoter hypermethylation of SHISA3 is common and contributes to the downregulation of this gene in many types of tumors, including NPC. SHISA3 suppressed NPC cell invasion and metastasis in vitro and in vivo by impeding the E3 ubiquitin ligase tripartite motif containing 21 (TRIM21)–mediated ubiquitination and degradation small G protein signaling modulator 1 (SGSM1) and by inhibiting the MAPK pathway activation. Silencing SGSM1 abrogated the inhibitory effect of SHISA3 on NPC cell migration and invasion. This newly identified SHISA3–TRIM21–SGSM1 axis could be a novel therapeutic target in NPC.

Significance:

These findings highlight the mechanism by which a newly identified tumor suppressor SHISA3 suppresses invasion and metastasis of nasopharyngeal carcinoma.
Towards Greater Inclusion in Cancer Genomics Studies
Authors: Huang Franklin W.
Published: December 2018

The study by Jaratlerdsiri and colleagues represents the first whole-genome sequencing study of prostate cancer from men in sub-Saharan Africa. Preliminary findings include a higher tumor mutation burden in these tumors compared with data from other available prostate cancer cohorts. Although larger studies are needed and greater effort and investment to include patients of African ancestry in cancer genomic studies overall, the findings begin to catalog the diversity of prostate cancer genomics in the African population, which has a high burden of disease and mortality from prostate cancer.

See related article by Jaratlerdsiri et al., p. 6736
A Pilot Trial of the Combination of Transgenic NY-ESO-1–reactive Adoptive Cellular Therapy with Dendritic Cell Vaccination with or without Ipilimumab
Authors: Nowicki Theodore S. , Berent-Maoz Beata , Cheung-Lau Gardenia , Huang Rong Rong , Wang Xiaoyan , Tsoi Jennifer , Kaplan-Lefko Paula , Cabrera Paula , Tran Justin , Pang Jia , Macabali Mignonette , Garcilazo Ivan Perez , Carretero Ignacio Baselga , Kalbasi Anusha , Cochran Alistair J. , Grasso Catherine S. , Hu-Lieskovan Siwen , Chmielowski Bartosz , Comin-Anduix Begoña , Singh Arun , Ribas Antoni
Published: December 2018

Purpose:

Transgenic adoptive cell therapy (ACT) targeting the tumor antigen NY-ESO-1 can be effective for the treatment of sarcoma and melanoma. Preclinical models have shown that this therapy can be improved with the addition of dendritic cell (DC) vaccination and immune checkpoint blockade. We studied the safety, feasibility, and antitumor efficacy of transgenic ACT with DC vaccination, with and without CTLA-4 blockade with ipilimumab.

Patients and Methods:

Freshly prepared autologous NY-ESO-1–specific T-cell receptor (TCR) transgenic lymphocytes were adoptively transferred together with NY-ESO-1 peptide-pulsed DC vaccination in HLA-A2.1–positive subjects alone (ESO, NCT02070406) or with ipilimumab (INY, NCT01697527) in patients with advanced sarcoma or melanoma.

Results:

Six patients were enrolled in the ESO cohort, and four were enrolled in the INY cohort. Four out of six patients treated per ESO (66%), and two out of four patients treated per INY (50%) displayed evidence of tumor regression. Peripheral blood reconstitution with NY-ESO-1–specific T cells peaked within 2 weeks of ACT, indicating rapid in vivo expansion. Tracking of transgenic T cells to the tumor sites was demonstrated in on-treatment biopsies via TCR sequencing. Multiparametric mass cytometry of transgenic cells demonstrated shifting of transgenic cells from memory phenotypes to more terminally differentiated effector phenotypes over time.

Conclusions:

ACT of fresh NY-ESO-1 transgenic T cells prepared via a short ex vivo protocol and given with DC vaccination, with or without ipilimumab, is feasible and results in transient antitumor activity, with no apparent clinical benefit of the addition of ipilimumab. Improvements are needed to maintain tumor responses.
CD33 in Alzheimer’s Disease – Biology, Pathogenesis, and Therapeutics: A Mini-Review
Authors: Zhao Lingzhi
Published: December 2018

Alzheimer’s disease (AD) affects nearly 50 million people worldwide, and currently no disease-modifying treatment is available. With continuous failure of anti-amyloid-beta- or tau-based therapies, identification of new targets has become an urgent necessity for AD prevention and therapy. Recently, conventional genetic approaches and computational strategies have converged on immune-inflammatory pathways as key events in the pathogenesis of AD. A number of genes have been highly linked to the onset and development of late-onset sporadic AD, the most common form of AD. Strikingly, most of these genes are involved in microglial biology. Mutations and/or differential expression of microglial receptors such as TREM2, CD33, and CR3 have been strongly associated with an increased risk of developing AD. The mechanistic actions of these risk factors in AD etiology have been actively investigated since they were identified. Whether these genes can be targeted for a disease-modifying treatment is under hot debate. CD33 is one of the top-ranked AD risk genes identified by genome-wide association studies. This review summarizes the recently advanced biology of CD33 and its association with AD. It also provides insights from a drug discovery perspective into the druggability, therapeutic strategies, and challenges to target CD33 for treating this devastating disorder.
Endoscopic Full-Thickness Resection of Colorectal Lesions with the New FTRD System: Single-Center Experience
Authors: Mão de-Ferro Susana , Castela Joana , Pereira Daniela , Chaves Paula , Dias Pereira António
Published: December 2018

Background and Aims: Endoscopic full-thickness resection (EFTR) is an emerging technique for the treatment of various conditions for which classic endoscopic resection techniques have failed or were considered to be at high risk for perforation. The full-thickness resection device (FTRD) is an over-the-scope system which allows a single-step EFTR. The aim of our study is to describe our experience in EFTR of colorectal lesions using the FTRD. Methods: Nine patients (10 colorectal lesions) were proposed for EFTR. Safety, R0 resection and endoscopic treatment success were evaluated. Results: Reasons for referral included nonlifting adenomas (n = 4), nonlifting adenoma recurrence (n = 5), and submucosal lesion (n = 1). EFTR was technically successful in all patients. The mean duration of the procedure was 55 min. R0 resection was obtained in all patients. No major complications were detected. All lesions were successfully treated by the endoscopic technique and no patient was referred for surgery. In patients with available follow-up (n = 6), no recurrence was detected. Conclusions: EFTR is a feasible, reasonable time-consuming, safe, and promising endoscopic resection technique. Key Messages: FTRD is an additional tool for difficult-to-treat colorectal lesions.
Cubilin Single Nucleotide Polymorphism Variants are Associated with Macroangiopathy While a Matrix Metalloproteinase-9 Single Nucleotide Polymorphism Flip-Flop may Indicate Susceptibility of Diabetic Nephropathy in Type-2 Diabetic Patients
Authors: Albert Christian , Kube Johanna , Albert Annemarie , Schanze Denny , Zenker Martin , Mertens Peter R.
Published: December 2018

Aim: Aim of this study was to investigate the association of genetic variants of functional polymorphisms of matrix metalloproteinase and Cubilin (CUBN) with diabetic nephropathy (DN), end-stage renal disease (ESRD), and risk of cardiovascular disease (CVD) in Caucasian type 2 diabetes (T2D) patients. Methods: 472 T2D-patients were genotyped for 3 single-nucleotide polymorphisms (SNPs; MMP-2 [rs2285053], MMP-9 [rs17576] and CUBN [rs1801239]). Genotyping was carried out by allelic discrimination using TaqMan SNP-genotyping-assay. Results: MMP-9 (Gln279Arg) AA-genotype (OR 0.17 [0.04–0.62, p = 0.008]) and the time elapsed since diagnosis of T2D without onset of proteinuria (OR 0.87 [0.79–0.97, p = 0.008]) were found to be independently associated with reduced risk of susceptibility to DN. On the contrary higher stages of chronic kidney disease (OR 1.93 [1.15–3.23], p = 0.012) and the presence of MMP-9 GG-genotype were independently associated with DN (OR 6.07 [1.60–22.99], p = 0.008). The CUBN CC or C-risk-allele of rs1801239 was associated with ESRD (OR 2.04 [1.07–3.87], p = 0.03) and peripheral artery disease (OR 2.08 [1.12–3.88], p = 0.021). We could not find an association with MMP-2, MMP-9, or CUBN with CVD in a composite clinical endpoint model. Conclusions: This study highlights that MMP-9 or CUBN-SNPs may exert effects on risk of susceptibility to DN or ESRD. We provide novel evidence on genetic susceptibility for macroangiopathy in patients with a missense variant of CUBN (Ile2984Val) in patients with T2D.
Cloacal Anomalies in Monoamniotic, Monochorionic Twins with Complete Urinary Tract Obstruction
Authors: Shields Lisa B.E. , Peppas Dennis S. , Rosenberg Eran
Published: December 2018

Cloacal anomalies (persistent cloaca) represent the most severe form of anorectal malformations in girls where the rectum, urethra, and vagina remain fused together inside the pelvis and drain into a single common perineal orifice. Infants with cloacal anomalies often succumb to poor lung development due to oligohydramnios. Cloacal anomaly in discordant monozygotic twins has rarely been reported in the literature. In this review, we present the first case of persistent cloaca and complete urinary tract obstruction in discordant monoamniotic twins.
Extending the Phenotype and Identification of a Novel Candidate Gene for Immunodeficiency in 5q11 Microdeletion Syndrome
Authors: Arora Veronica , Aggarwal Shruti , Bijarnia Sunita , Lall Meena , Joshi Anju , Dua-Puri Ratna , Arora Umang , Verma Ishwar
Published: December 2018

Array CGH has led to the delineation of innumerable microdeletion syndromes. We present a patient with a 7-Mb deletion at 5q11.2 with previously unreported features, such as immunodeficiency, asymmetry of hands and feet, joint laxity, and agenesis of corpus callosum. The clinical features of this patient are compared with 13 patients reported previously. A common critical region (CCR) of 1.4 Mb (54-55.4 Mb) is defined in all cases including the present one. Of the 14 genes present in CCR, IL6ST is proposed to be the candidate gene for immunodeficiency observed in some of these patients. IL6ST encodes gp130, a signal transduction protein for various interleukins and cytokines. It is involved in the generation of both T and B lymphocytes as well as the production of acute-phase reactants. Microdeletion 5q11.2 should be considered as a recognisable syndrome based on the common phenotype and the novel features described.
Vaccination and Host Marek's Disease-Resistance Genotype Significantly Reduce Oncogenic Gallid alphaherpesvirus 2 Telomere Integration in Host Birds
Authors: McPherson Marla C. , Cheng Hans H. , Smith Justin M. , Delany Mary E.
Published: December 2018

Marek's disease (MD) is an infectious disease characterized by lymphomas and high mortality in susceptible chickens. The causative and ubiquitous alpha-herpesvirus known as MD virus (MDV) integrates into host telomeres during early infection through latency, known to be an important phase for oncogenic transformation. Herein, we sought to determine the influence of vaccination and host genetics on the temporal dynamics of MDV-host genome interactions. We studied integration profiles using 2 MD vaccines that vary in protective efficacy in 2 genetic lines that differ in MD resistance/susceptibility. Virus integration of both oncogenic MDV and vaccine strains was observed in both MD susceptible and resistant birds, however, the lines differed in their dynamic telomere-integration profiles. Notably, the resistant host genotype exhibited a smaller percentage of replicating cells with the virus telomere-integrated only phenotype as compared to the susceptible genotype. Vaccination with Rispens, the most protective MD vaccine, also reduced the establishment of the virus telomere-integrated only phenotype, suggesting a significant role of the phenotype in MD lymphoma development. The effect of Rispens vaccination was most dramatic in the susceptible genotype. These results suggest important connections between vaccinal immunity, MDV telomere integration, virus-induced oncogenesis, and virus-host genome interactions in the context of host genetics and disease susceptibility.
Loss of Transfected Human Brain Micro-Vascular Endothelial Cell Integrity during Herpes Simplex Virus Infection
Authors: Lee Sau Har , Atiya Nadia , Wang Seok Mui , Manikam Rishya , Raju Chandramathi Samudi , Sekaran Shamala Devi
Published: December 2018

Objective: Herpes simplex virus infection through the neuronal route is the most well-studied mode of viral encephalitis that can persists in a human host for a lifetime. However, the involvement of other possible infection mechanisms by the virus remains underexplored. Therefore, this study aims to determine the temporal effects and mechanisms by which the virus breaches the human brain micro-vascular endothelial cells of the blood-brain barrier. Method: An electrical cell-substrate impedance-sensing tool was utilized to study the real-time cell-cell barrier or morphological changes in response to the virus infection. Results: Herpes simplex virus, regardless of type (i.e., 1 or 2), reduced the cell-cell barrier resistance almost immediately after virus addition to endothelial cells, with negligible involvement of cell-matrix adhesion changes. There is no exclusivity in the infection ability of endothelial cells. From 30 h after HSV infection, there was an increase in cell membrane capacitance with a subsequent loss of cell-matrix adhesion capability, indicating a viability loss of the infected endothelial cells. Conclusion: This study shows for the first time that destruction of human brain micro-vascular endothelial cells as an in vitro model of the blood-brain barrier could be an alternative invasion mechanism during herpes simplex virus infection.
Three-Dimensional Remnant Pancreatic Volumetry Predicts Postoperative Pancreatic Fistula in Pancreatic Cancer Patients after Pancreaticoduodenectomy
Authors: Miyamoto Ryoichi , Oshiro Yukio , Sano Naoki , Inagawa Satoshi , Ohkohchi Nobuhiro
Published: December 2018

Background: Postoperative pancreatic fistula (POPF) is a serious complication that can occur following pancreaticoduodenectomy (PD). Recent studies suggest that remnant pancreatic volume (RPV) values from preoperative multidetector computed tomography (MDCT) are highly predictive of POPF. We performed three-dimensional (3D) surgical simulation of PD including RPV measurements. The aim of this study was to determine whether 3D-measured RPV is predictive of POPF after PD. Methods: We used the SYNAPSE VINCENT® medical imaging system (Fujifilm Medical Co., Ltd., Tokyo, Japan) to construct 3D images after integrating MDCT and magnetic resonance cholangiopancreatography images. RPV was measured using this 3D image, which simulated actual intraoperative pancreatic parenchymal remnant volume. Ninety-one patients who underwent PD were retrospectively enrolled. Using multivariate analysis, RPV and other well-known POPF risk factors were independently assessed. Results: Multivariate analysis identified high RPV values (hazard ratio [HR] = 8.41, p = 0.01), pancreatic duct diameter < 3.0 mm (HR = 5.48, p < 0.01), no pathological fibrosis (HR = 3.41, p < 0.01), and body mass index > 25 kg/m2 (HR = 1.53, p = 0.02) as independent risk factors for POPF. Conclusion: The present study indicates that preoperative 3D-measured RPV is predictive of POPF after PD.
Septic Shock Predisposed by an Underlying Chronic Neutrophilic Leukemia with an Atypical Presentation; A Case Report
Authors: Mendiola Vincent Louie , Qian You-Wen , Jana Bagi
Published: December 2018

Background: Chronic neutrophilic leukemia (CNL) is an extremely rare myeloproliferative neoplasm (MPN). Due to the difficulty in its diagnosis, the diagnostic criterion was just recently revised in 2016. CNL is defined as: A clonal disorder with sustained primary neutrophilia, with normal neutrophil maturation, that does not meet other MPN criteria, as well as no identifiable mutations of the PDGFRA, PDGFRB or FGFR1 or PCM1-JAK2 genes, and, either, the presence of a CSF3R mutation, or if absent, the presence of sustained neutrophilia (> 3 months), splenomegaly and no other identifiable cause of reactive neutrophilia including the absence of a plasma cell neoplasm, or, if present, demonstration of myeloid cell clonality by cytogenetics. Only about 200 cases have been reported. Case Presentation: We report a 61-year-old Caucasian male patient who initially presented with unexplained leukocytosis. An outpatient work-up was planned to rule out a myeloproliferative disorder but the patient was acutely admitted for MRSA septic shock. The patient was stabilized prior bone marrow work-up and was then diagnosed with an atypical type of CNL (JAK2 positive, CSF3R negative). The patient refused further treatment due to social circumstances and requested palliative care instead. Conclusion: This case aims to present atypical findings of an extremely rare MPN. Even though a recent revision has been made to help in its diagnosis, atypical findings must still be considered. This, in turn, will help to further improve the current CNL diagnostic criteria.
A Matched Analysis on the Prognostic Impact of Race on Survival Endpoints of Women with Early-Stage Endometrial Cancer
Authors: Feldman Aharon , Chaugle Sadaf , Burmeister Charlotte , Munkarah Adnan , Elshaikh Mohamed A.
Published: December 2018

Objective: To compare survival endpoints between African American (AA) and non-AA (NAA) women with endometrial carcinoma (EC) stage I–II using a robust matching analysis. Methods and Materials: Patients were matched by stage, grade, adjuvant management (surveillance, vaginal brachytherapy or pelvic radiation treatment), age, and year of hysterectomy. Recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) were calculated. Results: A total of 758 patients were included. Body mass index and Age-Adjusted Charlson comorbidity index was significantly higher in AA compared to NAA women. There were no significant differences between the AA and NAA groups in regard to 5-year RFS (94 vs. 93%), DSS (96 vs. 98%) or 5-year OS (90 vs. 92%). On multivariate analysis of survival endpoints for the entire study cohort, it was found that race (AA vs. NAA) was not a significant predictor of RFS, DSS, or OS. Grade 3 tumors and the presence of lymphovascular space invasion (LVSI) were the only 2 independent predictors of RFS and DSS, while age-adjusted Charlson comorbidity score, grade 3, stage II and the presence of LVSI were independent predictors of shorter OS. Conclusions: When matched based on the tumor stage, grade, adjuvant treatment, age, and year of surgery, our study suggests that there is no statistically significant difference in any survival endpoints between AA and NAA women with early-stage EC. Based on these data, disparities in outcome likely do not stem from uterine cancer-related causes. The increased comorbidity burden in AA women is likely a factor contributing to the racial disparity in endometrial cancer.
Young-Onset Dementia with Lewy Bodies
Authors: Aiba Yosuke , Sakakibara Ryuji , Ogata Tsuyoshi , Iimura Ayako , Terayama Keiichiro , Suzuki Keiko , Katsuragawa Shuichi , Kato Yuuki , Tateno Fuyuki , Terada Hitoshi , Inaoka Tsutomu , Nakatsuka Tomoya
Published: December 2018

Young-onset (< 65 years) dementia is a challenging clinical problem. A 61-year-old man visited our clinic because of a 2-year history of mild cognitive impairment of the executive disorder type. He was initially suspected of having young-onset Alzheimer’s disease due to the lack of motor signs or hippocampal atrophy by conventional brain MRI. However, he proved to have anosmia, erectile dysfunction, hypersexuality, constipation, REM sleep behavior disorder, and emotional lability; imaging findings included positive brain perfusion SPECT, nigrosome MRI, DAT scan, and MIBG myocardial scintigraphy. All these clinical imaging features led to the correct diagnosis of young-onset dementia with Lewy bodies (YOD-DLB). It is hoped that this case report will help facilitate a future prospective study to diagnose and follow YOD-DLB patients with the aim of determining appropriate management and care.
Combined Phenotypes of Spondylometaphyseal Dysplasia-Kozlowski Type and Charcot-Marie-Tooth Disease Type 2C Secondary to a TRPV4 Pathogenic Variant
Authors: Faye Eden , Modaff Peggy , Pauli Richard , Legare Janet
Published: December 2018

TRPV4, a nonselective calcium permeable ion channel, is expressed broadly in many organs including bone and neurons. Pathogenic variants in TRPV4 are known to cause both a spectrum of skeletal dysplasias and neuropathies. Recent publications have documented a few patients who have a combined phenotype of skeletal dysplasia and neuropathy secondary to TRPV4 pathogenic variants. We present an additional patient who has an overlapping neuromuscular and skeletal phenotype secondary to a TRPV4 pathogenic variant. The patient has spondylometaphyseal dysplasia-Kozlowski type and Charcot-Marie-Tooth disease type 2C. This and prior reports illustrate that TRPV4-related skeletal dysplasias and TRPV4-related neuropathies are not fully distinct disorders secondary to unique sets of pathogenic variants as originally postulated, but rather are 2 phenotypes on the same spectrum that may or may not overlap. We suggest that evaluation for patients presenting with any TRPV4-related disorder include assessment for both skeletal and neurological findings.
Chronic Stress Combined with a Fructose Diet Reduces Hypothalamic Insulin Signaling and Antioxidative Defense in Female Rats
Authors: Kovačević Sanja , Nestorov Jelena , Matić Gordana , Elaković Ivana
Published: December 2018

Background: Increased fructose consumption and chronic exposure to stress have been associated with the development of obesity and insulin resistance. In the hypothalamus, a crossroad of stress responses and energy balance, insulin and glucocorticoids regulate the expression of orexigenic neuropeptides, neuropeptide Y (NPY) and agouti-related protein (AgRP), and anorexigenic neuropeptides, proopio­melanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART). Objectives: We investigated whether chronic stress and fructose diet disrupt these hormonal signaling pathways and appetite control in the hypothalamus, contributing to the development of insulin resistance and obesity. Potential roles of hypothalamic inflammation and oxidative stress in the development of insulin resistance were also analyzed. Methods: Insulin, glucocorticoid, and leptin signaling, expression of orexigenic and anorexigenic neuropeptides, and antioxidative and inflammatory statuses in the whole hypothalamus of fructose-fed female rats exposed to unpredictable stress for 9 weeks were analyzed using quantitative PCR and Western blotting. Results: Chronic stress combined with a fructose-enriched diet reduced protein content and stimulatory phosphorylation of Akt kinase, and elevated 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor expression, while alterations in appetite regulation (NPY, AgRP, POMC, CART, leptin receptor, and SOCS3 expression) were not observed. The expression of antioxidative defense enzymes (mitochondrial manganese superoxide dismutase 2, glutathione reductase, and catalase) and proinflammatory cytokines (IL-1β, IL-6, and TNFα) was reduced. Conclusions: Our results underline the combination of long-term stress exposure and fructose overconsumption as more detrimental for hypothalamic function than for either of the factors separately, as it enhanced glucocorticoid and impaired insulin signaling, antioxidative ­defense, and inflammatory responses of this homeostasis- regulating center.
Bridging the Gap between Brain-Derived Neurotrophic Factor and Glucocorticoid Effects on Brain Networks
Authors: Jeanneteau Freddy , Borie Amélie , Chao Moses V. , Garabedian Michael J.
Published: December 2018

Behavioral choices made by the brain during stress depend on glucocorticoid and brain-derived neurotrophic factor (BDNF) signaling pathways acting in synchrony in the mesolimbic (reward) and corticolimbic (emotion) neural networks. Deregulated expression of BDNF and glucocorticoid receptors in brain valuation areas may compromise the integration of signals. Glucocorticoid receptor phosphorylation upon BDNF signaling in neurons represents one mechanism underlying the integration of BDNF and glucocorticoid signals that when off balance may lay the foundation of maladaptations to stress. Here, we propose that BDNF signaling conditions glucocorticoid responses impacting neural plasticity in the mesocorticolimbic system. This provides a novel molecular framework for understanding how brain networks use BDNF and glucocorticoid signaling contingencies to forge receptive neuronal fields in temporal domains defined by behavioral experience, and in mood disorders.
Acervo de pesquisa, memórias e mulheres
Authors: Silva Janine Gomes da , Pedro Joana Maria , Wolff Cristina Scheibe
Published: December 2018

Este artigo apresenta a trajetória do Laboratório de Estudos de Gênero e História – LEGH, da Universidade Federal de Santa Catarina, bem como discute a importânciade acervos acadêmicos de pesquisa para contribuir na disseminação de informações sobre o período das ditaduras civil-militares do Cone Sul. Todo o material coletado sobre gênero, feminismos e ditaduras no Brasil, Argentina, Paraguai, Uruguai, Bolívia e Chile, vem propiciando várias análises, utilizandose das mais variadas fontes documentais e possibilitando um estudo comparativo a partir de diferentes pesquisas.
Mujeres y patrimonio cultural
Authors: Vassallo Jaqueline
Published: December 2018

Neste artigo, pretendemos refletir sobre as estratégias desenvolvidas pelo feminismo em relação à problematização, avaliação, visibilidade e institucionalização do patrimônio cultural das mulheres. Procuramos dar exemplos concretos de algumas estratégias elaboradas pelo feminismo acadêmico que foram seguidas por um grupo de arquivistas argentinos para a identificação de documentos relacionados com e sobre as mulheres, no Arquivo Geral e Histórico da Universidade Nacional de Córdoba e na Biblioteca da Faculdade de Filosofia e Ciências Humanas da referida Universidade, tanto na elaboração de instrumentos descritivos como na organização de arquivos pessoais.