bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of Probe-based Confocal Laser Endomicroscopy (pCLE) Criteria for Diagnosing Colon Polyp Histology
Authors: Vennelaganti Sreekar , Vennalaganti Prashanth , Mathur Sharad , Singh Satish , Jamal Mazen , Kanakadandi Vijay , Rai Tarun , Hall Matthew , Gupta Neil , Nutalapati Venkat , Alsop Benjamin , Hornung Benjamin , Sharma Prateek
Published: September 2017

Background:

Validated probe-based confocal endomicroscopy (pCLE) criteria for distinguishing hyperplastic polyps (HPs) and tubular adenomas (TA) have not yet been developed.

Aim:

To develop pCLE criteria for distinguishing HP from TA and evaluate its performance characteristics among experts.

Methods:

pCLE criteria for colon polyp histology were developed and tested in 2 phases prospectively. Phase I: 8 preliminary criteria were developed and tested internally. Criteria achieving an accuracy of >75% (epithelial surface: regular vs. irregular; goblet cells: increased vs. decreased; gland axis: horizontal vs. vertical; gland shape: slit/stellate vs. villiform; image scale: gray vs. dark) were evaluated in Phase II of study wherein external assessors evaluated these criteria in a separate set of pCLE videos. Accuracy and interobserver agreement (95% confidence intervals) were determined for colon histology prediction.

Results:

Phase I (criteria development/internal testing): 8 criteria were assessed by 4 pCLE experts using 28 videos (14 HP/14 TA). Five of 8 pCLE criteria met selection for phase II (accuracy >75%). Phase II (external validation): 36 pCLE colon polyp videos (HP 16/TA 20) were evaluated by 8 external assessors. Overall accuracy in diagnosis of colon polyp histology was 84.9% (95% confidence interval, 81.7-87.7). Of predictions made with high confidence (75%), histology was predicted with an accuracy of 91%, sensitivity 83%, specificity 100%, negative predictive value 87% and positive predictive value 98%. Interobserver agreement was substantial (κ=0.73).

Conclusions:

We demonstrate the development and validation of pCLE criteria for prediction of colon polyp histology. Using these criteria, overall accuracy in differentiating TA from HP was high with substantial interobserver agreement.
Surgical Treatment of Nonsyndromic Craniosynostosis
Authors: Klement Kristen A. , Adamson Karri A. , Horriat Narges L. , Denny Arlen D.
Published: September 2017

Studies on the treatment of nonsyndromic craniosynostosis demonstrate decreasing morbidity and mortality; however, complication rates still range from 5% to 14%. Here, the authors present their last 10 years’ experience treatment of nonsyndromic single suture craniosynostosis. A retrospective review was performed on patients who underwent open surgical treatment of nonsyndromic craniosynostosis over 10 years. Patient characteristics and clinical outcomes were reviewed. Radiological analysis of intracranial volumes was performed using Amira software. The authors’ technique for treatment of sagittal synostosis was the Foreshortening and Lateral Expansion of the Cranium Activated by Gravity (FLAG) procedure. The authors identified 106 patients with a median age of 0.8 years. Sagittal synostosis was most common (n = 65, 61%). Seventeen percent underwent distraction of the cranial vault; the remainder underwent traditional remodeling procedures. The average operative time was 131 minutes, blood loss was 296 mL (30 mL/kg), and intraoperative transfusion was 332 mL (34 mL/kg). There were 2 postoperative complications. Six patients required an additional major operation years later, most commonly for increased intracranial pressure. The authors separately analyzed 50 patients with sagittal synostosis treated with the FLAG procedure. There were no postoperative complications, and only 4 patients required reoperation. The average operative time for the FLAG procedure was 97.3 minutes. Intracranial volume increased by 191.45 mL (28.3–427.5 mL) with 28% average relative cranial vault expansion (4.5%–93.2%). Surgical correction of craniosynostosis using the FLAG technique is safe and effective with minimal morbidity and long standing results. Treatment should involve a structured approach, which minimizes operative times and decreases complication rates.
Laparoscopic Procedure is Not Independently Associated With the Development of Intra-Abdominal Abscess After Appendectomy: A Multicenter Cohort Study With Propensity Score Matching Analysis
Authors: Cao Jianguo , Tao Feng , Xing Hao , Han Jun , Zhou Xiaojun , Chen Tinghao , Wang Hong , Li Zhizhou , Zhou Yahao , Wang Shusheng , Yang Tian
Published: September 2017

Aim:

The aim of this study was to identify independent risk factors for postoperative intra-abdominal abscess (IAA) after appendectomy for patients with acute appendicitis.

Backgraound:

Although laparoscopic appendectomy (LA) has been performed universally, whether LA is associated with an increased incidence of postoperative IAA compared with open appendectomy (OA) remains controversial, which causes some surgeons’ increasing concerns.

Methods:

We retrospectively analyzed 6805 consecutive adult patients with acute appendicitis who underwent LA or OA at 7 general hospitals in China. Patient characteristics, operative variables, and surgical outcomes were collected and compared between patients who underwent LA and OA. Propensity score matching analysis was used to minimize the bias in patient selection differing from various procedure of appendectomy. Independent risk factors associated with the development of postoperative IAA after appendectomy were identified by univariate and multivariate logistic regression analysis in the propensity matched cohort.

Results:

Over a 3-year period, 2710 (39.8%) and 4095 (60.2%) patients underwent LA and OA respectively. Patients who underwent OA had more males, American Society of Anesthesiologists score 2-3, preoperative systemic inflammatory response syndrome, and perforated appendicitis than those who underwent LA (allP<0.01). Propensity score matched analysis created 2542 pairs of patients. Univariate analysis revealed that patients who underwent LA had a higher incidence of postoperative IAA than patients who underwent OA (6.7% vs. 5.3%;P=0.039). However, multivariate logistic regression analysis identified LA not to be an independent risk factor associated with the development of postoperative IAA (odds ratio, 1.053; 95% confidence interval, 0.922-1.657;P=0.216).

Conclusions:

The present study identified that laparoscopic procedure was not an independent risk factor associated with the development of postoperative IAA after appendectomy of acute appendicitis. Therefore, concerns of increased incidence of IAA because of laparoscopic procedure are unwarranted.
Denitrifying metabolism of the methylotrophic marine bacteriumMethylophaga nitratireducenticrescensstrain JAM1
Authors: Mauffrey Florian , Cucaita Alexandra , Constant Philippe , Villemur Richard
Published: September 2017

Methylophaga nitratireducenticrescensstrain JAM1 is a methylotrophic, marine bacterium that was isolated from a denitrification reactor treating a closed-circuit seawater aquarium. It can sustain growth under anoxic conditions by reducing nitrate (NO3−) to nitrite (NO2−), which accumulates in the medium. These physiological traits are attributed to gene clusters that encode two dissimilatory nitrate reductases (NarGHJI). M.nitratireducenticrescensstrain JAM1 also contains gene clusters encoding two putative nitric oxide reductase (NO) reductases and one putative nitrous oxide (N2O) reductase, suggesting that NO and N2O can be reduced by strain JAM1. In this study, we show that strain JAM1 can reduce NO to N2O and N2O to N2 and can sustain growth under anoxic conditions by reducing N2O as the sole electron acceptor. Although strain JAM1 lacks a gene encoding a dissimilatory copper-(NirK) or cytochrome cd1-type (NirS) NO2−reductase, NO3−-amended strain JAM1 cultures produce N2O, representing up to 6% of the N-input. NO2−was shown to be the key intermediate of this production process. In NO3−amended cultures, we analyzed denitrification genes in succession of net N2O-production and -consumption phases at the gene expression level. These phases were found to correlate with changes in the expression levels of the NO reductase genecnorB1andnnrS, which indicated NO production in the cultures.

Importance

By showing that all the three denitrification reductases are active, this demonstrates thatMethylophaga nitratireducenticrescensJAM1 is one of many bacteria species that maintain genes associated primarily with denitrification, but not necessarily related to the maintenance of the entire pathway. The reason to maintain such incomplete pathway could be related to the specific role of strain JAM1 in the denitrifying biofilm of a denitrification reactor from which it originates. The small production of N2O via NO in strain JAM1 did not involve Nar contrary to what was demonstrated inEscherichia coli. M. nitratireducenticrescensJAM1 is the only reportedMethylophagaspecies that has the capacity to grow under anoxic conditions by using NO3−and N2O as sole electron acceptors for its growth. It is also one of a few marine methylotrophs that is studied at the physiological and genetic levels in relation to its capacity to perform denitrifying activities.
Chromatin organization changes during the establishment and maintenance of the postmitotic state
Authors: Ma Yiqin , Buttitta Laura
Published: September 2017

Background

Genome organization changes during development as cells differentiate. Chromatin motion becomes increasingly constrained and heterochromatin clusters as cells become restricted in their developmental potential. These changes coincide with slowing of the cell cycle, which can also influence chromatin organization and dynamics. Terminal differentiation is often coupled with permanent exit from the cell cycle and existing data suggests a close relationship between a repressive chromatin structure and silencing of the cell cycle in postmitotic cells. Here we examine the relationship between chromatin organization, terminal differentiation and cell cycle exit.

Results

We focused our studies on theDrosophilawing, where epithelial cells transition from active proliferation to a postmitotic state in a temporally controlled manner. We find there are two stages of G0in this tissue, a flexible G0period where cells can be induced to re-enter the cell cycle under specific genetic manipulations and a state we call “robust”, where cells become strongly refractory to cell cycle re-entry. Compromising the flexible G0by driving ectopic expression of cell cycle activators causes a global disruption of the clustering of heterochromatin-associated histone modifications such as H3K27 trimethylation and H3K9 trimethylation, as well as their associated repressors, Polycomb and heterochromatin protein 1(HP1). However, this disruption is reversible. When cells enter a robust G0state, even in the presence of ectopic cell cycle activity, clustering of heterochromatin associated modifications are restored. If cell cycle exit is bypassed, cells in the wing continue to terminally differentiate, but heterochromatin clustering is severely disrupted. Heterochromatin-dependent gene silencing does not appear to be required for cell cycle exit, as compromising the H3K27 methyltransferaseEnhancer of zeste, and/or HP1 cannot prevent the robust cell cycle exit, even in the face of normally oncogenic cell cycle activities.

Conclusions

Heterochromatin clustering during terminal differentiation is a consequence of cell cycle exit, rather than differentiation. Compromising heterochromatin-dependent gene silencing does not disrupt cell cycle exit.
Identification of novel rare sequence variation underlying heritable pulmonary arterial hypertension
Authors: Gräf Stefan , Haimel Matthias , Bleda Marta , Hadinnapola Charaka , Southgate Laura , Li Wei , Hodgson Joshua , Liu Bin , Salmon Richard M. , Southwood Mark , Machado Rajiv D. , Martin Jennifer M. , Treacy Carmen M. , Yates Katherine , Daugherty Louise C. , Shamardina Olga , Whitehorn Deborah , Holden Simon , Aldred Micheala , Bogaard Harm J. , Church Colin , Coghlan Gerry , Condliffe Robin , Corris Paul A. , Danesino Cesare , Eyries Mélanie , Gall Henning , Ghio Stefano , Ghofrani Hossein-Ardeschir , Gibbs J. Simon R. , Girerd Barbara , Houweling Arjan C. , Howard Luke , Humbert Marc , Kiely David G. , Kovacs Gabor , MacKenzie Ross Robert V. , Moledina Shahin , Montani David , Newnham Michael , Olschewski Andrea , Olschewski Horst , Peacock Andrew J. , Pepke-Zaba Joanna , Prokopenko Inga , Rhodes Christopher J. , Scelsi Laura , Seeger Werner , Soubrier Florent , Stein Dan F. , Suntharalingam Jay , Swietlik Emilia , Toshner Mark R. , Vonk Noordegraaf Anton , van Heel David A. , Waisfisz Quinten , Wharton John , Wort Stephen J. , Ouwehand Willem H. , Soranzo Nicole , Lawrie Allan , Upton Paul D. , Wilkins Martin R. , Trembath Richard C. , Morrell Nicholas W.
Published: September 2017

Pulmonary arterial hypertension (PAH) is a rare disorder with a poor prognosis. Deleterious variation within components of the transforming growth factor-β pathway, particularly the bone morphogenetic protein type 2 receptor (BMPR2), underlie most heritable forms of PAH. Since the missing heritability likely involves genetic variation confined to small numbers of cases, we performed whole genome sequencing in 1038 PAH index cases and 6385 PAH-negative control subjects. Case-control analyses revealed significant overrepresentation of rare variants in novel genes, namelyATP13A3, AQP1andSOX17, and provided independent validation of a critical role forGDF2in PAH. We provide evidence for familial segregation of mutations inSOX17andAQP1with PAH. Mutations inGDF2, encoding a BMPR2 ligand, led to reduced secretion from transfected cells. In addition, we identified pathogenic mutations in the majority of previously reported PAH genes, and provide evidence for further putative genes. Taken together these findings provide new insights into the molecular basis of PAH and indicate unexplored pathways for therapeutic intervention.
Global connectivity of the frontoparietal cognitive control network is related to depression symptoms in the general population
Authors: Schultz Douglas H. , Ito Takuya , Solomyak Levi I. , Chen Richard H. , Mill Ravi D. , Anticevic Alan , Cole Michael W.
Published: September 2017

We all vary in our mental health, even among people not meeting diagnostic criteria for mental illness. Understanding this individual variability may reveal factors driving the risk for mental illness, as well as factors driving sub-clinical problems that still adversely affect quality of life. To better understand the large-scale brain network mechanisms underlying this variability we examined the relationship between mental health symptoms and resting-state functional connectivity patterns in cognitive control systems. One such system is the frontoparietal cognitive control network (FPN). Changes in FPN connectivity may impact mental health by disrupting the ability to regulate symptoms in a goal-directed manner. Here we test the hypothesis that FPN dysconnectivity relates to mental health symptoms even among individuals who do not meet formal diagnostic criteria but may exhibit meaningful symptom variation. We found that depression symptoms severity negatively correlated with between-network global connectivity (BGC) of the FPN. This suggests that decreased connectivity between the FPN and the rest of the brain is related to increased depression symptoms in the general population. These findings complement previous clinical studies to support the hypothesis that global FPN connectivity contributes to the regulation of mental health symptoms across both health and disease.

AUTHOR SUMMARY

Understanding how large-scale network interactions in the brain contribute to (or serve a protective role against) mental health symptoms is an important step toward developing more effective mental health treatments. Here we test the hypothesis that cognitive control networks play an important role in mental health by being highly connected to other brain networks and able to serve as a feedback mechanism capable of regulating symptoms in a goal-directed manner. We found that the more well-connected the frontoparietal cognitive control network was to other networks in the brain the less depression symptoms were reported by participants. These results contribute to our understanding of how brain network interactions are related to mental health symptoms, even in individuals who have not been diagnosed with a disorder.
Development and control of a robotic arm for percutaneous surgery
Authors: Zhou Chunlin , Wu Huifeng , Xu Xiang , Liu Yong , Zhu Qi , Pan Shuwen
Published: September 2017

Purpose

The purpose of this paper is to propose a robotic system for percutaneous surgery. The key component in the system, a robotic arm that can manipulate a puncture needle is presented. The mechanical design, the motion control and the force control method of the robotic arm are discussed in the paper.

Design/methodology/approach

The arm with an arc mechanism placed on a 3D Cartesian stage is developed as a puncture needle manipulator to locate the position of the needle tip, tune the needle’s posture and actuate the puncture motion under the visual guidance of two orthogonal X-ray images of a patient by a surgeon. A focusing method by using two laser spots is proposed to automatically move the needle tip to a surgery entry point on the skin. A dynamics model is developed to control the position of the needle mechanism and an explicit force control strategy is utilized to perform the needle insertion.

Findings

With the surgical system, a surgeon can easily perform puncture operation by taking two orthogonal real-time X-ray images as a visual feedback and accurately navigating the needle insertion. The laser-guided focusing method is efficient in placement of the needle tip. The explicit force control strategy is proved to be effective for holding constant and stable puncture force in experiments.

Originality/value

The robotic arm has an advantage in easy redirection of the needle because the rotation and the translation are decoupled in the mechanism. By adopting simple laser pens and a well-developed kinematics model, the system can handle the entry point, locating task automatically. The focusing method and the force control method proposed in the paper are useful for the present system and could be intuitive for similar surgical robots.
Indices of anti‐dengue immunoglobulin G subclasses in adult Mexican patients with febrile and hemorrhagic dengue in the acute phase
Authors: Posadas‐Mondragón Araceli , Aguilar‐Faisal José Leopoldo , Chávez‐Negrete Adolfo , Guillén‐Salomón Edith , Alcántara‐Farfán Verónica , Luna‐Rojas Lucero , Ávila‐Trejo Amanda Marineth , del Carmen Pacheco‐Yépez Judith
Published: September 2017

Heterologous secondary infections are at increased risk of developing dengue hemorrhagic fever (DHF) because of antibody‐dependent enhancement (ADE). IgG subclasses can fix and activate complement and bind to Fcɣ receptors. These factors may also play an important role in the development of ADE and thus in the pathogenesis of DHF. The aim of this study was to analyze the indices of anti‐dengue IgG subclasses in adult patients with febrile and hemorrhagic dengue in the acute phase. In 2013, 129 patients with dengue fever (DF) and 57 with DHF in Veracruz, Mexico were recruited for this study and anti‐dengue IgM and IgG determined by capture ELISA. Anti‐dengue IgG subclasses were detected by indirect ELISA. Anti‐dengue IgG2 and IgG3 subclasses were detected in patients with dengue. IgG1 increased significantly in the sera of patients with both primary and secondary infections and DHF, but was higher in patients with secondary infections. The IgG4 subclass index was significantly higher in the sera of patients with DHF than in that of those with DF, who were in the early and late acute phase of both primary and secondary infection. In conclusion, indices of subclasses IgG1 and IgG4 were higher in patients with DHF.
The expression of Spodoptera exigua P450 and UGT genes: tissue specificity and response to insecticides
Authors: Hu Bo , Zhang Shu‐Heng , Ren Miao‐Miao , Tian Xiang‐Rui , Wei Qi , Mburu David Kibe , Su Jian‐Ya
Published: September 2017

Cytochrome P450 and UDP‐glucosyltransferase (UGT) as phase I and phase II metabolism enzymes, respectively, play vital roles in the breakdown of endobiotics and xenobiotics. Insects can increase the expression of detoxification enzymes to cope with the stress from xenobiotics including insecticides. However, the molecular mechanisms for insecticide detoxification in Spodoptera exigua remain elusive, and the genes conferring insecticide metabolisms in this species are less well reported. In this study, 68 P450 and 32 UGT genes were identified. Phylogenetic analysis showed gene expansions in CYP3 and CYP4 clans of P450 genes and UGT33 family of this pest. P450 and UGT genes exhibited specific tissue expression patterns. Insecticide treatments in fat body cells of S. exigua revealed that the expression levels of P450 and UGT genes were significantly influenced by challenges of abamectin, lambda‐cyhalothrin, chlorantraniliprole, metaflumizone and indoxacarb. Multiple genes for detoxification were affected in expression levels after insecticide exposures. The results demonstrated that lambda‐cyhalothrin, chlorantraniliprole, metaflumizone and indoxacarb induced similar responses in the expression of P450 and UGT genes in fat body cells; eight P450 genes and four UGT genes were co‐up‐regulated significantly, and no or only a few CYP/UGT genes were down‐regulated significantly by these four insecticides. However, abamectin triggered a distinct response for P450 and UGT gene expression; more P450 and UGT genes were down‐regulated by abamectin than by the other four compounds. In conclusion, P450 and UGT genes from S. exigua were identified, and different responses to abamectin suggest a different mechanism for insecticide detoxification.
Case series of pleomorphic carcinomas of the lung treated with nivolumab
Authors: Kanazu Masaki , Uenami Takeshi , Yano Yukihiro , Nakatsubo Saeko , Hosono Yuki , Ishijima Mikako , Akazawa Yuki , Yamaguchi Toshihiko , Urasaki Koji , Mori Masahide , Yokota Soichiro
Published: September 2017

Pleomorphic carcinoma (PC) of the lung is a rare type of non‐small cell lung cancer, exhibiting aggressive behavior and resistance to chemotherapy and radiotherapy. A previous study reported that PCs expressed high levels of PD‐L1, suggesting the potential efficacy of immune checkpoint inhibitors in these tumors. We retrospectively reviewed the clinical records of three patients with PC of the lung treated with nivolumab: a 59‐year‐old woman (Case 1), a 66‐year‐old man (Case 2), and an 83‐year‐old man (Case 3). PD‐L1 was highly expressed in their tumor cells. Two cases showed a partial response with long progression‐free survival. However, in Case 2, brain and bone metastases progressed during nivolumab treatment in spite of high PD‐L1 expression. This case series indicates that nivolumab is effective to some extent for PC of the lung. However, the clinical course of patients treated with nivolumab should be carefully observed, even when PD‐L1 is highly expressed.
Reduced risk of decompensation and death associated with use of statins in patients with alcoholic cirrhosis. A nationwide case‐cohort study
Authors: Bang U. C. , Benfield T. , Bendtsen F.
Published: September 2017

Background

Reports have indicated that the use of statins may ameliorate the course of cirrhosis.

Aim

To determine the relationship between use of statins and mortality rate in patients with cirrhosis.

Methods

We did a retrospective case‐cohort analysis based on data from the Danish registers from the period 1995 through 2014. Index date was time of diagnosis of cirrhosis (ICD‐10: K703) and cohort entry depended on whether the patient was statin user or not. We used propensity score matching with a statin:non‐statin ratio of 1:2. We included the exposure to statins (ATC classification C10AA) from the index date until death or end of follow‐up based on prescription claims. Use of statins based on at least two statin claims as well as the longitudinal pattern over time of statin claims was tested against mortality. The main outcome was mortality rate.

Results

A total of 24 748 patients with alcoholic cirrhosis were identified and 5417 were eligible for matching. The mean age was 56 (SD 10) years and 36% were females. The prevalence of use of statins was 15%. We included 744 in the matched cohort. Mortality rates were 88 (95% CI 73‐105) per 1000 years for patients using statin and 127 (95% CI 114‐141) for non‐statin patients with a HR of 0.57 (95% CI 0.45‐0.71). A more regular pattern of statin claims was related to a lower risk of death.

Conclusions

Our results showed an association between regular use of statins and reduced mortality in patients with alcoholic cirrhosis.
Editorial: subgroups in irritable bowel syndrome—more than just diarrhoea and constipation? Authors' reply
Authors: Polster A. , Van Oudenhove L. , Jones M. , Öhman L. , Törnblom H. , Simrén M.
Published: September 2017

Linked Content

This article is linked to Black and Ford, and Patel et al papers. To view these articles visit https://doi.org/10.1111/apt.14238 and https://doi.org/10.1111/apt.13074.
Ribavirin steady‐state plasma level is a predictor of sustained virological response in hepatitis C–infected patients treated with direct‐acting antivirals
Authors: van Tilborg M. , Lieveld F. I. , Smolders E. J. , van Erpecum K. J. , de Kanter C. T. M. M. , Maan R. , van der Valk M. , Arends J. E. , Dofferhoff A. S. M. , Blokzijl H. , Bijmolen M. , Drenth J. P. H. , de Knegt R. J. , Burger D. M. ,   the HepNed Study Group
Published: September 2017

Background

In the era of highly effective direct‐acting antivirals (DAAs) for treatment of patients with chronic hepatitis C virus (HCV) infection, ribavirin (RBV) is still considered beneficial in certain patients.

Aim

To assess the association between RBV steady‐state plasma levels and sustained virological response (SVR).

Methods

Consecutive HCV‐infected patients treated with DAAs plus RBV from four Dutch academic medical centres were enrolled. RBV steady‐state plasma levels were prospectively measured at treatment week 8 using validated assays. Logistic regression analyses were performed to assess the influence of RBV steady‐state plasma level on SVR, and RBV therapeutic range was explored using area under the ROC curve analyses.

Results

A total of 183 patients were included, of whom 85% had one or more difficult‐to‐cure characteristics (ie treatment experienced, HCV genotype 3, cirrhosis). The majority was treated with a sofosbuvir‐based regimen and 163 (89%) patients achieved SVR. Median RBV dose was 12.9 (interquartile range 11.2‐14.7) mg/kg/d, and median RBV steady‐state plasma level was 2.66 (1.95‐3.60) mg/L. In multivariable analyses, higher RBV steady‐state plasma level (adjusted odds ratio 1.79 [95% CI 1.09‐2.93]) was an independent predictor of SVR. With regard to the optimal RBV therapeutic range, 2.28 mg/L was the optimal lower cut‐off for achieving SVR and 3.61 mg/L was the upper cut‐off for preventing significant anaemia (Haemoglobin < 10 g/dL).

Conclusion

In this cohort of mainly difficult‐to‐cure patients treated with DAAs plus RBV, higher RBV steady‐state plasma level was an independent predictor of SVR.
The body composition profile is associated with response to anti‐TNF therapy in Crohn's disease and may offer an alternative dosing paradigm
Authors: Ding N. S. , Malietzis G. , Lung P. F. C. , Penez L. , Yip W. M. , Gabe S. , Jenkins J. T. , Hart A.
Published: September 2017

Background

Anti‐tumour necrosis factor (TNF)s form a major part of therapy in Crohn's disease and have a primary nonresponse rate of 10%‐30% and a secondary loss of response rate of 5% per year. Myopenia is prevalent in Crohn's disease and is measured using body composition analysis tools.

Aim

To test the hypothesis that body composition can predict outcomes of anti‐TNF primary nonresponse and secondary loss of response.

Methods

Between January 2007 and June 2012, 106 anti‐TNF naïve patients underwent anti‐TNF therapy for Crohn's disease with body composition parameters analysed using CT scans to estimate body fat‐free mass. The outcome measures were primary nonresponse and secondary loss of response. COX‐regression analysis was used with 3 year follow‐up data.

Results

A total of 106 patients were included for analysis with 26 (24.5%) primary nonresponders and 29 (27.4%) with secondary loss of response to anti‐TNF therapy. Sex‐specific cut‐offs for muscle and fat were ascertained by stratification analysis. On univariate analysis, primary nonresponse was associated with low albumin (OR 0.94; 0.88‐0.99, P = .04) and presence of myopenia (OR 4.69; 1.83‐12.01, P = .001) when taking into account patient's medical therapy, severity of disease and body composition. On multivariate analysis, presence of myopenia was associated with primary nonresponse (OR 2.93; 1.28‐6.71, P = .01). Immunomodulator therapy was associated with decreased secondary loss of response (OR 0.48; 0.23‐0.98, P = .04). BMI was poorly correlated with lean body mass (r2 = 0.15, P = .54).

Conclusions

In this cohort study, body composition profiles did not correlate well with BMI. Myopenia was associated with primary nonresponse with potential implications for dosing and serves as an explanation for pharmacokinetic failure.
Saddle nose deformity and septal perforation in granulomatosis with polyangiitis
Authors: Coordes A. , Loose S.M. , Hofmann V.M. , Hamilton G.S. , Riedel F. , Menger D.J. , Albers A.E.
Published: September 2017

Background

Patients who have granulomatosis with polyangiitis (GPA, syn. M. Wegener) often develop an external nose deformity which may have devastating psychological effects. Therefore, reconstruction of nasal deformities by rhinoplasty may become necessary to achieve a normal appearance.

Objective of review

The aim of this systematic review was to investigate the efficacy and safety of surgical reconstruction in external nasal deformities and septal perforation in GPA patients.

Search strategy

A systematic literature search with defined search terms was performed for scientific articles archived in the MEDLINE‐Database up to 10 June 2016 (PubMed Advanced MEDLINE Search), describing management of cases or case series in GPA patients with saddle nose deformity and/or septal perforation.

Results

Eleven of 614 publications met the criteria for this analysis including 41 GPA patients undergoing external nasal reconstruction and/or septal reconstruction with a median follow‐up of 2.6 years. Overall, saddle nose reconstruction in GPA patients is safe even if an increased rate of revision surgery has to be expected compared with individuals without GPA undergoing septorhinoplasty. Most implanted grafts were autografts of calvarial bone or costal cartilage. For septal perforation reconstruction, few studies were available. Therefore, based on the available data for surgical outcomes, it is impossible to make evidence‐based recommendations. All included GPA patients had minimal or no local disease at the time of reconstructive surgery. Therefore, the relationship between disease activity and its impact on surgical outcomes remains unanswered. The potential impact of immune‐modulating medications on increased complication rates and the impact of prophylactic antibiotics are unknown.

Conclusions

This study systematically reviews the efficacy and safety of surgical reconstruction of external nasal deformities in GPA patients for the first time. Saddle nose reconstruction in GPA patients with minimal or no local disease is a safe procedure despite an increased rate of revision surgery. Further research is required regarding the impact of antibiotic prophylaxis, immune‐modulating therapy, long‐term outcomes and functional outcomes measured with subjective and objective parameters.
Size diversity and species diversity relationships in fish assemblages of Western Palearctic lakes
Authors: Brucet Sandra , Arranz Ignasi , Mehner Thomas , Argillier Christine , Beklioğlu Meryem , Benejam Lluís , Boll Thomas , Holmgren Kerstin , Lauridsen Torben L. , Svenning Jens-Christian , Winfield Ian J. , Jeppesen Erik
Published: September 2017

Body size, coupled with abundance and taxonomy, may help to understand the mechanisms shaping community structure. Since the body size of fish is closely related to their trophic niche, size diversity (based on individual body size) of fish communities may capture intraspecific variations in fish trophic niches that are not detected by species diversity. Thus, the relationship between size diversity and species diversity may help to integrate variation at both intraspecific and interspecific levels. We studied the relationship between species diversity and size diversity as a measure of the degree of overlap in size among species and thereby the potential overlap in niches in a community. We hypothesized that the relationship between size diversity and species would be different across the European continent due to different levels of size overlap in fish communities. The data were derived from samplings of fish communities using standardised benthic gill nets in 363 lakes. At the continental scale, size diversity increased with species diversity; at the ecoregion scale, the slope of the relation changed across the continent, with the greatest mismatch occurring in northern Europe where communities comprised only one or a few species, but each of which exhibited a great range in size. There was an increase in slope towards the south with significant relations for four out of six ecoregions. The steeper size diversity‐species diversity slope at lower latitudes is attributable to a lower overlap in fish size and thus likely to finer niche separation. Our results also suggest that size diversity is not a strong surrogate for species diversity in European lake fish communities. Thus, particularly in fish communities composed of few species, measuring size diversity may help to detect potential functional variation which may be neglected by measuring species diversity alone.
Active site geometry of a novel aminopropyltransferase for biosynthesis of hyperthermophile‐specific branched‐chain polyamine
Authors: Hidese Ryota , Tse Ka Man , Kimura Seigo , Mizohata Eiichi , Fujita Junso , Horai Yuhei , Umezawa Naoki , Higuchi Tsunehiko , Niitsu Masaru , Oshima Tairo , Imanaka Tadayuki , Inoue Tsuyoshi , Fujiwara Shinsuke
Published: September 2017

Branched‐chain polyamines are found exclusively in thermophilic bacteria and Euryarchaeota and play essential roles in survival at high temperatures. In the present study, kinetic analyses of a branched‐chain polyamine synthase from the hyperthermophilic archaeon Thermococcus kodakarensis (Tk‐BpsA) were conducted, showing that N4‐bis(aminopropyl)spermidine was produced by sequential additions of decarboxylated S‐adenosylmethionine (dcSAM) aminopropyl groups to spermidine, through bifunctional catalytic action. Tk‐BpsA catalyzed the aminopropylation of the linear‐chain polyamines spermidine, spermine, norspermidine, and the tertiary‐branched polyamines N4‐aminopropylspermidine and N4‐aminopropylnorspermidine, but not of short‐chain diamines, putrescine, and cadaverine, suggesting that Tk‐BpsA does not catalyze the aminopropylation of primary amino groups of diamines. X‐ray structural analyses of Tk‐BpsA in the presence or absence of the substrates spermidine and dcSAM revealed that a large, negatively charged cavity is responsible for the binding of branched‐chain substrates. The binding is different from that in the active site of linear polyamine spermidine/spermine synthases, and loop‐closures occur upon the binding of spermidine. Based on structural analyses, further kinetic studies were carried out for various mutants, revealing that Asp159, positioned between the reactive secondary amino group of the substrate polyamine and a sulfur atom of the product 5ʹ‐methylthioadenosine and in a Gly‐Asp‐Asp‐Asp motif, functions as a catalytic center, with reactions proceeding via a ping‐pong mechanism. Our study provides a novel aminopropyltransfer reaction mechanism, distinct from the SN2 displacement mechanism found in other known linear spermidine/spermine synthases.

Database

Atomic coordinates and structure factors have been deposited in the Protein Data Bank with PDB codes 5XNF for apo‐Tk‐BpsA, 5XNH for the binary complex, and 5XNC for the ternary complex.
Automated cell counts on CSF samples: A multicenter performance evaluation of the GloCyte system
Authors: Hod E. A. , Brugnara C. , Pilichowska M. , Sandhaus L. M. , Luu H. S. , Forest S. K. , Netterwald J. C. , Reynafarje G. M. , Kratz A.
Published: September 2017

Objectives

Automated cell counters have replaced manual enumeration of cells in blood and most body fluids. However, due to the unreliability of automated methods at very low cell counts, most laboratories continue to perform labor‐intensive manual counts on many or all cerebrospinal fluid (CSF) samples. This multicenter clinical trial investigated if the GloCyte System (Advanced Instruments, Norwood, MA), a recently FDA‐approved automated cell counter, which concentrates and enumerates red blood cells (RBCs) and total nucleated cells (TNCs), is sufficiently accurate and precise at very low cell counts to replace all manual CSF counts.

Methods

The GloCyte System concentrates CSF and stains RBCs with fluorochrome‐labeled antibodies and TNCs with nucleic acid dyes. RBCs and TNCs are then counted by digital image analysis. Residual adult and pediatric CSF samples obtained for clinical analysis at five different medical centers were used for the study. Cell counts were performed by the manual hemocytometer method and with the GloCyte System following the same protocol at all sites. The limits of the blank, detection, and quantitation, as well as precision and accuracy of the GloCyte, were determined.

Results

The GloCyte detected as few as 1 TNC/μL and 1 RBC/μL, and reliably counted as low as 3 TNCs/μL and 2 RBCs/μL. The total coefficient of variation was less than 20%. Comparison with cell counts obtained with a hemocytometer showed good correlation (>97%) between the GloCyte and the hemocytometer, including at very low cell counts.

Conclusions

The GloCyte instrument is a precise, accurate, and stable system to obtain red cell and nucleated cell counts in CSF samples. It allows for the automated enumeration of even very low cell numbers, which is crucial for CSF analysis. These results suggest that GloCyte is an acceptable alternative to the manual method for all CSF samples, including those with normal cell counts.
Globalism vs culture(s): a critique of transculturalism and the one world, one culture globalist narrative in Africa
Authors: Petrus Theodore
Published: September 2017

There can be little doubt that with the advances in mass communication and technologies, the phenomenon of transculturalism is well and truly underway. However, this global phenomenon did not originate with technological advances in mass communication. Although the internet and the spread of popular culture have been the most obvious examples of transculturalism, the phenomenon itself has a long history. The current global(ist) world emerged, at least as far as modern history is concerned, with colonialism, where the seed of transculturalism was planted. Arguably, we are now experiencing the fruits of that seed, which has germinated and become this giant tree with branches and roots permeating almost every level of human society. The resultant interconnectedness brought about by globalism and its process, globalisation, has, among other things, created transculturalism. Both cultural globalisation and transculturalism share the ideological position of the world moving towards a “one world culture”. This contribution seeks to critique this perspective by interrogating whether (a) such a global move towards “oneness” is in fact possible, and (b) if it is, whether such a one world culture would be beneficial. The discussion is presented with specific reference to the working of transculturalism in the African context.
Femtosecond assisted intracorneal segments implantation for mild to moderate keratoconus: long term results
Authors: Kontadakis G. , Parikakis E. , Kaprinis K. , Stoupaki M. , Nikas S. , Konstantinidou V. , Peponis V.
Published: September 2017

Purpose

To describe the 2 year results of femtosecond assisted intracorneal segments implantation for the treatment of mild to moderate keratoconus with the use of a femtosecond laser.

Methods

Prospective case series including 4 eyes of 4 consecutive patients with keratoconus. Patients where implanted with KC Solutions intrastromal segments (IS). Patients’ assessment included visual acuity measurement, manifest refraction, clinical examination and corneal topography and tomography. IS implantation was scheduled in patients with unsatisfying corrected visual acuity (CDVA) and contact lens intolerance. Planning of the operation was done based on the topography and refraction based on nomogram provided by the IS manufacturer. IS were implanted in intracorneal pocket created with the FS200 femtosecond laser. Comparisons were made between pre‐ to postoperative values with the Wilcoxon signed‐rank test.

Results

Preoperative average steep keratometry was 48.45D (range 45.6 to 51.6), whereas at 2 years postoperatively it was 46.73 (44.8 to 48.7), (p<0.05). Preoperatively corneal astigmatism on average was 4.95D (2 to 9.1) and refractive astigmatism was 3.94D (2 to 9), whereas postoperatively average corneal and refractive astigmatism was 2.75 (1.2 to 6) and 1.87 (range 0,5 to 5) (p<0.05 in both comparisons). CDVA improved in all cases by 1 to 2 lines of Snellen visual acuity. Average spherical equivalent refraction was ‐3.22 (‐1.87 to ‐4.5) preoperatively, and postoperatively it was reduced to ‐1,81 (‐0.50 to ‐3,5) (p<0.05). No statistically significant differences were found between the last and 6th month follow up results.

Conclusions

According to our pilot long term study, Implantation of KC Solutions intrastromal segments with the aid of a femtosecond laser improved all patients’ topographic and refractive astigmatism, visual acuity and refraction.
Evaluation of efficacy and safety of dexamethasone intravitreal implants between vitrectomized and non‐vitrectomized eyes in a real‐life study
Authors: Rezkallah A. , Malcles A. , Dot C. , Voirin N. , Agard E. , Vie A.L. , Denis P. , Kodjikian L.
Published: September 2017

Purpose

To compare the efficacy and safety of dexamethasone intravitreal implant (Ozurdex) between vitrectomized and non‐vitrectomized eyes in real‐life conditions and to evaluate the change in intravitreal DEX‐implant efficacy before and after pars‐plana vitrectomy (PPV) in patients vitrectomized during follow‐up

Methods

This was a bicentric, retrospective, observational study. Four hundred and one eyes in 361 patients were enrolled between October 2010 and February 2015. Sixty‐seven eyes were vitrectomized at baseline, 301 had no vitrectomy at the last visit. Fifteen eyes were vitrectomized during follow‐up and had at least one DEX‐implant intravitreal injection before and after PPV. Eighteen eyes vitrectomized during the follow‐up were excluded because these eyes did not have at least one intravitreal injection of DEX‐Implant after pars‐plana vitrectomy. Three hundred eighty‐three eyes in 343 patients were studied. We evaluated the efficacy and safety of OzurdexÓ between vitrectomized and non‐vitrectomized eyes and before and after PPV in patients vitrectomized during follow‐up. Main outcome measures included changes in best‐corrected visual acuity, central macular thickness and incidence of adverse effects.

Results

Variations of BCVA and CMT were not significantly different neither between non‐vitrectomized eyes and baseline‐vitrectomized eyes nor before and after PPV in patients vitrectomized during follow‐up. The IOP profile was the same between non‐vitrectomized eyes versus baseline‐vitrectomized eyes and before versus after PPV in patients vitrectomized during the follow‐up.

Conclusions

This large cohort shows that vitrectomy seems not to influence the efficacy and safety profile of DEXimplant regardless of the indication.
Imaging in uveitis: modalities and applications
Authors: Herbort C.P.
Published: September 2017

Uveitis has become a precise clinical science, in part thanks to the development of performing imaging methods. Laser flare photometry (LFP), although not an imaging method “stricto sensu”, measures back‐scattered photons from the anterior chamber produced by a laser beam and so establishes the exact level of intraocular inflammation at any time and allows precise monitoring of uveitis. Fluorescein angiography (FA) has been used for more than 50 years and gives indications on inflammation of superficial structures of the fundus, optic disc and the retinal pigment epithelium. Indocyanine green angiography (ICGA) became available in the early 1990ties and is essential in the precise investigation of the inflammatory, otherwise occult reaction in the choroidal compartment, giving panfundal information that is otherwise not available. Optical coherence tomography (OCT) analyses both the retina and choroid (in the enhanced depth mode ‐ EDI) of the posterior pole. Ultrasound biomicroscopy (UBM) is useful to analyse inflammation in the retro‐iridal space. Other imaging methods such as fundus autofluorescence (FAF) or OCT‐angiography are still being evaluated for their utility in uveitis.
Retinal microvascular imaging with adaptive optics
Authors: Kalitzeos A.
Published: September 2017

The human eye provides an accessible, transparent “window” to its retinal structures that can be examined in vivo. Retinal images obtained with conventional modalities such as optical coherence tomography (OCT), scanning laser ophthalmoscopy (SLO) and fundus imaging are degraded because even an emmetropic eye is optically imperfect and fraught with aberrations.

By implementing adaptive optics (AO) to the aforementioned imaging modalities (AO‐OCT, AOS0LO, AO flood‐illumination camera, respectively) we are able to measure and compensate for these aberrations in the living human eye in real time. Retinal structures including (but not limited to) the capillary vasculature, photoreceptors, the retinal pigment epithelium, the nerve fiber layer and ‐recently‐ the ganglion cell layer have been succesfully resolved with AO systems down to a cellular scale.

Here the focus is AOS0LO systems and imaging techniques currently available in 1) visualising the retinal microvasculature and 2) quantifying blood flow. Both confocal and non‐confocal AOS0LO detection schemes will be discussed.
Static vessel parameters in health and disease
Authors: Heitmar R.
Published: September 2017

Non‐invasive observation of the retinal circulation in vivo has seen more and more interest in clinical applications in recent years, not only because of ease of acquisition but also due to improved analysis software. Standardized semi‐automatic analysis of vessel calibers are useful markers in systemic vascular disease and have been shown to be linked with disease progression and future cardiovascular events. In recent years new vessel segmentation algorythms and analysis software has made it possible to assess not only vessel calibers but also parameters such as tortuosity, vessel density and branching patterns.

In summary these vessel parameters in conjunction with measurements of retinal metabolism, vessel dynamics and retinal structure allow us to gain a better insight into normal retinal physiology and retinal pathophysiology due to systemic vascular disease.