bluuebunny/crossref_metadata_2025 huggingface dataset:
Binocular vision alterations after refractive and cataract surgery: a review
Authors: García‐Montero María , Albarrán Diego César , Garzón‐Jiménez Nuria , Pérez‐Cambrodí Rafael J. , López‐Artero Esther , Ondategui‐Parra Juan Carlos
Published: September 2018

To review binocular and accommodative disorders documented after corneal or intraocular refractive surgery, in normal healthy prepresbyopic patients. A bibliographic revision was performed; it included works published before 1st July 2017 where accommodation and/or binocularity was assessed following any type of refractive surgical procedure. The search in Pubmed yielded 1273 papers, 95 of which fulfilled the inclusion criteria. Few publications reporting binocular vision and/or accommodative changes after refractive surgery in normal subjects were found. The reduction in fusional vergence is the most frequently reported alteration. Anisometropia is an important risk factor for postoperative binocular vision‐related complaints. Most diplopia‐related visual complaints, irrespective of the surgical procedure, were in fact misdiagnosed preoperative disorders. The preoperative evaluation of patients seeking spectacle/contact lens independence should include a complete binocular and accommodation assessment where parameters such as the phoric posture, accommodative amplitude and facility, near point of convergence, fusional reserves and accommodative convergence/accommodation coefficient are measured. This would allow the identification of risk factors that could compromise the success of the refractive surgery and cause clinical symptoms.
Electroretinogram abnormalities in nonanterior childhood uveitis
Authors: Brouwer Anna H. , van Genderen Maria. M. , de Wit Gerard C. , de Boer Joke H.
Published: September 2018

Purpose

A major point of concern in uveitis is the development of irreversible retinal changes after inflammation. In this study, we assess how nonanterior childhood uveitis affects retinal function using full‐field electroretinography (ERG).

Methods

Cross‐sectional study. ERGs of 63 uveitis eyes (33 children) were measured according to extended International Society for Clinical Electrophysiology of Vision (ISCEV) protocols. ERG abnormalities were investigated in relation to the following clinical parameters: demographics, uveitis characteristics, including severity of inflammation, treatment, best corrected visual acuity (BCVA), cystoid macular oedema (CME) on optical coherence tomography and fluorescein angiography score.

Results

The ERG showed abnormalities in 34 eyes (54%). The most frequent ERG abnormalities were prolonged implicit times of the cone b‐wave (37%; n = 23/63) and an abnormal 30‐Hz flicker response (implicit time and/or amplitude) (33%; n = 21/63). Factors associated with these ERG abnormalities were CME (p = 0.021) and 3+ vitreous cells (p = 0.021). BCVA in eyes with and without these ERG abnormalities did not statistically differ and was relatively good (median: 0.05 LogMAR, IQR: 0.00–0.15 LogMAR).

Conclusion

The ERG is frequently affected in childhood uveitis indicating a global retinal dysfunction. ERG abnormalities seem to be associated with a more severe posterior segment inflammation and a younger age. If an association between ERG abnormalities and long‐term visual outcome can be made in the future, these early ERG findings during the course of childhood uveitis have significance for treatment strategies.
The Composition of the São Brás Copper Hoard in Relation to the Bell Beaker Metallurgy in the South‐western Iberian Peninsula
Authors: Valério P. , Soares J. , Araújo M. F. , Alves L. C. , Tavares da Silva C.
Published: September 2018

A large ceramic vessel was discovered at São Brás (southern Portugal) containing a metallic hoard from the Chalcolithic/Early Bronze Age period. These weapons and tools were characterized by microanalytical techniques as being composed of copper with varying arsenic contents (2.2 ± 1.6 wt%) and minor amounts of lead, bismuth and iron. The collection shows a clear association between daggers and copper with a higher arsenic content, which can be explained by the high status of these silvery alloys. Finally, the compositional distribution of the hoard was compared with the metallurgy of the Bell Beaker and non–Bell Beaker communities inhabiting the south‐western Iberian Peninsula.
Pharmacokinetics and safety of single and multiple doses of rasagiline in healthy Japanese and caucasian subjects
Authors: Elgart Anna , Rabinovich‐Guilatt Laura , Eyal Eli , Gross Aviva , Spiegelstein Ofer
Published: September 2018

As of March 2018, rasagiline is approved for the treatment of Parkinson disease in 55 countries including Japan. The present study evaluated the pharmacokinetics (PK) and safety of rasagiline in healthy Japanese and Caucasian subjects following single and multiple administrations of three rasagiline doses. In this double‐blind, placebo‐controlled study, 64 healthy subjects (32 Japanese and 32 Caucasian) received either rasagiline (0.5, 1.0, or 2.0 mg) or placebo for 10 days with PK sampling for single‐dose administration on day 1 and for multiple administration on day 10. Regardless of administration schedule, rasagiline plasma concentrations and dose‐related increases in exposure parameters were similar between Japanese and Caucasians. Rasagiline accumulation (2‐fold for 0.5 mg and 3‐fold for 1.0 mg and 2.0 mg doses) following multiple administration was similar across the ethnic groups. Geometric mean ratios (GMR) comparing Japanese to Caucasians for AUC0‐24, Cmax and AUCinf following single administration were 1.38, 1.17 and 1.38 for 0.5 mg; 1.22, 1.20 and 1.22 at 1.0 mg; and 1.02, 1.00 and 1.02 at for 2.0 mg. GMR for AUCtau and Cmax,ss following multiple administration were 1.43 and 1.06 at 0.5 mg, 1.06 and 1.00 at 1.0 mg, and 1.09 and 1.07 at 2.0 mg. Safety measures were unremarkable and similar between Caucasian and Japanese subjects. Comparable systemic exposure and safety parameters were demonstrated for rasagiline administered to healthy Japanese and Caucasian subjects.
Gestational diabetes incidence and delivery outcomes in Western China: A prospective cohort study
Authors: Mak Jonathan K. L. , Lee Andy H. , Pham Ngoc Minh , Pan Xiong‐Fei , Tang Li , Binns Colin W. , Sun Xin
Published: September 2018

Background

Few studies have examined the age‐standardized incidence of gestational diabetes mellitus (GDM) for comparison between populations. Information on delivery outcomes is also lacking for Chinese women with GDM. Therefore, the present study aimed to determine age‐standardized GDM incidence and assess its association with maternal and neonatal outcomes.

Methods

A total of 1901 pregnant women were recruited in Chengdu, Sichuan Province. GDM was diagnosed between 24 and 28 weeks’ gestation using oral glucose tolerance tests. Age‐standardized incidence rates of GDM were calculated using the direct method. Delivery outcomes were extracted from medical records and compared between the GDM and non‐GDM groups.

Results

The age‐standardized GDM incidence was 18.3% (95% CI 15.6‐21.1) and increased with maternal age and prepregnancy body mass index (BMI). Women with GDM experienced longer length of stay in hospital, shorter gestation at delivery, and a higher risk of cesarean delivery. Their newborns were more likely to be macrosomic or small for gestational age, and to require neonatal intensive care.

Conclusions

The incidence of GDM was high in Western China, especially among older and overweight women. Moreover, women with GDM had higher rates of adverse delivery outcomes. The findings lend further support for the screening, prevention, and management of GDM in Chinese women.
Direct role of FLT3 in regulation of early lymphoid progenitors
Authors: Zriwil Alya , Böiers Charlotta , Kristiansen Trine A. , Wittmann Lilian , Yuan Joan , Nerlov Claus , Sitnicka Ewa , Jacobsen Sten E. W.
Published: September 2018

Given that FLT3 expression is highly restricted on lymphoid progenitors, it is possible that the established role of FLT3 in the regulation of B and T lymphopoiesis reflects its high expression and role in regulation of lymphoid‐primed multipotent progenitors (LMPPs) or common lymphoid progenitors (CLPs). We generated a Flt3 conditional knock‐out (Flt3fl/fl) mouse model to address the direct role of FLT3 in regulation of lymphoid‐restricted progenitors, subsequent to turning on Rag1 expression, as well as potentially ontogeny‐specific roles in B and T lymphopoiesis. Our studies establish a prominent and direct role of FLT3, independently of the established role of FLT3 in regulation of LMPPs and CLPs, in regulation of fetal as well as adult early B cell progenitors, and the early thymic progenitors (ETPs) in adult mice but not in the fetus. Our findings highlight the potential benefit of targeting poor prognosis acute B‐cell progenitor leukaemia and ETP leukaemia with recurrent FLT3 mutations using clinical FLT3 inhibitors.
Occupation and risk of cancer of the renal pelvis in Nordic countries
Authors: Michalek Irmina Maria , Martinsen Jan Ivar , Weiderpass Elisabete , Kjaerheim Kristina , Lynge Elsebeth , Sparen Pär , Tryggvadottir Laufey , Pukkala Eero
Published: September 2018

Objectives

To evaluate occupational variation in the incidence of the malignant neoplasm of the renal pelvis in the population of the Nordic countries: Denmark, Iceland, Finland, Norway and Sweden.

Materials and Methods

The study cohort comprised 14.9 million individuals. Data on occupational history were obtained from national censuses. Standardized incidence ratios (SIRs) were calculated for each occupation.

Results

The highest SIRs were found in seamen (1.51, 95% confidence interval [CI] 1.23–1.82), printers (1.39, 95% CI 1.11–1.71), welders (1.37, 95% CI 1.03–1.78), and public safety workers (1.35, 95% CI 1.12–1.62). The lowest SIRs were observed in forestry workers (0.47, 95% CI 0.35–0.62), gardeners (0.72, 95% CI 0.62–0.83) and woodworkers (0.81, 95% CI 0.72–0.91).

Conclusions

The study suggests that there is an association between profession and risk of malignancy of the renal pelvis. The possible associations between exposure to asbestos, heavy metals and welding fumes, and risk of developing the disease should be studied further.
Impact of 5α‐reductase inhibitor and α‐blocker therapy for benign prostatic hyperplasia on prostate cancer incidence and mortality
Authors: Van Rompay Maria I. , Curtis Nickel J. , Ranganathan Gayatri , Kantoff Philip W. , Solomon Keith R. , Lund Jennifer L. , McKinlay John B.
Published: September 2018

Objective

To investigate the use of 5α‐reductase inhibitors (5ARIs) and α‐blockers among men with benign prostatic hyperplasia (BPH) in relation to prostate cancer (PCa) incidence, severity and mortality.

Patients and Methods

A retrospective 20‐year cohort study in men residing in Saskatchewan, aged 40–89 years, with a BPH‐coded medical claim between 1995 and 2014, was conducted. Cox proportional hazards regression was used to compare incidence of PCa diagnosis, metastatic PCa, Gleason score 8–10 PCa, and PCa mortality among 5ARI users (n = 4 571), α‐blocker users (n = 7 764) and non‐users (n = 11 677).

Results

In comparison with both non‐users and α‐blocker users, 5ARI users had a ~40% lower risk of a PCa diagnosis (11.0% and 11.4% vs 5.8%, respectively), and α‐blocker users had an 11% lower risk of a PCa diagnosis compared with non‐users. Overall, the incidence of metastatic PCa and PCa mortality was not significantly different among 5ARI or α‐blocker users compared with non‐users (adjusted hazard ratios [HR] of metastatic PCa: 1.12 and 1.13, respectively, and PCa mortality: 1.11 and 1.18, respectively, P > 0.05 for both drugs), but both 5ARI and a‐blocker users had ~30% higher risk of Gleason score 8–10 cancer, adjusted HR 1.37, 95% confidence interval [CI] 1.03–1.82, P = 0.03, and adjusted HR 1.28, 95% CI 1.03–1.59, P = 0.02, respectively compared with non‐users.

Conclusion

The use of 5ARIs was associated with lower risk of PCa diagnosis, regardless of comparison group. Risk of high grade PCa was higher among both 5ARI users and α‐blocker users compared with non‐users; however, this did not translate into higher risk of PCa mortality.
Relationship between oxidative stress and lower urinary tract symptoms: results from a community health survey in Japan
Authors: Matsumoto Teppei , Hatakeyama Shingo , Imai Atsushi , Tanaka Toshikazu , Hagiwara Kazuhisa , Konishi Sakae , Okita Kazutaka , Yamamoto Hayato , Tobisawa Yuki , Yoneyama Tohru , Yoneyama Takahiro , Hashimoto Yasuhiro , Koie Takuya , Nakaji Shigeyuki , Ohyama Chikara
Published: September 2018

Objective

To investigate the relationship between oxidative stress and lower urinary tract symptoms (LUTS) in a community‐dwelling population.

Materials and Methods

The cross‐sectional study included 1 113 people who participated in the Iwaki Health Promotion Project of 2015 in Hirosaki, Japan. LUTS were assessed using structured questionnaires, including the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS). IPSS > 7, OABSS > 5, nocturia score > 1, or urge incontinence score > 1 were defined as moderate to severe symptoms. 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) and advanced glycation end products (AGEs) were measured by urine analysis and skin autofluorescence, respectively. The relationship between oxidative stress and LUTS was investigated using logistic regression analyses.

Results

This study included 431 men and 682 women. AGEs and 8‐OHdG levels were significantly higher in severe forms of LUTS. Multivariate logistic regression analyses showed that AGE levels were significantly associated with a higher frequency of nocturia but were not associated with IPSS, OABSS or urge incontinence. No significant association was observed between LUTS and 8‐OHdG levels.

Conclusions

We observed a significant association between AGE levels and nocturia score > 1. Further research is necessary to clarify a possible causal relationship between oxidative stress and nocturia.
Suture techniques during laparoscopic and robot‐assisted partial nephrectomy: a systematic review and quantitative synthesis of peri‐operative outcomes
Authors: Bertolo Riccardo , Campi Riccardo , Klatte Tobias , Kriegmair Maximilian C. , Mir Maria Carmen , Ouzaid Idir , Salagierski Maciej , Bhayani Sam , Gill Inderbir , Kaouk Jihad , Capitanio Umberto ,   the Young Academic Urologists (YAU) Kidney Cancer working group of the European Urological Association (EAU)
Published: September 2018

Objective

To summarize the available evidence on renorrhaphy techniques and to assess their impact on peri‐operative outcomes after minimally invasive partial nephrectomy (MIPN).

Materials and Methods

A systematic review of the literature was performed in January 2018 without time restrictions, usingMEDLINE, Cochrane and Web of Science databases according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement recommendations. Studies providing sufficient details on renorrhaphy techniques during laparoscopic or robot‐assisted partial nephrectomy and comparative studies focused on peri‐operative outcomes were included in qualitative and quantitative analyses, respectively.

Results

Overall, 67 and 19 studies were included in the qualitative and quantitative analyses, respectively. The overall quality of evidence was low. Specific tumour features (i.e. size, hilar location, anatomical complexity, nearness to renal sinus and/or urinary collecting system), surgeon's experience, robot‐assisted technology, as well as the aim of reducing warm ischaemia time and the amount of devascularized renal parenchyma preserved represented the key factors driving the evolution of the renorrhaphy techniques duringMIPNover the past decade. Quantitative synthesis showed that running suture was associated with shorter operating and ischaemia time, and lower postoperative complication and transfusion rates than interrupted suture. Barbed suture had lower operating and ischaemia time and less blood loss than non‐barbed suture. The single‐layer suture technique was associated with shorter operating and ischaemia time than the double‐layer technique. No comparisons were possible concerning renal functional outcomes because of non‐homogeneous data reporting.

Conclusions

Renorrhaphy techniques significantly evolved over the years, improving outcomes. Running suture, particularly using barbed wires, shortened the operating and ischaemia times. A further advantage could derive from avoiding a double‐layer suture.
Comparison of desmopressin, alarm, desmopressin plus alarm, and desmopressin plus anticholinergic agents in the management of paediatric monosymptomatic nocturnal enuresis: a network meta‐analysis
Authors: Song Pan , Huang Chuiguo , Wang Yan , Wang Qingwei , Zhu Wen , Yue Yiwei , Wang Wancong , Feng Jinjin , He Xiangfei , Cui Lingang , Wan Tingxiang , Wen Jianguo
Published: September 2018

Objective

To assess the efficacy of desmopressin, alarm, desmopressin plus alarm, and desmopressin plus anticholinergic agent (AA) therapy in the management of paediatric monosymptomatic nocturnal enuresis (MNE) using a network meta‐analysis.

Materials and methods

We searched the electronic databases PubMed, Cochrane Library, EMBASE and Web of Science from inception to 1 March 2018. Randomized controlled trials (RCTs) that compared desmopressin, alarm, desmopressin plus alarm, and desmopressin plus AAs were identified. The network meta‐analysis was conducted with software R 3.3.2 and STATA 14.0.

Results

Eighteen RCTs with a total of 1 649 participants were included. The meta‐analysis results showed that complete response (CR) and success rates with desmopressin plus AAs were higher than with desmopressin or alarm monotherapy. Success rates for desmopressin plus alarm therapy were higher than for alarm monotherapy. No obvious difference was observed between desmopressin plus AAs and desmopressin plus alarm therapy with regard to CR rate and success rate. The relapse rate with alarm monotherapy was much lower than with desmopressin monotherapy. Adverse events seemed to be infrequently and tolerable for all treatments. The ranking probability results were as follows: desmopressin plus AA ranked first for the outcomes of CR and success, desmopressin plus alarm therapy ranked first for mean number of wet nights per week, and alarm therapy had the lowest relapse rate.

Conclusions

The network meta‐analysis showed that desmopressin had similar efficacy to alarm therapy but a higher relapse rate. Desmopressin plus AA therapy was associated with better efficacy than and a similar relapse rate to desmopressin monotherapy. Desmopressin plus alarm therapy was similar to both desmopressin and alarm monotherapy in efficacy. All treatments, including desmopressin plus AAwere associated with tolerable adverse events; however, additional high‐quality studies are needed for further evaluation of these treatments.
Thrombospondin 1 and cathepsin D improve prostate cancer diagnosis by avoiding potentially unnecessary prostate biopsies
Authors: Steuber Thomas , Tennstedt Pierre , Macagno Annalisa , Athanasiou Alcibiade , Wittig Anja , Huber Ramy , Golding Bruno , Schiess Ralph , Gillessen Silke
Published: September 2018

Objectives

To investigate and further validate if two novel cancer‐related glycoproteins, discovered by a genetic‐guided proteomics approach, can distinguish benign disease from prostate cancer (PCa) in men with enlarged prostates.

Patients and Methods

A retrospective study was performed that included men with a total prostate‐specific antigen (PSA) concentration of 2.0–10 ng/mL, negative digital rectal examination and enlarged prostate (volume ≥35 mL). Serum samples were collected between 2011 and 2016 at a single centre from 474 men before they underwent prostate biopsy. Serum concentrations of thrombospondin 1 (THBS1) and cathepsin D (CTSD) glycoproteins were combined with the percentage of free PSA to total PSA ratio (%fPSA) to predict any or significant cancer at biopsy.

Results

The multivariable logistic regression model including THBS1, CTSD and %fPSA discriminated among biopsy‐positive and biopsy‐negative patients in the validation set with an area under the curve (AUC) of 0.86 (P < 0.001, 95% confidence interval (CI) 0.82–0.91), while %fPSA alone showed an AUC of 0.64 (P < 0.001, 95% CI 0.57–0.71). At 90% sensitivity for PCa, the specificity of the model was 62%, while %fPSA had a specificity of 23%. For high grade (Gleason score ≥ 7 in prostatectomy specimen) PCa, the specificity was 48% at 90% sensitivity, with an AUC of 0.83, (P < 0.001, 95% CI 0.77 to 0.88). Limitations of the study include the retrospective set‐up and single‐centre cohort.

Conclusions

A model combining two cancer‐related glycoproteins (THBS1 and CTSD) and %fPSA can improve PCa diagnosis and may reduce the number of unnecessary prostate biopsies because of its improved specificity for PCa when compared to %fPSA alone.
Lateral terminations of salt walls and megaflaps: An example from Gypsum Valley Diapir, Paradox Basin, Colorado, USA
Authors: Escosa Frederic O. , Rowan Mark G. , Giles Katherine A. , Deatrick Kyle T. , Mast Allison M. , Langford Richard P. , Hearon Thomas E. , Roca Eduard
Published: September 2018

Descriptions of exposed salt structures help improve the ability to interpret the geometry and evolution of similar structures imaged in seismic reflection data from salt‐bearing sedimentary basins. This study uses detailed geologic mapping combined with well and seismic data from the southeastern end of the Gypsum Valley diapir (Paradox Basin, Colorado), to investigate the three‐dimensional geometry of the terminations of both the salt wall and its associated megaflap. The salt wall trends NW‐SE and is characterized by highly asymmetric stratal architecture on its northeastern and southwestern flanks, with thicker, deeper, gently dipping strata in the depositionally proximal (NE) minibasin and thinned older strata rotated to near‐vertical in a megaflap on the distal (SW) side. The megaflap terminates to the SE through a decrease in maximum dip and ultimately truncation by a pair of radial faults bounding a down‐dropped block with lower dips. East of these faults, the salt wall termination is a moderately plunging nose of salt overlain by gently southeast‐dipping strata, separated from the down‐dropped NE minibasin by a counterregional fault. From this analysis, and by comparison with analogue structures located elsewhere in the Paradox Basin and in the northern Gulf of Mexico, we propose a series of simple end‐member models in which salt walls and megaflaps may terminate abruptly or gradually. We suggest that controlling factors in determining these geometries include the original thickness and spatial distribution of the deep salt, the presence of nearby diapirs (which determines the fetch area for salt flow into the diapir), spatial patterns of depositional loading, and variations in the nature and location of salt breakout through the roof of the initial salt structure.
Comparative mutational evaluation of multiple lung cancers by multiplex oncogene mutation analysis
Authors: Takahashi Yuta , Shien Kazuhiko , Tomida Shuta , Oda Shinsuke , Matsubara Takehiro , Sato Hiroki , Suzawa Ken , Kurihara Eisuke , Ogoshi Yusuke , Namba Kei , Yoshioka Takahiro , Torigoe Hidejiro , Yamamoto Hiromasa , Soh Junichi , Toyooka Shinichi
Published: September 2018

In patients presenting with synchronous or metachronous multiple lung cancer (MLC), it is important to distinguish between multiple primary lung cancer (MP) and intrapulmonary metastasis (IM). The present study was aimed at investigating the mutational profiles of synchronous/metachronous MLC and to compare the classification of paired tumors by multiplex gene mutation analysis with the histopathological evaluation. We carried out targeted sequencing of 20 lung cancer‐related oncogenes using next‐generation sequencing (NGS) in 82 tumors from 37 MLC patients who underwent surgical resection at our department. The patients were diagnosed as MP or IM cases based on the Martini and Melamed criteria, histopathological and gene mutational evaluations. Matching mutations between paired tumors was observed in 20 (54%) patients, who were diagnosed as IM cases by mutational evaluation. Patients who could not be clearly diagnosed by histopathological evaluation were classified as equivocal cases. Among the histopathological IM cases (n = 7), six (86%) were confirmed as IM cases also by mutational evaluation, and most of the paired tumors of these cases (n = 5) harbored multiple matching mutations. Among the histopathological MP cases (n = 17), mutational evaluation yielded a discordant diagnosis in eight (47%) cases. Of these, the paired tumors of four cases harbored multiple matching mutations, suggesting that the mutational diagnosis might be more suitable in these patients. Our findings suggest that multiplex mutational analysis could be a useful complementary tool for distinguishing between MP and IM in addition to histopathological evaluation.
Cinnamic acids derived compounds with antileishmanial activity target Leishmania amazonensis arginase
Authors: da Silva Edson Roberto , Brogi Simone , Grillo Alessandro , Campiani Giuseppe , Gemma Sandra , Vieira Paulo Cezar , Maquiaveli Claudia do Carmo
Published: September 2018

This study describes the activity of five natural hydroxycinnamic acids and derived compound: caffeic (1), rosmarinic (2), chlorogenic (3), and cryptochlorogenic (4), acids and isoverbascoside (5). All compounds inhibited Leishmania amazonensis arginase with IC50 —in range of 1.5—11 μM. Compounds 2 and 5 also showed activity against promastigotes of L. amazonensis with IC50 = 61 (28–133) μM and IC50 = 14 (9–24) μM, respectively. Further computational studies applying molecular docking simulations were performed on the competitive inhibitors to gain insight into the molecular basis for arginase inhibition and could be exploited to the development of new antileishmanials drug targeting parasite arginase.
The Earlier the Better? Individual Participant Data and Traditional Meta‐analysis of Age Effects of Parenting Interventions
Authors: Gardner Frances , Leijten Patty , Melendez‐Torres G.J. , Landau Sabine , Harris Victoria , Mann Joanna , Beecham Jennifer , Hutchings Judy , Scott Stephen
Published: September 2018

Strong arguments have been made for early intervention for child problems, stating that early is more effective than later, as the brain is more malleable, and costs are lower. However, there is scant evidence from trials to support this hypothesis, which we therefore tested in two well‐powered, state‐of‐the‐art meta‐analyses with complementary strengths: (a) Individual participant data (IPD) meta‐analysis of European trials of Incredible Years parenting intervention (k = 13, n = 1696; age = 2–11); (b) Larger, trial‐level robust variance estimation meta‐analysis of a wider range of parenting programs (k = 156, n = 13,378, Mage = 2–10) for reducing disruptive behavior. Both analyses found no evidence that intervention earlier in childhood was more effective; programs targeted at a narrower age range were no more effective than general ones.
Squamate areas of endemism in Cuba as determined by parsimony analysis of endemicity
Authors: Murray Christopher M. , Crother Brian I.
Published: September 2018

Cuba, the largest island in the Greater Antilles, hosts a high diversity of native squamate reptiles and is characterized by a complex geological history. The island has undergone repeated submergence and emergence, positioned on the dynamic border between the Caribbean and North American tectonic plates. Here, we infer current areas of endemism on Cuba based on squamate distributions using standard parsimony analysis of endemism under the “areas of endemism as individuals” hypothesis. We diagnose 29 areas of endemism, 14 of which are nested within other areas of endemism, from 52 squamate taxa. We suspect the current biotic pattern is a composite view of layered histories, and we summarize the geological history of the island to contemplate historical periods that left stronger marks on squamate distributions than others.
A scoring system to predict recurrence in patients with differentiated thyroid cancer
Authors: López‐Bru David , Palazón‐Bru Antonio , Folgado‐de la Rosa David M. , Gil‐Guillén Vicente F.
Published: September 2018

Objectives

Though predictive models have been constructed to determine the risk of recurrence in differentiated thyroid carcinoma, various aspects of these models are inadequate. Therefore, we aimed to construct, internally validate and implement on a mobile application a scoring system to determine this risk within 10 years.

Design

A retrospective cohort study in 1984‐2016.

Setting

A Spanish region.

Participants

We enrolled 200 patients with differentiated thyroid carcinoma without distant metastasis at diagnosis.

Main outcome measures

Time‐to‐recurrence. A risk table was constructed based on the sum of points to estimate the likelihood of recurrence. The model was internally validated and implemented as a mobile application for Android.

Results

Predictive factors were follicular histology, T, N and multifocality. This risk table had a C‐statistic of 0.723. The calibration was satisfactory.

Conclusions

This study provides an instrument able to predict rapidly and very simply which patients with differentiated thyroid carcinoma have a greater risk of recurrence.
Acceptability, effectiveness and safety of a Renew® anal insert in patients who have undergone restorative proctocolectomy with ileal pouch–anal anastomosis
Authors: Segal J. P. , Leo C. A. , Hodgkinson J. D. , Cavazzoni E. , Bradshaw E. , Lung P. F. C. , Ilangovan R. , Vaizey C. J. , Faiz O. D. , Hart A. L. , Clark S. K.
Published: September 2018

Introduction

Restorative proctocolectomy has gained acceptance in the surgical management of medically refractive ulcerative colitis and cancer prevention in familial adenomatous polyposis. Incontinence following restorative proctocolectomy occurs in up to 25% of patients overnight. The Renew® insert is an inert single‐use device which acts as an anal plug. The aim of this study was to assess the acceptability, effectiveness and safety of the Renew® insert in patients who have undergone restorative proctocolectomy. The device has yet to be assessed in patients who have undergone restorative proctocolectomy.

Method

This was a prospective study exploring the acceptability, effectiveness and safety of the Renew® insert in improving incontinence in patients who had undergone restorative proctocolectomy. A total of 15 patients with incontinence were asked to use the Renew® insert for 14 days following their standard care. The Incontinence Questionnaire–Bowels was used pre‐ and posttreatment to assess response and patients were asked to report the perceived acceptability, effectiveness and safety of the device at the end of the trial.

Results

The device was acceptable to 8/15 (53%) of patients and was effective in 6/15 (40%). Only 2/15 (13%) of patients raised any safety concerns, and these were minor. The device was associated with a significant reduction in night seepage (P = 0.034).

Conclusion

In a small study, the Renew® insert can be both acceptable and effective and is also associated with few safety concerns. It is also associated with significant reductions in night‐time seepage.
A new approach to kidney wait‐list management in the kidney allocation system era: Pilot implementation and evaluation
Authors: Cheng Xingxing S. , Busque Stephan , Lee Jenny , Discipulo Kevin , Hartley Christine , Tulu Zeynep , Scandling John D. , Tan Jane C.
Published: September 2018

Kidney transplant wait‐list management is becoming increasingly complex. We introduced a novel wait‐list management strategy at our center, the Transplant Readiness Assessment Clinic (TRAC), whereby patients whose Kidney Allocation Scores surpass a threshold are actively managed. From January 1, 2016 through June 30, 2017, we evaluated 195 patients through TRAC. Compared to pre‐TRAC systems at our institution, TRAC resulted in a higher proportion of activation at 18 months (38% vs 22%‐26%, P < 0.0001), despite being enriched in patients with long dialysis duration. TRAC also resulted in a higher proportion of wait‐list removal (15% vs 8%‐9%, P < 0.05) although combined wait‐list removal and death on wait‐list did not differ (18% vs 16%‐17%). Median time to activation was 356 days from TRAC evaluation. Of the transplant barriers, need for cardiovascular studies was the most common (31%), followed by other medical issues (23%), poor functional status (13%), and psychosocial issues (10%). By concentrating center resources on patients most likely to be transplanted after activation and performing active patient management close to the time of transplant, TRAC has the potential to significantly enhance kidney transplant success in regions with long wait‐times.
Differential diagnosis of mesenchymal neoplasms of the digestive tract by cell block and immunohistochemistry
Authors: Lopes César Vivian , Rigon Péttala , Zettler Cláudio Galleano , Hartmann Antônio Atalíbio
Published: September 2018

Objectives

To evaluate the diagnostic yield of the cell block (CB) technique with immunohistochemistry in patients with mesenchymal neoplasms of the gastrointestinal tract collected by endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA).

Methods

Tissue samples from consecutive patients with subepithelial lesions collected by EUS‐FNA, without analysis by on‐site cytopathology, were evaluated by the same pathologist only using CBs in AAF fixative. Sections were stained with haematoxylin‐eosin and underwent complementary immunohistochemical staining for SMA, CD117, DOG‐1 and S100 in the presence of mesenchymal neoplasms. Specimens were defined as diagnostic when sufficient tissue was present for histopathological evaluation and immunohistochemistry analysis. If they were insufficient for complete evaluation, the specimens were considered nondiagnostic.

Results

Between September 2012 and December 2016, a total of 158 patients (median age: 57 years, 64.5% women) underwent EUS‐FNA with an average of three needle passes for every lesion. The median lesion size was 17 mm. There were 113 mesenchymal neoplasms confirmed by immunohistochemistry (66 leiomyomas, 44 GISTs, two schwannomas, one leiomyosarcoma). The overall diagnostic yield of CBs was 84.17%. However, diagnosis was obtained in 98.5% (133/135) of the cases after exclusion of 23 cases in which EUS‐FNA sampling was insufficient or without tumoural tissue. Only two mesenchymal neoplasms were not confirmed by CBs even after immunohistochemistry.

Conclusions

CBs collected by EUS‐FNA and analysed by immunohistochemistry showed a high diagnostic yield in patients with mesenchymal neoplasms, even without on‐site cytopathology.
Clinicocytopathological spectrum, including uncommon forms, of nine cases of chordomas with immunohistochemical results, including brachyury immunostaining: A single institutional experience
Authors: Rekhi Bharat , Karmarkar Srushti
Published: September 2018

Objectives

To present clinical and cytopathological features of nine cases of chordomas, diagnosed over 9 years and confirmed by brachyury (T) immunostaining.

Methods

Conventional cytological smears, stained with Papanicolaou and May‐Grünwald Giemsa, along with corresponding histopathological (n = 8) and immunostained sections (n = 8) were reviewed. Immunohistochemical staining was performed on tissue sections by polymer detection technique.

Results

Nine tumours occurred in seven males and two females, with age ranging from 36 to 72 years (average = 58.7), in the sacrum (seven) and spine (two). On fine needle aspiration cytology, five cases were either diagnosed with or diagnosed with a suggestion of a chordoma, while three cases were diagnosed with chordoma as a differential diagnosis. On review, smears were moderately cellular, comprising myxoid stroma (9/9), epithelioid cells (9/9), physaliphorous cells (8/9), including binucleation (7/9), prominent nucleolisation (2/9), pleomorphic cells (2/9) and intranuclear inclusions (3/9). Immunohistochemically, tumour cells expressed cytokeratin (4/4), pan cytokeratin (4/4), epithelial membrane antigen (8/8), S100 protein (6/8) and brachyury (8/8). Five patients underwent surgical excision, including two who underwent adjuvant radiotherapy (RT) and four patients who underwent RT. During follow‐up (n = 8), a single patient developed recurrence and another presented with metastatic lesions. Finally, five patients were alive with disease (7‐53 months); a single patient was free of disease (4 months), and two patients died of disease; the latter cases displayed pleomorphic cells and intranuclear inclusions.

Conclusions

Chordomas can be primarily diagnosed by fine needle aspiration cytology in a typical clinicoradiological setting with a combination of key cytomorphological features. Pleomorphic cells and intranuclear inclusions are associated with a relatively aggressive subtype. An exact diagnosis has treatment implications and requires confirmation by brachyury immunostaining.
Agitated saline contrast echocardiography reveals cor triatriatum dexter
Authors: Theodoropoulos Konstantinos C. , Papachristidis Alexandros , Harries Derek , Sado Daniel M. , Monaghan Mark J.
Published: September 2018

We present the case of a 54‐year‐old man who had an unusual finding in contrast echocardiography with agitated saline. Partition of the right atrium in two compartments, an opacified and a non‐opacified one, was noted. Further assessment with a transesophageal echocardiogram revealed the presence of a membrane in the right atrium, with the final diagnosis being cor triatriatum dexter.
Environmentally cued hatching in the bird‐parasitic nest fly Philornis downsi
Authors: Sage Roxanne , Boulton Rebecca A. , Lahuatte Paola F. , Causton Charlotte E. , Cloutier Richard , Heimpel George E.
Published: September 2018

Under the hypothesis of environmentally cued hatching (ECH), eggs are stimulated to hatch by cues favouring larval survival. Here we investigated whether the bird‐parasitic nest fly Philornis downsi Dodge & Aitken (Diptera: Muscidae) exhibits ECH in response to the presence of suitable hosts and environmental conditions. Philornis downsi is an invasive in the Galapagos Islands and ECH could help to explain its success in a novel habitat. We found that the presence of hosts (nesting birds) per se does not accelerate hatching time in P. downsi, but that nesting birds do produce a microclimate, in terms of temperature and/or humidity that is conducive to faster hatching and higher hatching success. Eggs that are laid under extremely dry conditions die rather than delay their hatching time. We also found that P. downsi eggs hatch more rapidly when the substrate is very wet. Furthermore, larvae that hatch rapidly survive longer under starvation conditions. We suggest that eggs hatching more rapidly can either take advantage of optimal conditions for larval growth (host presence) or escape unfavourable microclimatic conditions (as larvae are mobile).
Inflammatory disorders associated with trisomy 8‐myelodysplastic syndromes: French retrospective case‐control study
Authors: Wesner Nadege , Drevon Louis , Guedon Alexis , Fraison Jean Baptiste , Trad Salim , Kahn Jean Emmanuel , Aouba Achille , Gillard Jerome , Ponsoye Matthieu , Hanslik Thomas , Gourguechon Clement , Liozon Eric , Laribi Kamel , Rossignol Julien , Hermine Olivier , Adès Lionel , Carrat Fabrice , Fenaux Pierre , Mekinian Arsene , Fain Olivier ,   GFM, MINHEMON (French Network of Dysimmune Disorders Associated to Hemopathies)
Published: September 2018

Objective

We report cases of myelodysplastic syndrome/myeloproliferative neoplasms (MDS/MPN) with trisomy 8 associated with inflammatory and autoimmune diseases (IADs).

Method

Data for 21 patients with trisomy 8‐MDS/MPN and IADs were analyzed and compared to 103 patients with trisomy 8‐MDS/MPN without IADs.

Results

The median age of MDS/MPN patients with IADs was 67 [59‐80]. The IADs were Behçet's‐like disease in 11 (52%) patients, inflammatory arthritis in 4 (19%) and Sjögren's syndrome, autoimmune hemolytic anemia, aseptic abscess, periarteritis nodosa, Sweet's syndrome and unclassified vasculitis in one patient each. Overall, 17/21 (81%) patients with IADs received treatment (88% with steroids), with complete and partial response in 7/17 (35%) and 8/17 (47%), respectively. The effect of MDS treatment on IADs could be assessed in seven patients receiving azacytidine: five achieved remission and two partial response. As compared with the 103 trisomy 8‐MDS/MPN cases without IADs, those with IADs were more often non‐European (P = 0.005) and had poor karyotype (P < 0.001). We found no difference in overall survival or acute myeloid leukemia progression between trisomy 8‐associated MDS/MPN with and without IADs.

Conclusion

The spectrum of IADs associated with trisomy 8‐positive MDS/MPN is dominated by Behçet's‐like disease. Steroid therapy is effective, but mostly sparing therapies are necessary. Azacytidine could be an effective alternative.
Contributions of nucleus accumbens dopamine to cognitive flexibility
Authors: Radke Anna K. , Kocharian Adrina , Covey Dan P. , Lovinger David M. , Cheer Joseph F. , Mateo Yolanda , Holmes Andrew
Published: September 2018

There is a compelling evidence that midbrain dopamine (DA) neurons and their projections to the ventral striatum provide a mechanism for motivating reward‐seeking behavior, and for utilizing information about unexpected reward prediction errors (RPEs) to guide behavior based on current, rather than historical, outcomes. When this mechanism is compromised in addictions, it may produce patterns of maladaptive behavior that remain obdurate in the face of contrary information and even adverse consequences. Nonetheless, DAergic contributions to performance on behavioral tasks that rely on the ability to flexibly update stimulus‐reward relationships remains incompletly understood. In the current study, we used a discrimination and reversal paradigm to monitor subsecond DA release in mouse NAc core (NAc) using in vivo fast‐scan cyclic voltammetry (FSCV). We observed post‐choice elevations in phasic NAc DA release; however, increased DA transients were only evident during early reversal when mice made responses at the newly rewarded stimulus. Based on this finding, we used in vivo optogenetic (eNpHR) photosilencing and (Channelrhodopsin2 [ChR2]) photostimulation to assess the effects of manipulating VTA‐DAergic fibers in the NAc on reversal performance. Photosilencing the VTA → NAc DAergic pathway during early reversal increased errors, while photostimulation did not demonstrably affect behavior. Taken together, these data provide additional evidence of the importance of NAc DA release as a neural substrate supporting adjustments in learned behavior after a switch in expected stimulus‐reward contingencies. These findings have possible implications for furthering understanding the role of DA in persistent, maladaptive decision‐making characterizing addictions.
Verbal working memory modulates afferent circuits in motor cortex
Authors: Suzuki Lorraine Y. , Meehan Sean K.
Published: September 2018

Verbal instruction and strategies informed by declarative memory are key to performance and acquisition of skilled actions. We previously demonstrated that anatomically distinct sensory–motor inputs converging on the corticospinal neurons of motor cortex are differentially sensitive to visual attention load. However, how loading of working memory shapes afferent input to motor cortex is unknown. This study used short‐latency afferent inhibition (SAI) to probe the effect of verbal working memory upon anatomically distinct afferent circuits converging on corticospinal neurons in the motor cortex. SAI was elicited by preceding a suprathreshold transcranial magnetic stimulus (TMS) with electrical stimulation of the median nerve at the wrist while participants mentally rehearsed a two‐ or six‐digit numeric memory set. To isolate different afferent intracortical circuits in motor cortex SAI was elicited, using TMS involving posterior–anterior (PA) or anterior–posterior (AP) monophasic current. Both PA and AP SAI were significantly reduced during maintenance of the six‐digit compared to two‐digit memory set. The generalized effect of working memory across anatomically distinct circuits converging upon corticospinal neurons in motor cortex is in contrast to the specific sensitivity of AP SAI to increased attention load. The common response across the PA and AP SAI circuits to increased working memory load may reflect an indiscriminate perisomatic mechanism involved in the voluntary facilitation of desired and/or suppression of unwanted actions during action selection or response conflict.
Study on site‐specific expression of bone formation and resorption factors in human dental follicles
Authors: Uribe Pamela , Plakwicz Pawel , Larsson Lena , Czochrowska Ewa , Westerlund Anna , Ransjö Maria
Published: September 2018

We sought to investigate site‐specific expression of bone‐regulatory factors expressed by human dental follicles and to compare the stimulated expression of tumour necrosis factor (ligand) superfamily, member 11/tumour necrosis factor receptor superfamily, member 11b (RANKL/OPG) in human dental follicle cells (HDFCs) from different patients. Analysis of bone‐regulatory markers in follicles from 12 different study participants was performed using RT‐qPCR and immunofluorescence; apical and coronal segments from each dental follicle were processed independently. Four additional dental follicles were used for cell cultures; HDFCs were precultured in osteogenic medium to initiate differentiation and thereafter cultured with 10−6M forskolin (FSK) to activate the protein kinase cAMP (PKA/cAMP) signalling pathway and induceRANKL/OPGexpression. We demonstrate thatRANKLexpression is significantly higher in the coronal part of follicles than in the apical part. High levels of collagen type 1 (COL1),alkaline phosphatase (ALP) and Gap‐junction protein, alpha 1, 43 kDa (CX43) were expressed, whereas expression of Sp7 transcription factor (OSX), bone morphogenetic protein 2 (BMP2),colony‐stimulating factor 1 (CSF‐1), chemokine (C‐C motif) ligand 2 (MCP1), andOPGwas low in all samples. The immunofluorescence localization ofCSF‐1,MCP1, osteocalcin (OCN), RANKL,andBMP2was not specific for either part of the follicles. In conclusion, a consistently high expression ofCX43suggests that gap‐junction communication in HDFCs is essential for the eruption process. Furthermore, the induced expression ofRANKLin HDFCs varies significantly between individuals and may relate to clinical variations in tooth eruption.