bluuebunny/crossref_metadata_2025 huggingface dataset:
Breeding versus survival: proximate causes of abrupt population decline under environmental change in a desert rodent, the midday gerbil (Meriones meridianus)
Authors: TCHABOVSKY Andrey , SAVINETSKAYA Ludmila , SURKOVA Elena
Published: December 2018

Studying abrupt ecological shifts under gradual environmental change caused, in particular, by human activity is important for understanding the fundamental aspects and underlying mechanisms of ecological resilience. One of the rare well‐documented examples of an abrupt ecological shift is the delayed step transition of the population of a desert rodent, the midday gerbil (Meriones meridianus), from high‐abundance (1994–2002) to low‐abundance (2003–2017) regimes. This was in response to landscape transformation from desert to steppe caused by the drastic reduction of livestock in the rangelands of southern Russia after the collapse of the USSR in the early 1990s. In this study, we tested whether demographic parameters were correlated with the observed abrupt downward population shift. We found that reproductive activity (the percentage of breeding females, the number of litters, fecundity and the number of young recruited per female) showed no trend over time and did not differ between periods of high and low abundance. In contrast, the adult sex ratio (SR = males: females) decreased significantly with time and was as much as twice more female‐biased for the low‐abundance population regime. However, SR was not related to any reproductive parameter, including the percentage of breeding females. We conclude that proximate reasons for an abrupt population decline inM. meridianusare not associated with the changes in breeding patterns or mate limitation caused by the Allee effect but relate to the increased mortality as a result of the desert landscape being fragmented by steppezation. The mortality is expected to be higher for males as the mobile and dispersing sex.
Ovarian metastases from ileal neuroendocrine tumour: Multimodality imaging
Authors: Montoriol Pierre‐François , Boudinaud Claire
Published: December 2018

We present a rare case of large bilateral ovarian tumours, secondarily revealing an ileal neuroendocrine tumour in a 71‐year‐old woman. Magnetic resonance examination showed bilateral ovarian, entirely solid lesions with a fibrous content and marked enhancement. Computed tomography was able to show a mesenteric retractile mass and a satellite suspicious ileal wall thickening. Gallium‐68 DOTATOC confirmed the suspicion of digestive neuroendocrine tumour metastatic to the ovaries and the final diagnosis was made following radical surgery. To the best of our knowledge, the mainly fibrous aspect at imaging, resembling that of the primary tumour, is the first to be described in English literature. Therefore, we think that in the presence of atypical bilateral, solid and mainly fibrous ovarian masses, careful search for a primary lesion along the digestive tract should be conducted.
Lung cancer outcome in the setting of chronic kidney disease: Does the glomerular filtration estimation formula matter?
Authors: Lu Ming‐Shian , Lu Hung‐I , Chen Tzu‐Ping , Chen Miao‐Fen , Lin Chien‐Chao , Tseng Yuan‐Hsi , Tsai Ying‐Huang
Published: December 2018

Background

The survival outcomes of lung cancer patients with coexisting chronic kidney disease (CKD) reported in the literature have been conflicting. We evaluate whether the survival of lung cancer patients with and without CKD differ significantly using two different formulas.

Methods

A retrospective, multicenter, propensity‐matched study of lung cancer patients with and without CKD was conducted. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/minute. Kaplan–Meier survival analysis was used to determine survival differences between CKD and non‐CKD patients using the Cockcroft–Gault formula (CKD–CG) compared to the Chronic Kidney Disease Epidemiology Collaboration Formula (CKD‐EPI).

Results

Baseline clinical characteristics did not differ statistically significantly between the groups. The CKD‐CG formula demonstrated median survival of 10.61 months (95% confidence interval [CI] 9.33–11.89) for the non‐CKD group compared to 10.58 months (95% CI 9.03–12.13) for the CKD group (P = 0.76). The CKD‐EPI formula demonstrated median survival of 9.10 months (95% CI 8.01–10.20) for the non‐CKD group compared to 7.59 months (95% CI 6.50–8.68) for the CKD group (P = 0.19). Cox regression analysis using both models revealed that CKD is not an independent risk factor for mortality in lung cancer patients. Although the CKD‐EPI formula revealed an increased risk of mortality and the CKD‐CG formula revealed decreased survival, these results were not statistically significant.

Conclusion

Lung cancer survival did not differ significantly between CKD and non‐CKD patients using either formula.
Morphological changes of physeal cartilage and secondary ossification centres in the developing femur of the house mouse (Mus musculus): A micro‐CT based study
Authors: Moncayo‐Donoso Miguelangel , Guevara Johana M. , Márquez-Flórez Kalenia , R. Fontanilla Marta , Barrera Luis A. , Garzón‐Alvarado Diego A.
Published: December 2018

In mammals, long bones are formed by ossification of a cartilaginous mould during early stages of development, through the formation of structures called the primary ossification centre, the secondary ossification centres (SOCs) and the physeal cartilages (PCs). The PC is responsible for long bone growth. The morphology of the PC and the SOCs varies during different stages of femoral growth. In this respect, several details involving the process of murine femoral development are lacking. In the present study, a morphological characterization of femur development from the embryonic period to adulthood in mice was studied using micro‐computed tomography (micro‐CT). To achieve this aim, femora were collected at embryonic day (E) 14.5, E16.5 and E18.5 and at postnatal day (P)1, P7, P14, P35, P46 and P52. CT images were obtained using a micro‐CT scanner (X‐SkyScan 1172; Micro Photonics) and analysed using the micro‐CT 3D visualization software Mimics (Materialise NV, Leuven, Belgium) and NRecon (Micro Photonics). The results of the present study revealed that the femur and its PCs and SOCs undergo morphological changes during different stages of development, including changes in their shape as well as position and thickness. These changes may be due to the response of the femur to mechanical loads imposed by muscle surrounding the bone during these stages of development. The result of the present study is important to improve our knowledge related to ossification and growth patterns of mouse femur during development.
Solar urticaria – An Australian case series of 83 patients
Authors: Photiou Louise , Foley Peter , Ross Gayle
Published: December 2018

Solar urticaria (SU) is a rare form of urticaria with a pathogenesis that is poorly understood. It affects all skin types, can be difficult to diagnose, and is challenging to manage effectively. We conducted a retrospective review of patients with SU in our institution. A total of 83 patients (56 females) were identified as having SU. The mean age was 32 years (7–74) at first development of symptoms/signs of SU. Pruritus was the most common symptom reported (79%). Of the 60 patients who underwent monochromator testing at least once, 35 had SU confirmed with most reacting to visible light and UVA, or to UVA alone. Antihistamines and sun avoidance remain the mainstay treatment for SU but other treatments, including omalizumab, are of potential interest in treating patients with recalcitrant SU. The characterisation of this large case series of patients may help dermatologists recognise and manage this rare disorder appropriately.
The Melanocortin 1 receptor and its influence on naevi and melanoma in dark‐skinned phenotypes
Authors: Smith David John Mackay
Published: December 2018

It is well appreciated that melanocortin 1 receptor variants can produce a fair skinned and red‐haired phenotype that has a strong association with increased melanoma risk. These patients are easily recognised and given appropriate attention. What may not be appreciated is that darker‐skinned individuals may also carry melanocortin 1 receptor variant alleles and that they can also be at increased risk of melanoma. Considering that melanocortin 1 receptor is crucial for melanocyte proliferation, regulation and differentiation do the naevi of these darker‐skinned individuals have specific features that help identify them as carrying one of these melanocortin 1 receptor variants and do melanomas that develop in dark‐skinned melanocortin 1 receptor variant carriers have particular characteristics?
Investor Sentiment, Anomalies, and Macroeconomic Conditions
Authors: Kim Dongcheol , Na Haejung
Published: December 2018

We examine whether the results supporting the sentiment‐related overpricing story by Stambaugh, Yu, and Yuan (J. Financial Economics, v. 104, p. 288–302) are still valid after controlling for macroeconomic conditions. We no longer find the results consistent with the sentiment‐related overpricing story after adjusting for the effect of macroeconomic conditions. The risk factors associated with macroeconomic conditions are mostly priced, and the average return spread in the anomalies is largely accounted for by the expected return spread implied by the risk factors. Their results might be a consequence of the use of an inadequately constructed sentiment index. It is premature to argue that the returns in the anomalies are driven by investor sentiment.
Repeated lipopolysaccharide exposure leads to placental endotoxin tolerance
Authors: Kim Maureen L. , Maloney Caroline , Klimova Natalia , Gurzenda Ellen , Lin Xinhua , Arita Yuko , Walker Treasure , Fazzari Melissa J. , Hanna Nazeeh
Published: December 2018

Problem

Placental infection induces increased levels of pro‐inflammatory cytokines, which have been implicated in the pathogenesis of pre‐term labor. Endotoxin tolerance is a phenomenon in which exposure to a dose of endotoxin makes tissue less responsive to subsequent exposures. The objective of our study was to determine whether repeated exposure to endotoxin will induce a tolerant phenotype in normal human second‐trimester placental tissue.

Methods of study

Human second‐trimester placental explants from elective termination of pregnancy were cultured and exposed to endotoxin (LPS). After 24 hours, the media was collected for analysis, and the explants were re‐exposed to LPS after adding fresh media for another 24 hours. This process was repeated for a total of 4 LPS doses. The media was collected from each day and analyzed for cytokine levels.

Results

The first LPS treatment stimulated the secretion of the pro‐inflammatory cytokines IL‐1β and TNF‐α. However, their production was significantly diminished with repeated LPS doses. Production of the anti‐inflammatory cytokines, IL‐1ra and IL‐10, was also stimulated by the first LPS treatment, but secretion was more gradually and moderately decreased with repeated LPS doses compared to the pro‐inflammatory cytokines. The ratios of the anti‐inflammatory/pro‐inflammatory mediators (IL‐1ra/IL‐1β and IL‐10/TNF‐α) indicate a progressively more anti‐inflammatory milieu with repeated LPS doses.

Conclusion

Repeated LPS exposure of human second‐trimester placental tissues induced endotoxin tolerance. We speculate that endotoxin tolerance at the maternal‐fetal interface will protect the fetus from exaggerated inflammatory responses after repeated infectious exposure.
People, systems and safety: resilience and excellence in healthcare practice
Authors: Smith A. F. , Plunkett E.
Published: December 2018

This article outlines recent developments in safety science. It describes the progression of three ‘ages’ of safety, namely the ‘age of technology’, the ‘age of human factors’ and the ‘age of safety management’. Safety science outside healthcare is moving from an approach focused on the analysis and management of error (‘Safety‐1’) to one which also aims to understand the inherent properties of safety systems that usually prevent accidents from occurring (‘Safety‐2’). A key factor in the understanding of safety within organisations relates to the distinction between ‘work as imagined’ and ‘work as done’. ‘Work as imagined’ assumes that if the correct standard procedures are followed, safety will follow as a matter of course. However, staff at the ‘sharp end’ of organisations know that to create safety in their work, variability is not only desirable but essential. This positive adaptability within systems that allows good outcomes in the presence of both favourable and adverse conditions is termed resilience. We argue that clinical and organisational work can be made safer, not only by addressing negative outcomes, but also by fostering excellence and promoting resilience. We outline conceptual and investigative approaches for achieving this that include ‘appreciative inquiry’, ‘positive deviance’ and excellence reporting.
The subthreshold micropulse laser treatment of the retina restores the oxidant/antioxidant balance and counteracts programmed forms of cell death in the mice eyes
Authors: De Cillà Stefano , Vezzola Diego , Farruggio Serena , Vujosevic Stela , Clemente Nausicaa , Raina Giulia , Mary David , Casini Giamberto , Rossetti Luca , Avagliano Laura , Martinelli Carla , Bulfamante Gaetano , Grossini Elena
Published: December 2018

Purpose

Subthreshold micropulse laser (SMPL) has been increasingly used for the treatment of different retinal and choroidal macular disorders. However, the exact mechanisms of action have not yet been clearly defined. Therefore, we aimed to examine the role of SMPL treatment in the modulation of oxidant/antioxidant systems, apoptosis and autophagy in the mice eyes.

Methods

A specific laser contact lens for retina was positioned on the cornea of 40 mice (20 young and 20 old) in order to focus the laser on the eye fundus for SMPL treatment. Within 6 months, 20 animals received one treatment only, whereas the others were treated three times. Eye specimens underwent histological analysis and were used for thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) quantification, as well as for the superoxide dismutase 1 (SOD1) and the selenoprotein thioredoxin reductase 1 (TrxR1) expression evaluation. Western blot was performed for nitric oxide synthase (NOS) subtypes detection and to examine changes in apoptotic/autophagy proteins expression.

Results

SMPL treatment reduced TBARS and increased GSH and SOD1 in the mice eyes. It also reduced cytochrome c, caspase 3 expression and activity and cleaved caspase 9, and increased Beclin 1, p62 and LC3β. The effects were more relevant in the elderly animals.

Conclusion

Our results showed that SMPL therapy restored the oxidant/antioxidant balance within retinal layers and modulated programmed forms of cell death. Further studies may confirm these data and could evaluate their relevance in clinical practice.
The Supply of Glass at Portus Ilicitanus (Alicante, Spain): A Meta‐Analysis of HIMT Glasses
Authors: de Juan Ares J. , Schibille N. , Vidal J. Molina , Sánchez de Prado M. D.
Published: December 2018

Portus Ilicitanus (Picola, Alicante) was the main sea harbour of the Roman Colonia Iulia Ilici Augusta and as such played a crucial role in the supply of fundamental commodities to the Iberian Peninsula. Excavations yielded large quantities of glass in fourth‐ and early fifth‐century contexts. Elemental analysis of 60 samples by laser ablation – inductively coupled plasma – mass spectrometry (LA–ICP–MS) confirmed that the glasses were imported from the Eastern Mediterranean. A majority of the glasses correspond to the HIMTa primary production group, which originates from Egypt. The statistical evaluation of published data of 589 HIMT glasses further revealed differential distribution patterns of the HIMTa and HIMTb subtypes between the Eastern and Western Mediterranean, suggesting chronological trends that are linked to wider geopolitical changes. This demonstrates the need for systematic large‐scale approaches to identify supply patterns and possible factors underlying geographical differences and/or chronological developments.
Adipocytes suppress differentiation of muscle cells in a co‐culture system
Authors: Seo Kangmin , Suzuki Takahiro , Kobayashi Ken , Nishimura Takanori
Published: December 2018

The development of adipose tissue in skeletal muscle is important for improving meat quality. However, it is still unclear how adipocytes grow in the proximity of muscle fibers. We hypothesized that adipocytes would suppress muscle cell growth so as to grow dominantly within muscle. In this study, we investigated the effect of adipocytes on the differentiation of muscle cells in a co‐culture system. The fusion index of C2C12 myoblasts co‐cultured with 3T3‐L1 adipocytes was significantly lower than that of the control. The expression of myogenin and myosin heavy chain in C2C12 muscle cells co‐cultured with 3T3‐L1 adipocytes was significantly lower than in the control. Furthermore, the expression of Atrogin‐1 and MuRF‐1 was higher in C2C12 muscle cells co‐cultured with 3T3‐L1 adipocytes than the control. These results suggest that 3T3‐L1 adipocytes suppress the differentiation of C2C12 myoblasts. In addition, 3T3‐L1 adipocytes induced the expression and secretion of IL‐6 in C2C12 muscle cells. The fusion index and myotube diameter were higher in C2C12 muscle cells co‐cultured with 3T3‐L1 cells in medium containing IL‐6‐neutralizing antibody than the control. Taken together, there is a possibility that adipocyte‐induced IL‐6 expression in muscle cells could be involved in the inhibition of muscle cell differentiation via autocrine.
Interculturality as a source of organisational positivity in expatriate work teams: An exploratory study
Authors: Bachkirov Alexandre Anatolievich
Published: December 2018

This study explored the issues related to interculturality and organisational positivity in culturally diverse teams (CDTs). The findings showed that interculturality in the expatriate settings of the Arabian Gulf is linked to organisational positivity, the manifestations of which include enjoyment, relationship building through concerted efforts to learn about others, and family‐like work environments. Interculturality‐driven organisational positivity is posited to encourage humanistic management, the attributes of which are sensitivity to human suffering, open‐mindedness, fairness, and respect. Organisational positivity is also theorised to improve CDT performance and stimulate professional and personal learning. Theoretical and practical implications of the findings are discussed.
Performance Pay and Applicant Screening
Authors: Jirjahn Uwe , Mohrenweiser Jens
Published: December 2018

Using German establishment data, we show that the relationship between intensity of individual‐based performance pay and intensity of applicant screening depends on the nature of production. In establishments with increased multitasking, performance pay is positively associated with applicant screening. By contrast, in establishments without increased multitasking, performance pay is negatively associated with applicant screening. We do not find a similar pattern of results for group‐based performance pay or profit‐sharing. Our findings fit the hypothesis that individual‐based performance pay induces a positive self‐sorting of employees if jobs are less multifaceted. In this case, employers with a high intensity of performance pay do not need intensive applicant screening to ensure a high quality of matches between workers and jobs. However, if jobs are more multifaceted, individual‐based performance pay can entail problems of adverse self‐sorting. In order to mitigate or overcome these problems, employers making intensive use of performance pay also screen applicants more intensively.
Histamine H3 receptor ligands by hybrid virtual screening, docking, molecular dynamics simulations, and investigation of their biological effects
Authors: Ghamari Nakisa , Zarei Omid , Reiner David , Dastmalchi Siavoush , Stark Holger , Hamzeh‐Mivehroud Maryam
Published: December 2018

Histamine H3 receptors (H3R), belonging to G‐protein coupled receptors (GPCR) class A superfamily, are responsible for modulating the release of histamine as well as of other neurotransmitters by a negative feedback mechanism mainly in the central nervous system (CNS). These receptors have gained increased attention as therapeutic target for several CNS related neurological diseases. In the current study, we aimed to identify novel H3R ligands using in silico virtual screening methods. To this end, a combination of ligand‐ and structure‐based approaches was utilized for screening of ZINC database on the homology model of human H3R. Structural similarity‐ and pharmacophore‐based approaches were employed to generate compound libraries. Various molecular modeling methodologies such as molecular docking and dynamics simulation along with different drug likeness filtering criteria were applied to select anti‐H3R ligands as promising candidate molecules based on different known parent lead compounds. In vitro binding assays of the selected molecules demonstrated three of them being active within the micromolar and submicromolar Ki range. The current integrated computational and experimental methods used in this work can provide new general insights for systematic hit identification for novel anti‐H3R agents from large compound libraries.
Pharmacophoric features for a very potent 5‐spirofluorenehydantoin inhibitor of cancer efflux pump ABCB1, based on X‐ray analysis
Authors: Żesławska Ewa , Kincses Annamária , Spengler Gabriella , Nitek Wojciech , Tejchman Waldemar , Handzlik Jadwiga
Published: December 2018

In order to extend knowledge about pharmacophoric features responsible for ABCB1 inhibitory properties of imidazolidin‐2,4‐dione derivatives, 1′‐[4‐(4‐(o‐methoxyphenyl)‐piperazin‐1‐yl)butyl]‐3′‐methyl‐spiro(fluoren‐9,5′‐imidazolidine)‐2′,4′‐dione (3) and its salt (4) with rhodanine‐3‐acetic acid (RA) were prepared and investigated by X‐ray diffraction method, as well as their efflux modulating effects in cancer cells (mouse T‐lymphoma), cytotoxic and antiproliferative activities were evaluated in vitro. The molecular geometry, intermolecular interactions, and crystal packing of base and acid forms of 3 were analyzed to see, if conformational changes influence the biological activities. The geometry of 2‐methoxyphenylpiperazine and 5‐spirofluorenehydantoin moieties was compared with other crystal structures containing these fragments. Our results indicated a very potent inhibitory action on ABCB1 pump, and significant cytotoxic and antiproliferative properties of 3 in T‐lymphoma, even more potent in the case of multidrug resistance cells. Furthermore, the compound 3 converted into the salt 4 of inactive acid (RA) has maintained both, the efflux pump inhibitory and antiproliferative activities, showing strong synergism with doxorubicin. A comparison of geometry of 3 in both crystal structures (3 and 4) shows a significant difference in the arrangement of piperazine ring with respect to the aliphatic linker.
Developmental Consequences of Child Abuse and Neglect: Implications for Intervention
Authors: Toth Sheree L. , Manly Jody T.
Published: December 2018

Child maltreatment is a heterogeneous phenomenon that frequently results in negative developmental trajectories across many domains of child functioning. In this article, we selectively review the literature on child maltreatment from the perspective of developmental psychopathology, emphasizing the central role of attachment in setting the path for developmental risks and providing opportunities for prevention and early intervention. Intervention research has highlighted the role of relational interventions in potentially promoting resilient functioning by supporting the development of more positive parent–child interactions. We describe an intervention called child–parent psychotherapy to illustrate the positive impact of a treatment for trauma that is informed by attachment theory and based on evidence, and we suggest how it can ameliorate outcomes for maltreated children.
Family Stress Processes and Children's Self‐Regulation
Authors: Duran Chelsea A.K. , Cottone Elizabeth , Ruzek Erik A. , Mashburn Andrew J. , Grissmer David W.
Published: December 2018

Economic hardship can affect children's development through child–caregiver interactions, which may mediate cascading effects of other family stress processes. This study examined, simultaneously, the relations of financial strain, caregiver general stress, and child–caregiver conflict—each measured at two time points—with child self‐regulatory outcomes in a high‐poverty sample (age 5–7 years; n = 343). Increase in child–caregiver conflict mediated negative relations between other processes and development of executive function. In contrast, only increase in financial strain had direct, negative association with development of delay of gratification and did not significantly mediate relations between any other process and children's outcomes. Results have implications for understanding effects of family stress on self‐regulatory outcomes and for interventions with low‐income families.
Comparison of recovery and outcome after left and right colectomy
Authors: Grass F. , Lovely J. K. , Crippa J. , Ansell J. , Hübner M. , Mathis K. L. , Larson D. W.
Published: December 2018

Aim

The present study aimed to compare functional recovery and surgical outcomes after left and right colectomies.

Method

Consecutive elective left and right colon resections for benign and malignant indications, performed between 2011 and 2016 and recorded in a prospectively maintained enhanced recovery database, were analysed. Demographic and surgical items, as well as functional recovery and 30‐day complications, were compared between left‐sided and right‐sided colectomies. Multivariable analysis was performed to identify risk factors for postoperative ileus (POI).

Results

In total, 1001 left and 1041 right colectomies were comparable regarding demographic factors; only body mass index (BMI) was higher in patients undergoing left‐sided resections (> 30 kg/m2: 33% vs 27%, P = 0.004). Malignancy (29% vs 67%, P < 0.001) and Crohn's disease (1% vs 31%, P < 0.001) were preponderant in right colectomies, whereas diverticular disease (68% vs 1%, P < 0.001) was the most common indication for left colectomy. Compliance with the enhanced recovery pathway (ERP) was comparable. While the minimally invasive approach was the preferred approach for both sides (61% vs 64%, P = 0.158), left colectomies took longer (180 ± 80 min vs 150 ± 70 min, P < 0.001), needed more perioperative fluids (3.1 ± 1.4 l vs 2.7 ± 1.5 l, P < 0.001) and resulted in greater postoperative weight gain (3.9 ± 6.5 kg vs 2.6 ± 6 kg, P = 0.025). Crohn's disease (OR = 2.64, 95% CI: 1.27–5.46) and fluid overload (OR = 2.02, 95% CI: 1.06–3.82) were independent risk factors for POI.

Conclusion

Despite equal ERP compliance, postoperative ileus was higher after right‐sided colectomies. This finding was associated with Crohn's disease and fluid overload.
A propensity‐score‐matched analysis of laparoscopic vs open surgery for rectal cancer in a population‐based study
Authors: Manchon‐Walsh P. , Aliste L. , Biondo S. , Espin E. , Pera M. , Targarona E. , Pallarès N. , Vernet R. , Espinàs J. A. , Guarga A. , Borràs J. M.
Published: December 2018

Aim

The oncological risk/benefit trade‐off for laparoscopy in rectal cancer is controversial. Our aim was to compare laparoscopic vs open surgery for resection of rectal cancer, using unselected data from the public healthcare system of Catalonia (Spain).

Methods

This was a multicentre retrospective cohort study of all patients who had surgery with curative intent for primary rectal cancer at Catalonian public hospitals from 2011 to 2012. We obtained follow‐up data for up to 5 years. To minimize the differences between the two groups, we performed propensity score matching on baseline patient characteristics. We used multivariate Cox proportional hazards regression analyses to assess locoregional relapse at 2 years and death at 2 and 5 years.

Results

Of 1513 patients with Stage I–III rectal cancer, 933 (61.7%) had laparoscopy (conversion rate 13.2%). After applying our propensity score matching strategy (2:1), 842 laparoscopy patients were matched to 517 open surgery patients. Multivariate Cox analysis of death at 2 years [hazard ratio (HR) 0.65, 95% CI 0.48, 0.87; P = 0.004] and 5 years (HR 0.61, 95% CI 0.5, 0.75; P < 0.001) and of local relapse at 2 years (HR 0.44, 95% CI 0.27, 0.72; P = 0.001) showed laparoscopy to be an independent protective factor compared with open surgery.

Conclusions

Laparoscopy results in lower locoregional relapse and long‐term mortality in rectal cancer in unselected patients with all‐risk groups included. Studies using long‐term follow‐up of cohorts and unselected data can provide information on clinically relevant outcomes to supplement randomized controlled trials.
Radiotherapy after local excision of rectal cancer may offer reduced local recurrence rates
Authors: Jones H. J. S. , Goodbrand S. , Hompes R. , Mortensen N. , Cunningham C.
Published: December 2018

Aim

Early rectal cancer can be managed effectively with local excision, which is now the standard of care for many T1 lesions. However, the presence of unexpected adverse histopathological factors may indicate an increased risk of local recurrence, prompting consideration of completion radical surgery. Many patients are unfit or prefer to avoid radical surgery, relying instead on surveillance and early detection of recurrent disease. Recently, radiotherapy has shown promise as an adjuvant therapy in this group. This study assesses local recurrence rates after local excision with adjuvant radiotherapy at a single centre.

Method

This was a retrospective review of a prospective database of all patients undergoing transanal endoscopic microsurgery (TEM) in a single institution. Data covering a 10‐year period were analysed.

Results

Of 197 patients undergoing TEM for rectal cancer, 33 (17%) had adjuvant radiotherapy because of adverse histopathological features. At 3.2 years’ median follow‐up, there were three instances of local recurrence (9.1%). Estimated local recurrence at 1 and 3 years was 0% and 6.9%, compared to 16.8% and 21.2% in a propensity‐score‐matched group who were followed by surveillance alone. Local recurrence was diagnosed at a median of 23 months post‐TEM in the radiotherapy group, compared to 8 months in the matched group.

Conclusion

Radiotherapy after TEM is associated with a trend towards a reduced rate of local recurrence, even for high‐risk disease. Radiotherapy would appear to offer a viable alternative to radical completion surgery in the presence of unforeseen adverse histopathological features, as long as a meticulous surveillance programme is in place.
Small cell lung cancer in the young: Characteristics, diagnosis and outcome data
Authors: Jiang Shiyu , Hao Xuezhi , Li Junling , Hu Xingsheng , Xiao Zefen , Wang Hongyu , Wang Yan , Sun Yan , Shi Yuankai
Published: December 2018

Background

Patients with small cell lung cancer (SCLC) younger than 40 years are limited in number. Our research aimed to assess the characteristics, diagnosis and outcomes of this patient population.

Methods

Records of patients under the age of 40 with SCLC at the Chinese Academy of Medical Sciences between January 2006 and December 2015 were reviewed and evaluated.

Results

One hundred and three patients (67.0% limited stage, 33.0% extensive stage) were included, along with 54 (52.4%) never‐smokers. The median diagnostic interval and the median survival time (MST) were 51.0 days and 24.0 months, respectively. A total of 41 (39.8%) patients claimed to have undergone antibiotic treatment before diagnosis, with a median duration of 2 weeks. In univariate analysis, survival was better for the limited stage group than the extensive stage group (MST, 28.0 vs. 13.0 months, P < 0.0001). Also, patients who received concurrent radiochemotherapy had better survival than those who received chemotherapy alone (MST, 29.0 vs. 18.0 months, P = 0.001). Patients with antibiotic treatment before SCLC diagnosis have worse prognosis than those without (MST, 21.0 vs. 27.0 months, P = 0.008). Moreover, a timely diagnosis (≤1 month) exerted a positive impact on the overall survival in limited stage patients (48.0 vs. 26.0 months, P = 0.047) and on progression‐free survival in extensive stage patients (6.0 vs. 3.0 months, P = 0.030). Multivariate analysis suggested that disease stage, history of antibiotic treatment before SCLC diagnosis and performance status independently correlated with survival.

Conclusion

Our study identified distinct characteristics and prognostic factors of SCLC patients under 40 years. More timely care may improve patient prognosis.
Longitudinal immunosuppression data can minimize misclassification bias in solid organ transplantation cohorts
Authors: Laaksonen Maarit A. , Webster Angela C. , McCaughan Geoff W. , Keogh Anne M. , Grulich Andrew E. , Vajdic Claire M.
Published: December 2018

Background

Most cohort studies investigating the effect of immunosuppression on transplant outcomes use drugs at first hospital discharge. We evaluated the extent of drug exposure misclassification and its impact on outcome prediction.

Methods

We retrospectively collected longitudinal immunosuppression data, at discharge and at 1, 5, 10, and 15 years after transplantation, and outcomes for solid organ transplant recipients 1984‐2006 (n = 3133). We compared the risk of death from exposure to individual immunosuppressive drugs (cyclosporine, tacrolimus, azathioprine, and mycophenolate) and dual therapies, as defined by discharge only vs longitudinal immunosuppression data, using adjusted Cox proportional hazards models.

Results

During a median follow‐up of 5.2 years, immunosuppressive drugs were altered for 947 (30%) recipients and 955 recipients died. Longitudinal receipt of cyclosporine and azathioprine were associated with an increased risk (HR 1.41, 95% CI 1.07‐1.89, and HR 1.34, 95% CI 1.00‐1.80), and mycophenolate with a reduced risk (HR 0.35, 0.16‐0.78), of death. Recipients on mycophenolate and tacrolimus dual therapy had a lower risk of death compared to those on azathioprine and cyclosporine dual therapy (HR 0.30, 0.10‐0.93). The increased risk of death associated with the receipt of cyclosporine or azathioprine was not shown in the analyses based on drugs allocated at discharge, and all of the associations between immunosuppressive regimens and death were strengthened in the analyses based on longitudinal immunosuppression data.

Conclusions

Cohort findings based on immunosuppressive drugs allocated at discharge should be interpreted with caution due to potential exposure misclassification. The use of granular, longitudinal data on immunosuppressive regimens could improve prediction.
Revision of the Capsaspora genome using read mating information adjusts the view on premetazoan genome
Authors: Denbo Seitaro , Aono Katsutoshi , Kai Takaaki , Yagasaki Rei , Ruiz‐Trillo Iñaki , Suga Hiroshi
Published: December 2018

The genome sequences of unicellular holozoans, the closest relatives to animals, are shedding light on the evolution of animal multicellularity, shaping the genetic contents of the putative premetazoans. However, the assembly quality of the genomes remains poor compared to the major model organisms such as human and fly. Improving the assembly is critical for precise comparative genomics studies and further molecular biological studies requiring accurate sequence information such as enhancer analysis and genome editing. In this report, we present a new strategy to improve the assembly by fully exploiting the information of Illumina mate‐pair reads. By visualizing the distance and orientation of the mapped read pairs, we could highlight the regions where possible assembly errors exist in the genome sequence of Capsaspora, a lineage of unicellular holozoans. Manual modification of these errors repaired 590 assembly problems in total and reassembled 84 supercontigs into 55. Our telomere prediction analysis using the read pairs containing the pan‐eukaryotic telomere‐like sequence identified at least 13 chromosomes. The resulting new assembly posed us a re‐annotation of 112 genes, including 15 putative receptor protein tyrosine kinases. Our strategy thus provides a useful approach for improving assemblies of draft genomes, and the new Capsaspora genome offers us an opportunity to adjust the view on the genome of the unicellular animal ancestor.
Wall motion tracking in fetal echocardiography—Application of low and high frame rates for strain analysis
Authors: Enzensberger Christian , Rostock Laura , Graupner Oliver , Götte Malena , Wolter Aline , Vorisek Carina , Herrmann Johannes , Axt‐Fliedner Roland
Published: December 2018

Objective

Compared to adults, fetal heart rates (HR) are elevated necessitating higher frame rates (FR) for strain analysis by speckle tracking echocardiography. The aim of this study was to investigate the influence of high FR compared to low FR on strain analysis in 2D speckle tracking.

Methods

Fetal echocardiography was prospectively performed and acquired from the apical or basal four‐chamber views of the heart. Images were optimized for clear delineation of myocardial walls and stored in either raw Digital Imaging and Communications in Medicine (DICOM) cine‐loop format for offline analysis with a low FR of 60 frames per second (fps) or in the original FR (acoustic FR = AFR). For each loop, right (RV) and left (LV) ventricular fetal longitudinal peak systolic strain (LPSS) values were assessed by 2D Wall Motion tracking.

Results

One hundred and three healthy fetuses were included with a mean gestational age of 26.3 ± 5.5 weeks. Mean AFR was 127 ± 26 fps. A mean FR/HR ratio was assessed of 0.42 and 0.90 between the low FR and AFR group, respectively. Relating to LPSS values, there was a significant difference between low FR and AFR for both ventricles (LV: −16.5% ± 3.9% (low FR) vs −13.6% ± 3.5% (AFR); and RV: −15.1% ± 3.6% (low FR) vs −12.6% ± 3.7% (AFR), both P < 0.001).

Conclusions

Fetal LV and RV LPSS values derived with high AFR were significantly lower than corresponding LPSS values analyzed with low FR of 60 fps. Future studies are needed to clarify the clinical importance of this relationship.
Impact of seed abundance on seed processing and dispersal by the red ant Myrmica rubra
Authors: Detrain Claire , Bologna Audrey
Published: December 2018

1. Myrmecochory sensu stricto is an ant–plant mutualism in which non‐granivorous ants disperse plant diaspores after feeding on their nutrient‐rich seed appendage, the elaiosome. Phenological traits associated with the diaspore can influence the behaviour of ants and thus their ultimate efficiency as seed dispersers.

2. This study investigated how a contrasting availability of seeds (20 vs. 200 seeds) from the diplochorous Chelidonium majus (Papaveraceae, Linnaeus) plant species influences the behaviour of Myrmica rubra (Formicidae, Linnaeus) ants, from the retrieval of seeds until their dispersal outside the ant nest.

3. Regardless of seed abundance, the ants collected the first diaspores at similar rates. Then, seed retrieval sped up over time for large seed sources until satiation took place with only one‐third of the tested colonies wholly depleting abundant seed sources.

4. No active recruitment by trail‐laying ants was triggered, even to an abundant seed source

5. In both conditions of seed abundance, the majority of the diaspores retrieved inside the nest were discarded with the elaiosome removed and were dispersed at similar distances from the nest.

6. The paper concludes with a discussion of how the quantity of seeds released by a plant with a dual mode of dispersal can potentially influence the behaviour of ant dispersers and hence the dispersal efficiency derived from myrmecochory.
Are PARKIN patients ideal candidates for dopaminergic cell replacement therapies?
Authors: Kunath Tilo , Natalwala Ammar , Chan Claire , Chen Yixi , Stecher Benjamin , Taylor Martin , Khan Sadaquate , Muqit Miratul M. K.
Published: December 2018

Parkinson's is a heterogeneous, complex condition. Stratification of Parkinson's subtypes will be essential to identify those that will benefit most from a cell replacement therapy. Foetal mesencephalic grafts can alleviate motor symptoms in some Parkinson's patients. However, on‐going synucleinopathy results in the grafts eventually developing Lewy bodies, and they begin to fail. We propose that Parkinson's patients with PARKIN mutations may benefit most from a cell replacement therapy because (a) they often lack synucleinopathy, and (b) their neurodegeneration is often confined to the nigrostriatal pathway. While patients with PARKIN mutations exhibit clinical signs of Parkinson's, post‐mortem studies to date indicate the majority lack Lewy bodies suggesting the nigral dopaminergic neurons are lost in a cell autonomous manner independent of α‐synuclein mechanisms. Furthermore, these patients are usually younger, slow progressing and typically do not suffer from complex non‐nigral symptoms that are unlikely to be ameliorated by a cell replacement therapy. Transplantation of dopaminergic cells into the putamen of these patients will provide neurons with wild‐type PARKIN expression to re‐innervate the striatum. The focal nature of PARKIN‐mediated neurodegeneration and lack of active synucleinopathy in most young‐onset cases makes these patients ideal candidates for a dopaminergic cell replacement therapy. Strategies to improve the outcome of cell replacement therapies for sporadic Parkinson's include the use of adjunct therapeutics that target α‐synuclein spreading and the use of genetically engineered grafts that are resistant to synucleinopathy.
Prefrontal cortex development and emergence of self‐regulatory competence: the two cardinal features of adolescence disrupted in context of alcohol abuse
Authors: Jadhav Kshitij S. , Boutrel Benjamin
Published: December 2018

Adolescence is a tumultuous period in the lifetime of an individual confronted to major changes in emotional, social and cognitive appraisal. During this period of questioning and doubt, while the executive functions are still maturing, the abstract reasoning remains vague and the response inhibition loose; ultimately the adolescent scarcely resists temptation. Consequently, adolescence is often associated with uninhibited risk‐taking, reckless behaviours, among which are alcohol and illicit drugs use. Here, we discuss how the development of the prefrontal cortex (which critically contributes to rational decision‐making and temporal processing of complex events) can be associated with the idiosyncratic adolescent behaviour, and potentially uncontrolled alcohol use. Most importantly, we present clinical and preclinical evidence supporting that ethanol exposure has deleterious effects on the adolescent developing brain. Ultimately, we discuss why a late maturing prefrontal cortex represents a ripe candidate to environmental influences that contribute to shape the adolescent brain but, potentially, can also trigger lifelong maladaptive responses, including increased vulnerability to develop substance use disorder later in life.
Convergent synaptic inputs to layer 1 cells of mouse cortex
Authors: Lam Ying‐Wan , Sherman S. Murray
Published: December 2018

We used whole cell recordings from slice preparations of mouse cortex to identify various inputs to neurons of layer 1. Two sensory cortical areas were targeted: a primary somatosensory area, namely, the barrel cortex of S1, and a higher order visual area, namely, V2M. Results were similar from both areas. By activating local inputs using photostimulation with caged glutamate, we also identified glutamatergic (and possibly GABAergic) inputs from all lower layers plus GABAergic inputs from nearby layer 1 neurons. However, the patterns of such inputs to layer 1 neurons showed great variation among cells. In separate experiments, we found that electrical stimulation of axons running parallel to the cortical surface in layer 1 also evoked a variety of convergent input types to layer 1 neurons, including glutamatergic “drivers” and “modulators” plus classic modulatory inputs, including serotonergic, nicotinic, α‐ and β‐adrenergic, from subcortical sites. Given that these layer 1 cells significantly affect the responses of other cortical neurons, especially via affecting the apical dendrites of pyramidal cells so important to cortical functioning, their role in cortical processing is significant. We believe that the data presented here lead to better understanding of the functioning of layer 1 neurons in their role of influencing cortical processing.
HCN4 knockdown in dorsal hippocampus promotes anxiety‐like behavior in mice
Authors: Günther Anne , Luczak Vincent , Gruteser Nadine , Abel Ted , Baumann Arnd
Published: December 2018

Hyperpolarization‐activated and cyclic nucleotide‐gated (HCN) channels mediate the Ih current in the murine hippocampus. Disruption of the Ih current by knockout of HCN1, HCN2 or tetratricopeptide repeat‐containing Rab8b‐interacting protein has been shown to affect physiological processes such as synaptic integration and maintenance of resting membrane potentials as well as several behaviors in mice, including depressive‐like and anxiety‐like behaviors. However, the potential involvement of the HCN4 isoform in these processes is unknown. Here, we assessed the contribution of the HCN4 isoform to neuronal processing and hippocampus‐based behaviors in mice. We show that HCN4 is expressed in various regions of the hippocampus, with distinct expression patterns that partially overlapped with other HCN isoforms. For behavioral analysis, we specifically modulated HCN4 expression by injecting recombinant adeno‐associated viral (rAAV) vectors mediating expression of short hairpin RNA against hcn4 (shHcn4) into the dorsal hippocampus of mice. HCN4 knockdown produced no effect on contextual fear conditioning or spatial memory. However, a pronounced anxiogenic effect was evident in mice treated with shHcn4 compared to control littermates. Our findings suggest that HCN4 specifically contributes to anxiety‐like behaviors in mice.
Risk factors of surgical site infection in geriatric orthopedic surgery: A retrospective multicenter cohort study
Authors: Ren Mingguang , Liang Weidong , Wu Zhiyu , Zhao Hongmei , Wang Jingwei
Published: December 2018

Aim

As we are experiencing the progressive aging of our population, risk management of geriatric orthopedic patients is extremely important. The present study was carried out to identify independent predictors of surgical site infection and to better define the threshold value of serum albumin on postoperative wound infection in older patients.

Methods

This retrospective multicenter study was carried out from January 2015 to June in 2017. A total of 3378 older patients (aged ≥60 years) were enrolled. We extracted the patients’ demographics, characteristics of disease, treatment‐related variables and indexes of laboratory examination. Receiver operating characteristic analysis was carried out to find the optimum cut‐off value for serum albumin. Univariate and multivariate logistic analysis models were carried out, respectively, to determine independent predictors of surgical site infection.

Results

A total of 123 patients developed wound infection in the present study. Surgical site infection prolonged hospitalization of patients by a mean of 14.2 days. The overall incidence was 3.64%, with 0.47% for deep infection and 3.16% for superficial infection. Independent predictors of surgical site infection identified by multivariate analysis were traumatic injury (odds ratio 12.42, 95% CI 6.80–22.12; P = 0.000), serum albumin <32.6 g/L (odds ratio 2.54, 95% CI 1.22–5.29; P = 0.013) and American Society of Anesthesiologists physical status index class 3 or higher (odds ratio 2.14, 95% CI = 1.24–3.69; P = 0.006).

Conclusions

We recommend that surgeons evaluate the nutritional status of older patients and optimize the perioperative strategy of supplementary nutrition support to reduce the risk of postoperative wound infection. Geriatr Gerontol Int 2019; 19: 213–217.