bluuebunny/crossref_metadata_2025 huggingface dataset:
Technologies of cryoprotectant‐free vitrification of human spermatozoa: asepticity as criterion of effectiveness
Authors: Isachenko V. , Rahimi G. , Mallmann P. , Sanchez R. , Isachenko E.
Published: October 2017

This review describes 120 years history of technology for cryoprotectant‐free cryopreservation of human spermatozoa by direct plunging into liquid nitrogen (vitrification). It is presented an explanation why cryoprotectant‐free vitrification for some human ejaculates is better than conventional freezing and vitrification with the presence of cryoprotectants. Special attention is given to the extremely high viability of viruses, bacteria and micoplasmas after cryoprotectant‐free cryopreservation in culture medium and even in distilled water. This fact increases the potential risk of disease transmission through liquid nitrogen. It is concretized the concept “asepticity” as obvious parameter for any medical assisted reproduction technology which includes the cooling of cells in liquid nitrogen. It is described the role of nonpermeable compounds of mediums for cryoprotectant‐free vitrification: carbohydrates, proteins, lipoproteins, antioxidants. This review summarizes concerned data regarding two groups of different current technologies for cryoprotectant‐free vitrification of human spermatozoa: with direct contact of spermatozoa with liquid nitrogen as well as with full isolation of these cells from liquid nitrogen (aseptic technologies).
Predictive value of pre‐operative inflammation‐based prognostic scores (neutrophil‐to‐lymphocyte ratio, platelet‐to‐lymphocyte ratio, and monocyte‐to‐eosinophil ratio) in testicular sperm extraction: a pilot study
Authors: Yucel C. , Keskin M. Z. , Cakmak O. , Ergani B. , Kose C. , Celik O. , Islamoglu E. , Ucar M. , Koc G. , Kozacioglu Z.
Published: October 2017

To investigate the ability of some hematologic prognostic scores demonstrating inflammation in predicting sperm presence in testicular sperm extraction (TESE). We retrospectively investigated the medical data of 430 patients with the diagnosis of non‐obstruc tive azoospermia (NOA) who had undergone TESE operation consecutively in our institution between the dates of January 2009 and February 2017. In all, 352 patients with the diagnosis of NOA, with bilaterally palpable vas deferens, who had undergone TESE for the first time, were included in the study. Patients with genetic anomalies, genital infection, history of surgery or vasectomy, chronic diseases, history of inflammatory, metabolic, rheumatologic, or malignant diseases, morbid obesity, with the diagnosis of clinical varicocele, or patients who had undergone TESE for the second time were excluded from the study. According to the results of TESE, the patients were divided into two groups as those with sperm retrieval and those without sperm retrieval. These groups were compared in terms of age, infertility duration, body mass index, hormone profile, hematologic parameters, neutrophil‐to‐lymphocyte ratio (NRL), monocyte‐to‐eosinophil ratio (MER), and platelet‐to‐lymphocyte ratio (PLR). The NLR and PLR levels were found to be significantly higher in patients without sperm retrieval at TESE compared to those with sperm retrieval. The logistic regression analysis showed NLR as an independent factor that showed the presence of spermatozoa at TESE (odds ratio: 4.786, %95 confidence interval: 2.667–8.589, p < 0.001). The area under the ROC curve (AUC) for the PLR was determined to be 0.574. As the calculated AUC value of the PLR was below 0.6, there was insufficient evidence determined at TESE to say that it was a reliable marker to indicate the presence of spermatozoa. The area of the MER value under the ROC curve was not statistically significant. It has been demonstrated that systemic inflammation negatively affects the probability of extracting spermatozoa in TESE and NLR is an independent factor indicating the presence of spermatozoa in TESE.
Male accessory gland inflammation, infertility, and sexual dysfunctions: a practical approach to diagnosis and therapy
Authors: Calogero A. E. , Duca Y. , Condorelli R. A. , La Vignera S.
Published: October 2017

The role of urogenital inflammation in causing infertility and sexual dysfunctions has long been a matter of debate in the international scientific literature. The most recent scientific evidences show that male accessory gland infection/inflammation could alter, with various mechanisms, both conventional and biofunctional sperm parameters, and determine worst reproductive outcome. At the same time, the high prevalence of erectile dysfunction and premature ejaculation in patients with male accessory gland infection/inflammation underlines the close link between these diseases and sexual dysfunctions. The aim of this review was to provide the reader the basis for a correct diagnosis of male accessory gland infection/inflammation and a subsequent appropriate therapeutic approach, particularly in patients with infertility and/or sexual dysfunction.
Valproate Plays a Protective Role against Migraine by Inhibiting Protein Kinase C Signalling in Nitroglycerin‐treated Mice
Authors: Yi Lian , Wu Qiong , Chen Nan , Song Ge , Wang Chao , Zou Qiaoge , Zhang Zhongling
Published: October 2017

Migraine is a common disease with a high morbidity. Valproate (VP) is used as an anti‐epilepsy drug in clinic. This study aimed to investigate the role of VP in nitroglycerin (NTG)‐induced migraine using a mouse model. NTG was employed by intraperitoneal injection to induce a migraine model in mice. The NTG administration caused mouse head discomforts, decreased tolerance to cold or hot stimulation and increased content of nitric oxide, calcitonin gene‐related peptide and neuropeptide Y in serum, which were ameliorated by intraperitoneal injection of VP. The levels of two inflammatory factors, interleukin (IL)‐1β and inducible nitric oxide synthase, in dura mater were increased by NTG treatment, while the increase was attenuated by application of VP. In addition, the phosphorylation levels of protein kinase C (PKC) α, γ, δ and ε were increased by NTG and decreased by VP. However, their total expression at the transcriptional and translational levels did not change significantly. Two substrates of PKC, cAMP‐response element binding protein 1 and signal transducer and activator of transcription 1 were also phosphorylated by NTG application, and the phosphorylation level was attenuated by VP, consistent with the change of PKC informs. Together, we demonstrated that VP prevented damage due to migraine by inhibiting PKC signalling in NTG‐injected mice, which may provide a basis for investigating the clinical treatment of migraine.
The prioritization of symptom beliefs over illness beliefs: The development and validation of the Pain Perception Questionnaire for Young People
Authors: Ghio Daniela , Thomson Wendy , Calam Rachel , Ulph Fiona , Baildam Eileen M. , Hyrich Kimme , Cordingley Lis
Published: October 2017

Objectives

To investigate the suitability of the revised Illness Perception Questionnaire (IPQ‐R) for use with adolescents with a long‐term pain condition and to validate a new questionnaire for use with this age group.

Design

A three‐phase mixed‐methods study.

Methods

Phase 1 comprised in‐depth qualitative analyses of audio‐recorded cognitive interviews with 20 adolescents with juvenile idiopathic arthritis who were answering IPQ‐R items. Transcripts were coded using framework analysis. A content analysis of their intended responses to individual items was also conducted. In Phase 2, a new questionnaire was developed and its linguistic and face validity were assessed with 18 adolescents without long‐term conditions. In Phase 3, the construct validity of the new questionnaire was assessed with 240 adolescents with juvenile idiopathic arthritis. A subset of 43 adolescents completed the questionnaire a second time to assess test–retest reliability. All participants were aged 11–16 years.

Results

Participants described both conceptual and response format difficulties when answering IPQ‐R items. In response, the Pain Perception Questionnaire for Young People (PPQ‐YP) was designed which incorporated significant modifications to both wording and response formats when compared with the IPQ‐R. A principal component analysis of the PPQ‐YP identified ten constructs in the new questionnaire. Emotional representations were separated into two constructs, responsive and anticipatory emotions. The PPQ‐YP showed high test–retest reliability.

Conclusions

Symptom beliefs appear to be more salient to adolescents with a long‐term pain condition than beliefs about the illness as a whole. A new questionnaire to assess pain beliefs of adolescents was designed. Further validation work may be needed to assess its suitability for use with other pain conditions.

Statement of contribution

What is already known on this subject?

Versions of the adult Revised Illness Perception Questionnaire (IPQ‐R) have been adapted for adolescents and children by changing item wording; however, research to assess the degree to which the underlying IPQ‐R constructs are relevant to adolescents with a long‐term condition had not been performed.

What the present study adds?

In adolescents, beliefs about symptoms of their condition are more salient than beliefs about the illness as a whole.

Question response formats for children and young people need to take account of age‐specific abilities.

A new questionnaire has been designed for adolescents with pain. It is theoretically congruent with the CS‐SRM.
Impact of bladder cancer on health‐related quality of life
Authors: Smith Angela B. , Jaeger Byron , Pinheiro Laura C. , Edwards Lloyd J. , Tan Hung‐Jui , Nielsen Matthew E. , Reeve Bryce B.
Published: October 2017

Objectives

To identify changes in health‐related quality of life (HRQoL) after diagnosis of bladder cancer in older adults in comparison with a group of adults without bladder cancer (controls).

Patients and Methods

Data from the Surveillance, Epidemiology and End Results registries were linked with Medicare Health Outcomes Survey (MHOS) data. Medicare beneficiaries aged ≥65 years in the period 1998–2013, who were diagnosed with bladder cancer between baseline and follow‐up through the MHOS, were matched with control subjects without cancer using propensity scores. Linear mixed models were used to estimate predictors of HRQoL changes.

Results

After matching, 535 patients with bladder cancer (458 non‐muscle‐invasive bladder cancer [NMIBC] and 77 with muscle‐invasive bladder cancer [MIBC]) and 2 770 control subjects without cancer were identified. Both patients with NMIBC and those with MIBC reported significant declines in HRQoL scores over time vs controls: physical component summary −2 and −5.3 vs −0.4, respectively; bodily pain −1.9 and −3.6 vs −0.7; role physical −2.7 and −4.7 vs −0.7; general health −2.4 and −6.1 vs 0; vitality −1.2 and −3.5 vs −0.1; and social functioning −2.1 and −5.7 vs −0.8. All scores ranged from 0 to 100. When stratified by time since diagnosis, HRQoL improved over 1 year for some domains (role physical), but remained lower across most domains.

Conclusions

After diagnosis, patients with bladder cancer experienced significant declines in physical, mental and social HRQoL relative to controls. Decrements were most pronounced among individuals with MIBC. Methods to better understand and address HRQoL decrements among patients with bladder cancer are needed.
Sigma‐1 receptor agonist increases axon outgrowth of hippocampal neurons via voltage‐gated calcium ions channels
Authors: Li Dong , Zhang Shu‐Zhuo , Yao Yu‐Hong , Xiang Yun , Ma Xiao‐Yun , Wei Xiao‐Li , Yan Hai‐Tao , Liu Xiao‐Yan
Published: October 2017

Introduction

Sigma‐1 receptors (Sig‐1Rs) are unique endoplasmic reticulum proteins that have been implicated in both neurodegenerative and ischemic diseases, such as Alzheimer's disease and stroke. Accumulating evidence has suggested that Sig‐1R plays a role in neuroprotection and axon outgrowth. The underlying mechanisms of Sig‐1R‐mediated neuroprotection have been well elucidated. However, the mechanisms underlying the effects of Sig‐1R on axon outgrowth are not fully understood.

Methods

To clarify this issue, we utilized immunofluorescence to compare the axon lengths of cultured naïve hippocampal neurons before and after the application of the Sig‐1R agonist, SA4503. Then, electrophysiology and immunofluorescence were used to examine voltage‐gated calcium ion channel (VGCCs) currents in the cell membranes and growth cones.

Results

We found that Sig‐1R activation dramatically enhanced the axonal length of the naïve hippocampal neurons. Application of the Sig‐1R antagonist NE100 and gene knockdown techniques both demonstrated the effects of Sig‐1R. The growth‐promoting effect of SA4503 was accompanied by the inhibition of voltage‐gated Ca2+ influx and was recapitulated by incubating the neurons with the L‐type, N‐type, and P/Q‐type VGCC blockers, nimodipine, MVIIA and ω‐agatoxin IVA, respectively. This effect was unrelated to glial cells. The application of SA4503 transformed the growth cone morphologies from complicated to simple, which favored axon outgrowth.

Conclusion

Sig‐1R activation can enhance axon outgrowth and may have a substantial influence on neurogenesis and neurodegenerative diseases.
The self‐sabotage of conservation: reply to Manfredo et al.
Authors: Ives Christopher D. , Fischer Joern
Published: October 2017

Article impact statement: To address conservation challenges conservation scientists must work to change social values.
Revisiting the challenge of intentional value shift: reply to Ives and Fischer
Authors: Manfredo Michael J. , Bruskotter Jeremy T. , Teel Tara L. , Fulton David C. , Oishi Shigehiro , Uskul Ayse K. , Redford Kent H. , Schwartz Shalom H. , Arlinghaus Robert , Kitayama Shinobu , Sullivan Leeann
Published: October 2017

Article impact statement: Conservation values are unlikely to change through intentional efforts.
Berberine inhibits the chemotherapy‐induced repopulation by suppressing the arachidonic acid metabolic pathway and phosphorylation of FAK in ovarian cancer
Authors: Zhao Yawei , Cui Lianzhi , Pan Yue , Shao Dan , Zheng Xiao , Zhang Fan , Zhang Hansi , He Kan , Chen Li
Published: October 2017

Objectives

Cytotoxic chemotherapy is an effective and traditional treatment of ovarian cancer. However, chemotherapy‐induced apoptosis may also trigger and ultimately accelerate the repopulation of the small number of adjacent surviving cells. This study mainly focused on the tumour cell repopulation caused by chemotherapy in ovarian cancer and the adjunctive/synergistic effect of Berberine on the prevention of tumour repopulation.

Materials and methods

The transwell system was used to mimic the co‐culture of surviving ovarian cancer cells in the microenvironment of cytotoxic chemotherapy‐treated dying cells. Tumour cell proliferation was observed by crystal violet staining. AA and PGE2 levels were measured by ELISA, and changes of protein expression were analysed by Western blot.

Results

Chemotherapy drug VP16 treatment triggered AA pathway, leading to the elevated PGE2 level, and ultimately enhanced the repopulation of ovarian cancer cells. Berberine can block the caspase 3‐iPLA2‐AA‐COX‐2‐PGE2 pathway by inhibiting the expression of iPLA2 and COX‐2. Berberine can also reverse the increased phosphorylation of FAK caused by abnormal PGE2 level and thus reverse the repopulation of ovarian cancer cells after VP16 treatment.

Conclusions

Our observation suggested that Berberine could inhibit the chemotherapy‐induced repopulation of ovarian cancer cells by suppressing the AA pathway and phosphorylation of FAK. And these findings implicated a novel combined use of Berberine and chemotherapeutics, which might prevent ovarian cancer recurrence by abrogating early tumour repopulation.
MicroRNAs: A novel potential biomarker for diagnosis and therapy in patients with non‐small cell lung cancer
Authors: Zhou Qun , Huang Shao‐Xin , Zhang Feng , Li Shu‐Jun , Liu Cong , Xi Yong‐Yong , Wang Liang , Wang Xin , He Qi‐Qiang , Sun Cheng‐Cao , Li De‐Jia
Published: October 2017

Background

Lung cancer is still one of the most serious causes of cancer‐related deaths all over the world. MicroRNAs (miRNAs) are defined as small non‐coding RNAs which could play a pivotal role in post‐transcriptional regulation of gene expression. Increasing evidence demonstrated dysregulation of miRNA expression associates with the development and progression of NSCLC.

Aims

To emphasize a variety of tissue‐specific miRNAs, circulating miRNAs and miRNA‐derived exosomes could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients.

Materials & Methods

In the current review, we paid attention to the significant discoveries of preclinical and clinical studies, which performed on tissue‐specific miRNA, circulating miRNA and exosomal miRNA. The related studies were obtained through a systematic search of Pubmed, Web of Science, Embase.

Results

A variety of tissue‐specific miRNAs and circulating miRNAs with high sensitivity and specificity which could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. In addition, we emphasize that the miRNA‐derived exosomes become novel diagnostic biomarkers potentially in these patients with NSCLC.

Conclusion

MiRNAs have emerged as non‐coding RNAs, which have potential to be candidates for the diagnosis and therapy of NSCLC.
Low‐dose basiliximab induction therapy in heart transplantation
Authors: Kittipibul Veraprapas , Tantrachoti Pakpoom , Ongcharit Pat , Ariyachaipanich Aekarach , Siwamogsatham Sarawut , Sritangsirikul Supaporn , Thammanatsakul Kanokwan , Puwanant Sarinya
Published: October 2017

We prospectively studied efficacy and safety outcomes of two 10‐mg doses of intravenous basiliximab on day 0 and day 4 for induction therapy in 17 consecutive de novo heart transplant recipients. By the 2‐week assessment post‐transplant, there were no deaths, graft failures, or acute cellular rejections (ACRs) ISHLT grade ≥ 2R. By the 1‐year assessment post‐transplant, there were 1 (6%) infectious death, no graft failures, 2 (12%) grade 2R ACRs, 6 (35%) asymptomatic cytomegalovirus (CMV) infections, and 4 (25%) treated infections. Our study was the first to show that low‐dose basiliximab induction in heart transplant resulted in favorable efficacy and safety outcomes. Additionally, calcineurin inhibitor (CNI) initiation in a low‐risk population could be safely delayed using the strategy of modified low‐dose postoperative basiliximab. This strategy also appears to allow subsequent early corticosteroid wean, although with the concomitant maintenance of higher CNI levels and higher dosing of mycophenolate.
Feasibility of diaphragm pacing in patients after bilateral lung transplantation
Authors: Testelmans Dries , Nafteux Philippe , Van Cromphaut Sophie , Vrijsen Bart , Vos Robin , De Leyn Paul , Decaluwé Herbert , Van Raemdonck Dirk , Verleden Geert M. , Buyse Bertien
Published: October 2017

Recent animal studies and intraoperative studies in humans suggested that phrenic nerve stimulation could attenuate ventilator‐induced diaphragm dysfunction. The purpose of the present study is to examine the safety and feasibility of diaphragm pacing during the weaning process after bilateral lung transplantation. Four patients, suffering from chronic pulmonary disease, were included, and diaphragm pacing was evaluated after lung transplantation. Implantation of electrodes at the end of the lung transplant procedure was possible in three of the four patients. In all implanted patients, stimulation of the diaphragm could trigger the ventilator. Implanted electrodes were completely removed by percutaneous retraction after up to 7 days of pacing. Adverse events related to pacing included occurrence of pain. Diaphragm pacing with temporary electrodes, inserted during surgery, is feasible and is able to trigger the ventilator in patients after bilateral lung transplantation. The use of intradiaphragmatic electrodes creates the additional opportunity to monitor the evolution of diaphragm electromyography during the postoperative weaning process.
A new scenario in the immunohistochemical diagnosis of cutaneous leishmaniasis
Authors: Fernandez‐Flores Angel
Published: October 2017

Cutaneous lesions of leishmaniasis are easy to diagnose when clinically obvious or when amastigotes are numerous in the biopsy. However, this is not always the case. In difficult cases, the diagnosis of leishmaniasis requires a reliable tool to identify the microorganisms. The identification of the parasite via microscope has a superior sensitivity to that of culture, and molecular techniques, such as polymerase chain reaction (PCR), highly improve the sensitivity of the diagnosis. Alternatively, immunohistochemistry has emerged as an affordable alternative to PCR. Several laboratories have produced their own antibodies against Leishmania and seem satisfied with the results. Nevertheless, most of these antibodies are not commercialized or standardized. Pathology also welcomed the unexpected positivity of amastigotes with certain clones of anti‐CD1a. The latter does not universally stain all species of Leishmania, with a low sensitivity for New World species. In conclusion, although anti‐CD1a is a reliable complementary tool in the diagnosis of leishmaniasis, pathologists should familiarize themselves with one of the specific antibodies against Leishmania and globalize its use, standardizing and adapting the technique.
The value of scattered trees for wildlife: Contrasting effects of landscape context and tree size
Authors: Le Roux Darren S. , Ikin Karen , Lindenmayer David B. , Manning Adrian D. , Gibbons Philip
Published: October 2017

Aim

The biodiversity value of scattered trees in modified landscapes is often overlooked in planning and conservation decisions. We conducted a multitaxa study to determine how wildlife abundance, species richness and community composition at individual trees are affected by (1) the landscape context in which trees are located; and (2) the size of trees.

Location

Canberra, south‐eastern Australia.

Methods

Trunk arthropod, bat and bird surveys were undertaken over 3 years (2012–2014) at 72 trees of three sizes (small (20–50 cm DBH), medium (51–80 cm), large (≥80 cm)) located in four landscape contexts (reserves, pasture, urban parklands, urban built‐up areas).

Results

Landscape context affected all taxa surveyed. Trunk arthropod communities differed between trees in urban built‐up areas and reserves. Bat activity and richness were significantly reduced at trees in urban built‐up areas suggesting that echolocating bats may be disturbed by high levels of urbanization. Bird abundance and richness were highest at trees located in modified landscapes, highlighting the value of scattered trees for birds. Bird communities also differed between non‐urban and urban trees. Tree size had a significant effect on birds but did not affect trunk arthropods and bats. Large trees supported higher bird abundance, richness and more unique species compared to medium and small trees.

Main conclusions

Scattered trees support a diversity of wildlife. However, landscape context and tree size affected wildlife in contrasting ways. Land management strategies are needed to collectively account for responses exhibited by multiple taxa at varying spatial scales. We recommend that the retention and perpetuation of scattered trees in modified landscapes should be prioritized, hereby providing crucial habitat benefits to a multitude of taxa.
Long‐term impairment attributable to congenital cytomegalovirus infection: a retrospective cohort study
Authors: Korndewal Marjolein J , Oudesluys‐Murphy Anne Marie , Kroes Aloys C M , van der Sande Marianne A B , de Melker Hester E , Vossen Ann C T M
Published: October 2017

Aim

This study aimed to estimate long‐term impairment attributable to congenital cytomegalovirus infection (cCMV).

Method

This nationwide cohort study retrospectively assessed cCMV in children born in 2008 in the Netherlands, testing 31 484 stored neonatal dried blood spots. Extensive medical data of cCMV‐positive children (n=133) and matched cCMV‐negative comparison children (n=274) up to 6 years of age were analysed.

Results

Moderate to severe long‐term impairment was diagnosed in 24.8% (33 out of 133) of all cCMV‐positive children (53.8% in symptomatic, 17.8% in asymptomatic), compared with 12.0% (33 out of 274) of cCMV‐negative children. Sensorineural hearing loss was seen only in five cCMV‐positive children (3.8%). Developmental delays were diagnosed more often in cCMV‐positive children than cCMV‐negative children: motor (12.0% vs 1.5%), cognitive (6.0% vs 1.1%), and speech–language (16.5% vs 7.3%). Long‐term impairment in multiple domains was more frequent in symptomatic (19.2%) and asymptomatic (8.4%) cCMV‐positive children than cCMV‐negative children (1.8%).

Interpretation

Children with cCMV were twice as likely to have long‐term impairment up to the age of 6 years, especially developmental delays and sensorineural hearing loss, than cCMV‐negative comparison children, with a risk difference of 12.8%. These insights into the risk of cCMV‐associated impairment can help optimize care and stimulate preventive measures.

What this paper adds

Congenital cytomegalovirus infection (cCMV) leads to impairment in 25% of cases.

Fifty per cent of children with cCMV symptoms at birth have long‐term impairment.

The risk difference of moderate to severe long‐term impairment between children with and without cCMV is 13%, attributable to cCMV.

cCMV leads to motor, cognitive, and speech–language developmental delay in children.
Corticosteroids in Duchenne muscular dystrophy: impact on the motor function measure sensitivity to change and implications for clinical trials
Authors: Schreiber Audrey , Brochard Sylvain , Rippert Pascal , Fontaine‐Carbonnel Stephanie , Payan Christine , Poirot Isabelle , Hamroun Dalil , Vuillerot Carole ,   MFM DMD Corticosteroids Group
Published: October 2017

Aim

To monitor the evolution of the motor function of ambulatory patients with Duchenne muscular dystrophy (DMD) treated by corticosteroids for 2 years in comparison with untreated patients.

Method

This observational, multicentre cohort study explores the evolution of the motor function measure (MFM) over a 24‐month period for 29 ambulant corticosteroids‐treated and 45 ambulant untreated patients with DMD.

Results

Significant differences were found between mean MFM scores in corticosteroids‐treated and untreated groups for domain 1 of the MFM (standing position and transfers; D1), domain 2 of the MFM (axial and proximal motor function; D2), and domain 3 of the MFM (distal motor function; D3). Subscores were between 0 months and 6 months, and 0 months and 24 months. For the D1 subscore specifically, there was a significant increase in the corticosteroids‐treated group (mean±standard deviation [SD] slope of change=12.6±15.5%/y), while a decrease was observed in the untreated group (−17.8±17.7%/y) between 0 months and 6 months (p<0.001). Sensitivity to change as assessed by standardized response means was high between 12 months and 24 months for D1 of both corticosteroids‐treated and untreated groups (1.0 and 1.2 respectively), and low for D2 and D3 of both treated and untreated groups.

Interpretation

Patients with DMD treated by corticosteroids present a different course of the disease as assessed by MFM, confirming the sensitivity to change of the MFM in this population.

What this paper adds

Corticosteroids have a quantitative impact on muscle strength 6 to 24 months after starting treatment.

Motor function measure is a valid outcome measure in Duchenne muscular dystrophy patients under corticosteroid treatment.
Left atrial volume changes are an early marker of end‐organ damage in essential hypertension: A multidisciplinary approach to an old problem
Authors: Kanar Batur , Ozben Beste , Kanar Hatice Selen , Arsan Aysu , Tigen Kursat
Published: October 2017

Purpose

Left atrial (LA) volume has been shown to be a predictor of adverse cardiovascular outcomes. The aim of this study was to evaluate the relation between LA phasic volumes and hypertensive end‐organ damage (EOD), by using real time three‐dimensional echocardiography (RT3DE) in patients with essential hypertension (HT).

Methods

The study included 95 essential hypertensive patients (60 ± 10 years, 37 males). The patients were divided into three according to the presence of EOD, namely microalbuminuria and retinal vascular changes detected by direct ophthalmoscopy. The first group had no EOD. The second group (EOD+ group) had either microalbuminuria or retinal vascular changes while the third group (EOD++ group) had both renal and retinal damage.

Results

The three groups did not differ with regard to age, sex, or metabolic profile. In RT3DE measurements, there were significant differences in LA phasic volumes (LA maximal volume index, LA minimal volume index, LA pre–atrial contraction volume index, LA total stroke volume index, and LA active stroke volume index, P < .001) among the groups. Moreover, patients with more extended EOD had significantly worse LA reservoir and conduit functions. In the logistic regression analysis, the LA active stroke volume index was an independent predictor of EOD (82% sensitivity and 92% specificity, area under the curve = 0.96, P < .001).

Conclusion

RT3DE measured LA phasic volumes and mechanical functions are associated with hypertensive EOD, which might serve as a surrogate endpoint for determining cardiovascular mortality and morbidity rates in patients with essential HT.
Autotransplantation of teeth to the anterior maxilla: A systematic review of survival and success, aesthetic presentation and patient‐reported outcome
Authors: Akhlef Yousra , Schwartz Ole , Andreasen Jens O. , Jensen Simon S.
Published: October 2017

Background/Aim

Autotransplantation of teeth to the anterior maxilla may be indicated after trauma or in patients with congenitally missing teeth. The aim of this systematic review was to report the current evidence concerning survival and success rate, aesthetic outcome, and patient‐reported outcome of autotransplanted teeth to the anterior maxilla.

Materials and Methods

A MEDLINE search followed by an additional hand search was performed to identify relevant literature. All levels of evidence except case reports were considered. Any publication reporting on 10 or more autotransplanted teeth to the anterior maxilla, and written in English were eligible for this systematic review.

Results

The systematic search identified 95 abstracts. Thirty‐seven full‐text articles were evaluated of which 17 could finally be included. Data on survival and success rate of the transplants could be extracted from 11 studies. Survival rates ranged between 93% and 100% (weighted mean: 96.7%, median: 100%) after 9 months to 22 years of observation (median: 8.75 years). No consensus regarding definition of success criteria of the transplants could be found in the literature. Two and four studies contained data on aesthetic and patient‐reported outcomes, respectively. In general, they reported favourable aesthetic results and high patient satisfaction.

Conclusion

The current available evidence suggests a high survival rate after autotransplantation of teeth to the anterior maxilla. However, the level of evidence is low. Limited data on aesthetic and patient‐reported outcomes warrant additional research in this field.
Methylphenidate, cognition, and epilepsy: A 1‐month open‐label trial
Authors: Adams Jesse , Alipio‐Jocson Valerie , Inoyama Katherine , Bartlett Victoria , Sandhu Saira , Oso Jemima , Barry John J. , Loring David W. , Meador Kimford J.
Published: October 2017

Objective

Cognitive difficulties are common in epilepsy. Beyond reducing seizures and adjusting antiepileptic medications, no well‐validated treatment exists in adults. Methylphenidate is used effectively in children with epilepsy and attention‐deficit/hyperactivity disorder, but its effects in adults have not been systematically evaluated. We hypothesized that methylphenidate can safely improve cognition in adults with epilepsy. We detail here the open‐label follow‐up to a double‐blind, placebo‐controlled, single‐dose study.

Methods

Thirty epilepsy patients entered a 1‐month open‐label methylphenidate trial after a double‐blind phase. Doses were titrated according to clinical practice and patient tolerance, ranging 20–40 mg/day. Primary measures included: Conners’ Continuous Performance Test (CPT), Symbol–Digit Modalities Test (SDMT), and Medical College of Georgia Memory Test (MCG). Secondary measures were: Beck Depression Inventory, 2nd Edition (BDI‐II), Beck Anxiety Inventory, Apathy Evaluation Scale (AES), Stimulant Side‐Effect Checklist, Adverse Events Profile, Quality of Life in Epilepsy‐89 (QOLIE‐89), and seizure frequency. Fourteen healthy, nonmedicated controls were tested concurrently.

Results

Twenty‐eight participants with epilepsy (13 men/15 women) completed the trial. Withdrawals occurred due to anxiety (n = 1) and fatigue (n = 1). Mean age was 36.4 years (range = 20–60). Epilepsy types were: focal (n = 21), generalized (n = 6), or unclassified (n = 1). Mean epilepsy duration was 12.3 years. Mean baseline seizure frequency was 2.8/month. There were significant improvements on methylphenidate forSDMT,MCG,CPT(the ability to discriminate between targets and nontargets [d′] hits, hit reaction time standard deviation, omissions, and commissions), andQOLIEsubscales (energy/fatigue, attention/concentration, memory, and language; paired t tests; p ≤ 0.002).BDI‐IIand additional subscales also improved, at a lower level of statistical significance. Effect sizes were moderate to large. Comparisons with untreated controls (n = 14) revealed greater improvement for epilepsy patients on omissions and commissions, with improvement trends on d′ and hits. Seizure frequency did not increase with methylphenidate treatment (2.8/month vs. 2.4/month).

Significance

Methylphenidate may be an effective and safe option for improving cognition and quality of life in epilepsy. Larger and longer double‐blind, placebo‐controlled clinical trials are needed.
Improving models of photosynthetic thermal acclimation: Which parameters are most important and how many should be modified?
Authors: Stinziano Joseph R. , Way Danielle A. , Bauerle William L.
Published: October 2017

Photosynthetic temperature acclimation could strongly affect coupled vegetation–atmosphere feedbacks in the global carbon cycle, especially as the climate warms. Thermal acclimation of photosynthesis can be modelled as changes in the parameters describing the direct effect of temperature on photosynthetic capacity (i.e., activation energy, Ea; deactivation energy, Hd; entropy parameter, ΔS) or the basal value of photosynthetic capacity (i.e., photosynthetic capacity measured at 25°C). However, the impact of acclimating these parameters (individually or in combination) on vegetative carbon gain is relatively unexplored. Here we compare the ability of 66 photosynthetic temperature acclimation scenarios to improve the ability of a spatially explicit canopy carbon flux model, MAESTRA, to predict eddy covariance data from a loblolly pine forest. We show that: (1) incorporating seasonal temperature acclimation of basal photosynthetic capacity improves the model's ability to capture seasonal changes in carbon fluxes and outperforms acclimation of other single factors (i.e., Ea or ΔS alone); (2) multifactor scenarios of photosynthetic temperature acclimation provide minimal (if any) improvement in model performance over single factor acclimation scenarios; (3) acclimation of Ea should be restricted to the temperature ranges of the data from which the equations are derived; and (4) model performance is strongly affected by the Hd parameter. We suggest that a renewed effort be made into understanding whether basal photosynthetic capacity, Ea, Hd and ΔS co‐acclimate across broad temperature ranges to determine whether and how multifactor thermal acclimation of photosynthesis occurs.
Characterizing Stream‐Aquifer Exchanges with Self‐Potential Measurements
Authors: Valois Remi , Cousquer Yohann , Schmutz Myriam , Pryet Alexandre , Delbart Célestine , Dupuy Alain
Published: October 2017

Characterizing the interactions between streams and aquifers is a major challenge in hydrology. Electrical self‐potential (SP) is sensitive to groundwater flow through the electrokinetic effect, which is proportional to Darcy velocity. SP surveys have been extensively used for the characterization of seepage flow in a variety of contexts. But to our knowledge, a model coupling SP and groundwater flow has never been implemented for the study of stream‐aquifer interactions. To address the issue, we first implemented a two‐dimensional model to a synthetic stream‐aquifer cross section. Results underline the very distinct nature of SP profiles in gaining or losing stream conditions. Second, we presented a field application in a transect crossing a stream in losing conditions. The coupled model successfully reproduced the observed SP profile. This inverse modeling of the SP signal provides quantitative data on hydrodynamic parameters (hydraulic conductivity, hydraulic heads) and geophysical parameters (coupling coefficient). Nevertheless, all relevant parameters cannot be uniquely estimated without precise prior information on at least some of these parameters. Our results confirm the potential of SP surveys on the characterization of stream‐aquifer exchanges. Recommendations on the collection of high‐quality data are also provided, along with a description of the contexts in which the methodology is likely to perform well.
Mediterranean archeology and environmental histories in the spotlight of the Anthropocene
Authors: Kearns Catherine
Published: October 2017

The last two decades have seen increasing scientific and humanistic research about anthropogenic impacts on earth systems such as climate, leading to a controversial proposal that we are living in an Anthropocene epoch, when humans have become unprecedented forces of global change. The status of the Anthropocene as a historiographical period poses an opportunity to consider how archeologists and historians conceive of environmental and social change in Mediterranean antiquity. Scholarship has tended to focus on regional landscapes or large‐scale climatic accounts of the rise and fall of societies and less on the politics and social dimensions of human–environment relationships. Although bridging the small and large scales of these interactions poses challenges, recent research on the island of Cyprus during the Archaic period highlights the possibilities of an archeological approach to the intersections between social and environmental Mediterranean histories and their material contexts.
Effect of the calcining temperatures of low‐grade bauxite on the mechanical property of mullite ceramics
Authors: Ren Qiang , Li Huanhuan , Wu Xiulan , Huo Zhezhe , Hai Ou , Lin Fei
Published: October 2017

The mullite ceramics with excellent properties were prepared using traditional sintering method, and the starting material was low‐grade bauxite without any other additives in this paper. The variations in physical and chemical properties in the process of sintering, the specific surface area of calcined bauxite at different calcining temperatures, and the phase composition of the mullite ceramic and its microstructure were investigated by thermal analysis, laser particle analysis, the X‐ray diffraction, and scanning electron microscope, respectively. The effect of calcining temperatures of raw bauxite on mechanical property and sintering mechanism of mullite ceramic were explored and researched. The results showed that the flexural strength can reach 180 MPa, a great difference existed in mullite ceramics prepared from calcined bauxite at different calcining temperatures, and the sintering mechanism included densification of raw bauxite, the activities of calcined bauxite powders, and crystals in calcined bauxite.
Safety of Atrovent® CFC-free inhaler: respiratory events reported from an observational cohort study in England
Authors: Osborne Vicki , Layton Deborah , Fogg Carole , Tong Edward , Shakir Saad A W
Published: October 2017

Objectives

The aim of the study was to identify any unexpected clinical events associated with starting the new CFC-free formulation of Atrovent® MDI in general practice in England.

Methods

An active surveillance cohort study was conducted with a focus on selected clinical events, including respiratory symptoms, in past users of Atrovent® CFC MDI (‘switchers’) and Atrovent® naïve users. Incidence density rate ratios (with 99% confidence intervals) for events occurring in the first 3 months of exposure (risk period-ID1-3) compared to 3 months prior to starting treatment (reference period-IDR) were calculated.

Results

The cohort consisted of 13 211 patients (median age 70 years, 50.1% female; 63.5% prior users of Atrovent® CFC MDI (‘switchers’)). Common respiratory events occurred at higher rates after starting treatment than before for switchers, for example lower respiratory tract infection (LRTI) [ID1/IDR = 1.45 (99% CI: 1.17, 1.81)] and worsening asthma [ID1/IDR = 1.58 (99% CI: 1.00, 2.51)]. Of these events only LRTI was significant for Atrovent® naïve patients [ID1/IDR = 1.42 (99% CI: 1.04, 1.95)].

Conclusions

The results of this study suggest effect modification of risk as a result of prior Atrovent® CFC MDI use. Overall, Atrovent® CFC-free MDI appeared to be reasonably well tolerated in the immediate postmarketing period and the safety profile appeared similar to that of the CFC formulation.
Role of Galectin‐3 in the pathophysiology underlying allergic lung inflammation in a tissue inhibitor of metalloproteinases 1 knockout model of murine asthma
Authors: Mammen Manoj J. , Sands Mark F. , Abou‐Jaoude Elaine , Aalinkeel Ravikumar , Reynolds Jessica L. , Parikh Neil U. , Sharma Umesh , Schwartz Stanley A. , Mahajan Supriya D.
Published: October 2017

Asthma is a chronic inflammatory respiratory disease characterized by airway inflammation, airway hyperresponsiveness and reversible airway obstruction. Understanding the mechanisms that underlie the various endotypes of asthma could lead to novel and more personalized therapies for individuals with asthma. Using a tissue inhibitor of metalloproteinases 1 (TIMP‐1) knockout murine allergic asthma model, we previously showed that TIMP‐1 deficiency results in an asthma phenotype, exhibiting airway hyperreactivity, enhanced eosinophilic inflammation and T helper type 2 cytokine gene and protein expression following sensitization with ovalbumin. In the current study, we compared the expression of Galectins and other key cytokines in a murine allergic asthma model using wild‐type and TIMP‐1 knockout mice. We also examined the effects of Galectin‐3 (Gal‐3) inhibition on a non‐T helper type 2 cytokine interleukin‐17 (IL‐17) to evaluate the relationship between Gal‐3 and the IL‐17 axis in allergic asthma. Our results showed a significant increase in Gal‐3, IL‐17 and transforming growth factor‐β1 gene expression in lung tissue isolated from an allergic asthma murine model using TIMP‐1 knockout. Gal‐3 gene and protein expression levels were also significantly higher in lung tissue from an allergic asthma murine model using TIMP‐1 knockout. Our data show that Gal‐3 may regulate the IL‐17 axis and play a pivotal role in the modulation of inflammation during experimental allergic asthma.
Rapid changes in serum cytokines and chemokines in response to inactivated influenza vaccination
Authors: Talaat Kawsar R. , Halsey Neal A. , Cox Amber B. , Coles Christian L. , Durbin Anna P. , Ramakrishnan Amritha , Bream Jay H.
Published: October 2017

Background

The timing of host cytokine responses to influenza vaccination is poorly understood.

Objectives

We examined serum cytokine kinetics following inactivated trivalent influenza vaccine (TIV) to better understand potential relationships between markers of inflammation and TIV‐related side effects.

Patients/Methods

Twenty healthy adult subjects received TIV. Cytokines/chemokines were assessed in intervals from 3 hours to 14 days. Antibody titers were measured at baseline and Day 14.

Results

Serum cytokine responses to TIV were evident as early as 3 hours post‐immunization. Compared to baseline, IFN‐γ and IP‐10 were significantly elevated 7 hours after TIV administration. Both remained elevated and peaked between 16 and 24 hours before returning to baseline by 44 hours post‐vaccination. Although IL‐8 levels were variable between subjects during the first 24 hours after TIV, by 44 hours, IL‐8 was significantly lower compared to baseline. Interestingly, IL‐8 levels remained significantly lower for up to 2 weeks after receiving TIV. Fifteen of 20 subjects reported mild adverse events. The one subject who reported moderate myalgias and injection site pain after vaccination displayed a distinctive, early cytokine response profile which included IL‐6, IL‐2, IL‐8, IP‐10, MCP‐1, TNF‐α, TARC, and MCP‐4.

Conclusions

Serum cytokines changed rapidly following TIV and generally peaked at 24 hours. Trivalent influenza vaccine‐induced reductions in IL‐8 occurred later (44 hours) and were sustained for 2 weeks. An outlier response coincided with the only moderate side effects to the vaccine. These data suggest that early cytokine/chemokine responses may provide additional insight into the pathogenesis of adverse events and immune reactivity to vaccination.
The expression and functional activities of smooth muscle myosin and non‐muscle myosin isoforms in rat prostate
Authors: Chen Ping , Yin Jing , Guo Yu‐ming , Xiao He , Wang Xing‐huan , DiSanto Michael E. , Zhang Xin‐hua
Published: October 2017

Benign prostatic hyperplasia (BPH) is mainly caused by increased prostatic smooth muscle (SM) tone and volume. SM myosin (SMM) and non‐muscle myosin (NMM) play important roles in mediating SM tone and cell proliferation, but these molecules have been less studied in the prostate. Rat prostate and cultured primary human prostate SM and epithelial cells were utilized. In vitro organ bath studies were performed to explore contractility of rat prostate. SMM isoforms, including SM myosin heavy chain (MHC) isoforms (SM1/2 and SM‐A/B) and myosin light chain 17 isoforms (LC17a/b), and isoform ratios were determined via competitive RT‐PCR. SM MHC and NM MHC isoforms (NMMHC‐A, NMMHC‐B and NMMHC‐C) were further analysed via Western blotting and immunofluorescence microscopy. Prostatic SM generated significant force induced by phenylephrine with an intermediate tonicity between phasic bladder and tonic aorta type contractility. Correlating with this kind of intermediate tonicity, rat prostate mainly expressed LC17a and SM1 but with relatively equal expression of SM‐A/SM‐B at the mRNA level. Meanwhile, isoforms of NMMHC‐A, B, C were also abundantly present in rat prostate with SMM present only in the stroma, while NMMHC‐A, B, C were present both in the stroma and endothelial. Additionally, the SMM selective inhibitor blebbistatin could potently relax phenylephrine pre‐contracted prostate SM. In conclusion, our novel data demonstrated the expression and functional activities of SMM and NMM isoforms in the rat prostate. It is suggested that the isoforms of SMM and NMM could play important roles in BPH development and bladder outlet obstruction.