bluuebunny/crossref_metadata_2025 huggingface dataset:
1.65 Å resolution structure of the AraC-family transcriptional activator ToxT fromVibrio cholerae
Authors: Li Jiaqin , Wehmeyer Graham , Lovell Scott , Battaile Kevin P. , Egan Susan M.
Published: August 2016

ToxT is an AraC-family transcriptional activator protein that controls the expression of key virulence factors inVibrio cholerae, the causative agent of cholera. ToxT directly activates the expression of the genes that encode the toxin-coregulated pilus and cholera toxin, and also positively auto-regulates its own expression from thetcppromoter. The crystal structure of ToxT has previously been solved at 1.9 Å resolution (PDB entry 3gbg). In this study, a crystal structure of ToxT at 1.65 Å resolution with a similar overall structure to the previously determined structure is reported. However, there are distinct differences between the two structures, particularly in the region that extends from Asp101 to Glu110. This region, which can influence ToxT activity but was disordered in the previous structure, can be traced entirely in the current structure.
Crystal structure of the YajQ-family protein XC_3703 fromXanthomonas campestrispv.campestris
Authors: Zhao Zhixin , Wu Zhen , Zhang Jun
Published: August 2016

As an important bacterial second messenger, bis-(3′,5′)-cyclic diguanylate (cyclic di-GMP or c-di-GMP) has been implicated in numerous biological activities, including biofilm formation, motility, survival and virulence. These processes are manipulated by the binding of c-di-GMP to its receptors. XC_3703 from the plant pathogenXanthomonas campestrispv.campestris, which belongs to the YajQ family of proteins, has recently been identified as a potential c-di-GMP receptor. XC_3703, together with XC_2801, functions as a transcription factor activating virulence-related genes, which can be reversed by the binding of c-di-GMP to XC_3703. However, the structural basis of how c-di-GMP regulates XC_3703 remains elusive. In this study, the structure of XC_3703 was determined to 2.1 Å resolution using the molecular-replacement method. The structure of XC_3703 consists of two domains adopting the same topology, which is similar to that of the RNA-recognition motif (RRM). Arg65, which is conserved among the c-di-GMP-binding subfamily of the YajQ family of proteins, together with Phe80 in domain II, forms a putative c-di-GMP binding site.
Does diet drive the evolution of head shape and bite force in chameleons of the genus Bradypodion?
Authors: Dollion Alexis Y. , Measey G. John , Cornette Raphaël , Carne Liza , Tolley Krystal A. , da Silva Jessica M. , Boistel Renaud , Fabre Anne‐Claire , Herrel Anthony
Published: August 2016

The head is a complex integrated system that is implicated in many vital functions. As such, its morphology is impacted by different and sometimes conflicting demands. Consequently, head shape varies greatly depending on the environment and dietary ecology of an organism. Moreover, given its role in territory defence and mating in lizards, it is also subjected to strong sexual selection in these animals.

We investigated the relationships between head shape, bite performance and diet in 14 of the 17 extant Bradypodion species to determine whether variation in diet can explain the observed diversity in bite force and head shape in this genus. We also evaluate differences between sexes in terms of the relationships between head shape, bite force and diet and predict tighter relationships in females given that the head in this sex is principally under natural selection.

Our results show that there is indeed a correlation between head shape, diet and bite force, but the direction and magnitude are sex‐dependent. Whereas we observed a correlation between absolute bite force and head shape in both sexes, size‐corrected bite force was correlated with mandible and quadrate shape in females only. Despite strong correlations between bite force and prey hardness, and between prey hardness and head shape, we did not find any relationship between head shape and prey evasiveness.

These data suggest that the cranial system in chameleons of the genus Bradypodion evolves under natural selection for the ability to eat large or hard prey. Moreover, significant differences in the ecomorphological relationships between the two sexes suggest that sexual selection plays a role in driving the evolution of bite force and head shape. These data suggest that ecomorphological relationships may be sex‐dependent.
Direct interactions between invasive plants and native pollinators: evidence, impacts and approaches
Authors: Stout Jane C. , Tiedeken Erin Jo
Published: August 2016

Invasive non‐native plants form interactions with native species and have the potential to cause direct and indirect impacts on those species, as well as the functioning of invaded ecosystems.

Many entomophilous invasive plants form interactions with resident pollinators; sometimes, these interactions are necessary for the reproductive success of the invader. However, the direct role native pollinators play in plant invasion is not well understood and varies according to invasive plant traits, including breeding system and pollination syndrome.

The majority of studies addressing impacts on plant–pollinator mutualisms have focussed on the indirect impacts of plant invasion for native plant pollination. Fewer studies have focussed on the direct effects of invasive plants on native flower visitors.

Impacts of invasive plants on native pollinators can occur at a range of scales: from the individual flower visitors (in terms of nutrition, health and fitness), to populations (size, density and growth rates), communities (richness, diversity and composition) and community‐level interactions (insect–flower interaction networks). Most research to date has focussed on community‐level impacts, with almost nothing known about the effects of invaders on native flower visitor individuals or populations.

Invasive plant traits, including reward quantity and quality, spatial and temporal availability and accessibility, modulate effects on native flower visitors, and thus, different plant species have different impacts. Similarly, flower visitors do not all respond in the same way to invasive plants. Thus, generalizations are difficult to make, but understanding impacts at the individual and population level for different visitor taxa is key to explaining community‐level impacts.

There have been varied approaches to determining impacts, with most studies attempting to compare invaded vs. non‐invaded habitats. The pros and cons of different approaches are discussed.

Since it is impractical to study every invasive plant in every ecological context in which it occurs, we recommend a better understanding of relevant individual‐level traits to predict direct interactions between invasive plants and native pollinators.

A Lay Summary is available for this article.
Dynamic changes in death cues modulate risks and rewards of corpse management in a social insect
Authors: Sun Qian , Haynes Kenneth F. , Zhou Xuguo
Published: August 2016

In social insects, the efficiency of exploitation of resources and colony defence are mediated by chemical communication. In colonies dependent on nutritionally limited resources, corpses represent both a food resource and a risk of pathogens. Because this risk vs. reward changes with time after death, behavioural plasticity in the response to corpses would be advantageous. How social insects regulate this trade‐off remains unknown.

We conducted quantitative behavioural bioassay and chemical analysis to study corpse management in the eastern subterranean termite, Reticulitermes flavipes. We hypothesized that R. flavipes responds differently towards corpses with prolonged post‐mortem time, and this behavioural plasticity is mediated by the dynamic change in death cues.

We show that R. flavipes uses a post‐mortem signalling system that depends on an early death cue that stimulates corpse retrieval and cannibalism, and late death cues that stimulate recruitment and burial. A blend of 3‐octanone and 3‐octanol is released immediately after death, with the alcohol (possibly in conjunction with the ketone) playing a clear role as a death cue. This cue enables the colony to recycle nutrients before decomposition occurs and before risk of pathogens increases. The accumulation of late death cues, decomposition products shared by diverse arthropods, elicits a behavioural switch from cannibalism to burial.

The ability to detect and respond to the dead is vital to group‐living animals. Our study reveals a behavioural shift in corpse management triggered by the interplay of an early death cue and late death cues, which balances risks and rewards associated with corpses. The post‐mortem chemical communication highlights the adaptation of a social insect to its ecological niche.
Peak season carbon exchange shifts from a sink to a source following 50+ years of herbivore exclusion in an Arctic tundra ecosystem
Authors: Lara Mark J. , Johnson David R. , Andresen Christian , Hollister Robert D. , Tweedie Craig E.
Published: August 2016

To date, the majority of our knowledge regarding the impacts of herbivory on arctic ecosystem function has been restricted to short‐term (<5 years) exclusion or manipulation experiments. Our understanding of long‐term responses of sustained herbivory and/or herbivore exclusion on arctic tundra ecosystem function is severely limited.

Recent evidence suggests lemming population outbreaks, which have historically been common in tundra regions, have become less frequent and in some cases disappeared. Here, we evaluate how 50+ years of lemming absence have impacted ecosystem carbon and energy exchange in an Arctic tundra region near Barrow, Alaska, using some of the oldest herbivore exclosures in the Arctic.

We show that sustained lemming absence dramatically altered peak growing season ecosystem function (i.e. thaw depth, water‐table, NDVI, albedo and land atmosphere CO2 and CH4 exchange) in all land cover types (i.e. wet, moist and dry) investigated but was most profound in wet tundra, where the long‐term absence of lemmings altered the largest carbon sink during peak growing season into a source to the atmosphere. Landscape‐level analysis suggests the long‐term absence of lemmings may increase peak growing season albedo by +6% and decrease net ecosystem exchange, CH4 flux and the combined radiative forcing potential by −96, −79 and −104%, respectively.

Identified long‐term functional responses to herbivory differed from many short‐term exclusion studies, as we found higher rates of carbon uptake where herbivores are present, associated with a shift in plant community composition (i.e. graminoid to moss), while short‐term studies typically report a reduction in carbon uptake where herbivores are present, associated with defoliation events that decrease above‐ground biomass/photosynthesis.

Synthesis. This work highlights the long‐term impact of herbivory on ecosystem function, which suggests (i) the measured response of arctic tundra to herbivory may be dependent on the duration of experimental observation, and (ii) if negative trends in lemming populations persist in arctic tundra regions, the historically strong carbon sink capacity may be severely reduced.
Taxonomic resolution is a determinant of biodiversity effects in arbuscular mycorrhizal fungal communities
Authors: Yang Haishui , Zhang Qian , Koide Roger T. , Hoeksema Jason D. , Tang Jianjun , Bian Xinmin , Hu Shuijin , Chen Xin
Published: August 2016

Arbuscular mycorrhizal fungi (AMF) are key regulators of ecosystem processes, yet how their biodiversity works in ecosystems remains poorly understood.

We documented the extent to which taxonomic resolution influenced the effect of biodiversity of AMF taxa on plant performance (growth, nutrient uptake and stress tolerance) in a meta‐analysis of 902 articles.

We found that the effect of biodiversity of AMF taxa depended on taxonomic resolution. Plant performance was positively promoted by AMF family richness, while no effect was found for fungal species richness. In addition, negative effect was found between AMF phylogenetic diversity and plant growth. This pattern can be explained by functional conservatism within AMF families and functional differentiation among AMF families.

Synthesis. Conservation of AMF communities to maintain a full complement of ecosystem functions requires the presence of diverse families and not simply diverse species within a family. This finding may be of key importance for the function of ecosystems under various environmental perturbations to which AMF families may respond differently.
Associations ofP2Y12Rgene polymorphisms with susceptibility to coronary heart disease and clinical efficacy of antiplatelet treatment with clopidogrel
Authors: Yang Hong‐Hui , Chen Yan , Gao Chuan‐Yu
Published: August 2016

Objective

To investigate the correlations of threeP2Y12 receptor (P2Y12R)gene polymorphisms (rs7428575 T>G, rs2046934 C>T, and rs3732759 A>G) with susceptibility to coronary artery disease (CHD) and clinical efficacy of clopidogrel treatment forCHD.

Methods

From May 2014 to May 2015, 178CHDpatients (the case group) and 182 healthy controls (the control group) were selected from our hospital. The platelet‐rich plasma (PRP) turbidimetry was used to measure the rate of adenosine diphosphate (ADP)‐induced platelet aggregation before and after clopidogrel treatment. Clopidogrel‐sensitive group was defined as a 10% or greater decrease in the rate of platelet aggregation after 10 days of clopidogrel treatment, while clopidogrel‐resistant group was defined as a <10% decrease. Genotyping was performed by denaturing high‐performance liquid chromatography (DHPLC). A haplotype analysis ofP2Y12Rgene polymorphisms was performed usingSHEsis software.

Results

There were significant differences in genotype and allele frequencies of rs2046934 C>T and rs3732759 A>G between the case and control groups (allP<.05). HaplotypesGTAandTTAwere negatively associated withCHDrisk (bothP<.05), but haplotypeTCAwas positively associated withCHDrisk (P=.005).CHDpatients in the clopidogrel‐sensitive group had higher frequencies ofTTgenotype of rs2046934 C>T and lower frequencies ofGGgenotype of rs3732759 A>G than those in the clopidogrel‐resistant group (bothP<.05).

Conclusions

P2Y12Rgene rs2046934 C>T and rs3732759 A>G polymorphisms might be associated with the risk ofCHDand the efficacy of clopidogrel treatment forCHD.
Warfarin persistence among atrial fibrillation patients – why is treatment ended?
Authors: Björck Fredrik , Ek Agnes , Johansson Lars , Själander Anders
Published: August 2016

Background and Aim

Warfarin treatment discontinuation is significant among patients with atrial fibrillation (AF). Studies mainly focused on whether the proportion of warfarin persistence and discontinuation are clinically appropriate are absent. This study evaluates warfarin persistence with focus on predictors for, and reasons to, warfarin discontinuation in AF patients.

Methods

From the national quality register AuriculA, all AF patients in Sundsvall, Sweden, on warfarin treatment on January 1, 2010 were included. These 478 patients were followed until discontinuation or study‐stop, December 31, 2013. By going through each patient's medical record, risk factors for thromboembolism, bleeding, and causes of discontinuation were obtained.

Results

Proportion of warfarin persistence was 0.91 (95% confidence interval [CI] 0.89–0.93) after 1 year and 0.73 (95% CI: 0.69–0.77) after 4 years. Previous intracranial bleeding, excessive alcohol use, anemia, and pulmonary or peripheral emboli were each associated with over two times higher risk of discontinuation (hazard ratio [HR] 5.66, CI 2.23–14.36; HR 2.54, CI 1.48–4.37; HR 2.40, CI 1.38–4.17; and HR 2.13, CI 1.02–4.46). Among patients discontinuing, 50.5% were due to questionable causes, such as sinus rhythm (33.9%), patients demand (10.1%), and falls (8.2%). The majority (43.1%) of treatment discontinuers were changed to aspirin, while 40.4% of them were left without medical stroke prophylaxis.

Conclusions

Although persistence to warfarin among AF patients proves higher than previously reported, there is room for improvement since half of the discontinuers have questionable reasons for treatment stop and the majority of them receive no other efficient stroke prophylaxis.
Similarity in spatial utilization distributions measured by the earth mover's distance
Authors: Kranstauber Bart , Smolla Marco , Safi Kamran
Published: August 2016

Estimating the similarity in space use (spatio‐temporal home range overlap) of animals is important for many questions regarding behavioural ecology, wildlife management and conservation. The current methods that calculate joint space use generally do not account for proximity in space use, as all of them rely on the differences between the exact spatial overlay of utilization distributions, while spatial distances between distributions should be considered to truly quantify similarity.

We implemented the earth mover's distance (EMD), a spatially explicit method, that quantifies similarity between utilization distributions by calculating the effort it takes to shape one utilization distribution landscape into another, hence EMD.

The EMD is a method commonly used in image retrieval applications, and we propose its use to calculate similarity in space use in the framework of movement ecology.

We show that the EMD is a consistent and useful as well as versatile measure of overlap and provide an easy to use implementation in the r package move.
A novel stereo‐video method to investigate fish–habitat relationships
Authors: Collins Danielle L. , Langlois Tim J. , Bond Todd , Holmes Thomas H. , Harvey Euan S. , Fisher Rebecca , McLean Dianne L.
Published: August 2016

Habitat complexity is known to influence the structure of fish assemblages. A number of techniques have previously been used to measure complexity, including quantitative in situ methods, which can be time‐consuming and labour‐intensive, and more rapid semi‐quantitative visual scoring methods. This study investigated the utility of a novel method for estimating complexity, whereby habitat height was measured using stereo‐photogrammetry from diver‐operated stereo‐video, traditionally used to sample fish assemblages.

This ‘stereo‐height’ method was compared to established in situ and visual scoring techniques and found to produce similar estimates of complexity. To determine how relevant the proposed method is for assessing ecological relationships, it was then used in conjunction with visual scoring of relief and point‐intercept samples of benthic composition to model fish–habitat associations in the Pilbara region of Western Australia.

Visual scores of relief were marginally stronger predictors of fish assemblage parameters and functional groups than the stereo‐height measurements, providing support for the visual scoring approach. The only exception was for corallivorous fishes, which were more strongly correlated with stereo‐height measurements. This study has presented a method for assessing habitat complexity using video imagery that is both comparable to traditional in situ techniques and useful for investigating fish–habitat relationships.

We suggest that future studies interested in collecting habitat complexity data from new or existing stereo‐video samples use both the stereo‐height and visual scoring methods presented here. Together these methods enable studies to rapidly and effectively assess fish–habitat relationships across a range of habitats without the need for in situ methods or solely relying on field observers trained in visual scoring techniques.
Depression, marijuana use and early‐onset marijuana use conferred unique effects on neural connectivity and cognition
Authors: Osuch E. A. , Manning K. , Hegele R. A. , Théberge J. , Neufeld R. , Mitchell D. , Williamson P. , Gardner R. C.
Published: August 2016

Objective

Marijuana (MJ) use is common. Research shows risks for psychiatric illnesses, including major depressive disorder (MDD) and cognitive deficits with MJ use, particularly early‐onset use. We investigated cognitive function, functional connectivity, and genetic risk with MDD alone and combined with MJ use, and differences between early‐vs. late‐onset/non‐MJ use in youth.

Method

A total of 74 youth in four groups were studied: healthy control, MDD, frequent MJ use and current/past MDD plus frequent MJ use. Psychiatric symptoms, cognitive performance and demographics were measured. Default mode network (DMN) brain connectivity was determined. Risk alleles in six genes of interest were evaluated.

Results

DMN differences among groups in reward‐processing and motor control regions were found; the effects of MJ use and MDD were distinct. Early‐onset MJ use was associated with lower IQ and hyperconnectivity within areas of the DMN. Early‐onset MJ use was associated with the BDNF risk allele.

Conclusions

Cognitive deficits linked with early‐onset MJ use were present within several years after MJ use began and may result from, predispose to, or share a common cause with early‐onset MJ use. The DMN was affected by MDD, MJ and their combination, as well as by early‐onset MJ use. BDNF carrier state may predispose to early‐onset MJ use.
Alcohol marketing and youth alcohol consumption: a systematic review of longitudinal studies published since 2008
Authors: Jernigan David , Noel Jonathan , Landon Jane , Thornton Nicole , Lobstein Tim
Published: August 2016

Background and Aims

Youth alcohol consumption is a major global public health concern. Previous reviews have concluded that exposure to alcohol marketing was associated with earlier drinking initiation and higher alcohol consumption among youth. This review examined longitudinal studies published since those earlier reviews.

Methods

Peer‐reviewed papers were identified in medical, scientific and social science databases, supplemented by examination of reference lists. Non‐peer‐reviewed papers were included if they were published by organizations deemed to be authoritative, were fully referenced and contained primary data not available elsewhere. Papers were restricted to those that included measures of marketing exposure and alcohol consumption for at least 500 underage people. Multiple authors reviewed studies for inclusion and assessed their quality using the National Heart, Lung and Blood Institute's Quality Assessment Tool for Observation Cohort and Cross‐Sectional Studies.

Results

Twelve studies (ranging in duration from 9 months to 8 years), following nine unique cohorts not reported on previously involving 35 219 participants from Europe, Asia and North America, met inclusion criteria. All 12 found evidence of a positive association between level of marketing exposure and level of youth alcohol consumption. Some found significant associations between youth exposure to alcohol marketing and initiation of alcohol use (odds ratios ranging from 1.00 to 1.69), and there were clear associations between exposure and subsequent binge or hazardous drinking (odds ratios ranging from 1.38 to 2.15). Mediators included marketing receptivity, brand recognition and alcohol expectancies. Levels of marketing exposure among younger adolescents were similar to those found among older adolescents and young adults.

Conclusions

Young people who have greater exposure to alcohol marketing appear to be more likely subsequently to initiate alcohol use and engage in binge and hazardous drinking.
Effectiveness of pharmacy‐based needle/syringe exchange programme for people who inject drugs: a systematic review and meta‐analysis
Authors: Sawangjit Ratree , Khan Tahir Mehmood , Chaiyakunapruk Nathorn
Published: August 2016

Aims

To appraise the evidence critically for effectiveness of pharmacy‐based needle/syringe exchange programmes (pharmacy‐based NSPs) on risk behaviours (RBs), HIV/HCV prevalence and economic outcomes among people who inject drugs (PWID).

Design

Systematic review and meta‐analysis.

Setting

Primary care setting.

Participants

Of 1568 studies screened, 14 studies with 7035 PWID were included.

Measures

PubMed, Embase, Web of Sciences, CENTRAL and Cochrane review databases were searched without language restriction from their inception to 27 January 2016. All published study designs with control groups that reported the effectiveness of pharmacy‐based NSP on outcomes of interest were included. Outcomes of interest are risk behaviour (RB), HIV/hepatitis C virus (HCV) prevalence and economic outcomes. The estimates of pooled effects of these outcomes were calculated as pooled odds ratio (OR) with 95% confidence interval (CI) using a random‐effects model. Heterogeneity was assessed by I2 and χ2 tests.

Findings

Most studies (nine of 14, 64.3%) were rated as having a serious risk of bias, while 28.6 and 7.1% were rated as having a moderate risk and low risk of bias, respectively. For sharing‐syringe behaviour, pharmacy‐based NSPs were significantly better than no NSPs for both main (OR = 0.50, 95% CI = 0.34–0.73; I2 = 59.6%) and sensitivity analyses, excluding studies with a serious risk of bias (OR = 0.52, 95% CI = 0.32–0.84; I2 = 41.4%). For safe syringe disposal and HIV/HCV prevalence, the evidence for pharmacy‐based NSPs compared with other NSP or no NSP was unclear, as few of the studies reported this and most of them had a serious risk of bias. Compared with the total life‐time cost of US$55 640 for treating a person with HIV infection, the HIV prevalence among PWID has to be at least 0.8% (for pharmacy‐based NSPs) or 2.1% (for other NSPs) to result in cost‐savings.

Conclusions

Pharmacy‐based needle/syringe exchange programmes appear to be effective for reducing risk behaviours among people who inject drugs, although their effect on HIV/HCV prevalence and economic outcomes is unclear.
Differential expression of apolipoprotein D in male reproductive system of rats by high‐fat diet
Authors: Lim W. , Bae H. , Song G.
Published: August 2016

Apolipoprotein D, a 29‐kDa secreted glycoprotein that belongs to the lipocalin superfamily, is widely expressed in various tissues and associated with lipid metabolism as a component of high‐density lipoproteins. Although Apolipoprotein D binds to small hydrophobic ligands including cholesterol, little is known about effects of high‐fat diet with cholesterol on expression of Apolipoprotein D in the male reproductive tract. Therefore, we investigated Apod expression in penises, prostate glands, and testes from rats fed a high‐fat diet including a high amount of cholesterol. Our previous research indicated that a high‐fat diet induces dyslipidemia leading to histological changes and dysfunction of male reproduction in rats. Consistent with these results, Apod mRNA expression was significantly (p < 0.001) decreased in penises and prostate glands (p < 0.01) and testes (p < 0.01) from rats fed a high‐fat diet as compared with normal diet. In addition, Apod mRNA and protein were detected predominantly in urethral epithelium and penile follicle from rats. Moreover, changes in expression of specific microRNAs (miR‐229b‐3p, miR‐423‐3p, and miR‐490‐3p) regulating Apod in the penises and prostate glands were negatively associated with Apod expression. Collectively, results of this study suggest that Apod is a novel regulatory gene in the male reproductive system, especially in penises of rats fed a high‐cholesterol diet, and that expression of Apod is regulated at the posttranscriptional level by target microRNAs.
Nicotinamide phosphoribosyltransferase production in human spermatozoa is influenced by maturation stage
Authors: Riammer S. , Garten A. , Schaab M. , Grunewald S. , Kiess W. , Kratzsch J. , Paasch U.
Published: August 2016

High amounts of nicotinamide phosphoribosyltransferase (NAMPT) were found in human seminal plasma. This enzyme influences energy metabolism and apoptosis and is essential for the regulation of cellular nicotinamide adenine dinucleotide (NAD)+ levels in somatic cells. NAD+ is required as a co‐substrate for dehydrogenases, which are potentially important for spermatogenesis. The functional significance of intra‐ and extracellular NAMPT in human reproduction, however, has not been defined yet. The objectives of the study were therefore to determine NAMPT protein expression in human spermatozoa and testes, the secretion of NAMPT by spermatozoa depending on their maturation stage and the impact of NAMPT enzymatic function on sperm viability, motility, fertilisation capacity and induction of apoptosis. Firstly, we detected NAMPT protein in different cell types of human testes. NAMPT protein was also detected in spermatozoa, with significantly higher amounts in immature than in mature ejaculated spermatozoa. Additionally, NAD+ levels were significantly higher in immature than in mature spermatozoa. Secondly, NAMPT was released into the supernatant of human spermatozoa, with significantly higher NAMPT levels in supernatant of immature spermatozoa compared with mature cells. Finally, the specific inhibition of the enzyme by FK866 did not influence motility, capacitation or apoptosis signalling. In summary, NAMPT is produced in human spermatozoa in a maturation‐dependent manner.
Beneficial effects of microsurgical varicocoelectomy on sperm maturation, DNA fragmentation, and nuclear sulfhydryl groups: a prospective trial
Authors: Alhathal N. , San Gabriel M. , Zini A.
Published: August 2016

There is evidence to show that varicocele repair can improve conventional sperm parameters but the effects on sperm chromatin integrity have not been fully elucidated. We sought to examine the effects of varicocelectomy on sperm maturation, nuclear chromatin integrity and nuclear sulfhydryl groups. We conducted a prospective study of consecutive infertile men (n=29) that underwent a microsurgical sub‐inguinal varicocelectomy for treatment of a clinically palpable varicocele and abnormal semen parameters. Six healthy sperm donors served as controls. We evaluated conventional sperm parameters and markers of sperm chromatin and DNA integrity (aniline blue (AB) staining, iodoacetamide fluorescein (IAF) fluorescence and, % DNA fragmentation index (%DFI) and percent high DNA stainability (%HDS) by sperm chromatin structure assay) before and 6 months after surgery. The sperm %DFI, %HDS, % 5‐IAF staining (diffuse head staining) and % AB staining (dark blue) were all significantly lower in the control group compared to infertile men with varicocele (8 vs. 20%, 4.0 vs. 9.6%, 1.7 vs. 16.3%, and 2.5 vs. 13.5% respectively). The %HDS and %DFI decreased significantly after surgery (from 10% to 6% and from 20% to 13%, respectively). Similarly, the %5‐IAF and %AB staining also decreased significantly after surgery (from 16.3% to 5.4%, and from 13.5% to 5.4%, respectively). We observed significant inversely relationships between sperm progressive motility and both %IAF staining and %DFI (r=−0.44 and −0.43, respectively). The data show that varicocelectomy is associated with an improvement in sperm DNA integrity and chromatin compaction using three different assays of sperm chromatin integrity.
Diagnostic value of qualitative and strain ratio elastography in the differential diagnosis of non‐palpable testicular lesions
Authors: Pozza C. , Gianfrilli D. , Fattorini G. , Giannetta E. , Barbagallo F. , Nicolai E. , Cristini C. , Di Pierro G. B. , Franco G. , Lenzi A. , Sidhu P. S. , Cantisani V. , Isidori A. M.
Published: August 2016

The purpose of this study was to evaluate prospectively the accuracy of qualitative and strain ratio elastography (SE) in the differential diagnosis of non‐palpable testicular lesions. The local review board approved the protocol and all patients gave their consent. One hundred and six patients with non‐palpable testicular lesions were consecutively enrolled. Baseline ultrasonography (US) and SE were correlated with clinical and histological features and ROC curves developed for diagnostic accuracy. The non‐palpable lesions were all ≤1.5 cm; 37/106 (34.9%) were malignant, 38 (35.9%) were benign, and 31 (29.2%) were non‐neoplastic. Independent risk factors for malignancy were as follows: size (OR 17.788; p = 0.002), microlithiasis (OR 17.673, p < 0.001), intralesional vascularization (OR 9.207, p = 0.006), and hypoechogenicity (OR, 11.509, p = 0.036). Baseline US had 89.2% sensitivity (95% CI 74.6–97.0) and 85.5% specificity (95% CI 75.0–92.8) in identifying malignancies, and 94.6% sensitivity (95% CI 86.9–98.5) and 87.1% specificity (95% CI 70.2–96.4) in discriminating neoplasms from non‐neoplastic lesions. An elasticity score (ES) of 3 out of 3 (ES3, maximum hardness) was recorded in 30/37 (81.1%) malignant lesions (p < 0.001). An intermediate score of 2 (ES2) was recorded in 19/38 (36.8%) benign neoplastic lesions and in 22/31 (71%) non‐neoplastic lesions (p = 0.005 and p = 0.001 vs. malignancies). None of the non‐neoplastic lesions scored ES3. Logistic regression analysis revealed a significant association between ES3 and malignancy (χ2 = 42.212, p < 0.001). ES1 and ES2 were predictors of benignity (p < 0.01). Overall, SE was 81.8% sensitive (95% CI 64.8–92.0) and 79.1% specific (95% CI 68.3–88.4) in identifying malignancies, and 58.6% sensitive (95% CI 46.7–69.9) and 100% specific (95% CI 88.8–100) in discriminating non‐neoplastic lesions. Strain ratio measurement did not improve the accuracy of qualitative elastography. Strain ratio measurement offers no improvement over elastographic qualitative assessment of testicular lesions; testicular SE may support conventional US in identifying non‐neoplastic lesions when findings are controversial, but its added value in clinical practice remains to be proven.
Characterization of cAMP‐phosphodiesterase activity in bovine seminal plasma
Authors: Bergeron A. , Aragon J. P. , Guillemette C. , Hébert A. , Sullivan R. , Blondin P. , Richard F. J.
Published: August 2016

The second messenger cyclic adenosine monophosphate (cAMP) has a central role in sperm physiology. Extracellular cAMP can be sequentially degraded into 5′AMP and adenosine by ecto‐phosphodiesterases (ecto‐PDE) and ecto‐nucleotidases, a phenomenon called extracellular cAMP‐adenosine pathway. As cAMP‐adenosine pathway is involved in sperm capacitation, we hypothesize that extracellular PDEs are functionally present in seminal plasma. Exclusively measuring cAMP‐PDE activity, total activity in bovine seminal plasma was 10.1 ± 1.5 fmoles/min/μg. Using different family‐specific PDE inhibitors, we showed that in seminal plasma, the major cAMP‐PDE activity was papaverine sensitive (47.5%). These data support the presence of PDE10 in bovine seminal plasma and was further confirmed by western blot. In epididymal fluid, total cAMP‐PDE activity was 48.2 ± 14.8 fmoles/min/μg and we showed that the major cAMP‐PDE activity was 3‐isobutyl‐methylxanthine insensitive and thus ascribed to PDE8 family. PDE10A mRNAs were found in the testis, epididymis, and seminal vesicles. cAMP‐PDE activity is present in bovine seminal plasma and epididymal fluid. The results suggest a role for ecto‐PDEs present in those fluids in the signaling pathways involved in sperm functions.
Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function through increased endothelial dysfunction, oxidative stress, apoptosis, and corporal fibrosis in a rat model
Authors: Hu Y. , Niu X. , Wang G. , Huang J. , Liu M. , Peng B.
Published: August 2016

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is an independent risk factor for the development of erectile dysfunction (ED). But the molecular mechanisms underlying the relationship between CP/CPPS and ED are still unclear. The aim of this study was to investigate the effect of CP/CPPS on erectile function in a rat model and the possible mechanisms. A rat model of experimental autoimmune prostatitis (EAP) was established to mimic human CP⁄CPPS. Then twenty 2‐month‐old male Sprague–Dawley rats were divided into EAP group and control group. Intracavernosal pressure (ICP) and mean arterial pressure (MAP) were measured during cavernous nerve electrostimulation, the ratio of max ICP/MAP was calculated. Blood was collected to measure the levels of serum C‐reactive protein (CRP), tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6) and testosterone, respectively. The expression of endothelial nitric oxide synthase (eNOS), cyclic guanosine monophosphate (cGMP) levels, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in corpus cavernosum were detected. We also evaluated the smooth muscle/collagen ratio and apoptotic index (AI). The ratio of max ICP/MAP in EAP group were significantly lower than that in control group. The levels of serum CRP, TNF‐α, IL‐1β, and IL‐6 in EAP group were all significantly higher than these in control group. The expression of eNOS and cGMP levels in corpus cavernosum of EAP rats were significantly downregulated. Furthermore, decreased SOD activity and smooth muscle/collagen ratio, increased MDA levels and AI were found in corpus cavernosum of EAP rats. In conclusion, CP/CPPS impaired penile erectile function in a rat model. The declines of eNOS expression and cGMP levels in corpus cavernosum may be an important mechanism of CP/CPPS‐induced ED. CP/CPPS also increased oxidative stress, cell apoptosis and decreased smooth muscle/collagen ratio in corpus cavernosum of rats, which were all important for erectile function.
Results of colon cancer surgery in patients over 75 years old
Authors: Pérez Domínguez Lucinda , Cáceres Alvarado Nieves , Toscano Novella Ángeles , Casal Núñez José Enrique
Published: August 2016

Background

Colon cancer is the second most frequent cause of death in both genders. Survival has increased since 1980, although this increase has been lower in patients ≥75 years old. We analyzed the results of surgical treatment for this pathology in this group of patients.

Methods

This retrospective, observational and descriptive study analyzed data relating to 315 patients undergoing colon cancer surgery between January 2010 and December 2011. Surgical results (surgical procedure, mean postoperative stay, isolated lymph nodes, postoperative morbidity and mortality) were compared between patients who were <75 and ≥75 years old.

Results

Statistical significance was observed in the percentages of hypertension (P = 0.001), cardiovascular disease (P = 0.006) and bronchopathy (P = 0.005) for the older group. No differences were found between the groups regarding surgical results, except higher postoperative morbidity and mortality in the ≥75 years old age group (P = 0.02 and P = 0.03, respectively). In the multivariate analysis, the factors associated with postoperative morbidity were age and preoperative albumin levels (P < 0.05). Cancer‐specific survival (CSS) was lower in older patients (P < 0.05). The multivariate analysis of survival determined that age and tumour stage are independent predictive factors (P = 0.004 and P = 0.039, respectively), unlike American Society of Anesthesiologists score.

Conclusions

Age does not influence the surgical results after colon cancer resection but is associated with increased postoperative morbidity and mortality. CSS is lower in patients who are ≥75 years old.
Efficacy of rectus muscle fragment welding in the control of presacral venous bleeding
Authors: Casal Núñez José Enrique , Pérez Domínguez Lucinda , Vigorita Vincenzo , Ruano Poblador Alejandro
Published: August 2016

Background

The incidence of presacral venous bleeding during rectal resection is low, but this complication can be severe and even lethal. Occasionally, the traditional methods – such as pelvic gauze packing and the use of metallic thumbtacks – are not effective. When combined with their complications and difficulties, these failures have resulted in numerous creative procedures with which to control this complication. In 1994, the indirect electrocoagulation method, which is performed via a fragment of the rectus abdominis muscle of the abdomen, was introduced to control presacral venous bleeding.

Methods

From January 2002 to December 2015, five of 872 patients with rectal cancer and one patient with rectal metastasis of gastric cancer developed presacral venous bleeding, and this technique was used in every case.

Results

Haemostasis was permanent in all cases. There were no complications such as infection or rebleeding.

Conclusion

In our experience, indirect electrocoagulation via a fragment of the rectus abdominis muscle of the abdomen is a rapid, easily executed and effective method for controlling presacral venous bleeding during rectal resection.
Findings at surveillance colonoscopy following surgery for colorectal cancer
Authors: Udayasiri Dilshan , Hollington Paul
Published: August 2016

Background

Colonoscopic surveillance following potentially curative surgery for colorectal cancer aims to detect treatable metachronous neoplasia. The timing and findings of colonoscopies for patients enrolled in an endoscopic surveillance programme were examined in this study.

Methods

A retrospective clinical audit was undertaken of 174 consecutive patients undergoing surgery for first‐presentation colorectal cancer, looking at the findings of subsequent surveillance colonoscopies.

Results

Sixty‐nine patients were fit for ongoing surveillance, with the median time to first colonoscopy being 14 months, and significant metachronous pathology was identified in 25%, comprising low‐risk adenomas, high‐risk adenomas, sessile serrated adenomas and one Dukes A carcinoma. Twenty‐seven patients underwent a second colonoscopy, with a median interval of 34 months between the investigations, and adenomas were identified in 30% of patients at the second surveillance colonoscopy. All polyps were colonoscopically resectable.

Conclusion

Colonoscopy at 1 and 4 years following bowel cancer resection may detect treatable pathology in a significant proportion of those patients fit for ongoing surveillance.
Risk factors of epithelial ovarian carcinomas among women with endometriosis: a systematic review
Authors: Thomsen Line H. , Schnack Tine H. , Buchardi Kristina , Hummelshoj Lone , Missmer Stacey A. , Forman Axel , Blaakaer Jan
Published: August 2016

Introduction

The objective of this review was to evaluate the published literature on epidemiologic risk factors for epithelial ovarian cancer among women with a diagnosis of endometriosis.

Material and methods

A systematic literature search was conducted in PubMed and Scopus. Studies comparing epidemiologic risk factors of epithelial ovarian cancer among women with endometriosis were included. A quality assessment was conducted using the Newcastle‐Ottawa Scale.

Results

Eight of 794 articles met the inclusion criteria. A lower risk of epithelial ovarian cancer was observed in women with documented complete surgical excision of endometriotic tissue and suggested among women with unilateral oophorectomy. The use of oral contraceptives (≥10 years) may be associated with a lower risk of epithelial ovarian cancer among women with endometriosis, whereas older age at endometriosis diagnosis (≥45 years, pre‐ or postmenopausal), nulliparity, hyperestrogenism (endogenous or exogenous), premenopausal status at endometriosis diagnosis, solid compartments as well as larger size of endometrioma (≥9 cm in diameter at endometriosis diagnosis) were all associated with an increased risk of ovarian cancer.

Conclusions

A subgroup of women with endometriosis characterized by endometriosis observed through surgery or imaging after the age of 45 years, nulliparity, postmenopausal status at endometriosis diagnosis, larger size of endometrioma (>9 cm) at endometriosis diagnosis, hyperestrogenism (endogenous or exogenous) and/or cysts with solid compartments may have an elevated risk of epithelial ovarian cancer. However, due to the limited number and size of studies in this area we cannot draw definitive conclusions. Further research into a risk factor profile among women with endometriosis is needed before clear recommendations can be made.
Penicillin G Treatment in Infective Endocarditis Patients – Does Standard Dosing Result in Therapeutic Plasma Concentrations?
Authors: Öbrink‐Hansen Kristina , Wiggers Henrik , Bibby Bo Martin , Hardlei Tore Forsingdal , Jensen Kaare , Kragh Thomsen Marianne , Brock Birgitte , Petersen Eskild
Published: August 2016

Penicillin G is frequently used to treat infective endocarditis (IE) caused by streptococci, penicillin‐susceptible staphylococci and enterococci. Appropriate antibiotic exposure is essential for survival and reduces the risk of complications and drug resistance development. We determined penicillin G plasma concentration [p‐penicillin] once weekly in 46 IE patients. The aim was to evaluate whether penicillin G 3 g every 6 hr (q6 h) resulted in therapeutic concentrations and to analyse potential factors that influence inter‐ and intra‐individual variability, using linear regression and a random coefficient model. [P‐penicillin] at 3 hr and at 6 hr was compared with the minimal inhibitory concentration (MIC) of the bacteria isolated from blood cultures to evaluate the following PK/PD targets: 50% fT > MIC and 100% fT > MIC. [P‐penicillin] varied notably between patients and was associated with age, weight, p‐creatinine and estimated creatinine clearance (eCLcr). Additionally, an increase in [p‐penicillin] during the treatment period showed strong correlation with age, a low eCLcr, a low weight and a low p‐albumin. Of the 46 patients, 96% had [p‐penicillin] that resulted in 50% fT > MIC, while 71% had [p‐penicillin] resulting in 100% fT > MIC. The majority of patients not achieving the 100% fT > MIC target were infected with enterococci. Streptococci and staphylococci isolated from blood cultures were highly susceptible to penicillin G. Our results suggest that penicillin G 3 g q6 h is suitable to treat IE caused by streptococci and penicillin‐susceptible staphylococci, but caution must be taken when the infection is caused by enterococci. When treating enterococci, therapeutic drug monitoring should be applied to optimize penicillin G dosing and exposure.
Oesophageal Obstruction from a Pharmacobezoar Resulting in Death
Authors: Mortensen Katrine Elisabeth , Munkholm Julie , Dalhoff Kim Peder , Hoegberg Lotte Christine Groth
Published: August 2016

Formation of an intestinal pharmacobezoar is a rare condition. It may form after intake of various oral pharmaceutical preparations of drugs, both as a result of an acute overdose and through chronic use of therapeutic doses of a drug. We report a case with a patient presenting with an oesophageal pharmacobezoar and complete obstruction of the oesophagus and severe toxic symptoms and death related to oral ingestion of multiple drugs.