bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of liver steatosis on the ability of serum ferritin levels to be predictive of liver iron concentration in non‐transfusion‐dependent thalassaemia patients
Authors: Ricchi Paolo , Meloni Antonella , Spasiano Anna , Costantini Silvia , Pepe Alessia , Cinque Patrizia , Filosa Aldo
Published: January 2018

This study analysed the impact of liver steatosis (LS) on the parameters of iron overload in 110 patients with non‐transfusion dependent thalassaemia (NTDT). LS was diagnosed by ultrasound. Liver iron concentration (LIC) measurements were available for 64 patients who underwent a magnetic resonance imaging (MRI) scan. LS was frequent (35·5%) and was significantly more prevalent in males than in females (49·0% vs. 24·6%, P = 0·008). Patients with LS had significant higher levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST ratio and ferritin than those without, but LIC values were comparable. An ALT/AST ratio >0·89 predicted the presence of LS with a sensitivity of 0·872 and a specificity of 0·901 (P < 0·0001). Ferritin levels correlated with LIC values (R = 0·558, P < 0·0001) but the correlation was stronger in patients without LS (R = 0·656, P < 0·0001) than in patients with LS (R = 0·426, P = 0·05). LS is a frequent issue in NTDT patients and should be suspected in the presence of an ALT/AST ratio >0·89. Recently, serum ferritin thresholds that predict clinically relevant LIC for guiding iron chelation therapy when MRI is unavailable have been determined. Our data show that LS may cause increase in ferritin levels and may be responsible for anticipating/exceeding chelation treatment in NTDT patients in the absence of LIC evaluation.
Routine outcome monitoring in CAMHS: how can we enable implementation in practice?
Authors: Waldron Samuel M. , Loades Maria E. , Rogers Libby
Published: January 2018

Background

Many CAMHS teams across the United Kingdom are now required to use Routine Outcome Monitoring (ROM). However, some clinicians hold negative attitudes towards ROM and various practical implementation issues have been identified.

Method

The aim of this study was to explore clinician experiences of using ROM in the context of an ‘enforced’ initial implementation initiative. Twenty clinicians were surveyed at the beginning (T1) and end (T2) of the six‐month period in a large UK CAMHS network adopting CYP‐IAPT practice. Changes in the use of and attitudes towards ROM were investigated, as well as barriers to implementation.

Results

Overall, a small but significant increase in clinician use of ROM was observed from T1 to T2, but attitudes towards ROM did not change significantly. On the whole, clinicians were more positive than negative about ROM during the implementation period, but key implementation challenges included clinician concerns about the value and (mis)use of ROM data, poor technological support and additional workload demands.

Conclusions

CAMHS clinicians will not necessarily become more receptive to ROM simply as a by‐product of being asked to use it more. Seeking clinician feedback at the early stages of implementation can help provide a focus for improvement efforts. Ideas for future research and important limitations of the study are discussed.
Political populations of large carnivores
Authors: Darimont Chris T. , Paquet Paul C. , Treves Adrian , Artelle Kyle A. , Chapron Guillaume
Published: January 2018

Article impact statement: Reporting of population data and associated policies are prone to political influence.
Clinical outcomes of stapled transanal rectal resection for obstructed defaecation syndrome at 10‐year follow‐up
Authors: Schiano di Visconte M. , Nicolì F. , Pasquali A. , Bellio G.
Published: January 2018

Aim

The long‐term efficacy of stapled transanal rectal resection (STARR) for surgical management of obstructed defaecation syndrome (ODS) has not been evaluated. Therefore, we investigated the long‐term efficacy (> 10 years) of STARR for treatment of ODS related to rectocele or rectal intussusception and the factors that predict treatment outcome.

Method

This study was a retrospective cohort analysis conducted on prospectively collected data. Seventy‐four consecutive patients who underwent STARR for ODS between January 2005 and December 2006 in two Italian hospitals were included.

Results

Seventy‐four patients [66 women; median age 61 (29–77) years] underwent STARR for ODS. No serious postoperative complications were recorded. Ten years postoperatively, 60 (81%) patients completed the expected follow‐up. Twenty‐three patients (38%) reported persistent perineal pain and 13 (22%) experienced the urge to defaecate. ODS symptoms recurred in 24 (40%) patients after 10 years. At the 10‐year follow‐up, 35% of patients were very satisfied and 28% would recommend STARR and undergo the same procedure again if necessary. In contrast, 21% of patients would not select STARR again. Previous uro‐gynaecological or rectal surgery and high constipation scores were identified as risk factors for recurrence.

Conclusions

Stapled transanal rectal resection significantly improves the symptoms of ODS in the short term. In the long term STARR is less effective, however.
Predicting global ascidian invasions
Authors: Lins Daniel M. , de Marco Paulo , Andrade Andre F. A. , Rocha Rosana M.
Published: January 2018

Aim

Many species of ascidians are invasive and can cause both ecological and economic losses. Here, we describe risk assessment for nineteen ascidian species and predict coastal regions that are more vulnerable to arrival and expansion.

Location

Global.

Methods

We used ensemble niche modelling with three algorithms (Random Forest, Support Vector Machine and MaxEnt) to predict ecologically suitable areas and evaluated our predictions using independent (area under the curve—AUC) and dependent thresholds (true skill statistics—TSS). Environmental variables were maximum and the range of sea surface temperature, mean salinity and maximum chlorophyll. We used our niche modelling results and a modified invasibility index to compare invasion risk among 15 coastal regions.

Results

Currently, the most invaded regions are in temperate latitudes of the Northern Hemisphere and Temperate Australasia, which are regions most prone for new invasions. In the tropics, the West and Central Indo‐Pacific are two regions of strong concern, the former with high risk of primary invasion by Botryllus schlosseri and Didemnum perlucidum. In the Southern Hemisphere, the Southwest and Southeast Atlantic are most at risk, both subject to invasion by Botrylloides violaceus, Didemnum vexillum, Molgula manhattensis and Styela clava among others. Regions most at risk of expansion of established invasive species are the Central Indo‐Pacific, Northwest Pacific, Mediterranean and West Indo‐Pacific.

Main conclusions

All regions studied have areas that are suitable and connected to receive new ascidian introductions or that may permit the spread of already established species. Risk comparison of primary introductions and expansion of established introduced ascidians among regions will allow managers to prioritize species of concern for each region both for monitoring future introductions or to enforce control actions towards established species to decrease the risk of regional expansion.
Optogenetically enhanced axon regeneration: motor versus sensory neuron‐specific stimulation
Authors: Ward Patricia J. , Clanton Scott L. , English Arthur W.
Published: January 2018

Brief neuronal activation in injured peripheral nerves is both necessary and sufficient to enhance motor axon regeneration, and this effect is specific to the activated motoneurons. It is less clear whether sensory neurons respond in a similar manner to neuronal activation following peripheral axotomy. Further, it is unknown to what extent enhancement of axon regeneration with increased neuronal activity relies on a reflexive interaction within the spinal circuitry. We used mouse genetics and optical tools to evaluate the precision and selectivity of system‐specific neuronal activation to enhance axon regeneration in a mixed nerve. We evaluated sensory and motor axon regeneration in two different mouse models expressing the light‐sensitive cation channel, channelrhodopsin (ChR2). We selectively activated either sensory or motor axons using light stimulation combined with transection and repair of the sciatic nerve. Regardless of genotype, the number of ChR2‐positive neurons whose axons had regenerated successfully was greater following system‐specific optical treatment, with no effect on the number of ChR2‐negative neurons (whether motor or sensory neurons). We conclude that acute system‐specific neuronal activation is sufficient to enhance both motor and sensory axon regeneration. This regeneration‐enhancing effect is likely cell autonomous.
Neurophysiology underlying influence of stimulus reliability on audiovisual integration
Authors: Shatzer Hannah , Shen Stanley , Kerlin Jess R. , Pitt Mark A. , Shahin Antoine J.
Published: January 2018

We tested the predictions of the dynamic reweighting model (DRM) of audiovisual (AV) speech integration, which posits that spectrotemporally reliable (informative) AV speech stimuli induce a reweighting of processing from low‐level to high‐level auditory networks. This reweighting decreases sensitivity to acoustic onsets and in turn increases tolerance to AV onset asynchronies (AVOA). EEG was recorded while subjects watched videos of a speaker uttering trisyllabic nonwords that varied in spectrotemporal reliability and asynchrony of the visual and auditory inputs. Subjects judged the stimuli as in‐sync or out‐of‐sync. Results showed that subjects exhibited greater AVOA tolerance for non‐blurred than blurred visual speech and for less than more degraded acoustic speech. Increased AVOA tolerance was reflected in reduced amplitude of the P1‐P2 auditory evoked potentials, a neurophysiological indication of reduced sensitivity to acoustic onsets and successful AV integration. There was also sustained visual alpha band (8–14 Hz) suppression (desynchronization) following acoustic speech onsets for non‐blurred vs. blurred visual speech, consistent with continuous engagement of the visual system as the speech unfolds. The current findings suggest that increased spectrotemporal reliability of acoustic and visual speech promotes robust AV integration, partly by suppressing sensitivity to acoustic onsets, in support of the DRM's reweighting mechanism. Increased visual signal reliability also sustains the engagement of the visual system with the auditory system to maintain alignment of information across modalities.
[18F]GE180 positron emission tomographic imaging indicates a potential double‐hit insult in the intrahippocampal kainate mouse model of temporal lobe epilepsy
Authors: Brackhan Mirjam , Bascuñana Pablo , Ross Tobias L. , Bengel Frank M. , Bankstahl Jens P. , Bankstahl Marion
Published: January 2018

Objective

Accumulating evidence suggests that brain inflammation, elicited by epileptogenic insults, is involved in epilepsy development. Noninvasive nuclear imaging of brain inflammation in animal models of epileptogenesis represents a diagnostic in vivo approach with potential for direct translation into the clinic. Here, we investigated up‐regulation of the translocator protein (TSPO) indicative of microglial activation by serial [18F]GE180 positron emission tomographic (PET) imaging in a mouse model of temporal lobe epilepsy.

Methods

As epileptogenic insult, a status epilepticus (SE) was induced in mice by intrahippocampal injection of kainate. Post‐SE mice injected with kainate and sham‐injected mice were subjected to [18F]GE180 PET scans before SE and at 2 days, 5‐7 days, 2 weeks, 3 weeks, 7 weeks, and 14 weeks postinsult. For data evaluation, brain regions ipsilateral and contralateral to the injection site were outlined by coregistration with a standard mouse brain atlas, and percentage of injected dose per cubic centimeter was calculated. In addition, a statistical parametric mapping analysis, comparing post‐SE mice to baseline, sham mice to baseline, and post‐SE to sham mice was performed.

Results

Following SE, elevations in [18F]GE180 uptake were most prominent in the ipsilateral hippocampus, occurring between 2 days and at least 7 weeks after SE, with a peak at 5‐7 days after SE. In the contralateral hippocampus and other epilepsy‐associated brain regions, increased tracer uptake was observed with a similar time profile but to a lesser extent. Moderate enhancement of tracer uptake was also evident in mice after sham surgery.

Significance

TSPO in vivo imaging reliably detects brain inflammation during epileptogenesis. These inflammatory processes most prominently affect the hippocampus ipsilateral to the injection site. Inflammation induced by the traumatic insult associated with surgery synergistically contributes to total brain inflammation and may also contribute to epileptogenesis. The revealed time course of neuroinflammation will help to identify appropriate time points for anti‐inflammatory, potentially antiepileptogenic treatment.
Impact of priming on global soil carbon stocks
Authors: Guenet Bertrand , Camino‐Serrano Marta , Ciais Philippe , Tifafi Marwa , Maignan Fabienne , Soong Jennifer L. , Janssens Ivan A.
Published: January 2018

Fresh carbon input (above and belowground) contributes to soil carbon sequestration, but also accelerates decomposition of soil organic matter through biological priming mechanisms. Currently, poor understanding precludes the incorporation of these priming mechanisms into the global carbon models used for future projections. Here, we show that priming can be incorporated based on a simple equation calibrated from incubation and verified against independent litter manipulation experiments in the global land surface model, ORCHIDEE. When incorporated into ORCHIDEE, priming improved the model's representation of global soil carbon stocks and decreased soil carbon sequestration by 51% (12 ± 3 Pg C) during the period 1901–2010. Future projections with the same model across the range of CO2 and climate changes defined by the IPCC‐RCP scenarios reveal that priming buffers the projected changes in soil carbon stocks — both the increases due to enhanced productivity and new input to the soil, and the decreases due to warming‐induced accelerated decomposition. Including priming in Earth system models leads to different projections of soil carbon changes, which are challenging to verify at large spatial scales.
A cohort study assessing the impact of small volume blood tubes on diagnostic test quality and iatrogenic blood loss in a cohort of adult haematology patients
Authors: Myles Nicholas , von Wielligh Jacoba , Kyriacou Mario , Ventrice Terry , To Luen B.
Published: January 2018

Background/Aim

To estimate the reduction in blood volume loss and impact on diagnostic test quality associated with introduction of small volume blood tubes in a cohort of haematology inpatients compared to a historical comparator group.

Methods

Prospective cohort study of haematology inpatients admitted to a tertiary referral hospital in Adelaide. Small volume blood tubes were used in an intervention cohort admitted between 2012 and 2013 and compared to a control cohort admitted between 2009 and 2010 where standard volume blood tubes had been used. The diagnostic test quality, specimen integrity and total reduction in blood loss associated with small volume blood tubes were estimated.

Results

Small volume blood tubes demonstrated acceptable collinearity on commonly assayed haematological and biochemical parameters. Small volume tubes were associated with a 42% reduction in blood volume loss equating to a saving of 8.5 mL per patient per day or 180 mL of blood loss over a 3‐week admission. Small volume blood tubes were associated with a slight but significantly increased rate of fibrin contamination of ethylenediaminetetraacetic acid samples (0.2–0.5% of specimens).

Conclusion

Small volume blood tubes are associated with a substantial reduction in total blood volume collected per day in haematology inpatients. They have similar diagnostic validity and sample integrity to that of standard volume containers.
A description of ‘Australian Lyme disease’ epidemiology and impact: an analysis of submissions to an Australian senate inquiry
Authors: Brown Jeremy D.
Published: January 2018

Background

Many Australian patients are diagnosed and treated for the scientifically and politically controversial diagnosis of an endemic form of ‘Australian Lyme Disease’. Patient advocacy led Senator John Madigan to propose an Australian Senate Inquiry into this illness.

Aim

To describe the symptomology and outcomes of patients diagnosed and treated with Lyme disease in Australia.

Methods

All public, first‐person submissions (n = 698) to the inquiry were reviewed and responses analysed for epidemiology, symptoms and impact against structured criteria.

Results

The most common symptoms described were fatigue (62.6%), disordered thinking (51.9%) and sensory disturbance (46.1%). Respondents reported experiencing symptoms for a median of 10 years and spent a median of $30 000 on diagnosis and treatment. Almost 10% of respondents self‐diagnosed after being exposed to a media report of Australian Lyme disease.

Conclusions

Patients diagnosed with Lyme disease in Australia display a symptomology similar to ‘medically unexplained physical symptoms’ syndromes, experience social and financial harms, and are at risk of nosocomial harms. Negative medical interactions and the media may contribute to patients seeking alternative and potentially non‐evidence‐based diagnoses and treatments.
Poor family functioning mediates the link between childhood adversity and adolescent nonsuicidal self‐injury
Authors: Cassels Matthew , van Harmelen Anne‐Laura , Neufeld Sharon , Goodyer Ian , Jones Peter B. , Wilkinson Paul
Published: January 2018

Background

Non‐suicidal self‐injury (NSSI) is a common harmful behavior during adolescence. Exposure to childhood family adversity (CFA) is associated with subsequent emergence of NSSI during adolescence. However, the pathways through which this early environmental risk may operate are not clear.

Aims

We tested four alternative hypotheses to explain the association between CFA and adolescent‐onset NSSI.

Methods

A community sample of n = 933 fourteen year olds with no history of NSSI were followed up for 3 years.

Results

Poor family functioning at age 14 mediated the association between CFA before age 5 and subsequent onset of NSSI between 14 and 17 years.

Conclusions

The findings support the cumulative suboptimal environmental hazards (proximal family relationships as a mediator) hypothesis. Improving the family environment at age 14 may mitigate the effects of CFA on adolescent onset of NSSI.
Women's Sexual Health and Aging
Authors: Granville Lisa , Pregler Janet
Published: January 2018

Older women are often sexually active, but physicians caring for older women rarely address sexual concerns. Although women's desire for sex declines with age, a majority of older women rate sex as having importance in their lives. Women identify emotional intimacy as an important reason for engaging in sexual relationships. Women are less likely than men to have an available spousal or intimate partner and more likely to have a partner with sexual difficulties of their own. Up to half of sexually active older women report a distressing sexual problem, with low desire and problems related to genitourinary syndrome (vulvovaginal atrophy) being most common. Difficulty with orgasm in older women is often associated with a partner's erectile dysfunction. Sexually transmitted infections (STIs) are increasingly prevalent in older women. A minority of older women report discussing sexual issues with a physician. Most commonly, the patient initiates discussions. Physicians should ask regularly and proactively about sexual activity and function. Important interventions include offering practical advice to common chronic medical conditions and sexual problems that confront older women; treating vulvovaginal atrophy; and providing STI screening, prevention strategies, and treatment when appropriate.
Diets with a low glycaemic load have favourable effects on prediabetes progression and regression: a prospective cohort study
Authors: He F.
Published: January 2018

Background

To date, no study assessing the associations among glycaemic index (GI), glycaemic load (GL) and progression to diabetes has focused specifically on prediabetes. Moreover, the available data on the association between these variables and regression to normal glucose regulation (NGR) are insufficient. Therefore, the present study aimed to evaluate the longitudinal associations amongGI,GLand prediabetes outcomes.

Methods

This prospective study included 640 adults aged 40–79 years with prediabetes at baseline. Dietary data were assessed using a previously validated 3‐day food record. The participants were divided into three groups according toGIandGLtertiles. Outcomes were defined based on annual oral glucose tolerance test results.

Results

During a median of 5 years of follow‐up, 127 incident cases of diabetes and 249 incident cases ofNGRwere identified. DietaryGLwas positively associated with the risk of developing diabetes and negatively associated with the likelihood of reachingNGRat least once. Comparing the highest and lowest tertiles ofGL, the multivariable‐adjusted hazard ratios (95% confidence intervals) were 1.85 (1.07–3.21) for progression and 0.65 (0.44‐0.96) for regression. No association was observed betweenGIand prediabetes outcomes in the fully adjusted models.

Conclusions

Among patients with prediabetes, high dietaryGLwas positively associated with diabetes risk. Furthermore, a low‐GLdiet contributed to an increased incidence of reachingNGR.
Decreased rates of cerebral protein synthesis measured in vivo in a mouse model of Tuberous Sclerosis Complex: unexpected consequences of reduced tuberin
Authors: Saré Rachel Michelle , Huang Tianjian , Burlin Tom , Loutaev Inna , Smith Carolyn Beebe
Published: January 2018

Tuberous sclerosis complex (TSC) is an autosomal dominant neurogenetic disorder affecting about 1 in 6000 people and is caused by mutations in either TSC1 or TSC2. This disorder is characterized by increased activity of mammalian target of rapamycin complex 1 (mTORC1), which is involved in regulating ribosomal biogenesis and translation initiation. We measured the effects of Tsc2 haploinsufficiency (Tsc2+/−) in 3‐month‐old male mice on regional rates of cerebral protein synthesis (rCPS) by means of the in vivo L‐[1‐14C]leucine method. This quantitative autoradiographic method includes an estimate of the integrated specific activity of the tracer amino acid in brain tissue. The estimate accounts for recycling of unlabeled amino acids from tissue protein breakdown by means of a factor (λ) that was determined in control and Tsc2+/− mice. The value of λ was higher in Tsc2+/− mice, indicating that a greater fraction of leucine in the tissue precursor pool for protein synthesis is derived from the plasma compared to controls, consistent with reduced rates of protein degradation. We determined rCPS in freely moving, awake male Tsc2+/− and control mice, and we used the determined values of λ in the calculation of rCPS. Unexpectedly, we found that rCPS were significantly decreased in 16 of the 17 brain regions analyzed in Tsc2+/− mice compared to controls. Our results indicate a complex role of mTORC1 in the regulation of cerebral protein synthesis that has not been previously recognized.

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Developmental patterns and variation among early theropods
Authors: Griffin C. T.
Published: January 2018

Understanding ontogenetic patterns is important in vertebrate paleontology because the assessed skeletal maturity of an individual often has implications for paleobiogeography, species synonymy, paleobiology, and body size evolution of major clades. Further, for many groups the only means of confidently determining ontogenetic status of an organism is through the destructive process of histological sampling. Although the ontogenetic patterns of Late Jurassic and Cretaceous dinosaurs are better understood, knowledge of the ontogeny of the earliest dinosaurs is relatively poor because most species‐level growth series known from these groups are small (usually, maximum ofn ~ 5) and incomplete. To investigate the morphological changes that occur during ontogeny in early dinosaurs, I used ontogenetic sequence analysis (OSA) to reconstruct developmental sequences of morphological changes in the postcranial ontogeny of the early theropodsCoelophysis bauriandMegapnosaurus rhodesiensis, both of which are known from large sample sizes (n = 174 and 182, respectively). I found a large amount of sequence polymorphism (i.e. intraspecific variation in developmental patterns) in both taxa, and especially inC. bauri, which possesses this variation in every element analyzed.Megapnosaurus rhodesiensisis similar, but it possesses no variation in the sequence of development of ontogenetic characters in the tibia and tarsus. Despite the large amount of variation in development, many characters occur consistently earlier or later in ontogeny and could therefore be important morphological features for assessing the relative maturity of other early theropods. Additionally, there is a phylogenetic signal to the order in which homologous characters appear in ontogeny, with homologous characters appearing earlier or later in developmental sequences of early theropods and the close relatives of dinosaurs, silesaurids. Many of these morphological features are important characters for the reconstruction of archosaurian phylogeny (e.g. trochanteric shelf). Because these features vary in presence or appearance with ontogeny, these characters should be used with caution when undertaking phylogenetic analyses in these groups, since a specimen may possess certain character states owing to ontogenetic stage, not evolutionary relationships.
Comparative efficacy of two anti‐aging products containing retinyl palmitate in healthy human volunteers
Authors: Farooq Umar , Mahmood Tariq , Shahzad Yasser , Yousaf Abid M , Akhtar Naveed
Published: January 2018

Background

No study yet described the comparative efficacy of two over‐the‐counter (OTC) anti‐aging products in Asian subjects using the techniques involving analysis of living skin.

Aim

We sought to evaluate the anti‐aging efficacy of two commercial formulations containing retinyl palmitate using a high‐resolution UVA video camera.

Method

Total 11 healthy male volunteers, agreed to participate in this single‐blind split‐face design study with the mean age of 25.5 years. Every night, volunteers applied one type of cream on the left side and other type of cream on the right side of the face, as directed according to the study design for 60 days. Measurements of the parameters were taken at 0, 1st, 7th, 15th, 30th, and 60th day of study period using noninvasive UVA video camera Visioscan® VC98. Cream applied on right side of the face labeled as “R” and on the left side as “L.”

Results

Sixty‐day use of the creams showed significant improvement in SELS parameters of the skin. Percent change in skin wrinkling (SEw) parameter calculated after 60 days was −6.68% after applying cream R and −8.27% after applying cream L.

Conclusion

We concluded that constituents in both creams have potentially influenced skin surface parameters, thus indicating that, these creams as a better option to lessen the effects of aging on facial skin on long‐term application.
Viceroys or Emperors? An Institution‐Based Perspective on Merger and Acquisition Prevalence and Shareholder Value
Authors: Maas A. J. J. (Ron) , Heugens P. P. M. A. R. (Pursey) , Reus Taco H.
Published: January 2018

We study how cross‐country variance in institutions that aim to address core agency problems influences consequential strategic decisions of firms around the world. Scholars frequently argue that the interests of minority shareholders are threatened by merger and acquisitions (M&As) due to principal‐agency problems. Rather than acting in shareholders’ best interests, managers potentially act as viceroys, using M&As to cushion themselves from risk and extract more pay. Yet equally salient is the issue of principal‐principal agency, where controlling shareholders can behave as emperors who use M&As to siphon off assets and profits, and appropriate wealth of shareholders with fewer control rights. Taking an institution‐based perspective on these ‘viceroy’ and ‘emperor’ problems, we conjecture that institutions aimed to address these agency problems can generate the desired outcome regarding M&A prevalence, but may also produce unintentional negative consequences for shareholder value as a side‐effect. Empirical evidence covering M&As from 73 countries supports our hypotheses.
Effect of feedingAcacia niloticapods to sheep on nutrient digestibility, nitrogen balance, ruminal protozoa and rumen enzymes activity
Authors: Abdullah M. A. M. , Farghaly M. M. , Youssef I. M. I.
Published: January 2018

This study was conducted to evaluate the effect of supplying two levels ofAcacia nilotica(A. nilotica) pods to rations of sheep on nutrient digestibility, nitrogen balance and rumen liquor parameters (pH, total protozoa count, protein concentration and enzymes activity). Twelve mature rams (50 ± 1.25 kg B.W.) were distributed into three groups, each with four rams. Animals in group one were considered as a control which fed a basal diet, consisting of concentrate mixture and Egyptian clover. The second group and the third one received the same basal diet with supplying the concentrate mixture by 1.5% and 3.0% ofA. niloticapods meal respectively. The experiment lasted for 3 weeks. It was found that supplementation ofA. niloticapods to the concentrate mixture at a rate of 1.5% and 3.0% significantly improved the total feed intake compared to the control. The digestibility of dry matter and crude fibre was significantly reduced withA. niloticasupplements, whereas the digestibility of crude protein was significantly improved. All of nitrogen intake and N‐retained were significantly increased in rams fed on concentrates with 1.5% and 3.0%A.  niloticapods when compared to the control. ThepHof ruminal fluid was not affected by the dietary treatments. Nevertheless, the total rumen protozoa count was significantly decreased inA. niloticapods supplemented groups. Also, the rumen protein concentration and the ruminal enzymes activity, especially α‐amylase, cellulase and protease, were lower inA. niloticapods supplemented treatments. In conclusions, inclusion of low levels ofA. niloticapods (1.5% and 3.0%) in the concentrates can be used as a natural protein protectant in ruminants by forming tannin protein complexes in the rumen to maximize the amino acids available in the lower digestive tract. Also, these levels can increase the protein digestibility as well as the N‐retained in the body .
Regulation of sporangium formation by the orphan response regulator TcrA in the rare actinomycete Actinoplanes missouriensis
Authors: Mouri Yoshihiro , Jang Moon‐Sun , Konishi Kenji , Hirata Aiko , Tezuka Takeaki , Ohnishi Yasuo
Published: January 2018

The rare actinomycete Actinoplanes missouriensis forms terminal sporangia containing a few hundred flagellated spores, which can swim in aquatic environments after release from sporangium. However, gene regulation for its characteristic morphological development is largely unknown. Here, we report the functional analysis of an orphan response regulator, TcrA, which is encoded next to the chemotaxis‐flagellar gene cluster. The tcrA null (ΔtcrA) mutant formed sporangium, in which sporulation proceeded. However, many distorted spores were produced and some spores ectopically germinated in the mutant sporangia. In addition, spores were hardly released from the mutant sporangia. A comparative RNA‐Seq analysis between the wild‐type and ΔtcrA strains showed that TcrA upregulated the transcription of more than 263 genes, which were integrated into 185 transcriptional units. In silico searches identified a 21‐bp direct repeat sequence, 5′‐nnGCA(A/C)CCG‐n4‐GCA(A/C)CCGn‐3′, as the TcrA box, which was confirmed by electrophoretic mobility shift assays. Finally, we identified 34 transcriptional units as the TcrA regulon. TcrA seems to regulate a few hundred genes through the transcriptional activation of three FliA‐family sigma factor genes besides its own regulon. We concluded that TcrA is a global transcriptional activator that controls many aspects of sporangium formation, including flagellar biogenesis, spore dormancy and sporangium dehiscence.
A widely conserved bacterial cytoskeletal component influences unique helical shape and motility of the spirochete Leptospira biflexa
Authors: Jackson Katrina M. , Schwartz Cindi , Wachter Jenny , Rosa Patricia A. , Stewart Philip E.
Published: January 2018

Leptospires and other members of the evolutionarily ancient phylum of Spirochaetes are bacteria often characterized by long, highly motile spiral‐ or wave‐shaped cells. Morphology and motility are critical factors in spirochete physiology, contributing to the ability of these bacteria to successfully colonize diverse environments. However, the mechanisms conferring the helical structure of Leptospira spp. have yet to be fully elucidated. We have identified five Leptospira biflexa bactofilin proteins, a recently characterized protein family with cytoskeletal properties. These five bactofilins are conserved in all species of the Leptospiraceae, indicating that these proteins arose early in the evolution of this family. One member of this protein family, LbbD, confers the optimal pitch distance in the helical structure of L. biflexa. Mutants lacking lbbD display a unique compressed helical morphology, a reduced motility and a decreased ability to tolerate cell wall stressors. The change in the helical spacing, combined with the motility and cell wall integrity defects, showcases the intimate relationship and coevolution between shape and motility in these spirochetes.
Evolutionary analyses of the avirulence effector AvrStb6 in global populations of Zymoseptoria tritici identify candidate amino acids involved in recognition
Authors: Brunner Patrick C. , McDonald Bruce A.
Published: January 2018

We analysed the population genetic diversity of AvrStb6, the first avirulence gene cloned from the wheat pathogen Zymoseptoria tritici, using 142 Z. tritici strains sampled from four wheat fields growing on three continents. Although AvrStb6 was located in a recombination hotspot, it was found in every strain, with 71 polymorphic sites that produced 41 distinct DNA haplotypes encoding 30 AvrStb6 protein isoforms. An AvrStb6 homologue was found in the closest known relative, Z. pseudotritici, but not in three other closely related Zymoseptoria species, indicating that this gene has emerged in Zymoseptoria quite recently. Two AvrStb6 homologues with nucleotide similarities greater than 70% were identified on chromosome 10 in all Z. tritici isolates, suggesting that AvrStb6 belongs to a multigene family of candidate effectors that has expanded recently through gene duplication. The AvrStb6 sequences exhibited strong evidence for non‐neutral evolution, including a large number of non‐synonymous mutations, with significant positive diversifying selection operating on nine of the 82 codons. It appears that balancing selection is operating across the entire gene in natural field populations. There was also evidence for co‐evolving codons within the gene that may reflect compensatory mutations associated with the evasion of recognition by Stb6. Intragenic recombination also appears to have affected the diversity of AvrStb6.
Efficacy of micafungin for the treatment of invasive candidiasis and candidaemia in patients with neutropenia
Authors: Chandrasekar Pranatharthi , Sirohi Bhawna , Seibel Nita L. , Hsu Jack W. , Azie Nkechi , Wu Chunzhang , Ruhnke Markus
Published: January 2018

Neutropenia is linked to the development of invasive candidiasis/candidaemia, for which micafungin has demonstrated efficacy, but evidence in patients with neutropenia is limited. The aim of this study was to evaluate the efficacy of micafungin for the treatment of invasive candidiasis/candidaemia in patients with neutropenia (<500 neutrophils/μL) and without neutropenia. This pooled, post hoc analysis of 2 Phase 3 trials compared micafungin 100 mg/d (adults) and 2 mg/kg/d (paediatrics) with L‐AmB 3 mg/kg/d (NCT00106288) and micafungin 100 mg/d and 150 mg/d with caspofungin 70 mg/d followed by 50 mg/d (adults) (NCT00105144); treatment duration 2‐4 weeks (≤8 weeks for chronic disseminated candidiasis). Effects of neutropenia duration and Candida spp. on efficacy outcomes (treatment success, clinical and mycological response) were examined. Of 685 patients, 77 had neutropenia. The most common infection in patients with/without neutropenia was due to C. tropicalis (31/77) and C. albicans (295/608) respectively. Overall success was numerically lower in patients with vs without neutropenia (63.6% vs 72.9%). Clinical and mycological response was similar between groups. Neutropenia duration or Candida spp. did not impact micafungin's overall success rate. This analysis supports evidence that micafungin is effective against invasive candidiasis/candidaemia in patients with neutropenia, irrespective of neutropenia duration or Candida spp., although overall success may be lower than in patients without neutropenia.
Revisiting the genomic hypomethylation hypothesis of aging
Authors: Unnikrishnan Archana , Hadad Niran , Masser Dustin R. , Jackson Jordan , Freeman Willard M. , Richardson Arlan
Published: January 2018

The genomic hypomethylation hypothesis of aging proposes that an overall decrease in global DNA methylation occurs with age, and it has been argued that the decrease in global DNA methylation could be an important factor in aging, resulting in the relaxation of gene expression regulation and abnormal gene expression. Since it was initially observed that DNA methylation decreased with age in 1974, 16 articles have been published describing the effect of age on global DNA methylation in various tissues from rodents and humans. We critically reviewed the publications on the effect of age on DNA methylation and the expression of the enzymes involved in DNA methylation to evaluate the validity of the hypomethylation hypothesis of aging. On the basis of the current scientific literature, we conclude that a decrease in the global methylation of the genome occurs in most if not all tissues/cells as an animal ages. However, age‐related changes in DNA methylation in specific regions or at specific sites in the genome occur even though the global DNA methylation does not change.
Genetic constraints on adaptation: a theoretical primer for the genomics era
Authors: Connallon Tim , Hall Matthew D.
Published: January 2018

Genetic constraints are features of inheritance systems that slow or prohibit adaptation. Several population genetic mechanisms of constraint have received sustained attention within the field since they were first articulated in the early 20th century. This attention is now reflected in a rich, and still growing, theoretical literature on the genetic limits to adaptive change. In turn, empirical research on constraints has seen a rapid expansion over the last two decades in response to changing interests of evolutionary biologists, along with new technologies, expanding data sets, and creative analytical approaches that blend mathematical modeling with genomics. Indeed, one of the most notable and exciting features of recent progress in genetic constraints is the close connection between theoretical and empirical research. In this review, we discuss five major population genetic contexts of genetic constraint: genetic dominance, pleiotropy, fitness trade‐offs between types of individuals of a population, sign epistasis, and genetic linkage between loci. For each, we outline historical antecedents of the theory, specific contexts where constraints manifest, and their quantitative consequences for adaptation. From each of these theoretical foundations, we discuss recent empirical approaches for identifying and characterizing genetic constraints, each grounded and motivated by this theory, and outline promising areas for future work.
Lessons from animal nutritionists: dietary amino acid requirement studies and considerations for healthy aging studies
Authors: Shoveller Anna K. , McKnight Leslie M. , Wood Katharine M. , Cant John P.
Published: January 2018

Dietary restriction (DR) increases median life span and protects against age‐related disease. Improved longevity can be achieved by restriction of dietary energy, protein, or amino acids (AAs), such as methionine (Met). Met requirements have been defined using methodologies that measure the dose response to Met when all other dietary variables are held constant and with outcomes focused on protein turnover. Here, we cover protein and sulfur AA requirements and discuss the terms “deficient,” “optimal,” and “excess” and how these need to be considered. We additionally discuss the effect of methyl‐donating compounds on sulfur AA metabolism and outcomes. We will discuss how the mechanistic target of rapamycin complex 1 (mTORC1) signaling network regulates protein turnover, lipogenesis and cell growth, proliferation, differentiation, and metabolism in response to hormones, AAs, and cellular energy status. Inhibition of mTORC1 signaling with rapamycin or genetic mutation increases median life span in model organisms, and mTORC1 inhibition may be responsible for some of the life span–extending effects of DR. Finally, we discuss how the sulfur AAs may regulate aspects of reactive oxygen species (ROS) mitigation. Overall, we suggest that approaches evaluating AA intake need to consider whole‐body protein synthesis and measures related to tissue‐specific and whole‐body metabolism that have been associated with longevity.
Myasthenic syndromes due to defects in COL13A1 and in the N‐linked glycosylation pathway
Authors: Beeson David , Cossins Judith , Rodriguez‐Cruz Pedro , Maxwell Susan , Liu Wei‐Wei , Palace Jacqueline
Published: January 2018

The congenital myasthenic syndromes (CMS) are hereditary disorders of neuromuscular transmission. The number of cases recognized, at around 1:100,000 in the United Kingdom, is increasing with improved diagnosis. The advent of next‐generation sequencing has facilitated the discovery of many genes that harbor CMS‐associated mutations. An emerging group of CMS, characterized by a limb‐girdle pattern of muscle weakness, is caused by mutations in genes that encode proteins involved in the initial steps of the N‐linked glycosylation pathway, which is surprising, since this pathway is found in all mammalian cells. However, mutations in these genes may also give rise to multisystem disorders (congenital disorders of glycosylation) or muscle disorders where the myasthenic symptoms constitute only one component within a wider phenotypic spectrum. We also report a CMS due to mutations in COL13A1, which encodes an extracellular matrix protein that is concentrated at the neuromuscular junction and highlights a role for these extracellular matrix proteins in maintaining synaptic stability that is independent of the AGRN/MuSK clustering pathway. Knowledge about the neuromuscular synapse and the different proteins involved in maintaining its structure as well as function enables us to tailor treatments to the underlying pathogenic mechanisms.
Maintenance interventions for overweight or obesity in children: a systematic review and meta‐analysis
Authors: van der Heijden L. B. , Feskens E. J. M. , Janse A. J.
Published: January 2018

Childhood obesity is associated with significant health consequences. Although several intervention programmes for children result in weight loss or stabilization in the short‐term, preventing relapse after treatment remains an important challenge. This systematic review summarizes the evidence about maintenance interventions after treatment in childhood obesity. Studies were identified by searching PubMed, Embase, Cochrane Library, Scopus, Web of Science, PsycINFO, CINAHL and SocINDEX. The primary outcome measure for this review was body mass index standard deviation score (BMI‐Z‐score). Data were pooled using quality effect models.

Eleven studies (1,532 participants, age 2–18 years) were included, covering a wide range of maintenance approaches. Included studies varied widely in methodological quality. Pooled analysis showed that the BMI‐Z‐score of maintenance intervention participants remained stable, whereas control participants experienced a slight increase. No differences were observed regarding intensity and duration of therapy. A slight preference for ‘face‐to‐face’ versus ‘on distance’ interventions was shown. In summary, this review shows that, although there is limited quality data to recommend one maintenance intervention over another, continued treatment does have a stabilizing effect on BMI‐Z‐score. Considering the magnitude of the problem of childhood obesity, this is an important finding that highlights the need for further research on weight loss maintenance.
Intestinal parasites: Associations with intestinal and systemic inflammation
Authors: Zavala G. A. , García O. P. , Camacho M. , Ronquillo D. , Campos‐Ponce M. , Doak C. , Polman K. , Rosado J. L.
Published: January 2018

The aim of the present study was to evaluate associations between intestinal parasitic infection with intestinal and systemic inflammatory markers in school‐aged children with high rates of obesity. Plasma concentrations of C‐Reactive Protein (CRP), leptin, TNF‐α, IL‐6 and IL‐10 were measured as systemic inflammation markers and count of stool leukocytes as marker of intestinal inflammation in 291 children (6‐10 years). Intestinal parasitic infection was measured by stool examination. Logistic regression analyses were performed to determine the odds of having high inflammatory markers for each parasite or group of parasites as compared to parasite‐free children while adjusting for sex, age, mother's educational level and percentage of body fat. The prevalence of soil‐transmitted helminths and intestinal protozoa infections was 12% and 36%, respectively. Parasitic infection was not associated with CRP, IL‐6, IL‐10 or TNF‐α. Children infected with Ascaris lumbricoides (aOR: 5.91, 95% CI: 1.97‐17.70) and Entamoeba coli (aOR: 8.46, 95% CI: 2.85‐25.14) were more likely to have higher stool leucocytes than parasite‐free children. Children with multiple infections (aOR: 10.60, 95% CI: 2.85‐25.14) were more likely to have higher leptin concentrations than parasite‐free children. Intestinal parasitic infection was not associated with systemic inflammation, but was associated with intestinal inflammation. Having multiple infections were associated with higher leptin concentrations.