bluuebunny/crossref_metadata_2025 huggingface dataset:
PSGfinder: fast identification of genes under divergent positive selection using the dynamic windows method
Authors: Tuberosa Joël , Montoya-Burgos Juan I.
Published: September 2017

Orthologous genes evolving under divergent positive selection are those involved in divergent adaptive trajectories between related species. Current methods to identify such genes are complex and conservative or present some imperfections, limiting genome-wide searches. We present a simple method, Dynamic Windows, to detect regions of protein-coding genes evolving under divergent positive selection. This method is implemented inPSGfinder, a user-friendly and flexible software, allowing rapid genome-wide screenings of regions with a dN/dS >1.PSGfinderadditionally includes an alignment cleaning procedure and an adapted multiple comparison correction to identify significant signals of positive selection.

Availability and Implementation

PSGfinderis a software that implements the DWin method, is written in Python and is freely available with its documentation at:https://genev.unige.ch/research/laboratory/Juan-Montoyaor at:https://github.com/joel-tuberosa/psgfinder

Contact

juan.montoya@unige.ch;joel.tuberosa@unige.ch
Copy number heterogeneity, large origin tandem repeats, and interspecies recombination in HHV-6A and HHV-6B reference strains
Authors: Greninger Alexander L. , Roychoudhury Pavitra , Makhsous Negar , Hanson Derek , Chase Jill , Krueger Gerhard , Xie Hong , Huang Meei-Li , Saunders Lindsay , Ablashi Dharam , Koelle David M. , Cook Linda , Jerome Keith R.
Published: September 2017

Quantitative PCR is the diagnostic pillar for clinical virology testing, and reference materials are necessary for accurate, comparable quantitation between clinical laboratories. Accurate quantitation of HHV-6 is important for detection of viral reactivation and inherited chromosomally integrated HHV-6 in immunocompromised patients. Reference materials in clinical virology commonly consist of laboratory-adapted viral strains that may be affected by the culture process. We performed next-generation sequencing to make relative copy number measurements at single nucleotide resolution of eight candidate HHV-6A and seven HHV-6B reference strains and DNA materials from the HHV-6 Foundation and Advanced Biotechnologies. 11 of 17 (65%) HHV6 candidate reference materials showed multiple copies of the origin of replication upstream of the U41 gene by next-generation sequencing. These large tandem repeats arose independently in culture-adapted HHV-6A and HHV-6B strains, measuring 1254 bp and 983 bp, respectively. Copy number measured between 4-10X copies relative to the rest of the genome. We also report the first interspecies recombinant HHV-6 strain with a HHV-6A GS backbone and >5.5kb region from HHV-6B Z29 from U41-U43 that covered the origin tandem repeat. Specific HHV-6A reference strains demonstrated duplication of regions at UL1/UL2, U87, and U89, as well as deletion in the U12-U24 region and U94/95 genes. HHV-6 strains derived from cord blood mononuclear cells from different labs on different continents revealed no copy number differences throughout the viral genome. These data indicate large origin tandem duplications are an adaptation of both HHV-6A and HHV-6B in culture and show interspecies recombination is possible within theBetaherpesvirinae.

Importance

Anything in science that needs to be quantitated requires a standard unit of measurement. This includes viruses, for which quantitation increasingly determines definitions of pathology and guidelines for treatment. However, the act of making standard or reference material in virology can alter its very usefulness through genomic duplications, insertions, and rearrangements. We used deep sequencing to examine candidate reference strains for HHV-6, a ubiquitous human virus that can reactivate in the immunocompromised population and is integrated into the human genome in every cell of the body for 1% of people worldwide. We found large tandem repeats in the origin of replication for both HHV-6A and HHV-6B that are selected for in culture. We also found the first interspecies recombinant between HHV-6A and HHV-6B, a phenomenon that is well-known in alphaherpesviruses but to date has not been seen in betaherpesviruses. These data critically inform HHV-6 biology and the standard selection process.
Demography and Selection Shape Transcriptomic Divergence in Field Crickets
Authors: Blankers Thomas , Vilaça Sibelle T. , Waurick Isabelle , Gray David A. , Matthias Hennig R. , Mazzoni Camila J. , Mayer Frieder , Berdan Emma L.
Published: September 2017

Gene flow, demography, and selection can result in similar patterns of genomic variation and disentangling their effects is key to understanding speciation. Here, we assess transcriptomic variation to unravel the evolutionary history ofGryllus rubensandGryllus texensis, cryptic field cricket species with highly divergent mating behavior. We infer their demographic history and screen their transcriptomes for footprints of selection in the context of the inferred demography. We find strong support for a long history of bidirectional gene flow, which ceased during the late Pleistocene, and a bottleneck inG. rubensconsistent with a peripatric origin of this species. Importantly, the demographic history has likely strongly shaped patterns of neutral genetic differentiation (empiricalFSTdistribution). Concordantly,FSTbased selection detection uncovers a large number of outliers, likely comprising many false positives, echoing recent theoretical insights. Alternative genetic signatures of positive selection, informed by the demographic history of the sibling species, highlighted a smaller set of loci; many of these are candidates for controlling variation in mating behavior. Our results underscore the importance of demography in shaping overall patterns of genetic divergence and highlight that examining both demography and selection facilitates a more complete understanding of genetic divergence during speciation.
SETDB1 prevents TET2-dependent activation of IAP retroelements in naïve embryonic stem cells
Authors: Deniz Özgen , de la Rica Lorenzo , Cheng Kevin C. L. , Spensberger Dominik , Branco Miguel R.
Published: September 2017

Background

Endogenous retroviruses (ERVs), which are responsible for 10% of spontaneous mouse mutations, are kept under control via several epigenetic mechanisms. The H3K9 histone methyltransferase SETDB1 is essential for ERV repression in embryonic stem cells (ESCs), with DNA methylation also playing an important role. It has been suggested that SETDB1 protects ERVs from TET- dependent DNA demethylation, but the relevance of this mechanism for ERV expression remains unclear. Moreover, previous studies have been performed in primed ESCs, which are not epigenetically or transcriptionally representative of preimplantation embryos.

Results

We used naïve ESCs to investigate the role of SETDB1 in ERV regulation and, in particular, its relationship with TET-mediated DNA demethylation. Naïve ESCs show an increased dependency on SETDB1 for ERV silencing when compared to primed ESCs, including at the highly mutagenic intracisternal A particles (IAPs). We found that, in the absence of SETDB1, TET2 activates IAP elements in a catalytic-dependent manner. Surprisingly, however, TET2 does not drive changes in DNA methylation levels at IAPs, suggesting that it regulates these transposons indirectly. Instead, SETDB1 depletion leads to a TET2-dependent loss of H4R3me2s, which is indispensable for IAP silencing during epigenetic reprogramming.

Conclusions

Our results demonstrate a novel and unexpected role for SETDB1 in protecting IAPs from TET2-dependent histone arginine demethylation.
Reclamation strategies for mined forest soils and overstorey drive understorey vegetation
Authors: Chen Han Y.H. , Biswas Shekhar R. , Sobey Timothy M. , Brassard Brian W. , Bartels Samuel F.
Published: September 2017

Understorey vegetation accounts for the majority of plant diversity in boreal forest ecosystems and contributes to ecosystem functioning. In restoration of degraded forested ecosystems, however, understorey vegetation is often restored passively, contrasting to clear strategies such as informed species choice and site improvement intervention for overstorey vegetation. The choice of overstorey‐centred restoration strategy may have important consequences for understorey vegetation.

We examined the effects of substrate material, overstorey type and time since reclamation (age) on understorey vegetation following reclamation of oil sands mining in Alberta, Canada. We sampled cover, richness, evenness and composition of understorey vegetation at 94 sites of conifer, mixedwood and broadleaf overstorey types on three reclamation substrates (overburden, secondary overburden and tailings sand), with age ranging from 4 to 30 years.

Total, woody and non‐woody understorey cover and species richness were the highest on secondary overburden and the lowest on tailings sand, and total cover also decreased with age. Woody cover and richness were the highest under broadleaf overstorey, while non‐woody cover and richness were the lowest under conifer overstorey. Overall species evenness was not significantly affected by substrate type, overstorey type or age, but woody evenness was the highest on secondary overburden and the lowest on tailings sand, and non‐woody evenness showed overstorey‐dependent responses to age. Species composition varied with substrate type, overstorey type and age. Indicator species analysis revealed that tailings sand with conifer overstorey favoured grasses, while overburden and secondary overburden supported a mix of grasses, forbs and shrubs.

Synthesis and applications. Our study demonstrates that overstorey‐centred reclamation strategies impact the abundance, diversity and composition of understorey plant communities following oil sands mining. Landforms constructed with secondary overburden substrates and revegetated with mixedwood or broadleaf tree species provide the most favourable habitats for understorey vegetation, while tailings sand provide a poor substrate for understorey species diversity and composition. We therefore recommend utilizing secondary overburden and overburden substrate material during landform construction, and employing revegetation prescriptions that target mixedwood and broadleaf overstorey types to promote productive and diverse understorey plant communities on the reclaimed landscape.
Synergistic effect of spexin and progesterone on pain sensitivity attenuation in ovariectomized rats
Authors: Moazen Parisa , Taherianfard Mahnaz , Ahmadi Soleimani Mohammad , Norozpor Mitra
Published: September 2017

Spexin is a central modulator of nociception. The aim of the present study was to investigate the effect of intra‐hippocampalCA3 (IHCA3) injection of spexin and spexin‐progesterone co‐administration on pain sensitivity in ovariectomized rat. Thirty‐five adult female rats were divided into five groups. Sham: the animals received injection of 0.5 μLACSFbyIHCA3. Experiments 1 and 2: the animals received injection of 0.5 μL of spexin bilaterally (10 and 30 nmol/rat respectively). Experiments 3 and 4: the animals received injection of 0.5 μL of spexin bilaterally (10 and 30 nmol/rat respectively) + subcutaneous (s.c.) injection of progesterone (5 mg/kg). Ovariectomy was performed in all groups to eliminate the effects of cyclic changes in the female rats. The formalin test (formalin 2.5%) was performed following the administration of spexin and progesterone. Results showed that bilateral injection of spexin inIHCA3 at both concentrations a significant (P < .05) decrease in the pain sensitivity in the two phases of formalin test. Similarly, the bilateral injection of spexin inIHCA3 at both concentrations following the s.c. injection of progesterone significantly (P < .05) decreases pain sensitivity in two phases of the formalin test. This pain attenuation due to the co‐administration of spexin and progesterone was more potent than spexin‐induced analgesia. According to the present results, spexin has a modulatory effect on pain sensitivity, which becomes more pronounced by progesterone administration.
Age‐dependent electrocardiographic changes in Pgc‐1β deficient murine hearts
Authors: Ahmad Shiraz , Valli Haseeb , Salvage Samantha C , Grace Andrew A , Jeevaratnam Kamalan , Huang Christopher L‐H
Published: September 2017

Increasing evidence implicates chronic energetic dysfunction in human cardiac arrhythmias. Mitochondrial impairment through Pgc‐1β knockout is known to produce a murine arrhythmic phenotype. However, the cumulative effect of this with advancing age and its electrocardiographic basis have not been previously studied. Young (12‐16 weeks) and aged (>52 weeks), wild type (WT) (n = 5 and 8) and Pgc‐1β−/− (n = 9 and 6), mice were anaesthetised and used for electrocardiographic (ECG) recordings. Time intervals separating successive ECG deflections were analysed for differences between groups before and after β1‐adrenergic (intraperitoneal dobutamine 3 mg/kg) challenge. Heart rates before dobutamine challenge were indistinguishable between groups. The Pgc‐1β−/− genotype however displayed compromised nodal function in response to adrenergic challenge. This manifested as an impaired heart rate response suggesting a functional defect at the level of the sino‐atrial node, and a negative dromotropic response suggesting an atrioventricular conduction defect. Incidences of the latter were most pronounced in the aged Pgc‐1β−/− mice. Moreover, Pgc‐1β−/− mice displayed electrocardiographic features consistent with the existence of a pro‐arrhythmic substrate. Firstly, ventricular activation was prolonged in these mice consistent with slowed action potential conduction and is reported here for the first time. Additionally, Pgc‐1β−/− mice had shorter repolarisation intervals. These were likely attributable to altered K+ conductance properties, ultimately resulting in a shortened QTc interval, which is also known to be associated with increased arrhythmic risk. ECG analysis thus yielded electrophysiological findings bearing on potential arrhythmogenicity in intact Pgc‐1β−/− systems in widespread cardiac regions.
Organic and Low‐Input Dairy Farming: Avenues to Enhance Sustainability and Competitiveness in the EU
Authors: Scollan Nigel , Padel Susanne , Halberg Niels , Hermansen John , Nicholas Pip , Rinne Marketta , Zanoli Raffaele , Zollitsch Werner , Lauwers Ludwig
Published: September 2017

Whether farming strategies built on continuing input intensification or relying on integrated natural resource management are more sustainable and competitive is at the core of the agricultural development debate. The five‐year (2011–16) Sustainable Organic and Low Input Dairying (SOLID) project, funded by the European Commission, involved 25 partners across 10 European countries and was designed to support innovation in European organic and low‐input dairy farming. Results show that such systems are very diverse, and need tailor‐made farm‐specific strategies and related policy measures. This article shows that low‐input dairying has country‐specific farm characteristics, and is potentially competitive when compared to more intensive dairying systems. Certified organic dairy farms commonly receive a price premium. Such market differentiation to attract a premium is not currently an eligible strategy for low‐input systems, but cost savings on input use are possible. Both low‐input and organic dairy farming systems can adopt innovative farming strategies to improve competitiveness. SOLID adopted a participatory approach for research and dissemination, by undertaking innovative science to answer practical problems. In working with farmers and other stakeholders, methodologies were developed to identify opportunities and novel strategies to enhance profitability, such as changes in breeding and feeding strategies, and provide support systems for on‐farm use.
Structural Features, Antitumor and Antioxidant Activities of Rice Bran Polysaccharides Using Different Extraction Methods
Authors: Han Wenfang , Li Jiangtao , Ding Yuqin , Xiong Shanbai , Zhao Siming
Published: September 2017

In this study, rice bran polysaccharides (RBP) were extracted using the hydrothermal method (RBP‐H), microwave‐assisted extraction (RBP‐M) and enzyme‐assisted extraction (RBP‐E). The prepared RBP samples exhibited the typical spectral patterns of polysaccharides, but differed in chemical composition, molecular features, antitumor and antioxidant activities. The molecular weights (Mw) of RBP‐H, RBP‐M, and RBP‐E were 1.03 × 105, 2.62 × 105, and 0.46 × 105 g/mol, respectively. In vitro, all RBP samples significantly inhibited mouse sarcoma S180 cells viability in a dose‐dependent manner. In vivo, RBP‐M or RBP‐E could not only inhibit the growth of the tumor, but also enhance the spleen index. In addition, RBP‐E could induce an enhancement of superoxide dismutase (SOD) and glutathione peroxidase activities and a scavenging effect on malondialdehyde. This study demonstrated that the effective antitumor activity of RBP may be owed to its enhancement of antioxidant activity function. The present work suggested that RBP, especially RBP‐E could be a safe and effective antitumor, bioactive agent or functional food.

Practical Application

Polysaccharides is extracted from rice bran (RBP) using hydrothermal, microwave‐assisted and enzyme‐assisted extraction methods. The results suggested that the antitumor activity of RBP was associated with enhancement of immunization and antioxidant. RBP could be explored as a natural antitumor and antioxidant agent applied in medicines and functional foods.
Development of a Multiplex PCR Assay for Detection of Pseudomonas fluorescens with Biofilm Formation Ability
Authors: Xu Yu , Chen Wanyi , You Chunping , Liu Zhenmin
Published: September 2017

Under the cold storage and processing conditions of raw milk, the psychrotrophic Pseudomonas fluorescens is usually found as predominant bacteria causing its spoilage. In this study, a multiplex PCR assay was developed for rapid and selective detection of P. fluorescens with biofilm formation ability. The target sequences were 2 genes (adnA and fliC) related to biofilm formation and flagella biosynthesis of P. fluorescens. The specificity of the mPCR assay was evaluated with 7 reference strains, isolated from raw milk, belonging to P. fluorescens, Pseudomonas fragi, Pseudomonas lundensis, Pseudomonas putida, Pseudomonas monteilii, and 2 unclassified Pseudomonas species (Pseudomonas sp1 and Pseudomonas sp8). The detection limit for the target strain was 102 CFU/mL. Seventy‐three strains were evaluated by the mPCR assay. The adnA gene was detected in 23 strains while fliC gene was detected in only 3 strains. However, both target genes (adnA and fliC) were detected by amplification in 12 strains belonging to P. fluorescens species. The biofilm formation ability of P. fluorescens following cultivation in 10% UHT milk at 30 °C or 4 °C were evaluated by the microtiter plate assay. The result showed that all the P. fluorescens strains with the target gene (adnA or fliC, or both 2 genes) had the biofilm‐forming ability. The phylogenetic analysis showed that adnA gene tree had a higher resolution than rpoB tree, and the strains in adnA phylogenetic dendrogram could be divided into 4 different groups according with the matrix of their biofilm‐forming ability. The results indicated a promising use of adnA gene as a taxonomic marker for subdividing P. fluorescens.

Practical Application

A mPCR assay targeting adnA and fliC genes showed rapid and reliable detection of P. fluorescens with biofilm formation ability, which could be useful to detect this contamination in milk samples.
Risk factors of lymph node metastasis in 1620 early gastric carcinoma radical resections in Jiangsu Province in China: A multicenter clinicopathological study
Authors: Chen Ling , Wang Yao Hui , Cheng Yu Qing , Du Ming Zhan , Shi Jiong , Fan Xiang Shan , Zhou Xiao Li , Zhang Yi Fen , Guo Ling Chuan , Xu Gui Fang , He Ya Min , Zhou Dan , Zou Xiao Ping , Huang Qin , Team The Jiangsu Province Early Gastric Carcinoma Multicenter Stu
Published: September 2017

OBJECTIVE

To investigate risk factors of lymph node metastasis (LNM) in early gastric carcinoma (EGC) in four tertiary medical centers in Jiangsu Province, China.

METHODS

Among 10 097 consecutive combined gastric cancer radical resections, 1903 EGC were identified and reviewed, 283 excluded and 1620 included in the study. All pathological and some endoscopic reports were reviewed for patients’ characteristics, tumor location, gross features, and the number of lymph nodes retrieved and involved. Two pathologists independently investigated the pathological features of tumor type, differentiation, invasion depth, lymphovascular invasion (LVI), and perineural invasion. The data were statistically analyzed to identify risk factors for LNM.

RESULTS

The average number of lymph nodes retrieved was 17.5 per patient. LNM was diagnosed in 15.5%. By univariate analysis, significant risk factors for LNM included age ≥ 41 years, female sex, size over 1 cm, submucosal invasion, poor differentiation, poorly cohesive carcinoma, micropapillary adenocarcinoma, adenocarcinoma mixed with signet‐ring cell carcinoma, LVI, perineural invasion, and distal gastric location. By multivariate analysis, independent risk factors for LNM were size ≥ 3 cm (odds ratio [OR] 1.9), poor differentiation (OR 2.5), adenocarcinoma mixed with signet‐ring cell carcinoma (OR 1.7), LVI (OR 5.8) and submucosal invasion (OR 2.9). In contrast, size < 3 cm and ulcer were not significant risk factors. Early cardiac carcinoma (OR 0.4) had significantly lower risk.

CONCLUSIONS

Independent risk factors for LNM in EGC in Chinese patients included tumor size ≥ 3 cm, poor differentiation, submucosal invasion, adenocarcinoma mixed with signet‐ring cell carcinoma and LVI. Early cardiac carcinoma had a significantly lower risk for LNM.
Post‐embryonic development of Chrysomya putoria (Diptera: Calliphoridae) in swine and bovine tissues in South America: implications for forensic entomology
Authors: Salazar‐Souza Mônica , Couri Marcia Souto , Aguiar Valéria Magalhães
Published: September 2017

Necrophagous diptera are used in forensic entomology to measure the post‐mortem interval (PMI) of cadavers. PMI estimates based on fly larvae, however, can be inaccurate when larval development is retarded, or accelerated, by the nutritional composition of the cadaveric tissue. We compared the post‐embryonic development of Chrysomya putoria (Wiedemann, 1830) on different tissues of pigs and cows. Forty newly hatched fly larvae per treatment were placed on 60 g of the following swine tissues: liver (T1), swine lung (T2), swine heart (T3), swine muscle (T4), bovine heart (T5), bovine lung (T6) and bovine muscle (T7). There were four replicates/treatment. Experiments were conducted in controlled conditions (28°C day/26°C night, RH 70% ± 10% and 12 h of photophase). Fly larvae reared on swine liver took longer to develop (5.2 days) than flies reared on other substrates (from 3.5 to 4.5 days), and this difference was statistically significant. The total duration of development on swine liver (T1) was significantly slower (8.7 days) when compared to the other treatments. Larvae reared on swine lungs (T2) were significantly heavier in the third instar (
 = 61.2 mg) than larvae reared on swine liver (T1), swine muscle (T4), bovine lung (T6) and bovine muscle (T7). Total larval survival was high (above 76%) in all treatments except for T1 (66%). There was no deviation from the expected adult sex ratio, and the percentage of abnormalities remained within the expected range. These results reinforce the idea that, to achieve greater accuracy in PMI estimates, the type of tissue on which the larvae develops needs to be taken into account.
Cancer multidisciplinary team meetings in practice: Results from a multi‐institutional quantitative survey and implications for policy change
Authors: Rankin Nicole M. , Lai Michelle , Miller Danielle , Beale Philip , Spigelman Allan , Prest Gabrielle , Turley Kim , Simes John
Published: September 2017

Aim

Multidisciplinary care is advocated as best practice in cancer care. Relatively little is documented about multidisciplinary team (MDT) meeting functioning, decision making and the use of evidence to support decision making in Australia. This descriptive study aimed to examine team functioning, the role of team meetings and evidence use in MDTs whose institutions are members of Sydney Catalyst Translational Cancer Research Centre.

Methods

We designed a structured 40‐item survey instrument about topics that included meeting purpose, organization, resources and documentation; caseload estimates; use of evidence and quality assurance; patient involvement and supportive care needs; and open‐ended items about the MDTs strengths and weaknesses. Participants were invited to participate via email and the survey was administered online. Data were analyzed using descriptive and comparative statistics.

Results

Thirty‐seven MDTs from seven hospitals participated (100% response) and represented common (70%) and rare tumor groups (30%). MDT meeting purpose was reported as treatment (100%) or diagnostic decision making (88%), or for education purposes (70%). Most MDTs based treatment decisions on group consensus (92%), adherence to clinical practice guidelines (57%) or other evidence‐based medicine sources (33%). The majority of MDTs discussed only a proportion of new patients at each meeting emphasizing the importance of educational aspects for other cases. Barriers exist in the availability of data to enable audit and reflection on evidence‐based practice. MDT strengths included collaboration and quality discussion about patients.

Conclusions

MDT meetings focus on treatment decision making, with group consensus playing a significant role in translating research evidence from guidelines into clinical decision making. With a varying proportion of patients discussed in each MDT meeting, a wider audit of multidisciplinary care would enable more accurate assessments of whether treatment recommendations are in accordance with best‐practice evidence.
Cigarette smoking significantly alters sperm DNA methylation patterns
Authors: Jenkins T. G. , James E. R. , Alonso D. F. , Hoidal J. R. , Murphy P. J. , Hotaling J. M. , Cairns B. R. , Carrell D. T. , Aston K. I.
Published: September 2017

Numerous health consequences of tobacco smoke exposure have been characterized, and the effects of smoking on traditional measures of male fertility are well described. However, a growing body of data indicates that pre‐conception paternal smoking also confers increased risk for a number of morbidities on offspring. The mechanism for this increased risk has not been elucidated, but it is likely mediated, at least in part, through epigenetic modifications transmitted through spermatozoa. In this study, we investigated the impact of cigarette smoke exposure on sperm DNA methylation patterns in 78 men who smoke and 78 never‐smokers using the Infinium Human Methylation 450 beadchip. We investigated two models of DNA methylation alterations: (i) consistently altered methylation at specific CpGs or within specific genomic regions and (ii) stochastic DNA methylation alterations manifest as increased variability in genome‐wide methylation patterns in men who smoke. We identified 141 significantly differentially methylated CpGs associated with smoking. In addition, we identified a trend toward increased variance in methylation patterns genome‐wide in sperm DNA from men who smoke compared with never‐smokers. These findings of widespread DNA methylation alterations are consistent with the broad range of offspring heath disparities associated with pre‐conception paternal smoke exposure and warrant further investigation to identify the specific mechanism by which sperm DNA methylation perturbation confers risk to offspring health and whether these changes can be transmitted to offspring and transgenerationally.
Testosterone does not affect agrin cleavage in mobility‐limited older men despite improvement in physical function
Authors: Gagliano‐Jucá T. , Storer T. W. , Pencina K. M. , Travison T. G. , Li Z. , Huang G. , Hettwer S. , Dahinden P. , Bhasin S. , Basaria S.
Published: September 2017

In a subset of men, sarcopenia and physical dysfunction occur due to destabilization of the neuromuscular junction (NMJ), which is manifested by elevated serum concentrations of C‐terminal agrin fragment (CAF). Testosterone administration improves physical function in some studies; however, its effects on serum circulating CAF concentrations remain unknown. Here we evaluate the effects of testosterone administration on circulating CAF levels in mobility‐limited men with low testosterone aged 65 or older participating in the Testosterone in Older Men with Mobility Limitations (TOM) Trial. We analyzed the difference in change in serum CAF levels between testosterone and placebo groups, as well as its association with muscle strength and physical function. Association of change in serum CAF levels with serum total (TT) and free testosterone (FT) was also evaluated. Men randomized to testosterone experienced significant improvement in muscle strength and physical function (assessed by loaded stair‐climbing power). However; testosterone administration was not associated with a reduction in serum CAF levels (effect size = −50.3 pm; 95% CI = −162.1 to 61.5 pm; p = 0.374); there was no association between changes in CAF levels with changes in TT (p = 0.670) or FT (p = 0.747). There was no association between changes in serum CAF levels with improvement in either muscle strength or stair‐climbing power. In conclusion, testosterone treatment in mobility‐limited older men with low to low‐normal testosterone levels did not reduce serum CAF levels. Additionally, testosterone‐induced improvements in muscle strength and physical function were not associated with changes in serum CAF concentrations. These findings suggest that improvement in physical function with testosterone replacement in older men with mobility limitations and elevated CAF levels is mediated by mechanisms other than stabilization of the NMJ.
Evaluation of sperm DNA quality in men presenting with testicular cancer and lymphoma using alkaline and neutral Comet assays
Authors: Kumar K. , Lewis S. , Vinci S. , Riera‐Escamilla A. , Fino M.‐G. , Tamburrino L. , Muratori M. , Larsen P. , Krausz C.
Published: September 2017

Despite more cancers in young men over the past two decades, improvements in therapies give a greater chance to live full lives following treatment. Sperm genomic quality is variable following cancer diagnosis, so its assessment is important if sperm cryopreservation is being considered. Here, we evaluated DNA damage using two DNA damage assays: an alkaline and for the first time, a neutral Comet assays in men presenting with testicular cancer (n = 19 for alkaline and 13 for neutral group) and lymphoma (n = 13 for alkaline and 09 for neutral group) compared with fertile donors (n = 20 for alkaline and 14 for neutral group). No significant differences were observed in any semen analysis parameters. In contrast, sperm DNA damage was higher in men with testicular cancer than in donors as assessed by both the alkaline (12.4% vs. 37.4%, p < 0.001) and neutral (7.5% vs. 13.4%; p < 0.05) Comet assays. Similar trends were observed in men with lymphoma. Here, sperm DNA damage was higher using both the alkaline (35.0% vs. 12.4%) and neutral (10.7% against 7.5% (p < 0.05) Comet assays. Moreover, the DNA strand breaks (particularly double‐strand breaks) were significantly more prominent in men with cancer having abnormal seminal parameters than normozoospermic ones. This study showed that sperm DNA testing using alkaline and neutral Comet assays is more sensitive than semen analysis in detecting impaired sperm quality in men presenting with cancer. It may provide a useful adjunct when considering storage prior to cancer investigations and assisted reproductive techniques (ART)‐based treatment.
Robotic surgery for rectal cancer
Authors: Nozawa Hiroaki , Watanabe Toshiaki
Published: September 2017

Laparoscopic surgery has gained acceptance as a less invasive approach in the treatment of colon cancer. However, laparoscopic surgery for rectal cancer, particularly cancer of the lower rectum, is still challenging because of limited accessibility. Robotic surgery overcomes the limitations of laparoscopy associated with anatomy and offers certain advantages, including 3‐D imaging, dexterity and ambidextrous capability, lack of tremors, motion scaling, and a short learning curve. Robotic rectal surgery has been reported to reduce conversion rates, particularly in low anterior resection, but it is associated with longer operative times than the conventional laparoscopic approach. Postoperative morbidities are similar between the robotic and conventional laparoscopic approaches, and oncological outcomes such as the quality of the mesorectum and the status of resection margins are also equivalent. The possible superiority of robotic surgery in terms of the preservation of autonomic function has yet to be established in research based on larger numbers of patients. Although robotic rectal surgery is safe, feasible, and appears to overcome some of the technical limitations associated with conventional laparoscopic surgery, the advantages provided by this technical innovation are currently limited. To justify its expensive cost, robotic surgery is more suitable for select patients, such as obese patients, men, those with cancer of the lower rectum, and those receiving preoperative chemoradiotherapy.
Mitigating depression among orphaned and vulnerable adolescents: a randomized controlled trial of interpersonal psychotherapy for groups in South Africa
Authors: Thurman Tonya R. , Nice Johanna , Taylor Tory M. , Luckett Brian
Published: September 2017

Background

Children and adolescents affected by HIV are at elevated risk of depression, yet research on related interventions in this population is scarce in sub‐Saharan Africa. This study sought to examine the effects of interpersonal psychotherapy for groups (IPTG) on depressive symptomology among orphaned and vulnerable adolescents in South Africa.

Method

A cluster randomized controlled trial wherein adolescents ages 14–17 enrolled in community‐based programming for HIV‐affected and vulnerable families were randomly assigned by geographic cluster to participate in a 16‐session IPTG intervention or the standard of care (n = 489). Baseline and postintervention surveys conducted with enrollees included standardized depression screening. Utilizing an intent‐to‐treat design, mixed effects models were performed to examine treatment effects for all participants and potential moderators including gender and baseline depression level (Clinical Trials registration: ClinicalTrials.gov NCT02386878).

Results

While 23% of adolescents in the intervention group did not attend any IPTG sessions, average attendance was 12 out of 16 possible sessions among participants. The intervention was not associated with changes in depression symptomology.

Conclusions

Results underscore the importance of mitigating participation barriers prior to intervention roll‐out and the need for increased evidence for psychological health interventions to mitigate depression among orphaned and vulnerable adolescents. This intervention and the study selectively targeted at‐risk adolescents versus using diagnostic mental health criteria for enrollment; more research is needed to identify the potential benefits and disadvantages of these approaches.
Parathyroid hormone: Data mining for age‐related reference intervals in adults
Authors: Farrell Christopher‐John L. , Nguyen Lan , Carter Andrew C.
Published: September 2017

Objective

Age‐related changes in parathyroid hormone (PTH) have been previously documented in adults. However, because of the limitations of traditional approaches to establishing reference intervals, age‐related reference intervals have not been defined. We sought to use a data mining approach to derive age‐related PTH reference intervals.

Design and Participants

Results from patients undergoing PTH testing over a 4‐year period were extracted from the database of a private pathology laboratory in New South Wales, Australia. Patients were included in the study if they were 18 years or older and had simultaneous determination of PTH, serum calcium, estimated glomerular filtration rate and 25‐hydroxyvitamin D (25‐OHD). Patients with abnormalities of serum calcium or renal function were excluded.

Measurements

Bhattacharya analysis of log‐transformed data was used to derive age‐related PTH reference intervals across adulthood.

Results

Results were available for 33 652 subjects. Among patients with optimal 25‐OHD status, older age was associated with higher PTH concentrations. Age‐related reference intervals were derived and showed a 63% increase in the upper and lower reference limits between the youngest (18‐29 years of age) and the oldest (80 years of age or older) age partitions. The appropriateness of using a single reference interval for patients of all ages was evaluated against objective criteria and was found to be unsatisfactory.

Conclusions

Data mining was demonstrated to be a useful tool for establishing age‐related PTH reference intervals. The technique demonstrated that increasing age is associated with higher PTH concentrations and that age‐related reference intervals are important for accurate result interpretation.
Outcomes of an international volunteer surgical project for patients with cleft lip and/or cleft palate: A mission in developing Laos
Authors: Goto Takahiro , Nishihara Kazuhide , Kataoka Keiichi , Goto Shinpei , Maruyama Tessho , Sunakawa Hajime , Natsume Nagato , Arasaki Akira
Published: September 2017

Cleft lip and/or palate (CL/P) is a common birth defect of complex etiology. CL/P surgery is generally performed in infancy to allow for improvements in esthetics, suckling, and speech disorders as quickly as possible. We have engaged in activities such as free‐of‐charge surgery for CL/P a total of 12 times from 2001 to 2016 in Lao People's Democratic Republic (Laos). The United Nations has designated Laos as a Least Developed Country; it is one of the poorest countries in Asia. We have carried out our activities for a long time, primarily in CL/P patients who cannot undergo surgery for financial reasons, and we have performed CL/P‐related surgeries for 283 patients up to 2016. When we began our activities in 2001, the mean age at first cheiloplasty was 11.6 years, which dropped over time until 2016 when the mean age was 1.8 years. A linear regression analysis showed a significant difference between the age at first lip plasty and the year of first operation (β = −0.35; P < 0.001). This was likely an effect of continuing to train local medical staff in surgical techniques and donating surgical tools and facilities over a period of 16 years while building a good relationship with local staff. However, the healthcare system in Laos is an obstacle to some patients who still cannot undergo CL/P surgery in infancy for financial reasons. We therefore need to support Laos to provide treatment on their own as we continue to carry out our activities for CL/P patients.
On the evaluation of a superpower sound processor for bone‐anchored hearing
Authors: Bosman A.J. , Kruyt I.J. , Mylanus E.A.M. , Hol M.K.S. , Snik A.F.M.
Published: September 2017

Objectives

Performance of a superpower bone‐anchored hearing aid (Baha), the Baha Cordelle from Cochlear Bone‐Anchored Solutions (BCD1), was compared to its successor, the Baha 5 SuperPower (BCD2).

Design

A comparative study in which each patient served as its own control.

Setting

Tertiary clinic.

Participants

Ten experienced BCD1 users with profound mixed hearing loss. For comparison, data from another study with 10 experienced users with a severe mixed hearing loss using a Cochlear Baha 5 power sound processor (BCD‐P) were included.

Main outcome measures

Speech reception thresholds in noise and APHAB and SSQ questionnaires.

Results

Speech reception thresholds for the digits‐in‐noise (DIN) test were significantly lower (P < 5%), that is more favourable, for BCD2 in the speech and noise frontal condition and in the speech frontal and noise contralateral condition than for BCD1. For the group with severe mixed loss fitted with BCD‐P, the SRTs were not significantly different (P > 5%) from the BCD2 values.

With the APHAB questionnaire scores were significantly lower, that is more favourable, for the ease of communication (P < 5%) and the background noise (P < 1%) domains for BCD2 than for BCD1. APHAB scores for the aversiveness of loud sounds domain were not significantly different for both devices (P > 5%). Scores for the speech and quality domains of the SSQ questionnaire were significantly higher, that is more favourable, for BCD2 than for BCD1. APHAB and SSQ scores for BCD‐P were not significantly different from those for BCD2 (P > 5%).

Conclusions

Data for BCD2 in profound mixed loss are similar to those for BCD‐P and a severe mixed loss. Of 10 patients, 2 expressed a strong preference for BCD2 over BCD1, and 7 patients had a preference for BCD2 over BCD1. One patient preferred BCD1 because of its built‐in telecoil facility.
Safety, quality and effect of complete mesocolic excision vs non‐complete mesocolic excision in patients with colon cancer: a systemic review and meta‐analysis
Authors: Wang C. , Gao Z. , Shen K. , Shen Z. , Jiang K. , Liang B. , Yin M. , Yang X. , Wang S. , Ye Y.
Published: September 2017

Aim

The application of complete mesocolic excision (CME) in colon cancer is controversial. We performed a meta‐analysis to compare the safety, quality and effect of CME with non‐complete mesocolic excision (NCME) in patients with colon cancer.

Method

We searched PubMed, ScienceDirect, the Cochrane Library and Scopus to identify studies comparing CME with NCME in colon cancer. We focused on three study outcome areas: safety (operation time, blood loss, complications, mortality); quality (large bowel length, distance from the tumour to the high vascular tie, area of mesentery, total lymph nodes); and effect (long‐term survival).

Results

A total of 8586 patients from 12 studies were included in the meta‐analysis. CME was associated with greater intra‐operative blood loss [weighted mean difference (WMD) 79.87, 95% CI: 65.88–93.86], more postoperative surgical complications (relative risk 1.23, 95% CI: 1.08–1.40), longer large bowel resection (WMD 47.06, 95% CI: 10.49–83.62), greater distance from the tumour to the high vascular tie (WMD 17.51, 95% CI: 15.16–19.87), larger area of mesentery (WMD 36.09, 95% CI: 18.06–54.13) and more lymph nodes (WMD 6.13, 95% CI: 1.97–10.28) than NCME. CME also had positive effects on 5‐year survival [hazard ratio (HR) 0.33, 95% CI: 0.13–0.81], 3‐year survival (HR 0.58, 95% CI: 0.39–0.86) and 3‐year survival for Stage III disease (HR 0.69, 95% CI: 0.60–0.80) compared with NCME.

Conclusion

Limited evidence suggests that CME is a more effective strategy for improving specimen quality and survival but with a higher complication rate.
Subthalamic nucleus and globus pallidus interna influence firing of tonically active neurons in the primate striatum through different mechanisms
Authors: Nakajima Asuka , Shimo Yasushi , Uka Takanori , Hattori Nobutaka
Published: September 2017

Both the subthalamic nucleus (STN) and the globus pallidus pars interna (GPi) are major targets for neuromodulation therapy for movement disorders. An example of such a therapy is deep brain stimulation (DBS). The striatum is the primary target for pharmacological treatment of these disorders. To further our understanding of both the functional relationships among motor nuclei and the mechanisms of therapies for movement disorders, it is important to clarify how changing the neuronal activity of one target, either by medication or by artificial electrical stimulation, affects the other connected nuclei. To investigate this point, we recorded single‐unit activity from tonically active neurons (TANs), which are putative cholinergic interneurons in the striatum, of healthy monkeys (Macaca fuscata) during electrical stimulation of the STN or GPi. Both STN stimulation and GPi stimulation reduced the TAN spike rate. Local infusion of a D2 receptor antagonist in the striatum blocked the reduction in spike rate induced by STN stimulation but not that induced by GPi stimulation. Further, STN stimulation induced phasic dopamine release in the striatum as revealed by in vivo fast‐scan cyclic voltammetry. These results suggest the presence of multiple, strong functional relationships among the STN, GPi, and striatum that have different pathways and imply distinct therapeutic mechanisms for STN‐ and GPi‐DBS.
Emotional well‐being in children with epilepsy: Family factors as mediators and moderators
Authors: Goodwin Shane W. , Wilk Piotr , Karen Campbell M. , Speechley Kathy N.
Published: September 2017

Objective

Our objective was to examine the relationships of factors associated with children's emotional well‐being 2 years after diagnosis, and to examine if these relationships are mediated or moderated by family factors.

Methods

Data came from a multicenter prospective cohort study of children with newly diagnosed epilepsy from across Canada (Health‐Related Quality of Life in Children with Epilepsy Study; HERQULES, n = 373). Emotional well‐being was assessed using the Quality of Life in Childhood Epilepsy Questionnaire (QOLCE‐55). The relationships between clinical factors, family factors, and emotional well‐being were assessed using multiple regression analyses.

Results

Family functioning, family stress, and repertoire of resources that the families had to adapt to stressful events were significantly associated with poor emotional well‐being 2 years after diagnosis (p < 0.05) in the multivariable analysis. The effect of parental depressive symptoms was partially mediated by family functioning and family stress (p < 0.01 and p = 0.02, respectively). Family resources acted as a moderator in the relationship between severity of epilepsy and emotional well‐being (p < 0.05).

Significance

Based on our findings, efforts to strengthen the family environment may warrant attention. We suggest that clinicians take a family centered care approach by including families in treatment planning. Family centered care has been shown to improve family well‐being and coping and in turn may reduce the impact of clinical factors on emotional well‐being to improve long‐term health‐related quality of life.